반응 #162524

반응 방정식

1-(6-(3,3-difluoroazetidin-1-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine

2,4-diamino-6-chloropyrimidine-5-carbonitrile

Et3N

→

title compound

2,4-Diamino-6-((1-(6-(3,3-difluoroazetidin-1-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)pyrimidine-5-carbonitrile

용매

DMF

EtOAc

반응 조건

후처리

1. 1
   세척washed with saturated NH4Cl (3×)
2. 2
   건조The combined organic layers were dried over MgSO4
3. 3
   여과filtered
4. 4
   농축concentrated
5. 5
   기타The product was precipitated with ether
6. 6
   여과filtered
7. 7
   기타purified by silica gel column chromatography
8. 8
   세척eluting with 1:1 EtOAc/hexane to 100% EtOAc to 9:1 EtOAc/MeOH gradient
9. 9
   기타The resulting yellow foam was further purified by preparative HPLC
10. 10
    세척eluting with 20-40% ACN in water (with 0.05% ammonium bicarbonate)
11. 11
    workup.ADDITIONThe fractions containing the desired product

실험 절차

To a 10 mL vial were added 1-(6-(3,3-difluoroazetidin-1-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (61 mg, 0.23 mmol) in DMF (2 mL) along with 2,4-diamino-6-chloropyrimidine-5-carbonitrile (38.8 mg, 0.229 mmol) and Et3N (0.064 mL, 0.46 mmol). The resulting yellow solution was heated to 90° C. and stirred for 5 hours. The reaction mixture was diluted with EtOAc and washed with saturated NH4Cl (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated. The product was precipitated with ether, filtered, and purified by silica gel column chromatography, eluting with 1:1 EtOAc/hexane to 100% EtOAc to 9:1 EtOAc/MeOH gradient. The resulting yellow foam was further purified by preparative HPLC eluting with 20-40% ACN in water (with 0.05% ammonium bicarbonate). The fractions containing the desired product were combined and lyophilized to give the title compound (racemate) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.29-1.43 (m, 3 H), 3.74-3.85 (m, 3 H), 4.18-4.37 (m, 2 H), 4.41-4.59 (m, 2 H), 5.38-5.52 (m, 1 H), 6.39-6.56 (m, 3 H), 6.57-6.65 (m, 2 H), 6.68-6.76 (m, 1H), 7.39-7.45 (m, 1 H), 7.46-7.53 (m, 1 H); ESI-MS m/z [M+H]+ calc'd for C18H19F2N9, 400.2; found 400.4.

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