반응 #612876

반응 방정식

TFA

DIPEA

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

tert-butyl 3-azabicyclo[3.1.0]hexan-1-ylcarbamate

Na2CO3

→

title compound

6-(1-Amino-3-azabicyclo[3.1.0]hexan-3-yl)-5-(1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

용매

EtOAc

DCM

iPrOH

반응 조건

후처리

1. 1
   기타was sealed
2. 2
   온도After cooling at RT
3. 3
   세척washed with brine
4. 4
   건조dried over Na2SO4
5. 5
   기타the solvent was evaporated off under reduced pressure
6. 6
   기타to give a residue which
7. 7
   온도cooled to 0° C.
8. 8
   workup.STIRRINGwas stirred at RT for 3 h
9. 9
   추출extracted with EtOAc
10. 10
    건조The combined extracts were dried over Na2SO4
11. 11
    기타the solvent was evaporated off under reduced pressure
12. 12
    기타to give a crude product which
13. 13
    기타was purified by preparative SFC (Column 2-EP, from 22% to 27% in 6 min)

실험 절차

DIPEA (96 μL, 0.55 mmol) was added to a mixture of 6-chloro-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 32.1, 117 mg, 0.25 mmol) and (tert-butyl 3-azabicyclo[3.1.0]hexan-1-ylcarbamate, 59.2 mg, 1.2 mmol) in iPrOH (250 μL) in a vial, which was sealed and the RM mixture was stirred at 140° C. for 18 h. After cooling at RT, the RM was dissolved in EtOAc, washed with brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a residue which was dissolved in DCM (1 mL), cooled to 0° C., treated with TFA (0.45 mL, 5.85 mmol) and was stirred at RT for 3 h. The RM was poured into 10% aq. Na2CO3 (10 mL) and extracted with EtOAc. The combined extracts were dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a crude product which was purified by preparative SFC (Column 2-EP, from 22% to 27% in 6 min) to afford the title compound as an amorphous white powder. HPLC (Condition 4) tR=4.2 min, UPLC-MS (Condition 3) tR=0.76 min, m/z=445.1 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 0.56-0.71 (m, 1H) 0.96-1.10 (m, 1H) 1.61-1.79 (m, 1H) 2.26 (s, 1H) 3.22-3.37 (m, 1H) 3.44 (d, J=1.00 Hz, 1H) 3.70 (d, J=1.00 Hz, 1H) 6.40 (d, J=1.56 Hz, 1H) 7.32 (d, J=8.60 Hz, 2H) 7.84 (d, J=8.99 Hz, 3H) 8.07 (d, J=2.35 Hz, 1H) 8.71 (br. s, 1H) 10.24 (s, 1H) 13.00 (br. s, 1H).

출처