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

HRID 406230Notes

Reaction equation

HRID 406230 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][C:26]([CH3:29])=[CH:25][CH:24]=1.BrC1N=[C:33]2[CH2:41][CH2:40][CH2:39][N:38](CCCCCCC(OCC)=O)[C:34]2=NC=1Cl.CC1(C)C(C)(C)OB(C2C=CN=CC=2)O1.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:38]1[CH:39]=[CH:40][C:41]([C:2]2[N:7]=[C:6]3[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]3=[N:4][C:3]=2[C:23]2[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=2)=[CH:33][CH:34]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 27346484-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 86681854Ethyl 7-(2-bromo-3-chloro-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoateHCID 86681856Ethyl 7-(3-chloro-2-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoate

Product 1

HCID 66665340Ethyl 7-(3-(pyridin-4-yl)-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

Procedure

A (3:1) mixture of ethyl 7-(3-chloro-2-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoate (Example 13.2, step 1) (30 mg, 0.072 mmol) and ethyl 7-(2-bromo-3-chloro-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoate (Example 13.1, step 2)(10 mg, 0.025 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (39.4 mg, 0.192 mmol) and potassium carbonate (39.9 mg, 0.288 mmol) in dioxane (2 ml) was degassed by bubbling nitrogen through (×3). Pd(Ph3P)4 (22.22 mg, 0.019 mmol) was added and the mixture was degassed by bubbling nitrogen through (×3). The reaction mixture was heated using microwave radiation at 150° C. for 2 hours. 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 material was purified by ion exchange [Isolute SCX-2 washing with MeOH and eluting with 2M NH3 in MeOH] to give a brown residue. The crude residue was purified by chromatography on silica eluting with 0-100% EtOAc in iso-hexane followed by 10% MeOH/DCM 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. temperatureThe reaction mixture was heated
  6. customat 150° C.
  7. customfor 2 hours
  8. additionThe mixture was diluted with water
  9. extractionextracted with EtOAc (×2)
  10. washThe combined extracts were washed with brine
  11. dry with materialdried (MgSO4)
  12. customevaporated under vacuum
  13. customThe crude material was purified by ion exchange [Isolute SCX-2 washing with MeOH and eluting with 2M NH3 in MeOH]
  14. customto give a brown residue
  15. customThe crude residue was purified by chromatography on silica eluting with 0-100% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-12eec117c2604d3fb6cc22f5776db70b
Source dataset
uspto-grants-2014_06
Patent number
US08754085B2

Reaction notes

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