Biphenyl → HCID 10211852, compound

HRID 2184434Notes

Reaction equation

HRID 2184434 reaction equation
C1(C2C=CC=CC=2)C=CC=CC=1.[CH3:13][C:14]1[CH:19]=[C:18]([C:20]([N:22]2[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[CH2:26][N:25]3[C:33]([C:36](O)=[O:37])=[CH:34][CH:35]=[C:24]3[CH2:23]2)=[O:21])[CH:17]=[CH:16][C:15]=1[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[C:45]([F:48])([F:47])[F:46].[CH3:49][NH:50][CH2:51][C@@H:52]([C@H:54]([C@@H:56]([C@@H:58]([CH2:60][OH:61])[OH:59])[OH:57])[OH:55])[OH:53].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>[CH3:49][N:50]([CH2:51][C@H:52]([OH:53])[C@@H:54]([OH:55])[C@H:56]([OH:57])[C@H:58]([OH:59])[CH2:60][OH:61])[C:36]([C:33]1[N:25]2[C:24]([CH2:23][N:22]([C:20]([C:18]3[CH:17]=[CH:16][C:15]([C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=4[C:45]([F:48])([F:46])[F:47])=[C:14]([CH3:13])[CH:19]=3)=[O:21])[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[CH2:26]2)=[CH:35][CH:34]=1)=[O:37]

Participants

9

Reactant 6

HCID 7095BiphenylHCID 8567N-Methyl-D-glucamineHCID 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 10211852HCID 10211852, compoundYield 79.3%

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 Example 1, Step F (1.0 g, 2.04 mmol), and N-methyl-D-glucamine (0.48 g, 2.46 mmol) in N,N-dimethylformamide (8 mL) was added 1-hydroxybenzotriazole (0.30 g, 2.22 mmol) and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.43 g, 2.24 mmol) followed by N,N-diisopropylethyl amine (0.55 mL, 3.09 mmol). The reaction mixture was stirred overnight, 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 a yellow foam. Purification by flash chromatography on silica gel using a solvent system of 10% methanol in chloroform provided 1.08 g of title compound 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 a yellow foam
  6. customPurification by flash chromatography on silica gel using a solvent system of 10% methanol in chloroform

Sources & evidence

ORD record
ord-c20bec05df8d4876bc64c20c11da5b35
Source dataset
uspto-grants-2005_05
Patent number
US06900200B2

Reaction notes

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