P-Anisidine → [(2,4-Dichloropyrimidin-5-yl)methyl](4-methoxyphenyl)amine

HRID 1243159Notes

Reaction equation

HRID 1243159 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([CH2:9]I)=[CH:4][N:3]=1.[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([NH2:19])=[CH:15][CH:14]=1.[OH-].[Na+]>C1(C)C=CC=CC=1.O>[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([CH2:9][NH:19][C:16]2[CH:17]=[CH:18][C:13]([O:12][CH3:11])=[CH:14][CH:15]=2)=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 7732P-AnisidineHCID 14798Sodium HydroxideHCID 219393522,4-Dichloro-5-(iodomethyl)pyrimidine

Product 1

HCID 21939303[(2,4-Dichloropyrimidin-5-yl)methyl](4-methoxyphenyl)amine

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 1140TolueneSolvent3×

Procedure

A 500-mL, three-necked flask equipped with a magnetic stirrer, thermometer, and nitrogen-inlet bubbler was charged with a solution of 2,4-dichloro-5-(iodomethyl)pyrimidine (85 g, ca. 253.2 mmol) (from Example 1c supra) in toluene (13.7 mL) from the previous step and toluene (96.3 mL, thus, a total of ca. 110 mL of toluene). After cooling with an ice-water bath, p-anisidine (31.18 g, 253.2 mmol) (Aldrich) was added. After stirring for 30 minutes, a solution of sodium hydroxide (13.54 g, 331.7 mmol) in water (50 mL) was added dropwise over 8 minutes, while maintaining the temperature of the reaction mixture at 10–15° C. hexanes (55 mL) was added and the mixture was stirred at 10–15° C. for 45 minutes, then at room temperature for 22 hours to give a slurry. TLC analysis of the supernatant indicated complete reaction. The slurry was diluted with water (100 mL) and the solid was collected by filtration, washed with cold water and cold (−50° C.) methanol (100 mL), and dried by suction to give [(2,4-dichloropyrimidin-5-yl)methyl](4-methoxyphenyl)amine as an off-white solid, 97% pure by HPLC analysis. (Yield 59.87 g, 83.2%).

Workup

  1. customA 500-mL, three-necked flask equipped with a magnetic stirrer
  2. temperatureAfter cooling with an ice-water bath
  3. additionwas added
  4. stirringthe mixture was stirred at 10–15° C. for 45 minutes
  5. customat room temperature for 22 hours to give a slurry
  6. customreaction
  7. filtrationthe solid was collected by filtration
  8. washwashed with cold water and cold (−50° C.) methanol (100 mL)
  9. customdried by suction

Sources & evidence

ORD record
ord-1b09948b7b0e47d0acfd4bde3deb0934
Source dataset
uspto-grants-2006_10
Patent number
US07115740B2

Reaction notes

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