Dimethylformamide → 5-Bromo-N-(2-cyclohexyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)-4-methylisoxazole-3-carboxamide
Reaction equation
CN(C=O)C.C(Cl)(=O)C(Cl)=O.[Br:12][C:13]1[O:17][N:16]=[C:15]([C:18]([OH:20])=O)[C:14]=1[CH3:21].[NH2:22][C:23]1[C:24](=[O:36])[N:25]([CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)[N:26]([CH3:29])[C:27]=1[CH3:28].C(N(CC)CC)C>C(Cl)Cl>[Br:12][C:13]1[O:17][N:16]=[C:15]([C:18]([NH:22][C:23]2[C:24](=[O:36])[N:25]([CH:30]3[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]3)[N:26]([CH3:29])[C:27]=2[CH3:28])=[O:20])[C:14]=1[CH3:21]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of DMF (5.33 mL, 68.8 mmol) in DCM (200 mL) was cooled to 0° C. and treated with oxalyl chloride (3.31 ml, 37.9 mmol). 5-bromo-4-methylisoxazole-3-carboxylic acid (7.09 g, 34.4 mmol) was added and stirred under ice cooling for 10 mins. 4-Amino-2-cyclohexyl-1,5-dimethyl-1H-pyrazol-3(2H)-one (Intermediate D) (7.92 g, 37.9 mmol) and triethylamine (14.39 ml, 103 mmol) were added at 0° C. and the mixture stirred at this temperature for 30 mins. The resulting mixture was diluted with DCM and washed with a saturated NaHCO3 (aq) solution. The organic layer was dried over MgSO4, filtered and the solvent removed under reduced pressure. The crude material was adsorbed onto silica and purification by chromatography eluting with 100% TBME afforded the title compound;
Workup
- stirringthe mixture stirred at this temperature for 30 mins
- washwashed with a saturated NaHCO3 (aq) solution
- dry with materialThe organic layer was dried over MgSO4
- filtrationfiltered
- customthe solvent removed under reduced pressure
- customThe crude material was adsorbed onto silica and purification by chromatography
- washeluting with 100% TBME
Sources & evidence
- ORD record
- ord-cc2f8a77f01b41deb666542b386424d8
- Source dataset
- uspto-grants-2016_08
- Patent number
- US09403810B2
Reaction notes
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