Hydrochloric Acid → 14-Cyclohexyl-5-methyl-7,8-dihydroimidazo[4,5,1-jk]indolo[1,2-d][1,4]-benzodiazepine-11-carboxylic acid

HRID 1518233Notes

Reaction equation

HRID 1518233 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:28]([O:30]C)=[O:29])=[CH:12][C:13]=3[N:14]3[C:20]=2[C:19]2[CH:21]=[CH:22][CH:23]=[C:24]4[N:25]=[C:26]([CH3:27])[N:17]([C:18]=24)[CH2:16][CH2:15]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl>O.CO.C1COCC1.O[Li].O>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:28]([OH:30])=[O:29])=[CH:12][C:13]=3[N:14]3[C:20]=2[C:19]2[CH:21]=[CH:22][CH:23]=[C:24]4[N:25]=[C:26]([CH3:27])[N:17]([C:18]=24)[CH2:16][CH2:15]3)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 68704456Methyl 14-cyclohexyl-5-methyl-7,8-dihydroimidazo[4,5,1-jk]indolo[1,2-d][1,4]benzodiazepine-11-carboxylate

Product 1

HCID 5914281614-Cyclohexyl-5-methyl-7,8-dihydroimidazo[4,5,1-jk]indolo[1,2-d][1,4]-benzodiazepine-11-carboxylic acidYield 68%

Reagents, catalysts & solvents 2

HCID 168937Lithium hydroxide, monohydrateSolventHCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
60 °C

Procedure

Methyl 14-cyclohexyl-5-methyl-7,8-dihydroimidazo[4,5,1-jk]indolo[1,2-d][1,4]benzodiazepine-11-carboxylate was dissolved in a mixture of H2O/MeOH/THF (1/1/1) (0.015 M) and LiOH.H2O added (4.4 eq). The reaction was stirred with heating at 60° C. for 3 h, before being allowed to cool to RT, acidified with 1N HCl (aq). The volatiles were removed in vacuo and the residue purified by RP-HPLC (stationary phase: column WATERS X-TERRA prep. C18, 5 microns. Mobile phase: MeCN/H2O buffered with 0.1% TFA). Fractions containing the pure compound were combined and freeze dried to afford the title compound as a white powder (68%). 1H NMR (400 MHz, DMSO-d6, 300 K) δ 8.30 (s, 1H), 7.99 (d, 1H, J 8.6), 7.79 (d, 1H, J 7.6), 7.68 (d, 1H, J 8.6), 7.67-7.56 (m, 2H), 5.39-5.29 (m, 1H), 4.80-4.72 (m, 1H), 4.38-4.29 (m, 1H), 4.23-4.14 (m, 1H), 3.14-3.06 (m, 1H), 2.73 (s, 3H), 2.19-2.06 (m, 3H), 1.98-1.90 (m, 1H), 1.78-1.72 (m, 2H), 1.55-1.42 (m, 3H), 1.24-1.14 (m, 1H); MS (ES+) m/z 400 (M+H)+.

Workup

  1. additionadded (4.4 eq)
  2. temperatureto cool to RT
  3. customThe volatiles were removed in vacuo
  4. customthe residue purified by RP-HPLC (stationary phase: column WATERS X-TERRA prep. C18, 5 microns. Mobile phase: MeCN/H2O buffered with 0.1% TFA)
  5. additionFractions containing the pure compound
  6. customfreeze dried

Sources & evidence

ORD record
ord-6c461d59b7ea4a169af53bcd15a64c07
Source dataset
uspto-grants-2012_07
Patent number
US08232390B2

Reaction notes

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