Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[NH2:2][C@H:3]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=1)[C:4]([N:6]1[CH2:9][C:8]([O:17][CH2:18][CH2:19][CH2:20][CH3:21])([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH3:16])[CH2:7]1)=[O:5].[NH:31]1[CH:35]=[C:34]([CH2:36][CH2:37][C:38](O)=[O:39])[N:33]=[N:32]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C>CN(C)C=O.O>[CH2:18]([O:17][C:8]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH3:16])[CH2:7][N:6]([C:4](=[O:5])[C@H:3]([NH:2][C:38](=[O:39])[CH2:37][CH2:36][C:34]2[N:33]=[N:32][NH:31][CH:35]=2)[CH2:22][C:23]2[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=2)[CH2:9]1)[CH2:19][CH2:20][CH3:21]
Reactant: CCCCOC1(c2ccccc2C)CN(C(=O)[C@H](N)Cc2ccc(OC)cc2)C1
Reactant: O=C(O)CCc1c[nH]nn1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: CCCCOC1(c2ccccc2C)CN(C(=O)[C@@H](Cc2ccc(OC)cc2)NC(=O)CCc2c[nH]nn2)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 44.5 %

Procedure:
146 mg (0.34 mmol) of (R)-2-amino-1-(3-butoxy-3-o-tolylazetidin-1-yl)-3-(4-methoxyphenyl)propan-1-one hydrochloride in 2 ml of dimethylformamide are added to a solution of 47 mg (0.34 mmol) of 3-(1H[1,2,3]triazol-4-yl)propanoic acid, 119 mg (0.37 mmol) of TBTU and 0.15 ml (1.1 mmol) of triethylamine in 2 ml of dimethylformamide. The reaction mixture is stirred for 2 hours at ambient temperature. The reaction is stopped by adding 10 ml of water and then extracted with ethyl acetate. The organic phases are combined, washed with a 1N solution of sodium hydroxide and then a saturated solution of sodium chloride, and dried over sodium sulphate. After filtration, the solvents are evaporated off and the residue is then purified by silica gel chromatography (eluent 90/10 ethyl acetate/heptane). 78.6 mg of N—[(R)-2-(3-butoxy-3-o-tolylazetidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethyl]-3-(1H[1,2,3]triazol-4-yl)propionamide are obtained in the form of a white powder with a yield of 45%.
Reaction SMILES: [C:1]([C:4](C(OCC)=O)([CH2:19][CH:20]=[CH:21][CH:22]([O:28]C(=O)C)[CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH2:5][CH2:6][CH2:7][C:8]1[CH:18]=[CH:17][C:11]([C:12]([O:14]CC)=[O:13])=[CH:10][CH:9]=1)(=[O:3])[CH3:2].[OH-].[Na+]>O.C(O)C>[C:1]([CH:4]([CH2:19][CH:20]=[CH:21][CH:22]([OH:28])[CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH2:5][CH2:6][CH2:7][C:8]1[CH:9]=[CH:10][C:11]([C:12]([OH:14])=[O:13])=[CH:17][CH:18]=1)(=[O:3])[CH3:2]
Reactant: CCCCCC(C=CCC(CCCc1ccc(C(=O)OCC)cc1)(C(C)=O)C(=O)OCC)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CCCCCC(O)C=CCC(CCCc1ccc(C(=O)O)cc1)C(C)=O

Procedure:
A solution of ethyl 4-(4-acetyl-4-ethoxycarbonyl-8-acetoxytridec-6-en-1-yl)benzoate (50.2 g., 0.1 mole) and sodium hydroxide (28.0 g., 0.7 mole) in water (300 ml.) and ethanol (350 ml.) is boiled under reflux for 3 hours. Solvents are removed under reduced pressure, the residue is dissolved in water, and the solution extracted with ether. The aqueous layer is acidified with concentrated hydrochloric acid to the Congo Red endpoint. The crude product separates as an oil. It is isolated in pure condition by column chromatography on silica gel with 4% methanol in chloroform as the eluant. 4-(4-Acetyl-8-hydroxytridec-6-en-1-yl)benzoic acid is obtained as a yellow, very viscous oil.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:13]([CH3:14])=[CH:12][C:11](Cl)=[CH:10][CH:9]1[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Li+].[Li+]>CO.[Pd]>[C:1]([O:5][C:6]([N:8]1[C:13]([CH3:14])=[CH:12][CH2:11][CH2:10][CH:9]1[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCCCCCCCCCCC1C=C(Cl)C=C(C)N1C(=O)OC(C)(C)C
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Li+]
Solvent: CO
Product: CCCCCCCCCCCC1CCC=C(C)N1C(=O)OC(C)(C)C
Yield: 68 %

Procedure:
To a stirred solution of 2.17g, (5.65 mmol) of 1-(tert-Butoxycarbonyl)-4-chloro-6-methyl-2-n-undecyl-1,2-dihydropyridine in 120 mL of MeOH at 0° C. was added 0.422 g (5.71 mmol) of lithium carbonate followed by of 5% Pd/C. The flask was evacuated and filled with hydrogen repeatedly. The system was placed under positive pressure from a balloon, and the reaction was monitored by removing aliquots with a syringe, concentrating the aliquot in vacuo, and examing its 1H NMR spectrum. Upon completion, the mixture was filtered through Celite, and concentrated by evaporation. The residue was dissolved in ether (20 mL), water(20 mL) was added, and the aqueous phase was extracted twice with ether(2×10 mL). The combined organic extracts were washed with 1M NaOH(2×20ml) and brine. The organic products were dried over K2CO3, filtered through Celite, and concentrated in vacuo to give the crude product. Purification by column chromatography, (silica gel, 10% ether in hexanes) afforded 1.35 g (70%) the product as a light yellow oil which was homogeneous by TLC analysis. 1H NMR (300 MHz) δ4.75 (br s, 1 H), 4.62 (m, 1 H), 2.21 (s, 3 H), 1.91-1.64 (m, 4 H), 1.52 (s, 9 H), 1.28 (br s, 20 H), 0.90 (t, 3H); 13C NMR (75 MHz) 154.1 (s), 133.5 (s), 110.4 (s), 79.6 (s), 52.1 (s), 32.3 (s), 30.1 (s), 30.0 (s), 29.9 (s), 28.5 (s), 26.7 (s), 23.5 (s), 23.2 (s), 19.8 (s), 14.4 (s) ppm. FT-IR (neat) 2928, 2860, 1694, 1457, 1368, 1352, 1168, 1124, 1095, 1073 cm−1.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10](SC)[N:11]=[N:12][CH:13]=2)=[CH:4][C:3]=1[C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1.[F:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1B(O)O>>[F:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:10]1[N:11]=[N:12][CH:13]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[C:3]([C:16]3[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=3)[CH:4]=2)[N:9]=1
Reactant: OB(O)c1ccccc1F
Reactant: CSc1nncc(-c2ccc(F)c(-c3cccnc3)c2)n1
Product: Fc1ccc(-c2cnnc(-c3ccccc3F)n2)cc1-c1cccnc1

Procedure:
5-[4-Fluoro-3-(pyridin-3-yl)phenyl]-3-methylsulfanyl-[1,2,4]triazine was coupled to 2-fluorophenylboronic acid by the method of Example 2 to give 3-(2-fluorophenyl)-5-[4-fluoro-3-(pyridin-3-yl)phenyl]-[1,2,4]triazine as a yellow solid: δH (400 MHz, CDCl3) 7.28-7.30 (1H, m), 7.33-7.47 (3H, m), 7.52-7.59 (1H, m), 7.97 (1H, dd, J 2.0, 8.2 Hz), 8.25-8.32 (2H, m), 8.44 (1H, dd, J 2.3, 7.4 Hz), 8.70 (1H, d, J 2.7 Hz), 8.89 (1H, s), 9.67 (1H, s); m/z (ES+) 347.
Reaction SMILES: [C:1]1([C:7]2[N:8]=[CH:9][N:10](C(OCC)C)[C:11]=2[C:12]2[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Li])CCC.[F:30][C:31]([F:39])([F:38])[C:32]([C:34]([F:37])([F:36])[F:35])=[O:33].C(=O)(O)[O-].[Na+]>O1CCCC1.CCCCCC>[C:1]1([C:7]2[N:8]=[C:9]([C:32]([C:34]([F:37])([F:36])[F:35])([C:31]([F:39])([F:38])[F:30])[OH:33])[NH:10][C:11]=2[C:12]2[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCOC(C)n1cnc(-c2ccccc2)c1-c1ccc(SC)cc1
Reactant: O=C(C(F)(F)F)C(F)(F)F
Agent: O=C([O-])O
Agent: [Li]CCCC
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CSc1ccc(-c2[nH]c(C(O)(C(F)(F)F)C(F)(F)F)nc2-c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred solution of 4-phenyl-5-(4-methylthiophenyl)-1-(α-ethoxyethyl)imidazole (15.5 g, 0.05 mole) in 175 ml of dry tetrahydrofuran was added 7.95 ml (0.052 mole) of N,N-tetramethylethylenediamine. The reaction mixture was cooled to -78° and 45.9 ml of 1.6 M n-butyl lithium in hexane was added dropwise. After stirring the mixture an additional 15 minutes, hexafluoroacetone (12.2 ml) was condensed in a jacketed addition funnel and added dropwise. The mixture was stirred for 1 hour with continued cooling and then 200 ml of saturated aqueous sodium bicarbonate solution was added dropwise. The reaction was warmed to room temperature, and the organic layer was separated. The solvent was evaporated in vacuo and the residue was stirred in 300 ml of ethanol and 300 ml of 2N aqueous hydrochloric acid. The ethanol was removed in vacuo and the reaction mixture was basified to pH=8 with saturated aqueous potassium carbonate. The product was extracted into ether, washed with 10% aqueous sodium bicarbonate and dried over anhydrous potassium carbonate. After concentration in vacuo, the residue was purified by flash chromatography on silica gel (85:15 hexane/ethyl acetate) followed by trituration with petroleum ether to afford 12.3 g of 4-phenyl-5-(4-methylthiophenyl)-α,α-bis(trifluoromethyl)-1H-imidazole-2-methanol, m.p. 119°-121°.
Reaction SMILES: [CH2:1]([C:8]1[C:9](=[O:20])[NH:10][N:11]([C:16](=[O:19])[CH2:17][CH3:18])[C:12]=1[CH:13]([CH3:15])[CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[C:27]([O:33][C@@H:34]1[C@@H:39]([O:40][C:41](=[O:46])[C:42]([CH3:45])([CH3:44])[CH3:43])[C@H:38]([O:47][C:48](=[O:53])[C:49]([CH3:52])([CH3:51])[CH3:50])[C@@H:37]([CH2:54][O:55][C:56](=[O:61])[C:57]([CH3:60])([CH3:59])[CH3:58])[O:36][C@H:35]1Br)(=[O:32])[C:28]([CH3:31])([CH3:30])[CH3:29]>C(#N)C>[CH2:1]([C:8]1[C:9]([O:20][C@@H:35]2[O:36][C@H:37]([CH2:54][O:55][C:56](=[O:61])[C:57]([CH3:60])([CH3:59])[CH3:58])[C@@H:38]([O:47][C:48](=[O:53])[C:49]([CH3:50])([CH3:51])[CH3:52])[C@H:39]([O:40][C:41](=[O:46])[C:42]([CH3:43])([CH3:44])[CH3:45])[C@H:34]2[O:33][C:27](=[O:32])[C:28]([CH3:31])([CH3:29])[CH3:30])=[N:10][N:11]([C:16](=[O:19])[CH2:17][CH3:18])[C:12]=1[CH:13]([CH3:14])[CH3:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)C(=O)OC[C@H]1O[C@@H](Br)[C@H](OC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@@H]1OC(=O)C(C)(C)C
Reactant: CCC(=O)n1[nH]c(=O)c(Cc2ccccc2)c1C(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCC(=O)n1nc(O[C@@H]2O[C@H](COC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@H](OC(=O)C(C)(C)C)[C@H]2OC(=O)C(C)(C)C)c(Cc2ccccc2)c1C(C)C
Temperature: 25 °C
Yield: 84.8 %

Procedure:
To a solution of 4-benzyl-1,2-dihydro-5-isopropyl-1-propionyl-3H-pyrazol-3-one (1.25 g) in acetonitrile (25 mL) were added potassium carbonate (0.951 g) and 2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyl bromide (2.79 g) under stirring at room temperature. In addition, the mixture was heated to 50° C. and stirred for 3 hours. After the completion of the reaction, the insoluble materials were removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=20/1) to give 4-benzyl-5-isopropyl-1-propionyl-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyl-oxy)-1H-pyrazole (3.00 g).
Reaction SMILES: [CH3:1][C:2]1([CH3:11])[O:7][CH2:6][C:5]([NH2:10])([CH2:8][CH3:9])[CH2:4][O:3]1.[C:12](O)(=[O:24])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23].C1CCC(N=C=NC2CCCCC2)CC1.ON1C2C=CC=CC=2N=N1>C(Cl)Cl>[CH3:11][C:2]1([CH3:1])[O:3][CH2:4][C:5]([NH:10][C:12](=[O:24])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])([CH2:8][CH3:9])[CH2:6][O:7]1
Reactant: CCCCCCCCCCCC(=O)O
Reactant: CCC1(N)COC(C)(C)OC1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Solvent: ClCCl
Product: CCCCCCCCCCCC(=O)NC1(CC)COC(C)(C)OC1

Procedure:
2,2-Dimethyl-5-amino-5-ethyl-1,3-dioxane is acylated wih dodecanoic acid in methylene chloride in the presence of DCC and 1-hydroxybenzo-triazole. Filtration and concentration gives the product.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([S:14][C:15]2[CH:20]=[CH:19][C:18]([C:21](=[O:30])[NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([Br:29])[CH:24]=3)=[CH:17][C:16]=2[NH:31][C:32]2[C:33]3[CH:41]=[CH:40][C:39]([CH3:42])=[N:38][C:34]=3[N:35]=[CH:36][N:37]=2)=[CH:10][CH:9]=1)(C)(C)C.[F:44][C:45]([F:50])([F:49])[C:46]([OH:48])=[O:47]>C(Cl)Cl>[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([S:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]([NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([Br:29])[CH:24]=3)=[O:30])=[CH:17][C:16]=2[NH:31][C:32]2[C:33]3[CH:41]=[CH:40][C:39]([CH3:42])=[N:38][C:34]=3[N:35]=[CH:36][N:37]=2)=[CH:10][CH:9]=1.[F:44][C:45]([F:50])([F:49])[C:46]([OH:48])=[O:47]
Reactant: Cc1ccc2c(Nc3cc(C(=O)Nc4cccc(Br)c4)ccc3Sc3ccc(NC(=O)OC(C)(C)C)cc3)ncnc2n1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1ccc2c(Nc3cc(C(=O)Nc4cccc(Br)c4)ccc3Sc3ccc(N)cc3)ncnc2n1

Procedure:
The product of Example 66 was treated with trifluoroacetic acid (3 mL) in methylene chloride (3 mL) at room temperature for 30 minutes. The solvents were removed under vacuum to provide the title compound as a trifluoroacetic acid salt. 1H NMR (300 MHz, DMSO-D6) δ ppm: 2.77 (s, 3 H) 6.65 (d, J=8.46 Hz, 2 H) 6.97 (d, J=8.46 Hz, 1 H) 7.16 (d, J=8.46 Hz, 2 H) 7.30 (m, 2 H) 7.72 (m, 1 H) 7.90 (m, 3 H) 8.05 (s, 1 H) 8.92 (s, 1 H) 9.01 (d, J=8.46 Hz, 1 H) 10.36 (s, 1 H) 11.78 (s, 1 H); MS (ESI+) m/z 557, 559 (M+H)+.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]#[C:11][CH2:12][CH2:13][OH:14])([O-:3])=[O:2].[CH3:15]I>C(#N)C.[Ag]=O>[CH3:15][O:14][CH2:13][CH2:12][C:11]#[C:10][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[N+:1]([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccccc1C#CCCO
Reactant: CI
Agent: O=[Ag]
Solvent: CC#N
Product: COCCC#Cc1ccccc1[N+](=O)[O-]
Temperature: 50 °C
Reaction time: 70 h

Procedure:
A solution of 2.9 g of 4-(2-nitrophenyl)but-3-yn-1-ol in 750 ml of acetonitrile is admixed at room temperature with 17.5 g of silver oxide and 9.4 ml of methyl iodide and stirred at 50° C. over 70 hours. The reaction mixture is clarified by filtration and the filtrate is concentrated by evaporation. The title compound is obtained as a yellow oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.34 (1:2 EtOAc-heptane); Rt=4.17.
Reaction SMILES: [CH:1]1([NH:5][CH2:6][C:7]2[CH:12]=[CH:11][C:10]([N:13]3[CH2:18][CH2:17][N:16]([C:19](=[O:21])[CH3:20])[CH2:15][CH2:14]3)=[CH:9][C:8]=2[F:22])[CH2:4][CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.[Cl:32][C:33]1[CH:34]=[C:35]([S:40](Cl)(=[O:42])=[O:41])[CH:36]=[C:37]([Cl:39])[CH:38]=1>ClCCl>[C:19]([N:16]1[CH2:15][CH2:14][N:13]([C:10]2[CH:11]=[CH:12][C:7]([CH2:6][N:5]([CH:1]3[CH2:2][CH2:3][CH2:4]3)[S:40]([C:35]3[CH:34]=[C:33]([Cl:32])[CH:38]=[C:37]([Cl:39])[CH:36]=3)(=[O:42])=[O:41])=[C:8]([F:22])[CH:9]=2)[CH2:18][CH2:17]1)(=[O:21])[CH3:20]
Reactant: CC(=O)N1CCN(c2ccc(CNC3CCC3)c(F)c2)CC1
Reactant: O=S(=O)(Cl)c1cc(Cl)cc(Cl)c1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(=O)N1CCN(c2ccc(CN(C3CCC3)S(=O)(=O)c3cc(Cl)cc(Cl)c3)c(F)c2)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 44.3 %

Procedure:
To a solution of 1-(4-(4-((cyclobutylamino)methyl)-3-fluorophenyl)piperazin-1-yl)ethanone (55 mg, 0.18 mmol) in dichloromethane (1 mL) was added N,N-diisopropylethylamine (0.047 mL, 0.27 mmol), followed by 3,5-dichlorobenzene-1-sulfonyl chloride (50 mg, 0.20 mmol) and the reaction was stirred at ambient temperature for 16 hours. The reaction was then concentrated and purified by preparative reverse phase HPLC to yield 41 mg of N-(4-(4-acetylpiperazin-1-yl)-2-fluorobenzyl)-3,5-dichloro-N-cyclobutylbenzenesulfonamide. 1H NMR (400 MHz, DMSO) δ 7.95 (t, J=1.8 Hz, 1H), 7.72 (d, J=1.8 Hz, 2H), 7.18 (t, J=8.9 Hz, 1H), 6.80-6.74 (m, 1H), 6.74-6.67 (m, 1H), 4.40 (s, 2H), 4.35-4.20 (m, 1H), 3.62-3.51 (m, 4H), 3.25-3.17 (m, 2H), 3.16-3.10 (m, 2H), 2.04 (s, 3H), 2.02-1.88 (m, 4H), 1.55-1.48 (m, 2H); LCMS (m/z) ES+ 514.0 [M+1]+.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[NH:15][C:14](=O)[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:17][CH3:18])[CH:12]=2)[N:7]=1)=[O:5])[CH3:2].O=P(Cl)(Cl)[Cl:21]>>[CH2:1]([O:3][C:4]([C:6]1[N:15]=[C:14]([Cl:21])[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:17][CH3:18])[CH:12]=2)[N:7]=1)=[O:5])[CH3:2]
Reactant: O=P(Cl)(Cl)Cl
Reactant: CCOC(=O)c1nc2ccc(OC)cc2c(=O)[nH]1
Product: CCOC(=O)c1nc(Cl)c2cc(OC)ccc2n1
Temperature: 100 °C

Procedure:
To 6-methoxy-4-oxo-3,4-dihydro-quinazoline-2-carboxylic acid ethyl ester (1.38 g, 5.438 mmol) was added POCl3 (25 mL) and the solution was heated at 100° C. for 1.5 h. The solution was concentrated under reduced pressure and the residue was dissolved in EtOAc and washed with water, brine, dried (Na2SO4) and concentrated under reduced pressure to give 1.22 g of 4-chloro-6-methoxy-quinazoline-2-carboxylic acid ethyl ester.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:17]2[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=2)=[CH:9][CH2:10][CH2:11][CH2:12][C:13]([O:15]C)=[O:14])=[CH:4][CH:3]=1.[Cl:23][C:24]1[CH:32]=[CH:31][C:27]([C:28](Cl)=[O:29])=[CH:26][CH:25]=1>C(N(CC)CC)C>[Cl:23][C:24]1[CH:32]=[CH:31][C:27]([C:28]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]([C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)=[CH:9][CH2:10][CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[CH:4][CH:3]=2)=[O:29])=[CH:26][CH:25]=1
Reactant: O=C(Cl)c1ccc(Cl)cc1
Reactant: COC(=O)CCCC=C(c1ccc(N)cc1)c1cccnc1
Solvent: CCN(CC)CC
Product: O=C(O)CCCC=C(c1ccc(NC(=O)c2ccc(Cl)cc2)cc1)c1cccnc1
Temperature: 50 °C

Procedure:
At 5°-10° C., 5 ml of triethylamine are added dropwise to a mixture of 3 g of methyl 6-(4-aminophenyl)-6-(3-pyridyl)-hex-5-enoate and 2.1 g of 4-chlorobenzoic acid chloride. After 30 minutes the reaction mixture is washed with water and evaporated down. The residue is mixed with 30 ml of ethanol and 5 ml of 10N sodium hydroxide solution and heated to 50° C. for 30 minutes. The reaction mixture is evaporated down and the residue is taken up in water. The agueous phase is washed with ethyl acetate, neutralised by the addition of citric acid and then extracted with ethyl acetate. The organic phase is washed with water, dried and evaporated down and the residue is recrystallised from ethyl acetate/diisopropylether.
Reaction SMILES: [C:1]([O:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([OH:15])=[CH:7][C:6]=1[O:16][CH3:17])(=[O:3])[CH3:2].CI.[CH2:20]1CCN2C(=NCCC2)CC1>O1CCCC1>[C:1]([O:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([O:15][CH3:20])=[CH:7][C:6]=1[O:16][CH3:17])(=[O:3])[CH3:2]
Reactant: C1CCC2=NCCCN2CC1
Reactant: COc1cc(O)c2ccccc2c1OC(C)=O
Solvent: CI
Solvent: C1CCOC1
Product: COc1cc(OC)c2ccccc2c1OC(C)=O

Procedure:
A solution of 1-acetyloxy-2-methoxy-4-hydroxynaphthalene (23.2 g) and methyl iodide (6.4 mL) in tetrahydrofuran (250 mL) was treated dropwise with a solution of DBU (16.5 mL) in tetrahydrofuran (50 mL). The resulting precipitate of DBU.HI was removed by filtration, and the filtrate evaporated. Recrystallization from methanol gave 1-acetyloxy-2,4-dimethoxynaphthalene, m.p. 116°-117° C.
Reaction SMILES: [CH3:1][NH2:2].[F:3][C:4]([F:32])([C:22]([F:31])([F:30])[C:23]([F:29])([F:28])[C:24]([F:27])([F:26])[F:25])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]C1C=C(C)C=CC=1S([O-])(=O)=O>O1CCCC1>[CH3:1][NH:2][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][C:4]([F:32])([F:3])[C:22]([F:31])([F:30])[C:23]([F:29])([F:28])[C:24]([F:27])([F:26])[F:25]
Reactant: Cc1ccc(S(=O)(=O)[O-])c(CCCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)F)c1
Reactant: CN
Solvent: C1CCOC1
Product: CNCCCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Temperature: 25 °C
Reaction time: 8 h
Yield: 96 %

Procedure:
4.12 g of methylamine is condensed in a solution of 3.89 g of 7,7,8,8,9,9,10,10,10-nonafluoro-decyltosylate in 10 ml of absolute tetrahydrofuran at −20° C., and it is stirred overnight in a pressure vessel at room temperature. After the pressure vessel was opened at −20° C., it is allowed to come to room temperature to allow excess methylamine to evaporate off. The reaction solution is taken up in dichloromethane, washed with water, dried on magnesium sulfate and concentrated by evaporation in a vacuum. 2.63 g of methyl-(7,7,8,8,9,9,10,10,10-nonafluoro-decyl)-amine is obtained as a crude product.
Reaction SMILES: [N:1]([N:3]1[CH:12]2[CH:7]([N:8]([N+:16]([O-:18])=[O:17])[CH2:9][CH2:10][N:11]2[N+:13]([O-:15])=[O:14])[N:6]([N+:19]([O-:21])=[O:20])[CH2:5][CH2:4]1)=[O:2].[N+]([O-])(O)=[O:23]>>[N+:16]([N:8]1[CH:7]2[CH:12]([N:3]([N+:1]([O-:23])=[O:2])[CH2:4][CH2:5][N:6]2[N+:19]([O-:21])=[O:20])[N:11]([N+:13]([O-:15])=[O:14])[CH2:10][CH2:9]1)([O-:18])=[O:17]
Reactant: O=[N+]([O-])O
Reactant: O=NN1CCN([N+](=O)[O-])C2C1N([N+](=O)[O-])CCN2[N+](=O)[O-]
Product: O=[N+]([O-])N1CCN([N+](=O)[O-])C2C1N([N+](=O)[O-])CCN2[N+](=O)[O-]
Temperature: 0 °C

Procedure:
A portion of 8-nitroso-1,4,5-trinitro-1,4,5,8-tetraazadecalin (1.0 g, 3.3 mmoles) was slowly added to 10 ml of well-stirred 100% nitric acid maintained at 0° C. over a 15-minute time period. The solution developed a light-yellow color. It was stirred for 5 additional minutes at 0° C., then the coupling bath was removed. The stirring was continued for 5 more minutes. The reaction mixture was quenched by pouring onto 20 g of ice. A white precipitate formed and was collected by vacuum filtration. It was washed well with water and dried. It weighed 0.72 g (2.2 mmoles, 68%) and decomposed at 236° C., but darkened above 200° C. It could be recrystallized to fine crystals by dissolving in hot cyclohexanone (1 g/10 ml) and adding an equal volume of ethanol. ##STR5##
Reaction SMILES: Cl.[NH2:2][OH:3].[Na].N[OH:6].[C:7](#[N:16])[C:8]1[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[CH:10][CH:9]=1>C(O)C>[C:7](=[N:2][OH:3])([NH2:16])[C:8]1[CH:15]=[CH:14][C:11]([C:12]([NH2:13])=[O:6])=[CH:10][CH:9]=1
Reactant: NO
Reactant: N#Cc1ccc(C#N)cc1
Agent: Cl
Agent: [Na]
Solvent: CCO
Product: NC(=O)c1ccc(C(N)=NO)cc1

Procedure:
A solution of 7 g hydroxylamine hydrochloride (0.10 mol) was dissolved in 15 ml of ethanol and cooled to 0°-5° C. To the mixture was added 2.3 g sodium (0.10 mol) dissolved in 30 ml ethanol. After generating the free hydroxylamine, 3.05 g of terephthalonitrile (23.8 mmol) suspended in 40 ml of ethanol was added dropwise to the ethanol solution. The mixture was then refluxed for 20 hours. The volume of solution was reduced to 5 ml, and upon cooling a precipitate formed which was filtered. The yield was 2.21 g (48%), m.p. 224-225° C (decomp.). The infrared spectrum (KBr pellet) showed formation of peaks at 2.91 μ and 2.98 μ (NH2), 306 μ (OH), and 6.07 and 6.26 μ (C=N).
Reaction SMILES: [CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:15])=[C:11](F)[CH:12]=3)[C:7](=[O:16])[C:6]([C:17]([OH:19])=[O:18])=[CH:5]2)[CH2:3][CH2:2]1.[Cl:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[CH2:26][NH:25][CH2:24]2.C1CCN2C(=NCCC2)CC1>CN(C=O)C>[Cl:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[CH2:26][N:25]([C:11]1[CH:12]=[C:13]3[C:8]([C:7](=[O:16])[C:6]([C:17]([OH:19])=[O:18])=[CH:5][N:4]3[CH:1]3[CH2:3][CH2:2]3)=[CH:9][C:10]=1[F:15])[CH2:24]2
Reactant: O=C(O)c1cn(C2CC2)c2cc(F)c(F)cc2c1=O
Reactant: Clc1ccc2c(c1)CNC2
Solvent: C1CCC2=NCCCN2CC1
Solvent: CN(C)C=O
Product: O=C(O)c1cn(C2CC2)c2cc(N3Cc4ccc(Cl)cc4C3)c(F)cc2c1=O
Temperature: 110 °C
Yield: 62.6 %

Procedure:
A mixture of 136 mg of 1-cyclopropyl-6,7-difluoro-1,4- dihydro-4-oxoquinoline-3-carboxylic acid, 123 mg of 5-chloroisoindoline, 122 mg of DBU, and 1.5 ml of anhydrous DMF was heated at 110° C. for 1.5 hours while stirring. The resulting reaction mixture was evaporated under reduced pressure to dryness. 20 ml of chloroform and 10 ml of 5% acetic acid were added to the residue thus obtained, and the mixture was stirred. The deposited crystals were collected by filtration and washed with water and then ethanol. The chloroform layer was separated, and washed with water, dried over anhydrous sodium sulfate, and condensed. The residue was crystallized by the addition of hot ethanol. After cooling the mixture, the crystals were collected by filtration. These crystals, combined with the crystals obtained above, were recrystallized from a mixed solvent of chloroform, methanol, and ethanol to obtain 128 mg of the target compound.