Triethylamine → HCID 18449083, compound

HRID 1270177Notes

Reaction equation

HRID 1270177 reaction equation
[CH:1]1([C:7]2[CH:32]=[CH:31][C:10]([C:11]([N:13]3[C:19]4[CH:20]=[C:21]([C:24]([O:26][CH3:27])=[O:25])[CH:22]=[CH:23][C:18]=4[CH2:17][N:16]4[CH:28]=[CH:29][CH:30]=[C:15]4[CH2:14]3)=[O:12])=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.O=C(Cl)[O:35][C:36](Cl)(Cl)[Cl:37].C(N(CC)CC)C.[CH3:48][N:49]1[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]1>ClCCl>[ClH:37].[CH:1]1([C:7]2[CH:32]=[CH:31][C:10]([C:11]([N:13]3[C:19]4[CH:20]=[C:21]([C:24]([O:26][CH3:27])=[O:25])[CH:22]=[CH:23][C:18]=4[CH2:17][N:16]4[C:28]([C:36]([N:52]5[CH2:53][CH2:54][N:49]([CH3:48])[CH2:50][CH2:51]5)=[O:35])=[CH:29][CH:30]=[C:15]4[CH2:14]3)=[O:12])=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 10426DiphosgeneHCID 531671-MethylpiperazineHCID 18449089HCID 18449089, compound

Product 1

HCID 18449083HCID 18449083, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of methyl 10-(4-cyclohexylbenzoyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-8-carboxylate of Step C (3.38 mmol) in dichloromethane (20 mL) was treated with diphosgene (1.1 equiv.) and triethylamine (1.5 equiv.) and stirred at room temperature overnight. The solvent was then removed in vacuo and the residue was dissolved in dichloromethane (20 mL), and then treated with triethylamine (1.5 equiv) and 1-methylpiperazine (1.5 equiv). The reaction mixture was washed with water, dried over anhydrous magnesium sulfate, filtered and evaporated to dryness. The residue was first chromatographed on silica gel eluting with 2% methanol in dichloromethane, and then chromatographed again eluting with 2% methanol in ethyl acetate to provide the title compound as a white crystalline solid, m.p. 166–168° C. This was converted to the hydrochloride salt by treatment of the free base in anhydrous ethanol with anhydrous hydrogen chloride in dioxane (1.1 equiv.). The salt so obtained was a white crystalline solid, m.p. 203° C. (dec.).

Workup

  1. customThe solvent was then removed in vacuo
  2. dissolutionthe residue was dissolved in dichloromethane (20 mL)
  3. washThe reaction mixture was washed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe residue was first chromatographed on silica gel eluting with 2% methanol in dichloromethane
  8. customchromatographed again
  9. washeluting with 2% methanol in ethyl acetate

Sources & evidence

ORD record
ord-8d3c9ade6fce4bb5bcdf0559c638ce61
Source dataset
uspto-grants-2007_04
Patent number
US07202239B2

Reaction notes

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