Hydrochloric Acid → 1-(2-{4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}ethyl)-7-(methyloxy)pyrido[2,3-b]pyrazin-2(1H)-one Hydrochloride

HRID 657000Notes

Reaction equation

HRID 657000 reaction equation
[O:1]1[C:10]2[CH:9]=[C:8]([CH2:11][N:12]([CH:20]3[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][N:28]4[C:33](=[O:34])[CH:32]=[N:31]C5C=CC(OC)=NC4=5)[CH2:22][CH2:21]3)C(=O)OC(C)(C)C)[N:7]=[CH:6][C:5]=2[O:4][CH2:3][CH2:2]1.[ClH:41].[C:42]([O-:45])(O)=O.[Na+]>C(Cl)(Cl)Cl.CO.O1CCOCC1>[ClH:41].[O:1]1[C:10]2[CH:9]=[C:8]([CH2:11][NH:12][CH:20]3[CH2:21][CH2:22][N:23]([CH2:26][CH2:27][N:28]4[C:33](=[O:34])[CH:32]=[N:31][C:6]5[N:7]=[CH:8][C:9]([O:45][CH3:42])=[CH:10][C:5]4=5)[CH2:24][CH2:25]3)[N:7]=[CH:6][C:5]=2[O:4][CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 578152431,1-Dimethylethyl (2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)(1-{2-[6-(methyloxy)-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl]ethyl}-4-piperidinyl)carbamate

Product 1

HCID 689911331-(2-{4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-1-piperidinyl}ethyl)-7-(methyloxy)pyrido[2,3-b]pyrazin-2(1H)-one HydrochlorideYield 23%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 1,1-dimethylethyl (2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)(1-{2-[6-(methyloxy)-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl]ethyl}-4-piperidinyl)carbamate (1.408 g, 2.551 mmol) in chloroform (20 ml) and MeOH (5 ml) was added 4M HCl in 1,4-dioxane (10 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 solid (266 mg, 23%).

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-d15f298dd7bd4937ab254ad34cca4da4
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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