Potassium Phosphate, Tribasic → 1-(phenylsulfonyl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-4-amine

HRID 1615994Notes

Reaction equation

HRID 1615994 reaction equation
[C:1]1([S:7]([N:10]2[C:18]3[CH:17]=[C:16](B4OC(C)(C)CC(C)(C)O4)[CH:15]=[C:14]([NH2:29])[C:13]=3[CH:12]=[N:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:31]1[CH:36]=[CH:35][N:34]=[C:33]2[NH:37][CH:38]=[CH:39][C:32]=12.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.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:1]1([S:7]([N:10]2[C:18]3[CH:17]=[C:16]([C:31]4[CH:36]=[CH:35][N:34]=[C:33]5[NH:37][CH:38]=[CH:39][C:32]=45)[CH:15]=[C:14]([NH2:29])[C:13]=3[CH:12]=[N:11]2)(=[O:8])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 222736434-Bromo-1H-pyrrolo[2,3-b]pyridineHCID 670292681-(Phenylsulfonyl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-1H-indazol-4-amine

Product 1

HCID 582680031-(phenylsulfonyl)-6-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-indazol-4-amineYield 48.8%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
80 °C

Procedure

1-(Phenylsulfonyl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-1H-indazol-4-amine (2 g, 4.84 mmol), 4-bromo-1H-pyrrolo[2,3-b]pyridine (0.953 g, 4.84 mmol), Pd(dppf)Cl2 (0.708 g, 0.968 mmol) and Tripotassium phosphate (3.08 g, 14.52 mmol) were divided between 2× microwave vials and dissolved in 1,4-dioxane (24 ml) and water (8.00 ml); 12 ml dioxane and 4 ml water in each vial. The mixtures were heated in the microwave at 80° C. for 20 min. Solvent was removed in vacuo and the residue was partitioned between DCM (100 ml) and water (100 ml). The organic layer was collected using a hydrophobic frit and the solvent removed in vacuo. DCM was added to dissolve the crude residue but a suspension resulted. The yellow solid was filtered off and dried in a vacuum oven for 30 mins to afford the title compound (919 mg). The filtrate was concentrated in vacuo and dissolved in DCM, then applied to the top of a 50 g silica SPE cartridge. This was eluted with 0-100% EtOAc/DCM over 60 mins on the FlashMaster II. The product-containing fractions were combined to give a further portion of the title compound as a yellow solid (220 mg).

Workup

  1. customSolvent was removed in vacuo
  2. customthe residue was partitioned between DCM (100 ml) and water (100 ml)
  3. customThe organic layer was collected
  4. customthe solvent removed in vacuo
  5. additionDCM was added
  6. dissolutionto dissolve the crude residue
  7. customa suspension resulted
  8. filtrationThe yellow solid was filtered off
  9. customdried in a vacuum oven for 30 mins

Sources & evidence

ORD record
ord-efd3b403863f43059b9bf070d6759b90
Source dataset
uspto-grants-2014_07
Patent number
US08765743B2

Reaction notes

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