3-Aminopyridine → HCID 89650076, compound

HRID 2174240Notes

Reaction equation

HRID 2174240 reaction equation
Cl[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=[C:4]([NH:13][C:14]([NH:16][CH2:17][CH3:18])=[O:15])[CH:3]=1.[NH2:19][C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH2:17]([NH:16][C:14](=[O:15])[NH:13][C:4]1[CH:3]=[C:2]([NH:19][C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=1)[CH3:18]

Participants

7

Reactant 3

HCID 100093-AminopyridineHCID 10796Cesium carbonateHCID 89651155HCID 89651155, compound

Product 1

HCID 89650076HCID 89650076, compoundYield 66%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of ethyl 4-chloro-6-(3-ethylureido)nicotinate, i (1.0 g, 3.70 mmol), in 1,4-dioxane (25 mL) was added 3-aminopyridine (0.435 g, 4.81 mmol) followed by Cs2CO3 (1.80 g, 5.55 mmol). The resulting solution was purged with nitrogen for 15 min followed by addition of Pd(OAc)2 (0.025 g, 0.11 mmol) and Xantphos (0.13 g, 0.22 mmol). The reaction mixture was again purged with nitrogen for 15 min and then heated at 80° C. overnight. The reaction mixture was cooled to room temperature, filtered through a celite bed, and the bed washed with EtOAc. The combined filtrate was concentrated under reduced pressure. Water was added to the residue and the mixture extracted with EtOAc (3×50 mL). The combined organic phase was washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product thus obtained was triturated with a mixture of 10% MeOH-Et2O to obtain compound ii as an off-white solid (0.80 g, 66%). 1H NMR (DMSO-d6, 400 MHz): δ 9.62 (s, 1H), 9.17 (s, 1H), 8.63 (s, 1H), 8.56 (d, J=2.4 Hz, 1H), 8.41 (d, J=4.4 Hz, 1H), 7.77 (m, 1H), 7.75 (br s, 1H), 7.48 (m, 1H), 7.20 (s, 1H), 4.32 (q, J=6.8 Hz, 2H), 3.11 (q, J=7.20 Hz, 2H), 1.33 (t, J=6.8 Hz, 3H) and 1.03 (t, J=7.20 Hz, 3H). [M+H]+ m/z=330.12.

Workup

  1. customThe resulting solution was purged with nitrogen for 15 min
  2. customThe reaction mixture was again purged with nitrogen for 15 min
  3. temperatureThe reaction mixture was cooled to room temperature
  4. filtrationfiltered through a celite bed
  5. washthe bed washed with EtOAc
  6. concentrationThe combined filtrate was concentrated under reduced pressure
  7. additionWater was added to the residue
  8. extractionthe mixture extracted with EtOAc (3×50 mL)
  9. washThe combined organic phase was washed with brine
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe crude product thus obtained
  14. customwas triturated with a mixture of 10% MeOH-Et2O

Sources & evidence

ORD record
ord-7e5100a2c283412cae8e4367d10ec246
Source dataset
uspto-grants-2015_06
Patent number
US09060515B2

Reaction notes

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