Dichloromethane → HCID 59023819, compound

HRID 1678214Notes

Reaction equation

HRID 1678214 reaction equation
[C:1]1([NH:7][C:8]([C:10]2[CH:11]=[C:12](Br)[CH:13]=[C:14]3[C:18]=2[NH:17][N:16]=[CH:15]3)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:20]1[CH:25]=[CH:24][CH:23]=[C:22](B(O)O)[CH:21]=1.C([O-])([O-])=O.[Cs+].[Cs+].ClCCl>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.COCCOC>[C:1]1([NH:7][C:8]([C:10]2[CH:11]=[C:12]([C:22]3[CH:21]=[N:20][CH:25]=[CH:24][CH:23]=3)[CH:13]=[C:14]3[C:18]=2[NH:17][N:16]=[CH:15]3)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 27343783-Pyridinylboronic acidHCID 59024153HCID 59024153, compound

Product 1

HCID 59023819HCID 59023819, compoundYield 27.8%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of N-phenyl-5-bromo-1H-indazole-7-carboxamide (Example #B.1.2, 0.05 g, 0.16 mmol) and pyridine-3-yl-boronic acid (0.11 g, 0.8 mmol), 1,2-dimethoxyethane (1.3 mL), water (0.7 mL), Cs2CO3 (0.16 g, 0.48 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (0.013 g, 0.016 mmol) was heated at about 150° C. in the microwave under an atmosphere of nitrogen for about 15 minutes. The crude product was filtered and the solvent was removed under reduced pressure. The residue was dissolved in DMSO then purified by reverse phase HPLC (Waters Symmetry C8 column (25×100 mm, 7 μm particle size) using a gradient of 10%-100% CH3CN/0.1% aqueous TFA over 8 min (10 min run time) at a flow rate of 40 mL/min) to yield N-phenyl-5-pyridin-3-yl-1H-indazole-7-carboxamide (0.014 g, 6%); (DMSO-d6, 400 MHz) δ 13.4 (bs, 1H), 10.5 (bs, 1H), 9.12 (d, 1H), 8.62 (d, 1H), 8.48 (s, 1H), 8.34 (s, 1H), 8.28 (m, 2H), 7.84 (d, 2H), 7.56 (m, 1H), 7.42 (m, 2H), 7.16 (m, 2H); RP-HPLC (Table 1, Method e) Rt=1.81 min; m/z: (M+H)+ 315.3.

Workup

  1. filtrationThe crude product was filtered
  2. customthe solvent was removed under reduced pressure
  3. dissolutionThe residue was dissolved in DMSO
  4. customthen purified by reverse phase HPLC (Waters Symmetry C8 column (25×100 mm, 7 μm particle size)
  5. customover 8 min
  6. custom(10 min run time)

Sources & evidence

ORD record
ord-7491a5982d524bf9977c354aee159c34
Source dataset
uspto-grants-2011_08
Patent number
US08008481B2

Reaction notes

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