Diisopropylethylamine → 4-[4-(5,5-Dimethyl-4H-1,3-thiazol-2-yl)piperazin-1-yl]-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidine

HRID 1505643Notes

Reaction equation

HRID 1505643 reaction equation
Cl[C:2]1[C:3]2[CH:10]=[C:9]([CH2:11][C:12]([F:15])([F:14])[F:13])[S:8][C:4]=2[N:5]=[CH:6][N:7]=1.[CH3:16][C:17]1([CH3:28])[S:21][CH:20]([N:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)[N:19]=[CH:18]1.C(N(CC)C(C)C)(C)C>C1COCC1>[CH3:16][C:17]1([CH3:28])[S:21][C:20]([N:22]2[CH2:27][CH2:26][N:25]([C:2]3[C:3]4[CH:10]=[C:9]([CH2:11][C:12]([F:15])([F:14])[F:13])[S:8][C:4]=4[N:5]=[CH:6][N:7]=3)[CH2:24][CH2:23]2)=[N:19][CH2:18]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 90404432HCID 90404432, compoundHCID 904050864-Chloro-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidine

Product 1

HCID 722010864-[4-(5,5-Dimethyl-4H-1,3-thiazol-2-yl)piperazin-1-yl]-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidineYield 82.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 0.5 g of 4-chloro-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidine (2.4 mmol), 0.56 g of 5,5-dimethyl-2-(piperazin-1-yl)-2,5-dihydrothiazole (2.8 mmol), and 0.91 g of N,N-diisopropylethylamine (7.1 mmol) in 20 mL of THF was refluxed for 6 h. After cooling, the mixture was partitioned between ethyl acetate and H2O. The combined organic extracts were washed with brine, dried over MgSO4 and concentrated to a pale yellow solid. Purification by silica gel column chromatography using dichloromethane/methanol (97:3) as eluent gave 0.82 g of 4-(4-(5,5-dimethyl-4,5-dihydrothiazol-2-yl)piperazin-1-yl)-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidine (compound 1) as a pale yellow solid. Its monohydrochloride salt was obtained by adding 1 equivalent of 1N HCl solution in diethyl ether to a solution of compound in ethanol. 1H NMR (400 MHz DMSO-d6): δ 8.46 (s, 1H), 7.70 (s, 1H), 4.37 (s, 1H), 4.09 (m, 4H), 3.81, (m, 4H), 3.45 (q, 2H, J=10.1 Hz), 1.61 (s, 6H). ESI MS [MH+]: 416.1.

Workup

  1. temperatureAfter cooling
  2. customthe mixture was partitioned between ethyl acetate and H2O
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated to a pale yellow solid
  6. customPurification by silica gel column chromatography

Sources & evidence

ORD record
ord-bfd518eaa4954097a53c59de99bc6be3
Source dataset
uspto-grants-2015_12
Patent number
US09216993B2

Reaction notes

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