Potassium Carbonate → 1-[4-[3-[4-(6-Chloro-1H-indazol-3-yl)-1-piperazinyl]propoxy]-3-methoxyphenyl]-ethanone

HRID 233834Notes

Reaction equation

HRID 233834 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][CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([C:34](=[O:36])[CH3:35])=[CH:30][C:29]=1[O:37][CH3:38]>C(#N)C>[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][CH2:26][O:27][C:28]4[CH:33]=[CH:32][C:31]([C:34](=[O:36])[CH3:35])=[CH:30][C:29]=4[O:37][CH3:38])[CH2:15][CH2:16]3)=[N:7][NH:8]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 73142644-(3-Chloropropoxy)-3-methoxyacetophenoneHCID 148234706-chloro-3-(1-piperazinyl)-1H-indazole

Product 1

HCID 158400151-[4-[3-[4-(6-Chloro-1H-indazol-3-yl)-1-piperazinyl]propoxy]-3-methoxyphenyl]-ethanoneYield 111.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 6-chloro-3-(1-piperazinyl)-1H-indazole (3.4 g, 14 mmol), K2CO3 (2.5 g, 18 mmol), 1-[4-(3-chloropropoxy)-3-methoxyphenyl]ethanone (3.8 g, 16 mmol), KI (200 mg), and acetonitrile (125 ml) was stirred at reflux under N2 for 30 hours. After standing at room temperature for 40 hours, the reaction was filtered and the filter cake was washed well with acetonitrile. The filtrate was concentrated to an oily solid, which was partitioned between water and ethyl acetate. The ethyl acetate extract was washed with water, dried with MgSO4, and concentrated to yield 6.9 g of a dark oil, which solidified after 2 days under vacuum. The product was purified by preparative HPLC (Waters Associates Prep LC/system 500 utilizing 2 silica gel columns and 6% methanol/methylene chloride as eluent) to yield 4.2 g. The material was recrystallized from ethanol to yield 3.4 g of glistening, beige, 1-[4-[3-[4-(6-chloro-1H-indazol-3-yl)-1-piperazinyl]propoxy]-3-methoxy-]-ethanone crystals, m.p.=132°-134° C.

Workup

  1. temperatureat reflux under N2 for 30 hours
  2. filtrationthe reaction was filtered
  3. washthe filter cake was washed well with acetonitrile
  4. concentrationThe filtrate was concentrated to an oily solid, which
  5. customwas partitioned between water and ethyl acetate
  6. extractionThe ethyl acetate extract
  7. washwas washed with water
  8. dry with materialdried with MgSO4
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-f17cb32a57324634b18915cc99827848
Source dataset
uspto-grants-1997_01
Patent number
US05593995

Reaction notes

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