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 657077Notes

Reaction equation

HRID 657077 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)Cl.CO>[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

7

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 60%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

A suspension of [3-(methyloxy)-6-oxopyrido[2,3-b]pyrazin-5(6H)-yl]acetaldehyde (185 mg 0.84 mmol) and 1,1-dimethylethyl (2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)-4-piperidinylcarbamate (for a synthesis see WO2004/058144 Example 99(h) (283 mg, 0.84 mmol) in chloroform (10 mL) and methanol (1.5 mL) was stirred at room temperature under argon for 1 h before addition of sodium triacetoxyborohydride (515 mg, 2.52 mmol). The reaction was stirred at rt overnight. A saturated solution of sodium bicarbonate (20 mL) was added to the reaction and the aqueous phase was extracted with 10% MeOH/DCM (3×50 mL).The combined organic phases were dried (MgSO4), filtered and evaporated and the residue was subjected to column chromatography on silica gel eluting with 0-10% methanol-DCM to afford 252 mg of the title compound (60%).

Workup

  1. extractionthe aqueous phase was extracted with 10% MeOH/DCM (3×50 mL).The combined organic phases
  2. dry with materialwere dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated

Sources & evidence

ORD record
ord-873a2399b9f04f839d27a58dcba400f2
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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