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A crystalline form of (R)-1-(chroman-2-yl)-N-((5-(4-fluorophenyl)pyridin-3- yl)methyl)methanamine hydrochloride

IP.com Disclosure Number: IPCOM000250900D
Publication Date: 2017-Sep-13
Document File: 4 page(s) / 144K

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A crystalline form of (R)-1-(chroman-2-yl)-N-((5-(4-fluorophenyl)pyridin-3-

yl)methyl)methanamine hydrochloride

Provided herein is a crystalline form of (R)-1-(chroman-2-yl)-N-((5-(4-

fluorophenyl)pyridin-3-yl)methyl)methanamine hydrochloride referred herein as

Compound I, having the following formula:

N

N H (R)

O

F

HCl

Samples of Compound I were prepared according to the processes described in the

examples below, and were analyzed by X-ray powder diffraction ("XRPD"). Figures

1-3 present the XRPD of the obtained crystalline form.

Figure 1 XRPD of the crystalline form of Compound I. The peak marked by an asterisk is a Silicon marker.

°2theta

CPS 

*

 

 

Figure 2 XRPD of the crystalline form of Compound I. The peak marked by an asterisk is a Silicon marker.

 

 

 

Figure 3 XRPD of the crystalline form of Compound I. The peak marked by an asterisk is a Silicon marker.

 

The crystalline form of Compound I is characterized by main XRPD peaks at 5.4,

10.9, 14.8, 16.7, 19.9, 25.1 and 26.2 ± 0.2 °2θ.

XRPD method

XRPD analysis was performed on ARL (SCINTAG) powder X-Ray diffractometer

model X’TRA equipped with a solid state detector. Copper radiation of 1.5418 Å was

*

CPS 

°2theta

CPS 

°2theta

used. Scanning parameters: range: 2-40 degrees two-theta; scan mode: continuous

scan; step size: 0.05°, and a rate of 3deg/min.

Examples Compound I starting material can be prepared for example according to the process described in US 7,045,629.

Example 1:

A round bottom flask was charge with (R)-chroman-2-ylmethanamine

hydrochloride (5 g, 0.025 mol, 1 eq) and MeOH (32 ml, 6.4 Vol). A slurry mixture

was observed. Then, a solution of 30% NaOMe in MeOH, (5 g, 1 eq) was added

dropwise. Oil bath was brought to 37 oC, and 5-(4-fluorophenyl)nicotinaldehyde (5.05

g, 0.025 mol, 1 eq) was added to the suspension. After 2.5 h the reaction mixture was

cooled by means of ice/NaCl bath and NaBH4 (1.05 g, 0.028 mol, 1.1 eq) was added

in portions. After 45 min water (15 ml) was added dropwise, followed by cooling with

an ice/NaCl bath and dropwise addition of 37% HCl solution until pH = 2.3 was

reached. Precipitate was observed, and the mixture was left to rest in the refrigerator

overnight. The solids were vacuum filtered rinsed with cooled MeOH and dried

overnight in vacuum oven at 40 oC to o...