Sodium Bicarbonate → tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(1-(2-(7-(1H-imidazol-1-yl)-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate

HRID 385659Notes

Reaction equation

HRID 385659 reaction equation
[N:1]1([C:6]2[CH:15]=[C:14]3[C:9]([CH:10]=[CH:11][C:12](=[O:19])[N:13]3[CH2:16][CH:17]=O)=[N:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.[O:20]1[C:29]2[CH:28]=[C:27]([CH2:30][N:31]([CH:39]3[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]3)[C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[N:26]=[CH:25][C:24]=2[O:23][CH2:22][CH2:21]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>ClCCl.C(Cl)(Cl)Cl.C(O)(=O)C>[O:20]1[C:29]2[CH:28]=[C:27]([CH2:30][N:31]([CH:39]3[CH2:44][CH2:43][N:42]([CH2:17][CH2:16][N:13]4[C:14]5[C:9](=[N:8][CH:7]=[C:6]([N:1]6[CH:5]=[CH:4][N:3]=[CH:2]6)[CH:15]=5)[CH:10]=[CH:11][C:12]4=[O:19])[CH2:41][CH2:40]3)[C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[N:26]=[CH:25][C:24]=2[O:23][CH2:22][CH2:21]1

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 57815312(7-(1H-imidazol-1-yl)-2-oxo-1,5-naphthyridin-1(2H)-yl)acetaldehydeHCID 578154611,1-Dimethylethyl (2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)-4-piperidinylcarbamate

Product 1

HCID 57815487tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(1-(2-(7-(1H-imidazol-1-yl)-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)carbamateYield 51%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 0.12 g of (7-(1H-imidazol-1-yl)-2-oxo-1,5-naphthyridin-1(2H)-yl)acetaldehyde in 1 mL of dichloromethane, a solution of 0.14 g of tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(piperidin-4-yl)carbamate in 1.4 mL of dichloromethane, and 23 μL of acetic acid and 0.13 g of sodium triacetoxyborohydride were added, and the mixture was stirred at room temperature for 1 hour 40 minutes. The reaction mixture was charged with chloroform, and a saturated aqueous sodium hydrogen carbonate solution and adjusted to pH 8.6, 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 water and 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 gradient elution with chloroform:methanol=19:1 to 93:7 to obtain 0.12 g of tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(1-(2-(7-(1H-imidazol-1-yl)-2-oxo-1,5-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate as a light yellow solid.

Workup

  1. customthe organic layer was separated
  2. extractionthe aqueous layer was extracted with chloroform
  3. washthe resultant solution was washed with water
  4. dry with materiala saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. customThe resultant residue was purified by basic silica gel column chromatography
  7. washelution with chloroform

Sources & evidence

ORD record
ord-409ad538074b4ad0ad1c5dd313fa88ad
Source dataset
uspto-grants-2013_02
Patent number
US08367831B2

Reaction notes

Loading…