Hydrochloric Acid → 3-Cyclopentyl-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-2-(R)-(4-methanesulfonyl-phenyl)-propionamide

HRID 546116Notes

Reaction equation

HRID 546116 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:33])[C@@H:16]([C:23]2[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][CH:24]=2)[CH2:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)=[N:10]1)(C)(C)C.Cl>C(O)C.C(OCC)(=O)C.C(Cl)Cl>[CH:18]1([CH2:17][C@H:16]([C:23]2[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][CH:24]=2)[C:15]([NH:14][C:11]2[CH:12]=[CH:13][N:9]([CH2:8][CH2:7][OH:6])[N:10]=2)=[O:33])[CH2:22][CH2:21][CH2:20][CH2:19]1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 67191478N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-cyclopentyl-2-(R)-(4-methanesulfonyl-phenyl)-propionamide

Product 1

HCID 671896413-Cyclopentyl-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-2-(R)-(4-methanesulfonyl-phenyl)-propionamideYield 787.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

N-{1-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-cyclopentyl-2-(R)-(4-methanesulfonyl-phenyl)-propionamide (135 mg, 0.26 mmol) was dissolved in ethanol (5 mL) and concentrated aqueous hydrochloric acid (100 μL) was added. The reaction stirred at 25° C. for 90 min. The reaction was diluted with ethyl acetate (50 mL), washed with water (20 mL), saturated aqueous brine solution (20 mL), dried over magnesium sulfate and concentrated in vacuo to give a beige foam. The foam was dissolved in methylene chloride (4 mL) and hexanes (4 mL) were added to crystallize the desired product. Collection by filtration followed by rinsing with excess hexanes afforded 3-cyclopentyl-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-2-(R)-(4-methanesulfonyl-phenyl)-propionamide (830 mg, 78%) as colorless crystals: ESI-LRMS m/e calcd for C20H27N3O4S [M+] 405.17, found 406.35 [M+H+]; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.05-1.21 (m, 2H, CH2), 1.38-1.82 (m, 8H, 4×CH2), 2.01-2.23 (m, 1H, CH), 3.17 (s, 3H, SO2CH3), 3.66 (q, J=5.5 Hz, 2H, OCH2), 3.89-3.95 (m, 1H, CH), 3.98 (t, J=5.5 Hz, 2H, NCH2), 4.80 (t, J=5.5 Hz, 1H, OH), 6.40 (d, Jo=2.2 Hz, 1H, Ar), 7.51 (d, Jo=2.2 Hz, 1H, Ar), 7.62 (d, Jo=8.5 Hz, 2H, Ar), 7.85 (d, Jo=8.5 Hz, 2H, Ar), 10.70 (s, 1H, NH).

Workup

  1. washwashed with water (20 mL), saturated aqueous brine solution (20 mL)
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. customto give a beige foam
  5. customto crystallize the desired product
  6. customCollection
  7. filtrationby filtration
  8. washby rinsing with excess hexanes

Sources & evidence

ORD record
ord-9277305346f04c45893e1e4c756d00bf
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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