Acetonitrile → 1-[4-[2-[4-(6-Chloro-1H-indazol-3-yl)1-piperazinyl]ethoxy]-3-methoxyphenyl]-ethanone

HRID 1420338Notes

Reaction equation

HRID 1420338 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([N:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Cl[CH2:24][CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([C:33](=[O:35])[CH3:34])=[CH:29][C:28]=1[O:36][CH3:37].C(#N)C>O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([N:11]3[CH2:12][CH2:13][N:14]([CH2:24][CH2:25][O:26][C:27]4[CH:32]=[CH:31][C:30]([C:33](=[O:35])[CH3:34])=[CH:29][C:28]=4[O:36][CH3:37])[CH2:15][CH2:16]3)=[N:7][NH:8]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 144071701-[4-(2-Chloroethoxy)-3-methoxyphenyl]ethanoneHCID 148234706-chloro-3-(1-piperazinyl)-1H-indazole

Product 1

HCID 219600041-[4-[2-[4-(6-Chloro-1H-indazol-3-yl)1-piperazinyl]ethoxy]-3-methoxyphenyl]-ethanoneYield 41.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 6-chloro-[3-(1-piperazinyl)]-1H-indazole (2.1 g, 8.9 mmol), K2CO3 (1.5 g, 10.7 mmol), KI (100 mg), 1-[4-(2-chloroethoxy)-3-methoxyphenyl]ethanone (2.2 g, 9.8 mml) and acetonitrile (70 ml) was stirred at reflux for 48 hours under N2. The cooled reaction was poured into water and the aqueous mixture was extracted with ethyl acetate. The organic extract was washed with water, dried with MgSO4 and concentrated to yield 6.0 of a light yellow oil. The oil was purified by preparative HPLC (Waters Associates prep LC/System 500, employing 2 silica gel columns and 5.5% methanol/methylene chloride as eluent). Concentration of later fractions provided 1.6 g of an off-white solid. This was combined with an additional sample (3.4 g total) and two consecutive recrystallizations from ethanol yielded 2.1 g (23%) of 1-[4-[2-[4-(6-chloro-1H-indazol-3-yl)-1-piperazinyl]ethoxy]-3-methozy-phenyl]ethanone as an off-white solid, m.p.=154°-156° C.

Workup

  1. temperatureat reflux for 48 hours under N2
  2. customThe cooled reaction
  3. extractionthe aqueous mixture was extracted with ethyl acetate
  4. extractionThe organic extract
  5. washwas washed with water
  6. dry with materialdried with MgSO4
  7. concentrationconcentrated
  8. customto yield 6.0 of a light yellow oil
  9. customThe oil was purified by preparative HPLC (Waters Associates prep LC/System 500, employing 2 silica gel columns and 5.5% methanol/methylene chloride as eluent)

Sources & evidence

ORD record
ord-1bf30b8afd3145a6866594f8b23a15c4
Source dataset
uspto-grants-1999_03
Patent number
US05889035

Reaction notes

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