2-Methyl-[1,2,6]thiadiazinane 1,1-dioxide → N-(4-fluorobenzyl)-8-hydroxy-5(6-methyl-1,1-dioxido-1,2,6-thiadiazinan-2yl)-1,6-naphthyridine-7-carboxamide

HRID 897352Notes

Reaction equation

HRID 897352 reaction equation
Br[C:2]1[N:11]=[C:10]([C:12]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)=[O:13])[C:9]([OH:23])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.[CH3:24][N:25]1[CH2:30][CH2:29][CH2:28][NH:27][S:26]1(=[O:32])=[O:31]>N1C=CC=CC=1>[F:22][C:19]1[CH:20]=[CH:21][C:16]([CH2:15][NH:14][C:12]([C:10]2[C:9]([OH:23])=[C:8]3[C:3]([CH:4]=[CH:5][CH:6]=[N:7]3)=[C:2]([N:27]3[CH2:28][CH2:29][CH2:30][N:25]([CH3:24])[S:26]3(=[O:32])=[O:31])[N:11]=2)=[O:13])=[CH:17][CH:18]=1

Participants

4

Reactant 2

HCID 100805602-Methyl-[1,2,6]thiadiazinane 1,1-dioxideHCID 223464015-bromo-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide

Product 1

HCID 22346404N-(4-fluorobenzyl)-8-hydroxy-5(6-methyl-1,1-dioxido-1,2,6-thiadiazinan-2yl)-1,6-naphthyridine-7-carboxamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of 5-bromo-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide (0.300 g, 0.80 mmol), 2-methyl-1,2,6-thiadiazinane 1,1-dioxide (0.144 g, 0.96 mmol) and Cu2O (0.086 g, 0.60 mmol) in pyridine (6.0 mL) were heated at reflux for 16 hr. The reaction was filtered and the solids washed with CHCl3 (100 mL). The filtrate was stirred for 1 hr with disodium ethylenediamine tetraacetate (0.5 g) in water (25 mL) in the presence of air. The organic extracts were stirred for 1 hr with disodium ethylenediamine tetraacetate (0.50 g in water 50 mL) in the presence of air. The organic extracts were dried (MgSO4) and the solvent evaporated in vacuo. The residue was purified by preparative HPLC (Gilson semi preparative HPLC system and a YMC Combiprep Pro Column (50×20 mm I.D., C18, S-5 um, 120A) eluting with 5-95% acetonitrile/water (0.1% TFA) at 15 ml/min) to afford the title compound after lyophilization.

Workup

  1. temperatureat reflux for 16 hr
  2. filtrationThe reaction was filtered
  3. washthe solids washed with CHCl3 (100 mL)
  4. stirringThe organic extracts were stirred for 1 hr with disodium ethylenediamine tetraacetate (0.50 g in water 50 mL) in the presence of air
  5. dry with materialThe organic extracts were dried (MgSO4)
  6. customthe solvent evaporated in vacuo
  7. customThe residue was purified by preparative HPLC (Gilson semi preparative HPLC system
  8. washa YMC Combiprep Pro Column (50×20 mm I.D., C18, S-5 um, 120A) eluting with 5-95% acetonitrile/water (0.1% TFA) at 15 ml/min)

Sources & evidence

ORD record
ord-0da5904189c545cbbd675bf7cf400b8e
Source dataset
uspto-grants-2005_07
Patent number
US06921759B2

Reaction notes

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