Water → Lixivaptan

HRID 440015Notes

Reaction equation

HRID 440015 reaction equation
[CH:1]1[CH:2]=[CH:3][N:4]2[CH2:10][C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[NH:7][CH2:6][C:5]=12.C(N(CC)C(C)C)(C)C.[CH3:24][C:25]1[CH:43]=[CH:42][C:41]([F:44])=[CH:40][C:26]=1[C:27]([NH:29][C:30]1[CH:38]=[CH:37][C:33]([C:34](Cl)=[O:35])=[C:32]([Cl:39])[CH:31]=1)=[O:28].O>C(Cl)Cl>[CH:1]1[CH:2]=[CH:3][N:4]2[CH2:10][C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[N:7]([C:34]([C:33]3[CH:37]=[CH:38][C:30]([NH:29][C:27](=[O:28])[C:26]4[CH:40]=[C:41]([F:44])[CH:42]=[CH:43][C:25]=4[CH3:24])=[CH:31][C:32]=3[Cl:39])=[O:35])[CH2:6][C:5]=12

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 10639786Benzoyl chloride, 2-chloro-4-[(5-fluoro-2-methylbenzoyl)amino]-HCID 1554704810,11-Dihydro-5H-benzo[e]pyrrolo[1,2-a][1,4]diazepine

Product 1

HCID 172997Lixivaptan

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1.84 g of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine in 25 ml of methylene chloride is added 1.30 g of N,N-diisopropylethylamine. While cooling in an ice bath, a solution of 3.45 g of [4-[(2-methyl-5-fluorobenzoyl)amino]-2-chlorobenzoyl chloride in 50 ml of methylene chloride is added. The reaction mixture becomes homogeneous after 5 minutes and is stirred at room temperature for 18 hours. Water is added and the separated organic layer washed with saturated sodium bicarbonate, dried with Na2SO4 and passed through a short pad of hydrous magnesium silicate. The methylene chloride is removed in vacuo to give 4.60 g of the desired product as a glass. A sample is crystallized from ethyl acetate to give crystalline solid, m.p. 191°-195° C.

Workup

  1. temperatureWhile cooling in an ice bath
  2. washthe separated organic layer washed with saturated sodium bicarbonate
  3. dry with materialdried with Na2SO4
  4. customThe methylene chloride is removed in vacuo

Sources & evidence

ORD record
ord-6722e231e5da4338b64794465f74859f
Source dataset
uspto-grants-1996_05
Patent number
US05516774

Reaction notes

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