N-methyl-2-pyrrolidone → 11-[4-(aminomethyl)-4-methylpiperidin-1-yl]-2,3-dihydro-1H-cyclopenta[4,5]pyrido[1,2-a]benzimidazole-4-carboxamide dihydrochloride

HRID 70797ノート

反応式

HRID 70797 の反応式
C(OC(=O)[NH:7][CH2:8][C:9]1([CH3:15])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)(C)(C)C.CCN(C(C)C)C(C)C.CN1C(=O)CCC1.[Cl:33][C:34]1[N:42]2[C:38](=[N:39][C:40]3[CH:46]=[CH:45][CH:44]=[CH:43][C:41]=32)[C:37]([C:47]([NH2:49])=[O:48])=[C:36]2[CH2:50][CH2:51][CH2:52][C:35]=12>O>[ClH:33].[ClH:33].[NH2:7][CH2:8][C:9]1([CH3:15])[CH2:10][CH2:11][N:12]([C:34]2[N:42]3[C:38](=[N:39][C:40]4[CH:46]=[CH:45][CH:44]=[CH:43][C:41]=43)[C:37]([C:47]([NH2:49])=[O:48])=[C:36]3[CH2:50][CH2:51][CH2:52][C:35]=23)[CH2:13][CH2:14]1

参加物

6

反応物 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 70650847tert-butyl N-((4-methylpiperidin-4-yl)methyl)carbamateHCID 86677058HCID 86677058、化合物

生成物 1

HCID 8667705711-[4-(aminomethyl)-4-methylpiperidin-1-yl]-2,3-dihydro-1H-cyclopenta[4,5]pyrido[1,2-a]benzimidazole-4-carboxamide dihydrochloride収率 78.5%

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

Tert-butyl[(4-methylpiperidin-4-yl)methyl]carbamate (343 mg), and DIPEA (348 μl) were added to an NMP (3 ml) solution of 11-chloro-2,3-dihydro-1H-cyclopenta[4,5]pyrido[1,2-a]benzimidazole-4-carboxamide (286 mg), and heating and stirring were performed at 200° C. for 60 minutes under microwave irradiation. After adding water to the reaction liquid, the resulting precipitate was collected by filtration and dried under reduced pressure. The resulting solid was suspended in chloroform, TFA was then added thereto and stirring was performed at room temperature for 1 hour. The reaction liquid was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (MeOH/chloroform). The resulting crude purified matter was dissolved in chloroform, a 4 M hydrochloric acid-EtOAc solution was then added thereto and stirring was performed at room temperature for 1 hour. The solvent was concentrated under reduced pressure and the residue was solidified using EtOH/Et2O to obtain 11-[4-(aminomethyl)-4-methylpiperidin-1-yl]-2,3-dihydro-1H-cyclopenta[4,5]pyrido[1,2-a]benzimidazole-4-carboxamide dihydrochloride (177 mg).

後処理

  1. temperatureheating
  2. customwere performed at 200° C. for 60 minutes under microwave irradiation
  3. customto the reaction liquid
  4. filtrationthe resulting precipitate was collected by filtration
  5. customdried under reduced pressure
  6. additionTFA was then added
  7. stirringstirring
  8. customThe reaction liquid
  9. concentrationwas concentrated under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (MeOH/chloroform)
  11. customThe resulting crude purified matter
  12. dissolutionwas dissolved in chloroform
  13. additiona 4 M hydrochloric acid-EtOAc solution was then added
  14. stirringstirring
  15. waitwas performed at room temperature for 1 hour
  16. concentrationThe solvent was concentrated under reduced pressure

出典と根拠

ORDレコード
ord-3792cd1e45f0486686d758298d99144c
出典データセット
uspto-grants-2014_09
特許番号
US08822688B2

反応ノート

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