1,2-Dimethoxyethane → 2,2-dimethyl-N-[4-methyl-2-[2-(methylthio)-4-pyrimidinyl]phenyl]propanamide

HRID 1780579Notes

Reaction equation

HRID 1780579 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([S:8][CH3:9])[N:3]=1.C(COC)OC.B([C:19]1[CH:24]=[C:23]([CH3:25])[CH:22]=[CH:21][C:20]=1[NH:26][C:27](=[O:32])[C:28]([CH3:31])([CH3:30])[CH3:29])(O)O.C(=O)(O)[O-].[Na+]>O.C(OCC)(=O)C.[Cl-].[Cl-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd+2]>[CH3:29][C:28]([CH3:31])([CH3:30])[C:27]([NH:26][C:20]1[CH:19]=[CH:24][C:23]([CH3:25])=[CH:22][C:21]=1[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([S:8][CH3:9])[N:3]=1)=[O:32]

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 971134-Chloro-2-methylthiopyrimidineHCID 516892Sodium BicarbonateHCID 19045057N-(2-borono-4-methylphenyl)-2,2-dimethylpropanamide

Product 1

HCID 190470412,2-dimethyl-N-[4-methyl-2-[2-(methylthio)-4-pyrimidinyl]phenyl]propanamideYield 79.9%

Reagents, catalysts & solvents 3

HCID 84124Bis(triphenylphosphine)palladium chlorideCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
50 °C

Procedure

A mixture of 16 g (0.1 mol) 4-chloro-2-(methylthio)pyrimidine, 0.150 g palladium bis(triphenylphosphine) dichloride, and 30 mL dimethoxyethane was stirred under nitrogen for 20 min, 25.8 g (0.11 mol) N-(2-borono-4-methyl phenyl)-2,2-dimethylpropanamide and a solution of 26 g sodium bicarbonate in 300 mL water was added, and the resulting mixture was heated to reflux for 5 h. After cooling to 50° C., 50 mL ethyl acetate was added and the reaction mixture was stirred until it reached room temperature. The reaction mixture was diluted with 300 mL ethyl acetate and washed successively with water and brine. The organic extracts were dried over magnesium sulfate, faltered, and evaporated to dryness. The crude product was purified by chromatography on silica gel using 40:1 chlorobutane/ethyl acetate mixture as eluent to yield 25.2 g of the title compound as white crystals melting at 119°-20° C. 1H NMR (CDCl3): δ 1.28 (s,9H), 2.38 (s,3H), 2.60 (s,3H) 7.30-8.6 (5H), 11.3(s,1H,NH).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux for 5 h
  3. stirringthe reaction mixture was stirred until it
  4. customreached room temperature
  5. washwashed successively with water and brine
  6. dry with materialThe organic extracts were dried over magnesium sulfate
  7. customevaporated to dryness
  8. customThe crude product was purified by chromatography on silica gel using 40:1 chlorobutane/ethyl acetate mixture as eluent

Sources & evidence

ORD record
ord-95c80df7d211486297ab7807c7f1de84
Source dataset
uspto-grants-1997_05
Patent number
US05631206

Reaction notes

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