Reaction SMILES: ClCCl.[CH2:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([NH:16][CH:17]3[CH2:25][C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[CH2:18]3)=[CH:13][N:14]=2)[C:9](=[O:26])[C:8]([C:27](O)=[O:28])=[CH:7]1)[CH3:5].C(Cl)(=O)C(C)(C)C.[NH:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1>CN(C1C=CN=CC=1)C.CN(C=O)C.C(N(CC)CC)C>[CH2:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:25][CH:17]1[NH:16][C:12]1[CH:11]=[C:10]2[C:15](=[N:14][CH:13]=1)[N:6]([CH2:4][CH3:5])[CH:7]=[C:8]([C:27]([N:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1)=[O:28])[C:9]2=[O:26]
Reactant: CCn1cc(C(=O)O)c(=O)c2cc(NC3Cc4ccccc4C3)cnc21
Reactant: C1COCCN1
Agent: CC(C)(C)C(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CCn1cc(C(=O)N2CCOCC2)c(=O)c2cc(NC3Cc4ccccc4C3)cnc21
Temperature: 12.5 °C
Reaction time: 12.5 h

Procedure:
160.0 L of dichloromethane (water content should be no more than 0.1%), 1-ethyl-6-(indan-2-ylamino)-4-oxo-1,8-naphthyridine-3-carboxylic acid (4.0 kg) and triethylamine (3.5 kg) were sequentially added to reactor at 25-30° C. under nitrogen atmosphere and the reaction mixture was cooled to 10-15° C. Pivaloyl chloride (4.1 kg) was slowly added to reaction mixture keeping the reaction temperature at 10-15° C. Then, the reaction temperature was raised to 25-30° C. and stirred. The reaction progress was monitored by TLC for disappearance of starting material. After completion of reaction (3-4 h), the reaction mixture was again cooled to 15-20° C. and morpholine (6.0 kg) was added with stirring, keeping the reaction temperature at 15-20° C. N,N-Dimethyl-4-aminopyridine (194 g) and DMF (2.0 L) were added to the reaction mixture at 15-20° C. and heated to reflux. The reaction progress was monitored by TLC for the disappearance of intermediate pivaloyl ester and found to be complete within 12-13 h. The reaction mixture was cooled to 15-20° C. and then quenched by addition of aqueous sodium bicarbonate solution (prepared by dissolving 5.6 kg of sodium bicarbonate in 56.0 L of water) with stirring. The organic layer was separated and washed with aqueous sodium chloride solution (prepared by dissolving 23.0 kg of sodium chloride in 57.0 L of water). The organic layer was separated and dried by stirring with anhydrous sodium sulphate (4.0 kg). The organic layer was filtered through a Nutsche filter and the sodium sulphate was washed with dichloromethane. The filtrate was transferred into a flask and evaporated under vacuum below 40° C. The resulting material in the flask was cooled to 25-30° C. and suspended in diethyl ether (40.0 L). The solid separated was filtered using a Nutsche filter and washed with diethyl ether (8.0 L) and the isolated wet solid was dissolved in dichloromethane (20.0 L). The solution (10.0 L) was then filtered through a silica gel plug (10.0 kg) with dichloromethane (36.0 L), followed by 10 L of 10% methanol in dichloromethane. The silica gel filter was dried under vacuum. Similarly, the remaining portion of solution (10.0 L) was filtered through another silica gel plug (10.0 kg). The combined filtrate was evaporated under vacuum below 40° C. and then residual solid was suspended in ethyl acetate (20.0 L) with stirring at 25-30° C. The solid separated was filtered through Nutsche filter and washed with ethyl acetate (4.0 L). The filter was dried under vacuum and then material was transferred to drying trays and dried at 40-45° C. Yield (2.36 kg). 1H NMR (DMSO-d6, 500 MHz): 1.49 (3H, t, J=7.2 Hz), 2.91(2H, dd, J=3.5 Hz, 16.0 Hz), 3.42-3.47(4H, m), 3.80(6H, s), 4.25-4.26(1H, bd), 4.40-4.48(3H, m), 7.20-7.25(4H, m), 7.82(1H, d, J=3.0 Hz), 8.09 (1H, s), 8.18(1H, d, J=3.0 Hz). 13C NMR (CDCl3, 150 MHz): 15.27, 39.87, 43.05, 46.66, 48.09, 53.93, 66.80, 67.40, 113.27, 116.71, 123.22, 124.92, 126.78, 140.87, 141.46, 141.83, 141.90, 143.84, 166.27, 173.38.