Tris(furan-2-yl)phosphane → 2,4-Diamino-6-methyl-5-[3,3-difluoro-3-(4-chlorophenyl)-1-propenyl]pyrimidine

HRID 1939674Notes

Reaction equation

HRID 1939674 reaction equation
O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.[NH2:17][C:18]1[N:23]=[C:22]([NH2:24])[C:21](I)=[C:20]([CH3:26])[N:19]=1.[F:27][C:28]([F:51])([C:44]1[CH:49]=[CH:48][C:47]([Cl:50])=[CH:46][CH:45]=1)[CH:29]=[CH:30][Sn](CCCC)(CCCC)CCCC>CN(C)C=O>[NH2:17][C:18]1[N:23]=[C:22]([NH2:24])[C:21]([CH:30]=[CH:29][C:28]([F:51])([F:27])[C:44]2[CH:49]=[CH:48][C:47]([Cl:50])=[CH:46][CH:45]=2)=[C:20]([CH3:26])[N:19]=1

Participants

5

Reactant 3

HCID 521585Tris(furan-2-yl)phosphaneHCID 158557925-Iodo-6-methylpyrimidine-2,4-diamineHCID 676317671,1-Difluoro-1-(4-chlorophenyl)-3-tributylstannyl-2-propene

Product 1

HCID 539487272,4-Diamino-6-methyl-5-[3,3-difluoro-3-(4-chlorophenyl)-1-propenyl]pyrimidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 0.04 gram (catalyst) of tri-2-furylphosphine and 0.04 gram (catalyst) of tris(dibenzylidineacetone)dipalladium(0) in 30 mL of N,N-dimethylformamide is purged with dry nitrogen gas and stirred at ambient temperature for five minutes. After this time 1.2 grams (0.0048 mole) of 2,4-diamino-5-iodo-6-methylpyrimidine (prepared in Step B of Example 3) is added in one portion. The reaction vessel is then immersed in an oil bath that is preheated to 60° C. where it is maintained for about five minutes. After this time, 3.1 grams (0.0064 mole) of 1,1-difluoro-1-(4-chlorophenyl)-3-tributylstannyl-2-propene is added in one portion to the reaction mixture. The reaction mixture is again purged with dry nitrogen gas, and the oil bath temperature is brought to 80°-85° C. where it is maintained for about 18 hours. After this time the reaction mixture is diluted with 200 mL of water and extracted with two 200 mL portions of ethyl acetate. The combined extracts are then washed with three 100 mL portions of an aqueous solution of 5% lithium chloride. The organic layer is concentrated under reduced pressure to a residue. The residue is purified by column chromatography, yielding 2,4-diamino-6-methyl-5-[3,3-difluoro-3-(4-chlorophenyl)-1-propenyl]pyrimidine.

Workup

  1. customis purged with dry nitrogen gas
  2. customThe reaction vessel is then immersed in an oil bath
  3. customis preheated to 60° C.
  4. temperatureis maintained for about five minutes
  5. customThe reaction mixture is again purged with dry nitrogen gas
  6. customis brought to 80°-85° C.
  7. temperatureis maintained for about 18 hours
  8. additionAfter this time the reaction mixture is diluted with 200 mL of water
  9. extractionextracted with two 200 mL portions of ethyl acetate
  10. washThe combined extracts are then washed with three 100 mL portions of an aqueous solution of 5% lithium chloride
  11. concentrationThe organic layer is concentrated under reduced pressure to a residue
  12. customThe residue is purified by column chromatography

Sources & evidence

ORD record
ord-2d7bd101fde642229ebe7891f24fae19
Source dataset
uspto-grants-1997_12
Patent number
US05696259

Reaction notes

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