Diisopropylethylamine → 2-((2-(6-Fluoro-2-oxoindolin-3-yl)ethyl)amino)-4-(((1R,3R)-3-hydroxy-2,2-dimethylcyclohexyl)amino)pyrimidine-5-carbonitrile

HRID 1749535Notes

Reaction equation

[OH:1][C@@H:2]1[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](SC)[N:10]=2)[C:3]1([CH3:20])[CH3:19].Cl.[NH2:22][CH2:23][CH2:24][CH:25]1[C:33]2[C:28](=[CH:29][C:30]([F:34])=[CH:31][CH:32]=2)[NH:27][C:26]1=[O:35].CCN(C(C)C)C(C)C>CC(N(C)C)=O>[F:34][C:30]1[CH:29]=[C:28]2[C:33]([CH:25]([CH2:24][CH2:23][NH:22][C:11]3[N:10]=[C:9]([NH:8][C@@H:4]4[CH2:5][CH2:6][CH2:7][C@@H:2]([OH:1])[C:3]4([CH3:20])[CH3:19])[C:14]([C:15]#[N:16])=[CH:13][N:12]=3)[C:26](=[O:35])[NH:27]2)=[CH:32][CH:31]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 4-(((1R,3R)-3-hydroxy-2,2-dimethylcyclohexyl)amino)-2-(methylthio)pyrimidine-5-carbonitrile (92 mg, crude), 3-(2-aminoethyl)-6-fluoroindolin-2-one hydrochloride (95 mg, 0.41 mmol) and DIEA (122 mg, 0.94 mmol) in DMA (2 mL) was stirred at 90° C. for 1 h. The solvent was evaporated and the residue was purified by standard methods to afford the title compound (36.7 mg, 0.083 mmol, 29% yield for two steps). 1H NMR (400 MHz, CD3OD) δ (ppm) 8.05 (s, 1H), 7.34-7.29 (m, 1H), 6.79-6.69 (m, 1H), 6.69-6.61 (m, 1H), 4.67-4.59 (m, 1H), 3.60-3.44 (m, 4H), 2.29-2.08 (m, 2H), 1.93-1.67 (m, 3H), 1.67-1.49 (m, 3H), 1.02-0.97 (m, 6H). MS (ESI) m/z 439.2 [M+H]+.

Workup

customThe solvent was evaporated
customthe residue was purified by standard methods

Sources & evidence

ORD record: ord-aa866693fff64e84838ce07d0d0d2542
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09156798B2

Reaction notes

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