4-Pyridinecarboxylic acid, 1-oxide → 1-(8-CHLORO-5,11-DIHYDRO[1]BENZOTHIEPINO[4,3-b]PYRIDIN-11-YL)-4-(4-PYRIDINYLCARBONYL)PIPERAZINE N4-OXIDE

HRID 1647255Notes

Reaction equation

HRID 1647255 reaction equation
[Cl:1][C:2]1[CH:22]=[CH:21][C:5]2[CH:6]([N:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[C:7]3[C:12]([CH2:13][S:14][C:4]=2[CH:3]=1)=[CH:11][CH:10]=[CH:9][N:8]=3.[C:23](O)(=[O:31])[C:24]1[CH:29]=[CH:28][N+:27]([O-])=[CH:26][CH:25]=1.O.[OH:34]N1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl>[Cl:1][C:2]1[CH:22]=[CH:21][C:5]2[CH:6]([N:15]3[CH2:16][CH2:17][N+:18]([O-:34])([C:23]([C:24]4[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=4)=[O:31])[CH2:19][CH2:20]3)[C:7]3[C:12]([CH2:13][S:14][C:4]=2[CH:3]=1)=[CH:11][CH:10]=[CH:9][N:8]=3

Participants

6

Reactant 4

HCID 261304-Pyridinecarboxylic acid, 1-oxideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 157805018-Chloro-5,11-dihydro-11-(1-piperazinyl)[1]benzothiepino[4,3-b]pyridine

Product 1

HCID 867487601-(8-CHLORO-5,11-DIHYDRO[1]BENZOTHIEPINO[4,3-b]PYRIDIN-11-YL)-4-(4-PYRIDINYLCARBONYL)PIPERAZINE N4-OXIDE

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of 8-chloro-5,11-dihydro-11-(1-piperazinyl)[1]benzothiepino[4,3-b]pyridine (251 mg, 0.762 mmol) and isonicotinic acid N-oxide (128 mg, 0.918 mmol) in dry dichloromethane (20 mL), add 1-hydroxybenzotriazole hydrate (123 mg, 0.909 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (175 mg, 0.912 mmol). Stir the resultant mixture at room temperature for 3 hours. Wash the reaction mixture successively with 2.5M aqueous sodium hydroxide (5 mL), water (4×10 mL), and brine (15 mL). Dry the washed solution over anhydrous magnesium sulfate, filter out the drying agent, and remove solvent from the filtrate under reduced pressure. Flash chromatograph the residue on silica gel, eluting with methanol/dichloromethane (1:9) to obtain the title compound as a 3/4 hydrate (240 mg, 70% yield): mp 162°-165.5° C. (melts to a viscous gum); MS (FAB) m/z 450 [M+ +1].

Workup

  1. washWash the reaction mixture successively with 2.5M aqueous sodium hydroxide (5 mL), water (4×10 mL), and brine (15 mL)
  2. dry with materialDry the washed solution over anhydrous magnesium sulfate
  3. filtrationfilter out the drying agent
  4. customremove solvent from the filtrate under reduced pressure
  5. washFlash chromatograph the residue on silica gel, eluting with methanol/dichloromethane (1:9)

Sources & evidence

ORD record
ord-1bbe4de8b91442fc8c9b2c079b031bd0
Source dataset
uspto-grants-1995_07
Patent number
US05430032

Reaction notes

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