Sodium Bicarbonate → 1-(2-(4-((3-oxo-3,4-dihydro-2H-pyrido(3,2-b)(1,4)oxazin-6-yl)methylamino)piperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one

HRID 385650Notes

Reaction equation

HRID 385650 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]([O:20][CH3:21])[CH:18]=3)[CH:13]=[CH:12][C:11]2=[O:22])[CH2:4][CH2:3]1.[O:23]=[C:24]1[CH2:29][O:28][C:27]2[CH:30]=[CH:31][C:32]([CH:34]=O)=[N:33][C:26]=2[NH:25]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.CO.C(O)(=O)C>[O:23]=[C:24]1[CH2:29][O:28][C:27]2[CH:30]=[CH:31][C:32]([CH2:34][NH:1][CH:2]3[CH2:3][CH2:4][N:5]([CH2:8][CH2:9][N:10]4[C:19]5[C:14](=[N:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=5)[CH:13]=[CH:12][C:11]4=[O:22])[CH2:6][CH2:7]3)=[N:33][C:26]=2[NH:25]1

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 218737373-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehydeHCID 578151881-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one

Product 1

HCID 250320771-(2-(4-((3-oxo-3,4-dihydro-2H-pyrido(3,2-b)(1,4)oxazin-6-yl)methylamino)piperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-oneYield 66.3%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

To a solution of 297 mg of 1-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one and 159 mg of 3-oxo-3,4-dihydro-2H-pyrido(3,2-b)(1,4)oxazine-6-carbaldehyde in 4 mL of chloroform and 1 mL of methanol, 0.11 mL of acetic acid was added, and the mixture was stirred at room temperature for 16 hours. To the reaction mixture, 299 mg of sodium triacetoxyborohydride was added, and the mixture was stirred for 1.5 hours. Thereto was added a saturated aqueous sodium hydrogen carbonate solution, and the organic layer was separated. The organic layer 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 silica gel column chromatography using silica gel; Silica Gel 60 made by KANTO CHEMICAL CO., INC., and an eluent of chloroform:methanol (mixing 5% of 28% ammonium water)=87:13 to obtain 275 mg of 1-(2-(4-((3-oxo-3,4-dihydro-2H-pyrido(3,2-b)(1,4)oxazin-6-yl)methylamino)piperidin-1-yl)ethyl)-7-methoxy-1,5-naphthyridin-2(1H)-one as a yellow foam.

Workup

  1. stirringthe mixture was stirred for 1.5 hours
  2. customthe organic layer was separated
  3. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe resultant residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-d20027baf8814268a0bce9d82eea32b2
Source dataset
uspto-grants-2013_02
Patent number
US08367831B2

Reaction notes

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