Sodium Bicarbonate → 7-fluoro-1-(2-(4-((3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methylamino)piperidin-1-yl)ethyl)quinoxalin-2(1H)-one

HRID 39995

Reaction equation

HRID 39995 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](=[CH:15][CH:16]=[C:17]([F:20])[CH:18]=3)[N:13]=[CH:12][C:11]2=[O:21])[CH2:4][CH2:3]1.[O:22]=[C:23]1[CH2:28][S:27][C:26]2[CH:29]=[CH:30][C:31]([CH:33]=O)=[N:32][C:25]=2[NH:24]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(O)(=O)C.C(Cl)(Cl)Cl>[F:20][C:17]1[CH:18]=[C:19]2[C:14]([N:13]=[CH:12][C:11](=[O:21])[N:10]2[CH2:9][CH2:8][N:5]2[CH2:4][CH2:3][CH:2]([NH:1][CH2:33][C:31]3[CH:30]=[CH:29][C:26]4[S:27][CH2:28][C:23](=[O:22])[NH:24][C:25]=4[N:32]=3)[CH2:7][CH2:6]2)=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 115935913-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehydeHCID 593979071-(2-(4-aminopiperidin-1-yl)ethyl)-7-fluoroquinoxalin-2(1H)-one

Product 1

HCID 159856347-fluoro-1-(2-(4-((3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methylamino)piperidin-1-yl)ethyl)quinoxalin-2(1H)-oneYield 49.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6212ChloroformSolvent

Procedure

To 10 mL of a chloroform solution containing 183 mg of 1-(2-(4-aminopiperidin-1-yl)ethyl)-7-fluoroquinoxalin-2(1H)-one and 114 mg of 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde, 36 μL of acetic acid was added, and stirred at room temperature for 1 hour. To the reaction mixture, 228 mg of sodium triacetoxyborohydride was added, and stirred overnight. Aqueous saturated sodium hydrogen carbonate solution was added, the organic layer was separated. The organic layer was washed with aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [Silica Gel; Fuji Silysia Chemical Ltd., Chromatorex-NH, eluent; chloroform:methanol=100:1] to give 135 mg of 7-fluoro-1-(2-(4-((3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)methylamino)piperidin-1-yl)ethyl)quinoxalin-2(1H)-one as a pale yellow solid.

Workup

  1. additionwas added
  2. stirringstirred overnight
  3. customthe organic layer was separated
  4. washThe organic layer was washed with aqueous saturated sodium chloride solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was removed under reduced pressure
  7. customThe residue thus obtained
  8. customwas purified by silica gel column chromatography [Silica Gel; Fuji Silysia Chemical Ltd., Chromatorex-NH, eluent; chloroform:methanol=100:1]

Sources & evidence

ORD record
ord-80e194e758184039b68e395f37f75ac3
Source dataset
uspto-grants-2013_09
Patent number
US08524738B2

Linked notes

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