반응 #68970

반응 방정식

(R)-5-(8-Chloroisoquinolin-3-ylamino)-3-(1-(dimethylamino)propan-2-yloxy)pyrazine-2-carbonitrile

3-Chloroperoxybenzoic acid

→

title compound

수율 73.1%

(R)-2-(6-(8-Chloroisoquinolin-3-ylamino)-3-cyanopyrazin-2-yloxy)-N,N-dimethylpropan-1-amine oxide

수율 73.1%

용매

DCM

DCM

water

반응 조건

후처리

1. 1
   workup.ADDITIONwas added dropwise to the solution
2. 2
   온도was then warmed to room temperature
3. 3
   기타the layers partitioned
4. 4
   추출the aqueous phase extracted with DCM
5. 5
   세척The combined organic phases were washed with brine
6. 6
   건조dried (Na2SO4)
7. 7
   농축concentrated to dryness
8. 8
   workup.DISSOLUTIONThe residue was dissolved in methanol
9. 9
   기타absorbed on to an SPE (TsOH) cartridge
10. 10
    세척The cartridge was washed with methanol
11. 11
    세척the compound eluted with 2 M and 7 M ammonia in methanol

실험 절차

(R)-5-(8-Chloroisoquinolin-3-ylamino)-3-(1-(dimethylamino)propan-2-yloxy)pyrazine-2-carbonitrile (30 mg, 0.078 mmol) was dissolved in DCM (1 mL) and cooled to −10° C. 3-Chloroperoxybenzoic acid (77% wt., 12 mg, 0.086 mmol) dissolved in DCM (1 mL) was added dropwise to the solution. The reaction mixture was stirred at −10° C. for 15 minutes, and was then warmed to room temperature. The reaction mixture was diluted with water, the layers partitioned and the aqueous phase extracted with DCM. The combined organic phases were washed with brine, dried (Na2SO4) and concentrated to dryness. The residue was dissolved in methanol and absorbed on to an SPE (TsOH) cartridge. The cartridge was washed with methanol and the compound eluted with 2 M and 7 M ammonia in methanol. Preparative HPLC afforded the title compound (23 mg, 0.057 mmol, 73%). 1H NMR (d6-DMSO, 400 MHz) δ 9.25 (s, 1H), 8.39 (s, 1H), 8.30 (s, 1H), 8.12 (s, 1H), 7.73-7.71 (m, 1H), 7.57-7.56 (m, 1H), 6.10-6.07 (m, 1H), 4.16-4.10 (m, 1H), 3.77 (br d, 1H, J=14 Hz), 3.43 (s, 3H), 3.28 (s, 3H), 1.44 (d, 3H, J=6.6 Hz). LC-MS (2) Rt=2.20 min; m/z (ESI+) 399 & 401 (M+H).

출처