1-(2-Fluorophenyl)piperazine → N-(3,5-bis(trifluoromethyl)phenyl)-2-(6-(4-(2-fluorophenyl)piperazine-1-carbonyl)-5-methyl-4-oxo thieno[2,3-d]pyrimidin-3(4H)-yl)acetamide

HRID 1094712노트

반응식

HRID 1094712 반응식
[F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([NH:13][C:14](=[O:30])[CH2:15][N:16]2[C:21](=[O:22])[C:20]3[C:23]([CH3:29])=[C:24]([C:26]([OH:28])=O)[S:25][C:19]=3[N:18]=[CH:17]2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CCN(C(C)C)C(C)C.[F:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1[N:49]1[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[F:10][C:9]([F:11])([F:12])[C:7]1[CH:6]=[C:5]([NH:13][C:14](=[O:30])[CH2:15][N:16]2[C:21](=[O:22])[C:20]3[C:23]([CH3:29])=[C:24]([C:26]([N:52]4[CH2:51][CH2:50][N:49]([C:44]5[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=5[F:42])[CH2:54][CH2:53]4)=[O:28])[S:25][C:19]=3[N:18]=[CH:17]2)[CH:4]=[C:3]([C:2]([F:32])([F:31])[F:1])[CH:8]=1

참가 물질

6

반응물 4

HCID 705291-(2-Fluorophenyl)piperazineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 453959523-(2-(3,5-Bis(trifluoromethyl)phenylamino)-2-oxoethyl)-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylic acid

생성물 1

HCID 25114230N-(3,5-bis(trifluoromethyl)phenyl)-2-(6-(4-(2-fluorophenyl)piperazine-1-carbonyl)-5-methyl-4-oxo thieno[2,3-d]pyrimidin-3(4H)-yl)acetamide수율 60%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 3-(2-(3,5-bis(trifluoromethyl)phenylamino)-2-oxoethyl)-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylic acid (0.24 g, 0.5 mmol) in DCM (5 mL) was added DIEA (0.3 mL, 1.5 mmol), 2-fluorophenylpiperazine (0.060 mL, 0.5 mmol), and HATU (0.25 g, 0.65 mmol). The reaction mixture was stirred at RT overnight. The organic layer was washed with sat. NaHCO3 aq. (20 mL), dried over Na2SO4, and concentrated to give crude product as a gummy solid. Purification by flash column chromatography using a mixture of Et2O:DCM (1:1) as the eluant afforded the 0.19 g of the desired product N-(3,5-bis(trifluoromethyl)phenyl)-2-(6-(4-(2-fluorophenyl)piperazine-1-carbonyl)-5-methyl-4-oxo thieno[2,3-d]pyrimidin-3(4H)-yl)acetamide, (yield: 60%).

후처리

  1. washThe organic layer was washed with sat. NaHCO3 aq. (20 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customto give crude product as a gummy solid
  5. customPurification by flash column chromatography
  6. additiona mixture of Et2O:DCM (1:1) as the eluant

출처 및 근거

ORD 기록
ord-fb8d58ff5d164af0bb391974696158a8
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08133998B2

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