Nitrogen → HCID 86690326, compound

HRID 1428676Notes

Reaction equation

HRID 1428676 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][N:11]1[C:15]2=[N:16][C:17](Cl)=[C:18](Br)[N:19]=[C:14]2[CH:13]=[C:12]1[CH:22]1[CH2:24][CH2:23]1)[CH3:2].N#N.[C:28]1(B(O)O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][N:11]1[C:15]2=[N:16][C:17]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[C:18]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[N:19]=[C:14]2[CH:13]=[C:12]1[CH:22]1[CH2:24][CH2:23]1)[CH3:2]

Participants

8

Reactant 4

HCID 947Nitrogen2×HCID 11430Potassium CarbonateHCID 66827Phenylboronic Acid2×HCID 86690327HCID 86690327, compound2×

Product 1

HCID 86690326HCID 86690326, compound

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalyst2×HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture comprising 7-(2-bromo-3-chloro-6-cyclopropyl-pyrrolo[2,3-b]pyrazin-5-yl)-heptanoic acid ethyl ester (Intermediate D) (400 mg, 0.933 mmol) in 1,4-dioxane (8 ml) degassed with N2 was treated with phenylboronic acid (120 mg, 0.980 mmol), potassium carbonate (284 mg, 2.052 mmol) and PdCl2(dppf)-CH2Cl2-adduct (76 mg, 0.093 mmol). The reaction mixture was stirred at 60° C. for 12 hours. After cooling to RT and degassing with N2, phenylboronic acid (171 mg, 1.399 mmol) and PdCl2(dppf)-CH2Cl2-adduct (76 mg, 0.093 mmol) were added and stirring continued at 110° C. for 24 hours. The mixture was treated with ice-cooled water and the aqueous was extracted with diethyl ether. The organic portion was dried (Na2SO4) and concentrated under reduced pressure. Purification of the crude product on silica eluting with 5% EtOAc in iso-hexane afforded the titled compound:

Workup

  1. temperatureAfter cooling to RT
  2. additionwere added
  3. stirringstirring
  4. waitcontinued at 110° C. for 24 hours
  5. additionThe mixture was treated with ice-
  6. extractionthe aqueous was extracted with diethyl ether
  7. dry with materialThe organic portion was dried (Na2SO4)
  8. concentrationconcentrated under reduced pressure
  9. customPurification of the crude product on silica eluting with 5% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-6d309dbaed124e328413a5f8bcc62521
Source dataset
uspto-grants-2015_01
Patent number
US08937069B2

Reaction notes

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