1-Pyrrolidinecarboxylic acid, 2,2'-([1,1'-biphenyl]-4,4'-diyldi-1H-iMidazole-5,2-diyl)bis-, 1,1'-bis(1,1-diMethylethyl) ester, (2S,2'S)- Chemical Properties

Boiling point:

890.2±65.0 °C(Predicted)

Density 

1.220±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO (Slightly), Methanol (Slightly)

form 

Solid

pka

12.83±0.10(Predicted)

color 

White to Off-White

InChI

InChI=1/C36H44N6O4/c1-35(2,3)45-33(43)41-19-7-9-29(41)31-37-21-27(39-31)25-15-11-23(12-16-25)24-13-17-26(18-14-24)28-22-38-32(40-28)30-10-8-20-42(30)34(44)46-36(4,5)6/h11-18,21-22,29-30H,7-10,19-20H2,1-6H3,(H,37,39)(H,38,40)/t29-,30-/s3

InChIKey

WPMTYMFNINZZHE-WBOANQFRNA-N

SMILES

C1(C2=CC=C(C3NC([C@@H]4CCCN4C(OC(C)(C)C)=O)=NC=3)C=C2)=CC=C(C2NC([C@@H]3CCCN3C(OC(C)(C)C)=O)=NC=2)C=C1 |&1:8,30,r|

1-Pyrrolidinecarboxylic acid, 2,2'-([1,1'-biphenyl]-4,4'-diyldi-1H-iMidazole-5,2-diyl)bis-, 1,1'-bis(1,1-diMethylethyl) ester, (2S,2'S)- Usage And Synthesis

Uses

(2S,2''S)-2,2''-([1,1''-Biphenyl]-4,4''-diyldi-1H-imidazole-5,2-diyl)bis-1-pyrrolidinecarboxylic Acid 1,1''-Bis(1,1-dimethylethyl) Ester is an antiviral agent and Daclatasvir (D101500) intermediate. Daclatasvir inhibits the HCV protein NS5A and thus can be used as a drug candidate for the treatment of hepatitis C (HCV).

Synthesis

General procedure for the synthesis of (2S,2'S)-di-tert-butyl 2,2'-(4,4'-([1,1'-biphenyl]-4,4'-diyl)bis(1H-imidazole-4,2-diyl))bis(pyrrolidine-1-carboxylate) from DACLATASVIR INTERMEDIATE - daclatasvir intermediate: a mixture of 3 (2 g, 3.01 mmol) and NH4OAc (4.65 g, 60.3 mmol) in toluene (30 mL) was heated to reflux at 130 °C for 15 hours. Upon completion of the reaction, the volatile components were removed by distillation under reduced pressure. The residue was partitioned between CH2Cl2 and H2O until saturation was reached. Saturated aqueous NaHCO3 was added to neutralize the aqueous phase. The aqueous phase was extracted with CH2Cl2, the organic phases were combined, dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The residue was purified by fast column chromatography (silica gel; 50% EtOAc/hexane as eluent) to give product 4 as a white solid (1.6 g, 85% yield).

References

[1] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 16, p. 3147 - 3150
[2] Patent: US2009/43107, 2009, A1. Location in patent: Page/Page column 8
[3] Patent: WO2010/138368, 2010, A1. Location in patent: Page/Page column 148-149
[4] Patent: KR101508022, 2015, B1. Location in patent: Paragraph 0136-0138
[5] Patent: CN106496199, 2017, A. Location in patent: Paragraph 0043; 0061; 0070; 0071; 0072

1-Pyrrolidinecarboxylic acid, 2,2'-([1,1'-biphenyl]-4,4'-diyldi-1H-iMidazole-5,2-diyl)bis-, 1,1'-bis(1,1-diMethylethyl) ester, (2S,2'S)-(1007882-23-6)Related Product Information

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• Daclatasvir
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