Dimethylformamide → Methyl 5-carbamoyl-1-(2-ethoxyethyl)-4-nitro-1h-pyrazole-3-carboxylate

Oxalyl chloride (1.2 mL, 13.76 mmol) and N,N-dimethylformamide (39 μL) were added to a solution of the carboxylic acid of step 2 (1.33 g, 4.63 mmol) in dichloromethane (20 mL) and the reaction mixture stirred at room temperature for 2 hours. The reaction mixture was concentrated in vacuo and azeotroped from dichloromethane (3×50 mL). The product was dissolved in tetrahydrofuran (50 mL), cooled in an ice bath, treated with 0.88 ammonia solution (10 mL) and stirred for 18 hours at room temperature. The mixture was concentrated in vacuo and the residue partitioned between dichloromethane (200 mL) and water (50 mL). The organics phase was dried over magnesium sulphate and concentrated in vacuo to yield the nitro product. 1H NMR (DMSO-D6, 400 MHz) δ: 1.06 (t, 3H), 3.40 (m, 2H), 3.77 (m, 2H), 3.84 (s, 3H), 4.38 (m, 2H), 8.35 (m, 1H), 8.46 (m, 1H). MS APCI+m/z 287 [MH]+.

1. concentrationThe reaction mixture was concentrated in vacuo
2. customazeotroped from dichloromethane (3×50 mL)
3. dissolutionThe product was dissolved in tetrahydrofuran (50 mL)
4. temperaturecooled in an ice bath
5. additiontreated with 0.88 ammonia solution (10 mL)
6. stirringstirred for 18 hours at room temperature
7. concentrationThe mixture was concentrated in vacuo
8. customthe residue partitioned between dichloromethane (200 mL) and water (50 mL)
9. dry with materialThe organics phase was dried over magnesium sulphate
10. concentrationconcentrated in vacuo

ORD record

ord-af46f66822f04e97ac6352e08cdf49f7

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796288B2