Phosphorus oxychloride → 4-Chloro-6-(2-chloro-4-pyridyl)-2-methylthio-5-(3-(trifluoromethyl)-phenyl)pyrimidine

HRID 897400Notes

Reaction equation

HRID 897400 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[N:13]=[C:12]([S:14][CH3:15])[N:11](C)[C:10](=O)[C:9]=2[C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=2)[CH:5]=[CH:4][N:3]=1.O=P(Cl)(Cl)[Cl:30].C(N(C(C)C)CC)(C)C>CCOC(C)=O>[Cl:30][C:10]1[C:9]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=2)=[C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[CH:7]=2)[N:13]=[C:12]([S:14][CH3:15])[N:11]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 223465686-(2-chloro-4-pyridyl)-3-methyl-2-methylthio-5-(3-(trifluoromethyl)-phenyl)-(3H)-pyrimidin-4-one

Product 1

HCID 223466514-Chloro-6-(2-chloro-4-pyridyl)-2-methylthio-5-(3-(trifluoromethyl)-phenyl)pyrimidine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

6-(2-chloro-4-pyridyl)-3-methyl-2-methylthio-5-(3-(trifluoromethyl)-phenyl)-(3H)-pyrimidin-4-one (2.05 g, 5 mmol), POCl3 (3.05 g, 20 mmol), and diisopropylethylamine (2.58 g, 20 mmol) in a 50-ml r.b.flask with a stir bar was stirred at 120° C. for 16 h. The reaction was cooled to RT, 20 ml of EtOAc and 5 g of SiO2 gel were added into the cooled solution, then solvents were evaporated in vacuo at 40° C. The brown solid was placed on a cake of SiO2 gel (˜20 g) and washed by 200 ml of 30% EtOAc in hexane. The brown filtrate was evaporated in vacuo to give an oil product; MS m/z (M+H)+ 416.2. The crude intermediate was used in the next step directly.

Workup

  1. customsolvents were evaporated in vacuo at 40° C
  2. washwashed by 200 ml of 30% EtOAc in hexane
  3. customThe brown filtrate was evaporated in vacuo
  4. customto give an oil product

Sources & evidence

ORD record
ord-c35c7e81b62241caad1f4acd909681a0
Source dataset
uspto-grants-2005_07
Patent number
US06921762B2

Reaction notes

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