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 1641868Notes

Reaction equation

HRID 1641868 reaction equation
[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

Participants

9

Reactant 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, compoundHCID 66738698HCID 66738698, compound

Product 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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-939437e3c85e4f5598fe610177c510b8
Source dataset
uspto-grants-2012_02
Patent number
US08115011B2

Reaction notes

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