1,2-Diaminocyclohexane → N4-(2-Ethylpyrazolo[1,5-a]pyridin-3-yl)tetrahydro-2H-4-pyrancarboxamide

HRID 347860

Reaction equation

HRID 347860 reaction equation
[CH2:1]([C:3]1[C:11](I)=[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][N:5]2[N:4]=1)[CH3:2].[O:13]1[CH2:18][CH2:17][CH:16]([C:19]([NH2:21])=[O:20])[CH2:15][CH2:14]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(N)CCCCC1N>[Cu](I)I.C1(C)C(C)=CC=CC=1>[CH2:1]([C:3]1[C:11]([NH:21][C:19]([CH:16]2[CH2:17][CH2:18][O:13][CH2:14][CH2:15]2)=[O:20])=[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][N:5]2[N:4]=1)[CH3:2]

Participants

7

Reactant 4

HCID 46101,2-DiaminocyclohexaneHCID 62657Potassium Phosphate, TribasicHCID 13197203Oxane-4-carboxamideHCID 161149332-Ethyl-3-iodopyrazolo[1,5-a]pyridine

Product 1

HCID 21084121N4-(2-Ethylpyrazolo[1,5-a]pyridin-3-yl)tetrahydro-2H-4-pyrancarboxamideYield 79.6%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 7237O-XyleneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-ethyl-3-iodopyrazolo[1,5-a]pyridine (350 g, 1.29 mol), tetrahydro-2H-4-pyrancarboxamide (249 g, 1.93 mol), copper iodide (49.0 g, 258 mmol), tripotassium phosphate (hydrate) (546 g, 2.57 mol), 1,2-cyclohexanediamine (mixture of cis and trans) (58.7 g, 514 mmol) and xylene (3500 mL) was stirred while heating at an external temperature of 120° C. (oil bath). The reaction mixture was heated and stirred for 6 hours, and then heating was terminated and upon reaching an internal temperature of 61.5° C., hot water (58° C., 3500 mL) was added to the reaction mixture and stirring was continued overnight. After adding 28% aqueous ammonia (1050 mL) to the reaction mixture and stirring for 1 hour, the precipitate was filtered out and washed with water (1750 mL) and ethyl acetate (1050 mL) and then dried under aeration at 60° C. overnight to afford 280 g of the title compound (major conformer:minor conformer=6:1) (79.6% yield).

Workup

  1. temperatureThe reaction mixture was heated
  2. stirringstirred for 6 hours
  3. temperatureheating
  4. customwas terminated
  5. customan internal temperature of 61.5° C., hot water (58° C., 3500 mL)
  6. additionwas added to the reaction mixture
  7. stirringstirring
  8. additionAfter adding 28% aqueous ammonia (1050 mL) to the reaction mixture
  9. stirringstirring for 1 hour
  10. filtrationthe precipitate was filtered out
  11. washwashed with water (1750 mL) and ethyl acetate (1050 mL)
  12. customdried under aeration at 60° C. overnight

Sources & evidence

ORD record
ord-cf5d113fca9e4aa98ce6238b4f679279
Source dataset
uspto-grants-2007_02
Patent number
US07176216B2

Linked notes

Loading…