p-Toluenesulfonic acid monohydrate → HCID 57920056, compound

HRID 19342Notes

Reaction equation

HRID 19342 reaction equation
[Cl:1][C:2]1[CH:36]=[CH:35][CH:34]=[CH:33][C:3]=1[O:4][C:5]1[CH2:9][N:8]([CH:10]([CH2:27][C:28]([F:31])([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:32])[CH:6]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[Cl:1][C:2]1[CH:36]=[CH:35][CH:34]=[CH:33][C:3]=1[O:4][C:5]1[CH2:9][N:8]([CH:10]([CH2:27][C:28]([F:31])([F:29])[F: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:32])[CH:6]=1

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 866352422-[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]-4,4,4-trifluoro-butyramide

Product 1

HCID 57920056HCID 57920056, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

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]-4,4,4-trifluoro-butyramide (164 mg, 0.31 mmol), methanol (5 mL) and p-toluenesulfonic acid monohydrate (15 mg). The mixture was stirred at 25° C. for 16 h and then concentrated in vacuo with silica gel (1.3 g). Purification by Biotage flash chromatography (Aspire 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]-4,4,4-trifluoro-butyramide (116 mg, 77%) as a white foam: HR-ES-MS m/z calculated for C20H20N4O5ClF3 [M+H]+ 489.1147, observed 489.1148; 1H NMR (300 MHz, DMSO-d6) δ ppm 2.80-3.13 (m, 2H), 3.20-3.32 (m, 2H), 3.70-3.81 (m, 1H), 3.87 (dd, J=13.4, 7.5 Hz, 1H), 4.10 (dd, J=13.4, 3.9 Hz, 1H), 4.38 (s, 2H), 4.72 (t, J=5.6 Hz, 1H), 4.84 (s, 1H), 4.95 (d, J=5.4 Hz, 1H), 5.18 (dd, J=9.4, 3.9 Hz, 1H), 6.43 (d, J=2.1 Hz, 1H), 7.31-7.41 (m, 1H), 7.42-7.53 (m, 2H), 7.56 (d, J=2.1 Hz, 1H), 7.65 (d, J=8.2 Hz, 1H), 10.92 (s, 1H).

Workup

  1. customIn a round bottom flask was placed
  2. concentrationconcentrated in vacuo with silica gel (1.3 g)
  3. customPurification by Biotage flash chromatography (Aspire column, 100% ethyl acetate to 5% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-81e8b36dd13a470d9d9b2b8e62bd87d4
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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