Triethylamine → 1-(2-(4-((3,4-dihydro-2H-pyrano(2,3-c)pyridin-6-ylmethyl)amino)piperidin-1-yl)ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one hydrochloride

HRID 656873Notes

Reaction equation

HRID 656873 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]([F:22])[CH:20]=3)[CH:15]=[CH:14][C:13]2=[O:23])[CH2:6][CH2:5]1.C([N:26]([CH2:29][CH3:30])[CH2:27][CH3:28])C.N1[C:36]2[O:37]CCO[C:35]=2[CH:34]=[C:33]([CH:41]=O)N=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl.CO>[ClH:1].[O:37]1[C:30]2=[CH:29][N:26]=[C:27]([CH2:28][NH:3][CH:4]3[CH2:5][CH2:6][N:7]([CH2:10][CH2:11][N:12]4[C:21]5[C:16](=[N:17][CH:18]=[C:19]([F:22])[CH:20]=5)[CH:15]=[CH:14][C:13]4=[O:23])[CH2:8][CH2:9]3)[CH:41]=[C:33]2[CH2:34][CH2:35][CH2:36]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 248916966,7-Dihydro-[1,4]dioxino[2,3-c]pyridazine-3-carbaldehydeHCID 674992211-[2-(4-Amino-1-piperidinyl)ethyl]-7-fluoro-1,5-naphthyridin-2(1H)-one Dihydrochloride

Product 1

HCID 689273251-(2-(4-((3,4-dihydro-2H-pyrano(2,3-c)pyridin-6-ylmethyl)amino)piperidin-1-yl)ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one hydrochlorideYield 30.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

A mixture of 1-[2-(4-amino-1-piperidinyl)ethyl]-7-fluoro-1,5-naphthyridin-2(1H)-one dihydrochloride (127 mg, 0.350 mmol) in chloroform (5 ml) and MeOH (0.1 ml) was treated with triethylamine (154 μl, 1.018 mmol) and stirred for 0.25 h before addition of 6,7-dihydro[1,4]dioxino[2,3-c]pyridazine-3-carbaldehyde (53 mg, 0.318 mmol). The reaction was stirred for 0.5 h before addition of NaBH(OAc)3 (202 mg, 0.954 mmol). The reaction was stirred for 0.5 h before addition of sat. aq NaHCO3 (50 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 (46 mg, 30%).

Workup

  1. extractionThe reaction was then extracted with 20% MeOH in DCM (3×200 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-26a379de25ef466a94a4d29fd503b074
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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