Water → 1-(2-(4-((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)piperidin-1-yl)ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one

HRID 1804731Notes

Reaction equation

HRID 1804731 reaction equation
[O:1]1[C:10]2[CH:9]=[C:8]([CH2:11][N:12]([CH:20]3[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][N:28]4[C:37]5[C:32](=[N:33][CH:34]=[C:35]([F:38])[CH:36]=5)[CH:31]=[CH:30][C:29]4=[O:39])[CH2:22][CH2:21]3)C(=O)OC(C)(C)C)[N:7]=[CH:6][C:5]=2[O:4][CH2:3][CH2:2]1.O.C(OCC)(=O)C.[OH-].[Na+]>FC(F)(F)C(O)=O>[O:1]1[C:10]2[CH:9]=[C:8]([CH2:11][NH:12][CH:20]3[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][N:28]4[C:37]5[C:32](=[N:33][CH:34]=[C:35]([F:38])[CH:36]=5)[CH:31]=[CH:30][C:29]4=[O:39])[CH2:22][CH2:21]3)[N:7]=[CH:6][C:5]=2[O:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 57815262tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(1-(2-(7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate

Product 1

HCID 248667011-(2-(4-((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)piperidin-1-yl)ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-oneYield 24.8%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 3.03 g of tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(1-(2-(7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate in 45 mL of trifluoroacetic acid was stirred for 1 hour and 30 minutes at room temperature. The reaction mixture was cooled with ice, added with 30 mL of water and 30 mL of ethyl acetate, and adjusted to pH 10 with a 2 mol/L sodium hydroxide aqueous solution. The organic layer was separated and the aqueous layer was extracted 7 times with ethyl acetate. The organic layer was combined therewith and the solvent was concentrated to 10 mL under reduced pressure, whereby insoluble matter was filtered out. The solvent was evaporated under reduced pressure, and the obtained residue was purified by basic silica gel column chromatography [eluate; chloroform:methanol=92:8], recrystallized from 3 mL of ethyl acetate to give 0.611 g of 1-(2-(4-((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)piperidin-1-yl)ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one (anhydrate) as a light yellow solid.

Workup

  1. temperatureThe reaction mixture was cooled with ice
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted 7 times with ethyl acetate
  4. concentrationthe solvent was concentrated to 10 mL under reduced pressure, whereby insoluble matter
  5. filtrationwas filtered out
  6. customThe solvent was evaporated under reduced pressure
  7. customthe obtained residue was purified by basic silica gel column chromatography [eluate; chloroform:methanol=92:8]
  8. customrecrystallized from 3 mL of ethyl acetate

Sources & evidence

ORD record
ord-1cbfd588c95948fa8f599b7a952f8817
Source dataset
uspto-grants-2013_01
Patent number
US08354426B2

Reaction notes

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