반응 #92081

반응 방정식

borane THF

compound 24c

(S)-(2-(6-amino-4-(trifluoromethyl)pyridin-3-yl)-4-(3-methylmorpholino)pyrrolo[2,1-f][1,2,4]triazin-6-yl)(4-(methylsulfonyl)piperazin-1-yl)methanone

hydrochloric acid

→

solid

수율 56.9%

(S)-5-(4-(3-methylmorpholino)-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine

수율 56.9%

용매

tetrahydrofuran

반응 조건

후처리

1. 1
   온도the reaction system was refluxed for 2 hours
2. 2
   온도cooled to below 0° C
3. 3
   온도afterwards refluxed for 1 hour
4. 4
   기타When most of hydrochloric acid was removed by rotation evaporation
5. 5
   추출After extracted for three times with ethyl acetate
6. 6
   건조the organic phase was dried over anhydrous sodium sulfate
7. 7
   기타the solvent was removed under reduced pressure
8. 8
   기타to give the crude product
9. 9
   기타The crude product was purified by column chromatography with dichloromethane/methanol (40:1)

실험 절차

At −40° C., 1 M borane-THF (80 mL) was added dropwise to the solution of compound 24c (1.8 g, 3.17 mmol) in 50 mL of tetrahydrofuran. After the reaction proceeded 0.5 hours at this temperature, the reaction system was refluxed for 2 hours, and then cooled to below 0° C. 100 mL of concentrated hydrochloric acid was added dropwise and afterwards refluxed for 1 hour. When most of hydrochloric acid was removed by rotation evaporation, the pH of the solution was adjusted to about 8 by using saturated sodium carbonate solution. After extracted for three times with ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give the crude product. The crude product was purified by column chromatography with dichloromethane/methanol (40:1) to afford white solid (56.9%). m.p. 262° C. 1H NMR (300 MHz, DMSO-d6): δ 8.34 (s, 1H), 7.68 (s, 1H), 6.88 (s, 1H), 6.82 (s, 1H), 6.77 (s, 2H), 4.87 (br s, 1H), 4.47 (br s, 1H), 3.96 (br s, 1H), 3.77-3.41 (m, 8H), 3.11 (s, 6H), 2.87 (s, 3H), 1.32 (s, 3H). LC-MS: 555 (M+1).

출처