Dimethyl Sulfoxide → 2-Chloro-4-((2-furylmethyl)amino)-5-((4-(nitrooxy)piperidyl)carbonyl)benzenesulfonamide

HRID 1180622Notes

Reaction equation

HRID 1180622 reaction equation
[CH:1]1[CH:2]=[C:3]([CH2:6][NH:7][C:8]2[C:13]([C:14]([OH:16])=O)=[CH:12][C:11]([S:17]([NH2:20])(=[O:19])=[O:18])=[C:10]([Cl:21])[CH:9]=2)[O:4][CH:5]=1.[N+:22]([O-:25])([OH:24])=[O:23].[CH3:26]S(C)=O.CCN=C=N[CH2:35][CH2:36][CH2:37][N:38]([CH3:40])C>C(OCC)(=O)C.CN(C1C=CN=CC=1)C.C(N(CC)CC)C>[Cl:21][C:10]1[CH:9]=[C:8]([NH:7][CH2:6][C:3]2[O:4][CH:5]=[CH:1][CH:2]=2)[C:13]([C:14]([N:38]2[CH2:37][CH2:36][CH:35]([O:23][N+:22]([O-:25])=[O:24])[CH2:26][CH2:40]2)=[O:16])=[CH:12][C:11]=1[S:17]([NH2:20])(=[O:19])=[O:18]

Participants

8

Reactant 4

HCID 679Dimethyl SulfoxideHCID 944Nitric AcidHCID 3440FurosemideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide

Product 1

HCID 112019742-Chloro-4-((2-furylmethyl)amino)-5-((4-(nitrooxy)piperidyl)carbonyl)benzenesulfonamideYield 85%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a mixture of furosemide (331 mg, 1 mmol) and nitrooxy-4-piperidyl, nitric acid salt (prepared as described in U.S. application Ser. No. 60/505,921, Example 16a) (209 mg, 1 mmol) in ethyl acetate (25 mL) and methylsulfoxide (10 mL) was added triethyl amine (0.125 mL) and the reaction mixture was stirred at room temperature for 10 minutes. To the resulting mixture were added successively EDAC (0.192 g, 1 mmol) followed by DMAP (0.122 g, 1 mmol). The resulting solution was then stirred under nitrogen atmosphere at room temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with water, aqueous NaHCO3, water, brine, dried over sodium sulfate, filtered, and the organic extracts were evaporated. The product was purified by column chromatography over silica gel using 5% methanol in dichloromethane to give the title compound (390 mg, 85% yield) as colorless thick oil. 1H NMR (CDCl3) δ 7.74(s, 1H), 7.47 (s, 1H), 6.83 (s, 1 H), 6.25-6.15 (m, 3H), 5.31 (s, 2H), 5.18 (m, 1H), 4.34 (d, J=5.2 Hz, 2H), 3.74-3.64 (m, 2 H), 3.53-3.52 (m, 2H), 2.02 (m, 2H), 1.79 (m, 2H); LRMS (APIMS) m/z 459 (MH+), 441 (M−H2O).

Workup

  1. customprepared
  2. stirringThe resulting solution was then stirred under nitrogen atmosphere at room temperature overnight
  3. washwashed with water, aqueous NaHCO3, water, brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customthe organic extracts were evaporated
  7. customThe product was purified by column chromatography over silica gel using 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-90c87f3011794160878412a41bcb9350
Source dataset
uspto-grants-2007_10
Patent number
US07282519B2

Reaction notes

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