Réaction #744079

Équation de réaction

1-[2-(4-amino-1-piperidinyl)ethyl]-7-(methyloxy)-1,5-naphthyridin-2(1H)-one dihydrochloride

NaBH(OAc)3

6,7-dihydro[1,4]dioxino[2,3-c]pyridazine-3-carbaldehyde

NaBH(OAc)3

NaBH(OAc)3

NaHCO3

triethylamine

→

title compound

1-(2-{4-[(6,7-dihydro[1,4]dioxino[2,3-c]pyridazin-3-ylmethyl)amino]-1-piperidinyl}ethyl)-7-(methyloxy)-1,5-naphthyridin-2(1H)-one Hydrochloride

Solvants

chloroform

MeOH

Conditions de réaction

Traitement

1. 1
   workup.ADDITIONwas added
2. 2
   ExtractionThe reaction was then extracted with 20% MeOH in DCM (3×200 ml)
3. 3
   AutreThe combined organic phases were dried
4. 4
   Autreevaporated
5. 5
   Autrethe crude residue purified by chromatography on silica gel using a 0-20% MeOH/DCM gradient

Mode opératoire

A mixture of 1-[2-(4-amino-1-piperidinyl)ethyl]-7-(methyloxy)-1,5-naphthyridin-2(1H)-one dihydrochloride (145 mg, 0.399 mmol) in chloroform (20 ml) and MeOH (2 ml) was treated with triethylamine (0.62 ml, 4.49 mmol) and stirred for 0.25 h before addition of 6,7-dihydro[1,4]dioxino[2,3-c]pyridazine-3-carbaldehyde (226 mg, 1.360 mmol). The reaction was stirred for 0.5 h before addition of NaBH(OAc)3 (577 mg, 2.72 mmol). After 1 h of stirring at rt more NaBH(OAc)3 (577 mg, 2.72 mmol) was added. After a further 1 h still more NaBH(OAc)3 (577 mg, 2.72 mmol) was added. The reaction was then stirred for a further 0.5 h before addition of sat. aq NaHCO3 (20 ml). The reaction was then extracted with 20% MeOH in DCM (3×200 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 (473 mg, 70%).

Source