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

HRID 2068089Notes

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:26]([N:29]1[CH2:34][CH2:33][N:32]([CH2:35][CH2:36]Cl)[CH2:31][CH2:30]1)(=[O:28])[CH3:27].C(=O)([O-])[O-].[K+].[K+].O>CN1CCCC1=O>[C:26]([N:29]1[CH2:34][CH2:33][N:32]([CH2:35][CH2:36][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])[CH2:31][CH2:30]1)(=[O:28])[CH3:27]

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-7-hydroxy-6-methoxyquinazoline (250 mg, 0.74 mmol), 1-acetyl-4-(2-chloroethyl)piperazine (144 mg, 0.81 mmol) and potassium carbonate (12 mg, 0.81 mmol) in N-methylpyrrolidinone (6 ml) was heated at 90° C. for 2 hours. The mixture was cooled and water added. After 30 minutes the solid was filtered off and dried under vacuum. The residue was purified by column chromatography eluting with methylene chloride/methanol (saturated with ammonia) (96/4) to give 7-[2-(4-acetylpiperazin-1-yl)ethoxy]-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline (310 mg, 58%) as a white solid.

Workup

temperatureThe mixture was cooled
filtrationAfter 30 minutes the solid was filtered off
customdried under vacuum
customThe residue was purified by column chromatography
washeluting with methylene chloride/methanol (saturated with ammonia) (96/4)

Sources & evidence

ORD record: ord-7c3c2b0021ca4ac288aa7befa0d6b637
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293902B2

Reaction notes

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