Potassium Carbonate → HCID 86666159, compound

HRID 2171284Notes

Reaction equation

HRID 2171284 reaction equation
C(=O)([O-])[O-].[K+].[K+].[Cl:7][C:8]1[N:15]=[C:14](Cl)[C:13]([F:17])=[CH:12][C:9]=1[C:10]#[N:11].[NH2:18][C@@H:19]1[CH2:24][CH2:23][CH2:22][CH2:21][C@@H:20]1[NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29]>C1COCC1>[Cl:7][C:8]1[N:15]=[C:14]([NH:18][C@@H:19]2[CH2:24][CH2:23][CH2:22][CH2:21][C@@H:20]2[NH:25][C:26](=[O:32])[O:27][C:28]([CH3:30])([CH3:29])[CH3:31])[C:13]([F:17])=[CH:12][C:9]=1[C:10]#[N:11]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 27338492,6-Dichloro-5-fluoro-3-pyridinecarbonitrile

Product 1

HCID 86666159HCID 86666159, compoundYield 59.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Potassium carbonate (3.62 g) and 2,6-dichloro-5-fluoronicotinonitrile (5.00 g) were added to a THF (50 ml) solution containing tert-butyl ((1S,2R)-2-aminocyclohexyl)carbamate (5.61 g), followed by reflux at 60° C. for 8 hours. Then, the solvent was distilled away at 70° C. 1,4-dioxane (100 ml) was added to the resulting solution, followed by stirring at 100° C. for 10 hours. The reaction solution was adjusted to room temperature. Ethyl acetate and 2M hydrochloric acid were added to the reaction solution. The organic layers were collected. The organic layers were washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure and the obtained residue was purified by silica gel chromatography (n-hexane:ethyl acetate=9:1 to 2:1). Diisopropyl ether was added to the obtained oily matter and a solid precipitate was collected by filtration. A white solid of tert-butyl ((1S,2R)-2-((6-chloro-5-cyano-3-fluoropyridin-2-yl)amino)cyclohexyl)carbamate (5.77 g) was thus obtained.

Workup

  1. distillationThen, the solvent was distilled away at 70° C
  2. addition1,4-dioxane (100 ml) was added to the resulting solution
  3. customwas adjusted to room temperature
  4. additionEthyl acetate and 2M hydrochloric acid were added to the reaction solution
  5. customThe organic layers were collected
  6. washThe organic layers were washed with saturated saline
  7. dry with materialdried over anhydrous sodium sulfate
  8. distillationThe solvent was distilled away under reduced pressure
  9. customthe obtained residue was purified by silica gel chromatography (n-hexane:ethyl acetate=9:1 to 2:1)
  10. additionDiisopropyl ether was added to the obtained oily matter
  11. filtrationa solid precipitate was collected by filtration

Sources & evidence

ORD record
ord-bd1ec680f5a94505a06f2fdacf72c1b9
Source dataset
uspto-grants-2015_06
Patent number
US09051310B2

Reaction notes

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