Reaktion #92081

Reaktionsgleichung

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

Ausbeute 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

Ausbeute 56.9%

Lösungsmittel

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe reaction system was refluxed for 2 hours
2. 2
   Temperaturcooled to below 0° C
3. 3
   Temperaturafterwards refluxed for 1 hour
4. 4
   SonstigeWhen most of hydrochloric acid was removed by rotation evaporation
5. 5
   ExtraktionAfter extracted for three times with ethyl acetate
6. 6
   Trocknenthe organic phase was dried over anhydrous sodium sulfate
7. 7
   Sonstigethe solvent was removed under reduced pressure
8. 8
   Sonstigeto give the crude product
9. 9
   SonstigeThe crude product was purified by column chromatography with dichloromethane/methanol (40:1)

Vorschrift

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).

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