methyl-(2-methyl-5-pyridin-3-yl-2H-pyrazol-3-yl)-amine → 2,N-dimethyl-N-(2-methyl-5-pyridin-3-yl-2H-pyrazol-3-yl)-3-methylsulfanyl-propionamide

HRID 2408170Notes

Reaction equation

HRID 2408170 reaction equation
[CH3:1][NH:2][C:3]1[N:4]([CH3:14])[N:5]=[C:6]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[CH:7]=1.[CH3:15][CH:16]([CH2:20][S:21][CH3:22])[C:17](Cl)=[O:18]>ClC(Cl)C>[CH3:15][CH:16]([CH2:20][S:21][CH3:22])[C:17]([N:2]([CH3:1])[C:3]1[N:4]([CH3:14])[N:5]=[C:6]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[CH:7]=1)=[O:18]

Participants

4

Reactant 2

HCID 67499915methyl-(2-methyl-5-pyridin-3-yl-2H-pyrazol-3-yl)-amineHCID 758176512-Methyl-3-(methylthio)propanoyl chloride

Product 1

HCID 674994562,N-dimethyl-N-(2-methyl-5-pyridin-3-yl-2H-pyrazol-3-yl)-3-methylsulfanyl-propionamide

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent2×

Procedure

To a solution of methyl-(2-methyl-5-pyridin-3-yl-2H-pyrazol-3-yl)-amine (150 mg, 0.8 mmol) under N2 in ice-cold dichloroethane (DCE; 2 mL) was added dropwise via pipette a solution of 2-methyl-3-methylsulfanyl-propionylchloride (146 mg, 0.9 mmol) in DCE (1.5 mL). After stirring for 10 minutes (min), a solution of 4-N,N-dimethylaminopyridine (DMAP; 107 mg, 0.9 mmol) in DCE (2 mL) was added dropwise. The ice bath was removed after 30 min, and the mixture was stirred at room temperature for 90 min and then at reflux for 14 h. The mixture was concentrated under reduced pressure and was purified by silica gel chromatography eluting with a gradient of EtOAc in hexane. The product, 2,N-dimethyl-N-(2-methyl-5-pyridin-3-yl-2H-pyrazol-3-yl)-3-methylsulfanyl-propionamide, was isolated as a yellow semi-solid (44 mg, 24%): 1H NMR (400 MHz, CDCl3) δ 9.00 (s, 1H), 8.58 (s, 1H), 8.08 (br d, J=7.0 Hz, 1H), 7.35 (br dd, J=7.3, 4.8 Hz, 1H), 6.58 (br s, 0.5H), 6.49 (br s, 0.5H), 3.89-3.79 (m, 3H), 3.25 (s, 3H), 2.96-2.80 (m, 1H), 2.42-2.40 (m, 1H), 2.02-1.99 (m, 3H), 2.62 (m, 1H), 1.15 (d, J=6.0 Hz, 3H); MS (m/z) 305.0 [M+1].

Workup

  1. customThe ice bath was removed after 30 min
  2. stirringthe mixture was stirred at room temperature for 90 min
  3. temperatureat reflux for 14 h
  4. concentrationThe mixture was concentrated under reduced pressure
  5. customwas purified by silica gel chromatography
  6. washeluting with a gradient of EtOAc in hexane

Sources & evidence

ORD record
ord-b9c16bd09e5a4ccda5383df2d3bb8e20
Source dataset
uspto-grants-2014_08
Patent number
US08815271B2

Reaction notes

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