Triethylamine → N-(1-azabicyclo[3.3.1]non-5-ylmethyl)-1H-indole-3-carboxamide

HRID 5380

반응식

HRID 5380 반응식
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([OH:12])=O)=[CH:2]1.S(Cl)(Cl)=O.[N:17]12[CH2:25][C:21]([CH2:26][NH2:27])([CH2:22][CH2:23][CH2:24]1)[CH2:20][CH2:19][CH2:18]2.C(N(CC)CC)C.C[O-].[Na+].CO>O1CCCC1>[N:17]12[CH2:25][C:21]([CH2:26][NH:27][C:10]([C:3]3[C:4]4[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=4)[NH:1][CH:2]=3)=[O:12])([CH2:22][CH2:23][CH2:24]1)[CH2:20][CH2:19][CH2:18]2

참가 물질

7

반응물 5

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 69867Indole-3-Carboxylic AcidHCID 19795986{1-Azabicyclo[3.3.1]nonan-5-yl}methanamineHCID 23694274Sodium methanolate methanol

생성물 1

HCID 9948164N-(1-azabicyclo[3.3.1]non-5-ylmethyl)-1H-indole-3-carboxamide수율 57.2%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

반응 조건

온도
55 °C

실험 절차

A cooled (0° C.) suspension/solution of indole-3-carboxylic acid (0.92 g, 5.7 mmol) in anhydrous tetrahydrofuran (10 mL) was treated dropwise with thionyl chloride (0.72 g, 6.0 mmol), and the solution was refluxed for one hour and concentrated in vacuo. A cooled (0° C.) solution of 1-azabicyclo[3.3.1]nonane-5-methanamine (0.96 g, 6.2 mmol) and triethylamine (1.22 g, 12 mmol) in anhydrous tetrahydrofuran (5 mL) was treated with a solution of the above prepared acid chloride in anhydrous tetrahydrofuran (10 mL), and the mixture was stirred at room temperature for 15 hours, at 55° C. for one hour, and cooled (0° C.). Sodium methoxide/methanol (25%, 2.6 g, 12 mmol) was added, and the solution was stirred for one hour and passed through a column of alumina (eluted with 1:1 methanol/tetrahydrofuran). The filtrate was concentrated in vacuo and taken up in 2-propanol and filtered. Ether was added dropwise to the filtrate until no more precipitation was observed, and the suspension was cooled (0° C.), filtered, and the solid was collected and dried in vacuo to afford (after a second crop) 0.97 g (57%) of the title compound as a colorless solid; mp 139.0°-141.5° C.

후처리

  1. temperaturethe solution was refluxed for one hour
  2. concentrationconcentrated in vacuo
  3. additionwas treated with a solution of the
  4. temperaturecooled (0° C.)
  5. stirringthe solution was stirred for one hour
  6. concentrationThe filtrate was concentrated in vacuo
  7. filtrationfiltered
  8. additionEther was added dropwise to the filtrate until no more precipitation
  9. temperaturethe suspension was cooled (0° C.)
  10. filtrationfiltered
  11. customthe solid was collected
  12. customdried in vacuo

출처 및 근거

ORD 기록
ord-29b0a5406f954cd686619309354da83b
출처 데이터셋
uspto-grants-1993_09
특허 번호
US05244907

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