Sitagliptin phosphate monohydrate Chemical Properties

Flash point:

274.3℃

storage temp. 

2-8°C

solubility 

≥23.8 mg/mL in DMSO; insoluble in EtOH; ≥30.6 mg/mL in H2O with ultrasonic

form 

solid

color 

White to off-white

optical activity

-5.53°(C=0.60g/100mL, NAOH, 20°C, 589nm)

InChI

InChI=1/C16H15F6N5O.H3O4P/c17-10-6-12(19)11(18)4-8(10)3-9(23)5-14(28)26-1-2-27-13(7-26)24-25-15(27)16(20,21)22;1-5(2,3)4/h4,6,9H,1-3,5,7,23H2;(H3,1,2,3,4)/t9-;/s3

InChIKey

IQFYVLUXQXSJJN-OVMXBOEKNA-N

SMILES

P(O)(O)(O)=O.C(C1=NN=C2CN(C(=O)C[C@H](N)CC3C=C(F)C(F)=CC=3F)CCN12)(F)(F)F |&1:15,r|

CAS DataBase Reference

654671-77-9(CAS DataBase Reference)

Safety Information

Risk Statements 

28-38-41-48-62-63

Safety Statements 

24/25-26-28-36/37/39

HS Code 

29335990

Sitagliptin phosphate monohydrate Usage And Synthesis

Chemical Properties

white crystalline

Uses

antimuscarinic

Uses

Sitagliptin Phosphate Monohydrate is a dipeptidyl peptidase-IV (DPPIV) inhibitor.

Biological Activity

sitagliptin phosphate monohydrate is the phosphate salt of its active component, sitagliptin, with one molecule of water. sitagliptin is a potent inhibitor of dipeptidyl peptidase 4 (dpp-4), an enzyme catalyzing the cleavage of peptides with an n-terminal alanine or proline amino acid residue, that selectively inhibits dpp-4 with 50% inhibition concentration ic50 value of 18 nm and shows no affinity towards other ddp enzymes (such as ddp-8 and ddp-9). the inhibition of dpp4 by sitagliptin has been found to be mediated by increasing levels of two dpp-4 substrates, including glucagon-like peptide-1 (glp-1) and gastric inhibitory polypeptide (gip). sitagliptin is currently being investigated in the treatment of type ii diabetes.gallwitz b. review of sitagliptin phosphate: a novel treatment for type 2 diabetes. vasc health risk manag. 2007;3(2):203-10.

Synthesis

The general procedure for the synthesis of (R)-3-amino-1-(3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-one as a raw material and its phosphate hydrate was carried out in the following manner: 8.14 g of (R)-3-amino-1-( 3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-one, 16.3 mL of isopropanol, and 7.3 mL of water, followed by the slow dropwise addition of 1.73 mL of 85% (v/v) phosphoric acid aqueous solution. The temperature of the reaction system was raised to 80 °C until complete dissolution to form a clear solution. The solution was then cooled to 70 °C and the reaction was continuously stirred at this temperature for 2 hours. Upon completion of the reaction, the mixture was cooled to 54 °C at a rate of 8 °C/h and then continued to cool to 22 °C at a rate of 16 °C/h, at which point a large amount of white solid precipitated. 57 mL of isopropanol was added slowly over a period of 40 minutes and stirring was continued for 15 minutes after addition. The white solid was collected by diafiltration and washed twice with 40.7 mL of mixed isopropanol-water solvent (V/V=11:1). Finally, the product was dried under vacuum at 25 °C and -0.08 MPa for 5.5 h to give 10.22 g of white crystalline solid. The purity was 99.91% by HPLC, the moisture content was 3.54% and the molar yield was 97.7%.

target

DPP-4

References

[1] Patent: CN105175422, 2018, B. Location in patent: Paragraph 0070; 0077; 0080; 0083; 0086; 0089; 0092; 0095
[2] Synthetic Communications, 2013, vol. 43, # 24, p. 3281 - 3286
[3] Patent: WO2006/33848, 2006, A1. Location in patent: Page/Page column 14
[4] Patent: WO2005/30127, 2005, A2. Location in patent: Page/Page column 13
[5] Patent: US2013/158265, 2013, A1. Location in patent: Paragraph 0204

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