Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:4][C:3]=1[C:17]1[N:18]=[CH:19][C:20]([NH2:23])=[N:21][CH:22]=1.Br[C:25]1[C:26]([S:31][CH:32]([CH3:34])[CH3:33])=[N:27][CH:28]=[CH:29][CH:30]=1>>[F:1][C:2]1[CH:7]=[C:6]([C:25]2[C:26]([S:31][CH:32]([CH3:34])[CH3:33])=[N:27][CH:28]=[CH:29][CH:30]=2)[CH:5]=[CH:4][C:3]=1[C:17]1[N:18]=[CH:19][C:20]([NH2:23])=[N:21][CH:22]=1
Reactant: CC1(C)OB(c2ccc(-c3cnc(N)cn3)c(F)c2)OC1(C)C
Reactant: CC(C)Sc1ncccc1Br
Product: CC(C)Sc1ncccc1-c1ccc(-c2cnc(N)cn2)c(F)c1

Procedure:
The title compound was prepared using methods analogous to those described in Example 376 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine and 3-bromo-2-(isopropylthio)pyridine. MS (ESI): mass calcd. for C18H17FN4S, 340.12; m/z found, 341.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.62-8.57 (m, 1H), 8.49-8.43 (m, 1H), 8.12 (d, J=1.5, 1H), 8.04-7.93 (m, 1H), 7.45-7.39 (m, 1H), 7.34-7.30 (m, 1H), 7.29-7.22 (m, 1H), 7.11-7.03 (m, 1H), 4.69 (s, 2H), 4.17-4.00 (m, 1H), 1.37 (d, J=6.8, 6H).
Reaction SMILES: [C:1](OC(=O)C)(=[O:3])C.C(O)=O.[CH2:11]([C:13]1[CH:26]=[CH:25][C:16]([O:17][C:18]2[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=2[NH2:20])=[C:15]([O:27][CH3:28])[CH:14]=1)[CH3:12]>C1COCC1>[CH2:11]([C:13]1[CH:26]=[CH:25][C:16]([O:17][C:18]2[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=2[NH:20][CH:1]=[O:3])=[C:15]([O:27][CH3:28])[CH:14]=1)[CH3:12]
Reactant: CC(=O)OC(C)=O
Reactant: CCc1ccc(Oc2ccccc2N)c(OC)c1
Solvent: C1CCOC1
Solvent: O=CO
Product: CCc1ccc(Oc2ccccc2NC=O)c(OC)c1
Temperature: 60 °C
Reaction time: 2 h
Yield: 126.4 %

Procedure:
To acetic anhydride (0.53 mmol; 51 μL) under argon, at 0° C., was added formic acid (0.66 mmol; 25 μL). The reaction was stirred 2 hours at 60° C. After cooling to 0° C., the mixture was diluted with 1 mL of dry THF, followed by a solution of 2-(4-ethyl-2-methoxyphenoxy)aniline (0.21 mmol; 50 mg) in dry THE (1 mL). The reaction was stirred 2 hours at room temperature. The mixture was concentrated in vacuo to give the title compound (72 mg; quantitative) as a brown oil, used without further purification.
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4].[H-].[Al+3].[Li+].[H-].[H-].[H-].O>CCOCC>[CH2:1]([O:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:10][NH2:11])=[CH:12][CH:13]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOc1ccc(C#N)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Solvent: O
Product: CCCCOc1ccc(CN)cc1
Temperature: 25 °C
Yield: 57 %

Procedure:
To a solution of 4-butoxybenzonitrile (4.6 g, 26.25 mmol) in Et2O (50 mL) was added lithium aluminum hydride (1.0 M in THF, 26.2 mL, 26.2 mmol) dropwise. The reaction was heated at reflux for 1 h and was cooled to room temperature. The reaction was carefully poured into water (50 mL) and was diluted with Et2O. The solids were removed by filtration through Celite with the aid of Et2O. The organic solution was washed with water followed by brine, dried (MgSO4), filtered, and concentrated in vacuo to provide 4-butoxybenzylamine (2.68 g). 1H NMR (400 MHz, CDCl3) δ 7.16 (m, 2H), 6.82 (m, 2H), 3.91 (m, 2H), 3.75 (s, 2H), 1.73 (m, 2H), 1.46 (m, 2H), 1.39 (m, 2H), 0.95 (t, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[N:10]([CH3:19])[C:9]2=[O:20])=[C:4]([OH:21])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:28](Br)[C:29]#[CH:30].O>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[CH:12]=[C:11]([C:15]([F:18])([F:16])[F:17])[N:10]([CH3:19])[C:9]2=[O:20])=[C:4]([O:21][CH2:30][C:29]#[CH:28])[CH:3]=1
Reactant: C#CCBr
Reactant: Cn1c(C(F)(F)F)cc(=O)n(-c2ccc(Cl)cc2O)c1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: C#CCOc1cc(Cl)ccc1-n1c(=O)cc(C(F)(F)F)n(C)c1=O
Temperature: 70 °C
Reaction time: 2 h
Yield: 89 %

Procedure:
22.6 g (70.5 mmol) of 3-(4-chloro-2-hydroxyphenyl-1-methyl-6-trifluoromethyluracil and 14.5 g (105.1 mmol) of potassium carbonate were suspended in 150 ml of N,N-dimethylformamide, and 11.2 g (94.1 mmol) of propargyl bromide was dropwise added thereto at room temperature. After stirring at 70° C. for 2 hours, the reaction solution was poured into water and extracted with ethyl acetate. The organic layer was washed sequentially with water and a saturated sodium chloride aqueous solution and then, dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. Then, the obtained crude crystals were washed with isopropyl ether to obtain 22.5 g (yield: 89.0%) of the desired product as pale brown powder. Melting point: 147-148° C.
Reaction SMILES: I([O-])(=O)(=O)=O.[Na+].[F:7][CH:8]([F:57])[C:9]([C:44]1[CH:49]=[CH:48][C:47]([C:50]2[CH:55]=[CH:54][C:53]([F:56])=[CH:52][N:51]=2)=[CH:46][CH:45]=1)([OH:43])[CH2:10][C:11]1[N:12]([C:24]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:13]=[C:14]([CH2:16][C:17]([CH3:23])([CH3:22])[CH:18]([OH:21])CO)[N:15]=1>O1CCCC1.O>[F:57][CH:8]([F:7])[C:9]([C:44]1[CH:45]=[CH:46][C:47]([C:50]2[CH:55]=[CH:54][C:53]([F:56])=[CH:52][N:51]=2)=[CH:48][CH:49]=1)([OH:43])[CH2:10][C:11]1[N:12]([C:24]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:13]=[C:14]([CH2:16][C:17]([CH3:23])([CH3:22])[CH:18]=[O:21])[N:15]=1
Reactant: CC(C)(Cc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c(CC(O)(c2ccc(-c3ccc(F)cn3)cc2)C(F)F)n1)C(O)CO
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C=O)Cc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c(CC(O)(c2ccc(-c3ccc(F)cn3)cc2)C(F)F)n1
Temperature: 25 °C

Procedure:
Sodium periodate was added to a solution of 4-(2-{3,3-difluoro-2-[4-(5-fluoropyridin-2-yl)phenyl]-2-hydroxypropyl}-1-trityl-1H-imidazol-4-yl)-3,3-dimethylbutane-1,2-diol (300 mg, 0.43 mmol) in tetrahydrofuran/water (2:1) (10 mL) at 0° C. After stirring at ambient temperature until complete (by LCMS), the reaction mixture was quenched with saturated aqueous sodium bicarbonate and extracted with methylene chloride. The combined organic extracts were dried (magnesium sulfate) and concentrated in vacuo. Chromatography over silica eluting with 0-40% ethyl acetate/hexane afforded 3-(2-{3,3-difluoro-2-[4-(5-fluoropyridin-2-yl)phenyl]-2-hydroxypropyl}-1-trityl-1H-imidazol-4-yl)-2,2-dimethylpropanal.
Reaction SMILES: C([C:8]1([CH:35]=[CH:34][C:33]([N:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)=[CH:32][CH2:31]1)[CH2:9][NH:10][NH:11][C:12](=[O:30])[CH:13]1[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[C:15]([C:23]([F:26])([F:25])[F:24])[C:14]1=[S:27](=[O:29])=[O:28])(OC(C)(C)C)=O.[ClH:42]>C(Cl)Cl.C(OCC)C>[N:36]1([C:33]2[CH:32]=[CH:31][C:8]([CH2:9][NH:10][NH:11][C:12](=[O:30])[CH:13]3[CH:18]=[C:17]([C:19]([F:21])([F:20])[F:22])[CH:16]=[C:15]([C:23]([F:24])([F:26])[F:25])[C:14]3=[S:27](=[O:29])=[O:28])=[CH:35][CH:34]=2)[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1.[ClH:42]
Reactant: CC(C)(C)OC(=O)C1(CNNC(=O)C2C=C(C(F)(F)F)C=C(C(F)(F)F)C2=S(=O)=O)C=CC(N2CCCCC2)=CC1
Agent: Cl
Solvent: ClCCl
Solvent: CCOCC
Product: O=C(NNCc1ccc(N2CCCCC2)cc1)C1C=C(C(F)(F)F)C=C(C(F)(F)F)C1=S(=O)=O
Reaction time: 12 h

Procedure:
A solution of 650 mg of N-(1-BOC-4-piperidinyl-benzylamino)-sulfonyl-3,5-bis-trifluoromethyl-benzamide in 5 ml of CH2Cl2 is treated with 60 ml of 3 N HCl (gas) in diethylether. The mixture obtained is stirred for ca. 12 hours and solvent is evaporated. N-(4-Piperidinyl-benzylamino)-sulfonyl-3,5-bis-trifluoromethyl-benzamide in the form of a hydrochloride is obtained. 1H-NMR (DMSO) δ:1.72-1.86 (m, 4H), 2.90 (m, 2H), 3.20-3.3 (m, 2H), 4.15 (m, 1H), 4.60 (s, 2H, CH2), 7.31 (t, 1H), 7.40 (t, 1H), 7.48 (d, 1H), 8.38 (s, 1H), 8.48 (s, 2H), 8.48 and 8.75 (broad, 2H, NH).
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[C:3]=1[CH2:4][NH:5][C:6]1[C:7](=O)[C:8](=[O:13])[C:9]=1[O:10]CC.ClCCl.[C:23]([NH2:27])([CH3:26])([CH3:25])[CH3:24]>>[C:23]([NH:27][C:7]1[C:8](=[O:13])[C:9](=[O:10])[C:6]=1[NH:5][CH2:4][C:3]1[C:15]([CH3:19])=[CH:16][CH:17]=[CH:18][C:2]=1[Cl:1])([CH3:26])([CH3:25])[CH3:24]
Reactant: CC(C)(C)N
Reactant: CCOc1c(NCc2c(C)cccc2Cl)c(=O)c1=O
Solvent: ClCCl
Product: Cc1cccc(Cl)c1CNc1c(NC(C)(C)C)c(=O)c1=O
Reaction time: 144 h

Procedure:
A mixture of 3,4-diethoxy-3-cyclobutene-1,2-dione (5 g, 29 mmol) and 2-chloro-6-methylbenzylamine (4.57 g, 29 mmol) in absolute ethanol (147 mL) was allowed to stand at room temperature for 4 days. The reaction mixture was concentrated under reduced pressure and suspended in dichloromethane (200 mL). The slurry was stirred at room temperature for 18 hours, filtered, rinsed with dichloromethane, and concentrated under reduced pressure to give 6.42 g (78%) of a solid. A portion of this solid, 3-(2-chloro-6-methyl-benzylamino)-4-ethoxy-cyclobut-3-ene-1,2-dione, (0.4 g, 1.43 mmol) was placed in t-butylamine (4 mL) and dichloromethane (4 mL) and allowed to stand at room temperature for 6 days. The solid was filtered, rinsed several times with ethyl acetate, and dried. This gave 0.31 g (71%) of the title compound as a white solid: mp 254°-257° C.; 1H NMR (DMSO-d6) δ7.46 (br s, 1H), 7.42 (br t, 1H), 7.38-7.22 (m, 3H), 4.93 (d, 2H), 2.40 (s, 3H), 1.34 (s, 9H) ppm. IR (KBr): 3200, 2960, 1790, 1650 cm-1 ; MS (m/z) 306/308 (M+).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:12]=[C:11]([N+:13]([O-:15])=[O:14])[CH:10]=[C:6]([C:7]([OH:9])=O)[CH:5]=1.C(Cl)(C(Cl)=O)=O.[CH2:23]([NH:26][CH2:27][CH2:28][CH3:29])[CH2:24][CH3:25]>C(Cl)Cl.CN(C=O)C>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:12]=[C:11]([N+:13]([O-:15])=[O:14])[CH:10]=[C:6]([C:7]([N:26]([CH2:27][CH2:28][CH3:29])[CH2:23][CH2:24][CH3:25])=[O:9])[CH:5]=1
Reactant: CCCNCCC
Reactant: COC(=O)c1cc(C(=O)O)cc([N+](=O)[O-])c1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CCCN(CCC)C(=O)c1cc(C(=O)OC)cc([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 109.6 %

Procedure:
A suspension of 5-nitro-isophthalic acid monomethyl ester (D77) (1.0 g, 4.44 mmol, 1 equiv) in CH2Cl2 (40 ml) was treated with (COCl)2 (655 mg, 5.2 mmol, 1.2 equiv) followed by a few drops of DMF. The resulting mixture was stirred for 1 h at room temperature and then dipropylamine (1.65 g, 15 mmol, 3.4 equiv) was added and the resulting solution stirred for a further 30 min. The solution was then washed with 2N aqueous HCl solution (50 ml), saturated aqueous NaHCO3 solution (50 ml), dried over MgSO4 and concentrated in vacuo to give 5-nitro-N,N-dipropyl-isophthalamic acid methyl ester (D87) (1.5 g, 110%) as a pale yellow oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]2[C:15](=O)[C:14](=[CH:17][C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=3)[CH2:13][S:12][CH2:11]2)[CH:5]=[CH:6][C:7]=1[Cl:8].[CH2:26]([NH:29][NH2:30])[CH2:27][CH3:28]>CO.C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[NH:30][N:29]([CH2:26][CH2:27][CH3:28])[C:15]3[C:14](=[CH:17][C:18]4[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=4)[CH2:13][S:12][CH2:11][C:10]2=3)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: CCCNN
Reactant: O=C1C(=Cc2ccc(Cl)c(Cl)c2)CSCC1=Cc1ccc(Cl)c(Cl)c1
Solvent: ClC(Cl)Cl
Solvent: CO
Product: CCCN1NC(c2ccc(Cl)c(Cl)c2)C2=C1C(=Cc1ccc(Cl)c(Cl)c1)CSC2
Yield: 68.5 %

Procedure:
A suspension of tetrahydro-3,5-bis-(3,4-dichlorophenylmethylene)-4H-thiopyran-4-one (6.5 g, 15 mmole) and n-propylhydrazine (1.1 g, 15 mmole) in methanol/chloroform (1:1, 250 ml) is heated at reflux temperature overnight. When the reaction mixture is slightly cooled, unreacted starting material precipitates out and is removed (about 2.2 g) by filtration. The filtrate is concentrated in vacuo and dissolved in CHCl3 and washed with dilute HCl and water. The organic layer is dried (anhydrous MgSO4) and concentrated in vacuo to give 5 g of a semi-solid material. This is applied to a wet-packed (hexane) Al2O3 column (neutral, activity I), and eluted with 0-100% ether/hexane. The major product is obtained eluting with 10-40% ether/hexane. The later fractions, eluted with 50-80% ether/hexane, are combined, concentrated and the residue crystallized from MeOH/CHCl3 to give 0.4 g of the product in crystalline form (99% pure), m.p. 161°-162.5° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([CH3:15])[CH:12]=[CH:11][CH:10]=1.[Se](=O)=[O:17]>O1CCOCC1>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([CH:15]=[O:17])[CH:12]=[CH:11][CH:10]=1
Reactant: Cc1cccc(-c2ccc(Cl)cc2Cl)n1
Reactant: O=[Se]=O
Solvent: C1COCCO1
Product: O=Cc1cccc(-c2ccc(Cl)cc2Cl)n1

Procedure:
1.5 g of 6-(2,4-dichlorophenyl)-2-methylpyridine was dissolved in 200 ml of 1,4-dioxane and treated with 1.05 g of selenium dioxide (Aldrich, Gold Label). The mixture was refluxed for 72 hours. An additional 1.2 g of selenium dioxide was added and the mixture was heated a further 48 hours. The solids were removed by filtration and the dioxane was evaporated to afford crude 6-(2,4-dichlorophenyl)-2-pyridinecarboxaldehyde which was chromatographed on silica-gel to afford 1.5 g of 6-(2,4-dichlorophenyl)-2-pyridinecarboxaldehyde as a white solid.
Reaction SMILES: C(OC([NH:11][C@@H:12]([CH2:17][N:18]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]([O:15][CH3:16])=[O:14])=O)C1C=CC=CC=1.[H][H]>CO>[NH2:11][C@@H:12]([CH2:17][N:18]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[C:13]([O:15][CH3:16])=[O:14]
Reactant: [H][H]
Reactant: COC(=O)[C@H](CN(c1ccccc1)c1ccccc1)NC(=O)OCc1ccccc1
Solvent: CO
Product: COC(=O)[C@@H](N)CN(c1ccccc1)c1ccccc1
Yield: 91 %

Procedure:
In order to eliminate the Z protecting group, 2.7 g (6.68 mmol) of the Z-protected derivative (10) were dissolved in 500 ml of methanol, and 100 mg of catalyst (10% Pd(OH)2—C) were supplied under a protective atmosphere of nitrogen. The inert gas was then displaced with a large excess of hydrogen and the mixture was shaken for 2 h in the hydrogen atmosphere. In order to terminate the reaction, the catalyst was filtered off and the filtrate was concentrated. 1.65 g (yield: 91%) of methyl 2-amino-3-diphenylaminopropionate (11) were obtained.
Reaction SMILES: [C:1]([N:14](OCC)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].B.C1C[O:28][CH2:27][CH2:26]1>C(N(CC)CC)C>[CH2:1]([NH:14][C:15]1[CH:16]=[CH:17][C:18]([O:28][CH2:27][CH3:26])=[CH:19][CH:20]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCCC(=O)N(OCC)c1ccccc1
Reactant: C1CCOC1
Agent: B
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCCNc1ccc(OCC)cc1
Reaction time: 20 h
Yield: 75 %

Procedure:
N-dodecanoyl-p-ethoxyaminobenzene (6g, 0.019 mole) was placed in a 250 ml round-bottom flask with Borane/THF complex (50 ml, 1M solution in tetrahydrofuran, stabilized with 5 mole percent sodium borohydride). The flask was flushed with nitrogen, stoppered with a drierite tube and allowed to stand at room temperature for 20 hours. Water was then added slowly to react with excess diborane. Formation of the amine salt was avoided by refluxing the reaction mixture with triethylamine (5 ml) for one hour. The mixture was cooled and the layers separated. The upper layer was washed with water (3 × 20 ml). A fourth wash emulsified the mixture. It was broken by addition of salt. The upper layer was dried with anh. sodium sulphate and evaporated to dryness yielding 5.56g (97%) of white plates of crude product. Crystallization from methanol afforded 4.3g (75%) of N-dodecyl-p-ethoxy-aminobenzene in the form of white plates, m.p. 38°-39° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10](=[O:15])[C:11]([F:14])([F:13])[F:12])=[CH:4][C:3]=1[C:16]1[NH:20][C:19](=[O:21])[N:18]([C:22]2[CH:31]=[CH:30][C:25]([C:26](OC)=[O:27])=[C:24]([O:32][CH3:33])[CH:23]=2)[N:17]=1.[F:34][C:35]([F:44])([F:43])[C:36]1[CH:37]=[C:38]([CH:40]=[CH:41][CH:42]=1)[NH2:39].C[Al](C)C>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10](=[O:15])[C:11]([F:12])([F:14])[F:13])=[CH:4][C:3]=1[C:16]1[NH:20][C:19](=[O:21])[N:18]([C:22]2[CH:31]=[CH:30][C:25]([C:26]([NH:39][C:38]3[CH:40]=[CH:41][CH:42]=[C:36]([C:35]([F:34])([F:43])[F:44])[CH:37]=3)=[O:27])=[C:24]([O:32][CH3:33])[CH:23]=2)[N:17]=1
Reactant: COC(=O)c1ccc(-n2nc(-c3cc(CNC(=O)C(F)(F)F)ccc3Cl)[nH]c2=O)cc1OC
Reactant: Nc1cccc(C(F)(F)F)c1
Agent: C[Al](C)C
Solvent: Cc1ccccc1
Product: COc1cc(-n2nc(-c3cc(CNC(=O)C(F)(F)F)ccc3Cl)[nH]c2=O)ccc1C(=O)Nc1cccc(C(F)(F)F)c1
Yield: 67.1 %

Procedure:
To a solution of methyl 4-(3-(2-chloro-5-((2,2,2-trifluoroacetamido) methyl)phenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)-2-methoxybenzoate (0.200 g, 0.413 mmol) in dry toluene (3 mL) was added 3-(trifluoromethyl)aniline (0.100 g, 0.619 mmol) followed by addition of trimethyl aluminium (2M solution in toluene) (2 mL). The reaction mass was refluxed for 3-4 h. The reaction mass was quenched in water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and concentrated to afford 0.170 g of desired product. 1H NMR (300 MHz, DMSO d6): δ 3.95 (s, 3H), 4.46 (d, J=6.0 Hz, 2H), 7.56 (t, J=6.0 Hz, 2H), 7.59-7.85 (m, 6H), 7.96 (d, J=7.8 Hz, 1H), 8.26 (s, 1H), 10.09 (s, 1H), 10.37 (s, 1H), 12.65 (s, 1H); MS (m/z): (M)+ 614.08.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[C:4]([F:11])[CH:3]=1.[Cl:12][C:13]1[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:14]=1[O:20][CH3:21].[Al+3].[Cl-].[Cl-].[Cl-].Cl>ClCCCl>[Cl:19][C:18]1[C:13]([Cl:12])=[C:14]([O:20][CH3:21])[CH:15]=[CH:16][C:17]=1[C:6]([C:5]1[CH:9]=[CH:10][C:2]([Cl:1])=[CH:3][C:4]=1[F:11])=[O:7]
Reactant: COc1cccc(Cl)c1Cl
Reactant: O=C(Cl)c1ccc(Cl)cc1F
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCCl
Product: COc1ccc(C(=O)c2ccc(Cl)cc2F)c(Cl)c1Cl
Temperature: 40 °C

Procedure:
To a mixture of 46 g of 4-chloro-2-fluorobenzoyl chloride and 38.9 g of 2,3-dichloroanisole in 150 ml of 1,2-dichloroethane, 32 g of AlCl3 is added gradually. The mixture is warmed to 40° C. with a vigorous evolution of gas. The mixture is poured into concentrated HCl and ice. The organic layer is separated and the aqueous layer is extracted with additional organic solvent. The combined organic extracts are washed with water, dried over Na2SO4 and evaporated. The crude product is triturated with hexane to give 2,3-dichloro-4-methoxy-4'-chloro-2'-fluorobenzophenone. An analytical sample is recrystallized from EtOH, mp 115°-116° C.
Reaction SMILES: C(#N)C.[CH:4]1[CH2:9][CH2:8][CH2:7][CH2:6][CH:5]=1.[C:10]([O:18]OC(C)(C)C)(=[O:17])[C:11]1C=CC=CC=1>[Cu+2].[Cu].C(O)(=O)C>[C:10]([O:18][CH:4]1[CH2:9][CH2:8][CH2:7][CH:6]=[CH:5]1)(=[O:17])[CH3:11]
Reactant: C1=CCCCC1
Reactant: CC(C)(C)OOC(=O)c1ccccc1
Agent: [Cu+2]
Agent: [Cu]
Solvent: CC(=O)O
Solvent: CC#N
Product: CC(=O)OC1C=CCCC1
Reaction time: 3 h

Procedure:
A mixture of 0.6 g of di-L-prolinato Copper (II), 0.7 g of copper powder, 15 ml of acetonitrile, 5 ml of acetic acid, 15 ml of cyclohexene and 5 ml of t-butyl peroxybenzoate was stirred at 20° to 25° C for 3 hours in a nitrogen atmosphere. After it was confirmed on TLC (thin layer chromatography) that the residual t-butyl peroxybenzoate was no longer present, the remaining copper powder was filtered off and the filtrate was admixed with 50 ml of benzene. The organic layer was successively washed with a 2N hydrochloric acid, an aqueous solution saturated with sodium chloride, an aqueous solution saturated with sodium hydrogen carbonate and an aqueous solution saturated with sodium chloride, and dried over anhydrous sodium sulfate. After removing the solvent, the residue was distilled under reduced pressure to obtain 1.40 g of 2-cyclohexenyl acetate. B.P. 75°-76° C/21 mmHg.
Reaction SMILES: [C:1]([O:12][CH3:13])(=[O:11])[C:2]1[CH:10]=[CH:9][C:7]([OH:8])=[C:4]([O:5][CH3:6])[CH:3]=1.C([O-])([O-])=O.[K+].[K+].[Br:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]Br>CC(C)=O>[CH3:13][O:12][C:1](=[O:11])[C:2]1[CH:10]=[CH:9][C:7]([O:8][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][Br:20])=[C:4]([O:5][CH3:6])[CH:3]=1
Reactant: BrCCCCCBr
Reactant: COC(=O)c1ccc(O)c(OC)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: COC(=O)c1ccc(OCCCCCBr)c(OC)c1
Temperature: 25 °C
Reaction time: 6 h
Yield: 82.4 %

Procedure:
To a solution of methyl vanillate (9.109 g, 50 mmol) in acetone (200 mL) were added K2CO3 (27.64 g, 200 mmol) and 1,5-dibromopentane (20.4 mL, 150 mmol). The resulting mixture was heated to reflux. After 6 h, TLC showed no starting material left. The mixture was cooled to rt, and the solid was removed by filtration. The filtrate was concentrated. Purification by flash chromatography (silica gel, 8:2 hexanes/EtOAc) afforded 4-(5-bromopentyloxy)-3-methoxy-benzoic acid methyl ester 15 as white solid (13.65 g, 82%): 1HNMR (300 MHz, CDCl3) δ 1.60-1.66 (m, 2H), 1.85-1.97 (m, 4H), 3.42 (t, J=5.0 Hz, 2H), 3.87 (s, 3H), 3.89 (s, 3H), 4.06 (t, J=5.0 Hz, 2H), 6.85 (d, J=6.3 Hz, 1H), 7.52 (d, J=1.5 Hz, 1H), 7.63 (dd, J=6.3, 1.5 Hz, 1H); EIMS m/z 353 and 355 ([M]++Na).
Reaction SMILES: Br[C:2]1[C:10]2[CH:9]([CH2:11][N+:12]([O-:14])=[O:13])[O:8][B:7]([OH:15])[C:6]=2[C:5]([O:16][CH2:17][CH3:18])=[CH:4][CH:3]=1.[CH3:19][Sn](C)(C)C>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:17]([O:16][C:5]1[C:6]2[B:7]([OH:15])[O:8][CH:9]([CH2:11][N+:12]([O-:14])=[O:13])[C:10]=2[C:2]([CH3:19])=[CH:3][CH:4]=1)[CH3:18]
Reactant: C[Sn](C)(C)C
Reactant: CCOc1ccc(Br)c2c1B(O)OC2C[N+](=O)[O-]
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Product: CCOc1ccc(C)c2c1B(O)OC2C[N+](=O)[O-]
Temperature: 90 °C
Reaction time: 8 h
Yield: 45.5 %

Procedure:
A mixture of 4-bromo-7-ethoxy-3-(nitromethyl)benzo[c][1,2]oxaborol-1(3H)-ol (200 mg, 0.63 mmol), tetramethylstannane (341.7 mg, 1.90 mmol) and Pd(PPh3)4 (Cat. 20 mg) in DMF (35 mL) was stirred overnight at 90° C. under N2 protection. The reaction was quenched by adding ice-water and the resulting mixture was extracted with ethyl acetate (3×30 mL). The combined extracts were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by prep-TLC to give the product (72 mg, yield 45.3%). 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 7.23-7.21 (d, 1H), 6.83-6.81 (d, 1H), 5.77-5.75 (m, 1H), 5.27-5.24 (m, 1H), 4.50-4.44 (m, 1H), 4.08-4.03 (m, 2H), 2.25 (s, 3H), 1.33-1.29 (t, 3H).
Reaction SMILES: [C:1]([C:3]1[O:4][CH:5]=[CH:6][CH:7]=1)#[N:2].[NH2:8][OH:9]>CCO>[OH:9][NH:8][C:1]([C:3]1[O:4][CH:5]=[CH:6][CH:7]=1)=[NH:2]
Reactant: N#Cc1ccco1
Reactant: NO
Solvent: CCO
Product: N=C(NO)c1ccco1
Temperature: 80 °C

Procedure:
2-Cyanofuran (150 mg, 1.61 mmol) was dissolved in EtOH (1.61 mL) and treated dropwise with aq. hydroxylamine (50% w/w, 296 μL, 4.83 mmol) at room temperature. The mixture was warmed at 80° C. for 1.5 h. Upon completion, the solvent was removed to afford a colorless oil that was used without purification (203 mg, quant.): 1H NMR (CDCl3, 500 MHz) δ 9.34 (br s, 1H), 7.42 (d, 1H, J=1.1 Hz), 6.79 (d, 1H, J=3.3 Hz), 6.42 (dd, 1H, J=1.8, 3.4 Hz), 5.09 (br s, 2H).