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

HRID 656900Notes

Reaction equation

HRID 656900 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.[O:32]1[C:37]2=[CH:38][N:39]=[C:40]([CH:42]=O)[CH:41]=[C:36]2[CH2:35][CH2:34][CH2:33]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl.CO>[ClH:1].[O:32]1[C:37]2=[CH:38][N:39]=[C:40]([CH2:42][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]([O:22][CH3:23])[CH:20]=5)[CH:15]=[CH:14][C:13]4=[O:24])[CH2:8][CH2:9]3)[CH:41]=[C:36]2[CH2:35][CH2:34][CH2:33]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 566403113,4-dihydro-2H-pyrano[2,3-c]pyridine-6-carbaldehydeHCID 674973941-[2-(4-Amino-1-piperidinyl)ethyl]-7-(methyloxy)-1,5-naphthyridin-2(1H)-one dihydrochloride

Product 1

HCID 688927231-(2-(4-((3,4-dihydro-2H-pyrano(2,3-c)pyridin-6-ylmethyl)amino)piperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one hydrochlorideYield 75%

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 (174 mg, 0.466 mmol) in chloroform (5 ml) and MeOH (0.1 ml) was treated with triethylamine (205 μl, 1.484 mmol) and stirred for 0.25 h before addition of 3,4-dihydro-2H-pyrano[2,3-c]pyridine-6-carbaldehyde (for a synthesis see WO2004058144, Example 126(e)) (69 mg, 0.424 mmol). The reaction was stirred for 0.5 h before addition of NaBH(OAc)3 (270 mg, 1.272 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 (157 mg, 75%).

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-edd8934813ab4b488dd6e9dcb1cba4d9
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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