1-((1,1-Dimethylethyl)dimethylsilyl)-1H-imidazole → Methyl 3-[(dipropylamino)carbonyl]-5-(1H-imidazol-2-yl)benzoate

HRID 348854노트

반응식

HRID 348854 반응식
[Si]([N:8]1[CH:12]=[CH:11][N:10]=[CH:9]1)(C(C)(C)C)(C)C.C([Li])CCC.[CH2:18]([N:21]([CH2:35][CH2:36][CH3:37])[C:22]([C:24]1[CH:25]=[C:26]([CH:31]=[C:32](I)[CH:33]=1)[C:27]([O:29][CH3:30])=[O:28])=[O:23])[CH2:19][CH3:20]>O1CCCC1.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH2:35]([N:21]([CH2:18][CH2:19][CH3:20])[C:22]([C:24]1[CH:25]=[C:26]([CH:31]=[C:32]([C:9]2[NH:8][CH:12]=[CH:11][N:10]=2)[CH:33]=1)[C:27]([O:29][CH3:30])=[O:28])=[O:23])[CH2:36][CH3:37]

참가 물질

8

반응물 3

HCID 1713851-((1,1-Dimethylethyl)dimethylsilyl)-1H-imidazoleHCID 21086179Methyl 3-[(dipropylamino)carbonyl]-5-iodobenzoateHCID 178418339Butyllithium

생성물 1

HCID 21086171Methyl 3-[(dipropylamino)carbonyl]-5-(1H-imidazol-2-yl)benzoate

시약·촉매·용매 4

HCID 3007855Zincchloride촉매HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
0 °C

실험 절차

To a −70° C. stirred solution of 1-tert-butyldimethylsilylimidazole (602 mg, 3.3 mmol) in tetrahydrofuran (10 mL) is added n-butyllithium (1.6 M in hexanes, 2.3 mL, 3.63 mmol). After 30 min, zinc chloride (1 M in diethyl ether, 9.9 mL, 9.9 mmol) is added and the reaction mixture is warmed to 0° C. for 1 h. To this mixture is then added methyl 3-[(dipropylamino)carbonyl]-5-iodobenzoate prepared by the method in EXAMPLE SP-281, step2 (1.17 g, 3 mmol) followed by palladium(0) tetrakis(triphenylphosphine) (173 mg, 0.15 mmol). The reaction mixture is heated at reflux for 15 h. The reaction mixture is diluted with ethyl acetate (50 mL), washed with water, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica gel, 1–5% methanol/methylene chloride) provides the title compound in pure form. 1H NMR (300 MHz, CDCl3) δ 8.64 (s, 1H), 8.14 (s, 1H), 7.97 (s, 1H), 7.19 (s, 2H), 3.96 (s, 3H), 3.51 (m, 2H), 3.32 (m, 2H), 1.73 (m, 2H), 1.57 (m, 2H), 1.01 (m, 3H), 0.73 (m, 3H).

후처리

  1. temperatureThe reaction mixture is heated
  2. temperatureat reflux for 15 h
  3. washwashed with water, and brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by flash column chromatography (silica gel, 1–5% methanol/methylene chloride)

출처 및 근거

ORD 기록
ord-d2fca137d18d4e1ab710b6551741663d
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07176242B2

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