Dimethylformamide → HCID 49871953, compound

HRID 1618107Notes

Reaction equation

HRID 1618107 reaction equation
Cl.[F:2][C:3]1([F:30])[CH2:8][CH2:7][CH:6]([N:9]2[CH2:14][CH2:13][CH:12]([N:15]3[C:23](=[O:24])[C:22]4[C:21]([C:25](O)=[O:26])=[CH:20][C:19]([F:28])=[CH:18][C:17]=4[CH:16]3[CH3:29])[CH2:11][CH2:10]2)[CH2:5][CH2:4]1.C[N:32](C)C=O.C(N(CC)C(C)C)(C)C>>[F:2][C:3]1([F:30])[CH2:4][CH2:5][CH:6]([N:9]2[CH2:10][CH2:11][CH:12]([N:15]3[C:23](=[O:24])[C:22]4[C:21]([C:25]([NH2:32])=[O:26])=[CH:20][C:19]([F:28])=[CH:18][C:17]=4[CH:16]3[CH3:29])[CH2:13][CH2:14]2)[CH2:7][CH2:8]1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 67194031HCID 67194031, compound

Product 1

HCID 49871953HCID 49871953, compoundYield 73.3%

Procedure

To a solution of 2-[1-(4,4-difluorocyclohexyl)piperidin-4-yl]-6-fluoro-1-methyl-3-oxo-2,3-dihydro-1H-isoindole-4-carboxylic acid hydrochloride (80 mg, 0.2 mmol) in N,N-dimethylformamide (2 mL) hydroxybenzotriazole ammonium salt (61 mg, 0.4 mmol), 1-ethyl-3-(3′-dimethylamino) carbodiimide hydrochloric acid salt (77 mg, 0.4 mmol) and N,N-diisopropylethylamine (0.14 mL, 1 mmol) were added. The reaction mixture was stirred at room temperature overnight. The solvent was removed under reduce pressure and the residue was dissolved in ethyl acetate. The solution was washed twice with sodium carbonate saturated aqueous solution, and the organic phase was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude was purified by flash chromatography (dichloromethane/methanol 96:4) to afford the title compound (60 mg, 73%) as a white solid.

Workup

  1. customThe solvent was removed
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. washThe solution was washed twice with sodium carbonate saturated aqueous solution
  4. dry with materialthe organic phase was dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude was purified by flash chromatography (dichloromethane/methanol 96:4)

Sources & evidence

ORD record
ord-59dbf763b7db4b9384a4390353a963be
Source dataset
uspto-grants-2014_07
Patent number
US08765972B2

Reaction notes

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