2-Bromopyridine → HCID 178477852, compound

HRID 1966006Notes

Reaction equation

HRID 1966006 reaction equation
Cl.[Cl:2][C:3]1[CH:28]=[CH:27][C:6]2[N:7]3[C:11]([CH2:12][NH:13][CH2:14][C:5]=2[CH:4]=1)=[N:10][N:9]=[C:8]3[C@H:15]1[CH2:20][CH2:19][C@H:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:17][CH2:16]1.Br[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=1>[Br-].C([N+](C)(C)C)CCCCCCCCCCCCCCC.C1(C)C=CC=CC=1.[OH-].[Na+].CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[Cl:2][C:3]1[CH:28]=[CH:27][C:6]2[N:7]3[C:11]([CH2:12][N:13]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=4)[CH2:14][C:5]=2[CH:4]=1)=[N:10][N:9]=[C:8]3[C@H:15]1[CH2:20][CH2:19][C@H:18]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:17][CH2:16]1

Participants

7

Reactant 2

HCID 79732-BromopyridineHCID 178478522HCID 178478522, compound

Product 1

HCID 178477852HCID 178477852, compoundYield 4%

Reagents, catalysts & solvents 4

HCID 5974Hexadecyltrimethylammonium BromideCatalystHCID 178418851HCID 178418851, compoundCatalystHCID 1140TolueneSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of trans-8-chloro-1-(4-phenyl-cyclohexyl)-5,6-dihydro-4H-2,3,5,10b-tetraaza-benzo[e]azulene hydrochloride (0.10 g, 0.24 mmol), 2-bromopyridine (0.057 g, 0.36 mmol) and cetyltrimethylammonium bromide (0.0040 g, 0.012 mmol) in toluene (2 ml) and 50% aqueous sodium hydroxide solution (0.04 ml) was degassed by freeze/thaw cycles. Addition of bis(tri-t-butylphosphine)palladium (0.012 g, 0.024 mmol) was followed by stirring at 90° C. for 18 h. The reaction mixture was partitioned between water (50 ml) and dichloromethane (50 ml). The layers were separated. The aqueous layer was extracted with one 50-ml portion of dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash-chromatography with n-heptane/ethyl acetate and ethyl acetate/2-propanol as eluent gave the title compound (0.004 g, 4%) as colorless oil.

Workup

  1. customwas degassed by freeze/thaw cycles
  2. customThe reaction mixture was partitioned between water (50 ml) and dichloromethane (50 ml)
  3. customThe layers were separated
  4. extractionThe aqueous layer was extracted with one 50-ml portion of dichloromethane
  5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification by flash-chromatography with n-heptane/ethyl acetate and ethyl acetate/2-propanol as eluent

Sources & evidence

ORD record
ord-a4f81211acff4ef69afb851be325bf80
Source dataset
uspto-grants-2013_04
Patent number
US08420633B2

Reaction notes

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