Piperidin-4-ol → 4-(4-Fluoro-2-methylindol-5-yloxy)-7-(3-(4-hydroxypiperidin-1-yl)propoxy)-6-methoxycinnoline

HRID 2180136Notes

Reaction equation

HRID 2180136 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.Br[CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:22]=[C:21]2[C:16]([C:17]([O:23][C:24]3[C:25]([F:34])=[C:26]4[C:30](=[CH:31][CH:32]=3)[NH:29][C:28]([CH3:33])=[CH:27]4)=[CH:18][N:19]=[N:20]2)=[CH:15][C:14]=1[O:35][CH3:36]>CN(C=O)C>[F:34][C:25]1[C:24]([O:23][C:17]2[C:16]3[C:21](=[CH:22][C:13]([O:12][CH2:11][CH2:10][CH2:9][N:5]4[CH2:6][CH2:7][CH:2]([OH:1])[CH2:3][CH2:4]4)=[C:14]([O:35][CH3:36])[CH:15]=3)[N:20]=[N:19][CH:18]=2)=[CH:32][CH:31]=[C:30]2[C:26]=1[CH:27]=[C:28]([CH3:33])[NH:29]2

Participants

4

Reactant 2

HCID 79341Piperidin-4-olHCID 22490022HCID 22490022, compound

Product 1

HCID 224900264-(4-Fluoro-2-methylindol-5-yloxy)-7-(3-(4-hydroxypiperidin-1-yl)propoxy)-6-methoxycinnolineYield 8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 4-hydroxypiperidine (0.5 g, 4.95 mmol) and 7-(3-bromopropoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxycinnoline (0.3 g, 0.65 mmol) in DMF (4 ml) was stirred at 60° C. for 30 minutes. The volatiles were removed under vacuum and the residue was purified by column chromatography eluting with ethyl acetate/methylene chloride (1/1) followed by ethyl acetate/methanol/methylene chloride (4/1/5) followed by methylene chloride/methanol saturated with ammonia (9/1). The fractions containing the expected product were combined and evaporated to give 4-(4-fluoro-2-methylindol-5-yloxy)-7-(3-(4-hydroxypiperidin-1-yl)propoxy)-6-methoxycinnoline (25 mg, 8%).

Workup

  1. customThe volatiles were removed under vacuum
  2. customthe residue was purified by column chromatography
  3. washeluting with ethyl acetate/methylene chloride (1/1)
  4. additionThe fractions containing the expected product
  5. customevaporated

Sources & evidence

ORD record
ord-a05d50690774417e8112e2bbb3a01e23
Source dataset
uspto-grants-2005_05
Patent number
US06887874B2

Reaction notes

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