Sodium Hydroxide → (+/-)-3-[2-(4-Hydroxy-piperidin-1-yl)-thiazol-4-yl]-3-[4-(7-methoxy-quinolin-8-yl)-[1,4]diazepan-1-yl]-propionic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

1,2-Dichloroethane (1.02 mL) was added to a mixture of 8-[1,4]diazepan-1-yl-7-methoxy-quinoline (1.00 g, 3.88 mmol) and 2-(4-hydroxy-piperidin-1-yl)-thiazole-4-carbaldehyde (824 mg, 3.88 mmol). The reaction was heated to 55° C. and stirred until homogeneous. Freshly crushed Ti(OMe)4 (1.00 g, 5.82 mmol) was then added and the reaction was stirred at 55° C. for 1 h. tert-Butyl-(1-methoxy-vinyloxy)-dimethyl-silane (1.02 mL, 4.66 mmol) was then added and the reaction was stirred at 55° C. for 18 h. CH2Cl2 was then added, followed by sat. aq. NaHCO3, then 1 N aq. NaOH. This mixture was then stirred for 5 min and filtered through celite, washing the filter cake with CH2Cl2. The filtrate was then washed once with H2O, dried over MgSO4, filtered, and concentrated. The crude product was purified on silica gel (99:1 to 90:10 CH2Cl2:(9:1 MeOH:NH4OH)) to give the product (660 mg, 38% yield).

Provenance & Evidence