D-threo-Pentitol, 2,5-anhydro-1,3,4-trideoxy-2-C-(2,4-difluorophenyl)-4-[[4-[4-[4-[[[1-[(1S,2S)-1-ethyl-2-(phenylmethoxy)propyl]hydrazino]carbonyl]amino]phenyl]-1-piperazinyl]phenoxy]methyl]-1-(1H-1,2,4-triazol-1-yl)-

Melting point / freezing point

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method A.1 (Melting / Freezing Temperature)

Version / remarks:

(2008)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 102 (Melting point / Melting Range)

Version / remarks:

(1995)

Deviations:

no

Test guideline 3

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

Test material information

Constituent 1

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 point

Melting / freezing point 1

Melting / freezing pt.:

144 °C

Decomposition:

yes

Decomp. temp.:

>= 225 °C

Melting / freezing point 2

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.