Citric Acid → 2-[[3-(1-hydroxy-3-oxo-4,4-dipropyl-2-naphthyl)-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-7-yl]oxy]acetamide

HRID 494449Notes

Reaction equation

HRID 494449 reaction equation
[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:15][CH2:16][CH3:17])([CH2:12][CH2:13][CH3:14])[C:4](=[O:18])[C:3]=1[C:19]1[NH:24][C:23]2[CH:25]=[CH:26][C:27]([OH:29])=[CH:28][C:22]=2[S:21](=[O:31])(=[O:30])[N:20]=1.Br[CH2:33][C:34]([NH2:36])=[O:35].C(=O)([O-])[O-].[Cs+].[Cs+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12][CH2:13][CH3:14])([CH2:15][CH2:16][CH3:17])[C:4](=[O:18])[C:3]=1[C:19]1[NH:24][C:23]2[CH:25]=[CH:26][C:27]([O:29][CH2:33][C:34]([NH2:36])=[O:35])=[CH:28][C:22]=2[S:21](=[O:30])(=[O:31])[N:20]=1

Participants

7

Reactant 4

HCID 311Citric AcidHCID 10796Cesium carbonateHCID 696322-BromoacetamideHCID 135436704HCID 135436704, compound

Product 1

HCID 1355183462-[[3-(1-hydroxy-3-oxo-4,4-dipropyl-2-naphthyl)-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-7-yl]oxy]acetamideYield 75.4%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A solution of the product of Example 2G (14 mg, 0.032 mmol), 2-bromoacetamide (9 mg, 0.064 mmol), cesium carbonate (22 mg, 0.067 mmol) and tetrabutylammonium iodide (3 mg) in N,N-dimethylformamide (0.5 mL) was stirred at 25° C. for 18 hours. The solution was acidified with 1M citric acid solution (1 mL) and extracted with ethyl acetate. The organic layer was washed with water (3×) and saturated sodium chloride solution, dried (Na2SO4), filtered and concentrated in vacuo. A suspension of the residue in acetonitrile (2 mL) was treated with 1N sodium hydroxide solution (26 μL) and stirred at 25° C. for 2 hours. The solution was lyophilized to afford the title compound (12 mg, 52%). 1H NMR (300 MHz, DMSO-d6): δ 8.12 (d, J=8.09 Hz, 1 H), 7.61 (m, 4 H), 7.31 (m, 2 H), 4.55 (s, 2 H), 2.15 (m, 2H), 1.87 (m, 2 H), 1.29 (m, 2 H), 0.87 (m, 2 H), 0.60 (m, 7 H).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with water (3×) and saturated sodium chloride solution
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. additionA suspension of the residue in acetonitrile (2 mL)
  7. additionwas treated with 1N sodium hydroxide solution (26 μL)

Sources & evidence

ORD record
ord-a27e0f5486804ef7b73e976b74d6c065
Source dataset
uspto-grants-2009_05
Patent number
US07538105B2

Reaction notes

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