Methanol → HCID 86613798, compound

Participants

Reaction Conditions

Reaction Steps

Heat at 110° C. a mixture of (+/−)-cis-6-benzylamino-4-[(3,5-bis-trifluoromethyl-benzyl)-cyano-amino]-2-ethyl-7-methyl-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid isopropyl ester (110 mg, 0.174 mmol), sodium azide (16 mg, 0.244 mmol) and triethyl amine hydrochloride (33 mg, 0.244 mmol) in dry toluene under a nitrogen atmosphere for 15 h. Then add more sodium azide (10 mg) and triethyl amine hydrochloride (25 mg) and heat the mixture for 20 h. Cool to room temperature, dilute with ethyl acetate, and wash with 1 N HCl. Dry the organic layer over anhydrous sodium sulfate, filter, and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate. Dissolve the residue in dry dichloromethane (1 mL), add triphenylphosphine (38 mg, 0.146 mmol), methanol (22 mg, 0.66 mmol) followed by diisopropylazodicarboxylate (0.046 mL, 0.104 mmol) and stir the mixture for 15 h at room temperature. Remove the solvent in vacuo and purify the residue by silica gel chromatography, eluting with ethyl acetate/hexanes to afford (+/−)-trans-4-[(3,5-bis-trifluoromethyl-benzyl)-2-methyl-2H-tetrazol-5-yl)-amino]-2-ethyl-6-benzylamino-7-methyl-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid isopropyl ester [15 mg, 16%, MS (ES+): 691 (M+H)] and (+/−)-cis-4-[(3,5-bis-trifluoromethyl-benzyl)-2-methyl-2H-tetrazol-5-yl)-amino]-2-ethyl-6-benzylamino-7-methyl-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid isopropyl ester [20 mg, 22%, MS (ES+): 691 (M+H)].

Provenance & Evidence