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

HRID 657078Notes

Reaction equation

HRID 657078 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.[N:17]1[C:22]2[O:23][CH2:24][CH2:25][O:26][C:21]=2[CH:20]=[C:19]([CH2:27][N:28]([CH:36]2[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]2)[C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[N:18]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl.CO>[N:17]1[C:22]2[O:23][CH2:24][CH2:25][O:26][C:21]=2[CH:20]=[C:19]([CH2:27][N:28]([CH:36]2[CH2:41][CH2:40][N:39]([CH2:15][CH2:14][N:9]3[C:7]4=[N:8][C:3]([O:2][CH3:1])=[CH:4][N:5]=[C:6]4[CH:12]=[CH:11][C:10]3=[O:13])[CH2:38][CH2:37]2)[C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[N:18]=1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 57815393(3-methoxy-6-oxopyrido(2,3-b)pyrazin-5(6H)-yl)acetaldehydeHCID 866353301,1-Dimethylethyl (6,7-dihydro[1,4]dioxino[2,3-c]pyridazin-3-ylmethyl)4-piperidinylcarbamate

Product 1

HCID 691857191,1-Dimethylethyl (6,7-dihydro[1,4]dioxino[2,3-c]pyridazin-3-ylmethyl)(1-{2-[3-(methyloxy)-6-oxopyrido[2,3-b]pyrazin-5(6H)-yl]ethyl}-4-piperidinyl)carbamateYield 74.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

A suspension of [3-(methyloxy)-6-oxopyrido[2,3-b]pyrazin-5(6H)-yl]acetaldehyde (240 mg, assuming 191 mg of aldehyde) and 1,1-dimethylethyl (6,7-dihydro[1,4]dioxino[2,3-c]pyridazin-3-ylmethyl)-4-piperidinylcarbamate (305 mg) in chloroform (10 mL) and methanol (1.5 mL) was stirred at room temperature under argon for 1 h before addition of sodium triacetoxyborohydride (553 mg). The reaction was stirred at rt overnight. A saturated solution of sodium bicarbonate (20 mL) was added to the reaction and the aqueous was extracted with 10% MeOH/DCM (3×50 mL). The combined organic phases were dried (MgSO4), evaporated and the residue was subjected to column chromatography on silica gel eluting with 0-10% methanol-DCM to afford 358 mg of the title compound (60%).

Workup

  1. extractionthe aqueous was extracted with 10% MeOH/DCM (3×50 mL)
  2. dry with materialThe combined organic phases were dried (MgSO4)
  3. customevaporated

Sources & evidence

ORD record
ord-051ec7ea061546f5a13dc1ffa4f440b4
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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