Isobutylene oxide → HCID 86686788, compound

HRID 1403152Notes

Reaction equation

[NH2:1][C:2]12[CH2:9][CH2:8][C:5]([CH2:10][NH:11][C:12]3[N:17]=[C:16]([N:18]4[C:22]5[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=5[N:20]=[C:19]4[CH:27]([F:29])[F:28])[CH:15]=[C:14]([N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)[N:13]=3)([CH2:6][CH2:7]1)[CH2:4][CH2:3]2.C(N(CC)C(C)C)(C)C.[CH3:45][C:46]1([CH3:49])[CH2:48][O:47]1>C(O)C>[F:29][CH:27]([F:28])[C:19]1[N:18]([C:16]2[CH:15]=[C:14]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[N:13]=[C:12]([NH:11][CH2:10][C:5]34[CH2:6][CH2:7][C:2]([NH:1][CH2:45][C:46]([CH3:49])([OH:47])[CH3:48])([CH2:9][CH2:8]3)[CH2:3][CH2:4]4)[N:17]=2)[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[N:20]=1

Participants

Conditions

Temperature: 140 °C

Procedure

N-[(4-Aminobicyclo[2.2.2]oct-1-yl)methyl]-4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(morpholin-4-yl)pyrimidin-2-amine (150 mg) was dissolved in ethanol (3 mL), and N,N-diisopropyl ethylamine (81 μL) and 2,2-dimethyloxirane (36 μL) were added thereto, followed by stirring at 120° C. for 1 hour and at 140° C. for 1 hour using a microwave reactor. The reaction solution was concentrated and the residue was purified by amino silica gel column chromatography (hexane:ethyl acetate=20:80, and subsequently chloroform:methanol=98:2) to obtain 1-({4-[({4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(morpholin-4-yl)pyrimidin-2-yl}amino)methyl]bicyclo[2.2.2]oct-1-yl}amino)-2-methylpropan-2-ol (148 mg) as a white amorphous substance.

Workup

concentrationThe reaction solution was concentrated
customthe residue was purified by amino silica gel column chromatography (hexane

Sources & evidence

ORD record: ord-271f03f3409f46c4b6c84cfd79879c2c
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08912180B2

Reaction notes

Loading…