Triethylamine → 3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-5-[(1-methyl-1H-indol-5-yl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 548657Notes

Reaction equation

HRID 548657 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]([CH3:28])[O:11][C:12]1[CH:13]=[C:14]([CH:24]=[C:25]([OH:27])[CH:26]=1)[C:15]([NH:17][C:18]1[CH:22]=[CH:21][N:20]([CH3:23])[N:19]=1)=[O:16])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:29][N:30]1[C:38]2[C:33](=[CH:34][C:35](B(O)O)=[CH:36][CH:37]=2)[CH:32]=[CH:31]1.C(N(CC)CC)C>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Si:1]([O:8][CH2:9][C@H:10]([CH3:28])[O:11][C:12]1[CH:13]=[C:14]([CH:24]=[C:25]([O:27][C:35]2[CH:34]=[C:33]3[C:38](=[CH:37][CH:36]=2)[N:30]([CH3:29])[CH:31]=[CH:32]3)[CH:26]=1)[C:15]([NH:17][C:18]1[CH:22]=[CH:21][N:20]([CH3:23])[N:19]=1)=[O:16])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27598671-Methyl-1H-indole-5-boronic acidHCID 536296323-[((1S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-1-methylethyl)oxy]-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Product 1

HCID 576631753-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethoxy)-5-[(1-methyl-1H-indol-5-yl)oxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamideYield 47.9%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 3-((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyloxy)-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (202 mg, 0.5 mmol), 1-methylindole-5-boronic acid (131 mg, 0.75 mmol), copper (II) acetate (138 mg, 0.75 mmol), triethylamine (0.35 mL, 2.5 mmol) and freshly activated 4A molecular sieves (1 g) in DCM (10 mL) was stirred at ambient temperature and under ambient atmosphere for 2 days. The reaction mixture was filtered through Celite, washed with DCM (2×10 mL), the DCM removed in vacuo and the residual oil partitioned between ethyl acetate (25 mL) and water (25 mL). The ethyl acetate layer was separated, washed with aqueous sodium hydrogen carbonate solution, brine, dried (MgSO4) and evaporated to a residue which was chromatographed on silica, eluting with 40% ethyl acetate in iso-hexane, to give the desired compound (128 mg).

Workup

  1. filtrationThe reaction mixture was filtered through Celite
  2. washwashed with DCM (2×10 mL)
  3. customthe DCM removed in vacuo
  4. customthe residual oil partitioned between ethyl acetate (25 mL) and water (25 mL)
  5. customThe ethyl acetate layer was separated
  6. washwashed with aqueous sodium hydrogen carbonate solution, brine
  7. dry with materialdried (MgSO4)
  8. customevaporated to a residue which
  9. customwas chromatographed on silica
  10. washeluting with 40% ethyl acetate in iso-hexane

Sources & evidence

ORD record
ord-ab2bf15035e043dfbd587cbebb92ac92
Source dataset
uspto-grants-2011_05
Patent number
US07943607B2

Reaction notes

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