Sodium hydride → 2-{4-[3-(dimethylamino)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl]phenoxy}ethanol

To a solution of 4-[3-(dimethylamino)-1-(4-methoxyphenyl)-1-H-pyrazol-5-yl]phenol (98.7 mg) in DMF (2 ml) was added sodium hydride 60% dispersion in mineral oil (15.3 mg). The mixture was stirred at ambient temperature for 1 hour. To the reaction mixture was added (2-bromoethoxy)-tert-butyldimethylsilane (153 mg) in DMF (1 ml) dropwise and the mixture was stirred at ambient temperature overnight. The mixture was poured into ice water, extracted with AcOEt, washed with H2O and saturated aqueous sodium chloride solution. The aqueous layer was reextracted with AcOEt. The combined organic layers were dried over magnesium sulfate, and concentrated in vacuo. The residue was dissolved in EtOH (2 ml) . To this solution was added concentrated hydrochloric acid (100 μl) and the mixture was stirred at ambient temperature for 3 hours. The mixture was concentrated invacuo, and the residue was partitioned between AcOEt and saturated aqueous sodium bicarbonate solution, washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by preparative thin layer silica gel chromatography developed by AcOEt/n-hexane=60%. The residual crystals were collected and washed with IPE to give 2-{4-[3-(dimethylamino)-1-(4-methoxyphenyl)-1-H-pyrazol-5-yl]phenoxy}ethanol (97 mg) as a white powder.

1. stirringthe mixture was stirred at ambient temperature overnight
2. extractionextracted with AcOEt
3. washwashed with H2O and saturated aqueous sodium chloride solution
4. dry with materialThe combined organic layers were dried over magnesium sulfate
5. concentrationconcentrated in vacuo
6. dissolutionThe residue was dissolved in EtOH (2 ml)
7. additionTo this solution was added concentrated hydrochloric acid (100 μl)
8. stirringthe mixture was stirred at ambient temperature for 3 hours
9. concentrationThe mixture was concentrated invacuo
10. customthe residue was partitioned between AcOEt and saturated aqueous sodium bicarbonate solution
11. washwashed with saturated aqueous sodium chloride solution
12. dry with materialdried over magnesium sulfate
13. concentrationconcentrated in vacuo
14. customThe residue was purified by preparative thin layer silica gel chromatography
15. customThe residual crystals were collected
16. washwashed with IPE

ORD record

ord-13154d5f9ffb49a8a16799dfb7543a10

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07183306B2