4-Pyridinecarboxylic acid, 1-oxide → 4-(8-CHLORO-5,11-DIHYDRO[1]BENZOTHIEPINO[4,3-b]PYRIDIN-11-YLIDENE)-1-(4-PYRIDINYLCARBONYL)PIPERIDINE N1-OXIDE

HRID 1647253Notes

Reaction equation

HRID 1647253 reaction equation
[Cl:1][C:2]1[CH:22]=[CH:21][C:5]2[CH:6](N3CCNCC3)[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]([OH:32])(=O)[C:24]1[CH:29]=[CH:28][N+:27]([O-])=[CH:26][CH:25]=1.O.[OH:34][N:35]1[C:39]2C=[CH:41][CH:42]=[CH:43][C:38]=2N=N1.Cl.CN(C)CCCN=C=NCC.N1C2C=CC=CC=2N=N1.N=C=N>ClCCl>[Cl:1][C:2]1[CH:22]=[CH:21][C:5]2[C:6](=[C:43]3[CH2:38][CH2:39][N+:35]([O-:34])([C:23]([C:24]4[CH:25]=[CH:26][N:27]=[CH:28][CH:29]=4)=[O:32])[CH2:41][CH2:42]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

8

Reactant 6

HCID 261304-Pyridinecarboxylic acid, 1-oxideHCID 160435CarbodiimideHCID 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]pyridineHCID 178418385HCID 178418385, compound

Product 1

HCID 867487584-(8-CHLORO-5,11-DIHYDRO[1]BENZOTHIEPINO[4,3-b]PYRIDIN-11-YLIDENE)-1-(4-PYRIDINYLCARBONYL)PIPERIDINE N1-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 (1.9 g, 5.73 mmol) and isonicotinic acid N-oxide (0.95 g, 6.83 mmol) in dry dichloromethane (60 mL), add 1-hydroxybenzotriazole hydrate (0.93 g, 6.88 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.32 g, 6.89 mmol). Stir the resultant mixture at room temperature for 20 hours; then introduce additional quantities of the benzotriazole (0.19 g, 1.43 mmol) and carbodiimide (0.27 g, 1.43 mmol), and continue stirring for another 6 hours at room temperature. Wash the reaction mixture successively with 2.5M aqueous sodium hydroxide (15 mL), water (3×10 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 dichloromethane/methanol/ammonium hydroxide (95:5:0.125) to obtain the title compound as a hemihydrate (2.29 g, 88% yield): m.p. 167°-169° C. (dec); MS (FAB) m/z 453 [M+ +1].

Workup

  1. washWash the reaction mixture successively with 2.5M aqueous sodium hydroxide (15 mL), water (3×10 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 dichloromethane/methanol/ammonium hydroxide (95:5:0.125)

Sources & evidence

ORD record
ord-38160465f8104744b172029d92f6736e
Source dataset
uspto-grants-1995_07
Patent number
US05430032

Reaction notes

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