反应详情

A solution of N-[3-(acetyl-methanesulfonyl-amino)-2,4-dioxo-7-trifluoromethyl-1,2,3,4-tetrahydro-quinazolin-6-ylmethyl]-acetamide (1.8 g, 4.13 mmol) in 2M aq HCl (5.2 mL) was stirred at 80° C. for 2 d. 2M hydrochloric acid (1 mL) was added every half day. Subsequently the solvent was evaporated and the light yellow residue was purified by ion-exchange resin (DOWEX 50*2-100, MeOH): the crude product was dissolved in MeOH, and mixed with a suspension of DOWEX in MeOH and the mixture was stirred at r.t. for 2 h. The resin was then filtered and washed with MeOH (this MeOH fraction was discarded). The resin was suspended in a solution of ammonia in MeOH (7M, 300 mL), stirred for 2 h, filtered and the filtrate was collected. The resin was treated two more times with a solution of ammonia in MeOH as described above and the filtrates were collected. The combined solvent fractions were evaporated to give N-(6-aminomethyl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulfonamide (1.12 g, 3.18 mmol, 77%) as a yellow solid, 1H-NMR (DMSO-d6, 400 MHz) 3.14 ppm (s, 3H, SO2—CH3); LC-MS rt=0.523 mn; MS: m/z 352.9 [M+H]+ Column: SunFireC18, 4.6*50 mn, 3.5 um; Positive MS Water/Acetonitrile 95:5 to 5:95 in 5 min, Flow: 1.5 mL/min

1. customSubsequently the solvent was evaporated
2. customthe light yellow residue was purified by ion-exchange resin (DOWEX 50*2-100, MeOH)
3. dissolutionthe crude product was dissolved in MeOH
4. additionmixed with a suspension of DOWEX in MeOH
5. filtrationThe resin was then filtered
6. washwashed with MeOH (this MeOH fraction
7. stirringstirred for 2 h
8. filtrationfiltered
9. customthe filtrate was collected
10. additionThe resin was treated two more times with a solution of ammonia in MeOH
11. customwere collected
12. customThe combined solvent fractions were evaporated