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

HRID 916407Notes

Reaction equation

HRID 916407 reaction equation
[F:1][C:2]1[C:10]([O:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([OH:24])=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH3:25])[NH:6]2.C(=O)([O-])[O-].[K+].[K+].[C:32]([N:35]1[CH2:40][CH2:39][N:38](OCCCCl)[CH2:37][CH2:36]1)(=[O:34])[CH3:33].CN1C[CH2:50][CH2:49][C:48]1=O>>[C:32]([N:35]1[CH2:36][CH2:37][N:38]([CH2:48][CH2:49][CH2:50][O:24][C:18]2[CH:17]=[C:16]3[C:21]([C:12]([O:11][C:10]4[C:2]([F:1])=[C:3]5[C:7](=[CH:8][CH:9]=4)[NH:6][C:5]([CH3:25])=[CH:4]5)=[N:13][CH:14]=[N:15]3)=[CH:20][C:19]=2[O:22][CH3:23])[CH2:39][CH2:40]1)(=[O:34])[CH3:33]

Participants

5

Reactant 4

HCID 11430Potassium CarbonateHCID 13387N-methyl-2-pyrrolidone2×HCID 666465241-Acetyl-4-(3-chloropropoxy)piperazineHCID 1355308324-((4-Fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-ol

Product 1

HCID 112721357-[3-(4-acetylpiperazin-1-yl)propoxy]-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazolineYield 71%

Conditions

Temperature
90 °C

Procedure

4-[(4-Fluoro-2-methyl-1H-indol-5-yl)oxy]-7-hydroxy-6-methoxyquinazoline (250 mg, 0.74 mmol), (prepared as described for the starting material in this example hereinbefore), and potassium carbonate (112 mg, 0.81 mmol) were stirred together in N-methylpyrrolidinone (3 ml). 1-Acetyl-4-(3-chloropropoxy)piperazine (166 mg, 0.81 mmol) in N-methylpyrrolidinone (1 ml) was added and the mixture heated at 90° C. for 3 hours. The mixture was cooled, filtered and concentrated under reduced pressure. The residue was purified by column chromatography eluting with methylene chloride/methanol (saturated with ammonia) (97/3) to give 7-[3-(4-acetylpiperazin-1-yl)propoxy]-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline (268 mg, 71%) as a white solid.

Workup

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by column chromatography
  5. washeluting with methylene chloride/methanol (saturated with ammonia) (97/3)

Sources & evidence

ORD record
ord-4374eb497d4346c6bfd3cdc213362b93
Source dataset
uspto-grants-2007_09
Patent number
US07268230B2

Reaction notes

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