Triethylamine → 5-Bromo-6-chloro-3-trimethylsilanylethynyl-pyrazin-2-ylamine

HRID 523023Notes

Reaction equation

HRID 523023 reaction equation
Br[C:2]1[C:3]([NH2:10])=[N:4][C:5]([Cl:9])=[C:6]([Br:8])[N:7]=1.C(N(CC)CC)C.[Si:18]([C:22]#[CH:23])([CH3:21])([CH3:20])[CH3:19]>C1COCC1.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:23]#[C:22][Si:18]([CH3:21])([CH3:20])[CH3:19])[C:3]([NH2:10])=[N:4][C:5]=1[Cl:9]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 457896623,5-Dibromo-6-chloropyrazin-2-amine

Product 1

HCID 900409205-Bromo-6-chloro-3-trimethylsilanylethynyl-pyrazin-2-ylamineYield 75.4%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-5 °C

Procedure

To a stirred solution of 3,5-dibromo-6-chloro-pyrazin-2-ylamine (5.0 g, 17.42 mmol) in anhydrous THF (40 mL) was added triethylamine (3.52 g, 34.84 mmol) and CuI (0.333 g, 1.74 mmol). The mixture was degassed with bubbling argon for 10 min then evacuated and back-filled with argon. It was purged thoroughly with argon for 20 min and Pd(PPh3)2Cl2 (0.355 g, 0.52 mmol) was added. The reaction mixture was cooled to −5° C., TMS-acetylene (1.90 g, 19.16 mmol) was added very slowly and the temperature was slowly increased to 15° C. during 3 h. The reaction mixture was diluted with water (30 mL) and extracted with ethyl acetate (100 mL×3). The combined organic layers were concentrated in vacuo then purified by chromatography (silica, 5% ethyl acetate in hexanes) to give 5-bromo-6-chloro-3-trimethylsilanylethynyl-pyrazin-2-ylamine (4.0 g, 75%) as a yellow solid. LC-MS: 304.0 (M+H).

Workup

  1. customThe mixture was degassed with bubbling argon for 10 min
  2. customthen evacuated
  3. additionback-filled with argon
  4. customIt was purged thoroughly with argon for 20 min
  5. temperaturethe temperature was slowly increased to 15° C. during 3 h
  6. extractionextracted with ethyl acetate (100 mL×3)
  7. concentrationThe combined organic layers were concentrated in vacuo
  8. customthen purified by chromatography (silica, 5% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-129dc6f612ac430b83134446eb3765bd
Source dataset
uspto-grants-2016_05
Patent number
US09334278B2

Reaction notes

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