Sodium Hydroxide → 2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-4-cyano-5-propyl-2H-pyrazole-3-carboxylic acid
Reaction equation
C([O:3][C:4]([C:6]1[NH:7][N:8]=[C:9]([CH2:13][CH2:14][CH3:15])[C:10]=1[C:11]#[N:12])=[O:5])C.[H-].[Na+].Br[CH2:19][C:20]1[CH:24]=[C:23]([C:25]2[S:26][C:27]([Cl:30])=[CH:28][CH:29]=2)[O:22][N:21]=1.[OH-].[Na+]>CN(C=O)C>[Cl:30][C:27]1[S:26][C:25]([C:23]2[O:22][N:21]=[C:20]([CH2:19][N:7]3[C:6]([C:4]([OH:3])=[O:5])=[C:10]([C:11]#[N:12])[C:9]([CH2:13][CH2:14][CH3:15])=[N:8]3)[CH:24]=2)=[CH:29][CH:28]=1Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
112 mg (0.5 mmol) of 4-cyano-5-propyl-2H-pyrazole-3-carboxylic acid ethyl ester was dissolved in 2 ml of DMF and 23.8 mg (0.6 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 166 mg (0.6 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
- temperaturewas cooled to −70° C.
- stirringThe reaction was stirred at room temperature for 3 h
- customThe product was purified by preparative RP-HPLC
- washeluting with a gradient of 0-100% acetonitrile in water (+0.01% trifluoroacetic acid)
- customAfter lyophilization the product was obtained as a white solid
Sources & evidence
- ORD record
- ord-0a8efd4c591746cc81037babda2395b1
- Source dataset
- uspto-grants-2011_03
- Patent number
- US07910606B2
Reaction notes
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