Diisopropylethylamine → 2-(((4-(2,2-Difluoropropoxy)pyrimidin-5-yl)methyl)amino)-4-(((1S,3R)-3-hydroxy-3-methylcyclohexyl)amino)pyrimidine-5-carbonitrile

HRID 1749506Notes

Reaction equation

[OH:1][C@:2]1([CH3:21])[CH2:7][CH2:6][CH2:5][C@H:4]([NH:8][C:9]2[C:14]([C:15]#[N:16])=[CH:13][N:12]=[C:11](S(C)(=O)=O)[N:10]=2)[CH2:3]1.[F:22][C:23]([F:35])([CH3:34])[CH2:24][O:25][C:26]1[C:31]([CH2:32][NH2:33])=[CH:30][N:29]=[CH:28][N:27]=1.CCN(C(C)C)C(C)C>C1COCC1>[F:35][C:23]([F:22])([CH3:34])[CH2:24][O:25][C:26]1[C:31]([CH2:32][NH:33][C:11]2[N:10]=[C:9]([NH:8][C@H:4]3[CH2:5][CH2:6][CH2:7][C@:2]([OH:1])([CH3:21])[CH2:3]3)[C:14]([C:15]#[N:16])=[CH:13][N:12]=2)=[CH:30][N:29]=[CH:28][N:27]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-(((1S,3R)-3-hydroxy-3-methylcyclohexyl)amino)-2-(methylsulfonyl)pyrimidine-5-carbonitrile (80 mg, crude), (4-(2,2-difluoropropoxyl)pyrimidin-5-yl)methanamine (50 mg 0.246 mmol), and DIEA (85 mg, 0.66 mmol) in THF (2 mL) was stirred at 100° C. in a microwave reactor for 1 h. The reaction was cooled to room temperature and the mixture was concentrated. The residue was purified by standard methods to give the desired product (26.1 mg, 0.060 mmol, 24% yield). 1H NMR (400 MHz, CD3OD) δ (ppm) 8.69 (s, 1H), 8.41 (s, 1H), 8.11 (s, 1H), 4.73-4.50 (m, 4H), 4.34-4.23 (m, 1H), 1.92-1.08 (m, 14H). MS (ESI) m/z 434.2 [M+H]+.

Workup

temperatureThe reaction was cooled to room temperature
concentrationthe mixture was concentrated
customThe residue was purified by standard methods

Sources & evidence

ORD record: ord-33c1eb4718c349d0872bf1ac656f46f2
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09156798B2

Reaction notes

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