N,N-Dimethylaniline → 7-Chloro-5-[[(2,3-difluorophenyl)methyl]thio]-thiazolo[4,5-d]pyrimidin-2-amine

HRID 731526

Reaction equation

HRID 731526 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[C:9](=O)[NH:8][C:7]([S:11][CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:14]=3[F:20])=[N:6][C:5]=2[N:21]=1.CN(C)C1C=CC=CC=1.P(Cl)(Cl)([Cl:33])=O>>[Cl:33][C:9]1[C:4]2[S:3][C:2]([NH2:1])=[N:21][C:5]=2[N:6]=[C:7]([S:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:14]=2[F:20])[N:8]=1

Participants

4

Reactant 3

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 1355311695-(2,3-Difluorobenzylthio)-2-aminothiazolo[4,5-d]pyrimidin-7-ol

Product 1

HCID 112216507-Chloro-5-[[(2,3-difluorophenyl)methyl]thio]-thiazolo[4,5-d]pyrimidin-2-amineYield 31%

Procedure

The product of step (c) (10.0 g) was suspended in phosphoryl chloride (55 ml). N,N-dimethylaniline (5.5 ml) added slowly and reaction mixture heated at reflux for 2 hours. Allowed to cool, then poured on to ice with vigorous stirring; temperature was not allowed to go above 45° C. (ice added). After approximately 20 minutes the temperature stabilized at 30° C. The solid that formed was collected by filtration and washed with water. Purified by column chromatography (EtOAc to 5% MeOH in EtOAc) to give 3.34 g of product. 31% yield.

Workup

  1. customreaction mixture
  2. temperatureheated
  3. temperatureat reflux for 2 hours
  4. temperatureAllowed to cool
  5. additionpoured on to ice with vigorous stirring
  6. customto go above 45° C.
  7. addition(ice added)
  8. customThe solid that formed
  9. filtrationwas collected by filtration
  10. washwashed with water
  11. customPurified by column chromatography (EtOAc to 5% MeOH in EtOAc)

Sources & evidence

ORD record
ord-a78f9fbfce444e5b9302ca7f268ac233
Source dataset
uspto-grants-2009_09
Patent number
US07585867B2

Linked notes

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