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

HRID 1715272노트

반응식

HRID 1715272 반응식
[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]

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-6e66f9bc25e34fc1868620ba6195c061
출처 데이터셋
uspto-grants-2010_09
특허 번호
US07799814B2

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