1,4-Dioxane → HCID 66692086, compound

HRID 520595Notes

Reaction equation

HRID 520595 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH2:12])[C:5]2[CH:6]=[N:7][N:8]([CH3:11])[C:9]=2[CH:10]=1.[CH3:13][C:14]1[CH:19]=[CH:18][C:17]([S:20]([N:23]2[C:27]3=[N:28][CH:29]=[CH:30][C:31](B(O)O)=[C:26]3[CH:25]=[CH:24]2)(=[O:22])=[O:21])=[CH:16][CH:15]=1.P([O-])([O-])([O-])=O.[K+].[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].O>[CH3:11][N:8]1[C:9]2[CH:10]=[C:2]([C:31]3[CH:30]=[CH:29][N:28]=[C:27]4[N:23]([S:20]([C:17]5[CH:18]=[CH:19][C:14]([CH3:13])=[CH:15][CH:16]=5)(=[O:21])=[O:22])[CH:24]=[CH:25][C:26]=34)[CH:3]=[C:4]([NH2:12])[C:5]=2[CH:6]=[N:7]1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 58255771HCID 58255771, compoundHCID 68226575HCID 68226575, compound

Product 1

HCID 66692086HCID 66692086, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

6-Bromo-1-methyl-1H-indazol-4-amine (300 mg), {1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}boronic acid (482 mg), tripotassium phosphate (845 mg) and Pd(dppf)Cl2 (97 mg) were added to 1,4-dioxane (7 ml) and water (3.5 ml). The reaction mixture was heated in the microwave at 100° C. for 15 min. After this time the reaction mixture was partitioned between water (20 ml) and DCM (20 ml). The organic layer was extracted then put through hydrophobic frits. The solvent was removed to afford a crude mixture. The residue was purified by column chromatography on silica (100 g) eluting with a gradient of 0-100% ethyl acetate:cyclohexane. Fractions containing desired product were combined and concentrated in vacuo to afford the title compound, 312 mg as an orange solid.

Workup

  1. customAfter this time the reaction mixture was partitioned between water (20 ml) and DCM (20 ml)
  2. extractionThe organic layer was extracted
  3. customThe solvent was removed
  4. customto afford a crude mixture
  5. customThe residue was purified by column chromatography on silica (100 g)
  6. washeluting with a gradient of 0-100% ethyl acetate
  7. additionFractions containing desired product
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d67037304fcc41e29a75369236f251f1
Source dataset
uspto-grants-2016_05
Patent number
US09326987B2

Reaction notes

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