Propargyl bromide → 2-(3-Ethynyl-8-methyl-quinolin-6-yloxy)-N-(2-methoxy-1-methyl-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl-acetamide

HRID 1962867노트

반응식

HRID 1962867 반응식
[C:1]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([CH:12]=1)=[CH:10][C:9]([O:13][CH:14]([S:25][CH3:26])[C:15]([NH:17][C:18]([CH2:22][O:23][CH3:24])([CH3:21])[CH2:19][OH:20])=[O:16])=[CH:8][C:7]=2[CH3:27])#[CH:2].[CH2:28](Br)[C:29]#[CH:30].[H-].[Na+]>C1COCC1>[C:1]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([CH:12]=1)=[CH:10][C:9]([O:13][CH:14]([S:25][CH3:26])[C:15]([NH:17][C:18]([CH3:21])([CH2:19][O:20][CH2:30][C:29]#[CH:28])[CH2:22][O:23][CH3:24])=[O:16])=[CH:8][C:7]=2[CH3:27])#[CH:2]

참가 물질

5

반응물 3

HCID 7842Propargyl bromide2회HCID 24758Sodium hydrideHCID 595653242-(3-ethynyl-8-methyl-quinolin-6-yloxy)-N-(2-hydroxy-1-methoxymethyl-1-methyl-ethyl)-2-methylsulfanyl-acetamide

생성물 1

HCID 866472522-(3-Ethynyl-8-methyl-quinolin-6-yloxy)-N-(2-methoxy-1-methyl-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl-acetamide수율 50.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
55 °C

실험 절차

To a solution of 2-(3-ethynyl-8-methyl-quinolin-6-yloxy)-N-(2-hydroxy-1-methoxymethyl-1-methyl-ethyl)-2-methylsulfanyl-acetamide (120 mg) in dry THF (10 ml) NaH (27 mg, 60% in oil) was added at room temperature under a nitrogen atmosphere. After 30 minute propargyl bromide (115 mg) was added to the reaction mixture. After stirring during 5 h one equivalent of NaH and one equivalent of propargyl bromide were added. The mixture was stirred during 4 h at 55° C., then quenched with water and diluted with ethyl acetate. The water phase was extracted twice with ethyl acetate and the combined organic phases dried over sodium sulfate, filtered and evaporated. The crude residue was purified by column chromatography (cyclohexane/ethyl acetate, 3:2) to give 2-(3-Ethynyl-8-methyl-quinolin-6-yloxy)-N-(2-methoxy-1-methyl-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl-acetamide (66 mg) as a light brown oil as a mixture of diastereoisomers.

후처리

  1. additionwere added
  2. customquenched with water
  3. additiondiluted with ethyl acetate
  4. extractionThe water phase was extracted twice with ethyl acetate
  5. dry with materialthe combined organic phases dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude residue was purified by column chromatography (cyclohexane/ethyl acetate, 3:2)

출처 및 근거

ORD 기록
ord-f3415ea93afd471cabb04fefe347490c
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415272B2

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