971
BANDICHHOR et al., Orient. J. Chem., Vol. 34(2), 963-972 (2018)
of carboxylic acid group, other broad band at 3207
cm-1 for amidic NH, 1682 cm-1 for carbonyl group of
carboxylic acid and the broad band at 1590 cm-1 for
carbonyl group of the amide group. The specific
optical rotation of alvimopan [α]25D +43.48 ° (C=1.01
DMSO). Based on the above spectral data the
molecular formula of alvimopan was confirmed as
C25H32N2O4 and the corresponding structure was
confirmed as ([[2(S)-[[4(R)-(3-Hydroxyphenyl)-
3R,4-dimethyl-1-piperidinyl]methyl]-1-oxo-3-
phenylpropyl]-amino]acetic acid.
carboxylic acid and the broad band at 1682.3 cm-1
for carbonyl group of the amide group. The specific
optical rotation of alvimopan [α]25D -47.22 ° (C=1.01
DMSO). Based on the above spectral data the
molecular formula of alvimopan impurity-2 was
confirmed as C25H32N2O4 and the corresponding
structure was confirmed as ([[2(R)-[[4(S)-(3-
H y d r o x y p h e n y l ) - 3 S , 4 - d i m e t h y l - 1 -
piperidinyl]methyl]-1-oxo-3-phenylpropyl]-
amino]acetic acid.
Compound 1C.
Compound 1a
ESI mass spectrum of alvimopan impurity-3
exhibited protonated molecule peak at m/z 425
[(MH)+] in positive ion mode, indicating the mass
ESI mass spectrum of alvimopan impurity-
1 exhibited protonated molecule peak at m/z 425
[(MH)+] in positive ion mode, indicating the mass of
impurity-1 is 424. In 1H NMR of alvimopan
impurity-1, the signal at 9.1 ppm broad singlet
corresponding to phenolic OH proton and another
singlet at 5.56-5.58 ppm corresponds to amide
proton of NH. The complete NMR signals
assignment was given inTable 4.In the IR spectrum,
a broad band at 3423.5 cm-1 for OH of carboxylic
acid group, other broad band at 3207.5 cm-1 for
amidic NH, 1681 cm-1 for carbonyl group of
carboxylic acid and the broad band at 1593.2 cm-1
for carbonyl group of the amide group. The specific
optical rotation of alvimopan [α]25D +53.21 ° (C=1.01
DMSO). Based on the above spectral data the
molecular formula of alvimopan impurity-
1(compound1a) was confirmed as C25H32N2O4 and
the corresponding structure was confirmed as
([[2(S)-[[4(R)-(3-Hydroxyphenyl)-3R,4-dimethyl-1-
piperidinyl]methyl]-1-oxo-3-phenylpropyl]-
amino]acetic acid.
1
of impurity-3 is 424. In H NMR of alvimopan
impurity-3, the signal at 9.17 ppm broad singlet
corresponding to phenolic OH proton and another
singlet at 5.56-5.58 ppm corresponds to amide
proton of NH. The complete NMR signals
assignment was given inTable 4.In the IR spectrum,
a broad band at 3425.6 cm-1 for OH of carboxylic
acid group, other broad band at 3209 cm-1 for amidic
NH, 1682 cm-1 for carbonyl group of carboxylic acid
and the broad band at 1593.2 cm-1 for carbonyl
group of the amide group. The specific optical
rotation of alvimopan [α]25D -52.40 ° (C=1.01 DMSO).
Based on the above spectral data the molecular
formula of alvimopan impurity-3 was confirmed as
C25H32N2O4 and the corresponding structure was
confirmed as ([[2(S)-[[4(S)-(3-Hydroxyphenyl)-
3S,4-dimethyl-1-piperidinyl]methyl]-1-oxo-3-
phenylpropyl]-amino]acetic acid.
CONCLUSION
The diastereomeric impurities of
alvimopan were prepared and characterized by
HPLC, Mass, IR, SOR and NMR (1H, 13C) techniques.
The contents of these impurities were also identified
in the alvimopan API and analytical method
validation was concluded based on these.
Compound 1b
ESI mass spectrum of alvimopan impurity-1
exhibited protonated molecule peak at m/z 425
[(MH)+] in positive ion mode, indicating the mass
1
of impurity-2 is 424. In H NMR of alvimopan
impurity-2, the signal at 9.17 ppm broad singlet
corresponding to phenolic OH proton and another
singlet at 5.56-5.58 ppm corresponds to amide
proton of NH. The complete NMR signals
assignment was given in table-3. In the IR spectrum,
a broad band at 3410.5 cm-1 for OH of carboxylic
acid group, other broad band at 3209.5 cm-1 for
amidic NH, 1592.2 cm-1 for carbonyl group of
ACKNOWLEDGEMENT
The authors wish to thank the
management of Dr. Reddy’s Laboratories Ltd., for
supporting this work and co-operation from the other
colleagues also highly appreciated.