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1,2-Dimethoxyethane → 5-(6-Butylamino-imidazo[1,2-b]pyridazin-3-yl)-indan-1-one

HRID 870676
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HRID 870676 반응식
Br[C:2]1[N:6]2[N:7]=[C:8]([NH:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:24]2[CH:25]=[C:26]3[C:30](=[CH:31][CH:32]=2)[C:29](=[O:33])[CH2:28][CH2:27]3)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].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].O>[CH2:12]([NH:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([C:24]3[CH:25]=[C:26]4[C:30](=[CH:31][CH:32]=3)[C:29](=[O:33])[CH2:28][CH2:27]4)=[CH:3][N:4]=2)[N:7]=1)[CH2:13][CH2:14][CH3:15]
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참가 물질

7

반응물 4

HCID 80711,2-DimethoxyethaneHCID 62657Potassium Phosphate, TribasicHCID 185417105-(tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-oneHCID 866963223-Bromo-6-(butylamino)imidazo[1,2-b]pyridazine

생성물 1

HCID 866963775-(6-Butylamino-imidazo[1,2-b]pyridazin-3-yl)-indan-1-one수율 85.3%

시약·촉매·용매 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매
HCID 962Water용매

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온도
80 °C

실험 절차

A mixture of 3-bromo-N-butylimidazo[1,2-b]pyridazin-6-amine (400 mg, 1.5 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-one (770 mg, 3.0 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (240 mg, 0.30 mmol), potassium phosphate (1.0 g, 4.5 mmol), DME (6 mL) and H2O (2 mL) was heated in a sealed vessel at 80° C. for 12 h. The reaction was cooled to RT, then the organic layer was separated and concentrated under reduced pressure to afford an oil that was purified by flash chromatography (SiO2) to afford 5-(6-butylamino-imidazo[1,2-b]pyridazin-3-yl)-indan-1-one (410 mg, 85%) as a pink solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.52 (s, 1H), 8.22 (d, J=8.1 Hz, 1H), 8.07 (s, 1H), 7.78 (s, 1H), 7.65 (d, J=8.1 Hz, 1H), 7.17 (t, J=5.4 Hz, 1H), 6.75 (d, J=9.6 Hz, 1H), 3.22-3.42 (m, 3H), 3.05-3.18 (m, 2H), 2.58-2.71 (m, 2H), 1.58-1.73 (m, 2H), 1.34-1.51 (m, 2H), 0.89-1.00 (m, 3H); LCMS (ESI) m/e 321.2 [(M+H)+, calcd for C19H21N4O 321.2].

후처리

  1. temperatureThe reaction was cooled to RT
  2. customthe organic layer was separated
  3. concentrationconcentrated under reduced pressure
  4. customto afford an oil that
  5. customwas purified by flash chromatography (SiO2)

출처 및 근거

ORD 기록
ord-ab9437289b1e42489a197ba131207848
출처 데이터셋
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08969565B2

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