Potassium Carbonate → 6-Cyano-4-(3-methylindol-5-yloxy)-7-(3-(pyrrolidin-1-yl)propoxy)quinoline

HRID 2222430Notes

Reaction equation

HRID 2222430 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:12]#[N:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:29][C:30]1[C:38]2[C:33](=[CH:34][CH:35]=[C:36]([OH:39])[CH:37]=2)[NH:32][CH:31]=1>CN(C=O)C>[C:12]([C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:14][CH2:15][CH2:16][CH2:17][N:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1)[N:5]=[CH:4][CH:3]=[C:2]2[O:39][C:36]1[CH:37]=[C:38]2[C:33](=[CH:34][CH:35]=1)[NH:32][CH:31]=[C:30]2[CH3:29])#[N:13]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1927343-methyl-1H-indol-5-olHCID 597122344-Chloro-6-cyano-7-(3-(pyrrolidin-1-yl)propoxy)quinoline

Product 1

HCID 102960636-Cyano-4-(3-methylindol-5-yloxy)-7-(3-(pyrrolidin-1-yl)propoxy)quinolineYield 56.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

A solution of 4-chloro-6-cyano-7-(3-(pyrrolidin-1-yl)propoxy)quinoline (200 mg, 0.63 mmol), (prepared as described for the starting material in Example 11), potassium carbonate (131 mg, 0.95 mmol) and 3-methyl-5-hydroxyindole (102.5 mg, 0.69 mmol), (Can. J. Chem. 1964, 42, 514), in DMF (6 ml) was stirred at 95° C. for 2 hours. After cooling, silica was added and the volatiles was removed under vacuum. The product was eluted with methylene chloride followed by methylene chloride/ethyl acetate (containing 20% methanol) (9/1 followed by 8/2) followed by methylene chloride/methanol (saturated with ammonia) (9/1 followed by 8/2). The fractions containing the expected product were combined and evaporated. The residue was triturated with ether, filtered and dried under vacuum to give 6-cyano-4-(3-methylindol-5-yloxy)-7-(3-(pyrrolidin-1-yl)propoxy)quinoline (151 mg, 56%).

Workup

  1. temperatureAfter cooling
  2. additionsilica was added
  3. customthe volatiles was removed under vacuum
  4. washThe product was eluted with methylene chloride
  5. additionThe fractions containing the expected product
  6. customevaporated
  7. customThe residue was triturated with ether
  8. filtrationfiltered
  9. customdried under vacuum

Sources & evidence

ORD record
ord-b70bef888f074cd2b460a98dc6ecb0d5
Source dataset
uspto-grants-2008_05
Patent number
US07371765B2

Reaction notes

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