Acetic Anhydride → (αR)-N-[1-[2-(Acetyloxy)ethyl]-1H-pyrazol-3-yl]-3-chloro-α-(cyclopentylmethyl)-4-(methylsulfonyl)benzeneacetamide

HRID 546114Notes

Reaction equation

HRID 546114 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:24][CH:25]2[CH2:29][CH2:28][CH2:27][CH2:26]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH2:21][CH2:22][OH:23])[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].[C:30](OC(=O)C)(=[O:32])[CH3:31]>N1C=CC=CC=1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:24][CH:25]2[CH2:26][CH2:27][CH2:28][CH2:29]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH2:21][CH2:22][O:23][C:30](=[O:32])[CH3:31])[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

5

Reactant 2

HCID 7918Acetic AnhydrideHCID 24889832HCID 24889832, compound

Product 1

HCID 24888985(αR)-N-[1-[2-(Acetyloxy)ethyl]-1H-pyrazol-3-yl]-3-chloro-α-(cyclopentylmethyl)-4-(methylsulfonyl)benzeneacetamideYield 60%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

2-(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-propionamide (prepared in Example 67, 102 mg, 0.27 mmol) was dissolved in pyridine (2 mL) and acetic anhydride (27 umL, 0.29 mmol) was added. The reaction stirred at 25° C. for 16 h. The solution was diluted with ethyl acetate (40 mL), washed with aqueous 1.0 M hydrochloric acid solution (3×15 mL), saturated aqueous brine solution (1×10 mL), dried over magnesium sulfate and concentrated in vacuo. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 50% ethyl acetate/hexanes to 75% ethyl acetate/hexanes) afforded acetic acid 2-{3-[2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-ethyl ester (78 mg, 60%) as a white foam: ESI-LRMS m/e calcd for C22H28ClN3O5S [M+] 481.1, found 482.3 [M+H+]; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.02-1.20 (m, 2 H, CH2), 1.39-1.79 (m, 8H, 4×CH2), 1.95 (s, 3H, COCH3), 2.01-2.19 (m, 1H, CH), 3.33 (s, 3H, SO2CH3), 3.86-3.95 (m, 1H, CH), 4.18-4.24 (m, 2H, OCH2), 4.29 (t, J=5.0 Hz, Hz, 2H, NCH2), 6.43 (d, Jo=2.3 Hz, 1H, Ar), 7.55-7.61 (m, 2H, Ar), 7.68 (d, Jm=1.7 Hz, 1H, Ar), 7.99 (d, Jo=8.2 Hz, 1H, Ar), 10.77 (s, 1H, NH).

Workup

  1. washwashed with aqueous 1.0 M hydrochloric acid solution (3×15 mL), saturated aqueous brine solution (1×10 mL)
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. customPurification by flash column chromatography (Merck silica gel 60, 40-63 μm; 50% ethyl acetate/hexanes to 75% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-3bb39a66059a4392ac46576b98dbde98
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

Loading…