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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
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HRID 1785148 반응식
[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
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 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-yne2회

생성물 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
수율 73%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-0a3ac54f66474a0b88147a0694c6ec41
출처 데이터셋
uspto-grants-2009_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07504408B2

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