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

HRID 1505642Notes

Reaction equation

HRID 1505642 reaction equation
[F:1][C:2]([F:15])([F:14])[CH2:3][C:4]1[S:13][C:7]2[N:8]=[CH:9][NH:10][C:11](=O)[C:6]=2[CH:5]=1.O=P(Cl)(Cl)[Cl:18]>CN(C=O)C>[Cl:18][C:11]1[C:6]2[CH:5]=[C:4]([CH2:3][C:2]([F:15])([F:14])[F:1])[S:13][C:7]=2[N:8]=[CH:9][N:10]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 904054626-(2,2,2-Trifluoroethyl)thieno[2,3-d]pyrimidin-4(1H)-one

Product 1

HCID 904050864-Chloro-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideCatalyst

Procedure

5.7 g of 6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4(3H)-one was added to 16 mL of POCl3 with one drop of DMF. The heterogeneous mixture was refluxed for 3 hs and then evaporated. The residue was quenched with ice and saturated ammonia solution and extracted with chloroform. Combined extracts were evaporated with silica gel and loaded on a short silica gel column. The column was eluted with hexane-ethyl acetate (5:1) to afford 5.9 g of 4-chloro-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidine. 1H NMR CDCl3 (300 MHz): 8.86 (s, 1H), 7.39 (s, 1H), 3.76 (q, 2H, J9.9 Hz). 13C NMR CDCl3 (75 MHz): 169.0, 154.7, 153.2, 129.9, 125.3, 123.5, 121.3, 35.9 (q, J33.0 Hz).

Workup

  1. temperatureThe heterogeneous mixture was refluxed for 3 hs
  2. customevaporated
  3. customThe residue was quenched with ice and saturated ammonia solution
  4. extractionextracted with chloroform
  5. customCombined extracts were evaporated with silica gel
  6. washThe column was eluted with hexane-ethyl acetate (5:1)

Sources & evidence

ORD record
ord-2497644c06ba4138a97657cae91b85d6
Source dataset
uspto-grants-2015_12
Patent number
US09216993B2

Reaction notes

Loading…