Diisopropylethylamine → 2-((3-Chloro-2-(trifluoromethyl)phenethyl)amino)-4-(((1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl)amino)pyrimidine-5-carbonitrile

HRID 1749492Notes

Reaction equation

[OH:1][C@H:2]1[CH2:7][CH2:6][C@@H:5]([NH:8][C:9]2[C:14]([C:15]#[N:16])=[CH:13][N:12]=[C:11](S(C)(=O)=O)[N:10]=2)[CH2:4][C:3]1([CH3:22])[CH3:21].[Cl:23][C:24]1[C:25]([C:33]([F:36])([F:35])[F:34])=[C:26]([CH2:30][CH2:31][NH2:32])[CH:27]=[CH:28][CH:29]=1.CCN(C(C)C)C(C)C>C1COCC1>[Cl:23][C:24]1[C:25]([C:33]([F:34])([F:35])[F:36])=[C:26]([CH:27]=[CH:28][CH:29]=1)[CH2:30][CH2:31][NH:32][C:11]1[N:10]=[C:9]([NH:8][C@@H:5]2[CH2:6][CH2:7][C@H:2]([OH:1])[C:3]([CH3:22])([CH3:21])[CH2:4]2)[C:14]([C:15]#[N:16])=[CH:13][N:12]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-(((1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl)amino)-2-(methylsulfonyl)pyrimidine-5-carbonitrile (75 mg, 0.23 mmol), 2-(3-chloro-2-(trifluoromethyl)phenyl)ethanamine (100 mg, crude) and DIEA (85 mg, 0.66 mmol) in THF (2 mL) was stirred at 100° C. in a microwave reactor for 1.5 h. After cooling to room temperature, the reaction mixture was concentrated and the residue was purified by standard methods to afford the title compound (42.2 mg, 0.090 mmol, 39% yield). 1H NMR (400 MHz, CD3OD) δ (ppm) 8.10-8.03 (m, 1H), 7.48-4.41 (m, 2H), 7.30 (m, 1H), 4.31-4.28 (m, 1H), 3.73-3.69 (m, 1H), 3.63-3.56 (m, 1H), 3.39-3.37 (m, 1H), 3.17-3.14 (m, 2H), 1.88-1.44 (m, 6H), 0.97 (s, 3H), 0.96 (s, 3H). MS (ESI) m/z 468.1 [M+H]+.

Workup

temperatureAfter cooling to room temperature
concentrationthe reaction mixture was concentrated
customthe residue was purified by standard methods

Sources & evidence

ORD record: ord-0827cf8c52cf444fa43a5f6ccf7c4ba7
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09156798B2

Reaction notes

Loading…