Diisopropylethylamine → 4-(6-chloro-5-methylpyrimidin-4-yl)-7-(2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine

HRID 241217

반응식

HRID 241217 반응식
Cl.[CH3:2][C:3]1[N:4](C(OC(C)CC)=O)[C:5]2[C:6]([N:22]=1)=[N:7][CH:8]=[C:9]([C:11]1[CH:12]=[CH:13][C:14]3[O:20][CH2:19][CH2:18][NH:17][CH2:16][C:15]=3[CH:21]=1)[CH:10]=2.Cl[C:31]1[C:36]([CH3:37])=[C:35]([Cl:38])[N:34]=[CH:33][N:32]=1.C(N(C(C)C)CC)(C)C>CN1CCCC1=O.C(OCC)(=O)C>[Cl:38][C:35]1[N:34]=[CH:33][N:32]=[C:31]([N:17]2[CH2:16][C:15]3[CH:21]=[C:11]([C:9]4[CH:10]=[C:5]5[NH:4][C:3]([CH3:2])=[N:22][C:6]5=[N:7][CH:8]=4)[CH:12]=[CH:13][C:14]=3[O:20][CH2:19][CH2:18]2)[C:36]=1[CH3:37]

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 8188604,6-Dichloro-5-methylpyrimidineHCID 668205501-methylpropyl 2-methyl-6-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridine-1-carboxylate hydrochloride

생성물 1

HCID 595865474-(6-chloro-5-methylpyrimidin-4-yl)-7-(2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine수율 31%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

A solution of 1-methylpropyl 2-methyl-6-(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridine-1-carboxylate hydrochloride (0.213 g, 0.512 mmol, example 6, step 2), 4,6-dichloro-5-methylpyrimidine (0.100 g, 0.613 mmol), and diisopropylethylamine (0.330 g, 2.56 mmol) in N-methylpyrrolidinone (2 mL) was stirred at room temperature for 17 h. The reaction mixture was diluted with ethyl acetate (100 mL), washed with saturated sodium bicarbonate (50 mL) and brine (25 mL), and dried over sodium sulfate. Filtration, concentration and purification by column chromatography on silica (97:3 dichloromethane/methanol) provided 4-(6-chloro-5-methylpyrimidin-4-yl)-7-(2-methyl-1H-imidazo[4,5-b]pyridin-6-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepine (0.06 g, 31% yield) as a white solid. 1H NMR (400 MHz, CD3OD) δ 8.50 (s, 1H), 8.22 (s, 1H), 8.04 (s, 1H), 7.60 (s, 1H), 7.50 (d, 1H), 7.08 (d, 1H), 4.81 (s, 2H), 4.39-4.32 (m, 2H), 4.03-3.97 (m, 2H), 2.64 (s, 3H), 2.37 (s, 3H); MS (EI) for C21H19ClN6O: 407 (MH+).

후처리

  1. washwashed with saturated sodium bicarbonate (50 mL) and brine (25 mL)
  2. dry with materialdried over sodium sulfate
  3. filtrationFiltration, concentration and purification by column chromatography on silica (97:3 dichloromethane/methanol)

출처 및 근거

ORD 기록
ord-3651305455da4668bae59b235a2de84c
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08648066B2

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