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 1094712ノート

反応式

HRID 1094712 の反応式
[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

参加物

6

反応物 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

生成物 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)acetamide収率 60%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-fb8d58ff5d164af0bb391974696158a8
出典データセット
uspto-grants-2012_03
特許番号
US08133998B2

反応ノート

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