Potassium Fluoride → N-[4-methyl-5-(3-thienyl)-1,3-thiazol-2-yl]acetamide

HRID 1364499Notes

Reaction equation

HRID 1364499 reaction equation
I[C:2]1[S:6][C:5]([NH:7][C:8](=[O:10])[CH3:9])=[N:4][C:3]=1[CH3:11].C([C:14]1[S:18][C:17](C2SC(NC(=O)C)=NC=2C)=[CH:16][CH:15]=1)=O.[F-].[K+].CC1(C)C(C)(C)OB(C2C=CSC=2)O1>C1(C)C=CC=CC=1.CO.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]>[CH3:11][C:3]1[N:4]=[C:5]([NH:7][C:8](=[O:10])[CH3:9])[S:6][C:2]=1[C:16]1[CH:15]=[CH:14][S:18][CH:17]=1

Participants

8

Reactant 4

HCID 522689Potassium FluorideHCID 27605974,4,5,5-Tetramethyl-2-(thiophen-3-yl)-1,3,2-dioxaborolaneHCID 11993393Acetamide, N-[5-(5-formyl-2-thienyl)-4-methyl-2-thiazolyl]-HCID 57417074N-(5-Iodo-4-methyl-2-thiazolyl)acetamide

Product 1

HCID 11993592N-[4-methyl-5-(3-thienyl)-1,3-thiazol-2-yl]acetamideYield 66%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

In a microwave tube, N-(5-iodo-4-methyl-1,3-thiazol-2-yl)acetamide, Intermediate 1 (564.2 mg; 2 mmol; 1 eq.) and Pd(dppf)Cl2 (73.2 mg; 0.10 mmol; 0.05 eq.) are suspended in Toluene (7 ml). A solution of potassium fluoride (464.8 mg; 8 mmol; 4 eq.) in MeOH (7 ml) is added. 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene (630.3 mg; 3 mmol; 1.50 eq.) is finally added as a solid. The resulting solution is flushed with argon, the tube is closed and heated under microwave action at 120° C. for 15 minutes. The reaction mixture is filtered over Celite and the solvents are evaporated. The resulting crude product is dissolved in EtOAc, washed with water and brine and dried over MgSO4. It is then purified by preparative HPLC, affording Compound (19) as white-off solid (316.7 mg; 66% yield). 1H NMR (DMSO-d6) δ 2.12 (s, 3H), 2.35 (s, 3H), 7.28 (dd, J=1.5, 4.9 Hz, 1H), 7.58 (dd, J=1.5, 3.0 Hz, 1H), 7.67 (dd, J=3.0, 4.9 Hz, 1H), 12.09 (s, 1H). M−(ESI): 237.03; M+(ESI): 239.03. HPLC, Rt: 2.92 min (purity: 99.6%).

Workup

  1. customThe resulting solution is flushed with argon
  2. customthe tube is closed
  3. filtrationThe reaction mixture is filtered over Celite
  4. customthe solvents are evaporated
  5. dissolutionThe resulting crude product is dissolved in EtOAc
  6. washwashed with water and brine
  7. dry with materialdried over MgSO4
  8. customIt is then purified by preparative HPLC

Sources & evidence

ORD record
ord-c9afaa78a96b4a8083d528118bedbedc
Source dataset
uspto-grants-2011_02
Patent number
US07888379B2

Reaction notes

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