Lithium Chloride → HCID 16070829, compound

HRID 1710726Notes

Reaction equation

HRID 1710726 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]([CH:11]2[CH2:13][CH2:12]2)=[O:10])[CH:5]=[N:4][C:3]=1[C:14]1[CH:19]=[CH:18][N:17]=[CH:16][C:15]=1[F:20].[F:21][C:22]1[C:23]([Sn](CCCC)(CCCC)CCCC)=[N:24][CH:25]=[C:26]([F:32])[C:27]=1[Si](C)(C)C.[Cl-].[Li+]>[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.O1CCOCC1>[F:21][C:22]1[C:23]([C:2]2[N:7]=[C:6]([NH:8][C:9]([CH:11]3[CH2:13][CH2:12]3)=[O:10])[CH:5]=[N:4][C:3]=2[C:14]2[CH:19]=[CH:18][N:17]=[CH:16][C:15]=2[F:20])=[N:24][CH:25]=[C:26]([F:32])[CH:27]=1

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 59457593HCID 59457593, compoundHCID 68498700HCID 68498700, compound

Product 1

HCID 16070829HCID 16070829, compoundYield 26%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

In a Schienk tube were charged N-[6-chloro-5-(3-fluoropyridin-4-yl)pyrazin-2-yl]cyclopropanecarboxamide (Preparation 10, 70 mg, 0.24 mmol), 3,5-difluoro-2-tributylstannanyl-4-trimethylsilylpyridine (prepared according to the procedure described in J. Med. Chem. 2006, 49(1), 35-38) (177.6 mg, 0.48 mmol), copper(I) iodide (2.28 mg, 12 μmol), lithium chloride (previously dried) (10.14 mg, 0.24 mmol) and dioxane (1.5 mL). The mixture was submitted to three vacuum-argon cycles, then tetrakis(triphenylphosphine)palladium(0) (27.64 mg, 24 μmol) was added and the mixture purged in the same way and the mixture was heated at 100° C. for 18 h. The reaction was concentrated, ethyl acetate (1 ml) and HCl 2N (5 ml) were added and the reaction was stirred at room temperature for 1 h. Ethyl acetate was added, the organic layer was separated, and the aqueous phase was extracted with ethyl acetate. The combined extracts were washed with water and the organic layer was dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography on silica flash, using dichloromethane/methanol (100:1) to yield the title compound (23 mg, 26%) as a yellowish solid.

Workup

  1. customprepared
  2. customthe mixture purged in the same way
  3. concentrationThe reaction was concentrated
  4. additionethyl acetate (1 ml) and HCl 2N (5 ml) were added
  5. additionEthyl acetate was added
  6. customthe organic layer was separated
  7. extractionthe aqueous phase was extracted with ethyl acetate
  8. washThe combined extracts were washed with water
  9. dry with materialthe organic layer was dried over magnesium sulphate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by column chromatography on silica flash

Sources & evidence

ORD record
ord-8fc97e576c5a4e30bb774de790052760
Source dataset
uspto-grants-2010_09
Patent number
US07790728B2

Reaction notes

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