Sodium Hydroxide → HCID 49787177, compound

Participants

Reaction Steps

A degassed solution of 5-chloro-7-morpholin-4-yl-2-(3-morpholin-4-yl-azetidin-1-ylmethyl)thiazolo[5,4-c]pyrimidine (210 mg, 0.51 mmol), 1-(phenylsulfonyl)-3-indoleboronic acid (231 mg, 0.77 mmol), Pd(PPh3)4 (60 mg, 0.052 mmol) and Cs2CO3 (332 mg, 1.03 mmol) in a mixture of 1,4-dioxane (8 mL) and water (4 mL) was subjected to microwave irradiation at 150° C. for 30 min. The reaction mixture was cooled to ambient temperature and loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with MeOH and the desired product was subsequently eluted using 2 M NH3 in MeOH. The eluent was collected and concentrated to give 5-(1-benzenesulfonyl-1H-indol-3-yl)-7-morpholin-4-yl-2-(3-morpholin-4-yl-azetidin-1-ylmethyl)-thiazolo[5,4-c]pyrimidine as a crude oil. Aqueous NaOH (12.5 M, 0.6 mL) was added to a solution 5-(1-benzenesulfonyl-1H-indol-3-yl)-7-morpholin-4-yl-2-(3-morpholin-4-yl-azetidin-1-ylmethyl)thiazolo[5,4-d]pyrimidine in 1,4-dioxane (6 mL) and IMS (6 mL). The reaction mixture was stirred at ambient temperature for 1 h, then concentrated in vacuo. The resultant residue was dissolved in MeOH then loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with MeOH and the desired product was subsequently eluted using 2 M NH3 in MeOH. The eluent was collected and concentrated to afford a sticky solid. The solid was purified by flash chromatography (Si-PPC, DCM: MeOH, 100:0 to 98:2 to 95:5) followed by trituration from hot MeOH to afford 117 as a tan solid (117 mg, 47%). LCMS (Method E): RT=7.47 min, [M+H]+ 492.2. 1H NMR (CDCl3, 400 MHz): δ 8.65-8.60 (m, 1H); 8.44 (s, 1H); 8.13 (d, J=2.8 Hz, 1H); 7.44-7.39 (m, 1H); 7.31-7.25 (m, 2H); 4.43 (t, J=4.6 Hz, 4H); 3.99 (s, 2H); 3.91 (t, J=4.7 Hz, 4H); 3.73 (t, J=4.5 Hz, 4H); 3.66 (t, J=5.8 Hz, 2H); 3.18-3.07 (m, 3H); 2.40-2.31 (m, 4H)

Provenance & Evidence