Dimethylformamide → N-(3-Formyl-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-2-(3-trifluoromethyl-4,5,6,7-tetrahydroindazol-1-yl)-acetamide

HRID 1162744Notes

Reaction equation

HRID 1162744 reaction equation
P(Cl)(Cl)(Cl)=O.CN([CH:9]=[O:10])C.[S:11]1[C:15]([NH:16][C:17](=[O:32])[CH2:18][N:19]2[C:27]3[CH2:26][CH2:25][CH2:24][CH2:23][C:22]=3[C:21]([C:28]([F:31])([F:30])[F:29])=[N:20]2)=[CH:14][C:13]2[CH2:33][CH2:34][CH2:35][CH2:36][C:12]1=2.C([O-])(=O)C.[Na+]>ClCCCl.C(Cl)Cl>[CH:9]([C:14]1[C:13]2[CH2:33][CH2:34][CH2:35][CH2:36][C:12]=2[S:11][C:15]=1[NH:16][C:17](=[O:32])[CH2:18][N:19]1[C:27]2[CH2:26][CH2:25][CH2:24][CH2:23][C:22]=2[C:21]([C:28]([F:31])([F:29])[F:30])=[N:20]1)=[O:10]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 517045Sodium AcetateHCID 59520488N-(4,5,6,7-Tetrahydro-benzo[b]thiophen-2-yl)-2-(3-trifluoromethyl-4,5,6,7-tetrahydro indazol-1-yl)-acetamide

Product 1

HCID 59520503N-(3-Formyl-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-2-(3-trifluoromethyl-4,5,6,7-tetrahydroindazol-1-yl)-acetamideYield 86.4%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Phosphorus oxychloride (399 μl, 4.28 mmol) was added dropwise to a stirred solution of DMF (332 μl, 4.28 mmol) in 1,2-dichloroethane (3 mL). A suspension of N-(4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-2-(3-trifluoromethyl-4,5,6,7-tetrahydroindazol-1-yl)-acetamide (1.64 g, 4.28 mmol) in 1,2-dichloroethane (80 mL) was added portionwise with stirring, and the mixture stirred at RT for 15 min. The resulting yellow solution was refluxed for 20 min. After cooling to RT, the mixture was added to a solution of sodium acetate (13.6 g, 166 mmol, in 130 mL of water) and the solution heated at 50° C. for 20 min. After cooling to RT, the solution was diluted with DCM (100 mL), and the phases separated. The aqueous layer was extracted with DCM (100 mL) and the combined organics washed with saturated sodium bicarbonate solution (100 mL), dried over sodium sulphate and concentrated in vacuo to afford the title compound as a yellow solid (1.52 g, 3.70 mmol, 86%).

Workup

  1. additionwas added portionwise
  2. stirringthe mixture stirred at RT for 15 min
  3. temperatureThe resulting yellow solution was refluxed for 20 min
  4. temperaturethe solution heated at 50° C. for 20 min
  5. temperatureAfter cooling to RT
  6. customthe phases separated
  7. extractionThe aqueous layer was extracted with DCM (100 mL)
  8. washthe combined organics washed with saturated sodium bicarbonate solution (100 mL)
  9. dry with materialdried over sodium sulphate
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d549cb16567347d0a5020b68fb023a23
Source dataset
uspto-grants-2010_10
Patent number
US07820707B2

Reaction notes

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