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

HRID 1482414Notes

Reaction equation

HRID 1482414 reaction equation
[Cl:1][C:2]1[C:6]([NH2:7])=[CH:5][N:4]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[N:3]=1.C(OCC)(=O)C.C(=O)(O)[O-].[Na+].[F:25][C:26]([F:36])([F:35])[CH2:27][CH2:28][S:29][CH2:30][CH2:31][C:32](Cl)=[O:33]>O>[Cl:1][C:2]1[C:6]([NH:7][C:32](=[O:33])[CH2:31][CH2:30][S:29][CH2:28][CH2:27][C:26]([F:25])([F:35])[F:36])=[CH:5][N:4]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[N:3]=1

Participants

6

Reactant 4

HCID 8857Ethyl Acetate2×HCID 516892Sodium BicarbonateHCID 674993943-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-amineHCID 867006283-((3,3,3-Trifluoropropyl)thio)propanoyl chloride

Product 1

HCID 86700584N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-3-((3,3,3-trifluoropropyl)thio)propanamideYield 72%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 100-mL, three-neck round bottom flask was charged with 3-chloro-(pyridin-3-yl)-1H-pyrazol-4-amine (1.00 g, 5.14 mmol) and ethyl acetate (10 mL). Sodium bicarbonate (1.08 g, 12.9 mmol) was added, followed by dropwise addition of 3-((3,3,3-trifluoropropyl)thio)propanoyl chloride (1.36 g, 6.17 mmol) at <20° C. The reaction was stirred at 20° C. for 2 hours, at which point thin layer chromatography analysis [Eluent: ethyl acetate] indicated that the reaction was complete. The reaction was diluted with water (50 mL) and the layers separated. The aqueous layer was extracted with ethyl acetate (20 mL) and the combined organic layers were concentrated to dryness to afford a light brown oil. The residue was purified by flash column chromatography using 30-60% ethyl acetate/hexanes. The fractions containing pure product were concentrated to dryness to afford a white solid (1.40 g, 72%): 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. customthe layers separated
  2. extractionThe aqueous layer was extracted with ethyl acetate (20 mL)
  3. concentrationthe combined organic layers were concentrated to dryness
  4. customto afford a light brown oil
  5. customThe residue was purified by flash column chromatography
  6. additionThe fractions containing pure product
  7. concentrationwere concentrated to dryness

Sources & evidence

ORD record
ord-fb8ca74c0d8d4257830026cddadf8f12
Source dataset
uspto-grants-2016_08
Patent number
US09414594B2

Reaction notes

Loading…