Propylene Oxide → 3-chloro-N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethylpropanamide

HRID 929302Notes

Reaction equation

HRID 929302 reaction equation
Cl.Cl.[Cl:3][C:4]1[C:8]([NH:9][CH2:10][CH3:11])=[CH:7][N:6]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[N:5]=1.C1OC1C.[Cl:22][CH2:23][CH2:24][C:25](Cl)=[O:26]>C(Cl)Cl>[Cl:22][CH2:23][CH2:24][C:25]([N:9]([C:8]1[C:4]([Cl:3])=[N:5][N:6]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[CH:7]=1)[CH2:10][CH3:11])=[O:26]

Participants

5

Reactant 3

HCID 6378Propylene OxideHCID 693643-Chloropropionyl chlorideHCID 86705836HCID 86705836, compound

Product 1

HCID 867005753-chloro-N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethylpropanamideYield 80.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine dihydrochloride (1.00 g, 3.38 mmol) in CH2Cl2 (7 mL) was added propylene oxide (1.00 mL, 13.5 mmol) followed by 3-chloropropanoyl chloride (0.360 mL, 3.72 mmol). This was stirred at room temperature for 16 hours, and then the reaction mixture was then diluted with CH2Cl2 and washed with water. The phases were separated, the organic were dried, concentrated and purified by silica gel chromatography eluting with 0%-50% acetone/hexanes to afford a white solid (0.850 g, 80%): mp 85-86° C.; 1H NMR (400 MHz, CDCl3) δ 8.96 (d, J=2.6 Hz, 1H), 8.64 (dd, J=4.7, 1.4 Hz, 1H), 8.05 (ddd, J=8.3, 2.7, 1.4 Hz, 1H), 7.98 (s, 1H), 7.47 (ddd, J=8.4, 4.8, 0.6 Hz, 1H), 3.80 (t, J=6.7 Hz, 2H), 3.74 (q, J=7.1 Hz, 2H), 2.64 (t, J=6.7 Hz, 2H), 1.18 (t, J=7.2 Hz, 3H); ESIMS m/z 313 ([M+H]+).

Workup

  1. washwashed with water
  2. customThe phases were separated
  3. customthe organic were dried
  4. concentrationconcentrated
  5. custompurified by silica gel chromatography
  6. washeluting with 0%-50% acetone/hexanes

Sources & evidence

ORD record
ord-8703e44bceab4575939bc0cd4e91309b
Source dataset
uspto-grants-2016_03
Patent number
US09295260B2

Reaction notes

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