Water → N-(4-chloro-2-(pyridin-3-yl)thiazol-5-yl)-N-ethyl-2-methyl-3-(methylthio)propanamide

HRID 882003Notes

Reaction equation

HRID 882003 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[S:5][C:6]=1[NH:7][C:8](=[O:14])[CH:9]([CH3:13])[CH2:10][S:11][CH3:12].C(=O)([O-])[O-].[Cs+].[Cs+].I[CH2:28][CH3:29].O>CN(C)C=O>[Cl:1][C:2]1[N:3]=[C:4]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)[S:5][C:6]=1[N:7]([CH2:28][CH3:29])[C:8](=[O:14])[CH:9]([CH3:13])[CH2:10][S:11][CH3:12]

Participants

6

Reactant 4

HCID 962WaterHCID 6340Iodoethane2×HCID 10796Cesium carbonateHCID 59580564N-(4-chloro-2-(pyridin-3-yl)thiazol-5-yl)-2-methyl-3-(methylthio)propanamide

Product 1

HCID 49805426N-(4-chloro-2-(pyridin-3-yl)thiazol-5-yl)-N-ethyl-2-methyl-3-(methylthio)propanamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a dry 50 ml round bottom flask equipped with magnetic stirrer, addition funnel, and nitrogen inlet was charged 1.0 g (3.05 mmoles) of N-(4-chloro-2-(pyridin-3-yl)-1,3-thiazol-5-yl)-2-methyl-3-(methylthio)propanamide and 10 mLs of anhydrous N,N-dimethyl formamide. To the resulting solution was then added 1.1 g (3.36 mmoles) of cesium carbonate powder in one portion, followed by the dropwise addition of 0.523 g (3.36 mmoles) of iodoethane in 5 mLs of anhydrous N,N-dimethyl formamide. The heterogeneous mixture was stirred at ambient temperature for 12 hours. Analysis of an aliquot indicated incomplete reaction. An additional 100 ul of iodoethane was added and the reaction was heated at 60° C. for 3 hours, then poured into 200 mLs of water and extracted with methylene chloride (3×100 mLs). The combined organic extracts were washed with water (100 mLs), saturated aqueous sodium chloride solution (100 mLs) dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum on a rotary evaporator. The crude product was purified by silica gel flash chromatography, eluting with a gradient of 100% hexane to 100% ethyl acetate over 20 minutes to yield a yellow oil which crystallized upon standing (0.38 g, 35%): mp 80-81° C.; 1H NMR (400 MHz, CDCl3) δ 9.12 (d, J=1.9 Hz, 1H), 8.72 (dd, J=4.8, 1.4 Hz, 1H), 8.22 (ddd, J=8.0, 2.2, 1.8 Hz, 1H), 7.43 (ddd, J=8.0, 4.8, 0.6 Hz, 1H), 4.03-3.80 (m, 1H), 3.80-3.59 (m, 1H), 2.97-2.68 (m, 2H), 2.60-2.39 (m, 1H), 2.03 (s, 3H), 1.30-1.16 (m, 6H); 13C NMR (101 MHz, DMSO-d6) δ 175.66, 162.63, 151.89, 147.14, 138.19, 133.49 133.23, 128.58, 123.90, 44.81, 38.94, 37.93, 18.16, 16.83, 12.90.

Workup

  1. customTo a dry 50 ml round bottom flask equipped with magnetic stirrer, addition funnel, and nitrogen inlet
  2. customreaction
  3. temperaturethe reaction was heated at 60° C. for 3 hours
  4. extractionextracted with methylene chloride (3×100 mLs)
  5. washThe combined organic extracts were washed with water (100 mLs), saturated aqueous sodium chloride solution (100 mLs)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum on a rotary evaporator
  9. customThe crude product was purified by silica gel flash chromatography
  10. washeluting with a gradient of 100% hexane to 100% ethyl acetate over 20 minutes
  11. customto yield a yellow oil which
  12. customcrystallized

Sources & evidence

ORD record
ord-480a72e753d841868cbedb5a76ec3e1a
Source dataset
uspto-grants-2015_03
Patent number
US08993769B2

Reaction notes

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