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

HRID 539749
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HRID 539749 반응식
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
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참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
촉매

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온도
150 °C

실험 절차

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)

후처리

  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)

출처 및 근거

ORD 기록
ord-d11ab9d574bf460cb8840eda05612d6a
출처 데이터셋
uspto-grants-2014_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08871767B2

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