(R)-N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionamide → (R)-3-cyclopentyl-2-(3,4-dichloro-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-propionamide

HRID 546199Notes

Reaction equation

HRID 546199 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:31])[C@@H:16]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[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>[CH:18]1([CH2:17][C@H:16]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[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:31])[CH2:19][CH2:20][CH2:21][CH2:22]1

Participants

4

Reactant 1

HCID 67188509(R)-N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionamide

Product 1

HCID 24889330(R)-3-cyclopentyl-2-(3,4-dichloro-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-propionamideYield 90%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 702EthanolSolvent

Conditions

Temperature
25 °C

Procedure

In a round bottom flask was placed (R)—N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionamide (128 mg, 0.25 mmol), ethanol (10 mL) and concentrated hydrochloric acid (2 drops). This solution was then stirred at 25° C. until all starting material is consumed (˜1 hr). The reaction was then diluted with ethyl acetate (30 mL) and transferred to a separatory funnel where it was washed with a saturated aqueous solution of sodium bicarbonate (10 mL). The aqueous layer was then extracted with ethyl acetate (3×10 mL). The organic layers were then combined dried over magnesium sulfate, filtered and concentrated in vacuo. Purification on an AnaLogix Intelliflash system (4 g column, 20% ethyl acetate/hexanes to 60% ethyl acetate/hexanes) afforded (R)-3-cyclopentyl-2-(3,4-dichloro-phenyl)-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-propionamide (89 mg, 90%) as a white foam: [α]30589=−22.2° (c=0.18, methylene chloride); ES-HRMS m/e calcd for C19H23N3O2Cl2 (M+H)+ 418.1059, observed 418.1061; 1H NMR (300 MHz, DMSO-d6) δ 1.10 (m, 2H, CH2), 1.35-1.79 (m, 8H, 4×CH2), 2.05 (m, 1H, CH), 3.67 (q, J=5.6 Hz, 2H, OCH2), 3.79 (m, 1H, ArCHCO), 4.00 (t, J=5.6 Hz, 2H, NCH2), 4.83 (t, J=5.4 Hz, 1H, OH), 6.40 (d, J=2.2 Hz, 1H, Ar), 7.34 (dd, Jm=2.0 Hz, Jo=8.2 Hz, 1H, Ar), 7.53 (d, J=2.2 Hz, 1H, Ar), 7.58 (d, Jo=8.2 Hz, 1H, Ar), 7.59 (s, 1H, Ar), 10.71 (s, 1H, NH).

Workup

  1. customIn a round bottom flask was placed
  2. customis consumed (˜1 hr)
  3. additionThe reaction was then diluted with ethyl acetate (30 mL)
  4. customtransferred to a separatory funnel
  5. washwhere it was washed with a saturated aqueous solution of sodium bicarbonate (10 mL)
  6. extractionThe aqueous layer was then extracted with ethyl acetate (3×10 mL)
  7. dry with materialThe organic layers were then combined dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification on an AnaLogix Intelliflash system (4 g column, 20% ethyl acetate/hexanes to 60% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-7fa8988b2438470c9af71df4f835f93d
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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