Phosphorus oxychloride → 4-Chloro-6-(4-fluorophenyl)-2-methylthieno[2,3-d]pyrimidine

HRID 718322Notes

Reaction equation

HRID 718322 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:18][C:11]3[N:12]=[C:13]([CH3:17])[NH:14][C:15](=O)[C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.O=P(Cl)(Cl)[Cl:30]>>[Cl:30][C:15]1[C:10]2[CH:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[S:18][C:11]=2[N:12]=[C:13]([CH3:17])[N:14]=1

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 66758458HCID 66758458, compound

Product 1

HCID 866624424-Chloro-6-(4-fluorophenyl)-2-methylthieno[2,3-d]pyrimidineYield 6%

Procedure

A solution of 6-(4-fluorophenyl)-2-methylthieno[2,3-d]pyrimidin-4(3H)-one (0.2 g, 0.77 mmol) and diisopropylethylamine (0.26 ml, 1.54 mmol) in POCl3 (4 ml) was stirred under N2 at 90° C. for 3.5 hours. The reaction mixture was allowed to cool down to room temperature and poured into an ice-bath. The aqueous phase was extracted with diethyl ether. The combined organic layers were washed with a half-saturated NaHCO3 solution and brine, dried over Na2SO4, and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (CH2Cl2/MeOH 50:1) to yield the title compound as a white solid (14 mg, 6%).

Workup

  1. additionpoured into an ice-bath
  2. extractionThe aqueous phase was extracted with diethyl ether
  3. washThe combined organic layers were washed with a half-saturated NaHCO3 solution and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude residue was purified by silica gel chromatography (CH2Cl2/MeOH 50:1)

Sources & evidence

ORD record
ord-4a53d5a33f334877bbad27b5c1c178dc
Source dataset
uspto-grants-2015_11
Patent number
US09193741B2

Reaction notes

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