Diethyl Ether → 4-(1h-Indazol-6-ylamino)-6-methoxy-7-[2-(4-methyl-piperazin-1-yl)-ethoxy]-quinoline-3-carbonitrile

HRID 1595802Notes

Reaction equation

HRID 1595802 reaction equation
Cl[CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([NH:17][C:18]3[CH:26]=[C:25]4[C:21]([CH:22]=[N:23][NH:24]4)=[CH:20][CH:19]=3)=[C:10]([C:15]#[N:16])[CH:11]=[N:12]2)=[CH:7][C:6]=1[O:27][CH3:28].[CH3:29][N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1.[I-].[Na+].CCOCC>COCCOC>[NH:24]1[C:25]2[C:21](=[CH:20][CH:19]=[C:18]([NH:17][C:9]3[C:8]4[C:13](=[CH:14][C:5]([O:4][CH2:3][CH2:2][N:33]5[CH2:34][CH2:35][N:30]([CH3:29])[CH2:31][CH2:32]5)=[C:6]([O:27][CH3:28])[CH:7]=4)[N:12]=[CH:11][C:10]=3[C:15]#[N:16])[CH:26]=2)[CH:22]=[N:23]1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 5238Sodium IodideHCID 531671-MethylpiperazineHCID 102940037-(2-Chloroethoxy)-4-(1H-indazol-6-ylamino)-6-methoxyquinoline-3-carbonitrile

Product 1

HCID 217048004-(1h-Indazol-6-ylamino)-6-methoxy-7-[2-(4-methyl-piperazin-1-yl)-ethoxy]-quinoline-3-carbonitrileYield 51.6%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
135 °C

Procedure

A reaction mixture of 196.5 mg (0.5 mmol) of the 7-(2-chloro-ethoxy)-4-(1H-indazol-6-ylamino)-6-methoxy-quinoline-3-carbonitrile, 500.9 mg (5 mmol) of 1-methylpiperazine and 74.5 mg (0.5 mmol) of sodium iodide in 10 mL of DME was heated at 135° C. for 15 hr under N2 in a sealed tube. After cooling, the solvent was removed and the residue was taken into 15 mL of brine. The aqueous solution was extracted with 15% methanol/methylene chloride. The organic solvent was dried over Na2SO4 and filtered. Removal of the solvent gave the crude product solid. Purification of the crude product on preparative TLC (developing solvent: 15% methanol/methylene chloride) to give a yellow foam solid. Trituration of the foam solid with ether yielded 117.9 mg (51.6%) of the product as a yellow solid, m.p. 179° C. (dec.), mass (electrospray, m/e): M+H 458.0.

Workup

  1. temperatureAfter cooling
  2. customthe solvent was removed
  3. extractionThe aqueous solution was extracted with 15% methanol/methylene chloride
  4. dry with materialThe organic solvent was dried over Na2SO4
  5. filtrationfiltered
  6. customRemoval of the solvent
  7. customgave the crude product solid
  8. customPurification of the crude product on preparative TLC (developing solvent: 15% methanol/methylene chloride)
  9. customto give a yellow foam solid

Sources & evidence

ORD record
ord-042a4a76342540c9ab58b5b69939e552
Source dataset
uspto-grants-2001_09
Patent number
US06288082B1

Reaction notes

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