Nitrogen → Ethyl 7-(3-chloro-2-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoate

HRID 517893Notes

Reaction equation

HRID 517893 reaction equation
Br[C:2]1[N:3]=[C:4]2[CH2:12][CH2:11][CH2:10][N:9]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:5]2=[N:6][C:7]=1[Cl:8].B(O)(O)[C:25]1[CH:26]=[CH:27][C:28]([CH3:31])=[CH:29][CH:30]=1.C(=O)([O-])[O-].[K+].[K+].N#N>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.O1CCOCC1>[Cl:8][C:7]1[N:6]=[C:5]2[N:9]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:10][CH2:11][CH2:12][C:4]2=[N:3][C:2]=1[C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 79799Tolylboronic acidHCID 86681854Ethyl 7-(2-bromo-3-chloro-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoate

Product 1

HCID 86681856Ethyl 7-(3-chloro-2-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-(2-bromo-3-chloro-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoate (Intermediate EB) (200 mg, 0.494 mmol), p-tolylboronic acid (Aldrich) (73.9 mg, 0.544 mmol) and potassium carbonate (205 mg, 1.482 mmol) were combined in a microwave vial. Dioxane (2 ml) was added and the flask was sealed and deoxygenated by evacuation/N2 purge (×3). Pd(Ph3P)4 (57.1 mg, 0.049 mmol) was added and the mixture was de-oxygenated by evacuation/N2 purge (×3) and heated at 150° C. for 3 hours using microwave radiation. The mixture was diluted with water and extracted with EtOAc (×2). The extracts were washed with brine, dried (MgSO4) and evaporated under reduced pressure. The residue was purified by chromatography on silica eluting with 20-100% EtOAc in iso-hexane followed by 10% MeOH in DCM to elute the bis product. Further purification by chromatography on silica eluting with 0-70% EtOAc in iso-hexane afforded a mixture of the titled compound (mono adduct) and the bis adduct (2:1 ratio).

Workup

  1. customthe flask was sealed
  2. customdeoxygenated by evacuation/N2
  3. custompurge (×3)
  4. custompurge (×3)
  5. additionThe mixture was diluted with water
  6. extractionextracted with EtOAc (×2)
  7. washThe extracts were washed with brine
  8. dry with materialdried (MgSO4)
  9. customevaporated under reduced pressure
  10. customThe residue was purified by chromatography on silica eluting with 20-100% EtOAc in iso-hexane
  11. washto elute the bis product
  12. customFurther purification by chromatography on silica eluting with 0-70% EtOAc in iso-hexane
  13. customafforded

Sources & evidence

ORD record
ord-a20046665e8a4a1e867289adc1dbbf6f
Source dataset
uspto-grants-2015_08
Patent number
US09115129B2

Reaction notes

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