2-aminoquinoline-6-carbaldehyde synthesis

Yield:791626-61-4 24%

Reaction Conditions:

Stage #1: 6-Iodo-quinolin-2-ylamine;carbon monoxidewith triethylamine;diphenylphosphinopropane;palladium diacetate in N,N-dimethyl-formamide at 20; under 3878.71 Torr; for 10 h;
Stage #2: carbon monoxidewith tri-n-hexylsilane in N,N-dimethyl-formamide at 80; under 3878.71 Torr; for 4 h;

Steps:

1.e

e) Preparation of 2-amino-quinoline-6-carbaldehyde A mixture of 6-iodo-quinolin-2-ylamine (200 mg, 0.74 mmol), triethylamine (0.26 mL, 1.85 mmol), diphenylpropylphosphine (dpp, 17 uL, 0.074 mmol) and palladium(II) acetate (17 mg, 0.074 mmol) in dry N,N-dimethylformamide (4 mL) in pressure tube was stirred under carbon monoxide at 75 psi at room temperature for 10 min. After addition of trihexylsilane (0.53 mL, 1.5 mmol), the mixture was then stirred under carbon monoxide at 75 psi at 80° C. for 4 h. The reaction was allowed to cool to 25[ ]C and then extracted with methylene chloride (2×50 mL). The combined organic layers were successively washed with water (3×50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70-230 mesh, ethyl acetate) afforded 2-amino-quinoline-6-carbaldehyde (30 mg, 24%) as a solid.

References:

US2006/63804,2006,A1 Location in patent:Page/Page column 10