Potassium Carbonate → Ethyl 7-(2-(pyridin-4-yl)-3-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoate

HRID 406228Notes

Reaction equation

HRID 406228 reaction equation
Cl[C:2]1[N:7]=[C:6]2[N:8]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:9][CH2:10][CH2:11][C:5]2=[N:4][C:3]=1[C:23]1[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=1.B(O)(O)[C:30]1[CH:31]=[CH:32][C:33]([CH3:36])=[CH:34][CH:35]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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>[N:26]1[CH:27]=[CH:28][C:23]([C:3]2[N:4]=[C:5]3[CH2:11][CH2:10][CH2:9][N:8]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:6]3=[N:7][C:2]=2[C:30]2[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=2)=[CH:24][CH:25]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 79799Tolylboronic acidHCID 86681855Ethyl 7-(3-chloro-2-(pyridin-4-yl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoate

Product 1

HCID 66666060Ethyl 7-(2-(pyridin-4-yl)-3-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoate

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of ethyl 7-(3-chloro-2-(pyridin-4-yl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoate (step 3) (58 mg, 0.144 mmol), p-tolylboronic acid (39.1 mg, 0.288 mmol) and potassium carbonate (59.7 mg, 0.432 mmol) in dioxane (2 ml) was degassed by bubbling nitrogen through (×3). Pd(Ph3P)4 (33.3 mg, 0.029 mmol) was added and the mixture was degassed by bubbling nitrogen through (×3). The mixture was heated at 150° C. for 2 hours using microwave irradiation. The mixture was diluted with water and extracted with EtOAc (×2). The combined extracts were washed with brine, dried (MgSO4) and evaporated under vacuum. The crude product was purified by chromatography on silica eluting with 50-100% EtOAc in iso-hexane followed by 5-10% THF in DCM. The fractions were evaporated under vacuum and the residue was purified by ion exchange using a Isolute SCX-2 cartridge, loading and washing with methanol and eluting with 2M NH3 in MeOH to afford the title compound;

Workup

  1. customwas degassed
  2. customby bubbling nitrogen through (×3)
  3. customthe mixture was degassed
  4. customby bubbling nitrogen through (×3)
  5. custommicrowave irradiation
  6. additionThe mixture was diluted with water
  7. extractionextracted with EtOAc (×2)
  8. washThe combined extracts were washed with brine
  9. dry with materialdried (MgSO4)
  10. customevaporated under vacuum
  11. customThe crude product was purified by chromatography on silica eluting with 50-100% EtOAc in iso-hexane
  12. customThe fractions were evaporated under vacuum
  13. customthe residue was purified by ion exchange
  14. washwashing with methanol
  15. washeluting with 2M NH3 in MeOH

Sources & evidence

ORD record
ord-d0755594c8f7477c821cccadc6034727
Source dataset
uspto-grants-2014_06
Patent number
US08754085B2

Reaction notes

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