반응 #162504

반응 방정식

(S)-1-(6-(2-(benzyloxy)pyridin-4-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine hydrochloride

(S)-4-(5-(1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)pyridin-2-ol hydrochloride

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

N-ethyl-N-isopropylpropan-2-amine

→

title compound

수율 46.3%

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

수율 46.3%

용매

acetonitrile

반응 조건

후처리

1. 1
   농축concentrated
2. 2
   workup.DISSOLUTIONThe residue was dissolved in MeOH (10 mL)
3. 3
   workup.ADDITIONPd/C (10%, 700 mg) was added
4. 4
   온도the reaction mixture was maintained under an atmosphere of hydrogen for 30 minutes
5. 5
   여과The mixture was filtered through Celite
6. 6
   농축concentrated
7. 7
   기타purified by preparative HPLC (basic mode)
8. 8
   세척eluting with 20-35% ACN in water
9. 9
   workup.ADDITIONThe fractions containing the desired product
10. 10
    농축concentrated in vacuo

실험 절차

A mixture of (S)-1-(6-(2-(benzyloxy)pyridin-4-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine hydrochloride (155 mg, 0.393 mmol) and (S)-4-(5-(1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)pyridin-2-ol hydrochloride (120 mg, 0.393 mmol) along with 2,4-diamino-6-chloropyrimidine-5-carbonitrile (100 mg, 0.590 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.205 mL, 1.18 mmol) were combined in acetonitrile (6 mL). The reaction mixture was heated in a microwave reactor at 120° C. for 2 hours and then concentrated. The residue was dissolved in MeOH (10 mL). Pd/C (10%, 700 mg) was added and the reaction mixture was maintained under an atmosphere of hydrogen for 30 minutes. The mixture was filtered through Celite and concentrated. The residue was taken up in DMF and purified by preparative HPLC (basic mode) eluting with 20-35% ACN in water. The fractions containing the desired product were combined and concentrated in vacuo to give the title compound (73 mg, 46%). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.22-1.32 (m, 3 H), 3.80 (br s, 3 H), 5.58 (quin, J=6.71 Hz, 1 H), 6.31 (d, J=6.83 Hz, 1 H), 6.48 (br s, 2 H), 6.52-6.63 (m, 5 H), 6.66 (d, J=7.81 Hz, 1 H), 7.52 (d, J=6.35 Hz, 1 H), 7.72 (d, J=2.93 Hz, 1 H), 7.80 (s, 1 H); ESI-MS m/z [M+H]+ calc'd for C20H19N9O, 402; found 402.

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