Hydrochloric Acid → 4-{3-[2-(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-benzoic acid

HRID 546070Notes

Reaction equation

HRID 546070 reaction equation
C[O:2][C:3](=[O:37])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[CH:15]=[CH:14][C:13]([NH:16][C:17](=[O:36])[C@@H:18]([C:25]3[CH:30]=[CH:29][C:28]([S:31]([CH3:34])(=[O:33])=[O:32])=[C:27]([Cl:35])[CH:26]=3)[CH2:19][CH:20]3[CH2:24][CH2:23][CH2:22][CH2:21]3)=[N:12]2)=[CH:6][CH:5]=1.Cl>O1CCOCC1.O>[Cl:35][C:27]1[CH:26]=[C:25]([C@@H:18]([CH2:19][CH:20]2[CH2:21][CH2:22][CH2:23][CH2:24]2)[C:17]([NH:16][C:13]2[CH:14]=[CH:15][N:11]([CH2:10][C:7]3[CH:6]=[CH:5][C:4]([C:3]([OH:37])=[O:2])=[CH:9][CH:8]=3)[N:12]=2)=[O:36])[CH:30]=[CH:29][C:28]=1[S:31]([CH3:34])(=[O:32])=[O:33]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 671923594-{3-[2-(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-benzoic acid methyl ester

Product 1

HCID 671891864-{3-[2-(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-benzoic acidYield 40.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

The 4-{3-[2-(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-benzoic acid methyl ester (prepared in example 44, 840 mg, 1.54 mmol) was dissolved in dioxane (20 mL) and 6.0 M aqueous hydrochloric acid (20 mL) was added. The reaction was heated to 80° C. in a sealed vial while stirring for 8 h. Upon cooling, the reaction was diluted with water (25 mL) and the product extracted into ethyl acetate (3×50 mL). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo to give the desired product, 4-{3-[2-(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-benzoic acid (328 mg, 40%) as a white powder: ESI-LRMS m/e calcd for C26H28ClN3O5S [M+] 529.1, found 530.2 [M+H+]; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.01-1.13 (m, 2H, CH2), 1.33-1.80 (m, 8H, 4×CH2), 1.94-2.19 (m, 1H, CH), 3.32 (s, 3 H, SO2CH3), 3.83-3.93 (m, 1H, CH), 5.26 (s, 2H, NCH2), 6.47 (d, J=2.2 Hz, 1H, Ar), 7.26 (d, Jo=8.4 Hz, 2H, Ar), 7.55 (dd, Jo=8.2, Jm=1.7 Hz. 1H, Ar), 7.65 (d, Jm=1.7 Hz, 1H, Ar), 7.74 (d, J=2.2 Hz, 1H, Ar), 7.87 (d, Jo=8.4 Hz, 2H, Ar), 7.97 (d, Jo=8.2 Hz, 1H, Ar), 10.78 (s, 1H, NH), 12.88 (br.s., 1H, CO2H).

Workup

  1. temperatureUpon cooling
  2. extractionthe product extracted into ethyl acetate (3×50 mL)
  3. dry with materialThe combined organic layers were dried over magnesium sulfate
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-aae7228b48cb43ffb633270cb65b95f4
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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