반응 #160993

반응 방정식

DIPEA

6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinamide

methyl-3-pyrrolidine carboxylate hydrochloride

→

title compound

Methyl 1-(5-((4-(chlorodifluoromethoxy)phenyl)carbamoyl)-3-(1H-pyrazol-5-yl)pyridin-2-yl)pyrrolidine-3-carboxylate

용매

iPrOH

반응 조건

후처리

1. 1
   기타in MW vial, which was flushed with argon
2. 2
   기타sealed
3. 3
   workup.ADDITIONThe RM was diluted with EtOAc
4. 4
   workup.ADDITIONtreated with brine
5. 5
   추출extracted with EtOAc
6. 6
   건조The combined extracts were dried over Na2SO4
7. 7
   기타the solvent was evaporated off under reduced pressure
8. 8
   기타to give the crude product which
9. 9
   기타was purified by flash chromatography (Silica gel column, n-heptane/EtOAc from 40% to 100% EtOAc)

실험 절차

DIPEA (181 μL, 1.035 mmol) was added to a mixture of 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinamide (Stage 36.1, 100 mg, 0.207 mmol), methyl-3-pyrrolidine carboxylate hydrochloride (44.5 mg, 0.269 mmol) and iPrOH (414 μL). in MW vial, which was flushed with argon, sealed and stirred at 130° C. for 24 h. The RM was diluted with EtOAc, treated with brine and extracted with EtOAc. The combined extracts were dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (Silica gel column, n-heptane/EtOAc from 40% to 100% EtOAc) followed by preparative TLC (Silica gel, eluent EtOAc). Additional lyophilization from 1,4-dioxane afforded the title compound as a white light solid. UPLC-MS (Condition 6) tR=1.09 min, m/z=492.1 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.90-2.02 (m, 1H) 2.02-2.14 (m, 1H) 3.06-3.20 (m, 1H) 3.23-3.48 (m, 4H) 3.61 (s, 3H) 6.35-6.48 (m, 1H) 7.34 (d, J=8.78 Hz, 2H) 7.79-7.90 (m, 1H) 7.89 (d, J=8.80 Hz, 2H) 8.03-8.13 (m, 1H) 8.70-8.83 (m, 1H) 10.26 (s, 1H).

출처