Hydrochloric Acid → 6-chloro-4-(2-{4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}ethyl)-1,2,4-benzotriazin-3(4H)-one 1-oxide Hydrochloride

HRID 657022Notes

Reaction equation

HRID 657022 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N+:10]([O-:11])=[N:9][C:8](=[O:12])[N:7]([CH2:13][CH2:14][N:15]3[CH2:20][CH2:19][CH:18]([N:21]([CH2:29][C:30]4[N:35]=[CH:34][C:33]5[O:36][CH2:37][CH2:38][O:39][C:32]=5[CH:31]=4)C(=O)OC(C)(C)C)[CH2:17][CH2:16]3)[C:6]=2[CH:40]=1.Cl.C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl.CO.O1CCOCC1>[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N+:10]([O-:11])=[N:9][C:8](=[O:12])[N:7]([CH2:13][CH2:14][N:15]3[CH2:16][CH2:17][CH:18]([NH:21][CH2:29][C:30]4[N:35]=[CH:34][C:33]5[O:36][CH2:37][CH2:38][O:39][C:32]=5[CH:31]=4)[CH2:19][CH2:20]3)[C:6]=2[CH:40]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 866353361,1-Dimethylethyl {1-[2-(6-chloro-1-oxido-3-oxo-1,2,4-benzotriazin-4(3H)-yl)ethyl]-4-piperidinyl}(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)carbamate

Product 1

HCID 866353376-chloro-4-(2-{4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}ethyl)-1,2,4-benzotriazin-3(4H)-one 1-oxide HydrochlorideYield 167.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 1,1-dimethylethyl {1-[2-(6-chloro-1-oxido-3-oxo-1,2,4-benzotriazin-4(3H)-yl)ethyl]-4-piperidinyl}(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)carbamate (81 mg, 0.141 mmol) in chloroform (1 ml) and MeOH (1 ml) was added 4M HCl in 1,4-dioxane (1 ml) and the reaction was stirred at rt for 0.5 h before evaporation, treatment with sat. aq NaHCO3 (50 ml). The reaction was then extracted with 20% MeOH in DCM (3×100 ml). The combined organic phases were dried, evaporated and the crude residue purified by chromatography on silica gel using a 0-20% MeOH/DCM gradient to provide the free base of the title compound as a yellow foam (60 mg, 90%).

Workup

  1. extractionThe reaction was then extracted with 20% MeOH in DCM (3×100 ml)
  2. customThe combined organic phases were dried
  3. customevaporated
  4. customthe crude residue purified by chromatography on silica gel using a 0-20% MeOH/DCM gradient

Sources & evidence

ORD record
ord-0774355e45e446838a113ab157bf5376
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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