Propargyl alcohol → methyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-hydroxyprop-1-ynyl)thiazole-4-carboxylate

HRID 1518276ノート

反応式

HRID 1518276 の反応式
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][N:20]([C:23]1[S:24][C:25](I)=[C:26]([C:28]([O-:30])=[O:29])[N:27]=1)[CH2:19][CH2:18]2)=[O:12].[CH2:32]([OH:35])[C:33]#[CH:34].[CH3:36]CN(C(C)C)C(C)C>C1COCC1.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][N:20]([C:23]1[S:24][C:25]([C:34]#[C:33][CH2:32][OH:35])=[C:26]([C:28]([O:30][CH3:36])=[O:29])[N:27]=1)[CH2:19][CH2:18]2)=[O:12]

参加物

8

反応物 3

HCID 7859Propargyl alcoholHCID 81531DiisopropylethylamineHCID 86644321HCID 86644321、化合物

生成物 1

HCID 59447607methyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-hydroxyprop-1-ynyl)thiazole-4-carboxylate収率 74.2%

試薬・触媒・溶媒 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of methyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-iodothiazole-4-carboxylate (8C) (1.2 g, 2.03 mmol) and prop-2-yn-1-ol (336 mg, 6 mmol) in THF (20 mL) was added Pd(Ph3P)4 (231 mg, 0.2 mmol), CuI (76 mg, 0.121 mmol), DIEA (520 mg, 4 mmol). The mixture was stirred under nitrogen at rt overnight. The mixture was then diluted with DCM (400 mL) and washed with water, brine, dried over Na2SO4, and concentrated under reduced pressure. The crude material was purified by column chromatography on a silica gel column eluting with 5% MeOH in DCM to provide 0.76 g (73%) of the desired product methyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-hydroxyprop-1-ynyl)thiazole-4-carboxylate (8D): LC/MS (APCI): m/z 505.1 (M+H)

後処理

  1. washwashed with water, brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customThe crude material was purified by column chromatography on a silica gel column
  5. washeluting with 5% MeOH in DCM

出典と根拠

ORDレコード
ord-9b318f06a57b4dd3952b181f2924bac1
出典データセット
uspto-grants-2012_07
特許番号
US08232273B2

反応ノート

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