Acetic Acid → HCID 178522942, compound

HRID 2299283Notes

Reaction equation

HRID 2299283 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[OH:13][C:14]1[C:19]([C:20]([OH:22])=O)=[CH:18][N:17]=[C:16]2[S:23][C:24]([I:26])=[CH:25][C:15]=12.[Cl:27][C:28]1[CH:35]=[CH:34][C:31]([CH2:32][NH2:33])=[CH:30][CH:29]=1.CC(O)=O>CN(C=O)C>[Cl:27][C:28]1[CH:35]=[CH:34][C:31]([CH2:32][NH:33][C:20]([C:19]2[C:14]([OH:13])=[C:15]3[CH:25]=[C:24]([I:26])[S:23][C:16]3=[N:17][CH:18]=2)=[O:22])=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 660364-ChlorobenzylamineHCID 682631,1'-CarbonyldiimidazoleHCID 178524746HCID 178524746, compound

Product 1

HCID 178522942HCID 178522942, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

Mercuric oxide (7.10 g) and iodine (8.32 g) are added portion-wise to a solution of ethyl 4-hydroxythieno[2,3-b]pyridine-5-carboxylate (J. Heterocyclic Chem. 1977, 14, 807) (5.22 g) in CHCl3 (90 mL). The reaction is stirred at rt for 18 h. The reaction mixture is filtered, and the solid is washed with CHCl3 (400 mL). The organic layer is washed with H2O (200 mL), dried with MgSO4, filtered, and concentrated in vacuo. The resulting orange solid is purified by column chromatography (CH2Cl2:heptane, 1:1). Fractions homogeneous by TLC are combined and concentrated in vacuo to yield 2.95 g (36%) of ethyl 4-hydroxy-2-iodothieno[2,3-b]pyridine-5-carboxylate as a pale yellow solid. Ethyl 4-hydroxy-2-iodothieno[2,3-b]pyridine-5-carboxylate (2.64 g) is suspended in 10% NaOH (21 mL) and heated to reflux. The reaction is stirred at reflux for 1 h and then cooled to rt. The reaction mixture is poured into H2O (80 mL). Conc. HCl is added until a precipitate forms, and 2.272 g (94%) of 4-hydroxy-2-iodothieno[2,3-b]pyridine-5-carboxylic acid is isolated as a white solid. Carbonyldiimidazole (1.34 g) is added to a solution of 4-hydroxy-2-iodothieno[2,3-b]pyridine-5-carboxylic acid (2.041 g) in DMF (58 mL). The reaction is heated to 60° C. and stirred for 18 h. The reaction mixture is cooled to rt, and 4-chlorobenzylamine (1.01 mL, 8.27) is added. The reaction is stirred at rt for 7 h. The reaction mixture is poured into 20% aqueous HOAc (180 mL), and the resulting white solid is filtered off. This material is recrystallized from methanol then toluene to yield 2.095 g (74%) of the title compound as a white solid.

Workup

  1. temperatureThe reaction mixture is cooled to rt
  2. stirringThe reaction is stirred at rt for 7 h
  3. filtrationthe resulting white solid is filtered off
  4. customThis material is recrystallized from methanol

Sources & evidence

ORD record
ord-a5358dd023154b5ea376138f0105a27e
Source dataset
uspto-grants-2002_12
Patent number
US06495683B2

Reaction notes

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