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

HRID 1432634

反応式

HRID 1432634 の反応式
Br[C:2]1[S:6][C:5]([C:7]2[N:11]3[N:12]=[C:13]([CH3:21])[CH:14]=[C:15]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[C:10]3=[N:9][C:8]=2[CH3:22])=[C:4]([CH3:23])[CH:3]=1.C([Sn](CCCC)(CCCC)[C:29]1[N:34]=[CH:33][CH:32]=[CH:31][N:30]=1)CCC.N#N.C1([As](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1COCC1>[CH2:17]([CH:16]([C:15]1[C:10]2[N:11]([C:7]([C:5]3[S:6][C:2]([C:29]4[N:34]=[CH:33][CH:32]=[CH:31][N:30]=4)=[CH:3][C:4]=3[CH3:23])=[C:8]([CH3:22])[N:9]=2)[N:12]=[C:13]([CH3:21])[CH:14]=1)[CH2:19][CH3:20])[CH3:18]

参加物

7

反応物 4

HCID 947NitrogenHCID 11773TriphenylarsineHCID 27632512-(Tributylstannyl)pyrimidineHCID 579329433-(5-Bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

生成物 1

HCID 579330298-(1-Ethyl-propyl)-2,6-dimethyl-3-(3-methyl-5-pyrimidin-2-yl-thiophen-2-yl)-imidazo[1,2-b]pyridazine収率 32.9%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
55 °C

実験手順

A solution of 3-(5-bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.30 g, 0.76 mmol), 2-tributylstannanyl-pyrimidine (0.34 g, 0.92 mmol) and THF (5 mL) is de-gassed with N2 for 10 minutes Triphenylarsine (0.047 g, 0.15 mmol) and Pd2(dba)3 (0.035 g, 0.038 mmol) is added and the solution heated at 55° C. for 48 hours and concentrated. The residue is purified by ISCO column chromatography (15%-30% EtOAc/hexane gradient), dissolved in acetonitrile (20 mL), washed with hexane (3×20 mL) and concentrated to furnished the title compound (0.097 g, 0.25 mmol, 32%). 1H NMR (CDCl3), δ 0.88 (t, J=7.4 Hz, 6H), 1.74-1.92 (m, 4H), 2.18 (s, 3H), 2.51 (s, 3H), 2.52 (s, 3H), 3.29-3.38 (m, 1H), 6.67 (s, 1H), 7.08 (t, J=4.8, 1H), 7.93 (s, 1H), 8.69 (s, 2H). LC/MS (m/z): calcd. for C22H25N5S (M+H)+: 392.3; found: 392.2.

後処理

  1. additionis added
  2. concentrationconcentrated
  3. customThe residue is purified by ISCO column chromatography (15%-30% EtOAc/hexane gradient)
  4. dissolutiondissolved in acetonitrile (20 mL)
  5. washwashed with hexane (3×20 mL)
  6. concentrationconcentrated

出典と根拠

ORDレコード
ord-5ba2830042f6465a811573cd35527de4
出典データセット
uspto-grants-2009_11
特許番号
US07612067B2

関連ノート

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