P-Anisidine → 2-Chloro-N-(4-methoxyphenyl)pyrimidin-4-amine

HRID 749107Notes

Reaction equation

C(=O)(O)[O-].[Na+].[Cl:6][C:7]1[N:12]=[C:11](Cl)[CH:10]=[CH:9][N:8]=1.[CH3:14][O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1>C(O)C.O>[Cl:6][C:7]1[N:12]=[C:11]([NH:20][C:19]2[CH:21]=[CH:22][C:16]([O:15][CH3:14])=[CH:17][CH:18]=2)[CH:10]=[CH:9][N:8]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Sodium bicarbonate (1.26 g, 11.9 mmol) is added to a slurry of 2,4-dichloropyrimidine (1.01 g, 6.78 mmol) in ethanol (30 mL) at 0° C. 4-Methoxyaniline (840 mg, 6.82 mmol) is added and the slurry stirred at 0° C. for 6 hours. The reaction mixture is warmed to room temperature for 1 hour, then diluted with water (50 mL) and extracted three times with CHCl3 (50 mL). The combined organic layers are washed with water (50 mL) and brine (50 mL), dried over sodium sulfate, filtered and concentrated in vacuo to give crude product which is purified over silica (10% Et2O/CH2Cl2) to afford 1.20 g (75% yield) of the desired product as a white solid. 1H NMR (300 MHz, CDCl3) δ 8.05 (d, J=5.8 Hz, 1H), 7.20 (d, J=9.0 Hz, 2H), 7.05 (br s, 1H), 6.94 (d, J=9.0 Hz, 2H), 6.41 (d, J=5.8 Hz, 1H), 3.83 (s, 3H); MS (ESI) m/z 236 (M+1).

Workup

temperatureThe reaction mixture is warmed to room temperature for 1 hour
extractionextracted three times with CHCl3 (50 mL)
washThe combined organic layers are washed with water (50 mL) and brine (50 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customto give crude product which
customis purified over silica (10% Et2O/CH2Cl2)

Sources & evidence

ORD record: ord-0f0e3cb7987b41ba8b0155df635ab353
Source dataset: uspto-grants-2008_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07402589B2

Reaction notes

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