p-Toluenesulfonic acid → HCID 57920158, compound

HRID 19181Notes

Reaction equation

HRID 19181 reaction equation
[F:1][C:2]1[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[C:3]=1[O:4][C:5]1[CH2:9][N:8]([CH:10]([CH2:27][C:28]2([F:33])[CH2:32][CH2:31][CH2:30][CH2:29]2)[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:34])[CH:6]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[F:1][C:2]1[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[C:3]=1[O:4][C:5]1[CH2:9][N:8]([CH:10]([CH2:27][C:28]2([F:33])[CH2:32][CH2:31][CH2:30][CH2:29]2)[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:34])[CH:6]=1

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 66899204HCID 66899204, compound

Product 1

HCID 57920158HCID 57920158, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 2-[4-(2,6-difluoro-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]-3-(1-fluoro-cyclopentyl)-propionamide (0.330 g, 0.60 mmol) in methanol (6 mL) was treated with p-toluenesulfonic acid (0.017 g, 0.09 mmol). The reaction mixture was stirred at room temperature overnight. The solvents were removed under vacuum and ethyl acetate was added to the residue. The resulting mixture was washed with saturated sodium bicarbonate, a saturated sodium chloride solution and dried over magnesium sulfate. The mixture was filtered and evaporated which afforded 2-[4-(2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-N-[1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-3-(1-fluoro-cyclopentyl)-propionamide (0.260 g, 87%) as a light yellow solid: 1H NMR (300 MHz, DMSO-d6) δ ppm 1.51-1.96 (m, 8H), 2.10-2.43 (m, 2H), 3.22-3.32 (m, 2H), 3.69-3.94 (m, 2H), 4.09 (dd, J=13.3, 3.3 Hz, 1H), 4.33 (d, J=18.3 Hz, 1H), 4.53 (d, J=18.3 Hz, 1H), 4.71 (t, J=5.3 Hz, 1H), 4.94 (d, J=5.1 Hz, 1H), 5.02 (s, 1H), 5.05-5.13 (m, 1H), 6.41 (s, 1H), 7.29-7.50 (m, 3H), 7.54 (s, 1H), 10.81 (s, 1H) HR-ES-MS m/z calculated for C24H27F3N4O5 [M+H]+, 509.2007 observed 509.2009.

Workup

  1. customThe solvents were removed under vacuum and ethyl acetate
  2. additionwas added to the residue
  3. washThe resulting mixture was washed with saturated sodium bicarbonate
  4. dry with materiala saturated sodium chloride solution and dried over magnesium sulfate
  5. filtrationThe mixture was filtered
  6. customevaporated which

Sources & evidence

ORD record
ord-8d4e7fabfb8044e599aee6bea6ecf32a
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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