Hydrochloric Acid → 3-Cyano-7-(3-morpholin-4-ylpropoxy)-5-(tetrahydro-2h-pyran-4-yloxy)-4-[4-(3-methoxyprop-1-ynyl)-2,3-methylenedioxyanilino]quinoline dihydrochloride salt

HRID 347441Notes

Reaction equation

HRID 347441 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:19][CH2:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)=[CH:9][C:10]=2[O:12][CH:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[N:5]=[CH:4][C:3]=1[C:29]#[N:30].[CH3:31][O:32][CH2:33][C:34]#[C:35][C:36]1[CH:42]=[CH:41][C:39]([NH2:40])=[C:38]2[O:43][CH2:44][O:45][C:37]=12.[ClH:46].CN(C)C(=N)N(C)C>C(O)CC.C(OCC)C>[ClH:1].[ClH:46].[C:29]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[NH:40][C:39]1[CH:41]=[CH:42][C:36]([C:35]#[C:34][CH2:33][O:32][CH3:31])=[C:37]3[O:45][CH2:44][O:43][C:38]=13)=[C:10]([O:12][CH:13]1[CH2:14][CH2:15][O:16][CH2:17][CH2:18]1)[CH:9]=[C:8]([O:19][CH2:20][CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)[CH:7]=2)#[N:30]

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 664601,1,3,3-TetramethylguanidineHCID 210827034-(3-Methoxyprop-1-ynyl)-2,3-methylendioxyanilineHCID 210827124-chloro-3-cyano-7-(3-morpholin-4-ylpropoxy)-5-(tetrahydro-2H-pyran-4-yloxy)quinoline

Product 1

HCID 210826953-Cyano-7-(3-morpholin-4-ylpropoxy)-5-(tetrahydro-2h-pyran-4-yloxy)-4-[4-(3-methoxyprop-1-ynyl)-2,3-methylenedioxyanilino]quinoline dihydrochloride salt

Reagents, catalysts & solvents 2

HCID 10311-PropanolSolventHCID 3283Diethyl EtherSolvent

Procedure

A mixture of 4-chloro-3-cyano-7-(3-morpholin-4-ylpropoxy)-5-(tetrahydro-2H-pyran-4-yloxy)quinoline (125 mg) and 4-(3-methoxyprop-1-ynyl)-2,3-methylendioxyaniline (179 mg) in 1-propanol (8 ml) was treated with a 11.0M solution of hydrogen chloride in diethyl ether (0.30 ml) then stirred and heated at reflux for 1 hour. The mixture was allowed to cool and neutralised by the addition of tetramethylguanidine (0.10 ml). The resulting solution was evaporated to dryness and the residue was purified by chromatography on a Biotage silica cartridge (20 g) eluting with a gradient of methanol in dichloromethane (1–10%). The fractions containing the product were combined and evaporated. The residue was dissolved in ethanol (8 ml) and treated with 2 equivalents of hydrogen chloride (1.0M in diethyl ether). The title compound was thus obtained as a white solid (130 mg); NMR Spectrum: (DMSOd6, 300K) 1.87 (m, 2H), 2.10 (m, 2H), 2.31 (m, 2H), 3.11 (m, 2H), 3.30 (m, 2H), 3.36 (s, 3H), 3.50 (m, 4H), 3.87 (m, 4H), 3.97 (m, 2H), 4.32 (m, 2H), 4.37 (s, 2H), 5.10 (m, 1H), 6.18 (s, 2H), 1.05 (m, 3H), 7.13 (s, 1H), 8.87 (s, 1H), 10.43 (s, 1H), 11.34 (s, 1H); Mass Spectrum: M+H+ 601.

Workup

  1. temperatureheated
  2. temperatureat reflux for 1 hour
  3. temperatureto cool
  4. customThe resulting solution was evaporated to dryness
  5. customthe residue was purified by chromatography on a Biotage silica cartridge (20 g)
  6. washeluting with a gradient of methanol in dichloromethane (1–10%)
  7. additionThe fractions containing the product
  8. customevaporated
  9. dissolutionThe residue was dissolved in ethanol (8 ml)

Sources & evidence

ORD record
ord-2d1922051fc543c592a44d88aa3c1ef6
Source dataset
uspto-grants-2007_02
Patent number
US07173135B2

Reaction notes

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