Potassium Hydroxide → 3-(6-cyclopropylpyrazin-2-yl)-1H-indole-5-carboxylic acid

HRID 634188Notes

Reaction equation

[CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[C:18]4[C:13](=[CH:14][CH:15]=[C:16]([C:19]([O:21]C)=[O:20])[CH:17]=4)[N:12](S(C4C=CC(C)=CC=4)(=O)=O)[CH:11]=3)[CH:7]=[N:6][CH:5]=2)[CH2:3][CH2:2]1.[OH-].[K+]>CO.O>[CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[C:18]4[C:13](=[CH:14][CH:15]=[C:16]([C:19]([OH:21])=[O:20])[CH:17]=4)[NH:12][CH:11]=3)[CH:7]=[N:6][CH:5]=2)[CH2:2][CH2:3]1

Participants

Conditions

Temperature: 60 °C

Procedure

An orange-brown suspension of methyl 3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indole-5-carboxylate (353.7 mg, 0.790 mmol) and KOH (310 mg, 5.53 mmol) in a mixture of MeOH (6.0 mL) and water (1.20 mL) was heated at 60° C. for 6 h. The mixture was subsequently cooled to RT and MeOH was removed in vacuo. 1.0 N aq HCl (4.0 mL) was added to the resulting slurry, and the precipitated solid was collected by vacuum filtration, washed with water (10 mL), and dried in vacuo to provide 3-(6-cyclopropylpyrazin-2-yl)-1H-indole-5-carboxylic acid (209.2 mg, 0.749 mmol, 95%) as a yellow solid: MS (ESI, pos. ion) m/z: 280.1 (M+1). 1H NMR (300 MHz, DMSO-d6) δ ppm 11.96 (1H, br. s.), 9.12 (1H, s), 8.91 (1H, s), 8.33-8.40 (2H, m), 7.80 (1H, dd, J=8.3, 1.2 Hz), 7.51 (1H, d, J=8.5 Hz), 2.23 (1H, br. s.), 1.17 (2H, br. s.), 1.11 (2H, m, J=7.9 Hz).

Workup

temperatureThe mixture was subsequently cooled to RT
customMeOH was removed in vacuo
addition1.0 N aq HCl (4.0 mL) was added to the resulting slurry
filtrationthe precipitated solid was collected by vacuum filtration
washwashed with water (10 mL)
customdried in vacuo

Sources & evidence

ORD record: ord-617e0bf0f29a4500ae7b173e5c4fdd25
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321756B2

Reaction notes

Loading…