Tetrahydrofuran → HCID 16119575, compound

HRID 491489Notes

Reaction equation

HRID 491489 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.C[Si](C)(C)[C:24]#[C:25][CH3:26].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1>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(O)C>[CH:17]([C:5]1[CH:4]=[C:3]([O:20][CH3:21])[C:2]([C:24]#[C:25][CH3:26])=[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 4

HCID 8028TetrahydrofuranHCID 803631-(Trimethylsilyl)prop-1-yne2×HCID 2724141Tetrabutylammonium Fluoride2×HCID 159538025-(5-Iodo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine

Product 1

HCID 16119575HCID 16119575, compoundYield 118.5%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 702EthanolSolvent

Conditions

Temperature
50 °C

Procedure

5-(5-Iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidine-2,4-diamine (1.0 g, 2.5 mmol), bis(triphenylphosphine)palladium dichloride (290 mg, 0.25 mmol), 1-(trimethylsilyl)-1-propyne (0.44 mL, 3 mmol) and tetrabutyl ammonium fluoride (3 mL, 3 mmol) were added to 20 mL dry THF under nitrogen. The reaction mixture was stirred under nitrogen at 50° C. for 22 hours, then 150 mg of bis(triphenylphosphine)-Palladium dichloride, 0.22 mL of 1-(trimethylsilyl)-1-propyne and 1.5 mL tetrabutyl ammonium fluoride, and 0.1 mL ethanol were added to the reaction mixture. The reaction mixture was stirred under nitrogen for 18 hours at 50° C. The reaction mixture was cooled and poured into saturated aqueous NaHCO4 and extracted into EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was chromatographed on 125 g of flash silica (2%-4% MeOH/CH2Cl2) to give 925 mg of 5-(2-isopropyl-4-methoxy-5-prop-1-ynyl-phenoxy)-pyrimidine-2,4-diamine, MS (M+H)=313.

Workup

  1. stirringThe reaction mixture was stirred under nitrogen for 18 hours at 50° C
  2. temperatureThe reaction mixture was cooled
  3. extractionextracted into EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was chromatographed on 125 g of flash silica (2%-4% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-97b35f3327824a2dae51866616c27a0c
Source dataset
uspto-grants-2009_05
Patent number
US07531547B2

Reaction notes

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