Dichloromethane → 7-(4-chlorophenyl)-8-(pyridin-4-yl)-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one

HRID 271410Notes

Reaction equation

HRID 271410 reaction equation
Br[C:2]1[C:3]2[N:4]([C:15](=[O:29])[N:16]([CH2:18][C:19]3[CH:20]=[N:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=3)[N:17]=2)[CH:5]=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=1.[N:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(Cl)Cl>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:14][C:11]1[CH:10]=[CH:9][C:8]([C:7]2[N:6]=[CH:5][N:4]3[C:15](=[O:29])[N:16]([CH2:18][C:19]4[CH:20]=[N:21][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:23][CH:24]=4)[N:17]=[C:3]3[C:2]=2[C:33]2[CH:34]=[CH:35][N:30]=[CH:31][CH:32]=2)=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 2734379(Pyridin-4-yl)boronic acidHCID 587728488-bromo-7-(4-chlorophenyl)-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one

Product 1

HCID 159536677-(4-chlorophenyl)-8-(pyridin-4-yl)-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-oneYield 22%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 8-bromo-7-(4-chlorophenyl)-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-one (24 mg, 0.05 mmol), pyridine-4-boronic acid (51 mg, 0.25 mmol), K3PO4 (53 mg, 0.25 mmol), and Pd(dppf)Cl2.CH2Cl2 (16 mg, 0.02 mmol) in THF (0.5 mL) at room temperature was degassed by bubbling with argon for 1 min. This was then stirred and heated at 100° C. in a sealed vessel for 3 h. Analysis by HPLC/MS indicated that starting material had been consumed. After the reaction mixture was cooled to room temperature, the solvent was removed under reduced pressure. The product was purified by silica gel column chromatography eluted with ethyl acetate-hexanes. This provided the title compound (5.3 mg) as a yellow solid. HPLC/MS (methanol-water with 10 mM NH4OAc): retention time=3.38 min, [M+H]30 =483.

Workup

  1. customby bubbling with argon for 1 min
  2. customhad been consumed
  3. temperatureAfter the reaction mixture was cooled to room temperature
  4. customthe solvent was removed under reduced pressure
  5. customThe product was purified by silica gel column chromatography
  6. washeluted with ethyl acetate-hexanes

Sources & evidence

ORD record
ord-2ddf468675c44c07a8cf8c4d72cbf39f
Source dataset
uspto-grants-2008_11
Patent number
US07452892B2

Reaction notes

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