18372-22-0

Pale Yellow Fine Powder

Methyl Indolyl-3-glyoxylate (cas# 18372-22-0) is a compound useful in organic synthesis.

Reactant for preparation of sotrastaurin analogs as protein kinase inhibitors 1 Reactant for synthesis of GSK-3 inhibitors 2 Reactant for Diels-Alder cycloaddition 3 Reactant for preparation of a Janus kinase 3 inhibitor 4 Reactant for synthesis of cephalandole alkaloids 5 Reactant for stereoselective preparation of COX-2 inhibitor as anticancer agent 6 Reactant for synthesis of cycloalkene indole carbazole alkaloids via ring-closing metathesis.

To a three-necked flask equipped with a magnetic stirrer and two addition funnels were added indole (10.1 g, 0.086 mol) and 100 mL of diethyl ether. Oxalyl chloride (7.3 mL, 0.086 mol) was added slowly and dropwise over 0.5 h at 0 °C under nitrogen protection. A yellow precipitate appeared in the reaction mixture and stirring was continued for 0.5 hr. Subsequently, the reaction mixture was cooled to -70 °C via a dry ice bath and sodium methanolate (25% methanol solution, 37.3 g, 0.173 mol) was added dropwise over 1 hour. After the dropwise addition, the reaction mixture was slowly warmed to 0 °C and 50 mL of water was added. The precipitate was collected by filtration, washed with water several times, and dried under vacuum at 60 ℃ to obtain methyl indole-3-glyoxylate as a yellow powder with 90% yield, which could be used in the next reaction without further purification. In another three-necked flask equipped with a magnetic stirrer and a dosing funnel, 3-indoleacetamide (8.0 g, 0.046 mol), indole-3-glyoxalic acid methyl ester (10.0 g, 0.049 mol) and 80 mL of tetrahydrofuran were added. A solution of potassium tert-butanolate (15.2 g, 0.135 mol) in 130 mL of tetrahydrofuran was slowly added dropwise over a period of 1.5 h at 0 °C under nitrogen protection. After the dropwise addition, the reaction mixture was slowly warmed to room temperature and stirring was continued for 3 hours. Subsequently, a 35% aqueous hydrochloric acid solution (64 mL) was added slowly and dropwise over 1 hour. Upon completion of the reaction, 200 mL of ethyl acetate and 100 mL of water were added and stirred until completely dissolved. The organic phase was separated, washed sequentially with water to neutral, brine once, and dried with anhydrous sodium sulfate. The desiccant was removed by filtration and the filtrate was concentrated. Add 1:1 (v/v) mixed solvent of ethyl acetate and n-hexane dropwise to the concentrated solution, and crystallize at 50~60°C to obtain 3,4-bisindolylmaleimide pure as red crystals.

[1] Chinese Chemical Letters, 2018, vol. 29, # 3, p. 513 - 516
[2] Journal of Materials Chemistry A, 2018, vol. 6, # 39, p. 18794 - 18798
[3] Archiv der Pharmazie, 2013, vol. 346, # 5, p. 349 - 358
[4] Patent: CN104693198, 2017, B. Location in patent: Paragraph 0035; 0036
[5] Patent: WO2018/132636, 2018, A1. Location in patent: Page/Page column 41