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 APCl+ 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-Eintrag

ord-2f00b25b73414a3684b873786cdb7878

Quelldatensatz

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08227475B2