1,3,5-TRIMETHYL-1H-PYRAZOLE-4-CARBOXYLICACID

The following were prepared as described above using the appropriate pyrazole ester:3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid1, 3-Dimethyl-1H-pyrazole-4-carboxylic acid1, 3, 5-Trimethyl-1H-pyrazole-4-carboxylic acid3-(Difluoromethyl)-1-(2-propenyl)-1H-pyrazole-4-carboxylic acid3-(Methylthio)-1-methyl-1H-pyrazole-4-carboxylic acid3-Bromo-1-methyl-1H-pyrazole-4-carboxylic acid3-Cyano-1-methyl-1H-pyrazole-4-carboxylic acid3-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid3-Iodo-1-methyl-1H-pyrazole-4-carboxylic acid...To a suspension of 6-(2-amino-5-chlorothiazol-4-yl)-3, 4-dihydroquinolin-2(1H)-one (0.05 g, 0.20 mmol) and Example 19; 2'-O-(3-{[(1, 3, 5-Trimethyl-1 H-pyrazol-4-yl)carbonyl]amino}propyl)-9-deoxo-9a- methyl-9a-aza-9a-homoerythromycin APS-Carbodiimide resin (PS-CDI, loading: 1.24 mmol/g; 390 mg, 0.806 mmol, 1.3eq) was added to a dry reaction vessel. The 1, 3, 5-trimethyl-1 H-pyrazole-4-carboxylic acid (60.2 mg, 0.391 mmol) and HOBt (35.2 mg, 0.261 mmol) diluted in a mixture of dry DCM (5 mL) and dry DMF (0.2 mL) were added to the dry resin. The mixture was stirred at room temperature for 5 minutes upon which 2'-O-(3-aminopropyl)-9-deoxo-9a-methyl-9a-aza-9a-homoerythromycin A, Intermediate 1 (300 mg, 0.372 mmol), dissolved in DCM (dried over molecular sieves) (7 mL) was added. The reaction mixture was heated by microwave at 75 0C for 7 minutes. HOBt was scavenged using PS-trisamine (loading:4.1 1 mmol/g) (318 mg, 5eq according to HOBt) for 4 hours at room temperature. The resin was removed from the reaction mixture by filtration and washed with DCM (2x10 mL). Solvent was evaporated in vacuum yielding 540 mg of transparent oil that was diluted in EtOAc (20 ml) and extracted with water (20 ml) at pH 4. Organic layer was discarded and aqueous extracted with DCM (20ml) at pH 5.5. Organic layer was discarded and aqueous extracted with DCM (3x20 ml) at pH 6. To the combined organic layers water (20 ml) was added, pH adjusted to 9 and layers separated. DCM was evaporated in vacuum yielding transparent oil which was precipitated from EtOAc/n-hexane, filtered off and dried at 50 0C for 5 hours yielding title compound (141 mg) as a white powder. MS (ES+): 942.58 [MH]+ 13C NMR (DMSO, 125 MHz) delta 177.5, 164.4, 144.9, 139.7, 1 14.9, 102.5, 94.7, 82.4, 80.6, 77.7, 77.4, 76.7, 75.3, 73.9, 73.2, 72.9, 71.3, 68.9, 67.2, 65.0, 64.0, 61.8, 49.2, 45.3, 42.2, 41.9, 40.9, 37.2, 36.1 , 35.8, 35.0, 32.1 , 30.5, 27.8, 26.3, 22.3, 21.8, 21.4, 21.3, 18.9, 18.0, 15.2, 13.3, 1 1.3, 10.5, 8.6, 7.1.

Molecular Weight:154.17
XLogP3:0.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:154.074227566
Monoisotopic Mass:154.074227566
Topological Polar Surface Area:55.1
Heavy Atom Count:11
Complexity:172
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes