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

HRID 517894Notes

Reaction equation

HRID 517894 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.[CH3:30][C:31]1[CH:36]=[CH:35][C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][N:32]=1.C(=O)([O-])[O-].[Na+].[Na+].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>[CH3:30][C:31]1[N:32]=[CH:33][C:34]([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:35][CH:36]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 164142722-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 86681856Ethyl 7-(3-chloro-2-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoate

Product 1

HCID 89689788Ethyl 7-(3-(6-methylpyridin-3-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

Conditions

Temperature
150 °C

Procedure

A mixture of step 1 (70 mg), 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (73.7 mg, 0.337 mmol) and 2M sodium carbonate (0.252 ml, 0.505 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 (38.9 mg, 0.034 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 combined organic extracts were washed with brine, dried (MgSO4) and evaporated under reduced pressure to a give a brown gum. The crude product was loaded onto an Isolute® SCX-2 cartridge and eluting with MeOH followed by 2M NH3 in MeOH. The methanolic ammonia fractions were concentrated under reduced pressure and further purification by chromatography on silica eluting with 0-100% EtOAc in iso-hexane to afford the titled compound;

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 combined organic extracts were washed with brine
  8. dry with materialdried (MgSO4)
  9. customevaporated under reduced pressure to
  10. customa give a brown gum
  11. washeluting with MeOH
  12. concentrationThe methanolic ammonia fractions were concentrated under reduced pressure and further purification by chromatography on silica eluting with 0-100% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-b186875c03e0490391bb6fe6718ed49a
Source dataset
uspto-grants-2015_08
Patent number
US09115129B2

Reaction notes

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