Cesium carbonate → 3-{[6-(Azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-5-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-methylethyl)oxy]-N-1,3-thiazol-2-ylbenzamide

HRID 1990116Notes

Reaction equation

HRID 1990116 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:7][C:8]([Si:11]([CH3:33])([CH3:32])[O:12][CH2:13][C@@H:14]([O:16][C:17]1[CH:18]=[C:19]([CH:28]=[C:29]([OH:31])[CH:30]=1)[C:20]([NH:22][C:23]1[S:24][CH:25]=[CH:26][N:27]=1)=[O:21])[CH3:15])([CH3:10])[CH3:9].[N:34]1([C:38]([C:40]2[CH:45]=[CH:44][C:43](Br)=[CH:42][N:41]=2)=[O:39])[CH2:37][CH2:36][CH2:35]1>CC(N(C)C)=O>[N:34]1([C:38]([C:40]2[N:41]=[CH:42][C:43]([O:31][C:29]3[CH:28]=[C:19]([CH:18]=[C:17]([O:16][C@@H:14]([CH3:15])[CH2:13][O:12][Si:11]([C:8]([CH3:9])([CH3:10])[CH3:7])([CH3:33])[CH3:32])[CH:30]=3)[C:20]([NH:22][C:23]3[S:24][CH:25]=[CH:26][N:27]=3)=[O:21])=[CH:44][CH:45]=2)=[O:39])[CH2:37][CH2:36][CH2:35]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 536296172-(Azetidin-1-ylcarbonyl)-5-bromopyridineHCID 59127134HCID 59127134, compound

Product 1

HCID 591271333-{[6-(Azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-5-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-methylethyl)oxy]-N-1,3-thiazol-2-ylbenzamide

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
160 °C

Procedure

Cesium carbonate (0.478 g, 1.47 mmol) was added to a mixture of 3-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-methylethyl)oxy]-5-hydroxy-N-1,3-thiazol-2-ylbenzamide (200 mg, 0.49 mmol), bromotris(triphenylphosphine)copper (46 mg, 0.049 mmol) and 2-(azetidin-1-ylcarbonyl)-5-bromopyridine (130 mg, 5.39 mmol) in DMA (5.0 mL) and the stirred mixture heated at 160° C. in a ‘Biotage initiator Microwave’ for 3 hours. The mixture was allowed to reach RT and pressure and was partitioned between ethyl acetate (50 mL) and water (50 mL). The ethyl acetate layer was separated, washed with water (5×50 mL), brine (50 mL), dried (MgSO4) and evaporated to a residue which was chromatographed on silica, eluting with a gradient of 0-100% ethyl acetate in isohexane, to give the desired compound. (47 mg).

Workup

  1. customto reach RT
  2. custompressure and was partitioned between ethyl acetate (50 mL) and water (50 mL)
  3. customThe ethyl acetate layer was separated
  4. washwashed with water (5×50 mL), brine (50 mL)
  5. dry with materialdried (MgSO4)
  6. customevaporated to a residue which
  7. customwas chromatographed on silica
  8. washeluting with a gradient of 0-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-d083a5e2d5ef423a9be4d75a75b54de1
Source dataset
uspto-grants-2010_01
Patent number
US07642259B2

Reaction notes

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