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 1518276Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1518276
[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]

Komponenten

8

Edukt 3

HCID 7859Propargyl alcoholHCID 81531DiisopropylethylamineHCID 86644321HCID 86644321, Verbindung

Produkt 1

HCID 59447607methyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(3-hydroxyprop-1-ynyl)thiazole-4-carboxylateAusbeute 74,2 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

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)

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-9b318f06a57b4dd3952b181f2924bac1
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08232273B2

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