Ethanol → 3-cyclopentyl-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-2(R)-(4-methanesulfonyl-3-methyl-phenyl)-propionamide

HRID 546136Notes

Reaction equation

HRID 546136 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])[C@@H:16]([C:23]2[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[C:25]([CH3:33])[CH:24]=2)[CH2:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)=[N:10]1)(C)(C)C.C(O)C>Cl.C(OCC)(=O)C>[CH:18]1([CH2:17][C@H:16]([C:23]2[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:30])=[O:31])=[C:25]([CH3:33])[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:34])[CH2:22][CH2:21][CH2:20][CH2:19]1

Participants

5

Reactant 2

HCID 702EthanolHCID 67188933HCID 67188933, compound

Product 1

HCID 248891533-cyclopentyl-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-2(R)-(4-methanesulfonyl-3-methyl-phenyl)-propionamideYield 83%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

In a flask containing N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-cyclopentyl-2(R)-(4-methanesulfonyl-3-methyl-phenyl)-propionamide (300 mg, 0.56 mmol) was added ethanol (10 mL) and concentrated hydrochloric acid (seven drops) and was stirred at 25° C. for 2 h. It was then diluted with ethyl acetate (100 mL) and washed with water (1×30 mL) and saturated aqueous brine solution (1×30 mL). The organic layer was then dried over sodium sulfate and absorbed onto silica gel (2.5 g) and purified on Biotage Flash chromatography system (40S column, silica gel, 5% methanol/ethyl acetate) afforded 3-cyclopentyl-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-2(R)-(4-methanesulfonyl-3-methyl-phenyl)-propionamide (194 mg, 83%) as a white foam: [α]28589=−19.0° (c=0.20, methanol); ES-HRMS m/e calcd for C21H29N3O4S (M+H)+ 420.1952, observed 420.1949; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.03-1.18 (m, 2H, CH2), 1.37-1.80 (m, 8H, 4×CH2), 2.06-2.17 (m, 1H, CH) ArCH3), 3.16 (s, 3H, SO2CH3), 3.66 (q, J=5.6 Hz, 2H, OCH2), 3.85 (dd, J=8.8 Hz, J=5.7 Hz, 1H, ArCH), 3.98 (t, J=5.6 Hz, 2H, NCH2), 4.82 (t, J=5.6 Hz, 1H, OH), 6.40 (d, J=2.2 Hz, 1H, Ar), 7.41-7.46 (m, 2H, Ar), 7.52 (d, J=2.2 Hz, 1H, Ar), 7.83 (d, Jo=8.5 Hz, 1H, Ar), 10.72 (s, 1H, NH).

Workup

  1. washwashed with water (1×30 mL) and saturated aqueous brine solution (1×30 mL)
  2. dry with materialThe organic layer was then dried over sodium sulfate
  3. customabsorbed onto silica gel (2.5 g)
  4. custompurified on Biotage Flash chromatography system (40S column, silica gel, 5% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-3cc08c410655472c8fceeb6fd87fe09b
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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