Diisopropylethylamine → tert-butyl 5-[[(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-propan-2-yloxyiminoacetyl]amino]pyrazole-1-carboxylate

The estimated 80% pure (E)-(3-chloro-4-methanesulfonyl-phenyl)-isopropoxyimino-acetic acid and (prepared as in Example 6, 99 mg, 0.31 mmol), 5-amino-pyrazole-1-carboxylic acid tert-butyl ester (625 mg, 0.34 mmol) and N,N-diisopropylethylamine (162 μL, 0.93 mmol) were combined in acetonitrile (1.25 mL) and cooled in an ice bath. O-(7-Azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (118 mg, 0.31 mmol) was added and the ice bath was removed. After stirring 2 h, the reaction mixture was evaporated in vacuo. The residue was treated with saturated aqueous sodium bicarbonate solution (1 mL) and extracted with chloroform (2×3 mL). The combined organic phases were dried over sodium sulfate and evaporated in vacuo. The residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 60% ethyl acetate/hexanes) to afford (E)-5-[2-(3-chloro-4-methanesulfonyl-phenyl)-2-isopropoxyimino-acetylamino]-pyrazole-1-carboxylic acid tert-butyl ester (30 mg, 20%) as a tan solid after lyophilization from aqueous acetonitrile: H1-NMR (400 MHz, CDCl3) δ=1.41 (6H, d, J=6.3 Hz), 1.72 (9H, s), 3.30 (3H, s), 4.66 (1H, m), 6.85 (1H, d, J=1.8 Hz), 7.60 (2H, m), 7.70 (1H, d, J=1.5 Hz), 8.20 (1H, d, J=8.0 Hz), 11.64 (1H, s).

1. temperaturecooled in an ice bath
2. customthe ice bath was removed
3. customthe reaction mixture was evaporated in vacuo
4. additionThe residue was treated with saturated aqueous sodium bicarbonate solution (1 mL)
5. extractionextracted with chloroform (2×3 mL)
6. dry with materialThe combined organic phases were dried over sodium sulfate
7. customevaporated in vacuo
8. customThe residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 60% ethyl acetate/hexanes)

ORD record

ord-aa58f40a9b5943caac4160135d5ec98f

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07902248B2