Hydrochloric Acid → HCID 59592945, compound

Participants

Reaction Steps

To a solution of (2-chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methanamine 27 from Example 11 (150 mg, 0.5 mmol) in DMF (4.5 mL) was added O-(7-azabenzotriazol-1-yl)-(N,N,N′,N′-tetramethyluronium hexafluorophosphate (400 mg, 1 mmol), N,N-diisopropylethylamine (550 μL, 3.2 mmol), then N-Boc glycine (270 mg, 1.5 mmol). The resulting solution stirred 30 min at room temperature. Excess hydroxylamine hydrochloride was added then the reaction was quenched with saturated aqueous NaHCO3. The aqueous layer was extracted with EtOAc. The combined organics were dried over Na2SO4, filtered, and concentrated in vacuo. A portion of the crude product (0.5 mmol) was dissolved in CH2Cl2 (15 mL), MeOH (15 mL), Et2O (6 mL), and 4 M HCl in dioxane (6 mL) was added. The resulting mixture stirred at room temperature overnight. The reaction mixture was concentrated in vacuo. A portion of the crude material (0.3 mmol) was dissolved in CH2Cl2 (8 mL) and Et3N (4 mL) and methanesulfonyl chloride (450 μL, 6 mmol) was added. The reaction mixture stirred at room temperature overnight. The reaction was quenched by the addition of water then extracted with EtOAc. The combined organics were dried over Na2SO4, filtered, and concentrated in vacuo. The crude material 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 330 after reverse phase HPLC purification (36 mg). MS (Q1) 502 (M)+

Provenance & Evidence