Piperazine → HCID 56677001, compound

HRID 68704Notes

Reaction equation

HRID 68704 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH3:17])=[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:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]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>[CH3:17][C:6]1[C:5]2[C:9](=[CH:10][C:2]([N:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]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

Participants

6

Reactant 4

HCID 4837PiperazineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 674498536-bromo-3-methyl-1-phenyl-1H-indazole

Product 1

HCID 56677001HCID 56677001, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Into a 100-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 6-bromo-3-methyl-1-phenyl-1H-indazole (1 g, 3.50 mmol, 1.00 equiv) in toluene (20 mL), piperazine (600 mg, 6.98 mmol, 2.00 equiv), Cs2CO3 (1.7 g, 5.21 mmol, 1.50 equiv), Pd(AcO)2 (20 mg, 0.09 mmol, 0.03 equiv), BINAP (20 mg, 0.03 mmol, 0.03 equiv). The resulting solution was stirred overnight at 100° C. in an oil bath. The resulting mixture was cooled, the solids were filtered out. The residue was applied onto a silica gel column with dichloromethane/methanol (20:1). The resulting residue (300 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 42% in 4 min, hold 42% in 3.5 min, up to 100% in 0.1 min, hold 100% in 1.4 min); Detector, UV 220NMnm to yield 3-methyl-1-phenyl-6-(piperazin-1-yl)-1H-indazole as a light yellow solid.

Workup

  1. customInto a 100-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. temperatureThe resulting mixture was cooled
  4. filtrationthe solids were filtered out
  5. customThe resulting residue (300 mg) was purified by Prep-HPLC with the following conditions (AGILENT Pre-HPLC (UV-Directed))
  6. waitmobile phase, water with 0.05% TFA and MeOH (10% MeOH up to 42% in 4 min
  7. customin 3.5 min
  8. waitup to 100% in 0.1 min
  9. customin 1.4 min

Sources & evidence

ORD record
ord-56e06886d496447fb58077df8060d6db
Source dataset
uspto-grants-2014_09
Patent number
US08822447B2

Reaction notes

Loading…