Hydrochloric Acid → HCID 11965458, compound

A solution of 2-amino-5-[3-(tetrahydro-pyran-2-yloxy)-propyl]-4-trifluoromethyl-benzoic acid methyl ester (1.00 g, 2.77 mmol) in THF (10 mL) was treated with (CCl3O)2CO (279 mg, 0.94 mmol) and the mixture was stirred at r.t. for 15 min under nitrogen. To this solution was added dropwise Et3N (0.39 mL, 2.77 mmol) and the mixture was further diluted with THF (20 mL), and stirred for another 3 h at r.t. The mixture was then treated with CH3SO2NHNH2 (305 mg, 2.77 mmol) and stirred for 16 h at r.t. Aqueous sodium hydroxide (1M, 10 mL, 10 mmol) was subsequently added and the solution was stirred for 3 h at r.t. The mixture was acidified with aqueous hydrochloric acid (4N) until pH=3-4, and then diluted with EtOAc. The layers were separated and the organic phase was washed once with water and then dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The white solid obtained was taken up in EtOAc and stirred at r.t. for 1 h. The suspension was filtered and the white solid was dried. This solid was then taken up in THF and this solution was acidified with aqueous hydrochloric acid (4M). The mixture was concentrated in vacuo to give a white solid, which was recrystallized in EtOAc. This solid was then purified by flash chromatography (silica gel 60, hexanes/EtOAc 2:1) to provide N-[6-(3-hydroxy-propyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide (100 mg, 0.26 mmol, 9%) as a white powder, m.p. 243-247° C., ESI-MS: m/z 382 [M+H]+, 1H-NMR (DMSO-d6, 400 MHz) 8.04 (s, 1H), 7.53 (s, 1H), 4.60 (m, 1H), 3.48 (m, 2H), 3.18 (s, 3H), 2.83, (m, 2H), 1.74 (m, 2H).

1. stirringstirred for another 3 h at r.t
2. stirringstirred for 16 h at r.t
3. stirringthe solution was stirred for 3 h at r.t
4. customThe layers were separated
5. washthe organic phase was washed once with water
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe white solid obtained
10. stirringstirred at r.t. for 1 h
11. filtrationThe suspension was filtered
12. customthe white solid was dried
13. concentrationThe mixture was concentrated in vacuo
14. customto give a white solid, which
15. customwas recrystallized in EtOAc
16. customThis solid was then purified by flash chromatography (silica gel 60, hexanes/EtOAc 2:1)

ORD record

ord-30eaa7904fbc4236b309b1db86eb3db0

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08012988B2