Dichloromethane → HCID 135997584, compound

HRID 1678250Notes

Reaction equation

HRID 1678250 reaction equation
ClCCl.Br[C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][N:9]=[C:8]2[C:14]1[NH:15][CH:16]=[CH:17][CH:18]=1.[N:19]1[CH:24]=[CH:23][CH:22]=[C:21](B(O)O)[CH:20]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.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]>[N:19]1[CH:24]=[CH:23][CH:22]=[C:21]([C:5]2[CH:6]=[C:7]3[C:11](=[CH:12][CH:13]=2)[NH:10][N:9]=[C:8]3[C:14]2[NH:15][CH:16]=[CH:17][CH:18]=2)[CH:20]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 27343783-Pyridinylboronic acidHCID 1357038631H-Indazole, 5-broMo-3-(1H-pyrrol-2-yl)-

Product 1

HCID 135997584HCID 135997584, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Procedure

[1,1′-Bis(diphenylphosphino)-ferrocene)dichloropalladium(II) 1:1 complex with dichloromethane (40.8 mg, 0.05 mmol) was added to a mixture containing 5-bromo-3-(1H-pyrrol-2-yl)-1H-indazole (Preparation #16c, 105 mg, 0.40 mmol), aqueous pyridine-3-boronic acid (1M, 1.0 mL), and Cs2CO3 (391 mg, 1.20 mmol) in DMF (2.0 mL) under a nitrogen atmosphere was added and the mixture was purged with N2 again, then heated at reflux for about 3 days. The reaction was cooled to ambient temperature and the organic layer was filtered through silica gel and concentrated under reduced pressure. The residue was further purified by preparative HPLC (Thermo Hypersil-Keystone 250×21.2 mm 8μ Hypersil® HS C18 column; 5% CH3CN/50 mM aqueous ammonium acetate hold for 5 min; 5-50% CH3CN/50 mM aqueous ammonium acetate over 20 min; 50-100% CH3CN/50 mM aqueous ammonium acetate over 1 min; hold at 100% CH3CN for 5 minutes, 21 mL/min). Product fractions were combined and concentrated to remove organic solvents and the lyophilized to yield 5-pyridin-3-yl-3-(1H-pyrrol-2-yl)-1H-indazole (44 mg, 42%) as an off-white powder. RP HPLC (Table 1, Method e) Rt=2.23; m/z: (MH)+ 261.

Workup

  1. additionwas added
  2. customthe mixture was purged with N2 again
  3. temperatureheated
  4. temperatureat reflux for about 3 days
  5. filtrationthe organic layer was filtered through silica gel
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was further purified by preparative HPLC (Thermo Hypersil-Keystone 250×21.2 mm 8μ Hypersil® HS C18 column; 5% CH3CN/50 mM aqueous ammonium acetate hold for 5 min; 5-50% CH3CN/50 mM aqueous ammonium acetate over 20 min; 50-100% CH3CN/50 mM aqueous ammonium acetate over 1 min; hold at 100% CH3CN for 5 minutes, 21 mL/min)
  8. concentrationconcentrated
  9. customto remove organic solvents

Sources & evidence

ORD record
ord-43e1110dd5c345e59f1d216685bb0edc
Source dataset
uspto-grants-2011_08
Patent number
US08008481B2

Reaction notes

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