Piperazine → HCID 56670165, compound

HRID 68700Notes

Reaction equation

HRID 68700 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:17][CH3:18])=[N:7][N:8]2[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:4][CH:3]=1.[NH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:17]([C:6]1[C:5]2[C:9](=[CH:10][C:2]([N:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)=[CH:3][CH:4]=2)[N:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:7]=1)[CH3:18]

Participants

7

Reactant 4

HCID 4837PiperazineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 674494686-bromo-3-ethyl-1-phenyl-1H-indazole

Product 1

HCID 56670165HCID 56670165, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Into a 50-mL 3-necked round-bottom flask, was placed a solution of 6-bromo-3-ethyl-1-phenyl-1H-indazole (0.10 g, 0.33 mmol, 1.00 equiv) in toluene (20 mL), piperazine (0.14 g, 1.628 mmol, 2.00 equiv), Cs2CO3 (0.16 g, 5.00 mmol, 1.50 equiv), Pd(OAc)2 (20 mg, 0.09 mmol, 0.03 equiv), BINAP (20 mg, 0.03 mmol, 0.03 equiv). The resulting solution was stirred for 20 h at 100° C. in an oil bath. The solids were filtered out. The residue was applied onto a silica gel column with dichloromethane/methanol (20:1). The resulting residue (50 mg) was purified by Prep-HPLC with the following conditions (AGILENT Pre-HPLC (UV-Directed)): Column, SunFire Prep C18, 5 um, 19*100 mm; mobile phase, water with 0.05% TFA and MeOH (10% MeOH up to 55% in 2.5 min, hold 55% in 2.5 min, up to 100% in 0.1 min, hold 100% in 0.3 min, down to 10% in 0.1 min); Detector, UV254 nm to yield 3-ethyl-1-phenyl-6-(piperazin-1-yl)-1H-indazole as a yellow solid.

Workup

  1. customInto a 50-mL 3-necked round-bottom flask, was placed
  2. filtrationThe solids were filtered out
  3. customThe resulting residue (50 mg) was purified by Prep-HPLC with the following conditions (AGILENT Pre-HPLC (UV-Directed))
  4. waitmobile phase, water with 0.05% TFA and MeOH (10% MeOH up to 55% in 2.5 min
  5. customin 2.5 min
  6. waitup to 100% in 0.1 min
  7. customin 0.3 min
  8. waitdown to 10% in 0.1 min)

Sources & evidence

ORD record
ord-5f1c2151320641e5892d355181f4bd2e
Source dataset
uspto-grants-2014_09
Patent number
US08822447B2

Reaction notes

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