Water → 5-{3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(2-methyl-pyridin-4-yl)-propyl]-phenyl}-pyridine-2-carbonitrile

HRID 1095907Notes

Reaction equation

HRID 1095907 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:22])[C:9]([C:15]2[CH:20]=[CH:19][N:18]=[C:17]([CH3:21])[CH:16]=2)([OH:14])[C:10]([F:13])([F:12])[F:11])=[C:4]([Cl:23])[CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[C:30]([C:32]1[CH:37]=[CH:36][C:35](B2OC(C)(C)C(C)(C)O2)=[CH:34][N:33]=1)#[N:31].O>O1CCOCC1>[Cl:23][C:4]1[CH:3]=[C:2]([C:35]2[CH:36]=[CH:37][C:32]([C:30]#[N:31])=[N:33][CH:34]=2)[CH:7]=[CH:6][C:5]=1[CH:8]([CH3:22])[C:9]([OH:14])([C:15]1[CH:20]=[CH:19][N:18]=[C:17]([CH3:21])[CH:16]=1)[C:10]([F:13])([F:12])[F:11]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 164141882-Cyanopyridine-5-boronic acid pinacol esterHCID 574212913-(4-Bromo-2-chloro-phenyl)-1,1,1-trifluoro-2-(2-methyl-pyridin-4-yl)-butan-2-ol

Product 1

HCID 666991305-{3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(2-methyl-pyridin-4-yl)-propyl]-phenyl}-pyridine-2-carbonitrile

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 3-(4-bromo-2-chloro-phenyl)-1,1,1-trifluoro-2-(2-methyl-pyridin-4-yl)-butan-2-ol (Example 60 step 1, 40 mg), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palldadium(II) (7 mg), Cs2CO3 (96 mg) and 2-cyanopyridine-5-boronic acid pinacol ester (CAS Reg. No. 741709-63-7, 45 mg) in dioxane (2 ml) and water (0.2 ml) was heated at 100° C. for 10 min in a sealed tube. The mixture was purified by prep. HPLC (C18-column, solvent gradient 30-98% CH3CN in 0.1% HCOOH[aq]) to give the title compound (32 mg) as a yellow solid. MS (m/e)=432.2 [M+H+].

Workup

  1. customThe mixture was purified by prep

Sources & evidence

ORD record
ord-aef2d6f7fa3d4a549d9217882d78e486
Source dataset
uspto-grants-2012_03
Patent number
US08138189B2

Reaction notes

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