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 1518276노트

반응식

HRID 1518276 반응식
[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]

참가 물질

8

반응물 3

HCID 7859Propargyl alcoholHCID 81531DiisopropylethylamineHCID 86644321HCID 86644321, 화합물

생성물 1

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

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

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)

후처리

  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

출처 및 근거

ORD 기록
ord-9b318f06a57b4dd3952b181f2924bac1
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08232273B2

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