IP Library Granted Patent US 10,221,183
Granted Patent B2
US 10,221,183 · App. 15/577,858 · Granted Mar 5, 2019

Crystal (6S,9aS)-N-benzyl-8-({6-[3-(4-ethylpiperazin-1-yl)azetidin-1-yl]pyridin-2-yl}methyl)-6-(2-fluoro-4-hydroxybenzyl)-4,7-dioxo-2-(prop-2-en-1-yl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide

Inventors: Ikuo Kushida (Tsukuba, JP); Yoko Ito (Tsukuba, JP)
Assignee: Eisai R&D Management Co., Ltd.
C07D487/04A61K31/53A61P35/00C07B2200/13
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Quick Facts
Patent No.
US 10,221,183
App. No.
15/577,858
Granted
Mar 5, 2019
Kind
B2
Abstract

The present invention provides a crystal of (6S,9aS)-N-benzyl-8-({6-[3-4-ethylpiperazin-1-yl)azetidin-1-yl]pyridin-2-yl}methyl)-6-(2-fluoro-4-hydroxybenzyl)-4,7-dioxo-2-(prop-2-en-1-yl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide.

Claims (8)

1. A crystal of (6S,9aS)-N-benzyl-8-({6-[3-(4-ethylpiperazin-1-yl)azetidin-1-yl]pyridin-2-yl}methyl)-6-(2-fluoro-4-hydroxybenzyl)-4,7-dioxo-2-(prop-2-en-1-yl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide, wherein the crystal comprises diffraction peaks at the diffraction angles (2θ±0.2°) of 5.8°, 6.4° and 10.1° in powder X-ray diffraction.

2. The crystal according to claim 1 , wherein the crystal further comprises diffraction peaks at the diffraction angles (2θ±0.2°) of 8.0° and 12.8° in powder X-ray diffraction.

3. The crystal according to claim 2 , wherein the crystal further comprises diffraction peaks at the diffraction angles (2θ±0.2°) of 14.2°, 16.0°, 18.9°, 19.7° and 23.1° in powder X-ray diffraction.

4. A crystal of (6S,9aS)-N-benzyl-8-({6-[3-(4-ethylpiperazin-1-yl)azetidin-1-yl]pyridin-2-yl}methyl)-6-(2-fluoro-4-hydroxybenzyl)-4,7-dioxo-2-(prop-2-en-1-yl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide, wherein the crystal comprises peaks at the chemical shifts (δ±0.5 ppm) of 141.1 ppm and 158.1 ppm in 13 C solid state NMR spectrum.

5. The crystal according to claim 4 , wherein the crystal further comprises peaks at the chemical shifts (δ±0.5 ppm) of 134.0 ppm and 165.1 ppm in 13 C solid state NMR spectrum.

6. The crystal according to claim 5 , wherein the crystal further comprises peaks at the chemical shifts (δ±0.5 ppm) of 12.6 ppm, 55.5 ppm and 118.5 ppm in 13 C solid state NMR spectrum.

7. A pharmaceutical composition comprising an effective amount of the crystal according to claim 1 and a pharmaceutically acceptable additive.

8. A pharmaceutical composition comprising an effective amount of the crystal according to claim 4 and a pharmaceutically acceptable additive.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 12, 2017
From: KUSHIDA, IKUO; ITO, YOKO
To: EISAI R&D MANAGEMENT CO., LTD.
Reel/Frame 044369/0179 →
Continuity (2)
Provisional Application 62183577 · Jun 23, 2015
Related Publication 20180141950A1 · May 24, 2018