Hexane → 4-(tert-butyl)-N-[3-(2-[{5-chloro-2-pyrimidinyl}oxy]ethoxy)-1-(2-hydroxyethyl)-4-(4-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamide

HRID 1062734Notes

Reaction equation

HRID 1062734 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[N:19]([CH2:20][CH2:21][O:22][Si](C(C)(C)C)(C)C)[N:18]=[C:17]([O:30][CH2:31][CH2:32][O:33][C:34]3[N:39]=[CH:38][C:37]([Cl:40])=[CH:36][N:35]=3)[C:16]=2[C:41]2[CH:46]=[CH:45][C:44]([CH3:47])=[CH:43][CH:42]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C.CCCCCC>C1COCC1.CCOCC>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([S:11]([NH:14][C:15]2[N:19]([CH2:20][CH2:21][OH:22])[N:18]=[C:17]([O:30][CH2:31][CH2:32][O:33][C:34]3[N:39]=[CH:38][C:37]([Cl:40])=[CH:36][N:35]=3)[C:16]=2[C:41]2[CH:46]=[CH:45][C:44]([CH3:47])=[CH:43][CH:42]=2)(=[O:13])=[O:12])=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 8058HexaneHCID 8857Ethyl AcetateHCID 2724141Tetrabutylammonium Fluoride2×HCID 234003224-(tert-butyl)-N-[1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3-(2-[{5-chloro-2-pyrimidinyl}oxy]ethoxy)-4-(4-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamide

Product 1

HCID 222819224-(tert-butyl)-N-[3-(2-[{5-chloro-2-pyrimidinyl}oxy]ethoxy)-1-(2-hydroxyethyl)-4-(4-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamideYield 74.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4-(tert-butyl)-N-[1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3-(2-[{5-chloro-2-pyrimidinyl}oxy]ethoxy)-4-(4-methylphenyl)-1H-pyrazol-5-yl]benzenesulfonamide (Preparation 27) (90 mg) and tetrabutylammonium fluoride (1.0M in THF, 0.13 ml) in anhydrous THF (2 ml) was stirred for 3 hours at room temperature. After this period, tlc analysis (2:1 ethyl acetate:hexane) showed that little reaction had occurred. A second aliquot of 1.0M tetrabutylammonium fluoride in THF (0.13 ml) was added to the reaction solution and the resulting mixture was stirred at room temperature overnight. The reaction mixture was diluted with ether (30 ml) and then extracted with 1.0M citric acid (20 ml) and water (20 ml). The organic phase was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on a Biotage Flash 12i cartridge at 10 psi using 60% ethyl acetate/hexane as eluent to give the title compound as a colourless oil (56 mg).

Workup

  1. waitAfter this period
  2. extractionextracted with 1.0M citric acid (20 ml) and water (20 ml)
  3. dry with materialThe organic phase was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by chromatography on a Biotage Flash 12i cartridge at 10 psi

Sources & evidence

ORD record
ord-46f7c259aae9465cafbdf75d6cb5f1f4
Source dataset
uspto-grants-2005_11
Patent number
US06962923B2

Reaction notes

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