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

反応式

HRID 241217 の反応式
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]

参加物

6

反応物 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

生成物 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-benzoxazepine収率 31%

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

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+).

後処理

  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)

出典と根拠

ORDレコード
ord-3651305455da4668bae59b235a2de84c
出典データセット
uspto-grants-2014_02
特許番号
US08648066B2

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