Methanol → HCID 135990644, compound

Participants

Reaction Steps

A mixture of 2.30 g (7.6 mmol) of 2-acetamido-8-acetyl-5,6,7,8-tetra hydro-7-hydroxypyrido[2,3-d]pyrimidin-4(3H)-one, 2.40 g (8.15 mmol) of dimethyl N-(4-aminobenzoyl)-L-glutamate, 5 g of 3A molecular sieves, 150 ml of methanol, and 4 ml of acetic acid was stirred with protection from moisture for 3 hours when "imine" formation was complete. Sodium cyanoborohydride (0.38 g) and 8 ml of acetic acid was added to the reaction. After 15 hours a trace of intermediate "imine" was detected by TLC and an additional 50 mg of sodium cyanoborohydride was added. After 1 hour the reaction was diluted with 500 ml of chloroform and filtered through a Celite pad to remove the insolubles. The chloroform solution was washed with four 50 ml portions of 5% aqueous sodium bicarbonate, two 50 ml portions of water, one 50 ml portion of brine, dried over magnesium sulphate and spin evaporated in vacuo. The resultant foam was triturated with 50 ml of ethyl acetate to give white crystals; yield, 2.75 g (65%), mp 144°-150°. Recrystallization from ethanol gave chromatographically pure material; yield, 1.70 g (40%), mp 135°-142°. An analytically pure sample was obtained from a previous run with mp 140°-143°; TLC: (C6H6 : EtOH/10:1); NMR (DMSO-d6)δ11.69 (br s, 2H, 2AcNH) 9.68 (br s, 1H, ring NH), 8.24 (br d, 1H, ArCONH), 7.65 (d, 2H, ArH), 6.53 (d, 2H, ArH), 6.17 (br t, 1H, CH2NH), 4.39 (m, 1H, CHCO2CH3), 3.63 (s, 3H, CO2CH3), 3.58 (s, 3H, CO2CH3), 3.01 (m, 2H, CH2NHAr), 2.43 (m, 2H, CH2CO2CH3), 2.1 (4H, pyrimidine --CH2 and CHCH2, masked by AcNH peaks), 2.14 (s, 3H, Ac), 2.01 (s, 3H, Ac), 1.72 (m, 2H, CH2CH2CH2).

Provenance & Evidence