Phosphorus oxychloride → 7-Chloro-2-(4-fluorophenyl)-5-methylthiazolo[5,4-d]pyrimidine

HRID 1396705Notes

Reaction equation

HRID 1396705 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]3[N:11]=[C:12]([CH3:18])[NH:13][C:14](=O)[C:15]=3[N:16]=2)=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.O=P(Cl)(Cl)[Cl:30]>>[Cl:30][C:14]1[C:15]2[N:16]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[S:9][C:10]=2[N:11]=[C:12]([CH3:18])[N:13]=1

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 667578242-(4-fluorophenyl)-5-methyl-thiazolo[5,4-d]pyrimidin-7(6H)-one

Product 1

HCID 866624397-Chloro-2-(4-fluorophenyl)-5-methylthiazolo[5,4-d]pyrimidineYield 40%

Conditions

Temperature
90 °C

Procedure

To a solution of 2-(4-fluorophenyl)-5-methyl-thiazolo[5,4-d]pyrimidin-7(6H)-one (0.40 g, 1.23 mmol) in POCl3 was added diisopropylethylamine (0.13 ml, 0.77 mmol). The reaction mixture was stirred under N2 at 90° C. for 3.5 hours. After cooling down to room temperature, the reaction mixture was poured into ice-water and the aqueous phase was extracted with diethyl ether. The combined organic layers were washed with a saturated NaHCO3 solution and brine, dried over Na2SO4 and concentrated under reduced pressure. The crude residue was purified by chromatography on silica gel (hexane/EtOAc 10:1) to yield the title compound as a white solid (42.8 mg, 40%).

Workup

  1. temperatureAfter cooling down to room temperature
  2. extractionthe aqueous phase was extracted with diethyl ether
  3. washThe combined organic layers were washed with a saturated NaHCO3 solution and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude residue was purified by chromatography on silica gel (hexane/EtOAc 10:1)

Sources & evidence

ORD record
ord-3f00d586888a4b5896bc5a0bbb1307b4
Source dataset
uspto-grants-2014_12
Patent number
US08901132B2

Reaction notes

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