4-Pyridinecarbothioamide → HCID 66747606, compound

HRID 2402015Notes

Reaction equation

HRID 2402015 reaction equation
Cl[CH:2]([C:8](=O)[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[C:18]([NH2:26])(=[S:25])[C:19]1[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=1>CC(O)C>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:9][C:8]2[N:26]=[C:18]([C:19]3[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=3)[S:25][C:2]=2[C:3]([O:5][CH2:6][CH3:7])=[O:4])=[CH:11][CH:12]=1

Participants

4

Reactant 2

HCID 27237884-PyridinecarbothioamideHCID 86667468HCID 86667468, compound

Product 1

HCID 66747606HCID 66747606, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a solution of ethyl 2-chloro-4-(4-chlorophenyl)-3-oxobutanoate (70.8 g, 257 mmol) in IPA (2.96 L) was added thioisonicotinamide (71.1 g, 515 mmol) and the resulting mixture was refluxed for 3 days. The reaction was cooled and concentrated in vacuo and the residue was partitioned between DCM (300 ml) and saturated sodium bicarbonate solution (200 mL). The layers were separated and the aqueous layer was extracted with DCM (100 mL). The combined DCM layers were washed with brine (100 mL), dried over MgSO4, filtered, and concentrated in vacuo to give crude product which was purified by silica gel chromatography (ethyl acetate/DCM=0/100→40/60) followed by recrystallization from ethyl acetate/hexanes to give 33 g of the title compound as yellow crystals. (36% yield). LC/MS (FA) ES+ 359. 1H NMR (400 MHz, CDCl3) δ: 8.74-8.72 (m, 2H), 7.81-7.80 (m, 2H), 7.36-7.32 (m, 2H), 7.27-7.23 (m, 2H), 4.54 (s, 2H), 4.38 (q, 2H, J=7.2 Hz), 1.40 (t, 3H, J=7.2 Hz).

Workup

  1. temperaturethe resulting mixture was refluxed for 3 days
  2. temperatureThe reaction was cooled
  3. concentrationconcentrated in vacuo
  4. customthe residue was partitioned between DCM (300 ml) and saturated sodium bicarbonate solution (200 mL)
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with DCM (100 mL)
  7. washThe combined DCM layers were washed with brine (100 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give crude product which
  12. customwas purified by silica gel chromatography (ethyl acetate/DCM=0/100→40/60)
  13. customfollowed by recrystallization from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-8b886c51b5f8467ab25a9d1a659d2925
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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