Water → 2-chloro-5-(1-methyl-1H-pyrazol-4-yl)nicotinonitrile

HRID 219292Notes

Reaction equation

HRID 219292 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5](B2OC(C)(C)C(C)(C)O2)[CH:4]=[N:3]1.Br[C:17]1[CH:18]=[N:19][C:20]([Cl:25])=[C:21]([CH:24]=1)[C:22]#[N:23].C(=O)([O-])[O-].[K+].[K+].O1CCOCC1.O>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:25][C:20]1[N:19]=[CH:18][C:17]([C:5]2[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=2)=[CH:24][C:21]=1[C:22]#[N:23]

Participants

7

Reactant 5

HCID 962WaterHCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 219482695-Bromo-2-chloronicotinonitrile

Product 1

HCID 580154822-chloro-5-(1-methyl-1H-pyrazol-4-yl)nicotinonitrileYield 61.7%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
60 °C

Procedure

A 48 mL tube was charged with 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (8.42 g, 40.5 mmol), 5-bromo-2-chloronicotinonitrile (8.00 g, 36.8 mmol), potassium carbonate (15.3 g, 110 mmol), PdCl2(dppf) (2.69 g, 3.68 mmol), 1,4-dioxane (135 mL, 1582 mmol) and water (23.9 mL, 1324 mmol), flushed with argon, sealed and then heated to 60° C. for 8 h. The reaction mixture was concentrated, adsorbed onto silica gel, and purified via MPLC eluting with 3% MeOH in DCM. 2-chloro-5-(1-methyl-1H-pyrazol-4-yl)nicotinonitrile (4.962 g, 61.7%) was obtained (with a small impurity). The material was taken forward crude.

Workup

  1. customflushed with argon
  2. customsealed
  3. concentrationThe reaction mixture was concentrated
  4. custompurified via MPLC
  5. washeluting with 3% MeOH in DCM

Sources & evidence

ORD record
ord-070ec2b05bb142b9b3eb0369ee206662
Source dataset
uspto-grants-2012_06
Patent number
US08198448B2

Reaction notes

Loading…