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

HRID 1364488Notes

Reaction equation

HRID 1364488 reaction equation
IC1SC(NC(=O)C)=NC=1C.C([C:14]1[S:18][C:17]([C:19]2[S:23][C:22]([NH:24][C:25](=[O:27])[CH3:26])=[N:21][C:20]=2[CH3:28])=[CH:16][CH:15]=1)=O.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]>[CH3:28][C:20]1[N:21]=[C:22]([NH:24][C:25](=[O:27])[CH3:26])[S:23][C:19]=1[C:17]1[S:18][CH:14]=[CH:15][CH:16]=1

Participants

6

Reactant 3

HCID 27793732-(Tri-n-butylstannyl)thiopheneHCID 11993393Acetamide, N-[5-(5-formyl-2-thienyl)-4-methyl-2-thiazolyl]-HCID 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 Compound (6) 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%).

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-a88ee0da510843f4941c9c020ff5664a
Source dataset
uspto-grants-2011_02
Patent number
US07888379B2

Reaction notes

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