Morpholine → HCID 59519519, compound

HRID 1162482Notes

Reaction equation

HRID 1162482 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][O:13][CH2:12][CH2:11]1.[S:16](Cl)(Cl)(=[O:18])=[O:17]>CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]([NH:9][S:16]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)(=[O:18])=[O:17])[C:5]([Cl:8])=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 24648Sulfuryl chlorideHCID 218583543-Amino-5-bromo-2-chloropyridine

Product 1

HCID 59519519HCID 59519519, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Conditions

Temperature
-40 °C

Procedure

A 50 mL round-bottomed flask was charged with 5-bromo-2-chloropyridin-3-amine (0.863 g, 4.2 mmol) and pyridine (5 mL). To this solution, DMAP (0.13 g, 1.0 mmol) and morpholine (0.36 mL, 4.2 mmol) were added in. The mixture was chilled to −40° C. in a dry ice/acetone bath. Then sulfuryl chloride (0.36 mL, 4.6 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 at 25° C. for 15 h. The mixture was diluted with aqueous sodium bicarbonate and extracted by DCM (3×). The combined organic was dried over sodium sulfate and concentrated in vacuo. Purification by silica gel chromatography (1 to 50% EtOAc/DCM) gave N-(5-bromo-2-chloropyridin-3-yl)morpholine-4-sulfonamide (0.55 g, 37% yield) as a tan crystalline solid. MS (ESI positive ion) m/z: 358 (M+1). 1H NMR (400 MHz, DMSO-d6): δ ppm 3.07-3.12 (m, 4H), 3.58-3.62 (m, 4H), 8.07 (d, J=2.15 Hz, 1H), 8.42 (d, J=2.35 Hz, 1H), 10.19 (s, 1H).

Workup

  1. additionAfter the addition
  2. customthe ice bath was removed
  3. stirringto stir under inert atmosphere at 25° C. for 15 h
  4. additionThe mixture was diluted with aqueous sodium bicarbonate
  5. extractionextracted by DCM (3×)
  6. dry with materialThe combined organic was dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customPurification by silica gel chromatography (1 to 50% EtOAc/DCM)

Sources & evidence

ORD record
ord-eb58287519804a1ea4d9dfb56c3d46a2
Source dataset
uspto-grants-2010_10
Patent number
US07820665B2

Reaction notes

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