Ethyl Acetate → 3-Chloro-N-(3-chloro-1-(pyridine-3-yl)-1H-pyrazol-4-yl)propanamide

HRID 515016Notes

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+].[Cl:25][CH2:26][CH2:27][C:28](Cl)=[O:29]>O>[Cl:25][CH2:26][CH2:27][C:28]([NH:7][C:6]1[C:2]([Cl:1])=[N:3][N:4]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[CH:5]=1)=[O:29]

Participants

Conditions

Temperature: 5 °C

Procedure

A 100 mL, three-neck round bottom flask was charged with 3-chloro-1-(pyridine-3-yl)-1H-pyrazol-4-amine (1.00 g, 5.14 mmol) and ethyl acetate (10 mL). Sodium bicarbonate (1.08 g, 6.17 mmol) was added and the reaction mixture was cooled to 5° C. 3-Chloropropanoyl chloride (0.783 g, 6.17 mmol) was added dropwise at <20° C. The reaction was allowed to warm up to 20° C. and stirred 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 white solid (1.40 g, 96%): mp 152-154° C.; 1H NMR (400 MHz, DMSO-d6) δ 10.04 (s, 1H), 9.07 (d, J=2.7 Hz, 1H), 8.89 (s, 1H), 8.54 (dd, J=4.7, 1.4 Hz, 1H), 8.23 (ddd, J=8.4, 2.7, 1.4 Hz, 1H), 7.54 (dd, J=8.4, 4.7, Hz, 1H), 3.90 (t, J=6.2 Hz, 2H), 2.94 (t, J=6.2 Hz, 2H); 13C NMR (101 MHz, DMSO-d6) δ 167.90, 147.50, 139.47, 135.46, 133.47, 125.51, 124.20, 122.47, 119.87, 40.63, 37.91; ESIMS m/z 285 ([M+H]+).

Workup

temperatureto warm up to 20° C.
customthe layers separated
extractionThe aqueous layer was extracted with ethyl acetate (20 mL)
concentrationthe combined organic layers were concentrated to dryness

Sources & evidence

ORD record: ord-51f990437f5140fc9b3db0751fe97f94
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09108946B2

Reaction notes

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