3-(Methylthio)propionyl Chloride → HCID 59580749, compound

HRID 2199202Notes

Reaction equation

HRID 2199202 reaction equation
[CH3:1][S:2][CH2:3][CH2:4][C:5](Cl)=[O:6].[CH3:8][NH:9][C:10]1[S:14][C:13]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)=[N:12][CH:11]=1>ClCCCl.CN(C1C=CN=CC=1)C>[CH3:8][N:9]([C:10]1[S:14][C:13]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)=[N:12][CH:11]=1)[C:5](=[O:6])[CH2:4][CH2:3][S:2][CH3:1]

Participants

5

Reactant 2

HCID 129214403-(Methylthio)propionyl ChlorideHCID 59580894N-methyl-2-(pyridin-3-yl)thiazol-5-amine

Product 1

HCID 59580749HCID 59580749, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 111,2-DichloroethaneSolvent3×

Procedure

A solution of 3-methylsulfanyl-propionyl chloride (120 mg, 0.9 mmol) in DCE (1 mL) was pipetted at a dropwise rate into an ice-cold suspension of methyl-(2-pyridin-3-yl-thiazol-5-yl)-amine (114 mg, 0.6 mmol) in DCE (5 mL), and the mixture was stirred for 5 min before adding a solution of DMAP (80 mg, 0.6 mmol) in DCE (1 mL). The ice bath was removed after 30 min, and the mixture was stirred at reflux under nitrogen for 15 min. The reaction mixture was cooled, diluted with DCE (70 mL), washed with saturated aqueous NaHCO3 (50 mL), dried over MgSO4 and purified by silica gel chromatography (3:1 ethyl acetate/hexanes) to afford a fine yellow powder (131 mg, 75%): mp 116-118° C.; 1H NMR (400 MHz, DMSO-d6) δ 9.08 (d, J=2.0 Hz, 1H), 8.61 (dd, J=4.8, 1.4 Hz, 1H), 8.24 (dt, J=9.8, 1.8 Hz, 1H), 7.81 (s, 1H), 7.51 (dd, J=7.7, 4.7 Hz, 1H), 3.56 (s, 3H), 3.02 (t, J=7.0 Hz, 2H), 2.76 (t, J=7.2 Hz, 2H), 2.12 (s, 3H); ESIMS m/z 294 (M+1).

Workup

  1. customThe ice bath was removed after 30 min
  2. stirringthe mixture was stirred
  3. temperatureat reflux under nitrogen for 15 min
  4. temperatureThe reaction mixture was cooled
  5. additiondiluted with DCE (70 mL)
  6. washwashed with saturated aqueous NaHCO3 (50 mL)
  7. dry with materialdried over MgSO4
  8. custompurified by silica gel chromatography (3:1 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-ba27e171e4284151ad25695d185cf611
Source dataset
uspto-grants-2016_06
Patent number
US09357780B2

Reaction notes

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