Hydrochloric Acid → HCID 54065044, compound

Participants

Reaction Steps

(3-Methyl-4-phenoxy-phenyl)-(6-piperidin-3-ylethynyl-quinazolin-4-yl)-amine (114 mg, 0.2 mmol) and tert-butyl N-(2-oxoethyl)carbamate (320 mg, 2.0 mmol) were dissolved in MeOH/H2O (5/0.5 mL) and the pH was adjusted to 5 with AcOH. The reaction was stirred at room temperature overnight and followed by the addition of NaBH3CN (13 mg, 0.2 mmol) over a period of 1 hour. After stirring for another hour, the reaction was concentrated and the residue was partitioned between CH2Cl2 (30 mL) and saturated Na2CO3 (20 mL). The separated organic layer was dried over sodium sulfate and concentrated. Purification by silica gel column using 5% MeOH in EtOAc gave the free base which was dissolved in MeOH. HCl gas was passed through the solution for 5 min and the deprotected product precipitated as HCl salt The mixture was diluted with EtOAc and the solid was collected by suction filtraton, rinsed with EtOAc, and further dried to afford 83 mg (71%) of yellow solid: 1H NMR (CD3OD) δ 1.71-1.82 (br, 2H), 2.0-2.12 (br, 2H), 2.27 (s, 3H), 3.00 (t, 1H), 3.03-3.19 (br, 2H), 3.40 (br, 1H), 3.50 (s, 2H), 3.62 (br d, 1H), 3.70 (m, 1H), 3.89 (br d, 1H), 6.93 (m, 3H), 7.08 (t, 1H), 7.33 (t, 2H), 7.52 (d, 1H), 7.64 (s, 1H), 7.79 (d, 1H), 8.05 (d, 1H), 8.75 (s, 1H), 8.77 (s, 1H); MS m/z (MH+) 476.1.

Provenance & Evidence