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Dimethylformamide → 4-{3-[(4-{[5-Chloro-7-(4-methoxypent-1-yn-1-yl)-1,3-benzodioxol-4-yl]amino}-6-methoxyquinazolin-7-yl)oxy]propyl}-1-methylpiperazin-2-one

HRID 1785148
ノート
印刷プレビュー

反応式

HRID 1785148 の反応式
[Cl:1][C:2]1[CH:10]=[C:9](I)[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:34][CH2:33][N:32]([CH3:35])[C:31](=[O:36])[CH2:30]3)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][N:14]=1.[CH3:37][O:38][CH:39]([CH3:43])[CH2:40][C:41]#[CH:42].C(NC(C)C)(C)C.CN(C=O)C>C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Cl:1][C:2]1[CH:10]=[C:9]([C:42]#[C:41][CH2:40][CH:39]([O:38][CH3:37])[CH3:43])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:34][CH2:33][N:32]([CH3:35])[C:31](=[O:36])[CH2:30]3)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][N:14]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 6228DimethylformamideHCID 7912DiisopropylamineHCID 688822194-[3-({4-[(5-Chloro-7-iodo-1,3-benzodioxol-4-yl)amino]-6-methoxyquinazolin-7-yl}oxy)propyl]-1-methylpiperazin-2-oneHCID 866015644-Methoxypent-1-yne2 回

生成物 1

HCID 688829434-{3-[(4-{[5-Chloro-7-(4-methoxypent-1-yn-1-yl)-1,3-benzodioxol-4-yl]amino}-6-methoxyquinazolin-7-yl)oxy]propyl}-1-methylpiperazin-2-one
収率 73%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 8857Ethyl Acetate溶媒

実験手順

4-[3-({4-[(5-Chloro-7-iodo-1,3-benzodioxol-4-yl)amino]-6-methoxyquinazolin-7-yl}oxy)propyl]-1-methylpiperazin-2-one (250 mg, 0.40 mmol) and 4-methoxypent-1-yne (120 mg, 1.2 mmol) in ethyl acetate (8 ml) stirred at room temperature, under an atmosphere of nitrogen, and treated with bis(triphenylphosphine)palladium(II) dichloride (28 mg, 10 mol %) followed by copper(I) iodide (8 mg, 10 mol %) and diisopropylamine (82 mg, 0.81 mmol). The reaction was stirred 2 hr then DMF (3 ml) added followed by a further 120 mg 4-methoxypent-1-yne. The mixture was stirred for 1 hr then evaporated and the residue partitioned between water and dichloromethane. The organic layer was separated, washed with brine, dried over magnesium sulphate and evaporated to an orange oil. Purified by column chromatography on silica using increasing concentrations of methanol in dichloromethane as eluent to give the title compound (174 mg, 73%) as a pale yellow solid; NMR Spectrum:(DMSOd6) 1.23 (d, 3H), 1.98 (quintet, 2H), 2.54 (t, 2H), 2.61 (dd, 1H), 2.65-2.75 (m, 3H), 2.82 (s, 3H), 3.01 (s, 2H), 3.27 (t, 2H), 3.30 (s, 3H), 3.53 (m, 1H), 3.92 (s, 3H), 4.18 (t, 2H), 6.13 (s, 2H), 7.06 (s, 1H), 7.22 (s(broad), 1H), 7.84 (s, 1H), 8.38 (s(broad), 1H), 9.49 (s, 1H); Mass Spectrum: M+H+ 596/598.

後処理

  1. stirringThe mixture was stirred for 1 hr
  2. customthen evaporated
  3. customthe residue partitioned between water and dichloromethane
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over magnesium sulphate
  7. customevaporated to an orange oil
  8. customPurified by column chromatography on silica using
  9. temperatureincreasing concentrations of methanol in dichloromethane as eluent

出典と根拠

ORDレコード
ord-0a3ac54f66474a0b88147a0694c6ec41
出典データセット
uspto-grants-2009_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07504408B2

反応ノート

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