Acetic Acid → HCID 178522934, compound

HRID 2299287Notes

Reaction equation

HRID 2299287 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[Br:13][C:14]1[S:26][C:17]2=[N:18][CH:19]=[C:20]([C:23]([OH:25])=O)[C:21]([OH:22])=[C:16]2[CH:15]=1.[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>[Br:13][C:14]1[S:26][C:17]2=[N:18][CH:19]=[C:20]([C:23]([NH:33][CH2:32][C:31]3[CH:34]=[CH:35][C:28]([Cl:27])=[CH:29][CH:30]=3)=[O:25])[C:21]([OH:22])=[C:16]2[CH:15]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 660364-ChlorobenzylamineHCID 682631,1'-CarbonyldiimidazoleHCID 178524745HCID 178524745, compound

Product 1

HCID 178522934HCID 178522934, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of ethyl 4-hydroxythieno[2,3-b]pyridine-5-carboxylate (J. Heterocyclic Chem. 1977, 14, 807) (1.00 g) in CHCl3 (26 mL) is added bromine (0.23 mL) dropwise. The reaction is stirred at rt for 2 h. The reaction mixture is poured into 2N HCl (30 mL), and the aqueous layer is extracted with CHCl3 (3×30 mL). The combined organic layers are washed with H2O (100.mL), dried with MgSO4, filtered and concentrated in vacuo to yield 0.840 g (62%) of the bromide as a yellow solid. This material (0.757 g) is suspended in 10% aqueous NaOH (7 mL) and heated to reflux. The reaction is stirred at reflux for 1 h. The reaction mixture is cooled to rt, and H2O (26 mL) is added. Conc. HCl is added until a precipitate forms. The precipitate is filtered off to yield 0.597 (87%) of the acid as a brown solid. Carbonyldiimidazole (0.530 g) is added to a solution of 2-bromo-4-hydroxy-thieno-[2,3-b]pyridine-5-carboxylic acid (0.597 g) in DMF (20 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) 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-78fcf47faf3841c9973f09954f3ffe80
Source dataset
uspto-grants-2002_12
Patent number
US06495683B2

Reaction notes

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