1-Propanesulfonamide, N-[3-[[5-(4-chlorophenyl)-1-(2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]carbonyl]-2,4-difluorophenyl]-

Water solubility

Administrative data

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-02-08 to 2010-04-30

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Deviations:

yes

Remarks:

The column elution method should have been used

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

Deviations:

yes

Remarks:

The column elution method should have been used

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Test material

Test material information

Constituent 1

Reference substance name:

N-{3-[5-(4-chlorophenyl)-1-(2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluorophenyl}propane-1-sulfonamide

EC Number:

806-798-4

Cas Number:

1262985-23-8

Molecular formula:

C30 H20 Cl3 F2 N3 O4 S

IUPAC Name:

N-{3-[5-(4-chlorophenyl)-1-(2,6-dichlorobenzoyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluorophenyl}propane-1-sulfonamide

Test material form:

not specified

Details on test material:

Purity: >98%

Results and discussion

Water solubility

Water solubility:

0.231 mg/L

Temp.:

20 °C

pH:

>= 5.1 - <= 7.1

Any other information on results incl. tables

The initially added amount of test substance was 1 g per litre deionised water. The measured concentrations were:

lst test series

0.232 mg/L after 48 h (i.e. 24 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 5.4

0.241 mg/L after 72 h (i.e. 48 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 5.5

0.642 mg/L after 96 h (i.e. 72 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 5.5

Since the results were increasing, a confirmation test with longer incubation times and more test vessels was performed.

2nd test series:

0.031 mg/L after 48 h (i.e. 24 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C) pH 5.5

0.330 mg/L after 72 h (i.e. 48 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 5.4

0.328 mg/L after 96 h (i.e. 72 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 6.2

0.055 mg/L after 120 h (i.e. 96 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 5.8

0.108 mg/L after 144 h (i.e. 120 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 6.6

0.178 mg/L after 168 h (i.e. 144 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 6.3

The values were well below a water solubility of 1 mg/L. However, due to the observed variations a subsequent 3rd test series was performed.

3rd test series

<0.05 mg/L after 48 h (i.e. 24 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C) pH 6.3

0.129 mg/L after 72 h (i.e. 48 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 6.9

0.110 mg/L after 96 h (i.e. 72 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 7.1

0.078 mg/L after 192 h (i.e. 168 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 6.9

0.032 mg/L after 240 h (i.e. 216 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 7.1

3.30 mg/L after 384 h (i.e. 360 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 7.1

The last determined concentration was much higher than the preceding five determinations. The solution was not clear indicating that very fine particles could not be retained by the filter. Therefore, a 4th test series was performed to confirm that the water solubility is well below 1 mg/L.

4th test series

0.157 mg/L after 48 h (i.e. 24 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C) pH 6.7

0.231 mg/L after 72 h (i.e. 48 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 6.7

0.461 mg/L after 96 h (i.e. 72 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 6.6

0.284 mg/L after 168 h (i.e. 144 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 5.1

0.115 mg/L after 216 h (i.e. 192 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 6.6

0.139 mg/L after 240 h (i.e. 216 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 6.8

Based on all six determinations of the 4th test series the water solubility of the test substance was calculated to be 0.231 mg/L (mean of six replicates).

This value essentially confirms the results of the preceding three test series.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): slightly soluble (0.1-100 mg/L)
Based on the measured concentrations, the water solubility was determined to be 0.231 mg/L at 20 +/- 0.5 °C.

Executive summary:

Method: The water solubility of the test substance was investigated by dissolving the test substance (1g per L) at 30°C for at least 24 h and equilibration at 20 +/- 0.5°C for again 24 h, both by using a magnetic stirrer. Undissolved test material was separated by filtration (MILLIPORE AP15 glass fibre filter). Subsequently a sample for the chemical analysis was taken. .

Results: Since the first test series showed increasing results and so a second test with longer incubation times was performed. The 2nd test series values were below a water solubility of 0.231 mg/L. Due to the observed variations a 3rd test series was conducted. The last determination in the 3rd test series was much higher than the preceding 5 determinations and so a 4th test series was conducted.

Conculsion: Based on the measured concentrations in the 4th test series, the water solubility was determined to be 0.231 mg/L at 20 +/- 0.5 °C.