1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-methyl-2-{[4-(2-{[(1-phenyl-1H-pyrazol-4-yl)carbonyl]amino}ethyl)-1,3-thiazol-2-yl]thio}propionic acid tert-butyl ester

HRID 914379

반응식

HRID 914379 반응식
[C:1]1([N:7]2[CH:11]=[C:10]([C:12]([OH:14])=O)[CH:9]=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:15]([O:19][C:20](=[O:33])[C:21]([S:24][C:25]1[S:26][CH:27]=[C:28]([CH2:30][CH2:31][NH2:32])[N:29]=1)([CH3:23])[CH3:22])([CH3:18])([CH3:17])[CH3:16].CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C)C=O.O>[C:15]([O:19][C:20](=[O:33])[C:21]([CH3:22])([S:24][C:25]1[S:26][CH:27]=[C:28]([CH2:30][CH2:31][NH:32][C:12]([C:10]2[CH:9]=[N:8][N:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH:11]=2)=[O:14])[N:29]=1)[CH3:23])([CH3:17])([CH3:16])[CH3:18]

참가 물질

7

반응물 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 1210261-phenyl-1H-pyrazole-4-carboxylic acidHCID 597594492-{[4-(2-Aminoethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid tert-butyl ester

생성물 1

HCID 597589112-methyl-2-{[4-(2-{[(1-phenyl-1H-pyrazol-4-yl)carbonyl]amino}ethyl)-1,3-thiazol-2-yl]thio}propionic acid tert-butyl ester수율 74.1%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

1-Phenyl-1H-pyrazole-4-carboxylic acid ethyl ester (4.1 g) synthesized in Reference Example 16 was dissolved in methanol (40 mL) and tetrahydrofuran (40 mL), aqueous sodium hydroxide solution (1 mol/L, 40 mL) was added, and the mixture was stirred at 60° C. for one hour. The reaction mixture was concentrated under reduced pressure, aqueous hydrochloric acid solution (1 mol/L, 50 mL) was added, and the precipitated solid was filtrated. The solid was dissolved in ethyl acetate, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give 1-phenyl-1H-pyrazole-4-carboxylic acid (2.5 g) as a white solid. This carboxylic acid (8.72 g) and 2-{[4-(2-aminoethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid tert-butyl ester (14 g) synthesized in Example 7 were dissolved in N,N-dimethylformamide (225 mL), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC) hydrochloride (10.65 g) and 1-hydroxybenztriazole (HOBt) monohydrate (10.62 g) were successively added thereto, and the mixture was stirred at room temperature for 6 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=1:1) to give the title compound (16.2 g) as a white solid.

후처리

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=1:1)

출처 및 근거

ORD 기록
ord-4618694a05454cd5829a12bd69477034
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08026370B2

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