Diethanolamine → 10-[(2-Methyl-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid bis-(2-hydroxy-ethyl)-amide

HRID 2184431Notes

Reaction equation

HRID 2184431 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C:8]([N:10]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[CH2:14][N:13]3[C:21]([C:24](O)=[O:25])=[CH:22][CH:23]=[C:12]3[CH2:11]2)=[O:9])[CH:5]=[CH:4][C:3]=1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[C:33]([F:36])([F:35])[F:34].[NH:37]([CH2:41][CH2:42][OH:43])[CH2:38][CH2:39][OH:40].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>CN(C)C=O.C(OCC)(=O)C>[OH:40][CH2:39][CH2:38][N:37]([CH2:41][CH2:42][OH:43])[C:24]([C:21]1[N:13]2[C:12]([CH2:11][N:10]([C:8]([C:6]3[CH:5]=[CH:4][C:3]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[C:33]([F:36])([F:34])[F:35])=[C:2]([CH3:1])[CH:7]=3)=[O:9])[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[CH2:14]2)=[CH:23][CH:22]=1)=[O:25]

Participants

8

Reactant 5

HCID 8113DiethanolamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 1027808210-(2-methyl-2'-trifluoromethyl-biphenyl-4-carbonyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid

Product 1

HCID 1021026710-[(2-Methyl-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid bis-(2-hydroxy-ethyl)-amideYield 78.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 10-[(2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Step F (0.50 g, 1.02 mmol) and diethanolamine (0.13 g, 1.24 mmol) in N,N-dimethylformamide (4 mL) was added 1-hydroxybenzotriazole (0.15 g, 1.11 mmol) and 1-[3-(dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride (0.22 g, 1.15 mmol) followed by N,N-diisopropylethyl amine (0.27 mL, 1.55 mmol). The reaction mixture was stirred overnight, then diluted with ethyl acetate and washed with water and saturated aqueous sodium bicarbonate. The organic phase was then dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give an orange oil. Purification by flash chromatography on silica gel using a solvent system of 5% methanol in chloroform provided the title compound (0.46 g) as a white foam.

Workup

  1. washwashed with water and saturated aqueous sodium bicarbonate
  2. dry with materialThe organic phase was then dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give an orange oil
  6. customPurification by flash chromatography on silica gel using a solvent system of 5% methanol in chloroform

Sources & evidence

ORD record
ord-1a81f3bd9d014e9f9997ffb94dc49b04
Source dataset
uspto-grants-2005_05
Patent number
US06900200B2

Reaction notes

Loading…