Triethylamine → 7-[(1-[2(R)-((1,1-dimethylethoxy)carbonyl)amino-4-methylpentanoyl]-2,3-dihydro-1H-indol-3-yl)methyl]quinazolino(3,2-A)-1,4-benzodiazepin-5,13-(5H,7H)-dione hydrate

HRID 638094

Reaction equation

HRID 638094 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](O)=[O:41])=[O:37])[CH3:34].Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O>[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]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 637604tert-Butoxycarbonyl-D-leucineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 202547197-[(2,3-Dihydro-1H-indol-3-yl)methyl]-quinazolino(3,2-A)-1,4-benzodiazepin-5,13-(6H,7H)-dione

Product 1

HCID 704799517-[(1-[2(R)-((1,1-dimethylethoxy)carbonyl)amino-4-methylpentanoyl]-2,3-dihydro-1H-indol-3-yl)methyl]quinazolino(3,2-A)-1,4-benzodiazepin-5,13-(5H,7H)-dione hydrate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

7-[(2,3-Dihydro-1H-indol-3-yl)methyl]quinazolino(3,2-A)-1,4-benzodiazepin-5,13-(6H,7H)-dione (250 mg, 0.612 mmole), 2(R)-((1,1-dimethylethoxy)carbonyl)amino-4-methylpentanoic acid (142 mg, 0.734 mmole), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (141 mg, 0.734 mmole), 1-hydroxybenzotriazole (99 mg, 0.734 mmole), and triethylamine (102 μl, 0.734 mmole) were mixed with 12 ml of dry dimethylformamide and the resulting mixture was protected from moisture and stirred at room temperature for 48 hours. The mixture was filtered, rotoevaporated and the residue partitioned between ethyl acetate and water. The organic phase was washed with saturated sodium bicarbonate solution, 10% citric acid and brine, then dried (MgSO4) and concentrated. The crude product thus obtained as a mixture of diastereomers was purified by preparative thick layer chromatography (silica gel, 97:3 hexane-ethyl acetate v/v) to afford isomer 2.

Workup

  1. filtrationThe mixture was filtered
  2. customthe residue partitioned between ethyl acetate and water
  3. washThe organic phase was washed with saturated sodium bicarbonate solution, 10% citric acid and brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-51d9afd6ec0749fbbee308ec339291d0
Source dataset
uspto-grants-1985_12
Patent number
US04559339

Linked notes

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