18-Crown-6 → 6-(2,3-dihydro-1H-inden-2-ylamino)-2-methyl-4-phenylquinoline-3-carboxylic acid

HRID 570384Notes

Reaction equation

HRID 570384 reaction equation
[CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]1[NH:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]=[C:16]([CH3:21])[C:15]([C:22]([O:24]C)=[O:23])=[C:14]2[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C1OCCOCCOCCOCCOCCOC1>CCO>[CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]1[NH:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]=[C:16]([CH3:21])[C:15]([C:22]([OH:24])=[O:23])=[C:14]2[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

4

Reactant 2

HCID 2855718-Crown-6HCID 68294847methyl 6-(2,3-dihydro-1H-inden-2-ylamino)-2-methyl-4-phenylquinoline-3-carboxylate

Product 1

HCID 601657356-(2,3-dihydro-1H-inden-2-ylamino)-2-methyl-4-phenylquinoline-3-carboxylic acidYield 94%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of the product of Step 3 (0.98 g, 2.4 mmol), 2MKOH aq (3.6 ml, 7.2 ml) and 18-crown-6 ether (0.63 g, 0.24 mmol) in EtOH (50 ml) was refluxed for 30 h under N2. After cooling to room temperature the organic solvent was removed under reduced pressure and the residue was diluted to 5 ml with H2O, filtered and the filtrate was acidified to pH˜5 with 10% aqueous citric acid. The precipitate formed was filtered off, washed with H2O, small volume of EtOH, Et2O and dried in vacuo to give pure product as a deep yellow solid (0.89 g, 93%). 1H NMR (300 MHz, DMSO-d6) δ 7.65 (d, J=9.0 Hz, 1H), 7.3-7.5(m, 5H), 7.06-7.18(m, 5H), 6.31(m, 1H), 6.28(d, J=2.4 Hz, 1H), 3.92(m, 1H), 3.08(dd, J=7, 16 Hz, 2H), 2.72(dd, J=7 Hz, 16H), 2.48(s, 3H). LCMS, Rt=1.48 min, >99%, m/z (%): 395 (M+·, 100).

Workup

  1. temperaturewas refluxed for 30 h under N2
  2. customwas removed under reduced pressure
  3. additionthe residue was diluted to 5 ml with H2O
  4. filtrationfiltered
  5. customThe precipitate formed
  6. filtrationwas filtered off
  7. washwashed with H2O, small volume of EtOH, Et2O
  8. customdried in vacuo

Sources & evidence

ORD record
ord-2f139a1a37b54259a133ec42b1516d21
Source dataset
uspto-grants-2015_05
Patent number
US09023848B2

Reaction notes

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