Reaction SMILES: COC(=O)CC(C1CC1)=O.COC(OC)N(C)C.CN(/C=C(/C(=O)C1CC1)\C(OC)=O)C.Cl.Cl.N(C1C=CC=C2C=1C=CC=N2)N.C[O:48][C:49]([C:51]1[CH:52]=[N:53][N:54]([C:59]2[CH:68]=[CH:67][CH:66]=[C:65]3[C:60]=2[CH:61]=[CH:62][CH:63]=[N:64]3)[C:55]=1[CH:56]1[CH2:58][CH2:57]1)=[O:50]>C(OCC)(=O)C.C(N(CC)CC)C>[CH:56]1([C:55]2[N:54]([C:59]3[CH:68]=[CH:67][CH:66]=[C:65]4[C:60]=3[CH:61]=[CH:62][CH:63]=[N:64]4)[N:53]=[CH:52][C:51]=2[C:49]([OH:50])=[O:48])[CH2:57][CH2:58]1
Reactant: COC(=O)c1cnn(-c2cccc3ncccc23)c1C1CC1
Agent: COC(=O)/C(=C\N(C)C)C(=O)C1CC1
Agent: COC(=O)CC(=O)C1CC1
Agent: COC(OC)N(C)C
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: O=C(O)c1cnn(-c2cccc3ncccc23)c1C1CC1
Temperature: 75 °C
Reaction time: 1 h

Procedure:
A 200 liter glass-lined reactor under nitrogen was charged with ethyl acetate (51 liters), methyl-3-cyclopropyl-3-oxopropanoate (4.90 kg) and N,N-dimethylformamide dimethylacetal (4.31 kg). The reactor was heated to about 75° C. for four hours. Completion of conversion to α-[(dimethylamino)methylene]-β-oxo-cyclopropanepropanoic acid, (αZ)-methyl ester was confirmed using thin-layer chromatography analysis (ethyl acetate/hexanes,1/1). The reactor was cooled to about 20° C. and the vessel was charged with 5-hydrazinoquinoline dihydrochloride (10.0 kg). Triethylamine (15.0 liters) was added to the reactor over about a one hour period. The reactor was then heated to about 75° C. under nitrogen and maintained at that temperature for four hours. Completion of the formation of 5-cyclopropyl-1-quinolin-5-yl-1H-pyrazole-4-carboxylic acid methyl ester was confirmed by HPLC. The reactor was then cooled to about 20° C. and ethyl acetate (17 liters) was added along with activated carbon (500 g) and filter aid (1.64 kg). A solution consisting of 66 liters of water and citric acid (20.7 kg) was then added. The resulting suspension was agitated for one hour and then filtered. The filter was rinsed with 15 liters of ethyl acetate. The filtrate formed two liquid layers upon standing. The lower, dark red aqueous layer was decanted and discarded. The upper, red organic layer was transferred to a 200 liter glass-lined reactor configured for vacuum distillation. The volume of the red organic layer was reduced by distillation under vacuum to a volume of 25 liters. Propan-2-ol (31 liters) was added to the distillation pot and the volume was reduced by vacuum distillation to 31 liters. A second propan-2-ol (31 liters) charge was made to the distillation pot and the volume was again reduced by vacuum distillation to 34 liters. The distillation apparatus was cooled to about 20° C. and reconfigured for reflux. Aqueous NaOH (50% solution, 6.90 kg) was added to the reconfigured apparatus containing the 5-cyclopropyl-1-quinolin-5-yl-1H-pyrazole-4-carboxylic acid methyl ester/isopropanol solution. The reactor was then heated to about 75° C. under nitrogen and maintained at that temperature for four hours. HPLC analysis of the reaction solution indicated that the conversion to 5-cyclopropyl-1-quinolin-5-yl-1H-pyrazole-4-carboxylic acid was complete. The reactor was then cooled to about 20° C. and the pH of the contents was adjusted to about pH 4 using concentrated hydrochloric acid. A brown suspension of solids formed as the pH was adjusted. The solids were isolated by filtration, rinsed with water and dried under vacuum at about 45° C. resulting in 6.10 kg of 5-cyclopropyl-1-quinolin-5-yl-1H-pyrazole-4-carboxylic acid as a brown solid.