Triethylamine → 5-(4-Isopropylsulfonylphenyl)-3-(2-trimethylsilylethynyl)pyrazin-2-amine

HRID 68654Notes

Reaction equation

HRID 68654 reaction equation
C(N(CC)CC)C.Br[C:9]1[C:10]([NH2:27])=[N:11][CH:12]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([S:21]([CH:24]([CH3:26])[CH3:25])(=[O:23])=[O:22])=[CH:17][CH:16]=2)[N:14]=1.[CH3:28][Si:29]([C:32]#[CH:33])([CH3:31])[CH3:30]>CN(C=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:24]([S:21]([C:18]1[CH:19]=[CH:20][C:15]([C:13]2[N:14]=[C:9]([C:33]#[C:32][Si:29]([CH3:31])([CH3:30])[CH3:28])[C:10]([NH2:27])=[N:11][CH:12]=2)=[CH:16][CH:17]=1)(=[O:23])=[O:22])([CH3:26])[CH3:25]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 580843723-Bromo-5-(4-(isopropylsulfonyl)phenyl)pyrazin-2-amine

Product 1

HCID 667639185-(4-Isopropylsulfonylphenyl)-3-(2-trimethylsilylethynyl)pyrazin-2-amineYield 79.7%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Triethylamine (47.58 g, 65.54 mL, 470.2 mmol) was added to a stirred suspension of 3-bromo-5-(4-isopropylsulfonylphenyl)pyrazin-2-amine (33.5 g, 94.04 mmol) in anhydrous DMF (234.5 mL). Copper(I) iodide (2.148 g, 11.28 mmol) was then added followed by Pd(PPh3)4 (5.433 g, 4.702 mmol). The stirred mixture was cooled to 0° C. in an ice-bath and (trimethylsilyl)acetylene (12.01 g, 17.28 mL, 122.3 mmol) was added dropwise over 10 minutes. The ice bath was then removed and the mixture allowed to warm to ambient temperature over 2 hours. The mixture was poured into EtOAc/water (500 mL/300 mL) and the mixture was filtered through a pad of celite. The organic phase was separated and the aqueous layer extracted with EtOAc. The combined organics were washed with water (×1) and brine (×1), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion™, 750 g column, eluting with 0 to 15% DCM/EtOAc, dry-loaded) to give the sub-title product as a dark yellow solid (28.0 g, 78% Yield). 1H NMR (400.0 MHz, DMSO) δ 0.15 (s, 9H, 1.03 (d, 6H), 3.29 (sept, 1H), 6.80 (br s, 2H), 7.74 (d, 2H), 8.05 (d, 2H) and 8.60 (s, 1H) ppm; MS (ES+) 375.1.

Workup

  1. customThe ice bath was then removed
  2. temperatureto warm to ambient temperature over 2 hours
  3. additionThe mixture was poured into EtOAc/water (500 mL/300 mL)
  4. filtrationthe mixture was filtered through a pad of celite
  5. customThe organic phase was separated
  6. extractionthe aqueous layer extracted with EtOAc
  7. washThe combined organics were washed with water (×1) and brine (×1)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by column chromatography (ISCO Companion™, 750 g column, eluting with 0 to 15% DCM/EtOAc, dry-loaded)

Sources & evidence

ORD record
ord-a4a5f3f495f34713bc0543ef2c0ff81c
Source dataset
uspto-grants-2014_09
Patent number
US08822469B2

Reaction notes

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