p-Toluenesulfonic acid monohydrate → HCID 44253479, compound

HRID 18963Notes

Reaction equation

HRID 18963 reaction equation
[CH:1]1([CH2:7][C@H:8]([N:22]2[CH2:26][C:25](=[O:27])[CH2:24][C:23]2=[O:28])[C:9]([NH:11][C:12]2[CH:16]=[CH:15][N:14]([CH2:17][C:18]([OH:21])([CH3:20])[CH3:19])[N:13]=2)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.O.[C:30]1(C)[CH:35]=CC(S(O)(=O)=O)=C[CH:31]=1>C(O)CC>[CH:1]1([CH2:7][C@H:8]([N:22]2[CH2:26][C:25]([O:27][CH2:31][CH2:30][CH3:35])=[CH:24][C:23]2=[O:28])[C:9]([NH:11][C:12]2[CH:16]=[CH:15][N:14]([CH2:17][C:18]([OH:21])([CH3:19])[CH3:20])[N:13]=2)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 66899573HCID 66899573, compound

Product 1

HCID 44253479HCID 44253479, compoundYield 105.5%

Reagents, catalysts & solvents 1

HCID 10311-PropanolSolvent

Conditions

Temperature
100 °C

Procedure

(S)-3-cyclohexyl-2-(2,4-dioxo-pyrrolidin-1-yl)-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide (100 mg, 0.26 mmol) was added to n-propyl alcohol (3 mL), and toluene-4-sulfonic acid hydrate (10 mg). The mixture was stirred at 100° C. for 3 h. The reaction mixture was concentrated and the crude product obtained was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g; 0% to 10% methanol/dichloromethane) to afford (S)-3-cyclohexyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(2-oxo-4-propoxy-2,5-dihydro-pyrrol-1-yl)-propionamide (24 mg, 22%) as an off-white solid: LR-ES-MS m/z calculated for C22H34N4O4 [M]+ 432, observed [M+H]+ 433; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.82-0.95 (m, 5H), 0.96-1.14 (m, 2H), 1.27 (d, J=6.0 Hz, 6H), 1.37-1.89 (m, 11H), 3.90 (d, J=17.6 Hz, 1H), 3.88 (s, 2H), 4.28 (d, J=17.6 Hz, 1H), 4.44 (d, J=6.0 Hz, 2H), 4.67 (s, 1H), 4.76 (dd, J=10.3, 3.9 Hz, 1H), 5.12 (s, 1H), 6.42 (d, J=1.5 Hz, 1H), 7.52 (d, J=1.5 Hz, 1H), 10.72 (s, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe crude product obtained
  3. customwas purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g; 0% to 10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-28f4f0b3bce74da5b363ca79c028c8be
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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