Hydrochloric Acid → 13-cyclohexyl-6-(morpholine-4-carbonyl)-6,7-dihydro-5H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

HRID 860714Notes

Reaction equation

HRID 860714 reaction equation
[OH-].[Na+].[CH:3]1([C:9]2[C:10]3[CH:11]=[CH:12][C:13]([C:35]([O:37]C)=[O:36])=[CH:14][C:15]=3[N:16]3[CH2:22][CH:21]([C:23]([N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[O:24])[CH2:20][C:19]4[CH:31]=[CH:32][CH:33]=[CH:34][C:18]=4[C:17]=23)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.Cl>CO.O1CCCC1>[CH:3]1([C:9]2[C:10]3[CH:11]=[CH:12][C:13]([C:35]([OH:37])=[O:36])=[CH:14][C:15]=3[N:16]3[CH2:22][CH:21]([C:23]([N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)=[O:24])[CH2:20][C:19]4[CH:31]=[CH:32][CH:33]=[CH:34][C:18]=4[C:17]=23)[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 16072613methyl 13-cyclohexyl-6,7-dihydro-6-(morpholinylcarbonyl)-5H-indolo[2,1-a][2]benzazepine-10-carboxylate

Product 1

HCID 1149652413-cyclohexyl-6-(morpholine-4-carbonyl)-6,7-dihydro-5H-indolo[2,1-a][2]benzazepine-10-carboxylic acidYield 83%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

Sodium hydroxide (200 μL, 0.2 mmol) was added to a solution of the preceding methyl ester (60 mg, 0.127 mmol) in methanol (1.2 mL) and tetrahydrofuran (1.2 mL) in a microwave vial. The vial was sealed and the contents heated at 90° C. for 10 min in a microwave apparatus, at which time the vial was cooled and additional NaOH was added (200 μL, 0.2 mmol). The solution was heated for another 5 min at 90° C. when LC/MS showed complete hydrolysis of the ester. The solution was acidified with dilute hydrochloric acid to precipitate the crude acid. The solid was collected and purified on the Shimadzu preparative liquid chromatograph. The product containing fraction was concentrated on a Speed Vac® to leave the titled compound as a colorless solid (50 mg, 83%). ESI-MS m/z 473 (MH+), 1H NMR (500 MHz, CD3OD) δ 1.24–1.35 (m, 1 H), 1.40–1.55 (m, 2 H), 1.60–1.68 (m, 1 H), 1.77–2.22 (m, 6 H), 2.76 (m, 1 H), 2.88–3.04 (m, 1 H), 3.44–3.51 (m, 1 H), 3.58–3.93 (m, 9 H), 4.47–4.59 (m, 1 H), 4.89 (m, 1 H), 7.31–7.43 (m, 1 H), 7.47 (m, 3 H), 7.72 (m, 1 H), 7.88 (m, 1 H), 8.16 (m, 1 H).

Workup

  1. customThe vial was sealed
  2. temperaturewas cooled
  3. temperatureThe solution was heated for another 5 min at 90° C. when LC/MS
  4. customto precipitate the crude acid
  5. customThe solid was collected
  6. custompurified on the Shimadzu preparative liquid chromatograph
  7. additionThe product containing fraction
  8. concentrationwas concentrated on a Speed Vac®

Sources & evidence

ORD record
ord-8b2153132f9c42b9ab4bf884fce1890f
Source dataset
uspto-grants-2006_12
Patent number
US07153848B2

Reaction notes

Loading…