Hydrochloric Acid → 6-chloro-5-[4-(2-oxopyrrolidin-1-yl)phenyl]-1H-indole-3-carboxylic acid

HRID 338374Notes

Reaction equation

HRID 338374 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13]C)=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:15]1[CH:20]=[CH:19][C:18]([N:21]2[CH2:25][CH2:24][CH2:23][C:22]2=[O:26])=[CH:17][CH:16]=1.[OH-].[Na+].Cl>CO.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:13])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:15]1[CH:16]=[CH:17][C:18]([N:21]2[CH2:25][CH2:24][CH2:23][C:22]2=[O:26])=[CH:19][CH:20]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 86698716methyl 6-chloro-5-[4-(2-oxopyrrolidin-1-yl)phenyl]-1H-indole-3-carboxylate

Product 1

HCID 866987176-chloro-5-[4-(2-oxopyrrolidin-1-yl)phenyl]-1H-indole-3-carboxylic acidYield 37.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

To a mixture of methyl 6-chloro-5-[4-(2-oxopyrrolidin-1-yl)phenyl]-1H-indole-3-carboxylate (112 mg, 0.30 mmol) in methanol (3 mL) and water (3 mL) was added sodium hydroxide (36 mg, 0.94 mmol). The reaction mixture was heated at 75° C. and stirred for 48 hours. The mixture was acidified to pH=4 using 1N hydrochloric acid and concentrated to give a brown solid. It was purified by reverse phase HPLC to give the title compound (40 mg, 37% yield) as a pale solid. MS (ES+) 355.1 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 12.11 (br. s, 1H), 11.95 (br. s, 1H), 8.07 (s, 1H), 7.95 (s, 1H), 7.75 (d, 2H), 7.62 (s, 1H), 7.43 (d, 2H), 3.89 (t, 2H), 2.53 (m, 2H), 2.09 (m, 2H).

Workup

  1. concentrationconcentrated
  2. customto give a brown solid
  3. customIt was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-3c949ec7e1074d4b82ae4d42aa7c5154
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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