HCID 69013867, compound → HCID 16048421, compound

HRID 2406418Notes

Reaction equation

HRID 2406418 reaction equation
[CH3:1][O:2][C:3]1[C:4]([O:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[CH:31]=2)=[C:5]2[C:10](=[C:11]([NH:13][CH2:14][CH2:15][CH2:16][N:17]3C(=O)C4=CC=CC=C4C3=O)[CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[CH3:28]>NN.C(O)C.[OH-].[K+]>[CH3:1][O:2][C:3]1[C:4]([O:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:37])([F:39])[F:38])[CH:31]=2)=[C:5]2[C:10](=[C:11]([NH:13][CH2:14][CH2:15][CH2:16][NH2:17])[CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[CH3:28]

Participants

5

Reactant 1

HCID 69013867HCID 69013867, compound

Product 1

HCID 16048421HCID 16048421, compoundYield 80%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 9321HydrazineSolventHCID 14797Potassium HydroxideSolvent

Procedure

A solution of the above phthalimide 10 in 100 mL of 65% hydrazine and 100 mL of ethanol was refluxed under argon for 3 hours. After cooling to room temperature, the solution was diluted with 10% aqueous KOH solution and extracted with dichloromethane three times. The combined extract was washed with brine, dried (K2CO3), concentrated, and column chromatographed on silica gel using dichloromethane and methanol as eluants to give 1.86 g (80% yield) of 6-methoxy-8-[(3-aminopropyl)amino]-4-methyl-5-(3-trifluoromethylphenyloxy)quinoline. 1H NMR (CDCl3) δ 8.40 (d, J=4 Hz, 1 H), 7.34 (t, J=8 Hz, 1 H), 7.21 (d, J=8 Hz, 1 H), 7.06 (m, 2 H), 6.93 (d, J=8 Hz, 1 H), 6.48 (s, 1 H), 6.4 (bs, 1 H, NH), 3.83 (s, 3 H, OMe), 3.42 (t, J=8 Hz, 2 H), 2.99 (t, J=8 Hz, 2 H), 2.62 (s, 3 H, Me), 1.98 (pentet, J=8 Hz, 2 H), 1.80 (bs, 2 H, NH2). 13C NMR (CDCl3) δ 160.0, 151.1, 145.0, 143.5, 142.7, 130.2, 125.2, 118.4, 118.2, 112.2, 107.5, 92.9, 56.8, 41.6, 40.4, 33.1, 23.4. The succinic acid salt was prepared by treating 0.457 g (1.12 mmol) of the quinoline with 0.134 g (1.13 mmol) of succinic acid in 10 mL of methanol. The resulting solution was concentrated to dryness, crystallized from diethyl ether to give a quantitative yield of the succinic acid salt PQ1.

Workup

  1. extractionextracted with dichloromethane three times
  2. extractionThe combined extract
  3. washwas washed with brine
  4. dry with materialdried (K2CO3)
  5. concentrationconcentrated
  6. customcolumn chromatographed on silica gel

Sources & evidence

ORD record
ord-178f20f3a2f7400dbbb9d8a5b23f71e4
Source dataset
uspto-grants-2014_08
Patent number
US08809368B2

Reaction notes

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