911637-19-9
| Name | GeMigliptin |
| CAS | 911637-19-9 |
| EINECS(EC#) | 1592732-453-0 |
| Molecular Formula | C18H19F8N5O2 |
| MDL Number | MFCD19443742 |
| Molecular Weight | 489.36 |
| MOL File | 911637-19-9.mol |
Chemical Properties
| Boiling point | 539.1±50.0 °C(Predicted) |
| density | 1.54±0.1 g/cm3(Predicted) |
| storage temp. | Store at -20°C |
| solubility | DMSO:74.0(Max Conc. mg/mL);151.21(Max Conc. mM) Ethanol:7.0(Max Conc. mg/mL);14.3(Max Conc. mM) Water:12.0(Max Conc. mg/mL);24.52(Max Conc. mM) |
| form | Solid |
| pka | 7.33±0.10(Predicted) |
| color | White to orange |
| InChI | InChI=1S/C18H19F8N5O2/c19-16(20)3-1-12(32)31(8-16)6-9(27)5-13(33)30-4-2-10-11(7-30)28-15(18(24,25)26)29-14(10)17(21,22)23/h9H,1-8,27H2/t9-/m0/s1 |
| InChIKey | ZWPRRQZNBDYKLH-VIFPVBQESA-N |
| SMILES | N1(C[C@@H](N)CC(N2CC3C(CC2)=C(C(F)(F)F)N=C(C(F)(F)F)N=3)=O)CC(F)(F)CCC1=O |
Safety Data
| Symbol(GHS) |  GHS07 |
| Signal word | warning |
| Hazard statements | H302-H335 |
| Precautionary statements | P264-P270-P301+P312-P330-P501-P261-P271-P304+P340-P312-P403+P233-P405 |
1,4-Addition of ethyl bromodifluoroacetate
(76) to ethyl acrylate (77) in the presence of
copper powder and tetramethylethylenediamine (TMEDA) gave
diester 78, which was selectively reduced with sodium borohydride
(NaBH4) to give alcohol 79 in 90% overall yield for the
two-step procedure. Alcohol 79 was then treated with perfluorobutanesulfonyl
chloride and triethylamine to give activated
alcohol 80 in 75% yield.
Boc-L-aspartic acid 4-tert-butyl ester (81) was treated
with ammonium bicarbonate and pyridine in the presence of
di-tert-butyl dicarbonate to give formamide 82. Dehydration of
82 to give nitrile 83 was accomplished through reaction with cyanuric
chloride in 95% overall yield for the two-step sequence.
Hydrogenation of 83 in the presence of Pearlman?ˉs catalyst provided butyl amine 84. Alkylation of 84 with activated alcohol
80 in triethylamine followed by cyclization in acetic acid afforded
difluoropyridone 85. Acidic hydrolysis of the ester proceeded with
concomitant removal of the Boc protecting group, and was followed
by reprotection of the amine with di-tert-butyl dicarbonate
to give acid 86 in 84% overall yield for the three-step procedure in
>97% ee. Coupling of 86 with fragment 75 in the presence of 1-hydroxybenzotriazole
(HOBT) and 1-ethyl-3-(3-dimethylaminopropyl)
carbodiimide (EDC) gave amide 87 in 51% yield. Removal
of the Boc group with thionyl chloride in ethanol followed by neutralization
with aqueous sodium hydroxide and salt formation
with L-tartaric acid provided gemigliptin L-tartrate hydrate (X) in
97.5% yield.
