Water → 4-(Bicyclo[1.1.1]pentan-1-ylamino)-2-(methylthio)pyrimidine-5-carbonitrile

HRID 2280833Notes

Reaction equation

Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]([S:10][CH3:11])[N:3]=1.CCN(C(C)C)C(C)C.Cl.[C:22]12([NH2:27])[CH2:26][CH:24]([CH2:25]1)[CH2:23]2.O>CS(C)=O>[C:22]12([NH:27][C:2]3[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]([S:10][CH3:11])[N:3]=3)[CH2:26][CH:24]([CH2:25]1)[CH2:23]2

Participants

Conditions

Temperature: 60 °C

Procedure

To a stirred solution of 4-chloro-2-(methylthio)pyrimidine-5-carbonitrile (3.0 g, 16 mmol) in DMSO (20 mL) was added DIEA (6.2 g, 48 mmol) and bicyclo[1.1.1]pentan-1-amine hydrochloride (1.9 g, 16 mmol; prepared according to Org. Lett., 13(17): 4746-4748 (2011)). The resulting mixture was stirred at 60° C. for 2 h and then poured into water. The mixture was extracted with ethyl acetate and the combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated to afford the crude product, which was purified by silica gel column chromatography (10% ethyl acetate in petroleum ether) to give the desired product (3.5 g, 14.9 mmol, 93% yield). MS (ESI) m/z=233.2 [M+1]+.

Workup

extractionThe mixture was extracted with ethyl acetate
dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated
customto afford the crude product, which
customwas purified by silica gel column chromatography (10% ethyl acetate in petroleum ether)

Sources & evidence

ORD record: ord-f32a0421d64546fdb02d439a02e40922
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139534B2

Reaction notes

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