Pyridine → N-(4-chloro-2-(pyridin-3-yl)thiazol-5-yl)-N,2-dimethyl-3-(methylthio)propanamide

HRID 1803457Notes

Reaction equation

HRID 1803457 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)[S:5][C:6]=1[NH:7][CH3:8].N1C=CC=CC=1.[CH3:21][CH:22]([CH2:26][S:27][CH3:28])[C:23](Cl)=[O:24]>ClC(Cl)C.O>[Cl:1][C:2]1[N:3]=[C:4]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)[S:5][C:6]=1[N:7]([CH3:8])[C:23](=[O:24])[CH:22]([CH3:21])[CH2:26][S:27][CH3:28]

Participants

6

Reactant 3

HCID 1049PyridineHCID 59580506(4-Chloro-2-pyridin-3-yl-thiazol-5-yl)-methylamineHCID 758176512-Methyl-3-(methylthio)propanoyl chloride

Product 1

HCID 49765044N-(4-chloro-2-(pyridin-3-yl)thiazol-5-yl)-N,2-dimethyl-3-(methylthio)propanamideYield 84%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of (4-chloro-2-pyridin-3-yl-thiazol-5-yl)-methylamine (200 mg, 0.88 mmol) in dichloroethane (2 mL) was added pyridine (83 mg, 1.05 mmol), N,N-dimethylaminopyridine (54 mg, 0.44 mmol) followed by 2-methyl-3-methylsulfanyl-propionyl chloride (160 mg, 1.05 mmol). The reaction mixture was stirred at ambient temperature for 16 hours. The reaction was diluted with water and the mixture was extracted with dichloromethane. The organic layer was dried over Na2SO4, filtered and concentrated. The crude product was purified by silica gel chromatography (0 to 100% ethyl acetate/hexanes) to afford a light yellow solid (250 mg, 84%): mp 70-73° C.; 1H NMR (300 MHz, CDCl3) δ 9.14 (s, 1H), 8.75 (d, J=3.8 Hz, 1H), 8.28-8.15 (m, 1H), 7.45 (dd, J=8.0, 4.9 Hz, 1H), 3.32 (s, 3H), 2.99-2.72 (m, 2H), 2.50 (d, J=7.5 Hz, 1H), 2.06 (d, J=2.5 Hz, 3H), 1.31-1.14 (m, 3H); ESIMS m/z 342 (M+1).

Workup

  1. extractionthe mixture was extracted with dichloromethane
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by silica gel chromatography (0 to 100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-0ff953785e624af08131d65d9da3a58f
Source dataset
uspto-grants-2013_01
Patent number
US08350044B2

Reaction notes

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