# US 12,600,712 B2 · Amino-pyrimidine amides

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- Number: US 12,600,712 B2
- Document ID: US12600712B2
- Status: Granted
- Kind: B2
- Application number: 18/062,644
- Filed: 2022-12-07
- Published: 2023-06-08
- Granted: 2026-04-14
- Earliest claimed: 2020-06-08
- Assignees: Hoffmann-La Roche Inc.
- Applicants: Hoffmann-La Roche Inc.
- Inventors: Angelica Beurier; Michail Konstantinos Bogdos; Luke Green; Christian Kramer; Dmitry Mazunin; Emmanuel Pinard; Hasane Ratni
- Web page: https://patentgrep.com/patent/US12600712B2

## CPC

- C07D 403/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 491/107: with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D 498/10: Spiro-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4 and R5 are as defined herein, compositions including the compounds and methods of using the compounds.

## Claims

### Claim 1

A compound of formula (I)
or a pharmaceutically acceptable salt thereof, wherein:
R1, R2, and R3 are independently selected from the group consisting of
i) H,
ii) C1-6-alkyl,
iii) C2-6-alkynyl,
iv) halogen,
v) halo-C1-6-alkyl,
vi) halo-C1-6-alkoxy,
vii) cyano, and
viii) cyano-C1-6-alkyl,
wherein at least one of R1 and R3 is other than H;
R4 and R5 are independently selected from the group consisting of
i) H,
ii) C1-6-alkyl,
iii) halogen, and
iv) halo-C1-6-alkyl,
or R4 and R5 together with the carbon atom to which they are attached form a heterocycloalkyl or a substituted C3-8-cycloalkyl, wherein the substituted C3-8-cycloalkyl is substituted with R6 and R7; and
R6 and R7 are independently selected from the group consisting of halogen, hydroxy, and C1-6-alkyl.

### Claim 2 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1, R2, and R3 are independently selected from the group consisting of
i) H,
ii) C1-6-alkyl,
iii) C2-6-alkynyl,
iv) halogen,
v) halo-C1-6-alkyl
vi) halo-C1-6-alkoxy, and
vii) cyano;
wherein at least one of R1 and R3 is other than H.

### Claim 3 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R4 and R5 are independently selected from the group consisting of
i) H and
ii) C1-6-alkyl,
or R4 and R5 together with the carbon atom to which they are attached form a 4-member heterocycloalkyl with a single oxygen or a substituted C4-cycloalkyl, wherein the substituted C4-cycloalkyl is substituted with R6 and R7.

### Claim 4 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R4 and R5 are independently selected from the group consisting of
i) H and
ii) methyl,
or R4 and R5 together with the carbon atom to which they are attached form an oxetane ring or a substituted C4-cycloalkyl, wherein the substituted C4-cycloalkyl is substituted with R6 and R7.

### Claim 5 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein
R6 and R7 are both halogen; or
R6 is hydroxy and R7 is C1-6-alkyl.

### Claim 6 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein
R6 and R7 are both fluorine; or
R6 is hydroxy and R7 is methyl.

### Claim 7 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein
R1, R2, and R3 are independently selected from the group consisting of
i) H,
ii) C1-6-alkyl,
iii) C2-6-alkynyl,
iv) halogen,
v) halo-C1-6-alkyl,
vi) halo-C1-6-alkoxy, and
vii) cyano;
wherein at least one of R1 and R3 is other than H;
R4 and R5 are independently selected from the group consisting of
i) H and
ii) methyl,
or R4 and R5 together with the carbon atom to which they are attached form an oxetane ring or a substituted C4-cycloalkyl, wherein the substituted C4-cycloalkyl is substituted with R6 and R7; and
R6 and R7 are both fluorine; or
R6 is hydroxy and R7 is methyl.

### Claim 8 (depends on 1)

The compound of claim 1, selected from the group consisting of
(2-((4-chloro-2,3-dihydro-1H-inden-2-yl) amino) pyrimidin-5-yl)(6-oxa-1-azaspiro[3.3]heptan-1-yl) methanone;
(2-((4,6-dichloro-2,3-dihydro-1H-inden-2-yl) amino) pyrimidin-5-yl)(6-oxa-1-azaspiro[3.3]heptan-1-yl) methanone;
(2-((6-chloro-4-methyl-2,3-dihydro-1H-inden-2-yl) amino) pyrimidin-5-yl)(6-oxa-1-azaspiro[3.3]heptan-1-yl) methanone;
(2-((4,5-dichloro-2,3-dihydro-1H-inden-2-yl) amino) pyrimidin-5-yl)(6-oxa-1-azaspiro[3.3]heptan-1-yl) methanone;
2-((5-(6-oxa-1-azaspiro[3.3]heptane-1-carbonyl) pyrimidin-2-yl) amino)-6-chloro-2,3-dihydro-1H-indene-4-carbonitrile;
(S)-2-((5-(6-oxa-1-azaspiro[3.3]heptane-1-carbonyl) pyrimidin-2-yl) amino)-6-chloro-2,3-dihydro-1H-indene-4-carbonitrile;
(2-((6-chloro-4-(difluoromethoxy)-2,3-dihydro-1H-inden-2-yl) amino) pyrimidin-5-yl)(6-oxa-1-azaspiro[3.3]heptan-1-yl) methanone;
(2-((5-chloro-4-methyl-2,3-dihydro-1H-inden-2-yl) amino) pyrimidin-5-yl)(6-oxa-1-azaspiro[3.3]heptan-1-yl) methanone;
(2-((6-chloro-4-(prop-1-yn-1-yl)-2,3-dihydro-1H-inden-2-yl) amino) pyrimidin-5-yl)(6-oxa-1-azaspiro[3.3]heptan-1-yl) methanone;
(2-((6-chloro-4-fluoro-2,3-dihydro-1H-inden-2-yl) amino) pyrimidin-5-yl)(6-oxa-1-azaspiro[3.3]heptan-1-yl) methanone;
(2-((5-chloro-4-fluoro-2,3-dihydro-1H-inden-2-yl) amino) pyrimidin-5-yl)(6-oxa-1-azaspiro[3.3]heptan-1-yl) methanone;
(S or R)-(2-((6-chloro-4-fluoro-2,3-dihydro-1H-inden-2-yl) amino) pyrimidin-5-yl)(6-oxa-1-azaspiro[3.3]heptan-1-yl) methanone;
(2-((6-chloro-4-(trifluoromethyl)-2,3-dihydro-1H-inden-2-yl) amino) pyrimidin-5-yl)(6-oxa-1-azaspiro[3.3]heptan-1-yl) methanone;
(S)-6-chloro-2-((5-(6,6-difluoro-1-azaspiro[3.3]heptane-1-carbonyl) pyrimidin-2-yl) amino)-2,3-dihydro-1H-indene-4-carbonitrile;
(S)-6-chloro-2-((5-(2,2-dimethylazetidine-1-carbonyl) pyrimidin-2-yl) amino)-2,3-dihydro-1H-indene-4-carbonitrile; and
(cis)-6-chloro-2-(S)-((5-(6-hydroxy-6-methyl-1-azaspiro[3.3]heptane-1-carbonyl) pyrimidin-2-yl) amino)-2,3-dihydro-1H-indene-4-carbonitrile;
or a pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 1)

A process to prepare a compound of claim 1, or a pharmaceutically acceptable salt thereof, the process comprising the reaction of a compound of formula (II) in the presence of a compound of formula (III) to provide a compound of formula (I), wherein R1, R2, R3, R4, and R5 are as defined in claim 1:

### Claim 10 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

### Claim 11 (depends on 8)

A pharmaceutical composition comprising a compound of claim 8, or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.