# US 8,148,391 B2 · Fused bicyclic derivatives of 2,4-diaminopyrimidine as ALK and c-Met inhibitors

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- Number: US 8,148,391 B2
- Document ID: US8148391B2
- Status: Granted
- Kind: B2
- Application number: 12/162,851
- Filed: 2007-10-23
- Published: 2009-09-03
- Granted: 2012-04-03
- Earliest claimed: 2006-10-23
- Assignees: Cephalon, Inc.
- Inventors: Gulzar Ahmed; Henry Joseph Breslin; Jason Burke; Matthew A. Curry; James L. Diebold; Bruce Dorsey; Benjamin J. Dugan; Daming Feng; Diane E. Gingrich; Tao Guo; Keith S. Learn; Joseph G. Lisko; Rong-Qiang Liu; Eugen Florin Mesaros; Karen Milkiewicz; Gregory R. Ott; Jay P. Theroff; Tho V. Thieu; Rabindranath Tripathy; Theodore L. Underiner; Gregory J. Wells; Craig A. Zificsak
- Web page: https://patentgrep.com/patent/US8148391B2

## CPC

- C07D 239/48: Two nitrogen atoms
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 403/14: containing three or more hetero rings
- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 405/14: containing three or more hetero rings
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 417/14: containing three or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention provides a compound of formula I or II or a pharmaceutically acceptable salt form thereof, wherein R1, R2, R3, R4, R5, A1, A2, A3, A4, and A5, are as defined herein. The compounds of formula I or II have ALK and/or c-Met inhibitory activity, and may be used to treat proliferative disorders.

## Claims

### Claim 1

A compound of formula I or II
or a pharmaceutically acceptable salt form thereof,
wherein
R1 is H, halogen, —NO2, —OR10, —C(═O)R10, —C(═O)OR10, —C(═O)NR12R13, —NR10R11, C1-6-alkyl, —C1-6-alkyl-OR10, —C1-6-alkyl-NR12R13, C1-6-haloalkyl, C2-6-alkenyl, C2-6-alkynyl, C6-15-aryl, 5-15 membered heteroaryl, C3-10 cycloalkyl, 3-15 membered heterocycloalkyl, pseudohalogen, —S(═O)nR10, —S(═O)2NR12R13, —OCH2F, —OCHF2, —OCF3, —NHOH, —OC(═O)R10, —OC(═O)NR12R13, —NR10C(═O)R11, —NR10C(═O)OR11, —NR10S(═O)2R11, —NR10C(═O)NR12R13, —NR10S(═O)2NR12R13, or —SCF3;
R2 is a group chosen from C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C6-15-aryl, C3-10-cycloalkyl, 3-15 membered heterocycloalkyl, and 5-15 membered heteroaryl, wherein the R2 group is optionally substituted by one or more members independently chosen from halogen, —NO2, —OR20, ═O, —C(═O)R20, —C(═O)OR20, —C(═O)NR22R23, —NR20R21, C1-6-alkyl-(R25)x, C6-15-aryl-(R25)x, 5-15 membered heteroaryl-(R25)x, C3-10 cycloalkyl-(R25)x, 3-15 membered heterocycloalkyl-(R25)x, pseudohalogen, —S(═O)nR20, —S(═O)2NR22R23, —OCH2F, —OCHF2, —OCF3, —NHOH, —OC(═O)R20, —OC(═O)NR22R23, —NR20C(═O)R21, —NR20C(═O)OR21, —NR20S(═O)2R21, —NR20C(═O)NR22R23, —NR20S(═O)2NR22R23, and —SCF3;
R3, R4, and R5 are independently chosen from H, halogen, —NO2, —OR30, —C(═O)R30, —C(═O)OR30, —C(═O)NR32R33, —NR30R31, C1-6-alkyl-(R35)x, C6-15-aryl-(R35)x, 5-15 membered heteroaryl-(R35)x, C3-10 cycloalkyl-(R35)x, 3-15 membered heterocycloalkyl-(R35)x, pseudohalogen, —S(═O)R30, —S(═O)2NR32R33, —OCH2F, —OCHF2, —OCF3, —NHOH, —OC(═O)R30, —OC(═O)NR32R33, —NR30C(═O)R31, —NR30C(═O)OR31, —NR30S(═O)2R31, —NR30C(═O)NR32R33, —NR30S(═O)2NR32R33, and —SCF3;
A1, A2, A3, A4, and A5 are each independently —CZ1Z2—, wherein:
(a) when any two of Z1 and Z2 are located on adjacent atoms, they may form a bond between the atoms,
(b) any of Z1 and Z2 may be independently chosen from H, halogen, —NO2, —OR40, —C(═O)R40, —C(═O)OR40, —C(═O)NR42R43, —NR40R41, C1-6-alkyl-(R45)x, C6-15-aryl-(R45)x, 5-15 membered heteroaryl-(R45)x, C3-10 cycloalkyl-(R45)x, 3-15 membered heterocycloalkyl-(R45)x, C2-6-alkenyl-(R45)x, C2-6-alkynyl-(R45)x, pseudohalogen, —S(═O)nR40, —S(═O)2NR42R43, —OCH2F, —OCHF2, —OCF3, —NHOH, —OC(═O)R40, —OC(═O)NR42R43, —NR40C(═O)R41, —NR40C(═O)OR41, —NR40S(═O)2R41, —NR40C(═O)NR42R43, —NR40S(═O)2NR42R43, and —SCF3, and
(c) any two of Z1 and Z2 may together form a group of formula -A6-A7-A8-A9-A10-,
wherein A6, A7, A8, A9, and A10 are independently chosen from a bond, —CZ4Z5—, —C(═O)—, —NZ6—, —S—, —S(═O)—, —S(═O)2—, or —O—, wherein:
(i) when any two of Z1, Z2, Z3, Z4, Z5, and Z6 are located on adjacent atoms, they may form a bond between the atoms, and
(ii) any of Z4, Z5, and Z6 may be independently chosen from H, halogen, —NO2, —OR50, —C(═O)R50, —C(═O)OR50, —C(═O)NR52R53, —NR50R51, C1-6-alkyl-(R55)x, C6-15-aryl-(R55)x, 5-15 membered heteroaryl-(R55)x, C3-10 cycloalkyl-(R55)x, 3-15 membered heterocycloalkyl-(R55)x, pseudohalogen, —S(═O)nR50, —S(═O)2NR52R53, —OCH2F, —OCHF2, —OCF3, —NHOH, —OC(═O)R50, —OC(═O)NR52R53, —NR50C(═O)R51, —NR50C(═O)OR51, —NR50S(═O)2R51, —NR50C(═O)NR52R53, —NR50S(═O)2NR52R53, and —SCF3;
R25, R35, R45, and R55 at each occurrence are independently chosen from halogen, —NO2, —OR60, ═O, —C(═O)R60, —C(═O)OR60, —C(═O)NR62R63, —NR60R61, C1-6-alkyl, C1-6-haloalkyl, C2-6-alkenyl, C2-6-alkynyl, C6-15-aryl, 5-15 membered heteroaryl, C3-10 cycloalkyl, 3-15 membered heterocycloalkyl, pseudohalogen, —S(═O)nR60, —S(═O)2NR62R63, —OCH2F, —OCHF2, —OCF3, —NHOH, —OC(═O)R60—OC(═O)NR62R63, —OP(═O)(OH)2, —NR60C(═O)R61, —NR60C(═O)OR61, —NR60S(═O)2R61, —NR60C(═O)NR62R63, —NR60S(═O)2NR62R63, and —SCF3, in which said C1-6-alkyl, C1-6-haloalkyl, C2-6-alkenyl, C2-6-alkynyl, C6-15-aryl, 5-15 membered heteroaryl, C3-10 cycloalkyl, and 3-15 membered heterocycloalkyl groups are optionally substituted by one or more substituents independently chosen from C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, halogen, cyano, C3-10 cycloalkyl, phenyl, 5-10 membered heteroaryl-(R79)x, 3-10 membered heterocycloalkyl, —N(R76)2, —C(═O)OR76, —C(═O)N(R76)2, ═O, and —OR76;
R10, R11, R20, R21, R30, R31, R40, R41, R50, R51, R60, R61 at each occurrence are independently chosen from H, C1-6-alkyl, C2-6-alkynyl, C1-6-haloalkyl, C6-15-aryl, 5-15 membered heteroaryl, C3-10 cycloalkyl, and 3-15 membered heterocycloalkyl, in which said C1-6-alkyl, C2-6-alkynyl, C1-6-haloalkyl, C6-15-aryl, 5-15 membered heteroaryl, C3-10 cycloalkyl, and 3-15 membered heterocycloalkyl groups are optionally substituted by one or more substituents independently chosen from C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, halogen, cyano, phenyl, 5-10 membered heteroaryl-(R79)x, 3-10 membered heterocycloalkyl, —N(R76)2, —C(═O)OR76, —C(═O)N(R76)2, ═O, and —OR76;
R12, R13, R22, R23, R32, R33, R42, R43, R52, R53, R62, and R63 at each occurrence are independently chosen from H, C1-6-alkyl, C2-6-alkynyl, C1-6-haloalkyl, C6-15-aryl, 5-15 membered heteroaryl, C3-10 cycloalkyl, and 3-15 membered heterocycloalkyl, in which said C1-6-alkyl, C2-6-alkynyl, C1-6-haloalkyl, C6-15-aryl, 5-15 membered heteroaryl, C3-10 cycloalkyl, and 3-15 membered heterocycloalkyl groups are optionally substituted by one or more substitutents independently chosen from C1-6-alkyl, halogen, C3-10 cycloalkyl, 3-10 membered heterocycloalkyl-(R87)x, —N(R86)2, cyano, C2-6-alkynyl, ═O, and —OR86;
or R12 and R13, R22 and R23, R32 and R33, R42 and R43, R52 and R53, or R62 and R63 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl group or a 5-15 membered heteroaryl group, in which said 3-15 membered heterocycloalkyl group or 5-15 membered heteroaryl group is optionally substituted by one or more substituents independently chosen from C1-6-alkyl, halogen, and —OH;
R76 and R86 at each occurrence are independently chosen from H, C1-6-alkyl-(R78)x, and —C(═O)—C1-6-alkyl;
R78 at each occurrence is independently chosen from ═O and phenyl;
R79 at each occurrence is ═O;
R87 at each occurrence is independently chosen from C1-6-alkyl;
n at each occurrence is independently chosen from 0, 1, and 2; and
x at each occurrence is independently chosen from 0, 1, 2, 3, 4, 5, and 6;
with the proviso that the compound is not:
(a)

### Claim 2 (depends on 1)

A pharmaceutical composition comprising a compound as defined in claim 1 and at least one pharmaceutically acceptable carrier, diluent, or excipient therefor.

### Claim 3 (depends on 2)

A pharmaceutical composition as defined in claim 2, wherein the compound is a compound of formula I or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 2)

A pharmaceutical composition as defined in claim 2, wherein the compound is a compound of formula II or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 1)

A compound of formula I as defined in claim 1, wherein said compound is:
4-[5-Chloro-4-(2-methylcarbamoyl-phenylamino)-pyrimidin-2-ylamino]-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-triene-12-carboxylic acid ethyl ester;
2-{5-Chloro-2-[12-(2-methoxy-ethyl)-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide;
2-[5-Chloro-2-(12-prop-2-ynyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;
2-[5-Chloro-2-(12-cyclopropanecarbonyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;
N-{(1R,2R)-2-[5-Chloro-2-(12-ethyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;
N-{2-[5-Chloro-2-(12-ethyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-phenyl}-methanesulfonamide;
2-[5-Chloro-2-(3-chloro-12-ethyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;
5-Chloro-4-[5-chloro-4-(2-methylcarbamoyl-phenylamino)-pyrimidin-2-ylamino]-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-triene-12-carboxylic acid ethyl ester;
3-Chloro-4-[5-chloro-4-(2-methylcarbamoyl-phenylamino)-pyrimidin-2-ylamino]-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-triene-12-carboxylic acid ethyl ester;
N-(2-{5-Chloro-2-[12-(2-methoxy-ethyl)-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino]-pyrimidin-4-ylamino}-phenyl)-methanesulfonamide;
N-((1R,2R)-2-{5-Chloro-2-[12-(2-methoxy-ethyl)-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
2-[2-(12-Aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-5-chloro-pyrimidin-4-ylamino]-N-methyl-benzamide;
2-[5-Chloro-2-(12-isopropyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;
2-[5-Chloro-2-(3-chloro-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;
N-{(1R,2R)-2-[2-(12-Aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-5-chloro-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;
N-{(1R,2R)-2-[5-Chloro-2-(12-isopropyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;
N-{(1R,2R)-2-[2-(12-sec-Butyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-5-chloro-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;
N-{(1R,2R)-2-[2-(12-sec-Butyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-5-chloro-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;
2-[5-Chloro-2-(3-chloro-12-isopropyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;
2-{5-Chloro-2-[3-chloro-12-(2-methoxy-ethyl)-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide;
2-{5-Chloro-2-[5-chloro-12-(2-methoxy-ethyl)-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide;
N-{(1R,2R)-2-[2-(12-sec-Butyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-5-chloro-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;
2-[2-(12-Aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-5-chloro-pyrimidin-4-ylamino]-3-chloro-N-methyl-benzamide;
3-Chloro-2-{5-chloro-2-[12-(2-methoxy-ethyl)-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide;
N-{(1R,2R)-2-[5-Chloro-2-(3-methoxy-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;
N-{(1R,2R)-2-[5-Chloro-2-(12-ethyl-3-methoxy-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;
(+/−)-2-[5-Chloro-2-(12-ethyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;
(+/−)-2-[5-Chloro-2-(12-methanesulfonyl-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-trien-4-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;
2-[5-Chloro-2-(7-oxo-6,7,8,9-tetrahydro-5H-benzocyclo-hepten-2-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;
(2-exo,3-exo)-3-[5-Chloro-2-(7-oxo-6,7,8,9-tetrahydro-5H-benzocyclo-hepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
N-{(1R,2R)-2-[5-Chloro-2-(7-oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;
2-[5-Chloro-4-(2-methoxy-4-morpholin-4-yl-phenylamino)-pyrimidin-2-ylamino]-5,6,8,9-tetrahydro-benzocyclohepten-7-one;
2-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;
N-{(1R,2R)-2-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;
2-[5-Chloro-2-(7,7-difluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;
N-{(1R,2R)-2-[5-Chloro-2-(7,7-difluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;
5-Chloro-N*2*-(7,7-difluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N*4* -(2-methoxy-4-morpholin-4-yl-phenyl)-pyrimidine-2,4-diamine;
2-{5-Chloro-4-[2-(1-methyl-1H-imidazol-2-yl)-phenylamino]-pyrimidin-2-ylamino}-5,6,8,9-tetrahydro-benzocyclohepten-7-one;
5-Chloro-N*4*-[2-(1-methyl-1H-imidazol-2-yl)-phenyl]-N*2*-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-pyrimidine-2,4-diamine;
5-Chloro-N*2*-(7,7-difluoro-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N*4*-[2-(1-methyl-1H-imidazol-2-yl)-phenyl]-pyrimidine-2,4-diamine;
2-{5-Chloro-2-[12-(2-methoxy-ethyl)-12-aza-tricyclo[7.2.1.0(2,7)]dodeca-2(7),3,5-trien-4-ylamino]-pyrimidin-4-ylamino}-3-fluoro-N-methyl-benzamide;
2-{5-Chloro-2-[12-(2-methoxy-ethyl)-12-aza-tricyclo[7.2.1.0(2,7)]dodeca-2(7),3,5-trien-4-ylamino]-pyrimidin-4-ylamino-}-3-fluoro-benzoic acid isopropyl ester;
5-Chloro-N*4*-(4-methoxy-2-pyrazol-1-yl-phenyl)-N*2*-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-pyrimidine-2,4-diamine;
2-[5-Chloro-4-(4-methoxy-2-pyrazol-1-yl-phenylamino)-pyrimidin-2-ylamino]-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ol;
(2-exo-3-exo)-3-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid methylamide;
(2-exo-3-exo)-3-[5-Chloro-2-(7-hydroxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid methylamide;
(1S,2S,3R,4R)-3-[2-((S)-7-Acetylamino-1-methoxy-9-oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-5-chloro-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
2-{5-Chloro-2-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide;
5-Chloro-N*4*-(2-ethyl-4-morpholin-4-yl-phenyl)-N*2*-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-pyrimidine-2,4-diamine;
(1R,2R)-2-5-Chloro-2-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino-cyclohexanecarboxylic acid amide;
1S,2R,3S,4R)-3-{5-Chloro-2-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]heptane-2-carboxylic acid amide;
5-Chloro-N*4*-[2-(1-methyl-1H-imidazol-2-yl)-phenyl]-N*2*-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-pyrimidine-2,4-diamine;
N-((1R,2R)-2-{5-Chloro-2-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
5-Chloro-N*4*-[2-(3-methyl-pyridin-2-yl)-phenyl]-N*2*-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-pyrimidine-2,4-diamine;
5-Chloro-N*4*-(2-methoxy-phenyl)-N*2*-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-pyrimidine-2,4-diamine;
5-Chloro-N*2*-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-(2-methoxy-4-morpholin-4-yl-phenyl)-pyrimidine-2,4-diamine;
2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide;
5-Chloro-N*2*-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-[2-(1-methyl-1H-imidazol-2-yl)-phenyl]-pyrimidine-2,4-diamine;
N-((1R,2R)-2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
5-Chloro-N*2*-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-(2-methoxy-phenyl)-pyrimidine-2,4-diamine;
2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-3-fluoro-N-methyl-benzamide;
(1S,2S,3R,4R)-3-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic;
(1S,2S,3R,4R)-3-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
N-((1R,2R)-2-[5-Chloro-2-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino-cyclohexyl)-methanesulfonamide;
N-((1R,2R)-2-[5-Chloro-2-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino-cyclohexyl)-methanesulfonamide;
(1S,2S,3R,4R)-3-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
5-Chloro-N*2*-[7-(2,2-difluoro-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-methyl-N*4*-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;
(1S,2S,3R,4R)-3-{5-Chloro-2-[1-methoxy-7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
5-Chloro-N*2*-[1-methoxy-7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-methyl-N*4*-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;
1S,2S,3R,4R)-3-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
1S,2S,3R,4R)-3-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;
2-{5-Chloro-2-[1-methoxy-7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;
N-((1R,2R)-2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
N-((1R,2R)-2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
N-((1R,2R)-2-{5-Chloro-2-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
N-((1R,2R)-2-{5-Chloro-2-[7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
-Chloro-N*2*-[7-(2,2-difluoro-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-(2-pyrazol-1-yl-phenyl)-pyrimidine-2,4-diamine;
5-Chloro-N*2*-[1-methoxy-7-(2,2,2-trifluoro-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-(2-pyrazol-1-yl-phenyl)-pyrimidine-2,4-diamine;
(1S,2S,3R,4R)-3-{5-Chloro-2-[1-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
(1S,2S,3R,4R)-3-{5-Chloro-2-[1-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
N-((1R,2R)-2-{5-Chloro-2-[1-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
N-((1R,2R)-2-{5-Chloro-2-[1-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
1-(2-{5-Chloro-2-[1-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-benzenesulfonyl)-pyrrolidin-3-ol;
1S,2S,3R,4R)-3-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
(1S,2S,3R,4R)-3-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
N-((1R,2R)-2-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
N-((1R,2R)-2-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
(1S,2S,3R,4R)-3-(5-Chloro-2-{1-methoxy-7-[(2-methoxy-ethyl)-methyl-amino]-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino}-pyrimidin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
(1S,2S,3R,4R)-3-(5-Chloro-2-{1-methoxy-7-[(2-methoxy-ethyl)-methyl-amino]-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino}-pyrimidin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
N-[(1R,2R)-2-(5-Chloro-2-{1-methoxy-7-[(2-methoxy-ethyl)-methyl-amino]-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino}-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide;
1-(2-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-benzenesulfonyl)-pyrrolidin-3-ol;
2-(2-{5-Chloro-4-[2-(pyrrolidine-1-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ylamino)-ethanol;
2-{2-[5-Chloro-4-(2-methoxy-4-morpholin-4-yl-phenylamino)-pyrimidin-2-ylamino]-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ylamino}-ethanol;
2-([5-[5-Chloro-2-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-2-fluoro-benzyl]-ethylamino)-ethanol;
6-{5-Chloro-2-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-4-methanesulfonyl-7-methoxy-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one;
5-Chloro-N*4*-(2-methoxy-4-morpholin-4-yl-phenyl)-N*2*-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-pyrimidine-2,4-diamine;
2-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N-ethyl-benzamide;
3-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
2-[5-Chloro-2-(1-methoxy-7-oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;
(1S,2S,3R,4R)-3-[5-Chloro-2-(1-methoxy-7-oxo-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
(1S,2S,3R,4R)-3-[5-Chloro-2-((R)-1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
(1S,2S,3R,4R)-3-[5-Chloro-2-((S)-1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
5-Chloro-N*2*-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N*4*-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;
N-{(1R,2R)-2-[5-Chloro-2-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;
N-[(1R,2R)-2-(5-Chloro-2-{7-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino}-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide;
(1S,2S,3R,4R)-3-(5-Chloro-2-{7-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino}-pyrimidin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
N-((1R,2R)-2-{5-Chloro-2-[7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
2-[5-Chloro-2-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N,N-dimethyl-benzenesulfonamide;
2-{5-Chloro-2-[7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;
5-Chloro-N*4*-(2-methoxy-phenyl)-N*2*-[7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-pyrimidine-2,4-diamine;
(1S,2S,3R,4R)-3-{5-Chloro-2-[7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
(2-{5-Chloro-2-[7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-phenoxy)-acetonitrile;
5-Chloro-N*4*-(2-methoxy-4-morpholin-4-yl-phenyl)-N*2*-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-pyrimidine-2,4-diamine;
N-((1R,2R)-2-{5-Chloro-2-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
N-((1R,2R)-2-{5-Chloro-2-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
(1S,2S,3R,4R)-3-{5-Chloro-2-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
(1S,2S,3R,4R)-3-{5-Chloro-2-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
2-{5-Chloro-2-[7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-3-fluoro-N-methyl-benzamide;
5-Chloro-N*2*-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N*4*-[2-(pyrrolidine-1-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;
5-Chloro-N*2*-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N*4*-(2-pyrazol-1-yl-phenyl)-pyrimidine-2,4-diamine;
3-[5-Chloro-2-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-azepan-2-one;
(1S,3R,4R)-3-[5-Chloro-2-((S)-1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid 2-methoxy-ethyl ester;
(1S,3R,4R)-3-[5-Chloro-2-((S)-1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid 2-methoxy-ethyl ester;
1-{2-[5-Chloro-2-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-benzenesulfonyl}-pyrrolidin-3-ol;
2-{5-Chloro-2-[7-(3-hydroxy-piperidin-1-yl)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;
1-(2-{5-Chloro-4-[2-(pyrrolidine-1-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-yl)-piperidin-3-ol;
(1S,2S,3R,4R)-3-{5-Chloro-2-[7-(3-hydroxy-piperidin-1-yl)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
(1S,2S,3R,4R)-3-{5-Chloro-2-[7-(3-hydroxy-piperidin-1-yl)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
2-{5-Chloro-2-[1-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;
2-{5-Chloro-2-[1-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;
1-{2-[5-Chloro-4-(2-methoxy-4-morpholin-4-yl-phenylamino)-pyrimidin-2-ylamino]-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-yl}-piperidin-3-ol;
5-Chloro-N*2*-[1-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;
2-[5-Chloro-2-(1-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;
(1S,2S,3R,4R)-3-{5-Chloro-2-[1-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
(1S,2S,3R,4R)-3-{5-Chloro-2-[1-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
N-Methyl-2-[2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-benzamide;
4-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-3-methoxy-N-propyl-benzamide;
(1S,2S,3R,4R)-3-[2-(7-Morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
7-[5-Chloro-2-(7-hydroxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-4-methoxy-2-methyl-2,3-dihydro-isoindol-1-one;
7-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-4-methoxy-2-methyl-2,3-dihydro-isoindol-1-one;
(1S,2S,3R,4R)-3-[5-Chloro-2-(1-methoxy-6-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
(1S,2S,3R,4R)-3-[5-Chloro-2-(1-methoxy-6-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
2-[5-Chloro-2-(1-methoxy-6-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N,N-dimethyl-benzenesulfonamide;
5-Chloro-N(2)-(1-methoxy-6-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N(4)-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;
2-[5-Chloro-2-(1-methoxy-6-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-benzoic acid isopropyl ester;
N-{(1R,2R)-2-[5-Chloro-2-(1-methoxy-6-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;
5-Chloro-N(4)-(2-methoxy-4-morpholin-4-yl-phenyl)-N(2)-(1-methoxy-6-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-pyrimidine-2,4-diamine;
(1S,2S,3R,4R)-3-{5-Chloro-2-[1-methoxy-6-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
2-{5-Chloro-2-[1-methoxy-6-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;
N-((1R,2R)-2-{5-Chloro-2-[1-methoxy-6-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
5-Chloro-N(2)-[1-methoxy-6-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N(4)-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;
(1S,2S,3R,4R)-3-{5-Chloro-2-[6-(2-hydroxy-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
2-(2-{5-Chloro-4-[2-(propane-2-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-ylamino)-ethanol;
(R)-1-(2-{5-Chloro-2-[6-(2-hydroxy-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-benzenesulfonyl)-pyrrolidin-3-ol;
(S)-1-(2-{5-Chloro-2-[6-(2-hydroxy-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-benzenesulfonyl)-pyrrolidin-3-ol;
2-(2-{5-Chloro-4-[2-(pyrrolidine-1-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-ylamino)-ethanol;
N-((1R,2R)-2-{5-Chloro-2-[6-(2-hydroxy-ethylamino)-1-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
(1S,2S,3R,4R)-3-[5-Chloro-2-(7-hydroxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
5-Chloro-N*4*-[2-(3-methoxy-pyridin-2-yl)-phenyl]-N*2*-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-pyrimidine-2,4-diamine;
2-{5-Chloro-4-[2-(3-methoxy-pyridin-2-yl)-phenylamino]-pyrimidin-2-ylamino}-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ol;
5-Chloro-N*4*-[2-(3-methyl-pyridin-2-yl)-phenyl]-N*2*-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-pyrimidine-2,4-diamine;
2-{5-Chloro-4-[2-(3-methyl-pyridin-2-yl)-phenylamino]-pyrimidin-2-ylamino}-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ol;
2-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N,N-dimethyl-benzenesulfonamide;
2-[5-Chloro-2-(7-hydroxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N,N-dimethyl-benzenesulfonamide;
5-Chloro-N*2*-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N*4*-(2-pyrazol-1-yl-phenyl)-pyrimidine-2,4-diamine;
2-[5-Chloro-4-(2-pyrazol-1-yl-phenylamino)-pyrimidin-2-ylamino]-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ol;
5-Chloro-N*2*-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N*4*-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;
2-{5-Chloro-4-[2-(propane-2-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ol;
(1S,2S,3R,4R)-3-[5-Chloro-2-(3-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
(1S,2S,3R,4R)-3-[5-Chloro-2-(3-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
2-[5-Chloro-2-(3-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N,N-dimethyl-benzenesulfonamide;
5-Chloro-N*2*-(3-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N*4*-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;
N-{(1R,2R)-2-[5-Chloro-2-(3-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;
5-Chloro-N*2*-(3-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)-N*4*-(2-pyrazol-1-yl-phenyl)-pyrimidine-2,4-diamine;
(1S,2S,3R,4R)-3-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acidamide;
(1S,2S,3R,4R)-3-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acidamide;
2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;
5-Chloro-N*2*-[7-(2,2-difluoro-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;
N-((1R,2R)-2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
N-((1R,2R)-2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
5-Chloro-N*2*-[7-(2,2-difluoro-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-(2-pyrazol-1-yl-phenyl)-pyrimidine-2,4-diamine;
5-Chloro-N*2*-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-[2-(pyrrolidine-1-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;
1-(2-{5-Chloro-2-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-benzenesulfonyl)-pyrrolidin-3-ol;
2-{5-Chloro-2-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;
5-Chloro-N*2*-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;
5-Chloro-N*2*-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-(2-pyrazol-1-yl-phenyl)-pyrimidine-2,4-diamine;
2-{5-Chloro-2-[3-methoxy-7-(2-methoxy-ethylamino)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide;
2-(2-{5-Chloro-4-[2-(pyrrolidine-1-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ylamino)-ethanol;
1-(2-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-benzenesulfonyl)-pyrrolidin-3-ol;
2-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;
2-(2-{5-Chloro-4-[2-(propane-2-sulfonyl)-phenylamino]-pyrimidin-2-ylamino}-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ylamino)-ethanol;
2-{2-[5-Chloro-4-(2-pyrazol-1-yl-phenylamino)-pyrimidin-2-ylamino]-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-ylamino}-ethanol;
2-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide;
2-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-benzoic acid 2-methoxy-ethyl ester;
N-((1R,2R)-2-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
N-((1R,2R)-2-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
(1S,2S,3R,4R)-3-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
(1S,2S,3R,4R)-3-{5-Chloro-2-[7-(2-hydroxy-ethylamino)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
1-(2-{5-Chloro-2-[3-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-benzenesulfonyl)-pyrrolidin-3-ol;
2-{5-Chloro-2-[3-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide;
5-Chloro-N*2*-[3-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl]-N*4*-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;
N-((1R,2R)-2-{5-Chloro-2-[3-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
N-((1R,2R)-2-{5-Chloro-2-[3-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
(1S,2S,3R,4R)-3-{5-Chloro-2-[3-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
(1S,2S,3R,4R)-3-{5-Chloro-2-[3-methoxy-7-(4-methyl-piperazin-1-yl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
(1S,2S,3R,4R)-3-[5-Chloro-2-(1-methoxy-8-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
2-[5-Chloro-2-(1-methoxy-8-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-N,N-dimethyl-benzenesulfonamide;
[2-(5-Chloro-2-{7-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino}-pyrimidin-4-ylamino)-3-fluoro-phenoxy]-acetonitrile;
3-Chloro-2-(5-chloro-2-{7-[4-(4-methyl-piperazin-1-yl)-piperidin-1-yl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino}-pyrimidin-4-ylamino)-N-methyl-benzamide; or
N-{(1R,2R)-2-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-N-methyl-methanesulfonamide;
or a pharmaceutically acceptable salt form thereof.

### Claim 6 (depends on 1)

A compound of formula II as defined in claim 1, wherein said compound is:
tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-triene-4,12-dicarboxylic acid 12-ethyl ester 4-methyl ester;
3-[5-Chloro-2-(4-methoxy-8-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-ylamino)-pyrimidin-4-ylamino]-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide;
2-[5-Chloro-2-(4-methoxy-8-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-ylamino)-pyrimidin-4-ylamino]-N,N-dimethyl-benzenesulfonamide;
5-Chloro-N(2)-(4-methoxy-8-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-yl)-N(4)-[2-(propane-2-sulfonyl)-phenyl]-pyrimidine-2,4-diamine;
N-{(1R,2R)-2-[5-Chloro-2-(2-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-ylamino)-pyrimidin-4-ylamino]-cyclohexyl}-methanesulfonamide;
5-Chloro-N*2*-(2-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-yl)-N*4*-(2-pyrazol-1-yl-phenyl)-pyrimidine-2,4-diamine;
2-[5-Chloro-2-(2-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-ylamino)-pyrimidin-4-ylamino]-N,N-dimethyl-benzenesulfonamide;
2-[5-Chloro-2-(2-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-ylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide;
N-((1R,2R)-2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-2-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
N-((1R,2R)-2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-2-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-methanesulfonamide;
5-Chloro-N*2*-[7-(2,2-difluoro-ethylamino)-2-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-yl]-N*4*-(2-pyrazol-1-yl-phenyl)-pyrimidine-2,4-diamine;
2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-2-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-ylamino]-pyrimidin-4-ylamino}-N,N-dimethyl-benzenesulfonamide; or
2-{5-Chloro-2-[7-(2,2-difluoro-ethylamino)-2-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-1-ylamino]-pyrimidin-4-ylamino}-N-methyl-benzamide;
or a pharmaceutically acceptable salt form thereof.

### Claim 7 (depends on 5)

A pharmaceutical composition comprising a compound as defined in claim 5 and at least one pharmaceutically acceptable carrier, diluent, or excipient therefor.

### Claim 8 (depends on 6)

A pharmaceutical composition comprising a compound as defined in claim 6 and at least one pharmaceutically acceptable carrier, diluent, or excipient therefor.