Hydrochloric Acid → N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(1-methyl-1H-indol-3-yl)-N-(2-pyrid in-3-ylethyl)acetamide hydrochloride

HRID 1504142Notes

Reaction equation

HRID 1504142 reaction equation
[CH2:1]([N:3]1[C:9](=[O:10])[C:8]([CH3:12])([CH3:11])[C:7](=[O:13])[N:6]([CH3:14])[C:5]2[CH:15]=[C:16]([CH2:19][NH:20][CH2:21][CH2:22][C:23]3[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=3)[CH:17]=[CH:18][C:4]1=2)[CH3:2].[CH3:29][N:30]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:32]([CH2:39][C:40](O)=[O:41])=[CH:31]1.ON1C2C=CC=CC=2N=N1.[ClH:53].CN(C)CCCN=C=NCC.Cl>C(#N)C.C(O)C.CC(O)C>[ClH:53].[CH2:1]([N:3]1[C:9](=[O:10])[C:8]([CH3:12])([CH3:11])[C:7](=[O:13])[N:6]([CH3:14])[C:5]2[CH:15]=[C:16]([CH2:19][N:20]([CH2:21][CH2:22][C:23]3[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=3)[C:40](=[O:41])[CH2:39][C:32]3[C:33]4[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=4)[N:30]([CH3:29])[CH:31]=3)[CH:17]=[CH:18][C:4]1=2)[CH3:2]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 2541662-(1-methyl-1H-indol-3-yl)acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 669599071-Ethyl-3,3,5-trimethyl-7-[(2-pyridin-3-yl-ethylamino)methyl]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione

Product 1

HCID 50991854N-(1-Ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-ylmethyl)-2-(1-methyl-1H-indol-3-yl)-N-(2-pyrid in-3-ylethyl)acetamide hydrochlorideYield 33.6%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 3776IsopropanolSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 1-ethyl-3,3,5-trimethyl-7-[(2-pyridine 3-ylethylamino)methyl]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione(0.5 g), 1-methyl-3-indoleacetic acid(0.27 g), and 1-hydroxybenzotriazole (HOBT) (0.24 g) in acetonitrile (10 ml), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (WSC) (0.30 g) was added and stirred at room temperature for 3 days. The reaction mixture was concentrated under reduced pressure. Ethyl acetate and water were added to the residue and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (hexane:ethyl acetate=1:3→0:1). The purified product was condensed under reduced pressure. A 1N-hydrogen chloride in ethanol solution (1.1 ml) was added to a 2-propanol solution (5 ml) of the residue, and the liquid was stirred at room temperature, and concentrated under reduced pressure. Ethanol and ether were added to the residue. The precipitated insoluble matter was separated, washed with ether, and dried to give the title compound(0.26 g) as a pale orange white amorphous.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionEthyl acetate and water were added to the residue
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue thus obtained
  7. customwas purified by silica gel column chromatography (hexane:ethyl acetate=1:3→0:1)
  8. customcondensed under reduced pressure
  9. stirringthe liquid was stirred at room temperature
  10. concentrationconcentrated under reduced pressure
  11. additionEthanol and ether were added to the residue
  12. customThe precipitated insoluble matter was separated
  13. washwashed with ether
  14. customdried

Sources & evidence

ORD record
ord-ad3bc02c33de43b89ebdd1f05eba9017
Source dataset
uspto-grants-2015_12
Patent number
US09212187B2

Reaction notes

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