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

HRID 1432610ノート

反応式

HRID 1432610 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.C1[CH2:28][O:27][CH2:26]C1.C([Li])CCC.ICOC>CCOC(C)=O>[CH2:17]([CH:16]([C:15]1[C:10]2[N:11]([C:7]([C:5]3[S:6][C:2]([CH2:26][O:27][CH3:28])=[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

6

反応物 4

HCID 8028TetrahydrofuranHCID 139376Iodomethyl methyl etherHCID 579329433-(5-Bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 178418339Butyllithium

生成物 1

HCID 579330158-(1-Ethyl-propyl)-3-(5-methoxymethyl-3-methyl-thiophen-2-yl)-2,6-dimethyl-imidazo[1,2-b]pyridazine収率 44%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

To a −78° C. 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) and THF (3 mL) is added 1.34 M n-Bu-Li (0.50 mL, 0.80 mmol). After 30 minutes iodo-methoxy-methane (0.097 mL, 1.15 mmol) is added and the solution warmed to ambient temperature. After 1 hour the solution is diluted with EtOAc (40 mL) washed with water (30 mL), brine (30 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (15%-20% EtOAc/hexane gradient) furnish the title compound (0.12 g, 0.34 mmol, 44%). 1H NMR (CDCl3), δ 0.87 (t, J=7.5 Hz, 6H), 1.72-1.90 (m, 4H), 2.09 (s, 3H), 2.45 (s, 3H), 2.49 (s, 3H), 3.28-3.37 (m, 1H), 3.44 (s, 3H), 4.61 (s, 2H), 6.65 (s, 1H), 6.93 (s, 1H). LC/MS (m/z): calcd. for C20H27N3OS (M+H)+: 358.3; found: 358.3.

後処理

  1. washwashed with water (30 mL), brine (30 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by ISCO column chromatography (15%-20% EtOAc/hexane gradient)

出典と根拠

ORDレコード
ord-c56ebcf8b6074bb6a97c073cd97a3213
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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