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

HRID 1962867ノート

反応式

HRID 1962867 の反応式
[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]

参加物

5

反応物 3

HCID 7842Propargyl bromide2 回HCID 24758Sodium hydrideHCID 595653242-(3-ethynyl-8-methyl-quinolin-6-yloxy)-N-(2-hydroxy-1-methoxymethyl-1-methyl-ethyl)-2-methylsulfanyl-acetamide

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
55 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-f3415ea93afd471cabb04fefe347490c
出典データセット
uspto-grants-2013_04
特許番号
US08415272B2

反応ノート

読み込み中…