3-Bromo-5-iodopyridine → 3-bromo-5-[1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrazol-4-yl]-pyridine

HRID 1914946Notes

Reaction equation

HRID 1914946 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6](I)[CH:7]=1.[N:9]1([CH2:14][CH2:15][N:16]2[CH:20]=[C:19](B3OC(C)(C)C(C)(C)O3)[CH:18]=[N:17]2)[CH2:13][CH2:12][CH2:11][CH2:10]1.O.O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:19]2[CH:18]=[N:17][N:16]([CH2:15][CH2:14][N:9]3[CH2:13][CH2:12][CH2:11][CH2:10]3)[CH:20]=2)[CH:7]=1

Participants

6

Reactant 3

HCID 8204093-Bromo-5-iodopyridineHCID 18407952Tripotassium phosphate trihydrateHCID 588858611-(2-(pyrrolidin-1-yl)ethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 673649723-bromo-5-[1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrazol-4-yl]-pyridine

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 5.43 g (19.1 mmol) 3-bromo-5-iodo-pyridine and 6.12 g (21.0 mmol) 1-(2-pyrrolidin-1-yl-ethyl)-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazol in 17 ml 1,2-dimethoxyethan was treated with 8.12 g (38.2 mmol) tri-potassium-phosphate-trihydrate and was heated to 80° C. under nitrogen. Then 403 mg (0.57 mmol) bis(triphenyl-phosphine)palladium(II)-chloride were added. The reaction mixture was stirred for 18 hours at 80° C. The reaction mixture was partitioned between water and dichloromethane. The organic phase was extracted several times with 1 N HCl and was washed with water. The aqueous phases were combined, basified with 50% aqueous NaOH. Brine and THF were added. The organic phase was separated and the aqueous phase was extracted several times with THF. The combined organic phases were dried over sodium sulfate and evaporated. The residue was chromatographed on a silica gel column with dichloromethane/methanol as eluent yielding 3-bromo-5-[1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrazol-4-yl]-pyridine as brown oil; HPLC-MS: 1.29 min, [M+H] 321/323.

Workup

  1. customThe reaction mixture was partitioned between water and dichloromethane
  2. extractionThe organic phase was extracted several times with 1 N HCl
  3. washwas washed with water
  4. additionBrine and THF were added
  5. customThe organic phase was separated
  6. extractionthe aqueous phase was extracted several times with THF
  7. dry with materialThe combined organic phases were dried over sodium sulfate
  8. customevaporated
  9. customThe residue was chromatographed on a silica gel column with dichloromethane/methanol as eluent

Sources & evidence

ORD record
ord-98fe5d5867aa4eeca3c286554b84a92d
Source dataset
uspto-grants-2013_12
Patent number
US08614226B2

Reaction notes

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