Formaldehyde → N6-(1-Methyl-4-piperidylmethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide

HRID 1010399ノート

反応式

HRID 1010399 の反応式
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:10]=[C:11]([CH:42]=[CH:43][C:44]=1[NH:45][C:46]([NH:48][CH:49]1[CH2:51][CH2:50]1)=[O:47])[O:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:40][CH3:41])=[C:20]([C:23]([NH:25][CH2:26][CH:27]3[CH2:32][CH2:31][N:30]([C:33](OC(C)(C)C)=O)[CH2:29][CH2:28]3)=[O:24])[CH:21]=2)[N:16]=[CH:15][CH:14]=1.C(=O)(O)[O-].[Na+].C=O.C([BH3-])#N.[Na+]>C(OCC)(=O)C.C(O)(=O)C>[CH3:33][N:30]1[CH2:29][CH2:28][CH:27]([CH2:26][NH:25][C:23]([C:20]2[CH:21]=[C:22]3[C:17](=[CH:18][C:19]=2[O:40][CH3:41])[N:16]=[CH:15][CH:14]=[C:13]3[O:12][C:11]2[CH:42]=[CH:43][C:44]([NH:45][C:46]([NH:48][CH:49]3[CH2:51][CH2:50]3)=[O:47])=[C:9]([Cl:8])[CH:10]=2)=[O:24])[CH2:32][CH2:31]1

参加物

8

反応物 5

HCID 712FormaldehydeHCID 6422Trifluoroacetic acidHCID 516892Sodium Bicarbonate2 回HCID 5003444Sodium cyanoborohydrideHCID 22936930tert-Butyl 4-((((4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolyl)carbonyl)amino)methyl)-1-piperidinecarboxylate

生成物 1

HCID 58931341N6-(1-Methyl-4-piperidylmethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide収率 58.4%

試薬・触媒・溶媒 2

HCID 176Acetic Acid溶媒HCID 8857Ethyl Acetate溶媒

実験手順

After adding trifluoroacetic acid (1 ml) to tert-butyl 4-((((4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolyl)carbonyl)amino)methyl)-1-piperidinecarboxylate (249 mg, 0.40 mmol) at room temperature, the mixture was stirred for 2 hours. The reaction solution was poured into saturated aqueous sodium bicarbonate for neutralization and extracted 3 times with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate. After distilling off the solvent, the residue was dissolved in tetrahydrofuran (5 ml)—methanol (5 ml), and then 37% aqueous formaldehyde (0.5 ml), acetic acid (0.05 ml) and sodium cyanoborohydride (50 mg, 0.8 mmol) were added in that order at room temperature and the mixture was stirred for 1 hour. The reaction solution was distributed between ethyl acetate and saturated aqueous sodium bicarbonate, and the organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine and dried over anhydrous sodium sulfate. After distilling off the solvent, ethyl acetate was used for crystallization and the crystals were filtered out and blow-dried to obtain the title compound (125.6 mg, 0.233 mmol, 58.4%) as white crystals.

後処理

  1. extractionextracted 3 times with ethyl acetate
  2. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  3. distillationAfter distilling off the solvent
  4. dissolutionthe residue was dissolved in tetrahydrofuran (5 ml)—methanol (5 ml)
  5. stirringthe mixture was stirred for 1 hour
  6. washthe organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. distillationAfter distilling off the solvent, ethyl acetate
  9. customwas used for crystallization
  10. filtrationthe crystals were filtered out and
  11. customblow-dried

出典と根拠

ORDレコード
ord-af54c978225b455785d4c8f7db41b619
出典データセット
uspto-grants-2011_07
特許番号
US07973160B2

反応ノート

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