Sodium Bicarbonate → 1-{2-[4-({[5-bromo-6-(hydroxymethyl)-3-pyridinyl]methyl}amino)-1-piperidinyl]ethyl}-7-fluoro-1,5-naphthyridin-2(1H)-one

HRID 1881737Notes

Reaction equation

HRID 1881737 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([F:20])[CH:18]=3)[CH:13]=[CH:12][C:11]2=[O:21])[CH2:4][CH2:3]1.[Br:22][C:23]1[CH:24]=[C:25]([CH:31]=O)[CH:26]=[N:27][C:28]=1[CH2:29][OH:30].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[Br:22][C:23]1[CH:24]=[C:25]([CH2:31][NH:1][CH:2]2[CH2:3][CH2:4][N:5]([CH2:8][CH2:9][N:10]3[C:19]4[C:14](=[N:15][CH:16]=[C:17]([F:20])[CH:18]=4)[CH:13]=[CH:12][C:11]3=[O:21])[CH2:6][CH2:7]2)[CH:26]=[N:27][C:28]=1[CH2:29][OH:30]

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 578151991-[2-(4-amino-1-piperidinyl)ethyl]-7-fluoro-1,5-naphthyridin-2(1H)-one2×HCID 866648855-Bromo-6-(hydroxymethyl)nicotinaldehyde2×

Product 1

HCID 468464911-{2-[4-({[5-bromo-6-(hydroxymethyl)-3-pyridinyl]methyl}amino)-1-piperidinyl]ethyl}-7-fluoro-1,5-naphthyridin-2(1H)-oneYield 25.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 1-[2-(4-amino-1-piperidinyl)ethyl]-7-fluoro-1,5-naphthyridin-2(1H)-one (Intermediate 21: 50.9 mg, 0.175 mmol) and 5-bromo-6-(hydroxymethyl)-3-pyridinecarbaldehyde (Intermediate 40: 37.9 mg, 0.175 mmol) in DCE (3 ml) was stirred under N2 at room temperature overnight. Then, sodium triacetoxyborohydride (112 mg, 0.526 mmol) was added and the mixture was stirred for 8 h at RT overnight. Saturated NaHCO3 was added and the aqueous phase was extracted twice with DCM. The combined organic phases were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by Flash-Master chromatography on a 2 g silica gel cartridge using DCM/MeOH 9/1 as eluent to give 1-{2-[4-({[5-bromo-6-(hydroxymethyl)-3-pyridinyl]methyl}amino)-1-piperidinyl]ethyl}-7-fluoro-1,5-naphthyridin-2(1H)-one (21.5 mg, 25%) as a white solid.

Workup

  1. stirringthe mixture was stirred for 8 h at RT overnight
  2. extractionthe aqueous phase was extracted twice with DCM
  3. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by Flash-Master chromatography on a 2 g silica gel cartridge

Sources & evidence

ORD record
ord-686c1f517a1f4f6ea48cd56a47260eed
Source dataset
uspto-grants-2012_11
Patent number
US08318940B2

Reaction notes

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