Triethylamine → Ethyl 1-cyclohexyl-7-[5-(2,4-diamino-pyrimidin-5-ylmethyl)-2,3-dimethoxy-phenylethynyl]-4-oxo-1,4-dihydro-quinoline-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

3 g of ethyl 7-bromo-1-cyclohexyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid (Example 13ad)) are dissolved in 35 ml of N,N-dimethylformamide to 90° C. under argon with 200 mg of bis(triphenylphosphine)palladium(II) dichloride and treated dropwise within one hour with a solution of 5-[3-ethynyl-4,5-dimethoxy-benzyl]-pyrimidine-2,4-diamine (Example 11b)) in 35 ml of N,N-dimethylformamide and 35 ml of triethylamine. The dark red solution is stirred at 90° C. for a further 1 hr. The reaction mixture is left to cool to room temperature and is poured into 150 ml of 10% aqueous sodium carbonate solution while stirring. After 15 min. the suspension is suction filtered and the residue is washed with 100 ml of water and then with 100 ml of diethyl ether and dried at room temperature in a high vacuum. The crude product is triturated with 50 ml of diethyl ether for one hour, filtered off under suction and dried in a high vacuum at room temperature. 3.83 g (83%) of ethyl 1-cyclohexyl-7-[5-(2,4-diamino-pyrimidin-5-ylmethyl)-2,3-dimethoxy-phenylethynyl]-4-oxo-1,4-dihydro-quinoline-3-carboxylate are obtained as a light yellow solid. M.p. 228°-230° C.

Provenance & Evidence