Cesium carbonate → 3-{[5-(azetidin-1-ylcarbonyl)-4-methyl-1,3-thiazol-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide

HRID 1990262Notes

Reaction equation

HRID 1990262 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[OH:7][C:8]1[CH:9]=[C:10]([CH:20]=[C:21]([O:23][C@H:24]2[CH2:28][CH2:27][O:26][CH2:25]2)[CH:22]=1)[C:11]([NH:13][C:14]1[CH:18]=[CH:17][N:16]([CH3:19])[N:15]=1)=[O:12].[N:29]1([C:33]([C:35]2[S:39][C:38](Br)=[N:37][C:36]=2[CH3:41])=[O:34])[CH2:32][CH2:31][CH2:30]1>C(#N)C>[N:29]1([C:33]([C:35]2[S:39][C:38]([O:7][C:8]3[CH:9]=[C:10]([CH:20]=[C:21]([O:23][C@H:24]4[CH2:28][CH2:27][O:26][CH2:25]4)[CH:22]=3)[C:11]([NH:13][C:14]3[CH:18]=[CH:17][N:16]([CH3:19])[N:15]=3)=[O:12])=[N:37][C:36]=2[CH3:41])=[O:34])[CH2:30][CH2:31][CH2:32]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 536296655-(Azetidin-1-ylcarbonyl)-2-bromo-4-methyl-1,3-thiazoleHCID 59127171HCID 59127171, compound

Product 1

HCID 536295703-{[5-(azetidin-1-ylcarbonyl)-4-methyl-1,3-thiazol-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide

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-N-(1-methyl-1H-pyrazol-3-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide (152 mg, 0.5 mmol) and 5-(azetidin-1-ylcarbonyl)-2-bromo-4-methyl-1,3-thiazole (144 mg, 0.55 mmol) in acetonitrile (5 mL) and the stirred mixture heated at 120° C. in a microwave reactor for 2 hours. The mixture was allowed to cool, the acetonitrile evaporated in vacuo, and 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 ethyl acetate, to give the desired compound as a solid which was further crystallised from an ethyl acetate/isohexane mixture (122 mg).

Workup

  1. temperatureto cool
  2. customthe 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 ethyl acetate

Sources & evidence

ORD record
ord-acba1ebdf7f846938fd42baa4d42a4bd
Source dataset
uspto-grants-2010_01
Patent number
US07642259B2

Reaction notes

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