Water → HCID 178474050, compound

HRID 2282309Notes

Reaction equation

HRID 2282309 reaction equation
Br[C:2]1[N:3]=[C:4]([C:20]2[CH:25]=[CH:24][N:23]=[C:22]([NH:26][C:27](=[O:29])[CH3:28])[CH:21]=2)[S:5][C:6]=1[C:7]1[N:11]=[CH:10][N:9](COCC[Si](C)(C)C)[N:8]=1.[CH3:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[C:32]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].O.C(O)(C(F)(F)F)=O>O1CCOCC1.C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[C:32]=1[C:2]1[N:3]=[C:4]([C:20]2[CH:25]=[CH:24][N:23]=[C:22]([NH:26][C:27](=[O:29])[CH3:28])[CH:21]=2)[S:5][C:6]=1[C:7]1[NH:11][CH:10]=[N:9][N:8]=1

Participants

10

Reactant 5

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 5833222,6-Dimethylphenylboronic acidHCID 58095236N-{4-[4-bromo-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]pyridin-2-yl}acetamide

Product 1

HCID 178474050HCID 178474050, compoundYield 7.5%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

The mixture of N-{4-[4-bromo-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]pyridin-2-yl}acetamide (0.0340 g, 0.0686 mmol), 2,6-dimethylphenylboronic acid (20.6 mg, 0.137 mmol), tetrakis(triphenylphosphine)palladium (0) (9.1 mg, 0.0073 mmol), and 2 M sodium carbonate in water (0.0850 mL, 0.170 mmol) in 1,4-dioxane (2.0 mL) in capped vial was heated to 140° C. for 19 hours. Additional tetrakis(triphenylphosphine)palladium(0) (7.1 mg, 0.0057 mmol) was added and the mixture was heated to 140° C. for 1 additional day. The mixture was filtered through celite/Na2SO4, washed with EtOAc, and evaporated under reduced pressure to give a crude intermediate. The material was treated with TFA (2.0 mL, 26 mmol) in dry DCM (2.0 mL) for 5 hours. The solvent was evaporated under reduced pressure and azeotroped with toluene to give a crude product. HPLC purification gave 0.002 g of pure product as a white powder (7.5%). LCMS: (FA) ES+ 391 and ES− 389. 1H NMR (400 MHz, d4-Methanol) δ 8.73 (s, 1H), 8.40 (d, J=5.84 Hz, 1H), 8.35 (s, 1H), 7.68 (d, J=5.84 Hz, 1H), 7.20 (m, 1H), 7.11 (s, 1H), 7.09 (d, J=7.35 Hz, 1H), 2.21 (s, 3H), 2.03 (s, 6H).

Workup

  1. temperaturethe mixture was heated to 140° C. for 1 additional day
  2. filtrationThe mixture was filtered through celite/Na2SO4
  3. washwashed with EtOAc
  4. customevaporated under reduced pressure
  5. customto give a crude intermediate
  6. customThe solvent was evaporated under reduced pressure
  7. customazeotroped with toluene
  8. customto give a crude product
  9. customHPLC purification

Sources & evidence

ORD record
ord-130b164ed4d04c1ab7c92f1ef0be8bd8
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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