Sodium Bicarbonate → 1-(2-{(3S,4R)-4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-3-hydroxy-1-piperidinyl}ethyl)-7-(methyloxy)-1,5-naphthyridin-2(1H)-one hydrochloride

HRID 657032Notes

Reaction equation

HRID 657032 reaction equation
[ClH:1].Cl.[NH2:3][C@@H:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][N:12]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([O:22][CH3:23])[CH:20]=3)[CH:15]=[CH:14][C:13]2=[O:24])[CH2:6][C@@H:5]1[OH:25].[O:26]1[C:35]2[CH:34]=[C:33]([CH:36]=O)[N:32]=[CH:31][C:30]=2[O:29][CH2:28][CH2:27]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(Cl)Cl.C(N(CC)CC)C.CO.C(Cl)(Cl)Cl>[ClH:1].[O:26]1[C:35]2[CH:34]=[C:33]([CH2:36][NH:3][C@@H:4]3[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][N:12]4[C:21]5[C:16](=[N:17][CH:18]=[C:19]([O:22][CH3:23])[CH:20]=5)[CH:15]=[CH:14][C:13]4=[O:24])[CH2:6][C@@H:5]3[OH:25])[N:32]=[CH:31][C:30]=2[O:29][CH2:28][CH2:27]1

Participants

9

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 218736682,3-Dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehydeHCID 674985761-{2-[(3S,4R)-4-amino-3-hydroxy-1-piperidinyl]ethyl}-7-(methyloxy)-1,5-naphthyridin-2(1H)-one Dihydrochloride

Product 1

HCID 689925311-(2-{(3S,4R)-4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-3-hydroxy-1-piperidinyl}ethyl)-7-(methyloxy)-1,5-naphthyridin-2(1H)-one hydrochloride

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

1-{2-[(3S,4R)-4-amino-3-hydroxy-1-piperidinyl]ethyl}-7-(methyloxy)-1,5-naphthyridin-2(1H)-one dihydrochloride (209 mg) was stirred in 9:1 v:v chloroform:MeOH (5 ml) at rt under argon and triethylamine (25011) was added. The mixture was stirred at rt for 10 mins., then 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carboxaldehyde (88 mg, for a synthesis see WO2004058144, Example 2(c) or WO03/087098, Example 19(d)) was added and the mixture was stirred at rt for 4 hours before being treated with sodium triacetoxyborohydride (360 mg) added in one portion. The mixture was then stirred at rt overnight. Saturated aqueous sodium hydrogen cabonate (2 ml) was then added and the organic phase was diluted with DCM to bring the total volume to ca. 50 ml. The organic phase was separated using a hydrophobic frit and the aqueous phase was extracted with DCM (2×10 ml). The combined organic extracts were evaporated under reduced pressure and purified by MDAP to give the free base of the title compound as colourless gum (30 mg).

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at rt for 4 hours
  3. additionadded in one portion
  4. stirringThe mixture was then stirred at rt overnight
  5. customThe organic phase was separated
  6. extractionthe aqueous phase was extracted with DCM (2×10 ml)
  7. customThe combined organic extracts were evaporated under reduced pressure
  8. custompurified by MDAP

Sources & evidence

ORD record
ord-a6baa734ad014c258bb3381508a12c39
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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