Dimethylformamide → HCID 16780526, compound

Temperature

0 °C

Oxalyl chloride (10 ml, 115 mmol) was added dropwise to a suspension of 5-isobutyl-4-nitro-1H-pyrazol-3-carboxylic acid (5.6 g, 26 mmol) in dichloromethane (70 ml) containing dimethylformamide (0.1 ml) under nitrogen at 0° C. The reaction was stirred at 0° C. for 0.5 hours, allowed to warm to room temperature and stirred for a further 2 hours. The solvent was removed under reduced pressure, the residue was azeotroped with dichloromethane (3×50 ml) and the residue was dissolved in toluene (100 ml). Ammonia gas was bubbled into the solution for 2 hours and the reaction was stirred under nitrogen at room temperature for 18 hours, concentrated under reduced pressure and the residue was suspended in methanol (250 ml). After filtration, the filtrates were concentrated under reduced pressure, the residue was dissolved in ethyl acetate (400 ml) and washed with water (50 ml). The organic phase was filtered, the filtrate was dried over MgSO4 and concentrated under reduced pressure. The filtered solid and residue from the filtrates were combined to give 5-isobutyl-4-nitro-1H-pyrazol-3-carboxylic acid amide (4.8 g) as an off-white solid. 1H NMR (400 MHz, DMSO-D6): δ=13.61-13.81 (1H, brs), 7.80-7.96 (1H, brs), 7.50-7.66 (1H, brs), 2.70-2.76 (2H, d), 1.90-2.01 (1H, m), 0.83-0.88 (6H, d) ppm. LRMS (electrospray): m/z [M+Na]+ 235, [2M+Na]+ 447, [M−H]+ 211, [2M−H]+ 423. Anal. Found C, 45.12; H, 5.68; N, 26.31. C8H12N4O3 requires C, 45.28; H, 5.70; N, 26.40%.

1. temperatureto warm to room temperature
2. stirringstirred for a further 2 hours
3. customThe solvent was removed under reduced pressure
4. customthe residue was azeotroped with dichloromethane (3×50 ml)
5. dissolutionthe residue was dissolved in toluene (100 ml)
6. customAmmonia gas was bubbled into the solution for 2 hours
7. stirringthe reaction was stirred under nitrogen at room temperature for 18 hours
8. concentrationconcentrated under reduced pressure
9. filtrationAfter filtration
10. concentrationthe filtrates were concentrated under reduced pressure
11. dissolutionthe residue was dissolved in ethyl acetate (400 ml)
12. washwashed with water (50 ml)
13. filtrationThe organic phase was filtered
14. dry with materialthe filtrate was dried over MgSO4
15. concentrationconcentrated under reduced pressure

ORD record

ord-4d89301debd64512a90e349080d2df92

Source dataset

uspto-grants-2005_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06967204B2