Water → 6-(4-Bromo-phenyl)-5-(4-chloro-phenyl)-3-methylsulfanyl-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one

HRID 1024598Notes

Reaction equation

HRID 1024598 reaction equation
[Br:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)=O)=[CH:4][CH:3]=1.C([O:20][C:21]([C:23]1[C:24]([S:35][CH3:36])=[N:25][N:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:27]=1[NH2:28])=O)C.O>O=S(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[Br:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]2[N:8]([C:9]3[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=3)[C:21](=[O:20])[C:23]3[C:24]([S:35][CH3:36])=[N:25][N:26]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)[C:27]=3[N:28]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 962WaterHCID 774372HCID 774372, compoundHCID 5189818Ethyl 5-amino-3-(methylthio)-1-phenyl-1H-pyrazole-4-carboxylate

Product 1

HCID 578994446-(4-Bromo-phenyl)-5-(4-chloro-phenyl)-3-methylsulfanyl-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 24386Thionyl ChlorideSolvent2×

Conditions

Temperature
150 °C

Procedure

A mixture of 4-bromo-N-(4-chloro-phenyl)-benzamide (1.14 g, 3.67 mmol) in SOCl2 (4.5 mL) is heated to 80° C. for 2 h before SOCl2 is removed in vacuo. The resulted imidoyl chloride intermediate is dissolved in anhydrous dichloroethane (18 mL) and transferred into a sealed tube. After adding 5-amino-3-methylsulfanyl-1-phenyl-1H-pyrazole-4-carboxylic acid ethyl ester (1.12 g, 4.04 mmol) and TiCl4 (0.80 mL, 7.3 mmol), the reaction tube is sealed and heated at 150° C. overnight. After cooling down to room temperature the reaction mixture is poured into water (200 mL) and extracted with chloroform (3×100 mL). The organic layers are combined, washed with brine, dried over MgSO4, concentrated, and purified by silica gel chromatography to provide 6-(4-bromo-phenyl)-5-(4-chloro-phenyl)-3-methylsulfanyl-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one as a white solid product; HPLC-MS calculated for C24H16BrClN4OS (M+H+) 523.0, found 523.0.

Workup

  1. customis removed in vacuo
  2. dissolutionThe resulted imidoyl chloride intermediate is dissolved in anhydrous dichloroethane (18 mL)
  3. customtransferred into a sealed tube
  4. customthe reaction tube is sealed
  5. temperatureAfter cooling down to room temperature the reaction mixture
  6. extractionextracted with chloroform (3×100 mL)
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-58131f16f77f42c695df36f5ffa4278a
Source dataset
uspto-grants-2014_05
Patent number
US08722691B2

Reaction notes

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