Tetrahydrofuran → HCID 57585129, compound

HRID 2077549Notes

Reaction equation

HRID 2077549 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH2:9])[C:5]([Cl:8])=[N:6][CH:7]=1.C1COCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH:25]1([S:31](Cl)(=[O:33])=[O:32])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1>C(Cl)Cl.O>[Br:1][C:2]1[CH:3]=[C:4]([NH:9][S:31]([CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)(=[O:33])=[O:32])[C:5]([Cl:8])=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 237554Cyclohexanesulfonyl chlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 218583543-Amino-5-bromo-2-chloropyridine

Product 1

HCID 57585129HCID 57585129, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a 50 ml round-bottom flask equipped with a stir bar, was added 5-bromo-2-chloropyridin-3-amine (0.250 g, 1 mmol) while under inert atmosphere. The solid was dissolved in THF (10 ml, 122 mmol), then sodium bis(trimethylsilyl)amide (0.650 g, 3 mmol) was added to the mixture and allowed to stir 5 minutes. Then cyclohexanesulfonyl chloride (0.5 ml, 4 mmol) was added into the mixture. The mixture was allowed to stir overnight, while under inert atmosphere. The progress of the reaction was monitored by LC/MS, which showed product and a small amount of bis-sulfone material in the mixture. The mixture was diluted with DCM and water. The organic layer was extracted with DCM (3×25 ml). Combined organics, dried over sodium sulfate, filtered and concentrated in vacuo. The crude was dissolved in methanol (5 ml), then potassium carbonate (0.250 g) was added to the mixture with stirring. After 20 minutes, the progress of the de-sulfonylation reaction was monitored by LC/MS, which showed mostly desired product. The mixture was filtered and concentrated in vacuo. The crude was purified by ISCO silica-gel chromatography, in a gradient of 1-15% ethyl acetate/hexanes. This gave N-(5-bromo-2-chloropyridin-3-yl)cyclohexanesulfonamide (0.140 g, 33% yield) as an off-white amorphous solid. MS (ESI pos. ion) m/z: 354 (MH+). Calc'd exact mass for C11H14BrClN2O2S: 353. 1H NMR (400 MHz, chloroform-d): 1.15-1.35 (m, 2H), 1.52-1.66 (m, 1H), 1.70 (d, J=4.52 Hz, 1H), 1.73 (s, 1H), 1.76-1.86 (m, 1H), 1.92 (d, J=11.54 Hz, 1H), 2.11-2.22 (m, 2H), 2.96-3.05 (m, 1H), 6.70 (s, 1H), 8.15-8.22 (m, 2H).

Workup

  1. customTo a 50 ml round-bottom flask equipped with a stir bar
  2. stirringto stir overnight, while under inert atmosphere
  3. extractionThe organic layer was extracted with DCM (3×25 ml)
  4. dry with materialCombined organics, dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe crude was dissolved in methanol (5 ml)
  8. additionpotassium carbonate (0.250 g) was added to the mixture
  9. stirringwith stirring
  10. waitAfter 20 minutes
  11. customthe progress of the de-sulfonylation reaction

Sources & evidence

ORD record
ord-abe9f574fe2c4c8a8fcf51640bc1baec
Source dataset
uspto-grants-2011_04
Patent number
US07928140B2

Reaction notes

Loading…