3-{3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-propionic acid tert-butyl ester → 3-{3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-propionic acid

HRID 545999Notes

Reaction equation

HRID 545999 reaction equation
C([O:5][C:6](=[O:35])[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]([Cl:33])[CH:24]=2)[CH2:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)=[N:10]1)(C)(C)C>FC(F)(F)C(O)=O.C(Cl)Cl>[Cl:33][C:25]1[CH:24]=[C:23]([C@@H:16]([CH2:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[C:15]([NH:14][C:11]2[CH:12]=[CH:13][N:9]([CH2:8][CH2:7][C:6]([OH:35])=[O:5])[N:10]=2)=[O:34])[CH:28]=[CH:27][C:26]=1[S:29]([CH3:32])(=[O:31])=[O:30]

Participants

3

Reactant 1

HCID 671898343-{3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-propionic acid tert-butyl ester

Product 1

HCID 671905033-{3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-propionic acidYield 97.1%

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Conditions

Temperature
60 °C

Procedure

3-{3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-propionic acid tert-butyl ester (prepared in example 8, 3.00 g, 5.72 mmol) was dissolved in 20% trifluoroacetic acid/methylene chloride (100 mL) and stirred under reflux at 60° C. for 2 h, after which time the solvent was removed in vacuo. The crude material was the purified by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 120 g; 0% ethyl acetate/hexanes to 75% ethyl acetate/hexanes) to afford 3-{3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-propionic acid (2.60 g, 97%) as a white solid: ESI-LRMS m/e calcd for C21H26ClN3O5S [M+] 509.18, found 510.0 [M+H+], 1019.7 [2M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.06-1.23 (m, 2H, CH2), 1.42-1.91 (m, 8H, 4×CH2), 2.12-2.29 (m, 1H, CH), 2.83 (t, J=6.4 Hz, 2H, COCH2), 3.25 (s, 3H, SO2CH3), 3.57 (t, J=7.5 Hz, 1H, CH), 4.36 (t, J=6.4 Hz, 2H, NCH2), 6.77 (d, J=2.5 Hz, 1H, Ar), 7.41 (d, J=2.5 Hz, 1 H, Ar), 7.48 (dd, Jo=8.1, Jm=1.5 Hz. 1H, Ar), 7.62 (d, Jm=1.5 Hz, 1H, Ar), 8.06 (d, Jo=8.1 Hz, 1H, Ar), 9.85 (br.s., 1H, CO2H), 10.38 (s, 1H, NH).

Workup

  1. customafter which time the solvent was removed in vacuo
  2. custompurified by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 120 g; 0% ethyl acetate/hexanes to 75% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-92b76018997d460eba77f586500c2295
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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