Diisopropylethylamine → 1-(4-ethynylbenzyl)-3,5-dimethyl-1H-pyrazol-4-yl-acetic acid tert.-butyl ester

HRID 1500400노트

반응식

HRID 1500400 반응식
[C:1]([O:5][C:6](=[O:23])[CH2:7][C:8]1[C:9]([CH3:22])=[N:10][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18](I)=[CH:17][CH:16]=2)[C:12]=1[CH3:13])([CH3:4])([CH3:3])[CH3:2].[CH:24](N(C(C)C)CC)(C)[CH3:25].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[C:1]([O:5][C:6](=[O:23])[CH2:7][C:8]1[C:9]([CH3:22])=[N:10][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:24]#[CH:25])=[CH:17][CH:16]=2)[C:12]=1[CH3:13])([CH3:4])([CH3:3])[CH3:2]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 2724141Tetrabutylammonium FluorideHCID 68390870tert-butyl 2-(1-(4-iodobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)acetate

생성물 1

HCID 867165361-(4-ethynylbenzyl)-3,5-dimethyl-1H-pyrazol-4-yl-acetic acid tert.-butyl ester

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

To a stirred solution of 1-(4-iodobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl-acetic acid tert.-butyl ester (12.2 g) in tetrahydrofuran (100 ml) at room temperature is added diisopropylethylamine (12.3 ml). The solution is degassed and put under argon. Ethynyltrimethylsilane (4.5 ml), copper(I)iodide (543 mg) and bis-(triphenylphosphine)-palladiumdichloride (1.0 g) are added. After 15 h of stirring, the reaction is absorbed onto Extrelute and purified by flash chromatography (4:1 isocratic-cyclohexane:ethyl acetate) to yield a solid (10.7 g; [M+H]=397; HPLC retention time 1.71 min (Method J)). The solid is dissolved in tetrahydrofuran (200 ml) and is stirred together with tetrabutylammonium fluoride (1 M in THF, 28 ml). After 15 h at room temperature, the reaction mixture is concentrated in vacuo. The residue is purified by flash chromatography (4:1 isocratic-cyclohexane:ethyl acetate) to yield 1-(4-ethynylbenzyl)-3,5-dimethyl-1H-pyrazol-4-yl-acetic acid tert.-butyl ester (6.8 g; [M+H]=325; HPLC retention time 1.47 min (Method J)).

후처리

  1. customThe solution is degassed
  2. additionEthynyltrimethylsilane (4.5 ml), copper(I)iodide (543 mg) and bis-(triphenylphosphine)-palladiumdichloride (1.0 g) are added
  3. customthe reaction is absorbed onto Extrelute
  4. custompurified by flash chromatography (4:1 isocratic-cyclohexane:ethyl acetate)
  5. customto yield a solid (10.7 g; [M+H]=397; HPLC retention time 1.71 min (Method J))
  6. waitAfter 15 h at room temperature
  7. concentrationthe reaction mixture is concentrated in vacuo
  8. customThe residue is purified by flash chromatography (4:1 isocratic-cyclohexane:ethyl acetate)

출처 및 근거

ORD 기록
ord-ceb58efe395445e0ab7fa5eb155f8599
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09206164B2

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