Pyridine → 2-Phenylamino-4-bromomethyl-6-cyclopropylpyrimidine

HRID 358802Notes

Reaction equation

HRID 358802 reaction equation
S(Br)([Br:3])=O.[C:5]1([NH:11][C:12]2[N:17]=[C:16]([CH2:18]O)[CH:15]=[C:14]([CH:20]3[CH2:22][CH2:21]3)[N:13]=2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.N1C=CC=CC=1.C(=O)([O-])O.[Na+]>C(OCC)C.O>[C:5]1([NH:11][C:12]2[N:17]=[C:16]([CH2:18][Br:3])[CH:15]=[C:14]([CH:20]3[CH2:22][CH2:21]3)[N:13]=2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

7

Reactant 4

HCID 1049Pyridine2×HCID 68176Thionyl bromideHCID 516892Sodium BicarbonateHCID 198740942-Anilino-4-hydroxymethyl-6-cyclopropylpyrimidine

Product 1

HCID 198740962-Phenylamino-4-bromomethyl-6-cyclopropylpyrimidine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×

Procedure

15.6 g (75 mmol) of thionyl bromide in 50 ml of diethyl ether are added dropwise within a period of half an hour, with stirring, to 12 g (50 mmol) of 2-phenylamino-4-hydroxymethyl-6-cyclopropylpyrimidine and 0.4 g (50 mmol) of pyridine in 350 ml of diethyl ether. After stirring for 2 hours at room temperature, a further 0.4 g (50 mmol) of pyridine are added and the mixture is heated under reflux for 5 hours. After cooling to room temperature, 200 ml of water are added and the pH is adjusted to 7 by the dropwise addition of 140 ml of saturated sodium hydrogen carbonate solution. The diethyl ether phase is separated off and then washed twice with 100 ml of water each time, dried over sodium sulfate and filtered, and the solvent is evaporated. The brown oil which remains is purified by column chromatography over silica gel (toluene/chloroform/diethyl ether/petroleum ether (b.p. 50°-70° C.): 5/3/1/1). After the eluant mixture has been evaporated off, the yellow oil is diluted with diethyl ether/petroleum ether (b.p. 50°-70° C.) and crystallised at reduced temperature. The yellow crystalline powder melts at 77.5°-79.5° C. Yield: 9.7 g (32 mmol; 64% of the theoretical yield).

Workup

  1. temperaturethe mixture is heated
  2. temperatureunder reflux for 5 hours
  3. temperatureAfter cooling to room temperature
  4. customThe diethyl ether phase is separated off
  5. washwashed twice with 100 ml of water each time
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent is evaporated
  9. customThe brown oil which remains is purified by column chromatography over silica gel (toluene/chloroform/diethyl ether/petroleum ether (b.p. 50°-70° C.): 5/3/1/1)
  10. customAfter the eluant mixture has been evaporated off
  11. additionthe yellow oil is diluted with diethyl ether/petroleum ether (b.p. 50°-70° C.)
  12. customcrystallised at reduced temperature
  13. custom64% of the theoretical yield)

Sources & evidence

ORD record
ord-64434950de2f47b9aa437d4a43d1a62f
Source dataset
uspto-grants-1991_03
Patent number
US04997941

Reaction notes

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