4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine → 7-chloro-8-(pyridin-4-yl)-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

HRID 2101284Notes

Reaction equation

HRID 2101284 reaction equation
Br[C:2]1[C:3]2[N:4]([C:9](=[O:23])[N:10]([CH2:12][C:13]3[CH:14]=[N:15][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:18]=3)[N:11]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].CC1(C)C(C)(C)OB([C:32]2[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=2)O1>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:8][C:7]1[CH:6]=[CH:5][N:4]2[C:9](=[O:23])[N:10]([CH2:12][C:13]3[CH:14]=[N:15][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:17][CH:18]=3)[N:11]=[C:3]2[C:2]=1[C:32]1[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=1

Participants

6

Reactant 2

HCID 27346484-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 577993578-bromo-7-chloro-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

Product 1

HCID 577994287-chloro-8-(pyridin-4-yl)-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-oneYield 20%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 8-bromo-7-chloro-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (389 mg, 0.955 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (783 mg, 3.823 mmol) in toluene (7 mL) and 2.0 M aqueous sodium carbonate (2.1 mL) was added (Ph3P)4Pd (165 mg, 0.143 mmol) in one portion, and the resulting yellow mixture was vigorously stirred under argon in a 100° C. oil bath for 2.5 h. HPLC/MS indicated that about 20% of the title compound had formed. Additional (Ph3P)4Pd (50 mg, 0.043 mmol) was added, and the reaction mixture was stirred at 100° C. under argon for 3.5 h more. After cooling to room temperature, the reaction mixture was partitioned between EtOAc and water. The EtOAc phase was washed with water, then saturated aqueous NaCl, dried over Na2SO4, and concentrated under reduced pressure to obtain a crude product, which was purified by silica gel (12 g) column chromatography eluting with a gradient of EtOAc (0-100%) in hexanes to obtain the title compound as a yellow foam (169 mg). HPLC/MS: retention time=2.04 min, [M+H]+=406.

Sources & evidence

ORD record
ord-4aa7baf34da5487680281cda3b9172f4
Source dataset
uspto-grants-2009_08
Patent number
US07572808B2

Reaction notes

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