Potassium Carbonate → 4-(4-Fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(3-(piperidin-1-yl)propoxy)cinnoline

HRID 2180146Notes

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

Participants

Conditions

Temperature: 95 °C

Procedure

A suspension of 4-(4-fluoro-2-methylindol-5-yloxy)-7-hydroxy-6-methoxycinnoline (0.2 g, 0.6 mmol), (prepared as described in Example 4), 1-(3-chloropropyl)piperidine (0.12 g, 0.72 mmol) and potassium carbonate (0.125 g, 0.9 mmol) in DMF (5 ml) was stirred at 95° C. for 2 hours. After cooling, the precipitate was filtered. The filtrate was diluted with methylene chloride and purified by column chromatography eluting with methanol/ethyl acetate/methylene chloride (1/4/5) followed by methanol/methylene chloride (1/9) followed by methanol saturated with ammonia/methylene chloride (1/9). The fractions containing the expected product were combined and evaporated to give 4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxy-7-(3-(piperidin-1-yl)propoxy)cinnoline (27 mg, 10%).

Workup

temperatureAfter cooling
filtrationthe precipitate was filtered
additionThe filtrate was diluted with methylene chloride
custompurified by column chromatography
washeluting with methanol/ethyl acetate/methylene chloride (1/4/5)
additionThe fractions containing the expected product
customevaporated

Sources & evidence

ORD record: ord-00c66058dfa54d9db9f44041b2952558
Source dataset: uspto-grants-2005_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06887874B2

Reaction notes

Loading…