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 1094712Notes

Reaction equation

HRID 1094712 reaction equation
[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

Participants

6

Reactant 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

Product 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)acetamideYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-fb8d58ff5d164af0bb391974696158a8
Source dataset
uspto-grants-2012_03
Patent number
US08133998B2

Reaction notes

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