1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-(2,2-difluorocyclopropyl)-3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile

HRID 1853065Notes

Reaction equation

[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[N:12]=[C:11]([C:13]3[CH:14]=[N:15][NH:16][CH:17]=3)[N:10]3[CH:18]=[CH:19][N:20]=[C:9]3[CH:8]=2)[CH:4]=[N:3]1.C1CCN2C(=NCCC2)CC1.[F:32][C:33]1([F:40])[CH2:35][CH:34]1[CH:36]=[CH:37][C:38]#[N:39]>C(#N)C>[F:32][C:33]1([F:40])[CH2:35][CH:34]1[CH:36]([N:15]1[CH:14]=[C:13]([C:11]2[N:10]3[CH:18]=[CH:19][N:20]=[C:9]3[CH:8]=[C:7]([C:5]3[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=3)[N:12]=2)[CH:17]=[N:16]1)[CH2:37][C:38]#[N:39]

Participants

Conditions

Temperature: 50 °C

Procedure

To a mixture of 7-(1-methyl-1H-pyrazol-4-yl)-5-(1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (200 mg; 0.754 mmol) and DBU (56 μL; 0.37 mmol) in acetonitrile (10 mL) was added 3-(2,2-difluorocyclopropyl)acrylonitrile (0.75 mmol). The mixture was stirred in a sealed vial at 50° C. for 24 hours. Further 3-(2,2-difluorocyclopropyl)acrylonitrile (0.4 mmol) was added and the mixture was stirred for a further 24 hours at 50° C. The solvent was removed under reduced pressure and the material was purified on silica gel, eluting with methylene chloride/6% ammonium hydroxide in methanol (50:1 to 15:1) to give 3-(2,2-difluorocyclopropyl)-3-(4-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile (160 mg) as a mixture of diastereoisomers. MS (apci) m/z=395.1 (M+H).

Workup

stirringthe mixture was stirred for a further 24 hours at 50° C
customThe solvent was removed under reduced pressure
customthe material was purified on silica gel
washeluting with methylene chloride/6% ammonium hydroxide in methanol (50:1 to 15:1)

Sources & evidence

ORD record: ord-9689bd4075844bb4a88469befc517e66
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08962596B2

Reaction notes

Loading…