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

HRID 271411Notes

Reaction equation

HRID 271411 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.[OH:30][CH2:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=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:26])([F:28])[F:27])=[CH:23][CH:24]=4)[N:17]=[C:3]3[C:2]=2[C:35]2[CH:36]=[CH:37][C:32]([CH2:31][OH:30])=[CH:33][CH:34]=2)=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 27347064-(Hydroxymethyl)benzeneboronic 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 159537027-(4-chlorophenyl)-8-(4-(hydroxymethyl)phenyl)-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-c]pyrimidin-3(2H)-oneYield 13.1%

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 (48 mg, 0.10 mmol), 4-(hydroxymethyl)phenylboronic acid (46 mg, 0.30 mmol), K3PO4 (63 mg, 0.30 mmol), and Pd(dppf)Cl2.CH2Cl2 (20 mg, 0.025 mmol) in THF (1 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 crude product was purified by silica gel column chromatography eluted with ethyl acetate-hexanes. This provided the title compound (6.7 mg) as a light yellow solid. HPLC/MS (methanol-water with 10 mM NH4OAc): retention time=3.53 min, [M+H]30 =512.

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 crude product was purified by silica gel column chromatography
  6. washeluted with ethyl acetate-hexanes

Sources & evidence

ORD record
ord-0ed6367523f84109810412437bde6d22
Source dataset
uspto-grants-2008_11
Patent number
US07452892B2

Reaction notes

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