Ethanol → HCID 67189473, compound

HRID 546215Notes

Reaction equation

HRID 546215 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:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=2)[CH2:17][C@H:18]2[CH2:22][CH2:21][C:20](=[O:23])[CH2:19]2)=[N:10]1)(C)(C)C.C(O)C>Cl.C(#N)C>[OH:6][CH2:7][CH2:8][N:9]1[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:34])[C@@H:16]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:32])([F:31])[F:33])[CH:25]=2)[CH2:17][C@H:18]2[CH2:22][CH2:21][C:20](=[O:23])[CH2:19]2)=[N:10]1

Participants

5

Reactant 2

HCID 702EthanolHCID 67188835HCID 67188835, compound

Product 1

HCID 67189473HCID 67189473, compoundYield 92.1%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
25 °C

Procedure

In a flask containing (R)—N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-((R)-3-oxo-cyclopentyl)-2-(3-trifluoromethyl-phenyl)-propionamide (70 mg, 0.13 mmol) was added ethanol (2 mL) and concentrated hydrochloric acid (three drops) and it was stirred at 25° C. for 1 h. It was then diluted with acetonitrile and absorbed onto silica gel (2 g) in vacuo and purified on Biotage Flash chromatography system (40S column, silica gel, 80% ethyl acetate/hexanes to 10% methanol/ethyl acetate) to afford (R)—N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-3-((R)-3-oxo-cyclopentyl)-2-(3-trifluoromethyl-phenyl)-propionamide (49 mg, 89%) as a yellow foam: [α]25589=−79.3° (c=0.14, methanol); ES-HRMS m/e calcd for C20H22N3O3F3 (M+H)+ 410.1686, observed 410.1687; 1H NMR (300 MHz, DMSO-d6) δ 1.51 (m, 1H, CH), 1.73-2.30 (m, 8H, 4×CH2), 3.66 (m, 2H, OCH2), 3.95 (m, 1H, ArCHCO), 3.99 (m, 2H, NCH2), 4.83 (t, J=5.4 Hz, 1H, OH), 6.41 (d, J=2.0 Hz, 1H, Ar), 7.54 (d, J=2.0 Hz, 1 H, Ar), 7.60 (m, 2H, Ar), 7.69 (brd, 1H, Ar), 7.73 (brs, 1H, Ar), 10.79 (s, 1H, NH).

Workup

  1. customabsorbed onto silica gel (2 g) in vacuo
  2. custompurified on Biotage Flash chromatography system (40S column, silica gel, 80% ethyl acetate/hexanes to 10% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-b6d8ddf37871415586fbae885025b0e0
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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