2,2'-Bipyridine → Methyl 5-(1,1-dioxido-1,2-thiazinan-2-yl)-8-{[(4-methylphenyl)sulfonyl]oxy}-1,6-naphthyridine-7-carboxylate

HRID 897365Notes

Reaction equation

HRID 897365 reaction equation
Br[C:2]1[N:11]=[C:10]([C:12]([O:14][CH3:15])=[O:13])[C:9]([O:16][S:17]([C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=2)(=[O:19])=[O:18])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.[S:27]1(=[O:34])(=[O:33])[CH2:32][CH2:31][CH2:30][CH2:29][NH:28]1.N1C=CC=CC=1C1C=CC=CN=1.O.C(N(CC(O)=O)CC(O)=O)CN(CC(O)=O)CC(O)=O>CN(C=O)C.O.[Cu-]=O>[O:33]=[S:27]1(=[O:34])[CH2:32][CH2:31][CH2:30][CH2:29][N:28]1[C:2]1[N:11]=[C:10]([C:12]([O:14][CH3:15])=[O:13])[C:9]([O:16][S:17]([C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=2)(=[O:19])=[O:18])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2

Participants

8

Reactant 4

HCID 14742,2'-BipyridineHCID 3035081,4-ButanesultamHCID 11339571Methyl 5-bromo-8-(tosyloxy)-1,6-naphthyridine-7-carboxylateHCID 86587466HCID 86587466, compound2×

Product 1

HCID 11386323Methyl 5-(1,1-dioxido-1,2-thiazinan-2-yl)-8-{[(4-methylphenyl)sulfonyl]oxy}-1,6-naphthyridine-7-carboxylate

Reagents, catalysts & solvents 3

HCID 178419072HCID 178419072, compoundCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
118 °C

Procedure

To a slurry of methyl 5-bromo-8-{[(4-methylphenyl)sulfonyl]oxy}-1,6-naphthyridine-7-carboxylate (7.55 g, 17.27 mmol) in degassed DMF (20 mL) in a pressure tube was added 1,2-thiazinane-1,1-dioxide (2.8 g, 20.7 mmol, prepared as in White et al, J. Org Chem. 1987, 52: 2162) followed by 2,2′-bipyridine (3.24 g, 20.7 mmol) and copper (I) oxide powder (2.96 g, 20.7 mmol). The pressure tube was closed and heated to 118 degrees C. overnight. Celite (0.5 g) was added to the resulting slurry and this was filtered through a plug of DMF wetted celite. The solids were washed with more DMF (10 mL) and the filtrate transferred to a large Erlenmeyer flask (1L) fitted with a 2 inch stirring bar. The volume was brought up to 200 mL with chloroform and a solution of ethylenediaminetetraacetic acid monohydrate (13.3 g, 35.7 mmol) in 140 mL of water was added. The biphasic mixture was vigorously stirred, open to the air, for 3 hours. The organic phase was separated and retreated with another solution of ethylenediaminetetraacetic acid monohydrate (13.3 g, 35.7 mmol) in 140 mL of water overnight (16 hrs). The organic was separated and washed with water and dried over Na2SO4, filtered, and reduced to a small volume in vacuo. The product solidified during solvent reduction. The solid was broken up and dried to afford the desired product.

Workup

  1. customThe pressure tube was closed
  2. customovernight
  3. additionCelite (0.5 g) was added to the resulting slurry
  4. filtrationthis was filtered through a plug of DMF wetted celite
  5. washThe solids were washed with more DMF (10 mL)
  6. customthe filtrate transferred to a large Erlenmeyer flask
  7. custom(1L) fitted with a 2 inch
  8. stirringThe biphasic mixture was vigorously stirred, open to the air, for 3 hours
  9. customThe organic phase was separated
  10. customThe organic was separated
  11. washwashed with water
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. customdried

Sources & evidence

ORD record
ord-241afb331e5142388ef306d596139fb8
Source dataset
uspto-grants-2005_07
Patent number
US06921759B2

Reaction notes

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