Diisopropylethylamine → 3-chloro-5-(2-((5-cyano-4-(((1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl)amino)pyrimidin-2-yl)amino)ethyl)pyridine 1-oxide

HRID 1749472Notes

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

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of 4-(((1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl)amino)-2-(methylsulfonyl)pyrimidine-5-carbonitrile (80 mg, crude), 3-(2-aminoethyl)-5-chloropyridine 1-oxide (80 mg, crude) and DIEA (169 mg, 1.31 mmol) in THF (2 mL) was stirred at 85° C. in a microwave reactor for 1 h. After cooling to room temperature, the reaction mixture was concentrated and the residue purified by standard methods to afford the title product (32.6 mg, 0.08 mmol, 22% yield, over three steps). 1H NMR (400 MHz, CD3OD) δ (ppm) 8.30 (s, 1H), 8.16 (s, 1H), 8.08 (s, 1H), 7.51 (s, 1H), 4.32-4.25 (m, 1H), 3.77-3.65 (m, 2H), 3.42-3.40 (s, 1H), 2.99-2.93 (m, 2H), 1.95-1.50 (m, 6H), 1.03 (s, 3H), 0.99 (s, 3H). MS (ESI) m/z 417.2 [M+H]+.

Workup

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

Sources & evidence

ORD record: ord-49172ec82a53446186bfac73420870b4
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09156798B2

Reaction notes

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