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Diisopropyl Ether → 4-Trimethylsilanylethynyl-thiazole-2-carboxylic acid-(6-acetyl-3-methoxy-2-methyl-phenyl)-amide

HRID 880741
Notes
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Reaction equation

HRID 880741 reaction equation
[C:1]([C:4]1[C:9]([NH:10][C:11]([C:13]2[S:14][CH:15]=[C:16](Br)[N:17]=2)=[O:12])=[C:8]([CH3:19])[C:7]([O:20][CH3:21])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[C:22]([Si:24]([CH3:27])([CH3:26])[CH3:25])#[CH:23].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC(C)C)(C)C>C(NC(C)C)(C)C.[Cu](I)I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([C:4]1[C:9]([NH:10][C:11]([C:13]2[S:14][CH:15]=[C:16]([C:23]#[C:22][Si:24]([CH3:27])([CH3:26])[CH3:25])[N:17]=2)=[O:12])=[C:8]([CH3:19])[C:7]([O:20][CH3:21])=[CH:6][CH:5]=1)(=[O:3])[CH3:2]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 7914Diisopropyl EtherHCID 11776TriphenylphosphineHCID 66111TrimethylsilylacetyleneHCID 56605318N-(6-acetyl-3-methoxy-2-methylphenyl)-4-bromo-1,3-thiazole-2-carboxamide

Product 1

HCID 672140214-Trimethylsilanylethynyl-thiazole-2-carboxylic acid-(6-acetyl-3-methoxy-2-methyl-phenyl)-amideYield 84%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 7912DiisopropylamineSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of compound 207b (10.12 g, 1 eq.) in diisopropylamine (40 mL) were added ethynyltrimethylsilane (5.7 mL, 1.5 eq.), triphenylphosphine (0.283 g, 0.04 eq.), copper iodide (0.206 g, 0.04 eq.), and PdCl2(PPh3)2 (0.38 g, 0.02 eq.). The mixture was stirred under nitrogen and heated to 80° C. (external temperature). After 10 min, the solvent was refluxed, and the mixture solidified and turned brown grey. DIPA (20 mL) was added to solubilize the reaction mixture. After 2.5 hrs, the reaction was complete and the mixture cooled down to room temperature. Diisopropyl ether (20 mL) was added. A grey solid was recovered by filtration, dissolved in dichloromethane, and washed with water. The organic layer was dried over Na2SO4, filtered, and concentrated to give black solid. The residue was purified by chromatography on silica gel (dichloromethane) to give compound 208b as a beige solid in 84% yield. 1H NMR (CDCl3, 400 MHz) δ (ppm) 0.29 (s, 9H), 2.13 (s, 3H), 2.58 (s, 3H), 3.93 (s, 3H), 6.81 (d, J=8.78 Hz, 1H), 7.69 (s, 1H), 7.76 (d, J=8.78 Hz, 1H), 11.05 (s, 1H).

Workup

  1. temperaturethe solvent was refluxed
  2. additionDIPA (20 mL) was added
  3. waitAfter 2.5 hrs
  4. temperaturethe mixture cooled down to room temperature
  5. filtrationA grey solid was recovered by filtration
  6. dissolutiondissolved in dichloromethane
  7. washwashed with water
  8. dry with materialThe organic layer was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give black solid
  12. customThe residue was purified by chromatography on silica gel (dichloromethane)

Sources & evidence

ORD record
ord-c5047986935045fd80e931a251674fb4
Source dataset
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08993595B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes