Piperidine → HCID 77231507, compound

HRID 2077610Notes

Reaction equation

HRID 2077610 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH2:9])[C:5]([Cl:8])=[N:6][CH:7]=1.[NH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.[S:16](Cl)(Cl)(=[O:18])=[O:17]>N1C=CC=CC=1.CN(C1C=CN=CC=1)C>[Br:1][C:2]1[CH:3]=[C:4]([NH:9][S:16]([N:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)(=[O:18])=[O:17])[C:5]([Cl:8])=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 8082PiperidineHCID 24648Sulfuryl chlorideHCID 218583543-Amino-5-bromo-2-chloropyridine

Product 1

HCID 77231507HCID 77231507, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Conditions

Temperature
40 °C

Procedure

To a 50 ml round-bottom flask equipped with a stir bar and charged with 5-bromo-2-chloropyridin-3-amine (0.245 g, 1.2 mmol) in pyridine (1.5 ml), was added DMAP (0.036 g, 0.30 mmol) and piperidine (0.12 ml, 1.2 mmol). The mixture was chilled to 40° C. in a dry ice/acetone bath. Then sulfuryl chloride (0.10 ml, 1.3 mmol) was added dropwise into the mixture while stirring. After the addition, the ice bath was removed and the mixture was allowed to stir under inert atmosphere overnight. The progress of the reaction was monitored by LC/MS, which showed desired product and consumption of starting material. The mixture was diluted with water (10 ml) and DCM (10 ml). The organic layer was collected by extracting with DCM (3×20 ml). Combined organics, dried over sodium sulfate, filtered and concentrated in vacuo. The crude was dissolved in DCM and purified by ISCO Silica-Gel Chromatography (80 gram column) in a gradient of 5-50% EtOAc/DCM over 20 minutes. The fractions with desired material were combined and concentrated. This gave N-(5-bromo-2-chloropyridin-3-yl)piperidine-1-sulfonamide (0.300 g, 72% yield) as a tan solid. MS (ESI pos. ion) m/z: 355 (MH+). Calc'd exact mass for C10H13BrClN3O2S: 354. 1H NMR (400 MHz, DMSO-d6): 1.42-1.58 (m, 8H), 1.71 (qd, J=5.69, 5.52 Hz, 2H), 3.28 (s, 1H), 8.02 (d, J=2.01 Hz, 1H), 8.38 (d, J=2.51 Hz, 1H).

Workup

  1. customTo a 50 ml round-bottom flask equipped with a stir bar
  2. additionAfter the addition
  3. customthe ice bath was removed
  4. stirringto stir under inert atmosphere overnight
  5. customdesired product and consumption of starting material
  6. additionThe mixture was diluted with water (10 ml) and DCM (10 ml)
  7. customThe organic layer was collected
  8. extractionby extracting with DCM (3×20 ml)
  9. dry with materialCombined organics, dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. dissolutionThe crude was dissolved in DCM
  13. custompurified by ISCO Silica-Gel Chromatography (80 gram column) in a gradient of 5-50% EtOAc/DCM over 20 minutes
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-3343a8cda1814c438f37e700ba37fc2a
Source dataset
uspto-grants-2011_04
Patent number
US07928140B2

Reaction notes

Loading…