Toluene → propane-1-sulfonic acid(2,4-difluoro-3-[5-(1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbony]-phenyl)-amide

HRID 60086Notes

Reaction equation

HRID 60086 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]([C:13]3[C:14]([F:27])=[C:15]([NH:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:23])=[O:22])[CH:16]=[CH:17][C:18]=3[F:19])=[O:12])=[CH:9][N:8](C(=O)C3C(Cl)=CC=CC=3Cl)[C:5]2=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:46]2[CH:47]=[C:48]3[C:52](=[CH:53][CH:54]=2)[NH:51][N:50]=[CH:49]3)O1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl.C(O)C>[F:27][C:14]1[C:13]([C:11]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([C:46]4[CH:47]=[C:48]5[C:52](=[CH:53][CH:54]=4)[NH:51][N:50]=[CH:49]5)[CH:3]=3)[NH:8][CH:9]=2)=[O:12])=[C:18]([F:19])[CH:17]=[CH:16][C:15]=1[NH:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:22])=[O:23]

Participants

8

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 177504691H-Indazole-5-boronic acid pinacol esterHCID 510010251-Propanesulfonamide, N-[3-[[5-bromo-1-(2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl]-2,4-difluorophenyl]-

Product 1

HCID 53261781propane-1-sulfonic acid(2,4-difluoro-3-[5-(1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbony]-phenyl)-amide

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 702EthanolSolvent

Conditions

Temperature
110 °C

Procedure

Into a microwave vial, propane-1-sulfonic acid {3-[5-bromo-1-(2,6-dichloro-benzoyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide (11, 0.100 g, 0.158 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indazole (12, 0.080 g, 0.33 mmol) and 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.07 g, 0.086 mmol, 1:1 complex with dichloromethane) are combined with 2.0 mL of toluene and 2.0 mL of ethanol. The mixture is stirred for 5 minutes, then potassium carbonate (0.475 mL, 1.0 M aqueous) is added and the reaction heated at 110° C. for 60 minutes in a microwave, followed by 140° C. for 45 minutes. The reaction is added to silica and the solvents are removed under vacuum. The resulting material is purified by silica gel column chromatography, eluting with a gradient of ethyl acetate (with 2% acetic acid):hexanes. Appropriate fractions are combined and concentrated under vacuum, then washed with acetonitrile to provide the desired compound (P-0001). MS (ESI) [M+H+]+=496.0.

Workup

  1. waitfollowed by 140° C. for 45 minutes
  2. additionThe reaction is added to silica
  3. customthe solvents are removed under vacuum
  4. customThe resulting material is purified by silica gel column chromatography
  5. washeluting with a gradient of ethyl acetate (with 2% acetic acid)
  6. concentrationconcentrated under vacuum
  7. washwashed with acetonitrile

Sources & evidence

ORD record
ord-f212b9dc60f74c139dace6b6deced8a2
Source dataset
uspto-grants-2016_09
Patent number
US09440969B2

Reaction notes

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