Hydrochloric Acid → 3-Cyano-7-methoxy-5-[(1-methylpiperidin-4-yl)oxy]-4-[4-(3-methoxyprop-1-ynyl)-2,3-methylenedioxyanilino]quinoline dihydrochloride salt

HRID 347437Notes

Reaction equation

HRID 347437 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:20][CH3:21])=[CH:9][C:10]=2[O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[N:5]=[CH:4][C:3]=1[C:22]#[N:23].[CH3:24][O:25][CH2:26][C:27]#[C:28][C:29]1[CH:35]=[CH:34][C:32]([NH2:33])=[C:31]2[O:36][CH2:37][O:38][C:30]=12.[ClH:39].C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl.C(#N)C>C(O)CC.C(OCC)C>[ClH:1].[ClH:39].[C:22]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[NH:33][C:32]1[CH:34]=[CH:35][C:29]([C:28]#[C:27][CH2:26][O:25][CH3:24])=[C:30]3[O:38][CH2:37][O:36][C:31]=13)=[C:10]([O:12][CH:13]1[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]1)[CH:9]=[C:8]([O:20][CH3:21])[CH:7]=2)#[N:23]

Participants

8

Reactant 5

HCID 313Hydrochloric Acid2×HCID 6342AcetonitrileHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 210827034-(3-Methoxyprop-1-ynyl)-2,3-methylendioxyanilineHCID 210827133-Quinolinecarbonitrile, 4-chloro-7-methoxy-5-[(1-methyl-4-piperidinyl)oxy]-

Product 1

HCID 210827003-Cyano-7-methoxy-5-[(1-methylpiperidin-4-yl)oxy]-4-[4-(3-methoxyprop-1-ynyl)-2,3-methylenedioxyanilino]quinoline dihydrochloride salt

Reagents, catalysts & solvents 2

HCID 10311-PropanolSolventHCID 3283Diethyl EtherSolvent2×

Procedure

A mixture of 4-chloro-3-cyano-7-methoxy-5-[(1-methylpiperidin-4-yl)oxy]quinoline (165 mg) and 4-(3-methoxyprop-1-ynyl)-2,3-methylendioxyaniline (123 mg) in 1-propanol (10 ml) was treated with a 1.0M solution of hydrogen chloride in diethyl ether (0.5 ml) then stirred and heated at reflux for 2 hours. On cooling a solid precipitated from the reaction mixture. The resulting suspension was basified with aqueous ammonia and evaporated to a gum. This residue was purified by multi-injection preparative RP HPLC [Kromasil C18 5 μm silica column, 100 mm×10 mm; eluted with a mixture of acetonitrile (55%) and 0.1% aqeous ammonia solution (45%)]. After isolation, the major product was converted to its dihydrochloride salt in acetonitrile using two equivalents of a 1.0M solution of hydrogen chloride in diethyl ether. The title compound was thus obtained as a yellow solid (81 mg); NMR Spectrum: (DMSOd6 & CD3COOD, 373K) 2.17 (m, 2H), 2.38 (m, 2H), 2.77 (s, 3H), 3.30 (m, 4H), 3.37 (s, 3H), 3.96 (s, 3H), 4.33 (s, 2H), 5.04 (m, 1H), 6.12 (s, 2H), 6.92 (d, 1H), 6.97 (m, 2H), 7.08 (s, 1H), 8.63 (s, 1H); Mass Spectrum: M+H+ 501.

Workup

  1. temperatureheated
  2. temperatureat reflux for 2 hours
  3. temperatureOn cooling a solid
  4. customprecipitated from the reaction mixture
  5. customevaporated to a gum
  6. customThis residue was purified by multi-injection preparative RP HPLC [Kromasil
  7. washeluted with a mixture of acetonitrile (55%) and 0.1% aqeous ammonia solution (45%)]

Sources & evidence

ORD record
ord-b9adfc7fb8c8441dbec4ac9d6110470d
Source dataset
uspto-grants-2007_02
Patent number
US07173135B2

Reaction notes

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