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

HRID 1950282Notes

Reaction equation

HRID 1950282 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.C[O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:20]=[C:21]3[C:25](=[CH:26][CH:27]=2)[CH:24]([OH:28])[CH2:23][CH2:22]3)=[C:15]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([O:36][CH2:37][CH2:38][N:39]3[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]3)=[CH:32][CH:31]=2)[CH:14]=1.C(N(CC)CC)C>ClCCl.O>[OH:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:20]=[C:21]3[C:25](=[CH:26][CH:27]=2)[C:24](=[O:28])[CH2:23][CH2:22]3)=[C:15]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([O:36][CH2:37][CH2:38][N:39]3[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]3)=[CH:32][CH:31]=2)[CH:14]=1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 230872715-{4-Methoxy-2-[4-(2-piperidin-1-ylethoxy)phenylamino]phenyl}indan-1-ol

Product 1

HCID 230872435-{4-Hydroxy-2-[4-(2-piperidin-1-ylethoxy)phenylamino]phenyl}indan-1-oneYield 7.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-78 °C

Procedure

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 stirring 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 solution 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).

Workup

  1. waitover 25 minutes
  2. stirringthe solution was stirred for 40 minutes
  3. stirringby stirring 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 solution 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)

Sources & evidence

ORD record
ord-19a88ad2d1384a55830bffaeb7571384
Source dataset
uspto-grants-2013_03
Patent number
US08399520B2

Reaction notes

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