p-Toluenesulfonic acid monohydrate → (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-4-methoxy-butyramide

HRID 19371Notes

Reaction equation

HRID 19371 reaction equation
[Cl:1][C:2]1[CH:35]=[CH:34][CH:33]=[CH:32][C:3]=1[O:4][C:5]1[CH2:9][N:8]([C@@H:10]([CH2:27][CH2:28][O:29][CH3:30])[C:11]([NH:13][C:14]2[CH:18]=[CH:17][N:16]([CH2:19][C@@H:20]3[CH2:24][O:23]C(C)(C)[O:21]3)[N:15]=2)=[O:12])[C:7](=[O:31])[CH:6]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[Cl:1][C:2]1[CH:35]=[CH:34][CH:33]=[CH:32][C:3]=1[O:4][C:5]1[CH2:9][N:8]([C@@H:10]([CH2:27][CH2:28][O:29][CH3:30])[C:11]([NH:13][C:14]2[CH:18]=[CH:17][N:16]([CH2:19][C@@H:20]([OH:21])[CH2:24][OH:23])[N:15]=2)=[O:12])[C:7](=[O:31])[CH:6]=1

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 67504039(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-4-methoxy-butyramide

Product 1

HCID 57920179(S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-4-methoxy-butyramideYield 92.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

In a round bottom flask under argon was placed (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-4-methoxy-butyramide (26 mg, 0.051 mmol) dissolved in methanol (3 mL). This mixture was treated with p-toluenesulfonic acid monohydrate (1.5 mg, 0.008 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 5% methanol/ethyl acetate) to afford (S)-2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-4-methoxy-butyramide (22 mg, 92%) as a light yellow foam: HR-ES-MS m/z calculated for C21H25N4O6Cl [M+H]+ 465.1536, observed 465.1536; 1H NMR (300 MHz, DMSO-d6) δ ppm 2.06 (br. s., 2H), 3.20 (s, 3H), 3.22-3.31 (m, 4H), 3.67-3.78 (m, 1H), 3.78-3.90 (m, 1H), 4.07 (dd, J=13.6, 3.9 Hz, 1H), 4.27 (d, J=18.4 Hz, 1H), 4.50 (d, J=18.4 Hz, 1H), 4.69 (t, J=5.4 Hz, 1H), 4.78 (s, 1H), 4.79-4.88 (m, 1H), 4.92 (d, J=5.4 Hz, 1H), 6.39 (d, J=2.1 Hz, 1H), 7.30-7.40 (m, 1H), 7.41-7.55 (m, 3H), 7.64 (d, J=7.2 Hz, 1H), 10.64 (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 5% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-ce0e5d81e78449a1bc39750c090ae95d
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

Loading…