Dichloromethane → (4-(5-Bromopyridin-3-yl)phenyl)-(4-isopropylpiperazin-1-yl)-methanone

HRID 1970962Notes

Reaction equation

HRID 1970962 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[CH:17]=[CH:16][C:15](B3OC(C)(C)C(C)(C)O3)=[CH:14][CH:13]=2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].C(=O)([O-])[O-].[Na+].[Na+].[Br:33][C:34]1[CH:35]=[N:36][CH:37]=[C:38](Br)[CH:39]=1.C(Cl)Cl>COCCOC.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]>[Br:33][C:34]1[CH:39]=[C:38]([C:15]2[CH:14]=[CH:13][C:12]([C:10]([N:7]3[CH2:6][CH2:5][N:4]([CH:1]([CH3:2])[CH3:3])[CH2:9][CH2:8]3)=[O:11])=[CH:17][CH:16]=2)[CH:37]=[N:36][CH:35]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 693693,5-DibromopyridineHCID 68756040(4-Isopropyl-piperazin-1-yl)-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-methanone

Product 1

HCID 68733155(4-(5-Bromopyridin-3-yl)phenyl)-(4-isopropylpiperazin-1-yl)-methanone

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of (4-isopropylpiperazin-1-yl)-(4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl) phenyl)-methanone (step 1) (1.0 eq, 778 mg) in DME (4 ml) and 2M sodium carbonate solution (2 eq, 2.2 ml) is treated with 3,5-dibromopyridine (1 eq, 514 mg) followed by PdCl2(dppf).DCM (0.1 eq, 159 mg). The resulting mixture is heated using microwave radiation at 90° C. for 1 h. The mixture is extracted with DCM and the organic extracts are washed with water. The solvent is removed in vacuo and the crude product is purified by chromatography on silica eluting with 0-100% EtOAc in iso-hexane followed by 0-5% MeOH in DCM to afford the title compound [M+H]+=388/390.

Workup

  1. temperatureThe resulting mixture is heated
  2. customat 90° C.
  3. customfor 1 h
  4. extractionThe mixture is extracted with DCM
  5. washthe organic extracts are washed with water
  6. customThe solvent is removed in vacuo
  7. customthe crude product is purified by chromatography on silica eluting with 0-100% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-9f6f8b2af2c549b0a2f40c293c5ce09c
Source dataset
uspto-grants-2013_04
Patent number
US08431578B2

Reaction notes

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