Ethyl Acetate → HCID 49805901, compound

HRID 241212Notes

Reaction equation

HRID 241212 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([N:11]2[CH2:17][C:16]3[CH:18]=[C:19]([C:22]4[CH:23]=[C:24]([NH2:29])[C:25]([NH2:28])=[CH:26][CH:27]=4)[CH:20]=[CH:21][C:15]=3[O:14][CH2:13][CH2:12]2)=[CH:3][CH:2]=1.[N:30]#[C:31]Br.C(OCC)(=O)C>CO.ClCCl>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([N:11]2[CH2:17][C:16]3[CH:18]=[C:19]([C:22]4[CH:27]=[CH:26][C:25]5[N:28]=[C:31]([NH2:30])[NH:29][C:24]=5[CH:23]=4)[CH:20]=[CH:21][C:15]=3[O:14][CH2:13][CH2:12]2)=[CH:3][CH:2]=1

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 10476Cyanogen Bromide2×HCID 66820332HCID 66820332, compound

Product 1

HCID 49805901HCID 49805901, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(4-quinolin-4-yl-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-benzene-1,2-diamine (90 mg, 0.14 mmol, synthesized according to the method of example 2) in methanol (1 mL) was added a 3M solution of cyanogen bromide in dichloromethane (0.10 mL), and the reaction mixture was stirred at room temperature for 8 d. During this time additional cyanogen bromide was added after 1 d (0.10 mL), 2 d (0.20 mL), 3 d (0.20 mL), and 4 d (0.20 mL) reaction time. Ethyl acetate (50 mL) was added, and the solution was washed with 0.5N aqueous sodium hydroxide (2×50 mL), water (50 mL), and brine (50 mL), dried over sodium sulfate, filtered and concentrated. Purification by preparative reverse phase HPLC (0.1% aqueous ammonium acetate-acetonitrile) provided the title Compound as the acetate salt (8 mg, 7% yield) as an off-white solid. 1H NMR (400 MHz, methanol-d4): 8.54 (d, 1H), 8.14 (d, 1H), 7.94 (d, 1H), 7.73 (m, 1H), 7.60-7.47 (m, 4H), 7.38 (m, 1H), 7.31 (d, 1H), 7.10 (d, 1H), 7.07 (d, 1H), 4.70 (s, 2H), 4.41 (m, 2H), 3.93 (m, 2H), 1.94 (s, 3H); MS (EI) for C25H21N5O: 408 (MH+).

Workup

  1. custom(0.10 mL), 2 d (0.20 mL), 3 d (0.20 mL), and 4 d (0.20 mL) reaction time
  2. washthe solution was washed with 0.5N aqueous sodium hydroxide (2×50 mL), water (50 mL), and brine (50 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by preparative reverse phase HPLC (0.1% aqueous ammonium acetate-acetonitrile)

Sources & evidence

ORD record
ord-a6a66a1e61794d2bb584d9fc3a0cf66b
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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