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

反応式

HRID 347321 の反応式
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]

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-1fe0c2e2add5479ca2262217a4ab0c73
出典データセット
uspto-grants-2007_02
特許番号
US07173136B2

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