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 638093

Reaktionsgleichung

Reaktionsgleichung von HRID 638093
[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]

Komponenten

7

Edukt 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

Produkt 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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

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-dimethylaminopropylcarbodiimide 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 1. HPLC shows isomer 1 to be 78% diastereomerically pure.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-e68520504c504716948da8779ef2cbf0
Quelldatensatz
uspto-grants-1985_12
Patentnummer
US04559339

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