Pyridine → 2-({[5-(3,5-Difluorophenyl)thiophen-2-yl]sulfonyl}amino)-5-methyl-1,3-thiazole-4-carboxylic acid

HRID 589793Notes

Reaction equation

HRID 589793 reaction equation
[NH2:1][C:2]1[S:3][C:4]([CH3:11])=[C:5]([C:7]([O:9]C)=[O:8])[N:6]=1.[F:12][C:13]1[CH:14]=[C:15]([C:20]2[S:24][C:23]([S:25](Cl)(=[O:27])=[O:26])=[CH:22][CH:21]=2)[CH:16]=[C:17]([F:19])[CH:18]=1.N1C=CC=CC=1>CC#N>[F:12][C:13]1[CH:14]=[C:15]([C:20]2[S:24][C:23]([S:25]([NH:1][C:2]3[S:3][C:4]([CH3:11])=[C:5]([C:7]([OH:9])=[O:8])[N:6]=3)(=[O:27])=[O:26])=[CH:22][CH:21]=2)[CH:16]=[C:17]([F:19])[CH:18]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 1132801Methyl 2-amino-5-methyl-1,3-thiazole-4-carboxylateHCID 835590965-(3,5-Difluorophenyl)thiophene-2-sulfonyl chloride2×

Product 1

HCID 866891992-({[5-(3,5-Difluorophenyl)thiophen-2-yl]sulfonyl}amino)-5-methyl-1,3-thiazole-4-carboxylic acidYield 9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of methyl 2-amino-5-methyl-1,3-thiazole-4-carboxylate (25 mg, 0.15 mmol), 5-(3,5-difluorophenyl)thiophene-2-sulfonyl chloride (43 mg, 0.15 mmol) (Intermediate 21) and pyridine (23 mg, 0.29 mmol) in MeCN (1 mL) was stirred at 50° C. for 2 days. After evaporation of the solvents, the residue was dissolved in THF (1 mL) and 2 M LiOH (1 mL) was added. The reaction mixture was stirred at room temperature over night. The reaction mixture was neutralized with 4 M HCl (0.3 mL) and the solvents were removed by evaporation. The crude material was dissolved in MeCN/water (1:1). The product precipitated and the title compound was obtained in 9% yield (5.8 mg). 1H NMR (400 MHz, MeOH-d4) δ ppm 2.56 (s, 3 H) 6.97 (tt, J=9.05, 2.27 Hz, 1 H) 7.26-7.34 (m, 2 H) 7.45 (d, J=3.91 Hz, 1 H) 7.58 (d, J=3.91 Hz, 1 H). MS (ESI+) m/z 417 [M+H]+.

Workup

  1. customAfter evaporation of the solvents
  2. dissolutionthe residue was dissolved in THF (1 mL)
  3. addition2 M LiOH (1 mL) was added
  4. customthe solvents were removed by evaporation
  5. dissolutionThe crude material was dissolved in MeCN/water (1:1)
  6. customThe product precipitated

Sources & evidence

ORD record
ord-ed6d80b841284cdba8264aefafcec0f5
Source dataset
uspto-grants-2016_01
Patent number
US09233946B2

Reaction notes

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