1-Methylpiperazine → 6-Methoxy-4(2-methylindol-5-yloxy)-7-(3-(4-methypiperazin-1-yl)propoxy)quinazoline

HRID 454077Notes

Reaction equation

HRID 454077 reaction equation
Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10]([O:16][C:17]3[CH:18]=[C:19]4[C:23](=[CH:24][CH:25]=3)[NH:22][C:21]([CH3:26])=[CH:20]4)=[N:11][CH:12]=[N:13]2)=[CH:8][C:7]=1[O:27][CH3:28].[CH3:29][N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1>>[CH3:28][O:27][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:6]=1[O:5][CH2:4][CH2:3][CH2:2][N:33]1[CH2:34][CH2:35][N:30]([CH3:29])[CH2:31][CH2:32]1)[N:13]=[CH:12][N:11]=[C:10]2[O:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][C:21]([CH3:26])=[CH:20]2

Participants

3

Reactant 2

HCID 531671-MethylpiperazineHCID 220308787-(3-Chloropropoxy)-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline

Product 1

HCID 220308076-Methoxy-4(2-methylindol-5-yloxy)-7-(3-(4-methypiperazin-1-yl)propoxy)quinazolineYield 32%

Procedure

A solution of 7-(3-chloropropoxy)-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (150 mg, 0.38 mmol), (prepared as described in Example 73), in 1-methylpiperazine (2 ml) was heated at 100° C. for 2 hours. After cooling, the mixture was partitioned between ethyl acetate and aqueous 5% sodium hydrogen carbonate. The organic layer was separated, washed with water, brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography on an isolute column eluting with methanol/ethyl acetate/methylene chloride (1/4/5 followed by 1/9/0) and 3M ammonia in methanol/methanol/methylene chloride (5/10/80). After removal of the solvent under vacuum, the solid was dissolved in the minimum of methylene chloride and ether/petroleum ether was added. The precipitate was collected by filtration, and dried under vacuum to give 6-methoxy-4-(2-methylindol-5-yloxy)-7-(3-(4-methypiperazin-1-yl)propoxy)quinazoline (55 mg, 32%).

Workup

  1. temperatureAfter cooling
  2. customthe mixture was partitioned between ethyl acetate and aqueous 5% sodium hydrogen carbonate
  3. customThe organic layer was separated
  4. washwashed with water, brine
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe residue was purified by column chromatography on an isolute column
  8. washeluting with methanol/ethyl acetate/methylene chloride (1/4/5 followed by 1/9/0) and 3M ammonia in methanol/methanol/methylene chloride (5/10/80)
  9. customAfter removal of the solvent under vacuum
  10. dissolutionthe solid was dissolved in the minimum of methylene chloride and ether/petroleum ether
  11. additionwas added
  12. filtrationThe precipitate was collected by filtration
  13. customdried under vacuum

Sources & evidence

ORD record
ord-599fe990ab74460abb5b29830b6d5557
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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