Formaldehyde → (4-Benzotriazol-1-yl-piperidin-1-yl)-(7-chloro-2-methyl-1,2,3,4-tetrahydro-pyrazino[1,2-a]indol-10-yl)-methanone

HRID 1097847Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1097847
Cl.[N:2]1([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([C:19]3[C:27]4[C:22](=[CH:23][C:24]([Cl:28])=[CH:25][CH:26]=4)[N:21]([CH2:29][CH2:30][NH:31][CH3:32])[CH:20]=3)=[O:18])[CH2:13][CH2:12]2)[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[N:3]1.[CH2:33](N(CC)CC)C.C=O.[C:42]([BH3-])#N.[Na+]>CO>[N:2]1([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([C:19]3[C:27]4[C:22](=[CH:23][C:24]([Cl:28])=[CH:25][CH:26]=4)[N:21]([CH2:29][CH2:30][N:31]([CH3:33])[CH3:32])[CH:20]=3)=[O:18])[CH2:13][CH2:12]2)[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[N:3]1.[N:2]1([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([C:19]3[C:27]4[CH:26]=[CH:25][C:24]([Cl:28])=[CH:23][C:22]=4[N:21]4[CH2:29][CH2:30][N:31]([CH3:42])[CH2:32][C:20]=34)=[O:18])[CH2:13][CH2:12]2)[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[N:3]1

Komponenten

7

Edukt 4

HCID 712FormaldehydeHCID 8471TriethylamineHCID 5003444Sodium cyanoborohydrideHCID 25001181(4-Benzotriazol-1-yl-piperidin-1-yl)-[6-chloro-1-(2-methylamino-ethyl)-1H-indol-3-yl]-methanone hydrochloride

Produkt 2

HCID 25001183(4-benzotriazol-1-yl-piperidin-1-yl)-[6-chloro-1-(2-dimethylamino-ethyl)-1H-indol-3-yl]-methanoneAusbeute 22 %HCID 25001184(4-Benzotriazol-1-yl-piperidin-1-yl)-(7-chloro-2-methyl-1,2,3,4-tetrahydro-pyrazino[1,2-a]indol-10-yl)-methanoneAusbeute 60 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A mixture of 0.20 g (0.41 mmol) (4-benzotriazol-1-yl-piperidin-1-yl)-[6-chloro-1-(2-methylamino-ethyl)-1H-indol-3-yl]-methanone hydrochloride, 0.057 ml (0.41 mmol) triethylamine and 0.10 g (3.3 mmol) paraformaldehyde in 4 ml methanol was heated at reflux for 7 h. After cooling to 0° C. 0. were added 052 g (0.82 mmol) sodium cyanoborohydride. The cooling bath was removed and the reaction mixture was stirred at room temperature for 16 h. Quenching with 1 M aqueous sodium hydroxide solution was followed by extraction with two portions of ethyl acetate. The combined organic extracts were dried over sodium sulfate and concentrated in vacuo. Flash chromatography gave 0.040 g (22%) (4-benzotriazol-1-yl-piperidin-1-yl)-[6-chloro-1-(2-dimethylamino-ethyl)-1H-indol-3-yl]-methanone as a white solid (ES-MS m/e (%): 451 (M+H+, 100)) and 0.11 g (60%) (4-benzotriazol-1-yl-piperidin-1-yl)-(7-chloro-2-methyl-1,2,3,4-tetrahydro-pyrazino[1,2-a]indol-10-yl)-methanone as a white solid (ES-MS m/e (%): 449 (M+H+, 100)).

Aufarbeitung

  1. temperaturewas heated
  2. temperatureat reflux for 7 h
  3. customThe cooling bath was removed
  4. customQuenching with 1 M aqueous sodium hydroxide solution
  5. extractionwas followed by extraction with two portions of ethyl acetate
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-2b073df6e4524f10bcda1265b75182b1
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08143281B2

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