2-(Tri-n-butylstannyl)thiophene → N-[4-methyl-5-(2-thienyl)-1,3-thiazol-2-yl]acetamide

HRID 1948391Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1948391
IC1SC(NC(=O)C)=NC=1C.[CH3:12][C:13]1[N:14]=[C:15]([NH:30][C:31](=[O:33])[CH3:32])[S:16][C:17]=1[C:18]1[S:19][C:20](S(NCC#C)(=O)=O)=[CH:21][CH:22]=1.C([Sn](CCCC)(CCCC)C1SC=CC=1)CCC>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:12][C:13]1[N:14]=[C:15]([NH:30][C:31](=[O:33])[CH3:32])[S:16][C:17]=1[C:18]1[S:19][CH:20]=[CH:21][CH:22]=1

Komponenten

6

Edukt 3

HCID 27793732-(Tri-n-butylstannyl)thiopheneHCID 11998301N-(4-methyl-5-{5-[(prop-2-yn-1-ylamino)sulfonyl]-2-thienyl}-1,3-thiazol-2-yl)acetamideHCID 57417074N-(5-Iodo-4-methyl-2-thiazolyl)acetamide

Produkt 1

HCID 11993489N-[4-methyl-5-(2-thienyl)-1,3-thiazol-2-yl]acetamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

N-(5-iodo-4-methyl-1,3-thiazol-2-yl)acetamide, Intermediate 1 (2 g; 7.09 mmol; 1 eq.) and Pd(dppf)Cl2 (0.52 g; 0.71 mmol; 0.10 eq.) are dissolved in DMF (35 ml). 2-(Tributylstannyl)thiophene (2.68 ml; 8.44 mmol; 1.19 eq.) is added. The reaction mixture is flushed with argon and heated at 100° C. for 1 h 30. Solvents are evaporated and the crude mixture is dissolved in EtOAc (100 ml), washed with water (3×100 ml). The aqueous phase are combined and extracted with EtOAc (2×50 ml). Combined organic phases is washed with brine and dried over MgSO4. After evaporation of the solvents, the crude product is purified by preparative HPLC, affording N-[4-methyl-5-(2-thienyl)-1,3-thiazol-2-yl]acetamide as white-off powder (1.24 g; 73.5%). 1H NMR (DMSO-d6) δ 2.16 (s, 3H), 2.42 (s, 3H), 7.15 (dd, J=3.8, 5.3 Hz, 1H), 7.20 (dd, J=1.1, 3.8 Hz, 1H), 7.60 (dd, J=1.1, 5.3 Hz, 1H), 12.19 (s, 1H). M− (ESI): 237.01; M+ (ESI): 239.01. HPLC, Rt: 3.01 min (purity: 98.7%).

Aufarbeitung

  1. customThe reaction mixture is flushed with argon
  2. customSolvents are evaporated
  3. dissolutionthe crude mixture is dissolved in EtOAc (100 ml)
  4. washwashed with water (3×100 ml)
  5. extractionextracted with EtOAc (2×50 ml)
  6. washCombined organic phases is washed with brine
  7. dry with materialdried over MgSO4
  8. customAfter evaporation of the solvents
  9. customthe crude product is purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-874aeffdb58a411488db582910b1f081
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08399497B2

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