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 1432625ノート

反応式

HRID 1432625 の反応式
[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]

参加物

9

反応物 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

生成物 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]pyridazine収率 10.1%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
110 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-a3466622400542bc9be8c9e9f022c812
出典データセット
uspto-grants-2009_11
特許番号
US07612067B2

反応ノート

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