methyl 13-cyclohexyl-6-hydroxy-6,7-dihydro-5H-indolo[2,1-a][2]benzazepine-10-carboxylate → methyl 13-cyclohexyl-6,7-dihydro-6-oxo-5H-indolo[2,1-a][2]benzazepine-10-carboxylate

HRID 1444622Notes

Reaction equation

HRID 1444622 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:26]([O:28][CH3:29])=[O:27])=[CH:12][C:13]=3[N:14]3[CH2:20][CH:19]([OH:21])[CH2:18][C:17]4[CH:22]=[CH:23][CH:24]=[CH:25][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1>C(Cl)Cl.CCOC(C)=O>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:26]([O:28][CH3:29])=[O:27])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19](=[O:21])[CH2:18][C:17]4[CH:22]=[CH:23][CH:24]=[CH:25][C:16]=4[C:15]=23)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

4

Reactant 1

HCID 16072721methyl 13-cyclohexyl-6-hydroxy-6,7-dihydro-5H-indolo[2,1-a][2]benzazepine-10-carboxylate

Product 1

HCID 58765241methyl 13-cyclohexyl-6,7-dihydro-6-oxo-5H-indolo[2,1-a][2]benzazepine-10-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution (0.05 M) of methyl 13-cyclohexyl-6-hydroxy-6,7-dihydro-5H-indolo[2,1-a][2]benzazepine-10-carboxylate in DCM was treated with DMP (1.3 eq) at 0° C. and left warming to RT and then stirred for 2 h under nitrogen. The solution was then diluted with EtOAc and washed with satd. NaHCO3, water, brine, dried over Na2SO4 and evaporated in vacuo to afford methyl 13-cyclohexyl-6-oxo-6,7-dihydro-5H-indolo[2,1-a][2]benzazepine-10-carboxylate. The crude material was dissolved in 1,2-DCE (0.05 M), 2-dimethylamino-ethylamine was added and the pH adjusted to 6 with AcOH and the solution left stirring for 30 min. NaBH(OAc)3 was added and the solution was left stirring at RT overnight. After diluting with EtOAc, the organic phase was washed with NaOH (1N), water, brine, dried over Na2SO4 and evaporated in vacuo to afford methyl 13-cyclohexyl-6-{[2-(dimethylamino)ethyl]amino}-6,7-dihydro-5H-indolo[2,1-a][2]benzazepine-10-carboxylate. Hydrolysis of the foregoing methyl ester was done with 1M aqueous KOH (6 eq) in dioxane (0.IM) at 60 ° C.; the reaction was complete in 2 h, and the title compound was obtained in 31% yield after RP-HPLC purification and lyophilisation (Conditions: Column: Waters X-TERRA MS C18, 10 micron, 19×150 mm; Gradient: A: H2O+0.1% TFA; B: MeCN+0.1% TFA; 75% A isocratic for 3 min, linear to 20% A in 12 min).

Workup

  1. waitleft
  2. washwashed with satd
  3. dry with materialNaHCO3, water, brine, dried over Na2SO4
  4. customevaporated in vacuo

Sources & evidence

ORD record
ord-d25f5c9382e54244a17d5a6df5abc009
Source dataset
uspto-grants-2010_02
Patent number
US07662809B2

Reaction notes

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