Cesium carbonate → 8-(1-Ethyl-propyl)-3-(5-fluoro-3-methyl-benzo[b]thiophen-2-yl)-6-methyl-2-trifluoromethyl-imidazo[1,2-b]pyridazine

HRID 226044ノート

反応式

HRID 226044 の反応式
[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2].Br[C:21]1[S:25][C:24]2[CH:26]=[CH:27][C:28]([F:30])=[CH:29][C:23]=2[C:22]=1[CH3:31].C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>CN1C(=O)CCC1.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]>[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([C:13]([C:21]3[S:25][C:24]4[CH:26]=[CH:27][C:28]([F:30])=[CH:29][C:23]=4[C:22]=3[CH3:31])=[C:14]([C:16]([F:18])([F:19])[F:17])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2]

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 667212022-Bromo-5-fluoro-3-methylbenzo[b]thiopheneHCID 688409078-(1-Ethyl-propyl)-6-methyl-2-trifluoromethyl-imidazo[1,2-b]pyridazine

生成物 1

HCID 577526508-(1-Ethyl-propyl)-3-(5-fluoro-3-methyl-benzo[b]thiophen-2-yl)-6-methyl-2-trifluoromethyl-imidazo[1,2-b]pyridazine収率 10%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
130 °C

実験手順

To a dry 10 ml round bottom flask with reflux condenser containing 8-(1-ethyl-propyl)-6-methyl-2-trifluoromethyl-imidazo[1,2-b]pyridazine (150 mg, 0.690 mmol), 2-bromo-5-fluoro-3-methyl-benzo[b]thiophene (186.1 mg, 0.759 mmol), and Cs2CO3 (472 mg, 1.45 mmol) in NMP (1.1 ml). The mixture is degassed with bubbling N2 for 15 min. Then add Pd2(dba)3 (32 mg, 0.0345 mmol) and PPh3 (36.2 mg, 0.138 mmol). Heat the reaction mixture at 130° C. and stir overnight. Dilute with H2O; extract with EtOAc (3×20 ml); dried (Na2SO4), filter and purify by HPLC to give title compound (29.5 mg, 0.068 mmol, 10%). 1H NMR (CDCl3): 0.931 (t, J=7.6 Hz, 6H), 1.912 (m, 4H), 2.286 (s, 3H), 2.552 (s, 3H), 3.386 (m, 1H), 6.877 (s, 1H), 7.224 (td, J=2.4, 9.0 Hz, 1H), 7.50 (dd, J=2.9, 9.8 Hz, 1H), 7.842 (dd, J=4.9, 9.0 Hz, 1H) ppm. ES-MS (m/z): calcd for C22H21F4N3S (M+H)+: 435.39. found: 436.2.

後処理

  1. temperatureTo a dry 10 ml round bottom flask with reflux condenser
  2. customThe mixture is degassed with bubbling N2 for 15 min
  3. extractionextract with EtOAc (3×20 ml)
  4. dry with materialdried (Na2SO4)
  5. filtrationfilter
  6. custompurify by HPLC

出典と根拠

ORDレコード
ord-417002ea858b4115a604cba58048daec
出典データセット
uspto-grants-2009_07
特許番号
US07557103B2

反応ノート

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