Sodium Hydroxide → HCID 59605353, compound

Participants

Reaction Steps

A degassed solution of 7-morpholin-4-yl-2-(3-morpholin-4-yl-azetidin-1-ylmethyl)-5-(tributylstannanyl)thiazolo[5,4-d]pyrimidine (200 mg, 0.30 mmol), 1-benzenesulfonyl-4-bromo-1H-pyrrolo[3,2-c]pyridine (132 mg, 0.39 mmol), PdCl2{PtBu2(Ph-p-Nme2)}2 (22 mg, 0.03 mmol) and copper(I) thiophene-2-carboxylate (12 mg, 0.06 mmol) in 1,4-dioxane (4 mL) was subjected to microwave irradiation at 140° C. for 20 minutes. 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 product was collected and concentrated to give 5-(1-benzenesulfonyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-7-morpholin-4-yl-2-(3-morpholin-4-yl-azetidin-1-ylmethyl)thioazolo[5,4-d]pyrimidine as a crude oil. Aqueous NaOH (12.5 M, 0.5 mL) was added to a solution of 5-(1-benzenesulfonyl-1H-pyrrolo[3,2-c]pyridin-4-yl)-7-morpholin-4-yl-2-(3-morpholin-4-yl-azetidin-1-ylmethyl)-thiazolo[5,4-d]pyrimidine in 1,4-dioxane (4 mL) and IMS (4 mL). The reaction mixture was stirred at ambient temperature for 45 min, then concentrated in vacuo. The 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 product was collected and concentrated to afford a solid. The solid was purified by flash chromatography (Si—PPC, DCM:MeOH, 100:0 to 98:2 to 96:4) to afford 152 as a yellow solid (56 mg, 38%). LCMS (Method E): RT=4.34 min, M+H +=493.2. 1H NMR (CDCl3, 400 MHz) δ 8.72 (bs, 1 H), 8.56 (d, J=5.7 Hz, 1 H), 7.41 (m, 2 H), 7.36 (d, J=3.2 Hz, 1 H), 4.49-4.44 (m, 4 H), 4.02 (s, 2 H), 3.90 (t, J=4.7 Hz, 4 H), 3.74-3.65 (m, 6 H), 3.16-3.07 (m, 3 H), 2.35 (m, 4 H)

Provenance & Evidence