# US 2013/0156700 A1 · Fluorine-18 and carbon-11 labeled radioligands for positron emission tomography (pet) imaging for lrrk2

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- Number: US 2013/0156700 A1
- Document ID: US20130156700A1
- Status: Published application
- Kind: A1
- Application number: 13/687,441
- Filed: 2012-11-28
- Published: 2013-06-20
- Earliest claimed: 2011-11-30
- Assignees: Genentech, Inc.
- Inventors: Jan Marik; Zachary Kevin Sweeney; Bryan K. Chan; Anthony Estrada
- Web page: https://patentgrep.com/patent/US20130156700A1

## CPC

- C07D 403/12: linked by a chain containing hetero atoms as chain links
- A61K 51/0453: {having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole}
- A61K 51/0455: {having six-membered rings with one nitrogen as the only ring hetero atom}
- A61K 51/0459: {having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine}
- C07D 239/48: Two nitrogen atoms
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

A method for positron emission tomography (PET) imaging of LRRK2 in tissue of a subject, the method comprising: administering a compound of formula I, formula II or formula III, or a pharmaceutically acceptable salt thereof to the subject, wherein the compound includes at least one C11 or F18 label thereon; allowing the compound to penetrate into the tissue of the subject; and collecting a PET image of the CNS or brain tissue of the subject

## Claims

### Claim 1

A method for positron emission tomography (PET) imaging of LRRK2 in tissue of a subject, the method comprising:
administering a compound of formula I, formula II or formula III, or a pharmaceutically acceptable salt thereof to the subject, wherein the compound includes at least one C11 or F18 label thereon;
allowing the compound to penetrate into the tissue of the subject; and
collecting a PET image of the CNS or brain tissue of the subject.

### Claim 2 (depends on 1)

The method of claim 1, further comprising introducing at least one C11 or F18 label onto the compound of formula I, formula II or formula III.

### Claim 3 (depends on 1)

The method of claim 1, wherein the compound is labeled with F18.

### Claim 4 (depends on 1)

The method of claim 1, wherein the compound is labeled with C11.

### Claim 5 (depends on 1)

The method of claim 1, wherein the compound is labeled with F18 on a C1-6alkoxy moiety.

### Claim 6 (depends on 1)

The method of claim 1, wherein the compound is labeled with C11 on a C1-6alkoxy moiety.

### Claim 7 (depends on 1)

The method of claim 1, wherein the compound is of formula I:
or pharmaceutically acceptable salts thereof,
wherein:
m is from 0 to 3;
X is: —NRa—; —O—; or —S(O)r— wherein r is from 0 to 2 and Ra is hydrogen or C1-6alkyl;
R1 is: C1-6alkyl; halo-C1-6alkyl; C2-6alkenyl; C2-6alkynyl; halo-C1-6alkyl; C1-6alkoxy-C1-6alkyl; hydroxy-C1-6alkyl; amino-C1-6alkyl; C1-6alkylsulfonyl-C1-6alkyl; C3-6cycloalkyl optionally substituted with C1-6alkyl or halo; C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl; tetrahydropyranyl; tetrahydrofuranyl; tetrahydro furanyl-C1-6alkyl; oxetanyl; or oxetan-C1-6alkyl;
or R1 and Ra together with the atoms to which they are attached may form a three to six membered ring that may optionally include an additional heteroatom selected from O, N and S, and which is substituted with oxo, halo or C1-6alkyl;
R2 is: halo; C1-6alkoxy; cyano; C2-6alkynyl; C2-6alkenyl; halo-C1-6alkyl; halo-C1-6alkoxy; C3-6cycloalkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl; C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl; tetrahydrofuranyl; tetrahydrofuranyl-C1-6alkyl; acetyl; oxetanyl; or oxetan-C1-6alkyl;
R3 is: —OR4; halo; cyano; C1-6alkyl; halo-C1-6alkyl; C3-6cycloalkyl optionally substituted with C1-6alkyl; C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl; tetrahydrofuranyl; tetrahydrofuranyl-C1-6alkyl; oxetanyl; or oxetan-C1-6alkyl;
R4 is: hydrogen; C1-6alkyl; halo-C1-6alkyl; C1-6alkoxy-C1-6alkyl; C3-6cycloalkyl optionally substituted with C1-6alkyl or halo; C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl or halo; tetrahydrofuranyl; tetrahydrofuranyl-C1-6alkyl; oxetanyl; or oxetan-C1-6alkyl;
R5 is: hydrogen; or C1-6alkyl;
n is 0 or 1;
R6 is: hydrogen; C1-6alkyl; C1-6alkoxy-C1-6alkyl; hydroxy-C1-6alkyl; amino-C1-6alkyl; C3-6cycloalkyl; C3-6cycloalkyl-C1-6alkyl; heterocyclyl; or heterocyclyl-C1-6alkyl; wherein the C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, heterocyclyl and heterocyclyl-C1-6alkyl each may be optionally substituted with one, two, three or four groups independently selected from: C1-6alkyl; halo-C1-6alkyl; C1-6alkoxy; halo-C1-6alkoxy; hydroxy; hydroxy-C1-6alkyl; halo; nitrile; C1-6alkyl-carbonyl; C1-6alkyl-sulfonyl; C3-6cycloalkyl; C3-6cycloalkyl-C1-6alkyl; C3-6cycloalkyl-carbonyl; amino; or heterocyclyl; or two of the groups together with the atoms to which they are attached may form a five or six-membered ring;
or R5 and R6 together with the nitrogen atom to which they are attached form a three- to seven-membered ring that optionally includes an additional heteroatom selected from O, N and S(O)n, and which is optionally substituted with one, two, three or four groups independently selected from: C1-6alkyl; halo-C1-6alkyl; C1-6alkoxy; halo-C1-6alkoxy; hydroxy; C1-6alkoxy-C1-6alkyl; hydroxy-C1-6alkyl; halo, nitrile; C1-6alkyl-carbonyl; C1-6alkyl-sulfonyl; C3-6cycloalkyl; C3-6cycloalkyl-C1-6alkyl; C3-6cycloalkyl-carbonyl; amino; or heterocyclyl; or two of the groups together with the atoms to which they are attached may form a five or six-membered ring; and
R7 is: halo; C1-6alkyl; C1-6alkoxy; halo-C1-6alkyl; or halo-C1-6alkoxy.

### Claim 8 (depends on 1)

The method of claim 1, wherein the compound is of formula II:
or pharmaceutically acceptable salts thereof,
wherein:
X is: —NRa—; or —O— wherein Ra is hydrogen or C1-6alkyl;
R1 is: C1-6alkyl; C2-6alkenyl; C2-6alkynyl; halo-C1-6alkyl; C1-6alkoxy-C1-6alkyl; hydroxy-C1-6alkyl; amino-C1-6alkyl; C1-6alkylsulfonyl-C1-6alkyl; C3-6cycloalkyl optionally substituted one or more times with C1-6alkyl; C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted one or more times with C1-6alkyl; heterocyclyl optionally substituted one or more times with R7; or heterocyclyl-C1-6alkyl optionally substituted one or more times with R7;
or X and R1 together form C1-6alkyl; C1-6alkoxy-C1-6alkyl; C3-6cycloalkyl optionally substituted one or more times with R6; or C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted one or more times with R6;
or R1 and Ra together with the atoms to which they are attached may form a three- to six-membered heterocyclic ring optionally substituted one or more times with R7;
R2 is: C1-6alkyl; halo; C1-6alkoxy; cyano; C2-6alkynyl; C2-6alkenyl; halo-C1-6alkyl; halo-C1-6alkoxy; C3-6cycloalkyl optionally substituted one or more times with R6; C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted one or more times with R6; —ORb wherein Rb is C1-6alkyl, C3-6cycloalkyl optionally substituted one or more times with R6, or C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted one or more times with R6; or —C(O)—Rc wherein Rc is C1-6alkyl, C1-6alkoxy, amino, or heterocyclyl optionally substituted one or more times with R7;
R3 is: hydrogen; C1-6alkyl; halo-C1-6alkyl; C2-6alkenyl; C2-6alkynyl; hydroxy-C1-6alkyl; C1-6alkoxy-C1-6alkyl; cyano-C1-6alkyl; C1-6alkylsulfonyl; C1-6alkylsulfonylC1-6alkyl; amino-C1-6alkyl; C3-6cycloalkyl optionally substituted one or more times with R6; C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted one or more times with R6; C3-6cycloalkyl-sulfonyl wherein the C3-6cycloalkyl portion is optionally substituted one or more times with R6; heterocyclyl optionally substituted one or more times with R7; heterocyclyl-C1-6alkyl wherein the heterocyclyl portion is optionally substituted one or more times with R7; aryl optionally substituted one or more times with R8; aryl-C1-6alkyl wherein the aryl portion is optionally substituted one or more times with R8; heteroaryl optionally substituted one or more times with R8; heteroaryl-C1-6alkyl wherein the heteroaryl portion is optionally substituted one or more times with R8; or —Y—C(O)—Rd;
Y is C2-6alkylene or a bond;
Rd is C1-6alkyl, C1-6alkoxy, amino, C1-6alkyl-amino, di-C1-6alkyl-amino, halo-C1-6alkyl-amino, di-halo-C1-6alkyl-amino, halo-C1-6alkyl, hydroxy-C1-6alkyl, hydroxy, C1-6alkoxy-C1-6alkyl, cyano-C1-6alkyl, C1-6alkylsulfonylC1-6alkyl, amino-C1-6alkyl, C3-6cycloalkyl optionally substituted one or more times with R6, C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted one or more times with R6 heterocyclyl optionally substituted one or more times with R7, or heterocyclyl-C1-6alkyl wherein the heterocyclyl portion is optionally substituted one or more times with R7;
R4 is: hydrogen; C1-6alkyl; halo; cyano; halo-C1-6alkyl; C2-6alkenyl; C2-6alkynyl; C1-6alkoxy; C1-6alkoxy-C1-6alkyl; hydroxy-C1-6alkyl; C3-6cycloalkyl optionally substituted one or more times with R6; C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted one or more times with R6; or —Y—C(O)—Rd;
R5 is: hydrogen; or C1-6alkyl;
each R6 is independently: C1-6alkyl; halo-C1-6alkyl; C1-6alkoxy; oxo; cyano; halo; or Y—C(O)—Rd;
each R7 is independently: C1-6alkyl; halo-C1-6alkyl; halo; oxo; C1-6alkoxy; C1-6alkylsulfonyl; C1-6alkoxy-C1-6alkyl; cyano; —Y—C(O)—Rd; heterocyclyl; heterocyclyl-C1-6alkyl; C3-6cycloalkyl; C3-6cycloalkyl-C1-6alkyl; or C3-6cycloalkylsulfonyl; and
each R8 is independently: oxo; C1-6alkyl; halo-C1-6alkyl; halo; C1-6alkyl-sulfonyl; C1-6alkoxy; C1-6alkoxy-C1-6alkyl; cyano; heterocyclyl; heterocyclyl-C1-6alkyl; —Y—C(O)—Rd; C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, or C3-6cycloalkyl-sulfonyl.

### Claim 9 (depends on 1)

The method of claim 1, wherein the compound is of formula III:
or pharmaceutically acceptable salts thereof,
wherein:
m is from 0 to 3;
X is: —NRa—; —O—; or —S(O)r— wherein r is from 0 to 2 and Ra is hydrogen or C1-6alkyl;
R1 is: C1-6alkyl; C1-6alkenyl; C1-6alkynyl; halo-C1-6alkyl; C1-6alkoxy-C1-6alkyl; hydroxy-C1-6alkyl; amino-C1-6alkyl; C1-6alkylsulfonyl-C1-6alkyl; C3-6cycloalkyl optionally substituted with C1-6alkyl; C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl; tetrahydrofuranyl; tetrahydrofuranyl-C1-6alkyl; oxetanyl; or oxetan-C1-6alkyl;
or R1 and Ra together with the atoms to which they are attached may form a three to six membered ring that may optionally include an additional heteroatom selected from O, N and S, and which is substituted with oxo, halo or C1-6alkyl;
R2 is: halo; C1-6alkoxy; cyano; C1-6alkynyl; C1-6alkenyl; halo-C1-6alkyl; halo-C1-6alkoxy; C3-6cycloalkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl; C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl; tetrahydrofuranyl; tetrahydro furanyl-C1-6alkyl; acetyl; oxetanyl; or oxetan-C1-6alkyl;
R3 and R4 each independently is: halo; C1-6alkyl; C1-6alkoxy; halo-C1-6alkyl; or halo-C1-6alkoxy; and
R5 is: C1-6alkyl-sulfonyl; cyano; heterocyclyl; heterocyclyl-C1-6alkyl; and carboxy.

### Claim 10 (depends on 1)

The method of claim 1, wherein the compound is selected from:
(4-(4-(cyclopropylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-2-fluoro-5-(2-fluoroethoxy)phenyl)(morpholino)methanone;
(5-(fluoromethoxy)-2-methyl-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(morpholino)methanone;
(3,3-difluoropyrrolidin-1-yl)(4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-5-(2-fluoroethoxy)-2-methoxyphenyl)methanone;
(5-chloro-4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-2-(fluoromethoxy)phenyl)(morpholino)methanone;
(5-chloro-4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-2-(fluoromethoxy)phenyl)(pyrrolidin-1-yl)methanone;
(3,3-difluoropyrrolidin-1-yl)(4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-5-(fluoromethoxy)-2-methoxyphenyl)methanone;
(5-(fluoromethoxy)-2-methyl-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(pyrrolidin-1-yl)methanone;
(3,3-difluoropyrrolidin-1-yl)(4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-2,5-dimethoxyphenyl)methanone;
(3,3-difluoropyrrolidin-1-yl)(5-(2-fluoroethoxy)-2-methoxy-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)methanone;
N4-ethyl-N2-(5-fluoro-2-(2-fluoroethoxy)-4-(morpholinomethyl)phenyl)-5-(trifluoromethyl)pyrimidine-2,4-diamine;
(5-(fluoromethoxy)-2-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(piperidin-1-yl)methanone;
(4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-2-fluoro-5-(2-fluoroethoxy)phenyl)(morpholino)methanone;
(5-(2-fluoroethoxy)-2-methyl-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(morpholino)methanone;
(5-(fluoromethoxy)-2-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(pyrrolidin-1-yl)methanone;
N2-(2-(2-fluoroethoxy)-4-(methylsulfonyl)phenyl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
(4-(4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-5-fluoro-2-(fluoromethoxy)phenyl)(pyrrolidin-1-yl)methanone;
(2-fluoro-5-(2-fluoroethoxy)-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(morpholino)methanone;
N2-(5-fluoro-2-(2-fluoroethoxy)-4-(morpholinomethyl)phenyl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
5-(fluoromethoxy)-2-methoxy-N,N-dimethyl-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)benzamide;
(5-(2-fluoroethoxy)-2-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(pyrrolidin-1-yl)methanone;
N2-(2-(2-fluoroethoxy)-4-(morpholinomethyl)phenyl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
(2-fluoro-5-(fluoromethoxy)-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(pyrrolidin-1-yl)methanone;
5-chloro-N2-(2-(2-fluoroethoxy)-4-(morpholinomethyl)phenyl)-N4-methylpyrimidine-2,4-diamine;
(4-(5-chloro-4-methoxypyrimidin-2-ylamino)-5-(fluoromethoxy)-2-methylphenyl)(pyrrolidin-1-yl)methanone;
5-chloro-N-(2-(2-fluoroethoxy)-4-(morpholinomethyl)phenyl)-4-methoxypyrimidin-2-amine;
5-chloro-N-(2-(2-fluoroethoxy)-4-(methylsulfonyl)phenyl)-4-methoxypyrimidin-2-amine;
5-chloro-N2-(2-(2-fluoroethoxy)-4-(methylsulfonyl)phenyl)-N4-methylpyrimidine-2,4-diamine;
(4-(5-chloro-4-methoxypyrimidin-2-ylamino)-3-(2-fluoroethoxy)phenyl)(morpholino)methanone;
N2-(4-(2-fluoroethoxy)-6-morpholinopyridin-3-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
(3-(2-fluoroethoxy)-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)(morpholino)methanone;
N2-(1-(1-(2-fluoroethyl)piperidin-4-yl)-5-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
5-chloro-N-(1-(1-(2-fluoroethyl)piperidin-4-yl)-5-methyl-1H-pyrazol-4-yl)-4-methoxypyrimidin-2-amine;
N2-(1-(1-(2-fluoroethyl)piperidin-4-yl)-3-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N2-(5-(fluoromethyl)-1-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N2-(1-(2-fluoroethyl)-3-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
N2-(1-(2-fluoroethyl)-5-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
(3-(2-fluoroethoxy)-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)(morpholino)methanone
(4-((5-chloro-4-methoxypyrimidin-2-yl)amino)-3-(2-fluoro ethoxy)phenyl)(morpholino)methanone;
(5-chloro-2-(fluoromethoxy)-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)(morpholino)methanone;
N2-(1-(1-(2-fluoroethyl)piperidin-4-yl)-5-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine;
(3,3-difluoropyrrolidin-1-yl)(4-((4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-5-(2-fluoroethoxy)-2-methoxyphenyl)methanone;
(5-chloro-4-((4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-(fluoromethoxy)phenyl)(morpholino)methanone;
(4-((4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-fluoro-5-methoxyphenyl)(morpholino)methanone;
(4-((4-(ethylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-fluoro-5-(fluoromethoxy)phenyl)(morpholino)methanone;
(2-fluoro-5-methoxy-4-((4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)(morpholino)methanone;
N2-(1-(2-fluoro-1,1,2,2-tetradeutero-ethyl)-5-methyl-1H-pyrazol-4-yl)-N4-methyl-5-(trifluoromethyl)pyrimidine-2,4-diamine; and
(4-(4-(cyclopropylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-2-fluoro-5-(2-fluoromethoxy)phenyl)(morpholino)methanone.

### Claim 11 (depends on 7)

The compound of claim 7, wherein n is 0.

### Claim 12 (depends on 11)

The compound of claim 11, wherein m is 0 or 1.

### Claim 13 (depends on 12)

The compound of claim 12, wherein R3 is C1-6alkoxy with a F18 or 11C atom thereon.

### Claim 14 (depends on 13)

The compound of claim 13, wherein R2 is trifluoromethyl.

### Claim 15 (depends on 14)

The compound of claim 14, wherein R3 is —O11CH3, —CH2CH218F, —CD2CD218F, —CH2CD218F, —CH218F, or —CD218F.

### Claim 16 (depends on 15)

The compound of claim 15, wherein R7 is fluoro.

### Claim 17 (depends on 16)

The compound of claim 16, wherein R1 is cyclopropyl.

### Claim 18

A LRRK2 PET ligand precursor compounds of formula IV:
or a pharmaceutically acceptable salt thereof,
wherein:
R1 is: C1-6alkyl; halo-C1-6alkyl; C2-6alkenyl; C2-6alkynyl; halo-C1-6alkyl; C1-6alkoxy-C1-6alkyl; hydroxy-C1-6alkyl; amino-C1-6alkyl; C1-6alkylsulfonyl-C1-6alkyl; C3-6cycloalkyl optionally substituted with C1-6alkyl or halo; C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl; tetrahydropyranyl; tetrahydrofuranyl; tetrahydro furanyl-C1-6alkyl; oxetanyl; or oxetan-C1-6alkyl;
R2 is: halo; C1-6alkoxy; cyano; C2-6alkynyl; C2-6alkenyl; halo-C1-6alkyl; halo-C1-6alkoxy; C3-6cycloalkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl; C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl; tetrahydrofuranyl; tetrahydrofuranyl-C1-6alkyl; acetyl; oxetanyl; or oxetan-C1-6alkyl;
R5 is: hydrogen; or C1-6alkyl;
R6 is: hydrogen; C1-6alkyl; C1-6alkoxy-C1-6alkyl; hydroxy-C1-6alkyl; amino-C1-6alkyl; C3-6cycloalkyl; C3-6cycloalkyl-C1-6alkyl; heterocyclyl; or heterocyclyl-C1-6alkyl; wherein the C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, heterocyclyl and heterocyclyl-C1-6alkyl each may be optionally substituted with one, two, three or four groups independently selected from: C1-6alkyl; halo-C1-6alkyl; C1-6alkoxy; halo-C1-6alkoxy; hydroxy; hydroxy-C1-6alkyl; halo; nitrile; C1-6alkyl-carbonyl; C1-6alkyl-sulfonyl; C3-6cycloalkyl; C3-6cycloalkyl-C1-6alkyl; C3-6cycloalkyl-carbonyl; amino; or heterocyclyl; or two of the groups together with the atoms to which they are attached may form a five or six-membered ring;
or R5 and R6 together with the nitrogen atom to which they are attached form a three- to seven-membered ring that optionally includes an additional heteroatom selected from O, N and S(O)n, and which is optionally substituted with one, two, three or four groups independently selected from: C1-6alkyl; halo-C1-6alkyl; C1-6alkoxy; halo-C1-6alkoxy; hydroxy; C1-6alkoxy-C1-6alkyl; hydroxy-C1-6alkyl; halo, nitrile; C1-6alkyl-carbonyl; C1-6alkyl-sulfonyl; C3-6cycloalkyl; C3-6cycloalkyl-C1-6alkyl; C3-6cycloalkyl-carbonyl; amino; or heterocyclyl; or two of the groups together with the atoms to which they are attached may form a five or six-membered ring; and
R7 is: halo; C1-6alkyl; C1-6alkoxy; halo-C1-6alkyl; or halo-C1-6alkoxy.

### Claim 19

A method of preparing a LRRK2 PET ligand of formula h:
the method comprising:
reacting a compound of formula f
with a radiolabeled alkylating agent g
R*-L
to provide the radiolabeled aminopyrimidine compound of formula h:
wherein:
R1 is: C1-6alkyl; halo-C1-6alkyl; C2-6alkenyl; C2-6alkynyl; halo-C1-6alkyl; C1-6alkoxy-C1-6alkyl; hydroxy-C1-6alkyl; amino-C1-6alkyl; C1-6alkylsulfonyl-C1-6alkyl; C3-6cycloalkyl optionally substituted with C1-6alkyl or halo; C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl; tetrahydropyranyl; tetrahydrofuranyl; tetrahydro furanyl-C1-6alkyl; oxetanyl; or oxetan-C1-6alkyl;
R2 is: halo; C1-6alkoxy; cyano; C2-6alkynyl; C2-6alkenyl; halo-C1-6alkyl; halo-C1-6alkoxy; C3-6cycloalkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl; C3-6cycloalkyl-C1-6alkyl wherein the C3-6cycloalkyl portion is optionally substituted with C1-6alkyl; tetrahydrofuranyl; tetrahydrofuranyl-C1-6alkyl; acetyl; oxetanyl; or oxetan-C1-6alkyl;
R5 is: hydrogen; or C1-6alkyl;
R6 is: hydrogen; C1-6alkyl; C1-6alkoxy-C1-6alkyl; hydroxy-C1-6alkyl; amino-C1-6alkyl; C3-6cycloalkyl; C3-6cycloalkyl-C1-6alkyl; heterocyclyl; or heterocyclyl-C1-6alkyl; wherein the C3-6cycloalkyl, C3-6cycloalkyl-C1-6alkyl, heterocyclyl and heterocyclyl-C1-6alkyl each may be optionally substituted with one, two, three or four groups independently selected from: C1-6alkyl; halo-C1-6alkyl; C1-6alkoxy; halo-C1-6alkoxy; hydroxy; hydroxy-C1-6alkyl; halo; nitrile; C1-6alkyl-carbonyl; C1-6alkyl-sulfonyl; C3-6cycloalkyl; C3-6cycloalkyl-C1-6alkyl; C3-6cycloalkyl-carbonyl; amino; or heterocyclyl; or two of the groups together with the atoms to which they are attached may form a five or six-membered ring;
or R5 and R6 together with the nitrogen atom to which they are attached form a three- to seven-membered ring that optionally includes an additional heteroatom selected from O, N and S(O)n, and which is optionally substituted with one, two, three or four groups independently selected from: C1-6alkyl; halo-C1-6alkyl; C1-6alkoxy; halo-C1-6alkoxy; hydroxy; C1-6alkoxy-C1-6alkyl; hydroxy-C1-6alkyl; halo, nitrile; C1-6alkyl-carbonyl; C1-6alkyl-sulfonyl; C3-6cycloalkyl; C3-6cycloalkyl-C1-6alkyl; C3-6cycloalkyl-carbonyl; amino; or heterocyclyl; or two of the groups together with the atoms to which they are attached may form a five or six-membered ring;
R7 is: halo; C1-6alkyl; C1-6alkoxy; halo-C1-6alkyl; or halo-C1-6alkoxy;
R* is C1-6alkyl with a F18 or 11C atom thereon; and
L is a leaving group.