Formaldehyde → 4-[5-Methyl-2-(4-methylpiperazin-1-yl)-1,3-thiazol-4-yl]benzoic acid

HRID 1366296

Reaction equation

HRID 1366296 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[S:15][C:16]([CH3:28])=[C:17]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([OH:27])=[O:26])=[CH:21][CH:20]=3)[N:18]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.CC(O)=O.C(O[Na])(C)=O.C=O.[BH3-]C#N.[Na+]>Cl.O1CCOCC1>[CH3:28][C:16]1[S:15][C:14]([N:11]2[CH2:10][CH2:9][N:8]([CH3:6])[CH2:13][CH2:12]2)=[N:18][C:17]=1[C:19]1[CH:24]=[CH:23][C:22]([C:25]([OH:27])=[O:26])=[CH:21][CH:20]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 575519874-[4-(4-Carboxyphenyl)-5-methylthiazol-2-yl]-piperazine-1-carboxylic acid tert-butyl esterHCID 178476574sodium;acetic acid;acetate

Product 1

HCID 598073194-[5-Methyl-2-(4-methylpiperazin-1-yl)-1,3-thiazol-4-yl]benzoic acidYield 95.7%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

4-[4-(4-Carboxyphenyl)-5-methylthiazol-2-yl]-piperazine-1-carboxylic acid tert-butyl ester (0.421 mmol) was dissolved in 4M HCl in 1,4-dioxane, and stirred at room temperature for 1 h. The solvent was then removed in vacuo, and the residue 4-(5-methyl-2-piperazin-1-yl-thiazol-4-yl)-benzoic acid was suspended in methanol (10 mL) and treated with AcOH/AcONa buffer (pH ˜5.5, 5 mL), and formaldehyde (0.547 mmol). The reaction mixture was stirred at room temperature for 1 h, then treated with NaCNBH3 (0.547 mmol) and stirred at room temperature overnight. The solvent was then removed under vacuum, and the residue was purified by column chromatography to afford the title compound (0.403 mmol, 95%).

Workup

  1. customThe solvent was then removed in vacuo
  2. stirringThe reaction mixture was stirred at room temperature for 1 h
  3. stirringstirred at room temperature overnight
  4. customThe solvent was then removed under vacuum
  5. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-460136c605de4a71a9241ddc726dabc2
Source dataset
uspto-grants-2011_02
Patent number
US07893067B2

Linked notes

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