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Intermediates of 4-amino-1-β-D-ribofuranosyl-1,3,5-triazin-2(1H)-one

IP.com Disclosure Number: IPCOM000178294D
Publication Date: 2009-Jan-22
Document File: 7 page(s) / 135K

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The IP.com Prior Art Database

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Intermediates of 4-amino-1-β-D-ribofuranosyl-1,3,5-triazin-2(1H)-one.

4-amino-1-β-D-ribofuranosyl-1, 3, 5-triazin-2(1H)-one ("AZA") of the following structure:

is an antineoplastic drug exhibiting activity against, e.g., leukemia, lymphoma and various solid tumours. AZA acts also as an inhibitor of DNA methyltransferase and was approved for the treatment of myelodispactic syndromes, a family of bone-marrow disorders. It is being marketed under the name VIDAZA® by Pharmion.

NH2

N N

N

O

HO

O

H

H

H

H

OH

OH

Herein will be described crystalline forms of intermediates in the synthesis of AZA.

4-amino-1,2-dihydro-1,3,5-triazin-2-one

Crystalline 4-amino-1,2-dihydro-1,3,5-triazin-2-one ("AZS') of the following formula,

N

NH2

N

N

H

O

is characterized by a PXRD pattern having peaks at about 11.6, 13.7, 16.6, 19.9, 25.2, 26.0, 26.9,
27.8, 29.1, 30.7, 32.1, 35.2 and 38.2 ± 0.2 deg. 2Θ, and by the following PXRD figure.

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AZS can be also characterized by FTIR spectrum having bands at about 3375, 3172, 2617, 1732, 1661, 1624, 1515, 1471, 1445, 1350, 1269, 1222, 1145, 1006, 984, 901, 813, 796, 773 and 610 cm-1,

and by the following FTIR figure.

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2-(Trimethylsilylamino)-4-(trimethylsilyloxy)-s-triazine

Crystalline 2-(Trimethylsilylamino)-4-(trimethylsilyloxy)-s-triazine ("Si-AZS") of the following formula,

NHSiMe3

N

SiO

is characterized by a PXRD pattern having peaks at about 11.6, 13.7, 16.6, 19.9, 25.2, 26.0, 26.9,
27.8, 29.1, 30.7, 32.1, 35.2 and 38.2 ± 0.2 deg. 2Θ, and by the following XRPD figure.

Si-AZS can be also characterized by a DSC thermogram having Endothermic peak at about 352°C, and a DSC thermogram of the following figure.

N

Me

3

N

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4-Amino-1-(2,3,5-tri-O-acetyl-β-D-ribosyl)-s-triazin-2(1H)-one

Crystalline 4-Amino-1-(2,3,5-tri-O-acetyl-β-D-ribosyl)-s-triazin-2(1H)-one ("TA-AZD") of the following formula,

O

N NH2

O

is characterized by a PXRD pattern having peaks at about 8.2, 10.9, 13.0, 13.3, 14.3, 16.4, 17.2,
20.4, 21.3, 23.7, 24.4, 25.1 and 27.4 ± 0.2 deg. 2Θ, and the following PXRD figure.

AcO

N

N

A

c

O

O

A

c

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TA-AZD can be also characterized by a DSC having Endothermic peak at about 158°C, and the DSC of the following figure.

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PXRD

XRD diffraction was performed on X-Ray powder diffractometer: PanAlytical X'pert Pro powder diffractometer equipped with X´celerator multichannel detector, detector active length 2.122 mm, Cu-tube, CuKα radiation, λ = 1.541874 Å; a stainless steel sample holder with zero background silicon plate. Scanning parameters: Range 4-40 degrees...