Potassium Iodide → ethyl (10R,15S)-3-oxo-1,4,12-triazatetracyclo[7.6.1.05,16.010,15]hexadeca-5,7,9(16)-triene-12-carboxylate

HRID 629315ノート

反応式

HRID 629315 の反応式
Br[C:2]1[C:10]2[NH:9][C@H:8]3[CH2:11][CH2:12][N:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:14][C@H:7]3[C:6]=2[CH:5]=[CH:4][CH:3]=1.Cl[CH2:21][C:22]([NH2:24])=[O:23].[I-].[K+].C(N(C(C)C)CC)(C)C.CNC(=O)CCl.C(=O)([O-])[O-].[K+].[K+].CNCCNC>[Cu](I)I.O1CCOCC1>[O:23]=[C:22]1[CH2:21][N:9]2[C@H:8]3[CH2:11][CH2:12][N:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:14][C@H:7]3[C:6]3[C:10]2=[C:2]([CH:3]=[CH:4][CH:5]=3)[NH:24]1

参加物

10

反応物 7

HCID 4875Potassium IodideHCID 6580ChloroacetamideHCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 667732-chloro-N-methylacetamideHCID 81531Diisopropylethylamine2 回HCID 59317960ethyl (4aS,9bR)-6-bromo-1H,2H,3H,4H,4aH,5H,9bH-pyrido(4,3-b)indole-2-carboxylate

生成物 1

HCID 20578971ethyl (10R,15S)-3-oxo-1,4,12-triazatetracyclo[7.6.1.05,16.010,15]hexadeca-5,7,9(16)-triene-12-carboxylate

試薬・触媒・溶媒 2

HCID 83717Copper iodide触媒HCID 312751,4-Dioxane溶媒2 回

反応条件

温度
103 °C

実験手順

Alternative to Example 5 above, (6bR,10aS)-ethyl 3,6b,9,10,10a-hexahydro-3-methyl-2-oxo-1H-pyrido[3′,4′:4,5]-pyrrolo[1,2,3-de]quinoxaline-8-carboxylate may also be made in a one pot method starting from Compound of Formula 1D. A 2 liter 4 neck round bottom flask is equipped with a mechanical stirrer, reflux condenser, N2 inlet, teflon covered K-type temperature probe with a controller, and a heating mantle. To the flask is charged (4aS,9bR)-ethyl 6-bromo-3,4,4a,5-tetrahydro-1H-pyrido[4,3-b]indole-2(9bH)-carboxylate (250 g, 769 mmol), chloroacetamide (124 g, 1153 mmol, 1.5 equiv), potassium iodide (191.5 g, 1160 mmol, 1.5 equiv), diisopropyl ethylamine (266 mL, 1531 mmol, 2.0 equiv), and dioxane (625 mL). The reaction is heated to reflux temperature of about 103° C. until less than 3% of the starting substrate is observed by HPLC (about 48 hours). Additional charge of N-methyl chloroacetamide and diisopropyl ethylamine maybe necessary. The reaction is then cooled to ca. 80° C., and at this temperature copper iodide (29.2 g, 153.8 mmol, 0.2 equiv), potassium carbonate (232.5 g, 1682 mmol, 2.2 equiv), dimethylethylene diamine (49.6 mL, 461 mmol, 0.6 equiv), and additional dioxane (375 mL) is added. The reaction is then re-heated to reflux and is monitored by HPLC. Reflux occurs at ca. 103° C. The reaction is monitored by HPLC.

後処理

  1. temperaturereflux condenser, N2 inlet
  2. temperatureThe reaction is heated
  3. customis observed by HPLC (about 48 hours)
  4. temperatureThe reaction is then cooled to ca. 80° C.
  5. temperatureThe reaction is then re-heated
  6. temperatureto reflux
  7. temperatureReflux
  8. customoccurs at ca. 103° C

出典と根拠

ORDレコード
ord-ed318e14b0fc47269d731443796a3e65
出典データセット
uspto-grants-2016_04
特許番号
US09315504B2

反応ノート

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