p-Toluenesulfonic acid monohydrate → HCID 57920108, compound

HRID 19351Notes

Reaction equation

HRID 19351 reaction equation
CC1(C)[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:36])[CH:15]([N:22]3[CH2:26][C:25]([O:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[Cl:34])=[CH:24][C:23]3=[O:35])[CH2:16][CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[N:9]2)[CH2:4][O:3]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[OH:6][C@@H:5]([CH2:4][OH:3])[CH2:7][N:8]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:36])[CH:15]([N:22]2[CH2:26][C:25]([O:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[Cl:34])=[CH:24][C:23]2=[O:35])[CH2:16][CH2:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[N:9]1

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 66899251HCID 66899251, compound

Product 1

HCID 57920108HCID 57920108, compoundYield 78.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

In a round bottom flask under argon was placed 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5-dimethyl-hexanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (14 mg, 0.026 mmol) in methanol (2 mL). To this mixture was then added p-toluenesulfonic acid monohydrate (1 mg, 0.004 mmol) and stirred at 25° C. for 16 h. After this time period, the mixture was concentrated in vacuo and purified by AnaLogix IntelliFlash flash chromatography (4 g column, 100% ethyl acetate to 40% methanol/ethyl acetate) To afford 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5-dimethyl-hexanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]amide (10 mg, 77%) as a white foam: HR-ES-MS m/z calculated for C24H31N4O5Cl [M+H]+ 491.2056, observed 491.2052; 1H NMR (300 MHz, CDCl3) δ ppm 0.91 (br. s., 9H), 1.04-1.35 (m, 2H), 1.79 (br. s., 1H), 1.99 (br. s., 1H), 3.38-3.84 (m, 2H), 3.97-4.29 (m, 4H), 4.41 (d, J=17.8 Hz, 1H), 4.66 (br. s., 1H), 4.86 (br. s., 1H), 6.65 (br. s., 1H), 7.26 (br. s., 4H), 7.47 (br. s., 1H), 9.56 (br. s., 1H).

Workup

  1. customIn a round bottom flask under argon was placed
  2. concentrationAfter this time period, the mixture was concentrated in vacuo
  3. custompurified by AnaLogix IntelliFlash flash chromatography (4 g column, 100% ethyl acetate to 40% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-129b2438bb0241f0841ba694eb69e939
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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