HCID 86682317, compound → HCID 71525480, compound

HRID 1477766Notes

Reaction equation

HRID 1477766 reaction equation
[CH3:1][C:2]([NH:10][C:11]([C:13]1[CH:18]=[N:17][C:16](Br)=[C:15]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=2)[N:14]=1)=[O:12])([C:4]1[N:8]=[C:7]([CH3:9])[O:6][N:5]=1)[CH3:3].[Br-].[CH:28]1([Zn+])[CH2:30][CH2:29]1>C1COCC1>[CH3:1][C:2]([NH:10][C:11]([C:13]1[CH:18]=[N:17][C:16]([CH:28]2[CH2:30][CH2:29]2)=[C:15]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=2)[N:14]=1)=[O:12])([C:4]1[N:8]=[C:7]([CH3:9])[O:6][N:5]=1)[CH3:3]

Participants

4

Reactant 2

HCID 86682317HCID 86682317, compoundHCID 178419765HCID 178419765, compound

Product 1

HCID 71525480HCID 71525480, compoundYield 26.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

5-Bromo-6-(3-chloro-phenyl)-pyrazine-2-carboxylic acid [1-methyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide (0.100 g, 229 μmol), and tetrakis-(triphenyl-phosphine)palladium (13.2 mg, 11.4 μmol) were dissolved in THF (2.5 mL). Cyclopropylzinc(II)bromide (0.5M in THF, 1800 μl, 900 μmol) was added drop by drop at 0° C. and the reaction mixture was stirred at room temperature for 1.5 hours and at reflux temperature overnight. The mixture was partitioned between water and ethyl acetate and the organic phase was dried with MgSO4, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 10 g, 5% to 40% ethyl acetate in n-heptane) to give the desired product (24 mg, 26%) as white solid; MS (EI): 398.2 (M+H). As side product 11 mg of 6-(3-chloro-phenyl)-5-cyclopropyl-pyrazine-2-carboxylic acid (cyano-dimethyl-methyl)-amide (Example 2) was isolated.

Workup

  1. temperatureat reflux temperature overnight
  2. customThe mixture was partitioned between water and ethyl acetate
  3. dry with materialthe organic phase was dried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (silica gel, 10 g, 5% to 40% ethyl acetate in n-heptane)

Sources & evidence

ORD record
ord-88b2751e40c745eaa8285bb4a3342c15
Source dataset
uspto-grants-2016_08
Patent number
US09403808B2

Reaction notes

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