1-Propanesulfonamide, N-[3-[[5-bromo-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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study done according to the respective guideline

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

EC Number:

806-756-5

Cas Number:

1262985-24-9

Molecular formula:

C24 H16 Br Cl2 F2 N3 O4 S

IUPAC Name:

N-{3-[5-bromo-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: >99%

Results and discussion

Water solubility

Water solubility:

0.57 mg/L

Incubation duration:

>= 48 - <= 240 h

Temp.:

20 °C

pH:

>= 5.5 - <= 7.3

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

0.776 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

0.1 64 mg/L after 72 h (i.e. 48 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 6.3

0.096 mg/L after 96 h (i.e. 72 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 5.7

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

2nd test series:

1.42 mg/L after 48 h (i.e. 24 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C) pH 7.0

0.584 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

0.745 mg/L after 96 h (i.e. 72 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 6.8

0.216 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

0.320 mg/L after 240 h (i.e. 216 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 7.3

0.932 mg/L after 384 h (i.e. 360 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C3), pH 6.9

Based on the 5 determinations the water solubility of the test substance was calculated to be 0.559 mg/L (mean of six replicates).

3rd test series

0.923 mg/L after 48 h (i.e. 24 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C) pH 6.8

0.098 mg/L after 72 h (i.e. 48 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 6.6

1.36 mg/L after 96 h (i.e. 72 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 6.5

1.29 mg/L after 168 h (i.e. 144 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 6.2

0.395 mg/L after 216 h (i.e. 192 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 6.3

0.744 mg/L after 240 h (i.e. 216 h at 30 ± 0.5 °C and 24 h at 20 ± 0.5 °C), pH 6.6

The mean value of the last two determinations was 0.570 mg/L. Therefore, the results of the 2nd test series (mean value of 0.559 mg/L) was essentially confirmed.

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 0.570 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: The first test series showed decreasing results and so a second test with longer incubation times was performed. The 2nd test series showed similar results as compared to the ones observed in the 1st test series. Since the variation were higher than 15% in the last three determinations, it was decided to calculate the average values of the last 5 determinations of the 2nd test series and perform a 3rd test series as a confirmatory test.

Conculsion: Based on the measured concentrations, the water solubility was determined to be 0.570 mg/L at 20 +/- 0.5 °C.