Chlorotrimethylsilane → 6-Benzyl-3-(2-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyridine

HRID 2252319Notes

Reaction equation

HRID 2252319 reaction equation
BrC(Br)C.Cl[Si](C)(C)C.[CH2:10](Br)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.Br[C:19]1[CH:20]=[CH:21][C:22]2[N:23]([C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[Cl:34])=[N:26][N:27]=2)[CH:24]=1>[Zn].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1COCC1>[CH2:10]([C:19]1[CH:20]=[CH:21][C:22]2[N:23]([C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[Cl:34])=[N:26][N:27]=2)[CH:24]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

8

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 7498Benzyl BromideHCID 112011,1-DibromoethaneHCID 179744786-Bromo-3-(2-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyridine

Product 1

HCID 102454236-Benzyl-3-(2-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyridineYield 7.1%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a flame-dried flash under nitrogen was added Rieke zinc (2.3 mL, 1.75 mmol). The total volume of the reaction was brought to 5 mL using dry THF. To the slurry was added dibromoethane (10.0 μL, 0.01 mmol), and the reaction warmed to 65° C. for 3 minutes. The reaction was then cooled to 35° C., and chlorotrimethylsilane (30.0 μL, 0.25 mmol) added, and the resulting reaction stirred for 30 minutes at 35° C. Benzyl bromide (55 uL, 0.46 mmol), was added and the reaction stirred a further 30 minutes at 35° C. To the mixture was then added 6-bromo-3-(2-chloro-phenyl)-[1,2,4]triazolo[4,3-a]pyridine (136 mg, 0.44 mmol) and Pd(PPh3)4 and the temperature increased to 50° C. Flash chromatography purification (elution with 35-85% ethyl acetate/hexane), followed by preparatory HPLC (15-80% water/acetonitrile) of the crude reaction mixture yielded the title compound (10 mg, 7%). MS (M+1)=320.4.

Workup

  1. temperatureThe reaction was then cooled to 35° C.
  2. customthe resulting reaction
  3. stirringthe reaction stirred a further 30 minutes at 35° C
  4. customFlash chromatography purification (elution with 35-85% ethyl acetate/hexane)
  5. customreaction mixture

Sources & evidence

ORD record
ord-6712876e00814d03bdfb79b1252510cc
Source dataset
uspto-grants-2008_01
Patent number
US07321040B2

Reaction notes

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