1,1'-Carbonyldiimidazole → 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 methyl-[(2-oxo-[1,3]dioxolan-4-yl)methyl]-amide

HRID 2184441Notes

Reaction equation

HRID 2184441 reaction equation
[OH:1][CH:2]([CH2:41][OH:42])[CH2:3][N:4]([CH3:40])[C:5]([C:7]1[N:16]2[C:10]([CH2:11][N:12]([C:21]([C:23]3[CH:28]=[CH:27][C:26]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=4[C:35]([F:38])([F:37])[F:36])=[C:25]([CH3:39])[CH:24]=3)=[O:22])[C:13]3[CH:20]=[CH:19][CH:18]=[CH:17][C:14]=3[CH2:15]2)=[CH:9][CH:8]=1)=[O:6].C(N(CC)C(C)C)(C)C.[C:52](N1C=CN=C1)(N1C=CN=C1)=[O:53]>ClCCl>[CH3:40][N:4]([CH2:3][CH:2]1[CH2:41][O:42][C:52](=[O:53])[O:1]1)[C:5]([C:7]1[N:16]2[C:10]([CH2:11][N:12]([C:21]([C:23]3[CH:28]=[CH:27][C:26]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=4[C:35]([F:37])([F:38])[F:36])=[C:25]([CH3:39])[CH:24]=3)=[O:22])[C:13]3[CH:20]=[CH:19][CH:18]=[CH:17][C:14]=3[CH2:15]2)=[CH:9][CH:8]=1)=[O:6]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 1021026810-[(2-Methyl-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid (2,3-dihydroxy-propyl)-methyl-amide

Product 1

HCID 1030422610-[(2-Methyl-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid methyl-[(2-oxo-[1,3]dioxolan-4-yl)methyl]-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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 (2,3-dihydroxypropyl)-methyl-amide of Example 2 (0.50 g, 0.87 mmol) in dichloromethane (17 mL) at 0° C. was added N,N-diisopropylethyl amine (0.30 mL, 1.72 mmol) followed by 1,1′-carbonyldiimidazole (0.14 g, 0.87 mmol). The reaction was allowed to warm to room temperature while stirring overnight then concentrated in vacuo to give a white solid. The residue was partitioned between dichloromethane and water. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a white foam. Purification by flash chromatography using a solvent system of 80% ethyl acetate in hexane provided the title product, which was redissolved in dichloromethane and evaporated to dryness in vacuo to a white foam (0.48 g).

Workup

  1. concentrationthen concentrated in vacuo
  2. customto give a white solid
  3. customThe residue was partitioned between dichloromethane and water
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a white foam
  8. customPurification by flash chromatography

Sources & evidence

ORD record
ord-44b6ed471bc848108635a9e2b3e8205e
Source dataset
uspto-grants-2005_05
Patent number
US06900200B2

Reaction notes

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