Sodium Bicarbonate → 1,1-Dimethylethyl (2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)(1-{2-[3-(methyloxy)-6-oxopyrido[2,3-b]pyrazin-5(6H)-yl]ethyl}-4-piperidinyl)carbamate

HRID 1510770Notes

Reaction equation

HRID 1510770 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[C:7]2[N:9]([CH2:14][CH:15]=O)[C:10](=[O:13])[CH:11]=[CH:12][C:6]2=[N:5][CH:4]=1.[O:17]1[C:26]2[CH:25]=[C:24]([CH2:27][N:28]([CH:36]3[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]3)[C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[N:23]=[CH:22][C:21]=2[O:20][CH2:19][CH2:18]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(Cl)Cl.C(Cl)(Cl)Cl.C(O)(=O)C>[O:17]1[C:26]2[CH:25]=[C:24]([CH2:27][N:28]([CH:36]3[CH2:41][CH2:40][N:39]([CH2:15][CH2:14][N:9]4[C:7]5=[N:8][C:3]([O:2][CH3:1])=[CH:4][N:5]=[C:6]5[CH:12]=[CH:11][C:10]4=[O:13])[CH2:38][CH2:37]3)[C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[N:23]=[CH:22][C:21]=2[O:20][CH2:19][CH2:18]1

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 57815393(3-methoxy-6-oxopyrido(2,3-b)pyrazin-5(6H)-yl)acetaldehydeHCID 578154611,1-Dimethylethyl (2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)-4-piperidinylcarbamate

Product 1

HCID 578154501,1-Dimethylethyl (2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)(1-{2-[3-(methyloxy)-6-oxopyrido[2,3-b]pyrazin-5(6H)-yl]ethyl}-4-piperidinyl)carbamateYield 112.4%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 0.12 g of (3-methoxy-6-oxopyrido(2,3-b)pyrazin-5(6H)-yl)acetaldehyde in 5 mL of methylene chloride, 0.18 g of tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(piperidin-4-yl)carbamate, 26 μL of acetic acid and 0.12 g of sodium triacetoxyborohydride were added, and the mixture was stirred at room temperature for 2 hours 30 minutes. To the reaction mixture, a saturated aqueous sodium hydrogen carbonate solution and chloroform were added, the organic layer was separated, and the aqueous layer was extracted with chloroform. 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 silica gel column chromatography using an eluent of chloroform:methanol=20:1 to obtain 0.32 g of tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(1-(2-(3-methoxy-6-oxopyrido(2,3-b)pyrazin-5(6H)-yl)ethyl)piperidin-4-yl)carbamate as a colorless oily substance.

Workup

  1. customthe organic layer was separated
  2. extractionthe aqueous layer was extracted with chloroform
  3. washthe resultant solution 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-c3b09e06370344a1b3aa77b85f028f71
Source dataset
uspto-grants-2012_07
Patent number
US08211908B2

Reaction notes

Loading…