Sodium Bicarbonate → 1-(2-(3-(((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)methyl)pyrrolidin-1-yl)ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one

HRID 385670Notes

Reaction equation

HRID 385670 reaction equation
Cl.[O:2]1[C:11]2[CH:10]=[C:9]([CH2:12][NH:13][CH2:14][CH:15]3[CH2:19][CH2:18][NH:17][CH2:16]3)[N:8]=[CH:7][C:6]=2[O:5][CH2:4][CH2:3]1.C[O-].[Na+].CO.[F:25][C:26]1[CH:35]=[C:34]2[C:29]([CH:30]=[CH:31][C:32](=[O:39])[N:33]2[CH2:36][CH:37]=O)=[N:28][CH:27]=1.C([BH3-])#N.[Na+].C(=O)([O-])O.[Na+]>CO.C(OCC)(=O)C.C(O)(=O)C>[O:2]1[C:11]2[CH:10]=[C:9]([CH2:12][NH:13][CH2:14][CH:15]3[CH2:19][CH2:18][N:17]([CH2:37][CH2:36][N:33]4[C:34]5[C:29](=[N:28][CH:27]=[C:26]([F:25])[CH:35]=5)[CH:30]=[CH:31][C:32]4=[O:39])[CH2:16]3)[N:8]=[CH:7][C:6]=2[O:5][CH2:4][CH2:3]1

Participants

9

Reactant 5

HCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 23694274Sodium methanolate methanolHCID 578152751,5-Naphthyridine-1(2H)-acetaldehyde, 7-fluoro-2-oxo-HCID 689235601-(2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-yl)-N-(pyrrolidin-3-ylmethyl)methanamine hydrochloride

Product 1

HCID 578153361-(2-(3-(((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)methyl)pyrrolidin-1-yl)ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-oneYield 14.2%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 0.10 g of 1-(2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-yl)-N-(pyrrolidin-3-ylmethyl)methanamine hydrochloride in 5 mL of methanol, 0.17 g of a 28% sodium methoxide/methanol solution, 66 mg of (7-fluoro-2-oxo-1,5-naphthyridin-1(2H)-yl)acetaldehyde, 0.10 g of molecular sieves 3 A, 33 μL of acetic acid and 18 mg of sodium cyanoborohydride were added at room temperature, and the mixture was stirred at the same temperature for 2 hours 30 minutes. To the reaction mixture, a saturated aqueous sodium hydrogen carbonate solution and ethyl acetate were added, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, the resultant solution was washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by basic silica gel column chromatography using an eluent of chloroform:methanol=30:1 to obtain 20 mg of 1-(2-(3-(((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)methyl)pyrrolidin-1-yl)ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one as a yellow oily substance.

Workup

  1. additionwere added at room temperature
  2. customthe organic layer was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washthe resultant solution was washed with a saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe resultant residue was purified by basic silica gel column chromatography

Sources & evidence

ORD record
ord-77975aaaefa245f6a85edd9a205d3b18
Source dataset
uspto-grants-2013_02
Patent number
US08367831B2

Reaction notes

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