Phenethyl bromide → 2-Chloro-4-(N-(2-phenylethyl)anilino)pyrimidine

HRID 347752Notes

Reaction equation

HRID 347752 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=1.[H-].[Na+].[CH2:17](Br)[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C=O)C>[Cl:1][C:2]1[N:7]=[C:6]([N:8]([CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 7666Phenethyl bromide2×HCID 24758Sodium hydride2×HCID 219953492-Chloro-N-phenylpyrimidin-4-amine

Product 1

HCID 210837402-Chloro-4-(N-(2-phenylethyl)anilino)pyrimidineYield 59%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Chloro-4-anilinopyrimidine (Reference Example A-9, 600 mg, 2.9 mmol) was dissolved in anhydrous DMF (8 ml) and sodium hydride (140 mg, 3.5 mmol, 60% in oil) was added portion wise. 10 min later phenethylbromide (478 μl, 3.5 mmol) was added and the mixture was stirred at ambient temperature for 5 hours. More sodium hydride (140 mg, 3.5 mmol, 60% in oil) and phenethylbromide (478 μl, 3.5 mnmol) were added and stirring was maintained overnight. The solvent was evaporated off and the residue partitioned between water and DCM. The organic phase was dried (MgSO4) the solvent evaporated. The crude product was purified by flash chromatography using first DCM then EtOAc/petroleum ether (25/75). The solvent was evaporated to give the title product as a white solid (530 mg, 59%). NMR (400 MHz, 353K): 2.90 (t, 2H), 4.10 (t, 2H), 6.15 (d, 1H), 7.25 (m, 7H), 7.45 (t, 1H), 7.65 (t, 2H), 8.00 (d, 1H); m/z: (ES+) 310 and 312 (MH+).

Workup

  1. stirringstirring
  2. temperaturewas maintained overnight
  3. customThe solvent was evaporated off
  4. customthe residue partitioned between water and DCM
  5. dry with materialThe organic phase was dried (MgSO4) the solvent
  6. customevaporated
  7. customThe crude product was purified by flash chromatography
  8. customThe solvent was evaporated

Sources & evidence

ORD record
ord-756d257b1d6e45c8bd89cf3c72c4bce3
Source dataset
uspto-grants-2007_02
Patent number
US07176212B2

Reaction notes

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