Dichloromethane → N-((4-chloro-5-(3-chloro-4-cyanophenyl)pyridin-3-yl)(cyclopropyl)methyl)-N-methylmethanesulfonamide

HRID 2407444Notes

Reaction equation

HRID 2407444 reaction equation
Br[C:2]1[C:3]([Cl:18])=[C:4]([CH:8]([CH:15]2[CH2:17][CH2:16]2)[N:9]([CH3:14])[S:10]([CH3:13])(=[O:12])=[O:11])[CH:5]=[N:6][CH:7]=1.[Cl:19][C:20]1[CH:27]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH:25]=[CH:24][C:21]=1[C:22]#[N:23].C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.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].O>[Cl:18][C:3]1[C:2]([C:26]2[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[C:20]([Cl:19])[CH:27]=2)=[CH:7][N:6]=[CH:5][C:4]=1[CH:8]([CH:15]1[CH2:17][CH2:16]1)[N:9]([CH3:14])[S:10]([CH3:13])(=[O:12])=[O:11]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 579261132-Chloro-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrileHCID 59578436N-((5-bromo-4-chloropyridin-3-yl)(cyclopropyl)methyl)-N-methylmethanesulfonamide

Product 1

HCID 59578406N-((4-chloro-5-(3-chloro-4-cyanophenyl)pyridin-3-yl)(cyclopropyl)methyl)-N-methylmethanesulfonamide

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-((5-bromo-4-chloropyridin-3-yl)(cyclopropyl)methyl)-N-methylmethanesulfonamide (1.03 g, 2.9 mmol) and 2-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (2.29 g, 8.7 mmol) in DMF (20 mL) was added PdCl2(dppf).CH2Cl2 (118 mg, 0.145 mmol) and 2M Na2CO3 in water (2.9 mL, 5.8 mmol), and the mixture was heated to 85° C. for 7 h. The mixture was cooled to room temperature, poured into water (100 mL), extracted with EtOAc (200 mL*3), washed with water (20 mL*3) and dried over Na2SO4. The mixture was purified by silica gel chromatography eluting with a 0-50% EtOAc-heptane gradient to give N-((4-chloro-5-(3-chloro-4-cyanophenyl)pyridin-3-yl)(cyclopropyl)methyl)-N-methylmethanesulfonamide. MS (ESI): m/z 410.1, 412.1 (M+H)+.

Workup

  1. extractionextracted with EtOAc (200 mL*3)
  2. washwashed with water (20 mL*3)
  3. dry with materialdried over Na2SO4
  4. customThe mixture was purified by silica gel chromatography
  5. washeluting with a 0-50% EtOAc-heptane gradient

Sources & evidence

ORD record
ord-8927332fe92b4174bda80ced7a2ab3cc
Source dataset
uspto-grants-2014_08
Patent number
US08809545B2

Reaction notes

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