Browse Prior Art Database

Solid state forms of disodium salt of of (2S)-3-methyl-2-[pentanoyl-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]amino]butanoic acid

IP.com Disclosure Number: IPCOM000250049D
Publication Date: 2017-May-23
Document File: 5 page(s) / 367K

Publishing Venue

The IP.com Prior Art Database

This text was extracted from a PDF file.
This is the abbreviated version, containing approximately 58% of the total text.

Solid state forms of disodium salt of

of (2S)-3-methyl-2-[pentanoyl-[[4-[2-(2H-tetrazol-5-

yl)phenyl]phenyl]methyl]amino]butanoic acid

Disodium salt of (2S)-3-methyl-2-[pentanoyl-[[4-[2-(2H-tetrazol-5-

yl)phenyl]phenyl]methyl]amino]butanoic acid (referred to as compound 1), has the

following formula:

The solid state forms of compound 1, can be further used in the preparation of

trisodium (S)-5-(4'-((N-(1-carboxylato-2-methylpropyl)pentanamido)methyl)-[1,1'-

biphenyl]-2-yl)tetrazol-1-ide 4-(((2S,4R)-1-([1,1'-biphenyl]-4-yl)-5-ethoxy-4-methyl-

5-oxopentan-2-yl)amino)-4-oxobutanoate hydrate, as described, for example, in

WO2017/009784.

The free acid of compound 1 ((S)-3-methyl-2-(N-{[2'-(2H-1,2,3,4-tetrazol-5-

yl)biphenyl-4-yl]methyl}pentanamido)butanoic acid) can be prepared according to

any methoad known in the art (for example; US5399578-example 16)

Figure 1: XRPD pattern of crystalline Form II of compound 1

Main XRPD peaks of From II:

4.6, 8.9, 13.3, 13.6, 15.4, 16.3, 17.3, 17.8, 21.1 and 21.8 ± 0.2 degrees two-theta ± 0.2 degrees

two-theta.

Figure 2: XRPD pattern of crystalline Form III of compound 1

5 10 15 20 25 30 35 2Theta (°)

0

2500

10000

22500

40000

In te

n si

ty (

co u

n ts

)

*Peak at 28.49 ° belongs to silicon.

Main XRPD peaks of From III:

5.5, 8.7, 10.9, 14.1, 16.1, 16.5, 17.6, 20.1, 23.7, 24.3 degrees two-theta ± 0.2 degrees two-

theta.

Figure 3: XRPD pattern of crystalline Form IV of compound 1

*Peak at 28.49 ° belongs to silicon.

5 10 15 20 25 30 35 2Theta (°)

0

400

1600

3600

6400 In

te n

si ty

( co

u n

ts )

5 10 15 20 25 30 35 2Theta (°)

0

400

1600

3600

6400

10000

In te

n si

ty (

co u

n ts

)

Main XRPD peaks of From IV:

6.3, 9.4, 9.6, 12.4, 12.6, 17.2, 18.2, 19.4, 19.6, 22.1 ± 0.2 degrees two-theta ± 0.2 degrees

two-theta.

Example 1: Preparation of compound 1, form II

Compound 1 (100 mg, prepared according to example 5 of US20030207930) was put

in an open Petri dish at 60% relative humidity for 7 days. After which sample was

analyzed by XRPD-Form II

Example 2: Preparation of compound 1, Form II

Compound I (Form IV prepared according to Example 5, 1g) was put in an open Petri

dish at 80% relative humidity for 24 hours. After which sample was analyzed by

XRPD.

XRPD is given in Figure 1.

Example 3: Preparation of compound 1, Form III

To a solution of (S)-3-methyl-2-(N-{[2'-(2H-1,2,3,4-tetrazol-5-yl)biphenyl-4-

yl]methyl}pentanamido)butanoic acid (5.0 gr) in 10.0 ml of absolute ethanol at 55 –

60 °C, 1.22 g of sodium carbonate was added and stirred for about 3 hours. Reaction

mixture is cooled to 35 – 40 °C, 40.0 ml of methyl tert-butyl ether was added and

stirred for about 1 hour. Suspension is cooled down to 20 – 25 °C and stirred for

about 16 hours. Crystals were filtered off, washed twice with 10.0 ml of methyl tert-

butyl ether an...