Registration Dossier

Administrative data

Endpoint:
melting point/freezing point
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 March 2012- 11 July 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and EC guidelines and according to the principles of GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method A.1 (Melting / Freezing Temperature)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 102 (Melting point / Melting Range)
Version / remarks:
(1995)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 830.7200 (Melting Point / Melting Range)
Version / remarks:
(1998)
Deviations:
no
GLP compliance:
yes
Type of method:
thermal analysis
Remarks:
(differential scanning calorimetry)

Test material

Constituent 1
Chemical structure
Reference substance name:
2,5-anhydro-4-{[4-(4-{4-[({1-[(2S,3S)- 2-(benzyloxy)pentan-3-yl]hydrazino}carbonyl)amino]phenyl}piperazin1-yl)phenoxy]methyl}-1,3,4-trideoxy-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-
EC Number:
701-059-1
Cas Number:
345217-03-0
Molecular formula:
C43H50F2N8O4
IUPAC Name:
2,5-anhydro-4-{[4-(4-{4-[({1-[(2S,3S)- 2-(benzyloxy)pentan-3-yl]hydrazino}carbonyl)amino]phenyl}piperazin1-yl)phenoxy]methyl}-1,3,4-trideoxy-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): PAZ-D
- Physical state: white powder
- Hygroscopic

Results and discussion

Melting / freezing pointopen allclose all
Melting / freezing pt.:
144 °C
Decomposition:
yes
Decomp. temp.:
>= 225 °C
Melting / freezing pt.:
417 K
Decomposition:
yes
Decomp. temp.:
>= 498 K

Any other information on results incl. tables

Preliminary TGA

From 275°C upwards the weight of the sample decreased significantly. At 378°C, the sample weight had decreased by 25%. After the experiment, a black molten residue remained in the sample container.

 

DSC experiments

Experiment 1: An endothermic peak between 125°C and 175°C (extrapolated onset temperature: 143.39°C), most likely due to melting. Between 225°C and 350°C, an endothermic peak followed by a first exothermic peak was observed. The effects were due to reaction and/or decomposition of the substance. A second exothermic peak was observed starting at 350°C, due to further reaction and/or decomposition of the substance. After the experiment, a red molten residue remained in the sample container.

 

Experiment 2: To investigate the melting peak between 125°C and 175°C, a repeated heating cycle was applied. With the first heating the extrapolated onset temperature of the melting peak was 143.49°C. During cooling, a glass transition was observed between 60°C and 30°C but no crystallisation. With the second heating, a glass transition was observed between 50°C and 75°C (inflection point: 56.62°C). A melting peak was not observed as expected (no crystallisation during cooling). An endothermic peak followed by an exothermic peak was observed starting at 225°C, due to reaction and/or decomposition of the substance. After the experiment, a yellow molten residue remained in the sample container.

 

Experiment 3: To investigate reaction and/or decomposition during melting, the experiment was stopped directly after the melting peak (extrapolated onset temperature: 143.78°C). After the experiment, a white/very slightly yellow, molten residue remained in the sample container. Although a minor discolouration was observed, the effect is most likely due to melting of the test substance.

 

TGA/DSC curves: see attachment.

Applicant's summary and conclusion

Conclusions:
In a differential scanning calorimetry study, the melting temperature of the substance was determined to be 144°C. Decomposition of the substance started at 225°C. The study was performed in accordance with EC A.1, OECD 102 and EPA OPPTS 830.7200 guidelines and according to the principles of GLP.