2-Bromopyridine → HCID 11651703, compound

HRID 1189145Notes

Reaction equation

HRID 1189145 reaction equation
[CH2:1]([N:5]1[CH:13]=[C:12]2[C:7]([CH:8]=[CH:9][CH:10]=[CH:11]2)=[N:6]1)[CH2:2][C:3]#[CH:4].[CH2:14]([N:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[N:19]1)[CH2:15][C:16]#[CH:17].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Br[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][N:48]=1>CN(C=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCN(CC)CC>[N:18]1[CH:24]=[CH:23][CH:22]=[CH:21][C:26]=1[C:4]#[C:3][CH2:2][CH2:1][N:5]1[CH:13]=[C:12]2[C:7]([CH:8]=[CH:9][CH:10]=[CH:11]2)=[N:6]1.[N:48]1[CH:49]=[CH:50][CH:51]=[CH:52][C:47]=1[C:17]#[C:16][CH2:15][CH2:14][N:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[N:19]1

Participants

10

Reactant 4

HCID 79732-BromopyridineHCID 11776TriphenylphosphineHCID 57691784HCID 57691784, compoundHCID 63655048HCID 63655048, compound

Product 2

HCID 11630158HCID 11630158, compoundYield 2%HCID 11651703HCID 11651703, compoundYield 3%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 2-(but-3-ynyl)-2H-indazole and 1-(but-3-ynyl)-1H-indazole (160 mg, 0.94 mmol) in DMF (0.5 mL) was added to a suspension of CuI (8.9 mg, 47 μmol), Et3N (2.5 mL), Pd(PPh3)2Cl2 (33 mg, 47 mmol), PPh3 (6.2 mg, 23 mmol) and 2-bromopyridine (149 mg, 0.94 mmol). The reaction mixture was heated at 120° C. for 900 s in a microwave. The reaction mixture was quenched with water, Et3N was evaporated and the aqueous phase was extracted with DCM. The organic phase was washed with a saturated solution of NH4OH, brine, dried over MgSO4, filtered and evaporated. The crude residue was purified by flash chromatography (DCM/MeOH 99:1) and SCX column (DCM, DCM/MeOH 98:2, DCM/MeOH/NH4OH 95:4:1 to 94:4:2) to yield 6.8 mg (27 μmol, 3%) of 2-(4-(pyridin-2-yl)but-3-ynyl)-2H-indazole as a yellow solid and 4.6 mg (19 μmol, 2%) of 1-(4-(pyridin-2-yl)but-3-ynyl)-1H-indazole as an orange oil.

Workup

  1. customThe reaction mixture was quenched with water, Et3N
  2. customwas evaporated
  3. extractionthe aqueous phase was extracted with DCM
  4. washThe organic phase was washed with a saturated solution of NH4OH, brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude residue was purified by flash chromatography (DCM/MeOH 99:1) and SCX column (DCM, DCM/MeOH 98:2, DCM/MeOH/NH4OH 95:4:1 to 94:4:2)

Sources & evidence

ORD record
ord-8cdb811ea56949ec9d23523198294cda
Source dataset
uspto-grants-2014_03
Patent number
US08674106B2

Reaction notes

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