5-bromo-1H-indazole → 1H-Indazole-5-carbonitrile

HRID 2403218Notes

Reaction equation

HRID 2403218 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.O.[CH3:41][N:42](C=O)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[C-]#N.[Zn+2].[C-]#N>[NH:7]1[C:8]2[C:4](=[CH:3][C:2]([C:41]#[N:42])=[CH:10][CH:9]=2)[CH:5]=[N:6]1

Participants

6

Reactant 3

HCID 7619295-bromo-1H-indazoleHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 21962138N,N-Dimethylformamide--water (1/1)

Product 1

HCID 111263841H-Indazole-5-carbonitrile

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
150 °C

Procedure

5-Bromo-1H-indazole (Fluorochem; 500 mg; 2.54 mmol), S-Phos (93.8 mg; 0.229 mmol), Pd2(dba)3 (93.0 mg; 0.102 mmol) and zinc cyanide (337.0 mg; 2.87 mmol) were suspended in degassed water:DMF (1:99, 11.5 mL) in a microwave vial and further degassed for 10 minutes in a sonicator. The vial was then sealed and heated in the microwave at 150° C. for 45 minutes. The solid material was removed by filtration and the crude material purified by flash chromatography on a Biotage 40+M column, eluting with DCM containing increasing amounts of methanol. The residue was recrystallised from chloroform/petrol to yield the title compound as an off white solid (1.33 g; 91%). 1H NMR (CDCl3, 400 MHz) δ 10.46 (1 H, br s), 8.20 (2 H, d, J=8.3 Hz), 7.61 (2 H, s).

Workup

  1. customfurther degassed for 10 minutes in a sonicator
  2. customThe vial was then sealed
  3. customThe solid material was removed by filtration
  4. customthe crude material purified by flash chromatography on a Biotage 40+M column
  5. washeluting with DCM containing
  6. temperatureincreasing amounts of methanol
  7. customThe residue was recrystallised from chloroform/petrol

Sources & evidence

ORD record
ord-6b5b782d5b184ed499b030d61ea9b55e
Source dataset
uspto-grants-2014_08
Patent number
US08802663B2

Reaction notes

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