Methanol → N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-((3,3,3-trifluoropropyl)thio)propanamide

HRID 515017Notes

Reaction equation

HRID 515017 reaction equation
Cl[CH2:2][CH2:3][C:4]([NH:6][C:7]1[C:8]([Cl:18])=[N:9][N:10]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[CH:11]=1)=[O:5].CO.[OH-].[K+].[F:23][C:24]([F:29])([F:28])[CH2:25][CH2:26][SH:27]>O.C(OCC)(=O)C>[Cl:18][C:8]1[C:7]([NH:6][C:4](=[O:5])[CH2:3][CH2:2][S:27][CH2:26][CH2:25][C:24]([F:29])([F:28])[F:23])=[CH:11][N:10]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[N:9]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 14797Potassium HydroxideHCID 177874113,3,3-Trifluoropropane-1-thiolHCID 917544613-Chloro-N-(3-chloro-1-(pyridine-3-yl)-1H-pyrazol-4-yl)propanamide

Product 1

HCID 86700584N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-((3,3,3-trifluoropropyl)thio)propanamideYield 92.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
20 °C

Procedure

A 100 mL, 3-neck round bottom flask was charged with 3-chloro-N-(3-chloro-1-(pyridine-3-yl)-1H-pyrazol-4-yl)propanamide (570 mg, 2.00 mmol) and methanol (10 mL), potassium hydroxide (135 mg, 2.40 mmol) was added, followed by 3,3,3-trifluropropane-1-thiol (312 mg, 2.40 mmol) The mixture was heated at 50° C. for 4 hours, at which point thin layer chromatography analysis [Eluent: ethyl acetate] indicated the reaction was complete to give exclusively a new product. It was cooled to 20° C. and diluted with water (20 mL) and ethyl acetate (20 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (20 mL). The organics were dried over sodium sulfate and concentrated to dryness to afford a light yellow oil, which solidified upon standing to give a light yellow solid (700 mg, 92%): mp 99-102° C.; 1H NMR (400 MHz, DMSO-d6) δ 9.92 (s, 1H), 9.05 (d, J=2.7 Hz, 1H), 8.86 (s, 1H), 8.54 (dd, J=4.5, 1.4 Hz, 1H), 8.21 (ddd, J=8.4, 2.7, 1.4 Hz, 1H), 7.54 (dd, J=8.4, 4.7 Hz, 1H), 2.86 (t, J=7.3 Hz, 2H), 2.74 (td, J=6.5, 5.6, 4.2 Hz, 4H), 2.59 (ddd, J=11.7, 9.7, 7.4 Hz, 2H); 13C NMR (101 MHz, DMSO-d6) δ 169.32, 147.49, 139.44, 135.47, 133.40, 126.60 (q, J=296 Hz), 125.49, 124.23, 122.30, 120.00, 35.18, 33.42 (q, J=27.2 Hz), 26.77, 23.05 (q, J=3.3 Hz); EIMS m/z 378 ([M]+).

Workup

  1. additionwas added
  2. customto give exclusively a new product
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (20 mL)
  5. dry with materialThe organics were dried over sodium sulfate
  6. concentrationconcentrated to dryness
  7. customto afford a light yellow oil, which

Sources & evidence

ORD record
ord-a9fee937bfbd47098255d9acb75fd798
Source dataset
uspto-grants-2015_08
Patent number
US09108946B2

Reaction notes

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