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

HRID 1948391ノート

反応式

HRID 1948391 の反応式
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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

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

反応条件

温度
100 °C

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-874aeffdb58a411488db582910b1f081
出典データセット
uspto-grants-2013_03
特許番号
US08399497B2

反応ノート

読み込み中…