Hydrochloric Acid → 4-({[2'-(Acetylamino)-4'-methyl-4,5'-bi-1,3-thiazol-2-yl]carbonyl}amino)-2-hydroxybenzoic acid

HRID 1715272Notes

Reaction equation

HRID 1715272 reaction equation
[C:1]([NH:4][C:5]1[S:6][C:7]([C:11]2[N:12]=[C:13]([C:16]([NH:18][C:19]3[CH:20]=[CH:21][C:22]4[C:27](=[O:28])[O:26]C(C)(C)[O:24][C:23]=4[CH:31]=3)=[O:17])[S:14][CH:15]=2)=[C:8]([CH3:10])[N:9]=1)(=[O:3])[CH3:2].[OH-].[Na+].Cl>C1COCC1>[C:1]([NH:4][C:5]1[S:6][C:7]([C:11]2[N:12]=[C:13]([C:16]([NH:18][C:19]3[CH:20]=[CH:21][C:22]([C:27]([OH:28])=[O:26])=[C:23]([OH:24])[CH:31]=3)=[O:17])[S:14][CH:15]=2)=[C:8]([CH3:10])[N:9]=1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 866219952'-(acetylamino)-N-(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-7-yl)-4'-methyl-4,5'-bi-1,3-thiazole-2 carboxamide

Product 1

HCID 119898634-({[2'-(Acetylamino)-4'-methyl-4,5'-bi-1,3-thiazol-2-yl]carbonyl}amino)-2-hydroxybenzoic acidYield 39.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2′-(acetylamino)-N-(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-7-yl)-4′-methyl-4,5′-bi-1,3-thiazole-2-carboxamide (150 mg; 0.33 mmol; 1 eq.) is dissolved in THF (6 ml). Sodium hydroxide (0.82 ml; 5 M; 4.09 mmol; 12.50 eq.) is added and the mixture is stirred at rt for 10 days. Hydrogen chloride (0.82 ml; 5 M; 4.09 mmol; 12.50 eq.) is added and the solvents are evaporated. The resulting crude product is purified by preparative HPLC. To remove the TFA, the compound is dissolved in THF and an excess of POL-Trisamine (Argonault) is added. The solution is filtrated and evaporated, affording Compound (31)(54 mg; 39%). Potassium salt of 4-({[2′-(acetylamino)-4′-methyl-4,5′-bi-1,3-thiazol-2-yl]carbonyl}amino)-2-hydroxybenzoic acid, Compound (31), is prepared by dissolving the parent compound (54 mg, 0.129 mmol) in THF (2 ml) and water (2 ml). Potassium hydroxide 0.5N solution (258 μl, 1 eq) is added. The mixture is stirred 10 min at rt, filtered through cotton and is lyophilized. Potassium salt of compound (31) is isolated as a yellow solid (21.6 mg; 36%).

Workup

  1. customthe solvents are evaporated
  2. customThe resulting crude product is purified by preparative HPLC
  3. customTo remove the TFA
  4. dissolutionthe compound is dissolved in THF
  5. additionan excess of POL-Trisamine (Argonault) is added
  6. filtrationThe solution is filtrated
  7. customevaporated

Sources & evidence

ORD record
ord-6e66f9bc25e34fc1868620ba6195c061
Source dataset
uspto-grants-2010_09
Patent number
US07799814B2

Reaction notes

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