Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][NH:2][C:3]([N:5]1[CH2:9][CH2:8][S:7][CH:6]1[C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1)=[S:4].[Cl:17][CH2:18][CH2:19]OS(C1C=CC(C)=CC=1)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:1][NH:2][C:3]([N:5]1[CH2:9][CH2:8][S:7][CH:6]1[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:19][CH2:18][Cl:17])=[CH:12][CH:11]=1)=[S:4]
Reactant: CNC(=S)N1CCSC1c1ccc(O)cc1
Reactant: Cc1ccc(S(=O)(=O)OCCCl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CNC(=S)N1CCSC1c1ccc(OCCCl)cc1
Temperature: 25 °C
Reaction time: 48 h
Yield: 49.4 %

Procedure:
A mixture of 5 g of N-methyl-2-(4-hydroxyphenyl)thiazolidine-3-carbothioamide, 4.6 g of 1-chloro-2-tosyloxyethane, 4 g of potassium carbonate and 20 ml of dimethylformamide is stirred at room temperature for 2 days and further stirred at 50° C. for 20 hours. The mixture is concentrated under reduced pressure to remove solvent. Water is added to the residue, and the aqueous mixture is extracted with ethyl acetate. The extract is washed with an aqueous 10% sodium hydroxide solution and water, and dried and then concentrated under reduced pressure to remove solvent. The residue is purified by silica gel chromatography (solvent, ethyl acetate:chloroform=2:8), and the resultant product is recrystallized from ethanol. 3.07 g of N-methyl-2-[4-(2-chloroethyloxy)phenyl]thiazolidine-3-carbothioamide are obtained. Yield: 51.9%.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([N:23]([CH3:25])[CH3:24])([CH2:21][CH3:22])[C:12]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)=[O:13])=[CH:6][CH:5]=1)([O-])=O.[H][H]>[Pd].C(O)C>[NH2:1][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([N:23]([CH3:25])[CH3:24])([CH2:21][CH3:22])[C:12]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)=[O:13])=[CH:6][CH:5]=1
Reactant: CCC(Cc1ccc([N+](=O)[O-])cc1)(C(=O)c1ccc(F)cc1)N(C)C
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CCC(Cc1ccc(N)cc1)(C(=O)c1ccc(F)cc1)N(C)C

Procedure:
7.0 g Palladium on charcoal (5%) are added to solution of 69.5 g (0.178 mol) 2-[(4-nitro-phenyl)methyl]-1-(4-fluorophenyl)-2-dimethylamino-1-butanone in 700 ml ethanol in an hydrogenation autoclave. Hydrogen is entered with a continuous increase of pressure to 5 bar at temperature between room temperature and 40° C. After 25 hours no further hydrogen uptake is observed. The catalyst is filtered off and the crude product obtained as yellowish oil after evaporation of the solvent. Thin film chromatography shows a main product and some minor by-products. The crude material is used without further purification in the next reaction step.
Reaction SMILES: [CH2:1]([N:3]([S:9]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[C:14]([F:19])[CH:13]=1)(=[O:11])=[O:10])[C:4](=[CH2:8])[C:5]([OH:7])=O)[CH3:2].CCOC(OC(OCC)=O)=O.[F:31][C:32]([F:48])([F:47])[C:33]1[CH:38]=[CH:37][C:36]([C:39]2[CH:44]=[C:43]([CH2:45][NH2:46])[CH:42]=[CH:41][N:40]=2)=[CH:35][CH:34]=1>C1COCC1>[CH2:1]([N:3]([S:9]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[C:14]([F:19])[CH:13]=1)(=[O:11])=[O:10])[C:4](=[CH2:8])[C:5]([NH:46][CH2:45][C:43]1[CH:42]=[CH:41][N:40]=[C:39]([C:36]2[CH:37]=[CH:38][C:33]([C:32]([F:48])([F:31])[F:47])=[CH:34][CH:35]=2)[CH:44]=1)=[O:7])[CH3:2]
Reactant: C=C(C(=O)O)N(CC)S(=O)(=O)c1ccc(F)c(F)c1
Reactant: NCc1ccnc(-c2ccc(C(F)(F)F)cc2)c1
Agent: CCOC(=O)OC(=O)OCC
Solvent: C1CCOC1
Product: C=C(C(=O)NCc1ccnc(-c2ccc(C(F)(F)F)cc2)c1)N(CC)S(=O)(=O)c1ccc(F)c(F)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 13.4 %

Procedure:
Acid 4G (500 mg, 1.7 mmol) was dissolved in 20 ml of THF and at rt DEPC (1.3 equiv, 0.34 ml) and [2-[4-(trifluoromethyl)phenyl]-4-pyridyl]methanamine 21A (1.1 equiv., 476 mg) were added to the solution. The mixture was stirred at rt overnight then evaporated. The residue was dissolved in AcOEt (30 mL) and washed with water (1×20 mL) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude by chromatographic column (EtOAc 1/petroleum ether 1) afforded 120 mg of a white solid. Yield=24% 1HNMR (DMSO, 200 MHz) δ 1.09 (3H, t, J=7.2 Hz), 3.45 (2H, q, J=6.8 Hz), 4.51 (2H, d, J=6 Hz), 5.31 (1H, s), 6.17 (1H, s), 7.38 (1H, dd, J=4.8 Hz, J′=1.2 Hz), 7.68 (2H, t, J=8.8 Hz), 7.83 (d, 3H), 8.02 (s, 1H), 8.32 (d, 2H, J=7.8), 8.67 (d, 1H, J=5.8), 8.93 (t, 1H). [M+1] 525.11 (C24H20F5N3O3S requires 524.98).
Reaction SMILES: O=[C:2]1[CH2:6][CH2:5][CH:4]([N:7]2[C:15](=[O:16])[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:8]2=[O:17])[CH2:3]1.Cl.[C:19]([C:21]1[CH:26]=[CH:25][C:24]([NH:27]N)=[CH:23][CH:22]=1)#[N:20]>CC(O)=O.O1CCOCC1.Cl.O>[O:17]=[C:8]1[C:9]2[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:15](=[O:16])[N:7]1[CH:4]1[CH2:5][C:6]2[NH:27][C:24]3[CH:23]=[CH:22][C:21]([C:19]#[N:20])=[CH:26][C:25]=3[C:2]=2[CH2:3]1
Reactant: N#Cc1ccc(NN)cc1
Reactant: O=C1CCC(N2C(=O)c3ccccc3C2=O)C1
Agent: Cl
Solvent: O
Solvent: C1COCCO1
Solvent: CC(=O)O
Product: N#Cc1ccc2[nH]c3c(c2c1)CC(N1C(=O)c2ccccc2C1=O)C3
Yield: 66.4 %

Procedure:
Mix (±)-2-(3-oxo-cyclopentyl)-isoindole-1,3-dione (12.7 g, 55.3 mmol) and 4-cyanophenylhydrazine-HCl (8.53 g, 50.3 mmol) in HOAc (200 mL) and 4N HCl dioxane (50 mL). Using mechanical stirring, heat the reaction to 90° C. for 18 h, then add additional 4N HCl dioxane (20 mL). Heat the reaction to 100° C. for 18 h. Dilute the reaction mixture with water (600 mL) and collect a black solid by vacuum filtration. Sonicate the solid with MeOH (200 mL), then collect and dry in a vacuum oven to give 10.94 g (66%) of a gray-brown solid. MS (m/z): 328 (M+1), 326 (M−1).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[NH:15][C:16](=[O:23])[C:17]3[NH:18][CH:19]=[N:20][C:21]=3[N:22]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33]>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[NH:15][C:16](=[O:23])[C:17]3[N:18]([CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:19]=[N:20][C:21]=3[N:22]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)CCl
Reactant: CC(C)(C)OC(=O)N1CCN(c2nc3nc[nH]c3c(=O)[nH]2)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)Cn1cnc2nc(N3CCN(C(=O)OC(C)(C)C)CC3)[nH]c(=O)c21
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of 4-(6-oxo-6,7-dihydro-1H-purin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester, 3 (1 g), potassium carbonate and dimethylforamide was stirred at room temperature for 2 h, then the solution of ClCH2COOEt (0.38 g/5 mL dimethylforamide) was added drop-wise into the reaction mixture, After stirring for 15 h, the solution was then partitioned between ethyl acetate and water. The ethyl acetate solution was washed with water, then it was dried over sodium sulfate and filtered, evaporated under reduced pressure, and purification of the residue by use of column chromatography to give 4.
Reaction SMILES: [CH3:1][C:2]1[N:11]([C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)[C:10](=[O:19])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][CH:30](O)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>O1CCCC1>[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][CH:30]([O:18][C:15]2[CH:16]=[CH:17][C:12]([N:11]3[C:10](=[O:19])[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[N:3]=[C:2]3[CH3:1])=[CH:13][CH:14]=2)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:21])[CH3:22]
Reactant: CC(C)(C)OC(=O)N1CCC(O)CC1
Reactant: Cc1nc2ccccc2c(=O)n1-c1ccc(O)cc1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Cc1nc2ccccc2c(=O)n1-c1ccc(OC2CCN(C(=O)OC(C)(C)C)CC2)cc1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
2-methyl-3-(4-hydroxyphenyl)-4(3H)quinazolinone synthesized according to Example 1-(1) and -(2) (1.0 g, 3.96 mmol), N-(t-butoxycarbonyl)-4-piperidinol (956 mg, 4.75 mmol) and triphenylphosphine (1.56 g, 5.94 mmol) were dissolved in dry tetrahydrofuran (2 mL) in a current of nitrogen, and cooled on an ice bath. Diethylazodicarboxylate (1.17 mL, 5.94 mmol) was dripped in at 0° C., and stirred at room temperature for 48 hours. The solvent was distilled off under reduced pressure, ether was added, the solid precipitate was filtered off, and the filtrate was concentrated. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=7/3), and the target substance (1.1 g, 64%) was obtained as a light brown solid.
Reaction SMILES: [CH3:1][C:2]1([C:7]2[O:11][C:10]([CH2:12][N:13]3[CH:17]=[C:16]([NH2:18])[CH:15]=[N:14]3)=[CH:9][CH:8]=2)[O:6]CCO1.[CH3:19][O:20][CH2:21][C:22]1[O:23][C:24]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[C:25]([C:27](O)=[O:28])[N:26]=1>>[C:2]([C:7]1[O:11][C:10]([CH2:12][N:13]2[CH:17]=[C:16]([NH:18][C:27]([C:25]3[N:26]=[C:22]([CH2:21][O:20][CH3:19])[O:23][C:24]=3[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[O:28])[CH:15]=[N:14]2)=[CH:9][CH:8]=1)(=[O:6])[CH3:1]
Reactant: COCc1nc(C(=O)O)c(-c2ccccc2)o1
Reactant: CC1(c2ccc(Cn3cc(N)cn3)o2)OCCO1
Product: COCc1nc(C(=O)Nc2cnn(Cc3ccc(C(C)=O)o3)c2)c(-c2ccccc2)o1

Procedure:
Following general procedure B followed by C, starting from 1-[5-(2-methyl-[1,3]dioxolan-2-yl)-furan-2-ylmethyl]-1H-pyrazol-4-ylamine and 2-methoxymethyl-5-phenyl-oxazole-4-carboxylic acid. LC-MS-conditions 02: tR=0.96 min; [M+H]+=421.6.
Reaction SMILES: [BH4-].[Na+].[CH3:3][S:4][CH2:5][C@@:6]12[C@@H:23]3[C@H:14]([C@H:15]4[C@@:19]([CH2:21][CH2:22]3)([CH3:20])[C:18](=[O:24])[CH2:17][CH2:16]4)[CH2:13][CH2:12][C:11]1=[CH:10][C:9](=[O:25])[CH2:8][CH2:7]2.CC(C)=O.C([O-])(O)=O.[Na+]>C1COCC1.CO.C(O)(=O)C>[CH3:3][S:4][CH2:5][C@@:6]12[C@@H:23]3[C@H:14]([C@H:15]4[C@@:19]([CH2:21][CH2:22]3)([CH3:20])[C@@H:18]([OH:24])[CH2:17][CH2:16]4)[CH2:13][CH2:12][C:11]1=[CH:10][C@H:9]([OH:25])[CH2:8][CH2:7]2
Reactant: CSC[C@]12CCC(=O)C=C1CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Agent: O=C([O-])O
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Solvent: CC(C)=O
Product: CSC[C@]12CC[C@@H](O)C=C1CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](O)CC[C@@H]12
Reaction time: 0.5 h
Yield: 79 %

Procedure:
0.6 g of NaBH4 was added to a solution of 6 g of 19-methylthioandrost-4-ene-3,17-dione in a mixture of 25 ml of THF and 25 ml of methanol. After 1/2 hour, 2 ml of acetone, followed by 5 ml of 50% acetic acid were added. After stirring for 1/2 hour, the mixture was poured out into 200 ml of 5% NaHCO3 solution. Subsequently, the product was extracted with CH2Cl2. After washing, drying and evaporating down the organic layer, the residue obtained was chromatographed using silica gel. In this manner, 4.8 g of 19-methylthioandrost-4-ene-3α,17β-diol were obtained, melting point 85°-87° C., (Rf =0.23 (toluene/ethyl acetate 7:3).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([C:8]2[C:13]([CH3:14])=[CH:12][C:11]([CH2:15][C:16]([OH:18])=O)=[CH:10][N:9]=2)[CH:5]=[CH:4][N:3]=1.[N:19]1[CH:24]=[CH:23][N:22]=[CH:21][C:20]=1[C:25]1[CH:26]=[CH:27][C:28]([NH2:31])=[N:29][CH:30]=1.C(N=C=NC(C)C)(C)C>C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([C:8]2[C:13]([CH3:14])=[CH:12][C:11]([CH2:15][C:16]([NH:31][C:28]3[CH:27]=[CH:26][C:25]([C:20]4[CH:21]=[N:22][CH:23]=[CH:24][N:19]=4)=[CH:30][N:29]=3)=[O:18])=[CH:10][N:9]=2)[CH:5]=[CH:4][N:3]=1
Reactant: Cc1cc(CC(=O)O)cnc1-c1ccnc(F)c1
Reactant: Nc1ccc(-c2cnccn2)cn1
Agent: CC(C)N=C=NC(C)C
Solvent: ClCCl
Product: Cc1cc(CC(=O)Nc2ccc(-c3cnccn3)cn2)cnc1-c1ccnc(F)c1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To the mixture of 2-(2′-fluoro-3-methyl-2,4′-bipyridin-5-yl)acetic acid 193-2 (50 mg, 0.2 mmol) and 5-(pyrazin-2-yl)pyridin-2-amine 86-3 (36 mg, 0.2 mmol) in DCM (1 mL) was added N,N′-Diisopropylcarbodiimide (46 μL, 0.3 mmol) at room temperature. The mixture was stirred at room temperature for 24 hours. The solvent was removed by rotary evaporation and the residue was dissolved in DMSO and then purified by reverse-phase HPLC to give 2-(2′-fluoro-3-methyl-2,4′-bipyridin-5-yl)-N-(5-(pyrazin-2-yl)pyridin-2-yl)acetamide 199 as white solid. MS m/z 401.2 (M+1); 1H NMR 400 MHz (DMSO-d6) δ11.07 (s, 1H), 9.25 (d, 1H, J=1.6 Hz), 9.05 (m, 1H), 8.66 (m, 1H), 8.57 (d, 1H, J=2.4 Hz), 8.47-8.45 (m, 2H), 8.28 (d, 1H, J=5.2 Hz), 8.16 (d, 1H, J=8.8 Hz), 7.71 (d, 1H, J=1.6 Hz), 7.51-7.49 (m, 1H), 7.31 (s, 1H), 3.82 (s, 2H), 2.31 (s, 3H).
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([NH2:24])[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:27])[F:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:29]([O:31][C:32]1[C:33]([OH:40])=[C:34]([CH:37]=[CH:38][CH:39]=1)[CH:35]=O)[CH3:30]>>[CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([NH:24][CH2:35][C:34]3[CH:37]=[CH:38][CH:39]=[C:32]([O:31][CH2:29][CH3:30])[C:33]=3[OH:40])[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:26])[F:27])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOc1cccc(C=O)c1O
Reactant: Nc1cccc(-c2c(Cc3ccccc3)cnc3c(C(F)(F)F)cccc23)c1
Product: CCOc1cccc(CNc2cccc(-c3c(Cc4ccccc4)cnc4c(C(F)(F)F)cccc34)c2)c1O

Procedure:
The title compound was prepared from {3-[3-benzyl-8-(trifluoromethyl)quinolin-4-yl]phenyl}amine and 3-ethoxy-2-hydroxybenzaldehyde according to the procedure of step 1, Example 66. MS (ESI) m/z 529; MS (ESI) m/z 527.
Reaction SMILES: [ClH:1].Cl.[CH3:3][NH:4][CH2:5][C:6]1[N:7]=[C:8]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:9]([CH2:11][S:12][C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)[CH:10]=1.OOS([O-])=O.[K+].[OH2:32].[OH2:33].O.O.O.S([O-])([O-])(=O)=S.[Na+].[Na+].C(=O)([O-])O.[Na+]>O.CC(C)=O>[ClH:1].[ClH:1].[CH3:3][NH:4][CH2:5][C:6]1[N:7]=[C:8]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:9]([CH2:11][S:12]([C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)(=[O:33])=[O:32])[CH:10]=1
Reactant: O
Reactant: CNCc1cn(CSc2ccc(C)cc2)c(-c2ccccc2)n1
Agent: Cl
Agent: O=C([O-])O
Agent: O=S([O-])([O-])=S
Solvent: CC(C)=O
Product: CNCc1cn(CS(=O)(=O)c2ccc(C)cc2)c(-c2ccccc2)n1
Temperature: 25 °C
Reaction time: 3 h
Yield: 40.7 %

Procedure:
To a solution of N-methyl-1-(1-{[(4-methylphenyl)thio]methyl}-2-phenyl-1H-imidazol-4-yl)methanamine dihydrochloride (250 mg) in water (10 mL) and acetone (10 mL) was added dropwise a solution of oxone (700 mg) in water (20 mL), and the mixture was stirred at room temperature for 3 hr. Sodium thiosulfate pentahydrate (783 mg) was added to the reaction mixture and the mixture was stirred for 24 hr. A saturated aqueous sodium hydrogen carbonate solution was added, and the mixture was extracted with a mixed solution of ethyl acetate-tetrahydrofuran (1:1). The extract was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent:ethyl acetate-methanol=1:0→7:3) and dissolved in methanol (5 mL). A 4 mol/L hydrogen chloride-ethyl acetate solution (1 mL) was added, and the mixture was concentrated under reduced pressure. The residue was crystallized from tetrahydrofuran to give the title compound as colorless crystals (yield 55 mg, yield 20%).
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([C:12]1[C:17]([CH3:18])=[CH:16][C:15]([F:19])=[CH:14][N:13]=1)=[N:7]2.[NH2:20][C:21]1[N:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][N:22]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:19][C:15]1[CH:16]=[C:17]([CH3:18])[C:12]([C:6]2[N:7]=[C:8]3[C:3]([C:2]([NH:20][C:21]4[N:22]=[CH:23][C:24]([C:27]([F:30])([F:28])[F:29])=[CH:25][N:26]=4)=[CH:11][CH:10]=[N:9]3)=[CH:4][CH:5]=2)=[N:13][CH:14]=1
Reactant: Nc1ncc(C(F)(F)F)cn1
Reactant: Cc1cc(F)cnc1-c1ccc2c(Cl)ccnc2n1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: Cc1cc(F)cnc1-c1ccc2c(Nc3ncc(C(F)(F)F)cn3)ccnc2n1

Procedure:
Heat a mixture of 5-chloro-2-(5-fluoro-3-methylpyridin-2-yl)-1,8-naphthyridine (81 mg, 0.3 mmol), 2-amino-5-trifluoromethylpyrimidine (96 mg, 0.6 mmol), xantphos (16.9 mg), Pd2(dba)3 (27.9 mg) and Cs2CO3 (193 mg) in dioxane (2.0 mL) at 100° C. for 4 hours. Cool the mixture, concentrate under vacuum, dilute with EtOAc/water (5.0 mL each), filter through celite, wash celite with EtOAc (2×5 mL) and dry combined organic layers with MgSO4. Filter the dried extract and concentrate under vacuum to afford crude product. Purify by preparative HPLC to afford title compound as a yellow solid. 1H NMR (400 MHZ, DMSO-D6) δ 10.92 (s, 1H), 9.0 (s, 2H), 8.92 (d, 1H, J=2.2 Hz), 8.58 (s, 1H), 8.17(d, 1H, J=1.1 Hz), 8.09 (m, 1H), 7.8 (d, 1H, J=2.4 Hz), 2.69 (s, 3H). MS=401.31 (M+H). The IC50 determined as described in Example 6 is less than 1 micromolar.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:13])[CH2:9][C:10](=[O:12])[CH3:11].CO[CH:16](OC)[N:17]([CH3:19])[CH3:18]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:13])[C:9](=[CH:16][N:17]([CH3:19])[CH3:18])[C:10](=[O:12])[CH3:11]
Reactant: COC(OC)N(C)C
Reactant: CC(=O)CC(=O)c1ccccc1Cl
Solvent: Cc1ccccc1
Product: CC(=O)C(=CN(C)C)C(=O)c1ccccc1Cl
Yield: 51 %

Procedure:
A mixture of crude 1-(2-chlorophenyl)butane-1,3-dione from the previous step and 1,1-dimethoxy-N,N-dimethylmethanamine (2.042 g, 17.14 mmol) in toluene (20 mL) was heated to reflux for 2 h and concentrated. Silica gel chromatography, using 70 to 100% ethyl acetate in hexanes gradient, gave 1-(2-chlorophenyl)-2-((dimethylamino)methylene)butane-1,3-dione as a red, viscous oil (2.20 g, 51% yield for 2 steps). MS (ES+) m/z: 252 (M+H); HPLC retention time: 2.51 min (Analytical HPLC Method D).
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([O:14][C@@H:15]([CH3:20])[C:16]([F:19])([F:18])[F:17])=[C:9]([CH:13]=1)[C:10]([OH:12])=O)(=[O:4])=[O:3].[N:21]1[CH2:24][CH:23]([OH:25])[CH:22]=1>>[OH:25][CH:23]1[CH2:24][N:21]([C:10]([C:9]2[CH:13]=[C:5]([S:2]([CH3:1])(=[O:3])=[O:4])[CH:6]=[CH:7][C:8]=2[O:14][C@@H:15]([CH3:20])[C:16]([F:19])([F:18])[F:17])=[O:12])[CH2:22]1
Reactant: C[C@H](Oc1ccc(S(C)(=O)=O)cc1C(=O)O)C(F)(F)F
Reactant: OC1C=NC1
Product: C[C@H](Oc1ccc(S(C)(=O)=O)cc1C(=O)N1CC(O)C1)C(F)(F)F
Yield: 43 %

Procedure:
Prepared in analogy to Example 1 from 5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-benzoic acid (Example A2(c)) and azetin-3-ol. The crude material was purified by flash chromatography (ethyl acetate/n-heptane) to yield the title compound as a white crystalline solid (yield 43%). MS (m/e): 367.9 (M+H+, 100%).
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH3:12][O:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[C:19](=[CH:23][C:24]1[CH:29]=[CH:28][C:27]([S:30]([CH3:32])=[O:31])=[CH:26][CH:25]=1)[C:18]([CH3:33])=[C:17]2[CH2:34][C:35]([OH:37])=[O:36]>CC(C)=O>[CH3:12][O:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[C:19](=[CH:23][C:24]1[CH:29]=[CH:28][C:27]([S:30]([CH3:32])(=[O:9])=[O:31])=[CH:26][CH:25]=1)[C:18]([CH3:33])=[C:17]2[CH2:34][C:35]([OH:37])=[O:36]
Reactant: COc1ccc2c(c1)C(CC(=O)O)=C(C)C2=Cc1ccc(S(C)=O)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: CC(C)=O
Product: COc1ccc2c(c1)C(CC(=O)O)=C(C)C2=Cc1ccc(S(C)(=O)=O)cc1

Procedure:
5-methoxy-2-methyl-1-(p-methylsulfonylbenzylidene)-3-indenylacetic acid is prepared by the addition of 1.0 mol of m-chloroperbenzoic acid per mol of 5-methoxy-2-methyl-1-(p-methylsulfinylbenzylidene)-3-indenylacetic acid in an acetone solution.
Reaction SMILES: [N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@H:3]([C:9]([OH:11])=O)[CH2:2]2.S(Cl)(Cl)=O.[Br:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[CH:19][CH:18]=1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[Br:16][C:17]1[CH:23]=[CH:22][C:20]([NH:21][C:9]([C@H:3]2[CH:4]3[CH2:5][CH2:6][N:1]([CH2:8][CH2:7]3)[CH2:2]2)=[O:11])=[CH:19][CH:18]=1
Reactant: O=C(O)[C@@H]1CN2CCC1CC2
Reactant: Nc1ccc(Br)cc1
Solvent: O=S(Cl)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(Nc1ccc(Br)cc1)[C@@H]1CN2CCC1CC2

Procedure:
6.6 g (about 34.4 mmol) of (S)-1-azabicyclo[2.2.2]octane-3-carboxylic acid are heated together with 106 ml of thionyl chloride under reflux for 1 h. The excess thionyl chloride is removed under reduced pressure, and residues are removed by azeotropic distillation together with toluene. The crude acid chloride obtained in this way is stirred together with 5.73 g (33.32 mmol) of 4-bromoaniline and 23.21 ml (133.27 mmol) of N,N-diisopropylethylamine in 30 ml of DMF at RT for 72 h. The solvent is removed under reduced pressure. The crude product is purified by chromatography on silica gel 60 (mobile phase: dichloromethane→dichloromethane/methanol/triethylamine 70:30:2). The solvent is removed under reduced pressure. Finally, the last residues of solvent are removed under high vacuum. 2.9 g (28% of theory) of the title compound are isolated in a purity of 76%.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([O:13][CH3:14])[CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[C:7]2[CH3:12].Br[CH:16]([N:22]1[C:26](=[O:27])[C:25]2=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]2[C:23]1=[O:32])[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].C(NC(C)C)(C)C>C(O)C.C(OCCO)C.CCOCC>[CH3:14][O:13][C:4]1[CH:5]=[C:6]2[C:11](=[C:2]([NH:1][CH:20]([CH3:21])[CH2:19][CH2:18][CH2:17][CH2:16][N:22]3[C:23](=[O:32])[C:24]4=[CH:31][CH:30]=[CH:29][CH:28]=[C:25]4[C:26]3=[O:27])[CH:3]=1)[N:10]=[CH:9][CH:8]=[C:7]2[CH3:12]
Reactant: COc1cc(N)c2nccc(C)c2c1
Reactant: CCCCCC(Br)N1C(=O)c2ccccc2C1=O
Solvent: CC(C)NC(C)C
Solvent: CCO
Solvent: CCOCC
Product: COc1cc(NC(C)CCCCN2C(=O)c3ccccc3C2=O)c2nccc(C)c2c1
Yield: 41.5 %

Procedure:
8-Amino-6-methoxy-4-methylquinoline (5.5 g, 0.03 mole), the above bromophthalimidohexane (8.2 g, 0.26 mole) and diisopropylamine (2.55 g) were dissolved in a mixture ethanol (4.3 ml) and 2-ethoxyethanol (4.3 ml). This solution was heated in a sealed tube at 150° for 3.5 hr. After cooling, the reaction mixture was diluted with ether (400 ml). Diisopropylamine hydrobromide was removed by filtration and the filtrate was concentrated to dryness. The residue crystallized upon trituration with EtOH (50 ml) to give the title compound (5.2 g, 47%), contaminated with a trace amount of starting material. Additional starting 8-aminoquinoline could be recovered from the ethanol filtrate.
Reaction SMILES: [OH:1][C:2]1[CH:13]=[CH:12][C:5]([C:6]([O:8][CH2:9]CC)=[O:7])=[CH:4][CH:3]=1.C(O)C(O)C.OCC([C@H]([C@@H]([C@@H](CO)O)O)O)=O.C(O)(C)C>O>[CH3:9][O:8][C:6]([C:5]1[CH:4]=[CH:3][C:2]([OH:1])=[CH:13][CH:12]=1)=[O:7]
Reactant: CCCOC(=O)c1ccc(O)cc1
Agent: O=C(CO)[C@@H](O)[C@H](O)[C@H](O)CO
Solvent: O
Solvent: CC(O)CO
Solvent: CC(C)O
Product: COC(=O)c1ccc(O)cc1
Yield: 0.2 %

Procedure:
A method for the preparation of an insecticidal gel composition comprising, admixing at 25° C. to 95° C. on a weight basis 14% to 22% of the gellant α-hydro-Ω-hydroxy-poly(oxyethylene)poly(oxypropylene)poly(oxyethylene) block copolymer having an average molecular weight 12,500, mp 56° C., Brookfield viscosity of 3100 at 77° C., surface tension of a 0.1% aqueous solution: 40.6 dynes/cm; 0.15% to 0.5% propyl p-hydroxybenzoate; 0% to 30% propylene glycol; 0.5% to 6% of a C17 -C19 unsaturated fatty acid; a C7 -C17 saturated fatty acid or a mixture of the fatty acids; 1% to 5% of formula (I) insecticide ##STR4## 10% to 40% high fructose (55%) corn syrup; 0% to 10% isopropyl alcohol; 0.2% to 0.5% methyl p-hydroxybenzoate and 25% to 60% of water to obtain a composition having water to gellant ratios of 2.3/1 to 3.0/1 and a viscosity of 1.4×106 centipoise to 2.1×106 centipoise in a temperature range of 25° C. to 45° C.