Dicyclohexylcarbodiimide → 7-[(1-[2(S)-((1,1-dimethylethoxy)carbonyl)amino-4-methylpentanoyl]-2,3-dihydro-1H-indol-3-yl)methyl]quinazolino(3,2-A)-1,4-benzodiazepin-5,13-(6H,7H)-dione hemihydrate

HRID 638091Notes

Reaction equation

HRID 638091 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]([CH2:10][CH:11]2[NH:17][C:16](=[O:18])[C:15]3[CH:19]=[CH:20][CH:21]=[CH:22][C:14]=3[N:13]3[C:23](=[O:31])[C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][C:29]=4[N:30]=[C:12]23)[CH2:2]1.[CH3:32][C:33]([CH3:47])([O:35][C:36]([NH:38][C@@H:39]([CH2:43][CH:44]([CH3:46])[CH3:45])[C:40]([OH:42])=[O:41])=[O:37])[CH3:34].ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O.C(N(CC)CC)C>[OH2:18].[CH3:34][C:33]([CH3:47])([O:35][C:36]([NH:38][C@@H:39]([CH2:43][CH:44]([CH3:45])[CH3:46])[C:40]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]([CH2:10][CH:11]2[NH:17][C:16](=[O:18])[C:15]3[CH:19]=[CH:20][CH:21]=[CH:22][C:14]=3[N:13]3[C:23](=[O:31])[C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][C:29]=4[N:30]=[C:12]23)[CH2:2]1)=[O:41])=[O:37])[CH3:32].[CH3:47][C:33]([CH3:32])([O:35][C:36]([NH:38][C@@H:39]([CH2:43][CH:44]([CH3:46])[CH3:45])[C:40]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]([CH2:10][CH:11]2[NH:17][C:16](=[O:18])[C:15]3[CH:19]=[CH:20][CH:21]=[CH:22][C:14]=3[N:13]3[C:23](=[O:31])[C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][C:29]=4[N:30]=[C:12]23)[CH2:2]1)=[O:42])=[O:37])[CH3:34]

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 83170L-Leucine, N-((1,1-dimethylethoxy)carbonyl)-HCID 202547197-[(2,3-Dihydro-1H-indol-3-yl)methyl]-quinazolino(3,2-A)-1,4-benzodiazepin-5,13-(6H,7H)-dione

Product 1

HCID 1317144657-[(1-[2(S)-((1,1-dimethylethoxy)carbonyl)amino-4-methylpentanoyl]-2,3-dihydro-1H-indol-3-yl)methyl]quinazolino(3,2-A)-1,4-benzodiazepin-5,13-(6H,7H)-dione hemihydrate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

7-[(2,3-Dihydro-1H-indol-3-yl)methyl]-quinazolino(3,2-A)-1,4-benzodiazepin-5,13-(6H,7H)-dione (50 mg, 0.122 mmole) was dissolved in 2 ml of dry dimethylformamide under nitrogen and treated at room temperature with 2-(S)-(1,1-dimethylethoxycarbonyl)amino-4-methylpentanoic acid (34 mg, 0.146 mmole), 1-hydroxybenzotriazole (20 mg, 0.146 mmole), and dicyclohexylcarbodiimide (30 mg, 0.146 mmole), respectively. The pH of the reaction mixture was adjusted to approximately 8 with triethylamine (20 μl) and the reaction was stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate and saturated sodium bicarbonate solution. The organic phase was washed with 10% citric acid and brine, then dried and concentrated. Silica gel chromatography (95:5 chloroform-methanol) afforded 23 mg of the analytical sample along with 19 mg recovered starting material.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was partitioned between ethyl acetate and saturated sodium bicarbonate solution
  3. washThe organic phase was washed with 10% citric acid and brine
  4. customdried
  5. concentrationconcentrated
  6. customSilica gel chromatography (95:5 chloroform-methanol) afforded 23 mg of the analytical sample along with 19 mg
  7. customrecovered

Sources & evidence

ORD record
ord-e44eb6a82de24209a7ba8670ed996ff2
Source dataset
uspto-grants-1985_12
Patent number
US04559339

Reaction notes

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