반응 #86421

반응 방정식

NaBH3CN

N-(2-(6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-ylamino)-5-(piperidin-4-yl)phenyl)acrylamide TFA salt

NaOAc

acetaldehyde

→

title compound

수율 10.0%

N-(2-(6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-ylamino)-5-(1-ethylpiperidin-4-yl)phenyl)acrylamide

수율 10.0%

용매

EtOH

반응 조건

후처리

1. 1
   workup.STIRRINGthe solution was stirred at room temperature for another 3 hours
2. 2
   기타After removal of all volatiles in vacuo
3. 3
   기타the residue was partitioned between DCM and water
4. 4
   추출The aqueous layer was extracted with chloroform twice
5. 5
   세척The combined extracts were washed with brine
6. 6
   건조dried over anhydrous Na2SO4
7. 7
   여과filtered
8. 8
   기타The filtrate was evaporated under vacuum
9. 9
   기타to give crude product, which
10. 10
    기타was purified by prep-HPLC

실험 절차

To a solution of N-(2-(6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-ylamino)-5-(piperidin-4-yl)phenyl)acrylamide TFA salt (35 g, 0.049 mmol) in EtOH (1 mL), was added NaOAc (4 g, 0.05 mmol) and aqueous acetaldehyde (1 mL, 0.9 mmol, 40%). After the mixture was stirred at room temperature for 1 hour, NaBH3CN (12 g, 0.18 mmol) was added, and the solution was stirred at room temperature for another 3 hours. After removal of all volatiles in vacuo, the residue was partitioned between DCM and water. The aqueous layer was extracted with chloroform twice. The combined extracts were washed with brine, dried over anhydrous Na2SO4 and filtered. The filtrate was evaporated under vacuum to give crude product, which was purified by prep-HPLC to afford the title compound (3 mg, yield: 10%). 1H NMR (400 MHz, MeOH-d4) δ 8.38 (s, 1H), 7.68 (s, 1H), 7.54 (d, 1H), 7.24 (dd, 1H), 6.83 (s, 1H), 6.46-6.35 (m, 3H), 5.81 (d, 1H), 3.97 (s, 6H), 3.74-3.70 (m, 2H), 3.37 (s, 3H), 3.26 (q, 2H), 3.17-3.11 (m, 2H), 2.99-2.96 (m, 1H), 2.26-2.22 (m, 2H), 2.06-1.99 (m, 2H), 1.43 (t, 3H); MS (ESI): 628 [M+H]+.

출처