1-Acetylpiperazine → 7-[3-(4-acetylpiperazin-1-yl)propoxy]-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline

HRID 916397Notes

Reaction equation

HRID 916397 reaction equation
Br[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[C:18]([F:27])=[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:28][CH3:29].[C:30]([N:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1)(=[O:32])[CH3:31]>CN(C=O)C>[C:30]([N:33]1[CH2:38][CH2:37][N:36]([CH2:2][CH2:3][CH2:4][O:5][C:6]2[CH:15]=[C:14]3[C:9]([C:10]([O:16][C:17]4[C:18]([F:27])=[C:19]5[C:23](=[CH:24][CH:25]=4)[NH:22][C:21]([CH3:26])=[CH:20]5)=[N:11][CH:12]=[N:13]3)=[CH:8][C:7]=2[O:28][CH3:29])[CH2:35][CH2:34]1)(=[O:32])[CH3:31]

Participants

4

Reactant 2

HCID 837951-AcetylpiperazineHCID 589602427-(3-Bromopropoxy)-4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazoline

Product 1

HCID 112721357-[3-(4-acetylpiperazin-1-yl)propoxy]-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazolineYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 7-(3-bromopropoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxyquinazoline (0.25 g, 0.543 mmol) and 1-acetylpiperazine (0.208 g, 1.63 mmol) in DMF (4 ml) was stirred at 80° C. for 2.5 hours. The volatiles were removed under vacuum and the residue was purified by column chromatography eluting with increasingly polar mixtures of methylene chloride and methanol. The fractions containing the expected product were combined and evaporated. The residue was triturated under diethyl ether and the resulting solid was filtered, washed with diethyl ether and dried under vacuum to give 7-(3-(4-acetylpiperazin-1-yl)propoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxyquinazoline (0.25 g, 0.543 mmol).

Workup

  1. customThe volatiles were removed under vacuum
  2. customthe residue was purified by column chromatography
  3. washeluting
  4. temperaturewith increasingly polar mixtures of methylene chloride and methanol
  5. additionThe fractions containing the expected product
  6. customevaporated
  7. customThe residue was triturated under diethyl ether
  8. filtrationthe resulting solid was filtered
  9. washwashed with diethyl ether
  10. customdried under vacuum

Sources & evidence

ORD record
ord-09f74c6ceb054fbd9b8e736ed7d01631
Source dataset
uspto-grants-2007_09
Patent number
US07268230B2

Reaction notes

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