Trifluoroacetic acid → Methyl 6-{[{2-[[3-(aminosulfonyl)propyl]-(methyl)amino]ethyl}(methyl)amino]methyl}-13-cyclohexyl-5-methyl-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepine-10-carboxylate

HRID 421963Notes

Reaction equation

HRID 421963 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:47]([O:49][CH3:50])=[O:48])=[CH:12][C:13]=3[N:14]3[C:20]=2[C:19]2[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=2[N:17]([CH3:25])[CH:16]([CH2:26][N:27]([CH3:46])[CH2:28][CH2:29][N:30]([CH3:45])[CH2:31][CH2:32][CH2:33][S:34](=[O:44])(=[O:43])[NH:35]C(=O)OC(C)(C)C)[CH2:15]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:35][S:34]([CH2:33][CH2:32][CH2:31][N:30]([CH3:45])[CH2:29][CH2:28][N:27]([CH2:26][CH:16]1[CH2:15][N:14]2[C:13]3[CH:12]=[C:11]([C:47]([O:49][CH3:50])=[O:48])[CH:10]=[CH:9][C:8]=3[C:7]([CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)=[C:20]2[C:19]2[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=2[N:17]1[CH3:25])[CH3:46])(=[O:43])=[O:44]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66674446methyl 13-cyclohexyl-5-methyl-6-(2,5,13,13-tetramethyl-9,9-dioxido-11-oxo-12-oxa-9-thia-2,5,10-triazatetradec-1-yl)-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepine-10-carboxylate

Product 1

HCID 66675171Methyl 6-{[{2-[[3-(aminosulfonyl)propyl]-(methyl)amino]ethyl}(methyl)amino]methyl}-13-cyclohexyl-5-methyl-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepine-10-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methyl 13-cyclohexyl-5-methyl-6-(2,5,13,13-tetramethyl-9,9-dioxido-11-oxo-12-oxa-9-thia-2,5,10-triazatetradec-1-yl)-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepine-10-carboxylate was dissolved in DCM (0.05M) and TFA was added. The mixture was left standing at RT. After 1 h all volatiles were evaporated in vacuo. The residual material was coevaporated with toluene. Methyl 6-{[{2-[[3-(aminosulfonyl)propyl]-(methyl)amino]ethyl}(methyl)amino]methyl}-13-cyclohexyl-5-methyl-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepine-10-carboxylate was obtained as a reddish sticky solid. The material was dissolved in MeOH/THF (0.05 M) and 1M aqueous KOH solution (4 eq.) was added. The mixture was stirred at RT overnight and then warmed for 5 h to 70° C. After cooling to RT the solution was diluted with water and adjusted with 1M aqueous HCl to pH 6. The resulting suspension was extracted with EtOAc. The combined organic phases were washed with brine and dried over Na2SO4. All volatiles were evaporated in vacuo. The residual material was used without further purification in the next reaction (95%). (ES+) m/z 611 (M+H)+.

Workup

  1. waitThe mixture was left
  2. customstanding at RT
  3. customAfter 1 h all volatiles were evaporated in vacuo

Sources & evidence

ORD record
ord-d367f07bb31344089948327bd58fb9a3
Source dataset
uspto-grants-2012_01
Patent number
US08101595B2

Reaction notes

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