反应详情

2-(6-(1,4-Diazabicyclo[3.2.2]nonan-4-yl)-2-(3-chlorophenyl)-4-oxoquinazolin-3(4H)-yl)acetic acid (Intermediate 11A) (49 mg, 0.11 mmol) and dimethylamine hydrochloride (18.2 mg, 0.22 mmol) were weighed into a round bottomed flask and dichloromethane (1 mL) added to form a suspension. Triethylamine (33.8 mg, 0.33 mmol) was added and the suspension stirred for 5 minutes before dropwise addition of 1-propanephosphonic acid cyclic anhydride as a 50% wt solution in ethyl acetate (107 mg, 0.17 mmol) and the resulting reaction mixture stirred for 2 hours. Reaction mixture was washed with sodium bicarbonate solution and the organics were separated using a hydrophobic frit. The solvent was removed under reduced pressure and then re-dissolved in methanol (1 mL) and purified by preparative-HPLC. To afford the title compound 2-(6-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-(3-chlorophenyl)-4-oxoquinazolin-3(4H)-yl)-N,N-dimethylacetamide (5.4 mg, 0.012 mmol).

1. customto form a suspension
2. customthe resulting reaction mixture
3. customReaction mixture
4. washwas washed with sodium bicarbonate solution
5. customthe organics were separated
6. customThe solvent was removed under reduced pressure
7. dissolutionre-dissolved in methanol (1 mL)
8. custompurified by preparative-HPLC