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 1484718Notes

Reaction equation

HRID 1484718 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-8c81c34d465140c3a3acbec8bee4a8a0
Source dataset
uspto-grants-2016_08
Patent number
US09422278B2

Reaction notes

Loading…