5-oxo-5,8-dihydro-pyrido-pyrimidines as inhibitors of C-FMS kinase
A technology of alkoxy and CH2, which can be used in anti-inflammatory agents, metabolic diseases, antiviral agents, etc., and can solve problems such as inflammation and joint damage
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0435] 8-Indan-5-yl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-5-oxo-5,8-dihydro-pyrido[2, 3-d]Pyrimidine-6-carboxylic acid ethyl ester (Compound 1)
[0436]
[0437] A. 3-(Indan-5-ylamino)-propionic acid ethyl ester
[0438] Tetrabutylammonium bromide (200 mg) was added to a mixture of 5-aminoindane (5 g, 37.6 mmol), ethyl 3-chloropropionate (4.7 mL, 37.6 mmol) and potassium carbonate (5.2 g, 37.6 mmol) middle. The mixture was stirred at 100°C for 16 hours. After cooling to room temperature (rt), the mixture was extracted into ethyl acetate (EtOAc), washed with water, brine, then sodium sulfate (Na 2 SO 4 )dry. Removal of the solvent and chromatography on silica gel eluting with EtOAc / hexanes (1:20-1:10, v / v) afforded 6.2 g (71%) of the title compound.
[0439] 1 H NMR (300MHz, CDCl 3 )δ(ppm): 7.03(d, J=7.6Hz, 1H), 6.55(s, 1H), 6.43(d, J=7.6Hz, 1H), 4.15(q, 2H), 3.86(br, 1H) , 3.43(t, 2H), 2.82(m, 4H), 2.60(t, 2H), 2.06(m, 2H), 1.27(t, 3H).
[0440] B, 4-[(2-eth...
Embodiment 2
[0459] 2-[4-(3-Dimethylamino-2-hydroxy-propyl)-phenylamino]-8-indan-5-yl-5-oxo-5,8-dihydro-pyrido[2 , 3-d] pyrimidine-6-carboxylic acid ethyl ester (compound 2)
[0460]
[0461] A, 2-(4-nitro-phenoxymethyl)-oxirane
[0462] Potassium carbonate (1.3 g, 9.6 mmol) was added to a mixture of 4-nitrophenol (1.11 g, 8 mmol) and epibromohydrin (1.37 mL, 16 mmol). The mixture was stirred at 100°C for 18 hours. After cooling, the residue was extracted into EtOAc. The organic layer was washed with water, brine, then Na 2 SO 4 dry. The solvent was removed in vacuo to give an orange residue which was purified by silica gel chromatography eluting with EtOAc / hexanes (1:10, v / v). The product was obtained as a yellow solid (0.8 g, 51%).
[0463] 1 H NMR (300MHz, CDCl 3 )δ(ppm): 8.21(m, 2H), 6.98(m, 2H), 4.37(dd, J=2.8Hz, 11.1Hz, 1H), 4.00(dd, J=5.9Hz, 11.1Hz, 1H), 3.90(m, 1H), 2.93(t, J=4.8Hz, 1H), 2.77(dd, J=2.8Hz, 4.8Hz, 1H).
[0464] B. 1-(4-Amino-phenoxy)-3-dimethylamino-pro...
Embodiment 3
[0472] 8-Indan-5-yl-2-(4-morpholin-4-yl-phenylamino)-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6 - Ethyl formate (compound 3)
[0473]
[0474] Using the procedure described in Example 1(g), the title compound was prepared from 4-morpholin-4-yl-aniline (6.5 mg, 0.036 mmol) and 8-indan-5-yl-2-methanesulfonyl- Prepared from ethyl 5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylate (from Example 1(e) (see above), 15 mg, 0.036 mmol). 11.9 mg of 8-indan-5-yl-2-(4-morpholin-4-yl-phenylamino)-5-oxo-5,8-dihydro-pyrido[2,3-d were obtained ] Pyrimidine-6-carboxylic acid ethyl ester as a yellow solid.
[0475] 1 H NMR (400MHz, CDCl 3 )δ(ppm): 9.38(br, 1H), 8.53(s, 1H), 7.69(br, 1H), 7.43(d, 1H), 7.23(m, 4H), 6.64(br, 2H), 4.36( q, 2H), 3.87 (m, 4H), 3.04 (m, 8H), 2.22 (m, 2H), 1.39 (t, 3H).
[0476] Mass spectrometry (LCMS, ESI pos.) calculated as C 29 H 29 N 5 O 4 : 512.24 (M+H), found: 512.4.
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More