Dimethylformamide → HCID 59828831, compound

HRID 1191072Notes

Reaction equation

HRID 1191072 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([NH:14][CH2:15][CH:16]3[CH2:18][CH2:17]3)[S:11][C:12]=2[CH3:13])=[CH:4][CH:3]=1.[CH3:19][N:20](C=O)C>ClCCl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:16]1([CH2:15][NH:14][C:10]2[S:11][C:12]([CH3:13])=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([C:19]#[N:20])=[CH:3][CH:4]=3)[N:9]=2)[CH2:18][CH2:17]1

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 59828834HCID 59828834, compound

Product 1

HCID 59828831HCID 59828831, compoundYield 52%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6344DichloromethaneSolvent

Procedure

Slurry 1-bromo-4-(2-cyclopropylmethylamino-5-methyl-thiazol-4-yl)-benzene (1.0 g, 3.09 mmol), 1,1′-bis-(diphenylphosphino)ferrocene (275 mg, 0.494 mmol), zinc cyanide (325 mg, 2.75 mmol) and tris(dibenzylideneacetone)dipalladium(0) (254 mg, 0.28 mmol) in DMF (6 mL) and heat in a sealed tube at 110° C. overnight. Cool the mixture to room temperature, dilute with dichloromethane (100 mL) and filter over Celite®. Concentrate in vacuo and purify the crude mixture by chromatography on silica gel (40 g) eluting with hexane/EtOAc (19:1 to 7:3 gradient over 30 min; 40 mL/min) to obtain the desired intermediate (416 mg, 52%) as a yellow solid. MS (ES+) m/z: 270 (M+H)+.

Workup

  1. filtrationfilter over Celite®
  2. concentrationConcentrate in vacuo
  3. custompurify the crude mixture by chromatography on silica gel (40 g)
  4. washeluting with hexane/EtOAc (19:1 to 7:3 gradient over 30 min; 40 mL/min)

Sources & evidence

ORD record
ord-0d1f34f633194195ae192f02a82d65fc
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

Loading…