{3-(Benzyloxycarbonyl-methyl)-1-[isopropyl-(4-methoxy-phenyl)-carbamoylmethyl]-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl}acetic acid benzyl ester → {3-(Benzyloxycarbonyl-methyl)-1-[isopropyl-(4-methoxy-phenyl)-carbamoylmethyl]-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl}acetic acid

HRID 343104Notes

Reaction equation

HRID 343104 reaction equation
[CH2:1]([O:8][C:9](=[O:56])[CH2:10][C:11]1([CH2:45][C:46]([O:48]CC2C=CC=CC=2)=[O:47])[C:17](=[O:18])[N:16]([C:19]([CH:31]([CH3:33])[CH3:32])([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:20](=[O:22])[NH2:21])[C:15]2[CH:34]=[CH:35][CH:36]=[CH:37][C:14]=2[N:13]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:12]1=[O:44])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(OCC)(=O)C.[Pd]>[CH2:1]([O:8][C:9]([CH2:10][C:11]1([CH2:45][C:46]([OH:48])=[O:47])[C:17](=[O:18])[N:16]([C:19]([CH:31]([CH3:33])[CH3:32])([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:20](=[O:22])[NH2:21])[C:15]2[CH:34]=[CH:35][CH:36]=[CH:37][C:14]=2[N:13]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:12]1=[O:44])=[O:56])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 1

HCID 86753588{3-(Benzyloxycarbonyl-methyl)-1-[isopropyl-(4-methoxy-phenyl)-carbamoylmethyl]-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl}acetic acid benzyl ester

Product 1

HCID 86753587{3-(Benzyloxycarbonyl-methyl)-1-[isopropyl-(4-methoxy-phenyl)-carbamoylmethyl]-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl}acetic acidYield 32.6%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

450 mg (0.6 mmols) of {3-(Benzyloxycarbonyl-methyl)-1-[isopropyl-(4-methoxy-phenyl)-carbamoylmethyl]-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl}acetic acid benzyl ester, prepared as in Intermediate 27, is dissolved in 100 mL of ethyl acetate and 45 mg of 10% Pd/C is added. The reaction mixture is then kept under a hydrogen atmosphere with stirring for 2.5 h. The solution is then filtered through celite and the solvent is removed in vacuo. The resulting white solid is purified by reverse phase MPLC in methanol/water 70/30 as eluent to afford 130 mg (32%) of the title compound as a white solid: 1H NMR (CDCl3, 300 MHz) δ7.38-6.54 (m, 18H), 5.29-4.88 (m, 4H), 4.23 (m, 1H), 3.83 (d, J=7.5, 3H), 3.23-2.69 (m, 4H), 1.08-1.02 (m, 6H); low resolution MS m/e 664.

Workup

  1. filtrationThe solution is then filtered through celite
  2. customthe solvent is removed in vacuo
  3. customThe resulting white solid is purified by reverse phase MPLC in methanol/water 70/30 as eluent

Sources & evidence

ORD record
ord-0190849fc4614cf5800ef73ea7104c43
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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