1-Hydroxybenzotriazole → (1S,2S)-2-(4-{3-fluoro-4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperazine-1-carbonyl)-cyclopentanecarboxylic acid benzyl ester

HRID 1641868노트

반응식

HRID 1641868 반응식
[F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:5]=[CH:4][C:3]=1[NH:14][C:15]([C:17]1[N:18]=[C:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[O:20][C:21]=1[C:22]([F:25])([F:24])[F:23])=[O:16].C1(C2OC(C(F)(F)F)=C(C(O)=O)N=2)C=CC=CC=1.NC1C=CC(N2CCNCC2)=CC=1F.[CH2:64]([O:71][C:72]([C@H:74]1[CH2:78][CH2:77][CH2:76][C@@H:75]1[C:79](O)=[O:80])=[O:73])[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)C(C)C)(C)C>ClCCl>[CH2:64]([O:71][C:72]([C@H:74]1[CH2:78][CH2:77][CH2:76][C@@H:75]1[C:79]([N:11]1[CH2:10][CH2:9][N:8]([C:6]2[CH:5]=[CH:4][C:3]([NH:14][C:15]([C:17]3[N:18]=[C:19]([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)[O:20][C:21]=3[C:22]([F:25])([F:24])[F:23])=[O:16])=[C:2]([F:1])[CH:7]=2)[CH2:13][CH2:12]1)=[O:80])=[O:73])[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1

참가 물질

9

반응물 7

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27764382-Phenyl-5-(trifluoromethyl)-oxazole-4-carboxylic acidHCID 66738585(1s,2s)-2-(Benzyloxycarbonyl)cyclopentanecarboxylic acidHCID 66738689HCID 66738689, 화합물HCID 66738698HCID 66738698, 화합물

생성물 1

HCID 66738142(1S,2S)-2-(4-{3-fluoro-4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperazine-1-carbonyl)-cyclopentanecarboxylic acid benzyl ester

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A mixture of 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (2-fluoro-4-piperazin-1-yl-phenyl)-amide (0.22 g, 0.5 mmol) prepared from 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid and 4-(4-amino-3-fluoro-phenyl)-piperazine using a procedure similar to the one described above, (1S,2S)-cyclopentane-1,2-dicarboxylic acid monobenzyl ester (0.26 g, 0.5 mmol), N-hydroxybenzotriazole (0.1 g, 0.74 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.14 g, 0.74 mmol), N,N-diisopropylethylamine (0.26 mL, 1.5 mmol) in anhydrous dichloromethane (4 mL) was stirred at room temperature for overnight. After the reaction, solvent was evaporated. The resulted mixture was mixed with water and extracted with ethyl acetate twice. The organic layers were collected, combined, washed with brine before dried over sodium sulfate, and then concentrated to give a solid. The crude product was purified by reverse phase HPLC (10%-80% acetonitrile in water) to gave (1S,2S)-2-(4-{3-fluoro-4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenyl}-piperazine-1-carbonyl)-cyclopentanecarboxylic acid benzyl ester as a yellow solid. LCMS calcd for C35H32F4N4O5 (m/e) 664, obsd 665 (M+H).

후처리

  1. customAfter the reaction, solvent
  2. customwas evaporated
  3. additionThe resulted mixture was mixed with water
  4. extractionextracted with ethyl acetate twice
  5. customThe organic layers were collected
  6. washwashed with brine
  7. dry with materialbefore dried over sodium sulfate
  8. concentrationconcentrated
  9. customto give a solid
  10. customThe crude product was purified by reverse phase HPLC (10%-80% acetonitrile in water)

출처 및 근거

ORD 기록
ord-939437e3c85e4f5598fe610177c510b8
출처 데이터셋
uspto-grants-2012_02
특허 번호
US08115011B2

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