Ethyl Acetate → 2-(N-(2-bromo-4-(2-propyl)phenyl)amino)-4-carbomethoxy-6-methylpyrimidine

HRID 1872061Notes

Reaction equation

HRID 1872061 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[C:4]([CH3:12])[N:3]=1.[Br:13][C:14]1[CH:20]=[C:19]([CH:21]([CH3:23])[CH3:22])[CH:18]=[CH:17][C:15]=1[NH2:16].C(OCC)(=O)C>O1CCOCC1>[Br:13][C:14]1[CH:20]=[C:19]([CH:21]([CH3:22])[CH3:23])[CH:18]=[CH:17][C:15]=1[NH:16][C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[C:4]([CH3:12])[N:3]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 5213372-Bromo-4-isopropylanilineHCID 2736835Methyl 2-chloro-6-methylpyrimidine-4-carboxylate

Product 1

HCID 183237202-(N-(2-bromo-4-(2-propyl)phenyl)amino)-4-carbomethoxy-6-methylpyrimidine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-chloro-4-carbomethoxy-6-methylpyrimidine (47 g, 252 mmol) and 2-bromo-4-(2-propyl)aniline (54.0 g, 252 mmol) in dioxane (400 mL) was stirred at reflux temperature for 20 h under a nitrogen atmosphere. The reaction mixture was cooled to ambient temperature and concentrated on a rotary evaporator. The residue was treated with a saturated sodium bicarbonate solution and extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate and filtered. Solvent was removed in vacuo to provide a red oil. Column chromatography (ethyl acetate:hexanes::1:1) gave the title product as a crude oil. Recrystallization from ether-hexanes, collection by filtration and drying in vacuo afforded the title compound as a solid (42.8 g, 47% yield): mp 75-76° C.; NMR (CDCl3, 300 MHz): 8.4 (d, 1H, J=8); 7.65 (br s, 1H), 7.4 (d, 1H, J=1), 7.3 (s, 1H), 7.2 (dd, 1H, J=8,1), 4.0 (s, 3H), 2.85 (septet, 1H, J=7), 2.5 (br s, 3H), 1.25 (d, 6H, J=7); Anal.(C16H18BrN3O2): C, 52.76, H, 4.98, N, 11.54, Br, 21.94; Found: C, 52.71, H, 4.99, N, 11.38, Br, 21.83.

Workup

  1. temperatureat reflux temperature for 20 h under a nitrogen atmosphere
  2. concentrationconcentrated on a rotary evaporator
  3. additionThe residue was treated with a saturated sodium bicarbonate solution
  4. extractionextracted three times with ethyl acetate
  5. dry with materialThe combined organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. customSolvent was removed in vacuo
  8. customto provide a red oil

Sources & evidence

ORD record
ord-a463760248324f078f203e7f522d6dd2
Source dataset
uspto-grants-2000_08
Patent number
US06107301

Reaction notes

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