Tetrahydrofuran → N-[5-(6-cyclopentylimidazo[2,1-f]pyridazin-2-yl)-2-(trifluoromethyl)phenyl]-dimethyl-propanamide

HRID 539749Notes

Reaction equation

HRID 539749 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]2=[N:8][C:9]([C:11]3[CH:12]=[CH:13][C:14]([C:24]([F:27])([F:26])[F:25])=[C:15]([NH:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[CH:16]=3)=[CH:10][N:4]2[N:3]=1.[Br-].[CH:29]1([Zn+])[CH2:31][CH2:30]1.[CH2:33]1COC[CH2:34]1>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]>[CH:30]1([C:2]2[CH:7]=[CH:6][C:5]3=[N:8][C:9]([C:11]4[CH:12]=[CH:13][C:14]([C:24]([F:27])([F:26])[F:25])=[C:15]([NH:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[CH:16]=4)=[CH:10][N:4]3[N:3]=2)[CH2:31][CH2:29][CH2:34][CH2:33]1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 86667850N-(5-(6-chloroimidazo[1,2-b]pyridazin-2-yl)-2-(trifluoromethyl)phenyl)pivalamideHCID 178419765HCID 178419765, compound

Product 1

HCID 67983831N-[5-(6-cyclopentylimidazo[2,1-f]pyridazin-2-yl)-2-(trifluoromethyl)phenyl]-dimethyl-propanamideYield 11%

Reagents, catalysts & solvents 1

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

Conditions

Temperature
150 °C

Procedure

A small vial is charged with N-[5-(6-chloroimidazo[2,1-f]pyridazin-2-yl)-2-(trifluoromethyl)phenyl]-2,2-dimethyl-propanamide (0.032 g, 0.08 mol), cyclopropylzinc bromide (0.12 mL, 2 M in THF, 0.24 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (6 mg, 0.01 mol), and THF (0.32 mL). The reaction vessel is purged with N2 and heated to 150° C. in the microwave for 2 hr. Sat. aqueous NH4Cl is added to the mixture and it is extracted with EtOAc. The combined organic layers are dried over Na2SO4, filtered, concentrated, and purified by silica gel chromatography (hexanes to ethyl acetate) to give the title compound (3.5 mg, 11% yield). LCMS m/z=431.5 [M+H]+, tR=3.21 min. (compound same as Example 316)

Workup

  1. customThe reaction vessel is purged with N2
  2. additionSat. aqueous NH4Cl is added to the mixture and it
  3. extractionis extracted with EtOAc
  4. dry with materialThe combined organic layers are dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by silica gel chromatography (hexanes to ethyl acetate)

Sources & evidence

ORD record
ord-d11ab9d574bf460cb8840eda05612d6a
Source dataset
uspto-grants-2014_10
Patent number
US08871767B2

Reaction notes

Loading…