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 241203노트

반응식

HRID 241203 반응식
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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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+).

후처리

  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

출처 및 근거

ORD 기록
ord-15db2907bfb043fa8e031ddd2d72cdc8
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08648066B2

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