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

HRID 656999Notes

Reaction equation

HRID 656999 reaction equation
CO[C:3]1[CH:16]=[N:15][C:6]2[N:7]=[CH:8][C:9](=O)[N:10](CC=O)[C:5]=2[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.[BH-](O[C:52]([CH3:54])=[O:53])(OC(C)=O)OC(C)=O.[Na+].[C:56]([O-:59])(O)=O.[Na+]>C(Cl)(Cl)Cl>[O:17]1[C:26]2[CH:25]=[C:24]([CH2:27][N:28]([CH:36]3[CH2:41][CH2:40][N:39]([CH2:9][CH2:8][N:7]4[C:52](=[O:53])[CH:54]=[N:10][C:5]5[CH:4]=[CH:3][C:16]([O:59][CH3:56])=[N:15][C:6]4=5)[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

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 57815437[7-(methyloxy)-2-oxopyrido[2,3-b]pyrazin-1(2H)-yl]acetaldehydeHCID 578154611,1-Dimethylethyl (2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)-4-piperidinylcarbamate

Product 1

HCID 578152431,1-Dimethylethyl (2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)(1-{2-[6-(methyloxy)-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl]ethyl}-4-piperidinyl)carbamateYield 73%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A mixture of [7-(methyloxy)-2-oxopyrido[2,3-b]pyrazin-1(2H)-yl]acetaldehyde (as the methyl hemiacetal) (969 mg, 3.510 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)) (1.22 g, 3.510 mmol) in chloroform (40 ml) was stirred for 1 h before addition of NaBH(OAc)3 (377 mg, 1.59 mmol). The reaction was stirred for 1 h more before addition of sat. aq NaHCO3 (100 ml). The reaction was then extracted with 10% MeOH in DCM (3×200 ml). The combined organic phases were dried, evaporated and the crude residue purified by chromatography on silica gel using a 0-10% MeOH/DCM gradient to provide the desired compound as an impure yellow foam (1.408 g, 73%).

Workup

  1. extractionThe reaction was then extracted with 10% MeOH in DCM (3×200 ml)
  2. customThe combined organic phases were dried
  3. customevaporated
  4. customthe crude residue purified by chromatography on silica gel using a 0-10% MeOH/DCM gradient

Sources & evidence

ORD record
ord-1912603140e04929978af2fac9397f61
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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