Hydrochloric Acid → 7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

HRID 1453367Notes

Reaction equation

HRID 1453367 reaction equation
[CH:1]1[C:11]2[C:10]3=[CH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19]([O:21]C)=[O:20])=[CH:17][C:18]=4[N:9]3[CH2:8][CH:7]=[CH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].Cl>C1COCC1.CO>[CH:1]1[C:11]2[C:10]3=[CH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19]([OH:21])=[O:20])=[CH:17][C:18]=4[N:9]3[CH2:8][CH:7]=[CH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 68832135methyl 7H-indolo[2,1-a][2]benzazepine-10-carboxylate

Product 1

HCID 666396797H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

Methyl 7H-indolo[2,1-a][2]benzazepine-10-carboxylate, 13-cyclohexyl-3-methoxy-6-[[[2-(dimethylamino)-2-oxoethyl]methylamino]carbonyl]- (117 mg, 0.21 mmol) was dissolved into THF/MeOH (1:1, 2 mL) and 1M NaOH (aq.) (0.5 mL, 0.5 mmol). The reaction mixture was heated in a sealed tube with microwave irradiation at 85° C. for 20 min. The reaction was cooled, neutralized with 1M HCl (aq.) (0.5 mL, 0.5 mmol) and concentrated to remove organic solvents. The residue was slurried with H2O and the solids were collected by filtration, flushed with H2O, and purified by preparative HPLC to yield 7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-3-methoxy-6-[[[2-(dimethylamino)-2-oxoethyl]methylamino]carbonyl]- (71 mg, 0.13 mmol, 63%) as a yellow solid. Mixture of amide rotamers: 1HNMR (500 MHz, CD3OD) δ 8.24 (br s, 1H), 7.88 (d, J=8.4 Hz, 1H), 7.71 (d, J=8.4 Hz, 1H), 7.56 (d, J=8.4 Hz, 1H), 7.18-6.88 (m, 2H), 7.14 (dd, J=8.4, 2.2 Hz, 1H), 5.14 (br s, 1H), 4.49-4.12 (m, 2H), 3.97-3.88 (m, 1H), 3.93 (s, 3H), 3.15-2.83 (m, 7H), 2.56 (s, 1.5H), 2.42 (s, 1.5H), 2.23-1.73 (m, 6H), 1.59-1.17 (m, 4H). LCMS: m/e 530 (M+H)+, ret time 1.40 min, column A, 2 minute gradient.

Workup

  1. temperatureThe reaction was cooled
  2. concentrationconcentrated
  3. customto remove organic solvents
  4. filtrationthe solids were collected by filtration
  5. customflushed with H2O
  6. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-2e98e26c798e4951b12149e77560ef8f
Source dataset
uspto-grants-2009_01
Patent number
US07473688B2

Reaction notes

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