4-Methylmorpholine → HCID 54162264, compound

Participants

Reaction Steps

Water (1 mL) is added to a solution containing (±)-1-(4-amino-quinazolin-7-ylmethyl)-4-[(5-chloro-thiophen-2-yloxy)-acetyl]-6-oxo-piperazine-2-carboxylic acid methyl ester (20 mg, 0.03 mmol), EXAMPLE 808, in a 1:1 mixture of THF/MeOH (2 mL). At ambient temperature, LiOH monohydrate (3 mg, 0.07 mmol) is then added. After 16 h, the reaction mixture is diluted with water and purified by reverse-phase HPLC [Buffer A: water w/0.1% TFA; Buffer B: CH3CN w/0.1% TFA; Gradient: 0% B to 60% B over 30 min] to provide 25 mg (>100%) of the associated acid as a white solid after lyophilization which is used directly in the next reaction. To a mixture containing (+/−)-1-(4-amino-quinazolin-7-ylmethyl)-4-[(5-chloro-thiophen-2-yloxy)-acetyl]-6-oxo-piperazine-2-carboxylic acid (12 mg, 0.02 mmol), N-methylmorpholine (19 mg, 0.19 mmol), and HATU (22 mg, 0.05 mmol) in anhydrous DMF (1 mL) is added MeNH2 hydrochloride (5 mg, 0.19 mmol). The reaction mixture is stirred 1 h at ambient temperature and then concentrated to dryness. The residue is dissolved in water and purified by reverse-phase HPLC [Buffer A: water w/0.1% TFA; Buffer B: CH3CN w/0.1% TFA; Gradient: 0% B to 60% B over 30 min] to provide 7 mg (58%) of the title compound as a white solid.

Provenance & Evidence