Imidazole 4 acetic acid, A methyl ester p38alpha Pathway 21 was converted to the title compound using the method described by Takacs.22 An L Ml solution of 6.45 g of triethyl phosphonoacetate in 100 ml of THF was applied to 78 under st Cooled ndigem stirring inert atmosphere re. An L Added solution of 12 ml of n BuLi in hexane dropwise. After 10 min, an L Solution of 1H-imidazole 4 vinegar Acid, methyl ester 1 in 60 ml of THF. After the mixture was stirred for 20 min, a L Solution of 27.5 ml of DIBAL was added in CH2Cl2. The mixture was stirred for 1.5 h and then slowly to room temperature for 2 h Na2SO410 solid was added followed by 3 ml of H 2 O. The mixture was filtered and removes the L Solvent. The residue was dissolved in ethyl acetate St, with saturated Ttigter Na2CO3, and dried. The product, which is a mixture of cis and trans isomers, was treated with NaOCH 3 in CH 3 OH to most of the material to the trans isomer, which was purified by chromatography on silica gel, which convert 5.9 g intermediaries. A 4.77 g portion of this hydrolyzed by Aufl Sen in 48 ml CH 3 OH with 9 ml of 5 M NaOH. After 2 h stirring, the mixture was neutralized to a pH of 4, 5 and extracted with ethyl acetate. The L Solution was dried and removed the L Solvents. The trityl group was removed by heating the material in a mixture of 40 ml of H 2 O, 40 ml EtOH and 5 ml of concentrated HCl for 1.5 h. The mixture was cooled, and solid trityl alcohol was filtered. The L Solvent was removed from the filtrate and the residual H 2 O was evaporated with toluene several times together, went Ing 1.3 g of crude HCl salt which was used in the n Next step without further purification. Acrylic Third acid An L Solution of 18 g of benzaldehyde 2, 23 drops of 12.6 g of malonic Acid and 6 of piperidine in 107 ml of pyridine was heated at 110 for 3 h. The mixture was washed with 600 ml of H 2 O and 30 ml of 5 N NaOH diluted added. The L Solution was washed twice with ether. The L Solution was extracted at pH 5, 6 anges Acidified, saturated Ttigter NaCl and ethyl acetate. The extract was dried and the L Solvents were removed.
The solid was dissolved in ether St, activated carbon was added and the mixture was filtered. The L Solution was concentrated, and 5.8 g of solid 70 was collected by filtration. MS m / z 192.1 a. Anal. C, H, N. Preparation of interim representatives. 6 April 7 ethoxy-nitroquinoline hydrochloride 3-carbonitrile. A suspension of 2.60 g of 4 benzyloxy chloroaniline 3, 3.1 g of 4-nitroquinoline chlorine 7 3 is methoxy-6 carbonitrile, 9 and 0.3 g of pyridine hydrochloride in 180 ml of i PrOH under a nitrogen atmosphere Re was with stirring for refluxed for 8 h. When the mixture Pimecrolimus was coooled, was a yellow solid was obtained, washed with i PrOH and ether to yield 4.9 g of yellow solid: mp 251 255, HRMS m / z 475.113 95 1 2 ¢, 81 MMU, 1 H-NMRä 10.98, 9.33, 8.88, 7.67, 2.0 Hz, 7.58, 7.51 7.35, 5.27, 4.36 6.8 Hz, 1, 43 Hz, 6, 8th Anal. H, N. C: calculated 60.89, found 59.38. 6 amino Acids 7th April ethoxyquinoline 3-carbonitrile. A sample of 4.6 g of 3 g in 138 ml of methanol was stirred under reflux. to this, 3.52 g of iron powder in 55 ml of acetic acid are suspended, and reflux was continued for 2 h. The reaction mixture was hot filtered and left to crystallize, thus 4.9 g yellow solid as the acetate salt.
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