Pyridine → 3-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamide

HRID 1990273Notes

Reaction equation

HRID 1990273 reaction equation
[N:1]1([C:5]([C:7]2[CH:8]=[C:9]([Cl:29])[C:10]([O:13][C:14]3[CH:15]=[C:16]([CH:20]=[C:21]([O:23][CH:24]([CH2:27][F:28])[CH2:25][F:26])[CH:22]=3)[C:17](O)=[O:18])=[N:11][CH:12]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1.N1C=CC=CC=1.[NH2:36][C:37]1[CH:42]=[N:41][C:40]([CH3:43])=[CH:39][N:38]=1>C(Cl)Cl>[N:1]1([C:5]([C:7]2[CH:8]=[C:9]([Cl:29])[C:10]([O:13][C:14]3[CH:15]=[C:16]([CH:20]=[C:21]([O:23][CH:24]([CH2:25][F:26])[CH2:27][F:28])[CH:22]=3)[C:17]([NH:36][C:37]3[CH:42]=[N:41][C:40]([CH3:43])=[CH:39][N:38]=3)=[O:18])=[N:11][CH:12]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 3132155-Methylpyrazin-2-amineHCID 59127163HCID 59127163, compound

Product 1

HCID 536295793-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamideYield 57.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-Chloro-N,N-2-trimethylpropenylamine (0.08 mL, 0.60 mmol) was added to a solution of 3-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-{[2-fluoro-1-(fluoromethyl)ethyl]oxy}benzoic acid (215 mg, 0.5 mmol) in DCM (5 mL) and the reaction stirred at RT for 30-40 minutes. Pyridine (0.08 mL, 1.0 mmol) and 2-amino-5-methylpyrazine (108 mg, 1.0 mmol) were added and the reaction stirred for 16 hours before being concentrated in vacuo and water (20 mL) added. The mixture was extracted with ethyl acetate (3×20 mL), washed with 1N hydrochloric acid (20 mL), a saturated solution of sodium hydrogen carbonate (20 mL), brine (20 mL), dried (MgSO4) and concentrated in vacuo. The crude product was chromatographed on silica, eluting with a gradient of 0-10% methanol in DCM, to give the desired compound as a white solid (150 mg). 1H NMR δ (CDCl3): 2.40 (quintet, 2H), 2.56 (s, 3H), 4.22-4.31 (m, 2H), 4.32-4.40 (m, 2H), 4.62-4.82 (m, 5H), 7.06 (t, 1H), 7.38 (t, 1H), 7.47 (t, 1H), 8.15 (s, 1H), 8.17 (s, 1H), 8.25 (d, 1H), 8.46 (s, 1H), 9.55 (s, 1H); m/z 518 (M+H)+, 516 (M−H)−

Workup

  1. stirringthe reaction stirred for 16 hours
  2. concentrationbefore being concentrated in vacuo and water (20 mL)
  3. additionadded
  4. extractionThe mixture was extracted with ethyl acetate (3×20 mL)
  5. washwashed with 1N hydrochloric acid (20 mL)
  6. dry with materiala saturated solution of sodium hydrogen carbonate (20 mL), brine (20 mL), dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude product was chromatographed on silica
  9. washeluting with a gradient of 0-10% methanol in DCM

Sources & evidence

ORD record
ord-d3b12bc9c7e747cda9243e5e5515a50b
Source dataset
uspto-grants-2010_01
Patent number
US07642259B2

Reaction notes

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