Methanol → HCID 57920028, compound

HRID 19327Notes

Reaction equation

HRID 19327 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]([CH:10]([CH2:27][CH:28]([F:30])[F:29])[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.CO.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>ClCCl>[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]([CH:10]([CH2:27][CH:28]([F:30])[F:29])[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

5

Reactant 3

HCID 887MethanolHCID 521998p-Toluenesulfonic acid monohydrateHCID 866352412-[4-(2-chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1-H-pyrazol-3-yl]-4,4-difluoro-butyramide

Product 1

HCID 57920028HCID 57920028, compoundYield 66.1%

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]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1-H-pyrazol-3-yl]-4,4-difluoro-butyramide (180 mg, 0.35 mmol), methanol (5 mL) and p-toluenesulfonic acid hydrate (20 mg). The 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]-N-[1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-4,4-difluoro-butyramide (109 mg, 66%) as a white foam: HR-ES-MS m/z calculated for C20H21N4O5ClF2 [M+Na]+ 493.1061, observed 493.1057; 1H NMR (300 MHz, DMSO-d6) δ ppm 2.43 (m, 2H), 3.19-3.31 (m, 2H), 3.76 (br. s., 1H), 3.85 (dd, J=13.3, 7.8 Hz, 1H), 4.08 (dd, J=13.3, 3.8 Hz, 1H), 4.35 (d, J=18.4 Hz, 1H), 4.45 (d, J=18.4 Hz, 1H), 4.70 (t, J=5.6 Hz, 1H), 4.81 (s, 1H), 4.93 (d, J=5.1 Hz, 1H), 4.94-5.02 (m, 1H), 6.10 (tt, J=56.1, 4.2 Hz, 1H), 6.40 (d, J=2.1 Hz, 1H), 7.31-7.39 (m, 1H), 7.41-7.52 (m, 2H), 7.53 (d, J=2.1 Hz, 1H), 7.64 (d, J=7.5 Hz, 1H), 10.76 (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-6bab658a0d1e4fa2932e64be94258763
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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