Phenyl isocyanate → HCID 19063681, compound

HRID 482350Notes

Reaction equation

HRID 482350 reaction equation
[C:1]1([N:7]=[C:8]=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:10][CH:11]1[C:17](=[O:18])[N:16]([CH2:19][C:20]([N:22]([CH:29]([CH3:31])[CH3:30])[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:21])[C:15]2[CH:32]=[CH:33][CH:34]=[CH:35][C:14]=2[C:13]([CH3:36])=[N:12]1>C(Cl)Cl>[CH:29]([N:22]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:20](=[O:21])[CH2:19][N:16]1[C:15]2[CH:32]=[CH:33][CH:34]=[CH:35][C:14]=2[C:13]([CH3:36])=[N:12][CH:11]([NH:10][C:8]([NH:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[O:9])[C:17]1=[O:18])([CH3:31])[CH3:30]

Participants

4

Reactant 2

HCID 7672Phenyl isocyanateHCID 19063695HCID 19063695, compound

Product 1

HCID 19063681HCID 19063681, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

According to Process A, phenyl isocyanate (0.065 mL, 0.602 mmol) is added to a solution of 2-(3-Amino-5-methyl-2-oxo-2,3-dihydro-benzo[e][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl-acetamide (219 mg, 0.602 mmol), prepared as in Intermediate 24, under nitrogen in DCM (3 mL). The reaction mixture is stirred at ambient temperature overnight and then concentrated in vacuo. The residue is dissolved in ethyl acetate, washed twice with 1N HCl, dried over anhydrous magnesium sulfate, and then concentrated again to a residue. The crude product is purified by reversed-phase HPLC on a C-18 column with 60% acetonitrile in aqueous trifluoroacetic acid (0.1% v/v) over 30 min. at 100 mL/min. Fractions containing the product are combined, frozen and lyophilized to provide the title compound as a white lyophile (92 mg, 0.190 mmol). 1H NMR (300 MHz, CDCl3) δ=1.02-1.25 (m, 6H); 2.59 (s, 3H); 4.08 (d, J=16.9 Hz, 1H); 4.17 (d, J=16.9 Hz, 1H); 4.93-5.00 (m, 1H); 5.56 (d, J=6.3 Hz, 1H); 7.02-7.61 (m, 14H); MS(FAB): [M+H]+ =484.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue is dissolved in ethyl acetate
  3. washwashed twice with 1N HCl
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated again to a residue
  6. customThe crude product is purified by reversed-phase HPLC on a C-18 column with 60% acetonitrile in aqueous trifluoroacetic acid (0.1% v/v) over 30 min. at 100 mL/min
  7. additionFractions containing the product
  8. temperaturefrozen

Sources & evidence

ORD record
ord-03bf3020e7c54bc1a0c664eccc7fbc3e
Source dataset
uspto-grants-1998_08
Patent number
US05795887

Reaction notes

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