Dimethylformamide → 4-amino-N-[1-(2,2-difluoro-ethyl)-piperidin-4-yl]-3-methoxy-benzamide
Reaction equation
N1(O[C:11](=[O:21])[C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[C:14]([O:19][CH3:20])[CH:13]=2)C2C=CC=CC=2N=N1.Cl.Cl.[F:24][CH:25]([F:34])[CH2:26][N:27]1[CH2:32][CH2:31][CH:30]([NH2:33])[CH2:29][CH2:28]1.CN(C)C=O.C(N(CC)CC)C>ClCCl>[NH2:18][C:15]1[CH:16]=[CH:17][C:12]([C:11]([NH:33][CH:30]2[CH2:29][CH2:28][N:27]([CH2:26][CH:25]([F:34])[F:24])[CH2:32][CH2:31]2)=[O:21])=[CH:13][C:14]=1[O:19][CH3:20]Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To a mixture of 1.07 g (3.78 mmole) of 4-amino-3-methoxy-benzoic acid benzotriazol-1-yl ester, 0.90 g (3.78 mmole) of 1-(2,2-difluoro-ethyl)-piperidin-4-ylamine dihydrochloride and 5 mL of dimethylformamide was added 2.63 mL of triethylamine. The mixture was stirred for 20 hours, then taken up in dichloromethane and washed twice with 100 mL of saturated aqueous sodium bicarbonate, once with 50 mL water, once with 50 mL brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with dichloromethane-methanol (gradient, 100:0-90:10) to give 1.05 g of 4-amino-N-[1-(2,2-difluoro-ethyl)-piperidin-4-yl]-3-methoxy-benzamide.
Workup
- washwashed twice with 100 mL of saturated aqueous sodium bicarbonate, once with 50 mL water, once with 50 mL brine
- dry with materialdried over anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe residue was purified by silica gel chromatography
- washeluting with dichloromethane-methanol (gradient, 100:0-90:10)
Sources & evidence
- ORD record
- ord-934855b7942f4bdf8c6747753f11c246
- Source dataset
- uspto-grants-2011_08
- Patent number
- US08003785B2
Reaction notes
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