Cesium carbonate → 3-(1-Benzothien-5-yloxy)-N-(1-methyl-1H-pyrazol-3-yl)-5-{(1S)-1-methyl-2-[(triisopropylsilyl)oxy]ethoxy}benzamide

HRID 548658Notes

Reaction equation

HRID 548658 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]([CH3:37])[CH2:25][O:26][Si:27]([CH:34]([CH3:36])[CH3:35])([CH:31]([CH3:33])[CH3:32])[CH:28]([CH3:30])[CH3:29])[CH:22]=1)[C:11]([NH:13][C:14]1[CH:18]=[CH:17][N:16]([CH3:19])[N:15]=1)=[O:12].Br[C:39]1[CH:40]=[CH:41][C:42]2[S:46][CH:45]=[CH:44][C:43]=2[CH:47]=1>CC(N(C)C)=O>[S:46]1[C:42]2[CH:41]=[CH:40][C:39]([O:7][C:8]3[CH:9]=[C:10]([CH:20]=[C:21]([O:23][C@@H:24]([CH3:37])[CH2:25][O:26][Si:27]([CH:34]([CH3:36])[CH3:35])([CH:28]([CH3:29])[CH3:30])[CH:31]([CH3:33])[CH3:32])[CH:22]=3)[C:11]([NH:13][C:14]3[CH:18]=[CH:17][N:16]([CH3:19])[N:15]=3)=[O:12])=[CH:47][C:43]=2[CH:44]=[CH:45]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 27765785-Bromo-1-benzothiopheneHCID 536296193-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)-5-[((1S)-1-methyl-2-{[tris(1-methylethyl)silyl]oxy}ethyl)oxy]benzamide

Product 1

HCID 576631673-(1-Benzothien-5-yloxy)-N-(1-methyl-1H-pyrazol-3-yl)-5-{(1S)-1-methyl-2-[(triisopropylsilyl)oxy]ethoxy}benzamideYield 34.5%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
200 °C

Procedure

Cesium carbonate (163 mg, 0.05 mmol) was added to a solution of 3-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)-5-{(1S)-1-methyl-2-[(triisopropylsilyl)oxy]ethoxy}benzamide (225 mg, 0.5 mmol), bromotris(triphenylphosphine)copper1 (93 mg, 0.1 mmol) and 5-bromobenzothiophene (107 mg, 0.5 mmol) in dimethylacetamide (2.5 mL) and the stirred mixture heated at 200° C. in a “Biotage Initiator” microwave for 4 hours. The mixture was cooled to ambient temperature and pressure, poured onto water (40 mL) and extracted with ethyl acetate (3×15 mL), the combined organic layers washed with brine, dried (MgSO4) and evaporated to a residue which was chromatographed on silica, eluting with 40% ethyl acetate in isohexane, to give the desired compound (100 mg).

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. additionpressure, poured onto water (40 mL)
  3. extractionextracted with ethyl acetate (3×15 mL)
  4. washthe combined organic layers washed with brine
  5. dry with materialdried (MgSO4)
  6. customevaporated to a residue which
  7. customwas chromatographed on silica
  8. washeluting with 40% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-cc02142da8e24b1bb23cc6fda2e316ce
Source dataset
uspto-grants-2011_05
Patent number
US07943607B2

Reaction notes

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