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

HRID 916473Notes

Reaction equation

HRID 916473 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:23]=[C:22]3[C:17]([C:18](Cl)=[N:19][CH:20]=[N:21]3)=[CH:16][C:15]=2[O:25][CH3:26])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[OH:27][C:28]1[CH:29]=[C:30]2[C:34](=[CH:35][CH:36]=1)[NH:33][C:32]([CH3:37])=[CH:31]2.C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:23]=[C:22]3[C:17]([C:18]([O:27][C:28]4[CH:29]=[C:30]5[C:34](=[CH:35][CH:36]=4)[NH:33][C:32]([CH3:37])=[CH:31]5)=[N:19][CH:20]=[N:21]3)=[CH:16][C:15]=2[O:25][CH3:26])[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 833362-methyl-1H-indol-5-olHCID 589602297-(3-(4-Acetylpiperazin-1-yl)propoxy)-4-chloro-6-methoxyquinazoline

Product 1

HCID 101521827-[3-(4-acetylpiperazin-1-yl)propoxy]-6-methoxy-4-[(2-methyl-1H-indol-5-yl)oxy]quinazolineYield 53.1%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 7-[3-(4-acetylpiperazin-1-yl)propoxy]-4-chloro-6-methoxyquinazoline (190 mg, 0.50 mmol), (prepared as described for the starting material in Example 4), 5-hydroxy-2-methylindole (81 mg, 0.55 mmol), (WO 00/47212, Example 48), and potassium carbonate (76 mg, 0.55 mmol) in DMA (6 ml) was stirred at 85° C. for 3 hours, allowed to cool to ambient temperature and the solvent evaporated under vacuum. The residue was purified by column chromatography eluting with methylene chloride/methanol (saturated with ammonia) (92/8) to give a white solid. This was triturated with a mixture of ether and acetone, filtered and dried to give 7-[3-(4-acetylpiperazin-1-yl)propoxy]-6-methoxy-4-[(2-methyl-1H-indol-5-yl)oxy]quinazoline (130 mg, 53%).

Workup

  1. custom(prepared
  2. temperatureto cool to ambient temperature
  3. customthe solvent evaporated under vacuum
  4. customThe residue was purified by column chromatography
  5. washeluting with methylene chloride/methanol (saturated with ammonia) (92/8)
  6. customto give a white solid
  7. customThis was triturated with a mixture of ether and acetone
  8. filtrationfiltered
  9. customdried

Sources & evidence

ORD record
ord-90c96f9b45f7413287e3237558a1ae29
Source dataset
uspto-grants-2007_09
Patent number
US07268230B2

Reaction notes

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