Cesium carbonate → 3-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-[(1-methylethyl)oxy]-N-(5-methylpyrazin-2-yl)benzamide

HRID 1011765Notes

Reaction equation

HRID 1011765 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[OH:7][C:8]1[CH:9]=[C:10]([CH:21]=[C:22]([O:24][CH:25]([CH3:27])[CH3:26])[CH:23]=1)[C:11]([NH:13][C:14]1[CH:19]=[N:18][C:17]([CH3:20])=[CH:16][N:15]=1)=[O:12].[N:28]1([C:32]([C:34]2[CH:35]=[C:36]([Cl:41])[C:37](Cl)=[N:38][CH:39]=2)=[O:33])[CH2:31][CH2:30][CH2:29]1>C(#N)C>[N:28]1([C:32]([C:34]2[CH:35]=[C:36]([Cl:41])[C:37]([O:7][C:8]3[CH:9]=[C:10]([CH:21]=[C:22]([O:24][CH:25]([CH3:27])[CH3:26])[CH:23]=3)[C:11]([NH:13][C:14]3[CH:19]=[N:18][C:17]([CH3:20])=[CH:16][N:15]=3)=[O:12])=[N:38][CH:39]=2)=[O:33])[CH2:31][CH2:30][CH2:29]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 536296165-(Azetidin-1-ylcarbonyl)-2,3-dichloropyridineHCID 591271623-Hydroxy-N-(5-methylpyrazin-2-yl)-5-[(propan-2-yl)oxy]benzamide

Product 1

HCID 160398303-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-[(1-methylethyl)oxy]-N-(5-methylpyrazin-2-yl)benzamideYield 69.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

Cesium carbonate (489 mg, 1.5 mmol) was added to a solution of 3-hydroxy-5-[(1-methylethyl)oxy]-N-(5-methylpyrazin-2-yl)benzamide (144 mg, 0.5 mmol) and 5-(azetidin-1-ylcarbonyl)-2,3-dichloropyridine (173 mg, 0.75 mmol) in acetonitrile (5 mL) and the stirred mixture heated at 120° C. in a microwave reactor for 1 hour. The mixture was cooled to RT and ambient pressure, the acetonitrile evaporated in vacuo, the residue partitioned between water (25 mL) and ethyl acetate (50 mL). The organic layer was washed with brine, dried (MgSO4) and evaporated to a residue which was chromatographed on silica, eluting with 75% ethyl acetate in isohexane, to give the desired compound (167 mg). 1H NMR δ (CDCl3): 1.3 (d, 6H), 2.3 (m, 2H), 2.5 (s, 3H), 4.1-4.3 (m, 4H), 4.55 (m, 1H), 6.85 (d, 1H), 7.2 (d, 1H), 7.3 (s, 1H), 8.05 (s, 1H), 8.1 (s, 1H), 8.2 (s, 1H) 8.3 (s, 1H) and 9.45 (s, 1H). m/z 482 (M+H)+.

Workup

  1. temperatureThe mixture was cooled to RT
  2. customambient pressure, the acetonitrile evaporated in vacuo
  3. customthe residue partitioned between water (25 mL) and ethyl acetate (50 mL)
  4. washThe organic layer was washed with brine
  5. dry with materialdried (MgSO4)
  6. customevaporated to a residue which
  7. customwas chromatographed on silica
  8. washeluting with 75% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-f98d1711a1e7404fb567890421471e24
Source dataset
uspto-grants-2011_07
Patent number
US07977328B2

Reaction notes

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