Hydrochloric Acid → HCID 89754176, compound

HRID 516644Notes

Reaction equation

HRID 516644 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]2[C:23]([C:24]3[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=3)=[CH:22][NH:21][N:20]=2)[C:14]=1[F:30])(=[O:11])=[O:10].[H-].[Na+].Cl.[C:34]([O:37][CH2:38][CH3:39])(=O)C>CN(C=O)C.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]2[C:23]([C:24]3[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=3)=[CH:22][N:21]([CH:38]3[CH2:39][CH2:34][O:37]3)[N:20]=2)[C:14]=1[F:30])(=[O:10])=[O:11]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 24758Sodium hydride2×HCID 178527473HCID 178527473, compound

Product 1

HCID 89754176HCID 89754176, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 2,5-Difluoro-N-[2-fluoro-3-(4-pyridin-4-yl-1H-pyrazol-3-yl)-phenyl]-benzenesulfonamide (200 mg, 0,465 mmol)(prepared as described in Example 15) in anhydrous DMF (4 mL) was added to sodium hydride (60% in mineral oil)(46 mg, 1.162 mmol, 2.5 eq) previously washed with n-hexane under argon atmosphere and cooled to 0° C. After stirring at 0° C. for 40 minutes, freshly prepared 3-oxetanol trifluoromethanesulfonyl ester (144 mg, 0.689 mmol, 1.5 eq) dissolved in dry DMF (1 mL) was added and the mixture was stirred at 0° C. for 1 h. A further addition of sodium hydride (40 mg) and 3-oxetanol trifluoro-methanesulfonyl ester (40 mg) was then made and the reaction mixture was then allowed to warm to room temperature during a night. The reaction mixture was then diluted with water and ethyl acetate. The aqueous phase was brought to pH 4-5 with HCl 2 N and extracted with ethyl acetate. The organic phase was dried over Na2SO4 and evaporated to dryness. The crude product was purified by flash chromatography on silica gel (ethyl acetate/n-hexane 7:3) affording 24 mg of the title product as a white solid. HPLC (254 nm): Rt: 6.99 min; 1H NMR (DMSO-d6) Shift: 10.68 (br. s., 1H), 8.52 (s, 1H), 8.36-8.40 (m, 2H), 7.51-7.59 (m, 1H), 7.31-7.49 (m, 4H), 721-7.29 (m, 1H), 7.02-7.08 (m, 2H), 5.64 (quip, J=6.9 Hz, 1H), 4.90-5.00 (m, 4H); HRMS (ESI) calcd for C23H18F3N4O3S [M+H]+ 487.1046. found 487.1043.

Workup

  1. washpreviously washed with n-hexane under argon atmosphere
  2. additionwas added
  3. stirringthe mixture was stirred at 0° C. for 1 h
  4. temperatureto warm to room temperature during a night
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic phase was dried over Na2SO4
  7. customevaporated to dryness
  8. customThe crude product was purified by flash chromatography on silica gel (ethyl acetate/n-hexane 7:3)

Sources & evidence

ORD record
ord-0e3c802a055a45eab99281f75b4bb828
Source dataset
uspto-grants-2015_08
Patent number
US09114137B2

Reaction notes

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