1H-ISOINDOLE-1,3(2H)-DIONE, 2-[[(5S)-2-OXO-3-[4-(3-OXO-4-MORPHOLINYL)PHENYL]-5-OXAZOLIDINYL]METHYL]- Chemical Properties

Melting point:

213-215°C

Boiling point:

702.9±55.0 °C(Predicted)

Density 

1.465±0.06 g/cm3(Predicted)

storage temp. 

Inert atmosphere,Room Temperature

solubility 

Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)

pka

0.99±0.20(Predicted)

form 

Solid

color 

White to Off-White

Water Solubility 

12mg/L at 20℃

InChI

InChI=1S/C22H19N3O6/c26-19-13-30-10-9-23(19)14-5-7-15(8-6-14)24-11-16(31-22(24)29)12-25-20(27)17-3-1-2-4-18(17)21(25)28/h1-8,16H,9-13H2/t16-/m1/s1

InChIKey

KUQNYAUTIWQAKY-MRXNPFEDSA-N

SMILES

C1(=O)C2=C(C=CC=C2)C(=O)N1C[C@@H]1OC(=O)N(C2=CC=C(N3CCOCC3=O)C=C2)C1

LogP

-0.2 at 25℃

1H-ISOINDOLE-1,3(2H)-DIONE, 2-[[(5S)-2-OXO-3-[4-(3-OXO-4-MORPHOLINYL)PHENYL]-5-OXAZOLIDINYL]METHYL]- Usage And Synthesis

Uses

1H-isoindole-1,3(2H)-dione, 2-[[(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-5-oxazolidinyl]methyl]- is an important intermediate for the synthesis of rivaroxaban, which is an anticoagulant and the first orally active direct factor Xa inhibitor.

Chemical Properties

White Solid

Uses

Rivaroxaban intermediate.

Flammability and Explosibility

Non flammable

Synthesis

The general procedure for the synthesis of 2-[[(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-5-oxazolidinyl]methyl]-1H-isoindole-1,3(2H)-dione from 4-(3-oxomorpholinyl)phenyl isocyanate and (S)-2-(ethoxylen-2-ylmethyl)isoindoline-1,3-dione was as follows: the (S)- 2-(oxiran-2-ylmethyl)isoindoline-1,3-dione (4.56 g, 22.46 mmol, 1.3 eq.) and 4-(4-isocyanatophenyl)morpholin-3-one (3.77 g, 17.29 mmol) were dissolved in isoamyl acetate (70 mL), respectively. The reaction mixture was heated to 120 °C, followed by the addition of magnesium chloride (0.12 g, 1.28 mmol). After the reaction lasted for 4 h, a white solid product (6.97 g, 95.5% yield) was obtained by filtration. The product was confirmed by mass spectrometry by ESI-MS (m/z): 422 (M + H), 444 (M + Na); 1H NMR (400 MHz, CDCl3) δ: 3.74 (m, 2H), 3.94 (m, 4H), 4.10 (m, 2H), 4.32 (s, 2H), 4.98 (m, 1H), 7.34 (d, 2H), and 7.56 (d, 2H), 7.75 (m, 2H), 7.88 (m, 2H) were characterized by NMR; HPLC purity was 98.82%.

References

[1] Patent: EP2837628, 2015, A1. Location in patent: Paragraph 0029
[2] Patent: US2015/38704, 2015, A1. Location in patent: Paragraph 0048-0051

1H-ISOINDOLE-1,3(2H)-DIONE, 2-[[(5S)-2-OXO-3-[4-(3-OXO-4-MORPHOLINYL)PHENYL]-5-OXAZOLIDINYL]METHYL]-(446292-08-6)Related Product Information

• Rivaroxaban Metabolite 8
• AcetaMide, N-[[(5S)-2-oxo-3-[4-(3-oxo-4-Morpholinyl)phenyl]-5-oxazolidinyl]Methyl]-
• 2-ThiophenecarboxaMide, N-[[(5S)-2-oxo-3-[4-(3-oxo-4-Morpholinyl)phenyl]-5-oxazolidinyl]Methyl]-
• 5-R-Rivaroxaban
• Rivaroxaban
• POLYSTYRENE IODOSOACETATE
• 1,2-Cyclohexanedione
• 4-(4-NITROPHENYL)MORPHOLIN-3-ONE
• (S)-(+)-Glycidyl Phthalimide
• 4-[4-(N-(3-chloro-(2R)-2-hydroxy-1-propyl)aMino)phenyl]Morpholin-3-one
• (S)-4-(4-(5-(Aminomethyl)-2-oxooxazolidin-3-yl)phenyl)morpholin-3-one.HCl
• 5-CHLOROTHIOPHENE-2-CARBONYL CHLORIDE
• Ethyl (R)-(-)-4-cyano-3-hydroxybutyate
• 3-MORPHOLINONE, 4-[4-[(5S)-5-(AMINOMETHYL)-2-OXO-3-OXAZOLIDINYL]PHENYL]-
• 4-(4-AMINOPHENYL)MORPHOLIN-3-ONE
• 5-Chloro-2-thiophenecarboxylic Acid
• m-(Trifluoromethyl)phenylacetic acid
• (S)-(+)-Epichlorohydrin