Cesium carbonate → 5-[2-(Acetylamino)-4-methyl-1,3-thiazol-5-yl]thiophene-2-carboxylic acid

HRID 1364487Notes

Reaction equation

HRID 1364487 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(C1SC(C2SC(NC(=O)C)=NC=2C)=CC=1)=O.OB(O)[C:31]1[S:35][C:34]([C:36]([OH:38])=[O:37])=[CH:33][CH:32]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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].O.CN(C=O)C>[C:8]([NH:7][C:5]1[S:6][C:2]([C:31]2[S:35][C:34]([C:36]([OH:38])=[O:37])=[CH:33][CH:32]=2)=[C:3]([CH3:11])[N:4]=1)(=[O:10])[CH3:9]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 27798075-Boronothiophene-2-carboxylic acidHCID 11993393Acetamide, N-[5-(5-formyl-2-thienyl)-4-methyl-2-thiazolyl]-HCID 57417074N-(5-Iodo-4-methyl-2-thiazolyl)acetamide

Product 1

HCID 119933965-[2-(Acetylamino)-4-methyl-1,3-thiazol-5-yl]thiophene-2-carboxylic acid

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

N-(5-iodo-4-methyl-1,3-thiazol-2-yl)acetamide, Intermediate 1 (550 mg; 1.95 mmol; 1 eq.), 5-(dihydroxyboryl)-2-thiophenecarboxylic acid (335.3 mg; 1.95 mmol; 1 eq.), cesium carbonate (1397.5 mg; 4.29 mmol; 2.20 eq.), Pd(dppf)Cl2 (57.1 mg; 0.08 mmol; 0.04 eq.) are put in a microwave reactor, followed by DMF (8 ml) and water (4 ml). The reaction mixture is flushed with argon and is heated under microwave action for 10 min at 150° C. It is filtered through a paper filter, diluted with HCl 1N solution (10 ml) and the desired product is extracted with EtOAc. Combined organic layer is dried over MgSO4, filtered and evaporated. The crude product is purified by preparative HPLC, affording Compound (4) as white-off solid (125 mg; 22.7%). 1H NMR (DMSO-d6) δ 2.14 (s, 3H), 2.44 (s, 3H), 7.21 (d, J=3.8 Hz, 1H), 7.67 (d, J=3.8 Hz, 1H), 12.30 (s, 1H), 13.15 (br s, 1H). M−(ESI): 281; M+(ESI): 283. HPLC, Rt: 2.54 min (purity: 99.9%).

Workup

  1. customThe reaction mixture is flushed with argon
  2. filtrationIt is filtered through a paper
  3. filtrationfilter
  4. additiondiluted with HCl 1N solution (10 ml)
  5. extractionthe desired product is extracted with EtOAc
  6. dry with materialCombined organic layer is dried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude product is purified by preparative HPLC

Sources & evidence

ORD record
ord-27b9f77766ed4159aa70e52e219e1c2f
Source dataset
uspto-grants-2011_02
Patent number
US07888379B2

Reaction notes

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