Hydrochloric Acid → 13-Cyclohexyl-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepine-10-carboxylic acid

HRID 860720Notes

Reaction equation

[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:25]([O:27]C)=[O:26])=[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[NH:17][CH2:16][CH2:15]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].Cl>CO.O>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:25]([OH:27])=[O:26])=[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[NH:17][CH2:16][CH2:15]3)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of (methyl (13-cyclohexyl-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepin-10-yl)-carboxylate), 5-(4-morpholinylcarbonyl) (25 mg, 0.05 mmol) in MeOH//THF (1:1, 1.6 mL) was added 1 M aqueous NaOH (0.80 mL). The reaction mixture was stirred and heated at 90° C. with microwave irradiation for 15 min in a sealed tube. The clear solution was diluted with H2O (1 mL), neutralized with 1M aqueous HCl (0.80 mL) and concentrated to remove organic solvents. The resultant solids were collected by filtration, washed with H2O and dried under vacuum to yield (13-cyclohexyl-6,7-dihydro-5H-indolo[1,2-d][1,4]benzodiazepin-10-yl)carboxylic acid, 5-(4-morpholinylcarbonyl) (21 mg, 0.05 mmol, 85%) as a light yellow solid. 1HNMR (300 MHz, DMSO-d6) δ 8.19 (s, 1H), 7.87 (d, J=8.4 Hz, 1H), 7.63 (dd, J=8.4, 1.5 Hz, 1H), 7.60–7.47 (m, 3H), 7.29 (dd, J=7.0, 1.5 Hz, 1H), 4.84 (br s, 2H), 3.98–3.55 (m, 4H), 3.23–3.05 (m, 2H), 2.88–2.69 (m, 5H), 2.12–1.63 (m, 6H), 1.51–1.06 (m, 4H). LCMS: m/e 472 (M−H)−, ret time 1.39 min, column A, 3 minute gradient.

Workup

concentrationconcentrated
customto remove organic solvents
filtrationThe resultant solids were collected by filtration
washwashed with H2O
customdried under vacuum

Sources & evidence

ORD record: ord-443742b107af41fe8ce0d472e7f936b8
Source dataset: uspto-grants-2006_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07153848B2

Reaction notes

Loading…