反応 #162516

反応方程式

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

2-amino-4-chloro-6-methylpyrimidine-5-carbonitrile

N-ethyl-N-isopropylpropan-2-amine

→

title compound

収率 58.2%

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

収率 58.2%

溶媒

acetonitrile

反応条件

後処理

1. 1
   濃縮concentrated
2. 2
   その他purified by preparative HPLC (basic mode)
3. 3
   洗浄eluting with 30-45% ACN in water
4. 4
   workup.ADDITIONThe fractions containing the desired compound
5. 5
   抽出extracted with EtOAc (200 mL)
6. 6
   乾燥The combined organic layers were dried over Na2SO4
7. 7
   ろ過filtered
8. 8
   濃縮concentrated in vacuo

実験手順

(S)-1-(6-(1-(Difluoromethyl)-1H-pyrazol-5-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (115 mg, 0.393 mmol), 2-amino-4-chloro-6-methylpyrimidine-5-carbonitrile (100 mg, 0.593 mmol), and N-ethyl-N-isopropylpropan-2-amine (0.21 mL, 1.2 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 taken up in DMF and purified by preparative HPLC (basic mode) eluting with 30-45% ACN in water. The fractions containing the desired compound were combined and extracted with EtOAc (200 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo to give the title compound (97 mg, 58%). 1H NMR (500 MHz, CD3OD) δ ppm 1.41-1.49 (m, 3 H), 3.88 (s, 3 H), 5.91 (q, J=6.67 Hz, 1 H), 6.63 (d, J=2.93 Hz, 1 H), 6.86 (d, J=2.44 Hz, 1 H), 7.49-7.77 (m, 2 H), 7.95 (s, 1 H), 8.19 (d, J=2.93 Hz, 1 H); ESI-MS m/z [M+H]+ calc'd for C19H18F2N10, 425; found 425.

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