Nitrogen → HCID 89689869, compound

HRID 517892Notes

Reaction equation

HRID 517892 reaction equation
[CH3:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH2:24][CH2:23][CH2:22][N:21]([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:11]3=[N:12][C:13]=2[C:14]2[CH:15]=N[C:17]([CH3:20])=[CH:18][CH:19]=2)=[CH:4][CH:3]=1.B(O)(O)[C:37]1C=CC(C)=CC=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>[CH3:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH2:24][CH2:23][CH2:22][N:21]([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:11]3=[N:12][C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([CH3:37])=[CH:20][CH:15]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 79799Tolylboronic acidHCID 89689993HCID 89689993, compound

Product 1

HCID 89689869HCID 89689869, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of ethyl 7-(3-chloro-2-(6-methylpyridin-3-yl)-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl) heptanoate (Example 5, step 1) (86 mg, 0.206 mmol), p-tolylboronic acid (56.1 mg, 0.413 mmol) and 2M sodium carbonate (0.309 ml, 0.619 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 (47.7 mg, 0.041 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 afforded 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-de34008e4ab6482b8263e73407e3dadf
Source dataset
uspto-grants-2015_08
Patent number
US09115129B2

Reaction notes

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