Diisopropylamine → HCID 57678432, compound

HRID 491490Notes

Reaction equation

HRID 491490 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(NC(C)C)(C)C.[C:29]([CH:31]1[CH2:33][CH2:32]1)#[CH:30]>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.O>[CH:31]1([C:29]#[C:30][C:2]2[C:3]([O:20][CH3:21])=[CH:4][C:5]([CH:17]([CH3:19])[CH3:18])=[C:6]([CH:16]=2)[O:7][C:8]2[C:9]([NH2:15])=[N:10][C:11]([NH2:14])=[N:12][CH:13]=2)[CH2:33][CH2:32]1

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 138823CyclopropylacetyleneHCID 159538025-(5-Iodo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine

Product 1

HCID 57678432HCID 57678432, compoundYield 89.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

5-(5-Iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidine-2,4-diamine (873 g, 2 mmol), bis(triphenylphosphine)palladium dichloride (140 mg, 0.2 mmol), and CuI (19 mg, 0.1 mmol) were added to 15 mL of degassed diisopropylamine under nitrogen in a screw cap flask. Ethynylcyclopropane (0.25 mL, 3 mmol) was added, and the flask was sealed and heated to 70° C. for 18 hours. The reaction mixture was cooled, poured into water, and extracted into dichloromethane. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was chromatographed on 100 g of flash silica (2%-3% MeOH/CH2Cl2) to give 605 mg of 5-(5-cyclopropylethynyl-2-isopropyl-4-methoxy-phenoxy)-pyrimidine-2,4-diamine. MP 225.5-226.8° C.; MS (M+H)=339.

Workup

  1. customcap flask
  2. customthe flask was sealed
  3. temperatureThe reaction mixture was cooled
  4. extractionextracted into dichloromethane
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was chromatographed on 100 g of flash silica (2%-3% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-f678434f154d47a1b84aed82c0f37a0c
Source dataset
uspto-grants-2009_05
Patent number
US07531547B2

Reaction notes

Loading…