Cesium carbonate → 3-{[6-(azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-5-[(1-methylethyl)oxy]-N-(5-methylpyrazin-2-yl)benzamide

HRID 1011769Notes

Reaction equation

HRID 1011769 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:39]=[CH:38][C:37](Br)=[CH:36][N:35]=2)=[O:33])[CH2:31][CH2:30][CH2:29]1>CC(N(C)C)=O>[N:28]1([C:32]([C:34]2[N:35]=[CH:36][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])=[CH:38][CH:39]=2)=[O:33])[CH2:31][CH2:30][CH2:29]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 536296172-(Azetidin-1-ylcarbonyl)-5-bromopyridineHCID 591271623-Hydroxy-N-(5-methylpyrazin-2-yl)-5-[(propan-2-yl)oxy]benzamide

Product 1

HCID 160398643-{[6-(azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-5-[(1-methylethyl)oxy]-N-(5-methylpyrazin-2-yl)benzamideYield 32.2%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
160 °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 2-(azetidin-1-ylcarbonyl)-5-bromopyridine (181 mg, 0.75 mmol) and bromotris(triphenylphosphine)copper (93 mg, 0.1 mmol) in DMA (5 mL) and the stirred mixture heated at 160° C. in a microwave reactor for 4 hours. The mixture was cooled to RT and ambient pressure, partitioned between water (75 mL) and ethyl acetate (50 mL), the organic layer washed with brine, dried (MgSO4) and evaporated in vacuo. The residue was chromatographed on silica, eluting with 75% ethyl acetate in isohexane, to give the desired compound (crystallised from ether) (72 mg). 1H NMR δ (CDCl3): 1.3 (d, 6H), 2.3 (m, 2H), 2.5 (s, 3H), 4.2 (t, 2H), 4.5 (m, 1H), 4.65 (t, 2H), 6.7 (s, 1H), 7.05 (s, 1H), 7.2 (s, 1H), 7.3 (d, 1H), 8.0 (br, 2H), 8.3 (br, 2H) and 9.45 (s, 1H). m/z 448 (M+H)+. Mpt (melting onset) 125.7° C.

Workup

  1. temperatureThe mixture was cooled to RT
  2. customambient pressure, partitioned between water (75 mL) and ethyl acetate (50 mL)
  3. washthe organic layer washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated in vacuo
  6. customThe residue was chromatographed on silica
  7. washeluting with 75% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-1e25466e4464477a865b9643b92f3d03
Source dataset
uspto-grants-2011_07
Patent number
US07977328B2

Reaction notes

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