Dimethyl Sulfoxide → 5-{4-Hydroxy-2-[4-(2-piperidin-1-ylethoxy)phenylamino]phenyl}indan-1-one

Temperature

-78 °C

To dichloromethane (2 ml) was added oxalyl chloride (0.22 ml) under a nitrogen atmosphere, the solution was cooled at −78° C., a solution of dimethylsulfoxide (245 mg) in dichloromethane (2 ml) was added dropwise thereto over 10 minutes, and then solution was stirred for 45 minutes. A solution of 5-{4-methoxy-2-[4-(2-piperidin-1-ylethoxy)phenylamino]phenyl}indan-1-ol (552 mg) in dichloromethane (4 ml) was added dropwise thereto over 25 minutes, the solution was stirred for 40 minutes, then triethylamine (0.85 ml) was added dropwise thereto followed by sttirring for 20 minutes while warming from −78° C. to room temperature. Water was added thereto followed by stirring, the solution was extracted with ethyl acetate, then sequentially washed with water and brine, and the solvent was evaporated in vacuo. Obtained by purifying the residue by NH silica gel column chromatography (hexane-ethyl acetate system), to a solution of the resulting 5-{4-methoxy-2-[4-(2-piperidin-1-ylethoxy)phenylamino]phenyl}indan-1-one (118 mg) in methanesulfonic acid (3 ml) was added DL-methionine (110 mg), the solution was stirred for 5 hours at 80° C., then water was added thereto, the solution was stirred, and neutralized with aqueous ammonia. The soultion was extracted with ethyl acetate, then sequentially washed with water and brine, and the solvent was evaporated in vacuo. The residue was purified by NH silica gel column chromatography (ethyl acetate-methanol system) to provide the title compound (42 mg).

1. waitover 25 minutes
2. stirringthe solution was stirred for 40 minutes
3. waitby sttirring for 20 minutes
4. temperaturewhile warming from −78° C. to room temperature
5. stirringby stirring
6. extractionthe solution was extracted with ethyl acetate
7. washsequentially washed with water and brine
8. customthe solvent was evaporated in vacuo
9. customObtained
10. customby purifying the residue by NH silica gel column chromatography (hexane-ethyl acetate system)
11. additionto a solution of the resulting 5-{4-methoxy-2-[4-(2-piperidin-1-ylethoxy)phenylamino]phenyl}indan-1-one (118 mg) in methanesulfonic acid (3 ml) was added DL-methionine (110 mg)
12. stirringthe solution was stirred for 5 hours at 80° C.
13. additionwater was added
14. stirringthe solution was stirred
15. extractionThe soultion was extracted with ethyl acetate
16. washsequentially washed with water and brine
17. customthe solvent was evaporated in vacuo
18. customThe residue was purified by NH silica gel column chromatography (ethyl acetate-methanol system)

ORD record

ord-cd2878bf6c364e359055267ae7303e48

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07960412B2