Methyl 2-chloroacrylate → dimethyl 13-cyclohexyl-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepine-6,10-dicarboxylate

HRID 1518221Notes

Reaction equation

Cl[C:2](=[CH2:7])[C:3]([O:5][CH3:6])=[O:4].[Cl-].C([N+](CC)(CC)CCCC)C.C(=O)([O-])[O-].[K+].[K+].[NH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[C:33]1[NH:34][C:35]2[C:40]([C:41]=1[CH:42]1[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]1)=[CH:39][CH:38]=[C:37]([C:48]([O:50][CH3:51])=[O:49])[CH:36]=2.C[Si](C=[N+]=[N-])(C)C>CC#N>[CH:42]1([C:41]2[C:40]3[CH:39]=[CH:38][C:37]([C:48]([O:50][CH3:51])=[O:49])=[CH:36][C:35]=3[N:34]3[C:33]=2[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[NH:26][CH:2]([C:3]([O:5][CH3:6])=[O:4])[CH2:7]3)[CH2:43][CH2:44][CH2:45][CH2:46][CH2:47]1

Participants

Conditions

Temperature: 60 °C

Procedure

Methyl chloroacrylate (1.7 eq), triethylbutyl ammonium chloride (0.2 eq) and potassium carbonate (6 eq) were added to a solution of methyl 2-(2-aminophenyl)-3-cyclohexyl-1H-indole-6-carboxylate in dry MeCN (0.02 M). The mixture was heated at 60° C. overnight. The mixture was allowed to cool to RT, filtered and concentrated in vacuo. The residue was taken up in MeOH and 5 eq of trimethylsilyldiazomethane (2 N solution in hexanes) added dropwise. Volatiles were then removed in vacuo and the crude product was purified by flash chromatography (SiO2; 2:8 EtOAc/PE) to afford the title compound as a solid (45%). MS (ES+) m/z 433 (M+H)+.

Workup

temperatureto cool to RT
filtrationfiltered
concentrationconcentrated in vacuo
customVolatiles were then removed in vacuo
customthe crude product was purified by flash chromatography (SiO2; 2:8 EtOAc/PE)

Sources & evidence

ORD record: ord-a5f0c9c7c6ff4e33b5d17667af8bb145
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08232390B2

Reaction notes

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