4-Chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile → 3-Cyano-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]-4-[4-(3-methoxyprop-1-ynyl)benzofuran-7-ylamino]quinoline

HRID 347321

Reaction equation

HRID 347321 reaction equation
C[Si](C)(C)N[Si](C)(C)C.[Na].[CH3:11][O:12][CH2:13][C:14]#[C:15][C:16]1[C:21]2[CH:22]=[CH:23][O:24][C:20]=2[C:19]([NH2:25])=[CH:18][CH:17]=1.Cl[C:27]1[C:36]2[C:31](=[CH:32][C:33]([O:39][CH2:40][CH2:41][CH2:42][N:43]3[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]3)=[C:34]([O:37][CH3:38])[CH:35]=2)[N:30]=[CH:29][C:28]=1[C:50]#[N:51]>CN(C=O)C>[C:50]([C:28]1[CH:29]=[N:30][C:31]2[C:36]([C:27]=1[NH:25][C:19]1[C:20]3[O:24][CH:23]=[CH:22][C:21]=3[C:16]([C:15]#[C:14][CH2:13][O:12][CH3:11])=[CH:17][CH:18]=1)=[CH:35][C:34]([O:37][CH3:38])=[C:33]([O:39][CH2:40][CH2:41][CH2:42][N:43]1[CH2:44][CH2:45][N:46]([CH3:49])[CH2:47][CH2:48]1)[CH:32]=2)#[N:51]

Participants

5

Reactant 3

HCID 117491774-Chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrileHCID 21082722[4-(3-Methoxyprop-1-ynyl)benzofuran-7-yl]amineHCID 45051731Sodium hexamethyidisilazane

Product 1

HCID 98719693-Cyano-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]-4-[4-(3-methoxyprop-1-ynyl)benzofuran-7-ylamino]quinoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hexamethyldisilazane (1M solution in THF; 0.63 ml) was added to a mixture of [4-(3-methoxyprop-1-ynyl)benzofuran-7-yl]amine (0.06 g) and 4-chloro-3-cyano-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline (0.106 g) in DMF (5 ml) that was cooled to 0° C. The resultant mixture was stirred and allowed to warm to ambient temperature for 16 hours. The reaction mixture was reduced in vacuo and partitioned between ethylacetate and water. The organics were washed with water, saturated brine and dried with magnesium sulfate. The solvent was removed in vacuo and the residue purified by column chromatography on silica using a gradient of 0–10% methanol/dichloromethane as eluent. The product fractions were combined and reduced in vacuo and the residue dissolved in minimal dichloromethane, diluted with diethyl ether and precipitated as an HCl salt by the addition of 1.0M ethereal HCl. The resultant solid was centrifuged and washed with diethyl ether (X3) and dried to give the title compound as a yellow solid. (0.077 g); NMR Spectrum: (DMSOd6 @ 373K) 2.30 (m, 2H), 2.80 (s, 3H), 3.15–3.20 (m, 2H), 3.36–3.50 (m, 11H), 4.02 (s, 3H), 4.37 (t, 2H), 4.45 (s, 2H), 7.01 (s, 1H), 7.35 (d, 1H), 7.44 (d, 1H), 7.59 (s, 1H), 8.00 (s, 1H), 8.11 (s, 1H), 8.65 (s, 1H); Mass Spectrum: M+H+ 540.14.

Workup

  1. temperatureto warm to ambient temperature for 16 hours
  2. custompartitioned between ethylacetate and water
  3. washThe organics were washed with water, saturated brine
  4. dry with materialdried with magnesium sulfate
  5. customThe solvent was removed in vacuo
  6. customthe residue purified by column chromatography on silica using a gradient of 0–10% methanol/dichloromethane as eluent
  7. dissolutionthe residue dissolved in minimal dichloromethane
  8. additiondiluted with diethyl ether
  9. customprecipitated as an HCl salt by the addition of 1.0M ethereal HCl
  10. washwashed with diethyl ether (X3)
  11. customdried

Sources & evidence

ORD record
ord-1fe0c2e2add5479ca2262217a4ab0c73
Source dataset
uspto-grants-2007_02
Patent number
US07173136B2

Linked notes

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