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

HRID 657011Notes

Reaction equation

HRID 657011 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]([F:22])[CH:20]=3)[CH:15]=[CH:14][C:13]2=[O:23])[CH2:6][C@@H:5]1[OH:24].C(N(CC)CC)C.[O:32]1[C:41]2[CH:40]=[C:39]([CH:42]=O)[N:38]=[CH:37][C:36]=2[O:35][CH2:34][CH2:33]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(Cl)Cl.CO.C(Cl)(Cl)Cl>[ClH:1].[O:32]1[C:41]2[CH:40]=[C:39]([CH2:42][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]([F:22])[CH:20]=5)[CH:15]=[CH:14][C:13]4=[O:23])[CH2:6][C@@H:5]3[OH:24])[N:38]=[CH:37][C:36]=2[O:35][CH2:34][CH2:33]1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 218736682,3-Dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehydeHCID 689924211-{2-[(3S,4R)-4-amino-3-hydroxy-1-piperidinyl]ethyl}-7-fluoro-1,5-naphthyridin-2(1H)-one dihydrochloride

Product 1

HCID 689956971-(2-{(3S,4R)-4-[(2,3-dihydro[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)amino]-3-hydroxy-1-piperidinyl}ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one hydrochloride

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

1-{2-[(3S,4R)-4-Amino-3-hydroxy-1-piperidinyl]ethyl}-7-fluoro-1,5-naphthyridin-2(1H)-one dihydrochloride (247 mg, 0.6513 mmol) was stirred in 9:1 v:v chloroform:MeOH (10 ml) at rt under argon and triethylamine (318 μL, 3.5 eq.) was added. The mixture was stirred at rt for 10 mins., then 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carboxaldehyde (108 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 2 hours before being treated with sodium triacetoxyborohydride (414 mg) added in one portion. The mixture was then stirred at rt overnight. Saturated aqueous sodium hydrogen cabonate (5 ml) was then added and the organic phase was diluted with DCM to bring the total volume to ca. 100 ml. The organic phase was separated using a hydrophobic frit and the aqueous phase was extracted with DCM (2×50 ml). The combined DCM extracts were evaporated under reduced pressure and purified by MDAP to give the free base of the title compound as a white foam (130 mg).

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at rt for 2 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 (2×50 ml)
  7. customThe combined DCM extracts were evaporated under reduced pressure
  8. custompurified by MDAP

Sources & evidence

ORD record
ord-ec2312a7cb08451fb26fcf0f72c88c45
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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