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 241203Notes

Reaction equation

HRID 241203 reaction equation
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

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

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+).

Workup

  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

Sources & evidence

ORD record
ord-15db2907bfb043fa8e031ddd2d72cdc8
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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