Ammonia → HCID 178513950, compound

HRID 1403160Notes

Reaction equation

[F:1][CH:2]([F:34])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]=[C:10]([NH:20][C@H:21]3[CH2:26][CH2:25][C@H:24]([C:27](O)=[O:28])[CH2:23][CH2:22]3)[CH:9]=2)[C:6]2[CH:30]=[CH:31][CH:32]=[CH:33][C:5]=2[N:4]=1.ClC(OCC(C)C)=O.C[N:44]1CCOCC1.N>O1CCCC1>[F:34][CH:2]([F:1])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]=[C:10]([NH:20][C@H:21]3[CH2:22][CH2:23][C@H:24]([C:27]([NH2:44])=[O:28])[CH2:25][CH2:26]3)[CH:9]=2)[C:6]2[CH:30]=[CH:31][CH:32]=[CH:33][C:5]=2[N:4]=1

Participants

Conditions

Temperature: 0 °C

Procedure

trans-4-({6-[2-(Difluoromethyl)-1H-benzimidazol-1-yl]-2-(morpholin-4-yl)pyrimidin-4-yl}amino)cyclohexanecarboxylic acid (232 mg) was dissolved in tetrahydrofuran (2.3 mL), and isobutyl chloroformate (70 μL) and 4-methylmorpholine (60 μL) were added thereto at 0° C., followed by stirring at 0° C. for 30 minutes and at room temperature for 2 hours. Subsequently, 28% aqueous ammonia (300 μL) was added thereto at 0° C., followed by stirring for 2 hours. The solvent was evaporated under reduced pressure and purified by silica gel chromatography (hexane:ethyl acetate=40:60-0:100 and chloroform:methanol-100:0-95:5) to obtain trans-4-({6-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-2-(morpholin-4-yl)pyrimidin-4-yl}amino)cyclohexanecarboxamide (230 mg).

Workup

customat 0° C.
customat 0° C.
stirringby stirring for 2 hours
customThe solvent was evaporated under reduced pressure
custompurified by silica gel chromatography (hexane:ethyl acetate=40:60-0:100 and chloroform:methanol-100:0-95:5)

Sources & evidence

ORD record: ord-73be95a5046e44f4ae584106117a6e49
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08912180B2

Reaction notes

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