Methanol → HCID 57920093, compound

HRID 19321Notes

Reaction equation

HRID 19321 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]([F:21])([F:20])[F:19])=[N:9]2)[CH2:4][O:3]1.CO.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>ClCCl>[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]([F:20])([F:19])[F:21])=[N:9]1

Participants

5

Reactant 3

HCID 887MethanolHCID 521998p-Toluenesulfonic acid monohydrateHCID 669001492-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5,5-trifluoro-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide

Product 1

HCID 57920093HCID 57920093, compoundYield 71.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

In a round bottom flask was placed 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5,5-trifluoro-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide (210 mg, 0.39 mmol), methanol (5 mL) and p-toluenesulfonic acid hydrate (17 mg). This mixture was stirred at 25° C. for 16 h and then diluted with dichloromethane and concentrated in vacuo with silica gel (2 g). Purification by Biotage flash chromatography (Aspire, 40 g column, 100% ethyl acetate to 5% methanol/ethyl acetate) afforded 2-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-5,5,5-trifluoro-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide (140 mg, 71%) as a white foam: HR-ES-MS m/z calculated for C21H21N4O5ClF3 [M+H]+ 503.1304, observed 503.1300; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.88-2.46 (m, 4H), 3.20-3.33 (m, 2H), 3.68-3.82 (m, 1H), 3.86 (dd, J=13.4, 7.2 Hz, 1H), 4.09 (dd, J=13.4, 3.9 Hz, 1H), 4.32 (d, J=18.1 Hz, 1H), 4.53 (m, J=18.1 Hz, 1H), 4.72 (t, J=5.4 Hz, 1H), 4.78 (dd, J=9.1, 5.1 Hz, 1H), 4.83 (s, 1H), 4.94 (d, J=5.1 Hz, 1H), 6.42 (d, J=2.1 Hz, 1H), 7.33-7.40 (m, 1H), 7.42-7.57 (m, 3H), 7.66 (d, J=8.2 Hz, 1H), 10.75 (s, 1H).

Workup

  1. customIn a round bottom flask was placed
  2. concentrationconcentrated in vacuo with silica gel (2 g)
  3. customPurification by Biotage flash chromatography (Aspire, 40 g column, 100% ethyl acetate to 5% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-9b9054ec58414a0497ba237b39fb60ab
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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