Aniline → 6-chloro-2-methyl-N-phenylpyrimidin-4-amine

HRID 601056Notes

Reaction equation

HRID 601056 reaction equation
[CH3:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([Cl:9])[N:3]=1.CCN(C(C)C)C(C)C.[NH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>O1CCOCC1>[Cl:9][C:4]1[N:3]=[C:2]([CH3:1])[N:7]=[C:6]([NH:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:5]=1

Participants

5

Reactant 3

HCID 6115AnilineHCID 81531DiisopropylethylamineHCID 2349974,6-Dichloro-2-methylpyrimidine

Product 1

HCID 450717646-chloro-2-methyl-N-phenylpyrimidin-4-amineYield 64.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

2-Methyl-4,6-dichloropyrimidine (430 mg; 2.64 mMol) was refluxed in p-dioxane 10 mL with DIEA (575 uL; 426 mg; 3.3 mMol) and aniline (239 uL; 247 mg; 2.65 mMol) for 48 hrs under N2. The solvent was removed under reduced pressure and the residue partitioned between ethyl acetate and 0.5 N HCl. The organic fraction was washed with water, brine, and dried over Na2SO4) and the solvent removed under reduced pressure. Crude material was triturated with MTBE, suction filtered to isolate and washed with more MTBE and air dried to afford 375 mg of white solid, 64.5% yield. 1H NMR (500 MHz DMSO-d6) d 8.9 (s, 1H), 7.7 (s, 1H), 7.55 (m, 2H), 7.27 (t, 2H), 6.95 (t, 1H), 6.0 (s, 1H) 2.25 (s, 3H) ppm

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue partitioned between ethyl acetate and 0.5 N HCl
  3. washThe organic fraction was washed with water, brine
  4. dry with materialdried over Na2SO4) and the solvent
  5. customremoved under reduced pressure
  6. customCrude material was triturated with MTBE, suction
  7. filtrationfiltered
  8. customto isolate
  9. washwashed with more MTBE and air
  10. customdried

Sources & evidence

ORD record
ord-2b59c0261a1d46938f046a929b76825b
Source dataset
uspto-grants-2011_03
Patent number
US07902239B2

Reaction notes

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