Potassium Carbonate → 4-(7-Azaindol-5-yloxy)-6-methoxy-7-[3-(4-prop-2-yn-1-ylpiperazin-1-yl)propoxy]quinazoline

HRID 2068123Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][N:21]([CH2:24][C:25]#[CH:26])[CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[OH:27][C:28]1[CH:29]=[C:30]2[C:34](=[N:35][CH:36]=1)[NH:33][CH:32]=[CH:31]2.C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O>[NH:33]1[C:34]2[C:30](=[CH:29][C:28]([O:27][C:2]3[C:11]4[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]5[CH2:23][CH2:22][N:21]([CH2:24][C:25]#[CH:26])[CH2:20][CH2:19]5)=[C:9]([O:12][CH3:13])[CH:10]=4)[N:5]=[CH:4][N:3]=3)=[CH:36][N:35]=2)[CH:31]=[CH:32]1

Participants

Conditions

Temperature: 85 °C

Procedure

4-Chloro-6-methoxy-7-[3-(4-prop-2-yn-1-ylpiperazin-1-yl)propoxy]quinazoline (300 mg, 0.8 mmol) was dissolved in dimethylacetamide (10 ml). 5-Hydroxy-7-azaindole (118 mg, 0.88 mmol), (prepared as described for the starting material in Example 2), and potassium carbonate (122 mg, 0.88 mmol) were added and the mixture heated to 85° C. for 1.5 hours. The reaction mixture was cooled, filtered and concentrated. The resulting residue was preabsorbed on silica and eluted with methylene chloride/methanol (saturated with ammonia) (90/10) to give 4-(7-azaindol-5-yloxy)-6-methoxy-7-[3-(4-prop-2-yn-1-ylpiperazin-1-yl)propoxy]quinazoline (288 mg, 76%).

Workup

additionwere added
temperatureThe reaction mixture was cooled
filtrationfiltered
concentrationconcentrated
customThe resulting residue was preabsorbed on silica
washeluted with methylene chloride/methanol (saturated with ammonia) (90/10)

Sources & evidence

ORD record: ord-06ba54b780b94a2cb647c4d5621fc3f6
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293902B2

Reaction notes

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