Trimethylsilylacetylene → HCID 57678393, compound

HRID 491486Notes

Reaction equation

HRID 491486 reaction equation
I[C:2]1[C:3]([O:20][CH3:21])=[CH:4][C:5]([CH:17]([CH3:19])[CH3:18])=[C:6]([CH:16]=1)[O:7][C:8]1[C:9]([NH2:15])=[N:10][C:11]([NH2:14])=[N:12][CH:13]=1.[CH3:22][Si:23]([C:26]#[CH:27])([CH3:25])[CH3:24].C(N(C(C)C)CC)(C)C>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.[Cu]I.C1COCC1>[CH:17]([C:5]1[CH:4]=[C:3]([O:20][CH3:21])[C:2]([C:27]#[C:26][Si:23]([CH3:25])([CH3:24])[CH3:22])=[CH:16][C:6]=1[O:7][C:8]1[C:9]([NH2:15])=[N:10][C:11]([NH2:14])=[N:12][CH:13]=1)([CH3:19])[CH3:18]

Participants

7

Reactant 3

HCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 159538025-(5-Iodo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine

Product 1

HCID 57678393HCID 57678393, compoundYield 91.8%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

5-(5-Iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidine-2,4-diamine (2.0 g, 5 mmol), bis(triphenylphosphine)-Palladium dichloride (700 mg, 1 mmol) and CuI (100 mg, 0.5 mmol) were added to 14 mL dry THF under nitrogen. Trimethylsilyl acetylene (1.4 mL, 10 mmol) was added, followed by 7 mL diisopropylethylamine. The reaction mixture was stirred at 50° C. under nitrogen for 17 hours, then was allowed to cool for two hours with stirring. The reaction mixture was poured into 15% aqueous NHCl and extracted into EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was chromatographed on 150 g of flash silica (2%-4% MeOH/CH2Cl2) to give 1.70 g of 5-(2-Isopropyl-4-methoxy-5-trimethylsilanylethynyl-phenoxy)-pyrimidine-2,4-diamine, MS (M+H)=371.

Workup

  1. temperatureto cool for two hours
  2. stirringwith stirring
  3. additionThe reaction mixture was poured into 15% aqueous NHCl
  4. extractionextracted into EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was chromatographed on 150 g of flash silica (2%-4% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-88b2d1ea6c264e2789004622f8974eaf
Source dataset
uspto-grants-2009_05
Patent number
US07531547B2

Reaction notes

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