HCID 67187757, compound → 2-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-3-(tetrahydro-furan-3-yl)-propionamide

HRID 546161Notes

Reaction equation

HRID 546161 reaction equation
C([Si](C)(C)[O:6][CH2:7][CH2:8][N:9]1[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:34])[CH:16]([C:23]2[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[C:25]([Cl:33])[CH:24]=2)[CH2:17][CH:18]2[CH2:22][CH2:21][O:20][CH2:19]2)=[N:10]1)(C)(C)C>Cl.C(O)C>[Cl:33][C:25]1[CH:24]=[C:23]([CH:16]([CH2:17][CH:18]2[CH2:22][CH2:21][O:20][CH2:19]2)[C:15]([NH:14][C:11]2[CH:12]=[CH:13][N:9]([CH2:8][CH2:7][OH:6])[N:10]=2)=[O:34])[CH:28]=[CH:27][C:26]=1[S:29]([CH3:32])(=[O:30])=[O:31]

Participants

4

Reactant 1

HCID 67187757HCID 67187757, compound

Product 1

HCID 671885082-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-3-(tetrahydro-furan-3-yl)-propionamideYield 69%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 702EthanolSolvent

Conditions

Temperature
25 °C

Procedure

In a flask containing N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(tetrahydro-furan-3-yl)-propionamide (138 mg, 0.25 mmol) was added ethanol (6 ml) and concentrated hydrochloric acid (5 drops) and was stirred at 25° C. for 2 h. The reaction was then concentrated in vacuo to remove the ethanol, diluted with ethyl acetate (50 ml) and washed with a saturated aqueous sodium bicarbonate solution. The organic layer was then dried over magnesium sulfate, filtered and concentrated in vacuo. Purification on an AnaLogix Intelliflash system (12 g column, 5% methanol/ethyl acetate) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-3-(tetrahydro-furan-3-yl)-propionamide (76 mg, 69%) as an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ ppm 1.45-1.57 (m, 1H, CH of CH2), 1.68-1.84 (m, 1H, CH of CH2), 1.88-2.02 (m, 2 H, 2×CH of 2×CH2), 2.06-2.22 (m, 1H, CH), 3.22-3.30 (m, 1H, OCH of OCH2), 3.31 (s, 3H, SO2CH3), 3.53-3.77 (m, 5H, ArCH, SiOCH2, and 2×OCH of 2×OCH2), 3.83-3.93 (m, 1H, OCH of OCH2), 3.97-4.02 (m, 2H, NCH2), 4.82 (t, J=5.4 Hz, 1H, OH), 6.42 (d, J=2.2 Hz, 1H, Ar), 7.54 (d, J=2.2 Hz, 1H, Ar), 7.60 (2×dd, Jo=8.3 Hz, Jm=1.7 Hz, 1H, Ar), 7.71, 7.72 (2×d, Jm=1.7 Hz, 1H, Ar), 8.01 (d, Jo=8.3 Hz, 1H, Ar), 10.81, 10.82 (2×s, 1H, NH).

Workup

  1. concentrationThe reaction was then concentrated in vacuo
  2. customto remove the ethanol
  3. additiondiluted with ethyl acetate (50 ml)
  4. washwashed with a saturated aqueous sodium bicarbonate solution
  5. dry with materialThe organic layer was then dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification on an AnaLogix Intelliflash system (12 g column, 5% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-4105626630cf41cfaed2863a5f5c082f
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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