반응 #84141

반응 방정식

5-(2-Chloro-primidin-4-yl)-2-((S)-3-fluoro-pyrrolidin-1-yl)-nicotinonitrile

3-amino-N-(1-methyl-piperidin-4-yl)-benzamide

NaOtBu

→

title compound

3-{-4-[5-Cyano-6-((S)-3-fluoro-pyrrolidin-1-yl)-pyridin-3-yl]-pyrimidin-2-ylamino}-N-(1-methyl-piperidin-4-yl)-benzamide

용매

1,4-dioxane

반응 조건

후처리

1. 1
   기타Nitrogen was bubbled through the stirred mixture for 5 minutes
2. 2
   기타The solvent was evaporated in vacuo
3. 3
   workup.DISSOLUTIONthe residue dissolved in DMSO (3 mL)
4. 4
   기타The crude product was purified by reversed phase preparative LC-MS
5. 5
   workup.ADDITIONFractions containing desired product
6. 6
   기타the MeOH evaporated in vacuo
7. 7
   온도The aqueous solution was frozen (−78° C.)
8. 8
   기타the solvent evaporated in vacuo (freeze dried)

실험 절차

5-(2-Chloro-primidin-4-yl)-2-((S)-3-fluoro-pyrrolidin-1-yl)-nicotinonitrile (8) (100 mg, 0.329 mmol), 3-amino-N-(1-methyl-piperidin-4-yl)-benzamide (115 mg, 0.493 mmol), Pd2(dba)3 (30 mg, 0.0327 mmol), NaOtBu (48 mg, 0.499 mmol) and Dave-Phos (130 mg, 0.330 mmol) were dissolved in 1,4-dioxane (3 mL). Nitrogen was bubbled through the stirred mixture for 5 minutes. The reaction mixture was then stirred at 120° C. in the microwave (250 W, stirring) for 2 hours. The solvent was evaporated in vacuo and the residue dissolved in DMSO (3 mL). The crude product was purified by reversed phase preparative LC-MS. Fractions containing desired product were combined and the MeOH evaporated in vacuo. The aqueous solution was frozen (−78° C.) and the solvent evaporated in vacuo (freeze dried). The title compound was obtained as an off-white solid (68 mg, 38%); LCMS, Rt=4.94 min (Method A), m/z 501 (MH+).

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