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

HRID 1360854Notes

Reaction equation

HRID 1360854 reaction equation
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

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

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 h30. 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+ (ES): 239.01. HPLC, Rt: 3.01 min (purity: 98.7%).

Workup

  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

Sources & evidence

ORD record
ord-40be32e3c37a46a7b6babd2782b1c5ac
Source dataset
uspto-grants-2011_02
Patent number
US07879888B2

Reaction notes

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