반응 #162525

반응 방정식

1-(1-methyl-6-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine

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

Et3N

→

title compounds

2,4-Diamino-6-((1-(1-methyl-6-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-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 desired compound 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 product

실험 절차

To a 10 mL vial were added 1-(1-methyl-6-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (81 mg, 0.30 mmol), 2,4-diamino-6-chloropyrimidine-5-carbonitrile (50.4 mg, 0.297 mmol) and Et3N (0.083 mL, 0.60 mmol) in DMF (2 mL). 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 desired compound 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 product were combined and lyophilized to give the title compounds (racemate) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.28-1.40 (m, 3 H), 3.71-3.82 (m, 3 H), 3.96-4.07 (m, 2 H), 4.14-4.25 (m, 2 H), 4.72-4.85 (m, 4 H), 5.44-5.58 (m, 1 H), 6.37-6.45 (m, 1 H), 6.45-6.55 (m, 2H), 6.55-6.66 (m, 2 H), 6.68-6.79 (m, 1 H), 7.08-7.16 (m, 1 H), 7.37-7.45 (m, 1 H); ESI-MS m/z [M+H]+ calc'd for C20H23N9O, 406.2; found 406.5.

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