Acetic Acid → HCID 178482112、化合物

温度

60 °C

1553d) N-[2-(5-Chloro-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamide was dissolved in Methylene chloride (10 mL, 200 mmol) and m-Chloroperbenzoic acid (235 mg, 1.05 mmol) was added. After 90 min, additional m-Chloroperbenzoic acid (135 mg, 0.602 mmol) was added. Formation of the sulfoxide was concomitant with sulfone formation. After 1 h, the mixture was partitioned between satd. NaHCO3 (20 mL) and EtOAc (50 mL); the aq. was extracted with EtOAc (2×20 mL) and the comb. org. washed with brine:satd. NaHCO3 (40 mL). After drying, the mixture was conc. in vacuo. The crude N-[2-(5-Chloro-2-methanesulfinyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamide was dissolved in 1,4-Dioxane (4.00 mL) then treated with 5.0 M of Sodium hydroxide in Water (1.00 mL, 5.00 mmol) and heated to 60° C. for 2 h. The mixture was cooled, treated with Acetic acid (0.400 mL, 7.04 mmol) and water (2 mL), then partitioned between water and DCM (30 mL each), sept. and extr. with DCM (3×20 mL), dried and conc. in vacuo. The residue was applied to a 5 g ISCO cartridge, then purified (24 g SiO2, 10-100% EtOAc:Hex) to afford N-[2-(5-Chloro-2-hydroxy-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamide (0.129 g; Yield=47.2% over 4 steps) as an orange foam. LCMS (HPLC): 0.76 min, m/z=353 (M+H); 1H-NMR (DMSO-d6): 11.87 (br s, 1H), 9.01 (s, 1H), 7.69 (m, 2H), 7.59 (m, 2H), 7.50 (m, 1H), 6.99 (s, 1H), 3.19 (s, 3H), 2.84 (s, 3H).

1. waitAfter 1 h
2. customthe mixture was partitioned between satd
3. extractionthe aq. was extracted with EtOAc (2×20 mL)
4. washwashed with brine
5. customAfter drying
6. dissolutionThe crude N-[2-(5-Chloro-2-methanesulfinyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamide was dissolved in 1,4-Dioxane (4.00 mL)
7. temperatureThe mixture was cooled
8. custompartitioned between water and DCM (30 mL each)
9. dry with materialwith DCM (3×20 mL), dried and conc. in vacuo
10. custompurified (24 g SiO2, 10-100% EtOAc:Hex)

ORDレコード

ord-9543be70e31a4a8f933b1d5fda2e924c

出典データセット

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08471005B2