4-Methylmorpholine → (S)-5-(3-(Difluoromethoxy)phenyl)-1-ethyl-N-(4-(morpholin-2-yl)phenyl)-1H-pyrazole-3-carboxamide hydrochloride

温度

60 °C

(S)-Tert-butyl 2-(4-(3-(3-(difluoromethoxy)phenyl)-1H-pyrazole-5-carboxamido)phenyl)morpholine-4-carboxylate: In a 25 mL round-bottomed flask, 3-(3-(difluoromethoxy)phenyl)-1H-pyrazole-5-carboxylic acid (515 mg, 2.03 mmol, Eq: 1.1) (preparation described in example 40), (5)-tert-butyl 2-(4-aminophenyl)morpholine-4-carboxylate (513 mg, 1.84 mmol, Eq: 1.00) (preparation described in example 1), N-Methylmorpholine (559 mg, 608 μl, 5.53 mmol, Eq: 3) and HBTU (1.05 g, 2.76 mmol, Eq: 1.5) were combined with DMF (2 ml) to give a yellow solution. The reaction mixture was stirred overnight at 60° C. The mixture was poured into water (10 ml) and extracted twice with EtOAc. The organic layers were washed with NaHCO3, brine, dried over MgSO4, filtered and concentrated in vacuo to give a brown crude mixture. This mixture was diluted with Heptane, stirred for 15 minutes and the suspension was filtered. The resulting solid was washed several times with Heptane to afford the desired compound as a brown solid (550 mg, 58.0%).

1. customto give a yellow solution
2. extractionextracted twice with EtOAc
3. washThe organic layers were washed with NaHCO3, brine
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customto give a brown crude mixture
8. stirringstirred for 15 minutes
9. filtrationthe suspension was filtered
10. washThe resulting solid was washed several times with Heptane

ORDレコード

ord-adcece56e475470181442a1c7dfdd7dc

出典データセット

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09073911B2