Cesium carbonate → (2-Methylindol-5-yloxy)-7-(3-(pyrrolidin-1-yl)propoxy)quinoline

HRID 2222421Notes

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

Participants

Conditions

Temperature: 95 °C

Procedure

A suspension of 4-chloro-6-cyano-7-(3-(pyrrolidin-1-yl)propoxy)quinoline (150 mg, 0.48 mmol), (prepared as described for the starting material in Example 11), 5-hydroxy-2-methylindole (84 mg, 0.57 mmol) and cesium carbonate (200 mg, 0.72 mmol) in DMF (6 ml) was heated at 95° C. for 2 hours. After cooling, the mixture was filtered and the filtrate was evaporated under vacuum. The residue was purified by column chromatography eluting with methylene chloride, followed by ethyl acetate, followed by methanol/methylene chloride (1/9) followed by methylene chloride/methanol saturated with ammonia (9/1 followed by 85/15) to give 6-cyano-((2-methylindol-5-yloxy)-7-(3-(pyrrolidin-1-yl)propoxy)quinoline (112 mg, 46%).

Workup

custom(prepared
temperatureAfter cooling
filtrationthe mixture was filtered
customthe filtrate was evaporated under vacuum
customThe residue was purified by column chromatography
washeluting with methylene chloride

Sources & evidence

ORD record: ord-d68b95e5e71f40e58f318e3f094950b9
Source dataset: uspto-grants-2008_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07371765B2

Reaction notes

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