Bromobenzene → 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(morpholin-4-yl)-N-[(1-phenylpiperidin-4-yl)methyl]pyrimidin-2-amine

HRID 1403147노트

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HRID 1403147 반응식
[F:1][CH:2]([F:32])[C:3]1[N:7]([C:8]2[CH:13]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]=[C:10]([NH:20][CH2:21][CH:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)[N:9]=2)[C:6]2[CH:28]=[CH:29][CH:30]=[CH:31][C:5]=2[N:4]=1.Br[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].COCCOC>[F:32][CH:2]([F:1])[C:3]1[N:7]([C:8]2[CH:13]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]=[C:10]([NH:20][CH2:21][CH:22]3[CH2:23][CH2:24][N:25]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[CH2:26][CH2:27]3)[N:9]=2)[C:6]2[CH:28]=[CH:29][CH:30]=[CH:31][C:5]=2[N:4]=1

참가 물질

7

반응물 4

HCID 7961BromobenzeneHCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 866867774-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-morpholin-4-yl-N-(piperidin-4-ylmethyl)pyrimidin-2-amine

생성물 1

HCID 866867734-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(morpholin-4-yl)-N-[(1-phenylpiperidin-4-yl)methyl]pyrimidin-2-amine

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 80711,2-Dimethoxyethane용매

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온도
130 °C

실험 절차

To a mixture of 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-morpholin-4-yl-N-(piperidin-4-ylmethyl)pyrimidin-2-amine (50 mg) and 1,2-dimethoxyethane (1 mL) were added bromobenzene (24 μL), tris(dibenzylideneacetone)dipalladium (0) (6.5 mg), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (11 mg), and potassium phosphate (96 mg), and the mixture was stirred in a microwave reactor at 130° C. for 1 hour. The reaction mixture was filtered through celite, and to the filtrate was added silica gel, followed by concentrating under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate) to obtain 4-[2-(difluoromethyl)-1H-benzimidazol-1-yl]-6-(morpholin-4-yl)-N-[(1-phenylpiperidin-4-yl)methyl]pyrimidin-2-amine (39 mg) as a white powder.

후처리

  1. filtrationThe reaction mixture was filtered through celite
  2. additionto the filtrate was added silica gel
  3. concentrationby concentrating under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate)

출처 및 근거

ORD 기록
ord-cffc402997cb4c589a25c6f48d208e66
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08912180B2

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