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

HRID 1470447Notes

Reaction equation

HRID 1470447 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-805cd0708fde40f5a3c87f0d1118d26f
Source dataset
uspto-grants-2015_04
Patent number
US09006446B2

Reaction notes

Loading…