p-Toluenesulfonic acid monohydrate → (S)-4-methyl-2-[4-(naphthalen-1-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide

HRID 19077Notes

Reaction equation

HRID 19077 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:37])[C@@H:15]([N:20]3[CH2:24][C:23]([O:25][C:26]4[C:35]5[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=5)[CH:29]=[CH:28][CH:27]=4)=[CH:22][C:21]3=[O:36])[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:9]2)[CH2:4][O:3]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO.C(OCC)(=O)C>[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:37])[C@@H:15]([N:20]2[CH2:24][C:23]([O:25][C:26]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH:29]=[CH:28][CH:27]=3)=[CH:22][C:21]2=[O:36])[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:9]1

Participants

5

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 66899177(S)-4-methyl-2-[4-(naphthalen-1-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide

Product 1

HCID 44252459(S)-4-methyl-2-[4-(naphthalen-1-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amideYield 80.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of (S)-4-methyl-2-[4-(naphthalen-1-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (0.43 g, 0.83 mmol) in methanol (8.38 mL) at 25° C. was treated with p-toluenesulfonic acid monohydrate (24 mg, 0.12 mmol). The reaction was stirred at 25° C. overnight. At this time, the reaction was diluted with ethyl acetate (50 mL) and was washed with a saturated aqueous sodium bicarbonate solution (1×100 mL) and a saturated aqueous sodium chloride solution (1×100 mL), dried over sodium sulfate, filtered and concentrated in vacuo. Purification by Analogix flash chromatography (40 g, 2.5-4% methanol/dichloromethane) afforded (S)-4-methyl-2-[4-(naphthalen-1-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide (0.32 g, 80%) as an off-white solid: HR-ES-MS m/z calculated for C26H30N4O5 [M+H]+ 479.2289, observed 479.2287; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.91 (d, J=6.3 Hz, 3H), 0.96 (d, J=6.3 Hz, 3H), 1.43-1.67 (m, 2H), 1.71-1.84 (m, 1H), 3.20-3.32 (m, 2H), 3.70-3.82 (m, 1H), 3.87 (dd, J=13.5, 7.5 Hz, 1H), 4.09 (dd, J=13.5, 3.8 Hz, 1H), 4.39 (d, J=18.1 Hz, 1H), 4.66-4.77 (m, 3H), 4.89 (dd, J=10.4, 5.0 Hz, 1H), 4.95 (d, J=5.4 Hz, 1H), 6.43 (d, J=2.1 Hz, 1H), 7.48-7.66 (m, 5H), 7.91 (d, J=8.2 Hz, 1H), 7.99-8.09 (m, 2H), 10.77 (s, 1H).

Workup

  1. washwas washed with a saturated aqueous sodium bicarbonate solution (1×100 mL)
  2. dry with materiala saturated aqueous sodium chloride solution (1×100 mL), dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification by Analogix flash chromatography (40 g, 2.5-4% methanol/dichloromethane)

Sources & evidence

ORD record
ord-68948e2c02f743b6a832a9f45f5f1a87
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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