2-Bromo-5-fluoropyridine → HCID 59457554, compound

HRID 1710724Notes

Reaction equation

HRID 1710724 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.C[Sn](C)C.C[Sn](C)C.Cl[C:18]1[N:23]=[C:22]([NH:24][C:25]([CH:27]2[CH2:29][CH2:28]2)=[O:26])[CH:21]=[N:20][C:19]=1[C:30]1[CH:35]=[CH:34][N:33]=[CH:32][C:31]=1[F:36]>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.C1(C)C=CC=CC=1>[F:36][C:31]1[CH:32]=[N:33][CH:34]=[CH:35][C:30]=1[C:19]1[N:20]=[CH:21][C:22]([NH:24][C:25]([CH:27]2[CH2:29][CH2:28]2)=[O:26])=[N:23][C:18]=1[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 27831712-Bromo-5-fluoropyridineHCID 6327618HexamethylditinHCID 59457593HCID 59457593, compound

Product 1

HCID 59457554HCID 59457554, compoundYield 15%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

An oven dried resealable Schlenk tube was charged with 2-bromo-5-fluoropyridine (0.52 g, 2.9 mmol), hexamethylditin (0.97 g, 2.9 mmol) and toluene (15 mL). The Schlenk tube was subjected to three cycles of evacuation-backfilling with argon, and tetrakis(triphenylphosphine)palladium (0.162 g, 0.14 mmol) was added. After three new cycles of evacuation-backfilling with argon, the Schlenk tube was capped and placed in an oil bath at 80° C. After 5 hours, the mixture was cooled and N-[6-chloro-5-(3-fluoropyridin-4-yl)pyrazin-2-yl]cyclopropanecarboxamide (Preparation 10, 0.424 g, 1.45 mmol) and further tetrakis(triphenylphosphine)palladium (0.162 g, 0.14 mmol) were added. The mixture was heated to 110° C. and stirred overnight. The mixture was concentrated, ethyl acetate was added and the organic solution was washed with 4% aqueous sodium bicarbonate solution, brine, dried (MgSO4) and evaporated. The residue was purified by silica gel chromatography (CH2Cl2/MeOH 98:2). The appropriate fractions were concentrated to leave a solid which, upon washing with a mixture of hexane and ethyl acetate, gave the title compound (0.077 g, 15%) as an off-white solid.

Workup

  1. customAn oven dried resealable Schlenk tube
  2. additionwas added
  3. customAfter three new cycles of evacuation-backfilling with argon, the Schlenk tube was capped
  4. customplaced in an oil bath at 80° C
  5. temperaturethe mixture was cooled
  6. concentrationThe mixture was concentrated
  7. additionethyl acetate was added
  8. washthe organic solution was washed with 4% aqueous sodium bicarbonate solution, brine
  9. dry with materialdried (MgSO4)
  10. customevaporated
  11. customThe residue was purified by silica gel chromatography (CH2Cl2/MeOH 98:2)
  12. concentrationThe appropriate fractions were concentrated
  13. customto leave a solid which
  14. washupon washing with a mixture of hexane and ethyl acetate

Sources & evidence

ORD record
ord-440264e656504ba282ffbf0fdd399a1e
Source dataset
uspto-grants-2010_09
Patent number
US07790728B2

Reaction notes

Loading…