Methanol → HCID 16040144, compound

HRID 1175859Notes

Reaction equation

HRID 1175859 reaction equation
C(N(CC)CC)C.C([SiH](CC)CC)C.[N:15]1([S:19]([C:22]2[CH:23]=[C:24](Br)[C:25]([O:28][C:29]3[CH:30]=[C:31]([CH:41]=[C:42]([O:44][C@@H:45]([CH3:49])[CH2:46][O:47][CH3:48])[CH:43]=3)[C:32]([NH:34][C:35]3[CH:39]=[CH:38][N:37]([CH3:40])[N:36]=3)=[O:33])=[N:26][CH:27]=2)(=[O:21])=[O:20])[CH2:18][CH2:17][CH2:16]1.CO>C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:15]1([S:19]([C:22]2[CH:23]=[CH:24][C:25]([O:28][C:29]3[CH:30]=[C:31]([CH:41]=[C:42]([O:44][C@@H:45]([CH3:49])[CH2:46][O:47][CH3:48])[CH:43]=3)[C:32]([NH:34][C:35]3[CH:39]=[CH:38][N:37]([CH3:40])[N:36]=3)=[O:33])=[N:26][CH:27]=2)(=[O:21])=[O:20])[CH2:16][CH2:17][CH2:18]1

Participants

7

Reactant 4

HCID 887MethanolHCID 8471TriethylamineHCID 12052TriethylsilaneHCID 53629627HCID 53629627, compound

Product 1

HCID 16040144HCID 16040144, compoundYield 45.9%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Triethylamine (0.025 mL, 0.18 mmol) then triethylsilane (0.96 mL, 6.03 mmol) were added to palladium(II) acetate (12 mg) in DCM (2 mL) and stirred under argon for 15 mins. 3-{[5-(Azetidin-1-ylsulfonyl)-3-bromopyridin-2-yl]oxy}-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide (0.175 g, 0.3 mmol) in DCM (2 mL) was added dropwise and the reaction stirred at RT for 24 hours. Methanol was added, the reaction filtered through celite and the solvent removed in vacuo. Ethyl acetate (30 mL) was added and the mixture washed with water (30 mL), citric acid (30 mL), brine (30 mL), dried (MgSO4), filtered and the solvent removed in vacuo to give a white solid. This was chromatographed on silica, eluting with a gradient of 0-100% ethyl acetate in isohexane, to give the desired compound (69 mg).

Workup

  1. stirringthe reaction stirred at RT for 24 hours
  2. filtrationthe reaction filtered through celite
  3. customthe solvent removed in vacuo
  4. additionEthyl acetate (30 mL) was added
  5. washthe mixture washed with water (30 mL), citric acid (30 mL), brine (30 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent removed in vacuo
  9. customto give a white solid
  10. customThis was chromatographed on silica
  11. washeluting with a gradient of 0-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-8cfa842b85eb4525aa37163bcaf16161
Source dataset
uspto-grants-2010_11
Patent number
US07842694B2

Reaction notes

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