Nitrogen → 3-[3-Chloro-5-(6-methyl-pyridin-2-yl)-thiophen-2-yl]-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

HRID 1432625노트

반응식

HRID 1432625 반응식
[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([CH:13]=[C:14]([CH3:16])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2].Br[C:18]1[S:22][C:21]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([CH3:29])[N:24]=2)=[CH:20][C:19]=1[Cl:30].C([O-])([O-])=O.[Cs+].[Cs+].N#N.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>CCOC(C)=O.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].CN(C=O)C>[Cl:30][C:19]1[CH:20]=[C:21]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([CH3:29])[N:24]=2)[S:22][C:18]=1[C:13]1[N:8]2[N:9]=[C:10]([CH3:12])[CH:11]=[C:6]([CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])[C:7]2=[N:15][C:14]=1[CH3:16]

참가 물질

9

반응물 5

HCID 947NitrogenHCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 688412672,6-Dimethyl-8-(pentan-3-yl)imidazo[1,2-b]pyridazineHCID 688441482-(5-Bromo-4-chloro-thiophen-2-yl)-6-methyl-pyridine

생성물 1

HCID 579329983-[3-Chloro-5-(6-methyl-pyridin-2-yl)-thiophen-2-yl]-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine수율 10.1%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

반응 조건

온도
110 °C

실험 절차

A solution of 8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.39 g, 1.78 mmol), 2-(5-bromo-4-chloro-thiophen-2-yl)-6-methyl-pyridine (0.59 g, 2.04 mmol), Cs2CO3 (1.23 g, 3.77 mmol), and DMF (5 mL), is de-gassed with N2 for 15 minutes. PPh3 (0.089 g, 0.34 mmol) and Pd2(dba)3 (0.079 g, 0.86 mmol) is added and the solution heated at 110° C. for 48 hours. The solution is diluted with EtOAc (30 mL), washed with sat. NH4Cl (25 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (20%-30% EtOAc/hexane gradient) and is chromatographed (19×300 C18 Symmetry column, 20-45% water: 0.1% TFA/ACN: 0.1% TFA gradient) furnish the title compound (0.078 g, 0.18 mmol, 10%). Spectrum identical to Method A.

후처리

  1. washwashed with sat. NH4Cl (25 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by ISCO column chromatography (20%-30% EtOAc/hexane gradient)
  6. customis chromatographed (19×300 C18 Symmetry column, 20-45% water: 0.1% TFA/ACN: 0.1% TFA gradient)

출처 및 근거

ORD 기록
ord-a3466622400542bc9be8c9e9f022c812
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07612067B2

반응 노트

불러오는 중…