Sodium Hydroxide → 2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-cyano-5-thiophen-2-yl-2H-pyrazole-3-carboxylic acid

HRID 604414Notes

Reaction equation

HRID 604414 reaction equation
C([O:3][C:4]([C:6]1[NH:7][N:8]=[C:9]([C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)[C:10]=1[C:11]#[N:12])=[O:5])C.[H-].[Na+].Br[CH2:21][C:22]1[CH:26]=[C:25]([C:27]2[S:28][C:29]([Cl:32])=[CH:30][CH:31]=2)[O:24][N:23]=1.[OH-].[Na+]>CN(C=O)C>[Cl:32][C:29]1[S:28][C:27]([C:25]2[O:24][N:23]=[C:22]([CH2:21][N:7]3[C:6]([C:4]([OH:3])=[O:5])=[C:10]([C:11]#[N:12])[C:9]([C:13]4[S:14][CH:15]=[CH:16][CH:17]=4)=[N:8]3)[CH:26]=2)=[CH:31][CH:30]=1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 111501463-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazoleHCID 178470417HCID 178470417, compound

Product 1

HCID 574743632-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-cyano-5-thiophen-2-yl-2H-pyrazole-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

287 mg (1.2 mmol) of 4-Cyano-5-thiophen-2-yl-2H-pyrazole-3-carboxylic acid ethyl ester was dissolved in 2 ml of DMF and 51.1 mg (1.3 mmol) of sodium hydride (60% in mineral oil) were added at RT. After stirring for 20 min at room temperature the solution was cooled to −70° C. and 355 mg (1.3 mmol) of 3-bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole were added. The reaction was stirred at room temperature for 3 h. The reaction solution was treated with 1 ml of 2N aqueous NaOH for 16 h at room temperature. The product was purified by preparative RP-HPLC eluting with a gradient of 0-100% acetonitrile in water (+0.01% trifluoroacetic acid). After lyophilization the product was obtained as a white solid.

Workup

  1. temperaturewas cooled to −70° C.
  2. stirringThe reaction was stirred at room temperature for 3 h
  3. customThe product was purified by preparative RP-HPLC
  4. washeluting with a gradient of 0-100% acetonitrile in water (+0.01% trifluoroacetic acid)
  5. customAfter lyophilization the product was obtained as a white solid

Sources & evidence

ORD record
ord-31bf24c3663c475188d74cfe5a4b574a
Source dataset
uspto-grants-2011_03
Patent number
US07910606B2

Reaction notes

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