1,1'-Carbonyldiimidazole → N-(1-Azabicyclo[3.3.1]non-5-ylmethyl)-5-chloro-2-methoxy-4-(methylamino)benzamide

HRID 5378ノート

反応式

HRID 5378 の反応式
[Cl:1][C:2]1[C:3]([NH:13][CH3:14])=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[N:27]12[CH2:35][C:31]([CH2:36][NH2:37])([CH2:32][CH2:33][CH2:34]1)[CH2:30][CH2:29][CH2:28]2>O1CCCC1.CO>[N:27]12[CH2:35][C:31]([CH2:36][NH:37][C:7](=[O:9])[C:6]3[CH:10]=[C:2]([Cl:1])[C:3]([NH:13][CH3:14])=[CH:4][C:5]=3[O:11][CH3:12])([CH2:32][CH2:33][CH2:34]1)[CH2:30][CH2:29][CH2:28]2

参加物

6

反応物 3

HCID 682631,1'-CarbonyldiimidazoleHCID 116942165-Chloro-2-methoxy-4-(methylamino)benzoic acidHCID 19795986{1-Azabicyclo[3.3.1]nonan-5-yl}methanamine

生成物 1

HCID 19795975N-(1-Azabicyclo[3.3.1]non-5-ylmethyl)-5-chloro-2-methoxy-4-(methylamino)benzamide収率 73.3%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

A solution of 5-chloro-2-methoxy-4-(methylamino)benzoic acid (1.08 g, 5 mmol) in anhydrous tetrahydrofuran (7 mL) under nitrogen was treated with 1,1'-carbonyldiimidazole (0.90 g, 5.5 mmol), stirred one hour, degassed under a stream of nitrogen for 10 minutes, and cooled (0° C.). A solution of 1-azabicyclo[3.3.1]nonane-5-methanamine (0.82 g, 5.3 mmol) in tetrahydrofuran (3 mL) was added dropwise, and stirring was continued at room temperature for 18 hours. The suspension was diluted with enough methanol to dissolve the solid, then the solution was filtered through a short column of alumina (eluted with 20% methanol/tetrahydrofuran). The filtrate was concentrated in vacuo, triturated from cold ether, and recrystallized from acetonitrile to afford 1.29 g (73%) of colorless crystals; mp 188°-190° C. (second phase), first phase melting point 175° C.

後処理

  1. customdegassed under a stream of nitrogen for 10 minutes
  2. stirringstirring
  3. waitwas continued at room temperature for 18 hours
  4. dissolutionto dissolve the solid
  5. filtrationthe solution was filtered through a short column of alumina (eluted with 20% methanol/tetrahydrofuran)
  6. concentrationThe filtrate was concentrated in vacuo
  7. customtriturated from cold ether
  8. customrecrystallized from acetonitrile

出典と根拠

ORDレコード
ord-2a7ae11fb7f447428407b154948c0592
出典データセット
uspto-grants-1993_09
特許番号
US05244907

反応ノート

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