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 1097847Notes

Reaction equation

HRID 1097847 reaction equation
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

Participants

7

Reactant 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

Product 2

HCID 25001183(4-benzotriazol-1-yl-piperidin-1-yl)-[6-chloro-1-(2-dimethylamino-ethyl)-1H-indol-3-yl]-methanoneYield 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)-methanoneYield 60%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

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)).

Workup

  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

Sources & evidence

ORD record
ord-2b073df6e4524f10bcda1265b75182b1
Source dataset
uspto-grants-2012_03
Patent number
US08143281B2

Reaction notes

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