2,2'-Bipyridine → HCID 86694126, compound

HRID 707245Notes

Reaction equation

HRID 707245 reaction equation
[Cl:1][C:2]1[C:7]([NH:8][C:9](=O)OC(C)(C)C)=[CH:6][C:5]([F:16])=[CH:4][N:3]=1.F[C:18](F)(F)[C:19](O)=O.C(=O)([O-])[O-].[Na+].[Na+].N1C=CC=CC=1C1C=CC=CN=1.C1(B(O)O)CC1>ClCCl.C(OCC)(=O)C.ClCCCl>[Cl:1][C:2]1[C:7]([NH:8][CH:9]2[CH2:19][CH2:18]2)=[CH:6][C:5]([F:16])=[CH:4][N:3]=1

Participants

9

Reactant 5

HCID 14742,2'-BipyridineHCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 2760897Cyclopropylboronic acidHCID 866941243-N-Boc-aMino-2-chloro-5-fluoropyridine2×

Product 1

HCID 86694126HCID 86694126, compoundYield 71.4%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

Tert-butyl (2-chloro-5-fluoropyridin-3-yl)carbamate (Intermediate 36) (0.500 g, 2.027 mmol) was dissolved in dichloromethane (5 mL) and treated with trifluoroacetic acid (0.5 mL). The mixture was stirred at 45° C. for 1 hour then cooled to room temperature. The solution was evaporated to dryness under reduced pressure and the crude amine partitioned between 50% saturated sodium bicarbonate (80 mL) and ethyl acetate (60 mL). The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. The solid amine intermediate was combined with anhydrous cupric acetate (0.375 g, 2.065 mmol), sodium carbonate (1.00 g, 9.43 mmol), 2,2′-bipyridyl (0.325 g, 2.081 mmol) and cyclopropylboronic acid (0.305 g, 3.55 mmol). 1,2-Dichloroethane (5 mL) was added and the mixture heated at 70° C. in air. After 2 hours, the mixture was cooled and diluted with ethyl acetate (300 mL). It was washed with a mixture of saturated ammonium chloride (50 mL), water (100 mL), and ammonium hydroxide (20 mL) before drying with magnesium sulfate and evaporating to dryness under reduced pressure. Purification using silica chromatography (hexane to ethyl acetate gradient) gave 2-chloro-N-cyclopropyl-5-fluoropyridin-3-amine (0.270 g, 1.447 mmol, 71.4% yield).

Workup

  1. temperaturethen cooled to room temperature
  2. customThe solution was evaporated to dryness under reduced pressure
  3. customthe crude amine partitioned between 50% saturated sodium bicarbonate (80 mL) and ethyl acetate (60 mL)
  4. dry with materialThe organic was dried with magnesium sulfate
  5. customevaporated to dryness under reduced pressure
  6. temperaturethe mixture heated at 70° C. in air
  7. waitAfter 2 hours
  8. temperaturethe mixture was cooled
  9. washIt was washed with a mixture of saturated ammonium chloride (50 mL), water (100 mL), and ammonium hydroxide (20 mL)
  10. dry with materialbefore drying with magnesium sulfate
  11. customevaporating to dryness under reduced pressure
  12. customPurification

Sources & evidence

ORD record
ord-1160cde122444513be8b2a6665d5c09e
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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