Morpholine → HCID 59631315, compound

HRID 1431376Notes

Reaction equation

HRID 1431376 reaction equation
[NH2:1][C:2]1[C:3]([F:9])=[N:4][CH:5]=[C:6](Br)[CH:7]=1.[NH:10]1[CH2:17][CH2:16]C[C@H:11]1[C:12](O)=[O:13].C(=O)([O-])[O-].[K+].[K+].N1CCOCC1>CS(C)=O.[Cu]I>[F:9][C:3]1[C:2]([NH2:1])=[CH:7][C:6]([N:10]2[CH2:11][CH2:12][O:13][CH2:16][CH2:17]2)=[CH:5][N:4]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 177501445-Bromo-2-fluoropyridin-3-amine

Product 1

HCID 59631315HCID 59631315, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
90 °C

Procedure

A stirred mixture of 3-amino-5-bromo-2-fluoropyridine (0.96 g, 5.02 mmol), L-proline (0.12 g, 1.01 mmol), potassium carbonate (1.39 g, 10.1 mmol), copper(I) iodide (0.096 g, 0.50 mmol), and morpholine (1.31 mL, 15.04 mmol) in dry DMSO (3.0 mL) was purged three times with argon and placed under vacuum three times, then the mixture was heated to 90° C. After 21.5 h, the reaction was cooled to rt, then treated with water. After extracting twice with EtOAc, the organics were combined and dried over anhydrous sodium sulfate. After filtration and concentration the residue was purified on basic alumina (10-50% EtOAc in hexanes) to afford a white solid as 2-fluoro-5-morpholinopyridin-3-amine. 1H NMR (400 MHz, DMSO-d6) δ ppm 6.96 (1H, t, J=2.6 Hz), 6.75 (1H, dd, J=9.6, 2.7 Hz), 5.25 (2H, br. s.), 3.80 (4H, m), 3.08 (4H, m). Mass Spectrum ESI (pos.) m/e: 198.1 (M+H)+.

Workup

  1. customwas purged three times with argon
  2. temperaturethe reaction was cooled to rt
  3. additiontreated with water
  4. extractionAfter extracting twice with EtOAc
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationAfter filtration and concentration the residue
  7. customwas purified on basic alumina (10-50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-e759bd64f36c4741bdf74f683968f81a
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

Loading…