1,1'-Carbonyldiimidazole → 4-Amino-5-chloro-N-(1-(3-methoxypropyl)piperidin-4-yl)-2,3-dihydrobenzofuran-7-carboxamide hydrate

HRID 1459454ノート

反応式

HRID 1459454 の反応式
[NH2:1][C:2]1[C:7]2[CH2:8][CH2:9][O:10][C:6]=2[C:5]([C:11]([OH:13])=O)=[CH:4][C:3]=1[Cl:14].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:27][O:28][CH2:29][CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][CH:35]([NH2:38])[CH2:34][CH2:33]1>O1CCCC1.C(N1C=CN=C1)(N1C=CN=C1)=O.COCCCN1CCC(N)CC1>[OH2:10].[NH2:1][C:2]1[C:7]2[CH2:8][CH2:9][O:10][C:6]=2[C:5]([C:11]([NH:38][CH:35]2[CH2:36][CH2:37][N:32]([CH2:31][CH2:30][CH2:29][O:28][CH3:27])[CH2:33][CH2:34]2)=[O:13])=[CH:4][C:3]=1[Cl:14]

参加物

7

反応物 3

HCID 682631,1'-CarbonyldiimidazoleHCID 106324014-Amino-5-chloro-2,3-dihydrobenzofuran-7-carboxylic acidHCID 120880931-(3-Methoxypropyl)-4-piperidinamine

生成物 1

HCID 183607994-Amino-5-chloro-N-(1-(3-methoxypropyl)piperidin-4-yl)-2,3-dihydrobenzofuran-7-carboxamide hydrate収率 181.1%

試薬・触媒・溶媒 3

HCID 682631,1'-Carbonyldiimidazole触媒HCID 120880931-(3-Methoxypropyl)-4-piperidinamine触媒HCID 8028Tetrahydrofuran溶媒3 回

実験手順

Reaction under N2 flow. 4-Amino-5-chloro-2,3-dihydro-7-benzofurancarboxylic acid (0.18 mol) was dissolved in tetrahydrofuran (360 ml) and this solution was stirred and cooled to ±3° C. 1,1'-Carbonylbis-1H-imidazole (0.18 mol) was added in one portion and cooling was stopped. The mixture was stirred for 75 minutes (became homogeneous after 30 minutes). A solution of 1-(3-methoxypropyl)-4-piperidinamine (0.18 mol) in tetrahydrofuran (90 ml) was added dropwise (exothermic temperature rise from 23° C. to 27° C.). The reaction mixture was stirred for 24 hours. More 1,1'-Carbonylbis-1H-imidazole (0.0125 mol) was added and the reaction mixture was stirred for 75 minutes. More 1-(3-methoxypropyl)-4-piperidinamine (0.0125 mol) was added (in 10 ml THF). The resulting reaction mixture was stirred for 3 hours at room temperature, then for 2.5 hours at reflux temperature. Then, the mixture was stirred for 13 hours, allowing it to cool to room temperature. The solvent was evaporated. The residue was stirred for 8 hours in water (360 ml) and the precipitate was filtered off, washed with water, then dried (vacuum; 30° C.), yielding 62.9 g (95%) 4-amino-5-chloro-2,3-dihydro-N-[1-(3-methoxypropyl)-4-piperidinyl]-7-benzofurancarboxamide monohydrate; mp. 90.7° C. (comp. 2).

後処理

  1. customReaction under N2 flow
  2. temperaturecooled
  3. customto ±3° C
  4. temperaturecooling
  5. stirringThe mixture was stirred for 75 minutes (became homogeneous after 30 minutes)
  6. stirringThe reaction mixture was stirred for 24 hours
  7. stirringthe reaction mixture was stirred for 75 minutes
  8. customThe resulting reaction mixture
  9. stirringwas stirred for 3 hours at room temperature
  10. temperaturefor 2.5 hours at reflux temperature
  11. stirringThen, the mixture was stirred for 13 hours
  12. customThe solvent was evaporated
  13. stirringThe residue was stirred for 8 hours in water (360 ml)
  14. filtrationthe precipitate was filtered off
  15. washwashed with water
  16. customdried (vacuum; 30° C.)

出典と根拠

ORDレコード
ord-55cddf6ea88340eb976bf9a930851a14
出典データセット
uspto-grants-1998_12
特許番号
US05854260

反応ノート

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