4-Methylmorpholine → N,N-dimethyl-6-(4-quinolin-4-yl-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-benzimidazol-2-amine

HRID 241203ノート

反応式

HRID 241203 の反応式
CO[C:3](=O)[NH:4][C:5]1[NH:9][C:8]2[CH:10]=[C:11]([C:14]3[CH:15]=[CH:16][C:17]4[O:23][CH2:22][CH2:21][N:20]([C:24]5[C:33]6[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=6)[N:27]=[CH:26][CH:25]=5)[CH2:19][C:18]=4[CH:34]=3)[CH:12]=[CH:13][C:7]=2[N:6]=1.F[P-](F)(F)(F)(F)F.Cl[C:44](N(C)C)=[N+](C)C.CN1CCOCC1>CN(C)C=O.C(OCC)(=O)C>[CH3:44][N:4]([CH3:3])[C:5]1[NH:9][C:8]2[CH:10]=[C:11]([C:14]3[CH:15]=[CH:16][C:17]4[O:23][CH2:22][CH2:21][N:20]([C:24]5[C:33]6[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=6)[N:27]=[CH:26][CH:25]=5)[CH2:19][C:18]=4[CH:34]=3)[CH:12]=[CH:13][C:7]=2[N:6]=1

参加物

6

反応物 3

HCID 79724-MethylmorpholineHCID 10989639Chloro-N,N,N',N'-tetramethylformamidinium HexafluorophosphateHCID 59586222Methyl [6-(4-quinolin-4-yl-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-benzimidazol-2-yl]carbamate

生成物 1

HCID 59586593N,N-dimethyl-6-(4-quinolin-4-yl-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-benzimidazol-2-amine収率 48%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of 4-(4-quinolin-4-yl-2,3,4,5-tetrahydrobenzoxazepin-7-yl)benzene-1,2-diamine (example 2) (50 mg, 0.13 mmol), N-(chloro(dimethylamino)methylene)-N-methylmethanaminium hexafluorophosphate (44 mg, 0.16 mmol) and N-methylmorpholine (0.20 g, 1.9 mmol) in N,N-dimethylformamide (10 mL) was heated to 140° C. for 1 hour. After cooling the reaction was diluted with ethyl acetate (80 mL), and washed twice with water (2×20 mL) and brine (20 mL). The solution was dried over anhydrous sodium sulfate, filtered and concentrated to a solid residue. The residue was then taken into N,N-dimethylformamide (3 mL), then diluted with chloroform (15 mL). The resulting solid was collected by filtration and the filter cake was precipitated once more using the same technique to give N,N-dimethyl-6-(4-quinolin-4-yl-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-benzimidazol-2-amine (27 mg, 48% yield) as a gray powder. 1H NMR (400 MHz, d6-DMSO): 8.56 (d, 1H), 8.30 (d, 1H), 8.06-7.97 (m, 2H), 7.90 (br s, 1H), 7.72 (t, 1H), 7.62 (br s, 1H), 7.56 (m, 2H), 7.48 (d, 1H), 6.99 (dd, 2H), 5.28 (s, 2H), 4.61 (s, 2H), 4.38 (s, 2H), 3.28 (s, 6H); MS (EI) for C27H25N5O: 436 (MH+).

後処理

  1. temperatureAfter cooling the reaction
  2. washwashed twice with water (2×20 mL) and brine (20 mL)
  3. dry with materialThe solution was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to a solid residue
  6. additiondiluted with chloroform (15 mL)
  7. filtrationThe resulting solid was collected by filtration
  8. customthe filter cake was precipitated once more

出典と根拠

ORDレコード
ord-15db2907bfb043fa8e031ddd2d72cdc8
出典データセット
uspto-grants-2014_02
特許番号
US08648066B2

反応ノート

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