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

HRID 546209Notes

Reaction equation

HRID 546209 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:35])[C@@H:16]([C:23]2[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[C:25]([C:33]#[N:34])[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(#N)C>[C:33]([C:25]1[CH:24]=[C:23]([C@@H:16]([CH2:17][CH:18]2[CH2:19][CH2:20][CH2:21][CH2:22]2)[C:15]([NH:14][C:11]2[CH:12]=[CH:13][N:9]([CH2:8][CH2:7][OH:6])[N:10]=2)=[O:35])[CH:28]=[CH:27][C:26]=1[S:29]([CH3:32])(=[O:30])=[O:31])#[N:34]

Participants

5

Reactant 2

HCID 702EthanolHCID 67190407(R)-N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

Product 1

HCID 24889157(R)-2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-propionamideYield 77%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalystHCID 6342AcetonitrileSolvent

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}-2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (102 mg, 0.19 mmol), ethanol (2 mL), and concentrated hydrochloric acid (3 drops). It was stirred at 25° C. for 1 h. The reaction was then diluted with some acetonitrile and concentrated with silica gel (2 g) in vacuo and purified on a Biotage Flash chromatography system (40S column, silica gel, 100% ethyl acetate to 10% methanol/ethyl acetate) to afford (R)-2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-propionamide (63 mg, 77%) as a light yellow solid: [α]30589=−40.0° (c=0.10, methanol); ES-HRMS m/e calcd for C21H26N4O4S (M+H)+ 431.1748, observed 431.1749; 1H NMR (400 MHz, DMSO-d6) δ 1.12 (m, 2H, CH2), 1.38-1.78 (m, 8H, 4×CH2), 2.12 (m, 1H, CH), 3.36 (s, 3H, SO2CH3), 3.67 (m, 2H, OCH2), 3.86 (m, 3H, ArCHCO and NCH2), 4.83 (t, J=5.3 Hz, 1 H, OH), 6.41 (d, J=2.2 Hz, 1H, Ar), 7.54 (d, J=2.2 Hz, 1H, Ar), 7.95 (dd, Jm=1.6 Hz, Jo=8.2 Hz, 1H, Ar), 8.11 (d, Jm=1.6 Hz, 1H, Ar), 8.11 (d, Jo=8.2 Hz, 1H, Ar), 10.83 (s, 1H, NH).

Workup

  1. customIn a round bottom flask was placed
  2. concentrationconcentrated with silica gel (2 g) in vacuo
  3. custompurified on a Biotage Flash chromatography system (40S column, silica gel, 100% ethyl acetate to 10% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-4606d249a5164a479b8d20cf6d3e1259
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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