Dimethyl Sulfoxide → 2-(cyclopropylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexyl-amino)pyrimidine-5-carboxamide

HRID 2280767Notes

Reaction equation

[CH:1]1([NH:4][C:5]2[N:10]=[C:9]([NH:11][C@@H:12]3[CH2:17][CH2:16][C@@H:15]([CH3:18])[C@H:14]([OH:19])[CH2:13]3)[C:8]([C:20]#[N:21])=[CH:7][N:6]=2)[CH2:3][CH2:2]1.CS(C)=[O:24]>[OH-].[Na+].OO>[CH:1]1([NH:4][C:5]2[N:10]=[C:9]([NH:11][C@@H:12]3[CH2:17][CH2:16][C@@H:15]([CH3:18])[C@H:14]([OH:19])[CH2:13]3)[C:8]([C:20]([NH2:21])=[O:24])=[CH:7][N:6]=2)[CH2:2][CH2:3]1

Participants

Conditions

Temperature: 50 °C

Procedure

2-(Cyclopropylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexylamino)pyrimidine-5-carbonitrile (265 mg, 0.922 mmol) was dissolved in DMSO (9.222 mL). To the solution was added 10 drops of 50% aqueous sodium hydroxide followed by 10 drops of 30% aqueous hydrogen peroxide at room temperature. The resulting reaction mixture was stirred at 50° C. for 2 h and was then added slowly to 60 mL of ice water. The resulting precipitate was stirred for 30 min, filtered, and washed with water. The solids were dried in a vacuum oven overnight at 45° C. to afford 2-(cyclopropylamino)-4-((1R,3R,4R)-3-hydroxy-4-methylcyclohexyl-amino)pyrimidine-5-carboxamide (229 mg, 0.750 mmol, 81% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.73-8.95 (m, 1H), 8.18-8.42 (m, 1H), 7.17-7.37 (m, 1H), 4.39-4.62 (m, 1H), 3.75-3.99 (m, 1H), 2.81-3.06 (m, 1H), 2.53-2.74 (m, 1H), 2.09-2.34 (m, 1H), 1.82-2.05 (m, 1H), 1.50-1.69 (m, 1H), 0.99-1.24 (m, 3H), 0.81-0.98 (m, 4H), 0.50-0.67 (m, 2H), 0.26-0.47 (m, 2H). MS (ESI) m/z 306.3 [M+1]+.

Workup

customThe resulting reaction mixture
stirringThe resulting precipitate was stirred for 30 min
filtrationfiltered
washwashed with water
customThe solids were dried in a vacuum oven overnight at 45° C.

Sources & evidence

ORD record: ord-30013dfd71a843e6a801bd5c6726a289
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139534B2

Reaction notes

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