Triethylamine → 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

HRID 656897Notes

Reaction equation

HRID 656897 reaction equation
[ClH:1].Cl.[NH2:3][CH:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][N:12]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([O:22][CH3:23])[CH:20]=3)[CH:15]=[CH:14][C:13]2=[O:24])[CH2:6][CH2:5]1.C(N(CC)CC)C.[N:32]1[C:37]2[O:38][CH2:39][CH2:40][O:41][C:36]=2[CH:35]=[C:34]([CH:42]=O)[N:33]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl.CO>[ClH:1].[N:32]1[C:37]2[O:38][CH2:39][CH2:40][O:41][C:36]=2[CH:35]=[C:34]([CH2:42][NH:3][CH:4]2[CH2:5][CH2:6][N:7]([CH2:10][CH2:11][N:12]3[C:21]4[C:16](=[N:17][CH:18]=[C:19]([O:22][CH3:23])[CH:20]=4)[CH:15]=[CH:14][C:13]3=[O:24])[CH2:8][CH2:9]2)[N:33]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride3×HCID 248916966,7-Dihydro-[1,4]dioxino[2,3-c]pyridazine-3-carbaldehydeHCID 674973941-[2-(4-Amino-1-piperidinyl)ethyl]-7-(methyloxy)-1,5-naphthyridin-2(1H)-one dihydrochloride

Product 1

HCID 689925201-(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 HydrochlorideYield 242.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

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%).

Workup

  1. additionwas added
  2. extractionThe reaction was then extracted with 20% MeOH in DCM (3×200 ml)
  3. customThe combined organic phases were dried
  4. customevaporated
  5. customthe crude residue purified by chromatography on silica gel using a 0-20% MeOH/DCM gradient

Sources & evidence

ORD record
ord-4ac996d14a3e44fda9e36645379b5be8
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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