ethyl 4-chloro-5-methyl-5h-pyrrolo[3,2-d]pyrimidine-7-carboxylate synthesis

Yield:1234616-53-5 72%

Reaction Conditions:

Stage #1: 4-chloro-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid ethyl esterwith sodium hydride in N,N-dimethyl-formamide;mineral oil at 0; for 0.333333 h;
Stage #2: methyl iodide in N,N-dimethyl-formamide;mineral oil at 0 - 20;

Steps:

AU.D

Ethyl 4-chloro-5H-pyrrolo[3,2-J]pyrimidine-7-carboxylate (500 mg, 2.22 mmol) was dissolved in TV^V-dimethylformamide (4 mL, 50 mmol) and cooled to 0 °C . Sodium hydride (60% in mineral oil, 115.2 mg) was added, and the mixture was stirred at 0°C for 20 minutes. Methyl iodide (165.5 uL, 2.659 mmol) was added, and the mixture was slowly warmed to room temperature. The mixture was quenched with ammonium chloride solution and extracted with dichloromethane three times. The combined extracts were washed with brine, dried over sodium sulfate and concentrated. The crude product was purified using flash chromatography (gradient elution: 0-100% ethyl acetate + 15% MeOH in heptanes) to yield ethyl 4-chloro-5-methyl-5H-pyrrolo[3,2-J]pyrimidine-7-carboxylate as a solid (380 mg, 72%). ¹H NMR (500 MHz, DMSO-J₆) δ 8.77 (s, IH), 8.65 (s, IH), 4.30 (q, J= 7.1 Hz, 2H), 4.16 (s, 3H), 1.32 (t, J= 7.1 Hz, 3H).

References:

WO2011/25940,2011,A1 Location in patent:Page/Page column 85-86