Acetic Acid → HCID 87302718, compound

Participants

Reaction Steps

To 2-chloro-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde 10 from Example 3 (100 mg, 0.35 mmol) in 1,2-dichloroethane (2 mL) was added acetic acid (20 μL, 0.35 mmol), and 3-N-BOC-aminoazetidine (78 mg, 0.5 mmol) then Na(OAc)3BH (90 mg, 0.42 mmol). The reaction stirred overnight at room temperature then was quenched with water and extracted with DCM. The combined organics were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was dissolved in CH2Cl2 (10 mL), MeOH (10 mL), and 4 M HCl in dioxane (10 mL) was added. The resulting mixture stirred at room temperature for 1 h then was concentrated in vacuo. The crude material was dissolved in CH2Cl2 (5 mL) and Et3N (4 mL) and methanesulfonyl chloride (110 μL, 1.4 mmol) was added. The reaction mixture stirred at room temperature overnight then was quenched by the addition of water and extracted with EtOAc. The combined organics were dried over Na2SO4, filtered, and concentrated in vacuo to give N-(1-((2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)azetidin-3-yl)methanesulfonamide which was utilized in a Suzuki coupling according to General Procedure A using 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole 7 to provide 381 after reverse phase HPLC purification (2 mg). MS (Q1) 500 (M)+

Provenance & Evidence