Sodium Bicarbonate → 6-(((1-(2-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)ethyl)piperidin-4-yl)amino)methyl)-2H-pyrido(3,2-b)(1,4)thiazin-3(4H)-one

HRID 39861Notes

Reaction equation

HRID 39861 reaction equation
Cl.[NH2:2][CH:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10][N:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=3)[N:14]=[CH:13][C:12]2=[O:23])[CH2:5][CH2:4]1.[O:24]=[C:25]1[CH2:30][S:29][C:28]2[CH:31]=[CH:32][C:33]([CH:35]=O)=[N:34][C:27]=2[NH:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(OCC)(=O)C.C(N(CC)CC)C.C(O)(=O)C.CN(C)C=O>[CH3:22][O:21][C:18]1[CH:19]=[C:20]2[C:15]([N:14]=[CH:13][C:12](=[O:23])[N:11]2[CH2:10][CH2:9][N:6]2[CH2:5][CH2:4][CH:3]([NH:2][CH2:35][C:33]3[CH:32]=[CH:31][C:28]4[S:29][CH2:30][C:25](=[O:24])[NH:26][C:27]=4[N:34]=3)[CH2:8][CH2:7]2)=[CH:16][CH:17]=1

Participants

9

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 115935913-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehydeHCID 675393541-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one hydrochloride

Product 1

HCID 159825356-(((1-(2-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)ethyl)piperidin-4-yl)amino)methyl)-2H-pyrido(3,2-b)(1,4)thiazin-3(4H)-oneYield 28.1%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 2 mL of an N,N-dimethylformamide solution containing 63 mg of 1-(2-(4-aminopiperidin-1-yl)ethyl)-7-methoxyquinoxalin-2(1H)-one hydrochloride, 36 mg of 3-oxo-3,4-dihydro-2H-pyrido(3,2-b)(1,4)thiazine-6-carbaldehyde, 0.14 mL of acetic acid and 0.12 mL of triethylamine were added, and stirred for 3 hours, thereafter 53 mg of sodium triacetoxyborohydride was added, and stirred at room temperature for 45 min. Aqueous saturated 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 extracts were combined, 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 basic silica gel column chromatography [eluent; chloroform:methanol=10:1], to give 25 mg of 6-(((1-(2-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)ethyl)piperidin-4-yl)amino)methyl)-2H-pyrido(3,2-b)(1,4)thiazin-3(4H)-one as a white solid.

Workup

  1. additionwere added
  2. stirringstirred at room temperature for 45 min
  3. customthe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. washwashed with aqueous saturated sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was removed under reduced pressure
  8. customThe residue thus obtained
  9. customwas purified by basic silica gel column chromatography [eluent; chloroform:methanol=10:1]

Sources & evidence

ORD record
ord-bde83e7072624152aa3289af3fcdf44c
Source dataset
uspto-grants-2013_09
Patent number
US08524738B2

Reaction notes

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