Trimethyl-2-propynylsilane → 5-Bromo-6-chloro-3-(3-(trimethylsilyl)prop-1-ynyl)pyrazin-2-amine

HRID 1521903Notes

Reaction equation

HRID 1521903 reaction equation
Br[C:2]1[C:3]([NH2:10])=[N:4][C:5]([Cl:9])=[C:6]([Br:8])[N:7]=1.[CH3:11][Si:12]([CH3:17])([CH3:16])[CH2:13][C:14]#[CH:15]>C1COCC1.O.[Cl-].[Na+].O.[Cu]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>[Br:8][C:6]1[N:7]=[C:2]([C:15]#[C:14][CH2:13][Si:12]([CH3:17])([CH3:16])[CH3:11])[C:3]([NH2:10])=[N:4][C:5]=1[Cl:9]

Participants

8

Reactant 2

HCID 83378Trimethyl-2-propynylsilaneHCID 457896623,5-Dibromo-6-chloropyrazin-2-amine

Product 1

HCID 866903235-Bromo-6-chloro-3-(3-(trimethylsilyl)prop-1-ynyl)pyrazin-2-amine

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

3,5-Dibromo-6-chloropyrazin-2-amine (step 1) (400 mg, 1.392 mmol) in dry THF (10 ml) was degassed with nitrogen and treated with trimethyl(prop-2-ynyl)silane (0.218 ml, 1.462 mmol), TEA (0.582 ml, 4.18 mmol), CuI (26.5 mg, 0.139 mmol) and Pd(PPh3)2Cl2 (98 mg, 0.139 mmol). After stirring at room temperature for 2 hours, the reaction mixture was diluted with water (100 ml) and brine and extracted with DCM (×3). The combined organic extracts were concentrated under reduced pressure. Purification of the crude product by chromatography on silica eluting with 0-20% EtOAc in iso-hexane afforded the titled compound;

Workup

  1. extractionextracted with DCM (×3)
  2. concentrationThe combined organic extracts were concentrated under reduced pressure
  3. customPurification of the crude product by chromatography on silica eluting with 0-20% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-4f3ffdd70f8a46769ad5d758f4f47614
Source dataset
uspto-grants-2015_07
Patent number
US09073932B2

Reaction notes

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