Water → HCID 22640014, compound

HRID 2415096Notes

Reaction equation

HRID 2415096 reaction equation
[NH2:1][C:2]1[C:7]([Cl:8])=[C:6]([CH3:9])[N:5]=[C:4]([CH3:10])[N:3]=1.[H-].[Na+].[CH2:13]([O:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Cl)=[CH:23][CH:22]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O>CN1CCCC1=O>[ClH:8].[CH2:13]([O:20][C:21]1[CH:22]=[CH:23][C:24]([CH2:25][NH:1][C:2]2[C:7]([Cl:8])=[C:6]([CH3:9])[N:5]=[C:4]([CH3:10])[N:3]=2)=[CH:27][CH:28]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 700424-Benzyloxybenzyl chlorideHCID 5938434-Amino-5-chloro-2,6-dimethylpyrimidine

Product 1

HCID 22640014HCID 22640014, compoundYield 126.5%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent3×

Procedure

A solution of 73.4 g (0.465 mol) of 4-amino-5-chloro-2,6-dimethylpyrimidine in 370 ml of anhydrous N-methylpyrrolidone is added dropwise over 45 min under a nitrogen atmosphere at room temperature to a suspension of 19.5 g (0.49 mol) of sodium hydride (60% suspension in liquid paraffin) in 80 ml of anhydrous N-methylpyrrolidone. The mixture is stirred at room temperature for 1 h and then cooled to 4° C. Then a solution of 111.0 g (0.465 mol) of 4-benzyloxybenzyl chloride in anhydrous N-methylpyrrolidone is added dropwise, with vigorous stirring, at a rate such that the internal temperature does not rise higher than 5° C. (about 1 h). Thereafter, the mixture is warmed to room temperature and stirred for 1 h. The solution is subsequently poured into 4 l of water and extracted with ethyl acetate (3×1 l). The combined organic extracts are washed with water (2 l), dried over sodium sulfate and concentrated. The oil (180 g) which remains is dissolved in 400 ml of isopropanol and is admixed dropwise with stirring with 100 ml of saturated ethereal hydrochloric acid. Thereafter, further ethyl acetate is added and the mixture is stirred at room temperature for 1 h for complete precipitation of the hydrochloride. The precipitate is filtered off with suction, washed with ethyl acetate (500 ml) and dried in a vacuum drying cabinet at 40° C. 114.8 g (63%) of the title compound are isolated as a beige solid. m.p.: 227° C.

Workup

  1. temperaturecooled to 4° C
  2. customdoes not rise higher than 5° C.
  3. custom(about 1 h)
  4. temperatureThereafter, the mixture is warmed to room temperature
  5. stirringstirred for 1 h
  6. extractionextracted with ethyl acetate (3×1 l)
  7. washThe combined organic extracts are washed with water (2 l)
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. dissolutionThe oil (180 g) which remains is dissolved in 400 ml of isopropanol
  11. stirringwith stirring with 100 ml of saturated ethereal hydrochloric acid
  12. additionThereafter, further ethyl acetate is added
  13. stirringthe mixture is stirred at room temperature for 1 h for complete precipitation of the hydrochloride
  14. filtrationThe precipitate is filtered off with suction
  15. washwashed with ethyl acetate (500 ml)
  16. customdried in a vacuum
  17. customdrying cabinet at 40° C

Sources & evidence

ORD record
ord-1496e450d7d64b2886bc6280df152be1
Source dataset
uspto-grants-2004_11
Patent number
US06818642B2

Reaction notes

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