Diisopropylamine → N-(2-Hydroxy-2-methylpropyl)-1-methyl-4-nitro-1H-pyrazole-3-carboxamide
Reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([N+:7]([O-:9])=[O:8])[C:4]([C:10]([OH:12])=O)=[N:3]1.[NH2:13][CH2:14][C:15]([CH3:18])([OH:17])[CH3:16].C(NC(C)C)(C)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>C1COCC1.C(OCC)(=O)C>[OH:17][C:15]([CH3:18])([CH3:16])[CH2:14][NH:13][C:10]([C:4]1[C:5]([N+:7]([O-:9])=[O:8])=[CH:6][N:2]([CH3:1])[N:3]=1)=[O:12]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 2.5 °C
Procedure
To a suspension of 1-methyl-4-nitro-1H-pyrazole-3-carboxylic acid (0.9 g, 5.26 mmol) and 1-amino-2-methylpropan-2-ol (469 mg, 5.26 mmol) in THF (20 mL) cooled to 0-5° C. were added N,N-diisopropylamine (3.67 mL, 21.0 mmol) and 1-propanephosphonic acid cyclic anhydride (8.37 mL, 13.1 mmol, 50% solution in ethyl acetate). The mixture was stirred at 70° C. for 16 hours, cooled to ambient temperature, poured into ethyl acetate (50 mL) and extracted with HCl (1 M, 20 mL). The organic phase was washed with water and brine. The aqueous layers were back-extracted separately with ethyl acetate and dichloromethane. The combined organic layers were dried and concentrated in vacuo to give 1.4 g crude product. The crude material was purified by silica gel chromatography using a methanol/ethyl acetate gradient to give the title compound as colorless foam (391 mg, 31% yield).
Workup
- temperaturecooled to ambient temperature
- extractionextracted with HCl (1 M, 20 mL)
- washThe organic phase was washed with water and brine
- extractionThe aqueous layers were back-extracted separately with ethyl acetate and dichloromethane
- customThe combined organic layers were dried
- concentrationconcentrated in vacuo
- customto give 1.4 g crude product
- customThe crude material was purified by silica gel chromatography
Sources & evidence
- ORD record
- ord-a5873c0601024180b817abf2468b720c
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08623866B2
Reaction notes
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