Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[Si]([C:5]#[N:6])(C)C.[NH2:7][C:8]1[CH:12]=[C:11]([CH3:13])[NH:10][N:9]=1.[C:14]1(=O)[CH2:17][CH2:16][CH2:15]1>ClCCl>[CH3:13][C:11]1[CH:12]=[C:8]([NH:7][C:14]2([C:5]#[N:6])[CH2:17][CH2:16][CH2:15]2)[NH:9][N:10]=1
Reactant: O=C1CCC1
Reactant: Cc1cc(N)n[nH]1
Reactant: C[Si](C)(C)C#N
Solvent: ClCCl
Product: Cc1cc(NC2(C#N)CCC2)[nH]n1
Temperature: 25 °C
Reaction time: 40 h
Yield: 76 %

Procedure:
Trimethylsilyl cyanide (0.532 ml, 4.0 mmol) was added dropwise to the mixture of 3-amino-5-methylpyrazole (0.194 g, 2.0 mmol) and cyclobutanone (0.154 g, 2.2 mmol). The reaction mixture was stirred at room temperature for 40 h and then concentrated under vacuum to obtain a dark liquid which was subjected to chromatography (dichloromethane) to yield 16a (0.267 g, 1.52 mmol, 76%) as a off-white powder.
Reaction SMILES: Cl[C:2]1[C:7]([CH:8]=[O:9])=[CH:6][N:5]=[C:4]2[NH:10][CH:11]=[CH:12][C:3]=12.[CH:13]1([NH2:19])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.O>C(O)CO>[CH:13]1([NH:19][C:2]2[C:7]([CH:8]=[O:9])=[CH:6][N:5]=[C:4]3[NH:10][CH:11]=[CH:12][C:3]=23)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1
Reactant: NC1CCCCC1
Reactant: O=Cc1cnc2[nH]ccc2c1Cl
Solvent: O
Solvent: OCCO
Product: O=Cc1cnc2[nH]ccc2c1NC1CCCCC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 70.6 %

Procedure:
4-Chloro-1H-pyrrolo[2,3-b]pyridine-5-carbaldehyde (845 mg, 4.68 mmol) and cyclohexylamine (2.5 mL, 22 mmol) in ethylene glycol (2 mL) were stirred at 170° C. for 1 hour under microwave irradiation. The reaction mixture was allowed to cool to room temperature and, after addition of water, extracted with chloroform. The organic layer was stirred with 2 M hydrochloric acid (20 mL) for 1 hour, and the organic layer was separated. The aqueous layer was adjusted to pH 9 or above with 10 M aqueous sodium hydroxide and extracted with chloroform. The organic layers were combined, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol=10/1 (v/v)) to give the title compound as a pale yellow oil (804 mg, yield 71%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[Cl:29])[CH2:5][N:6]1[CH2:11][CH2:10][O:9][CH:8]([CH2:12][NH:13][C:14](=[O:25])[O:15]C2C=CC([N+]([O-])=O)=CC=2)[CH2:7]1.[C:30]([NH:33][C:34]1[CH:35]=[C:36]([CH:39]=[CH:40][CH:41]=1)[CH2:37][NH2:38])(=[O:32])[CH3:31]>>[CH:14]([OH:25])=[O:15].[Cl:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[Cl:29])[CH2:5][N:6]1[CH2:11][CH2:10][O:9][CH:8]([CH2:12][NH:13][C:14]([NH:38][CH2:37][C:36]2[CH:35]=[C:34]([NH:33][C:30](=[O:32])[CH3:31])[CH:41]=[CH:40][CH:39]=2)=[O:25])[CH2:7]1
Reactant: O=C(NCC1CN(Cc2ccc(Cl)c(Cl)c2)CCO1)Oc1ccc([N+](=O)[O-])cc1
Reactant: CC(=O)Nc1cccc(CN)c1
Product: CC(=O)Nc1cccc(CNC(=O)NCC2CN(Cc3ccc(Cl)c(Cl)c3)CCO2)c1
Product: O=CO
Yield: 34.4 %

Procedure:
Example 52 was prepared in an analogous manner to Example 43 from Intermediate 10 (0.04 g) and 3-acetamidobenzylamine (0.022 g), and purified by Mass Directed Automated Preparative HPLC to yield the title compound (0.008 g).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:31])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH2:15][C:14]([C:20]3[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]([Cl:27])[CH:21]=3)([C:16]([F:19])([F:18])[F:17])[O:13][N:12]=2)=[CH:7][C:6]=1[N+:28]([O-])=O)[CH3:2].O.C(O)(=O)C>C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:31])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH2:15][C:14]([C:20]3[CH:21]=[C:22]([Cl:27])[CH:23]=[C:24]([Cl:26])[CH:25]=3)([C:16]([F:17])([F:18])[F:19])[O:13][N:12]=2)=[CH:7][C:6]=1[NH2:28])[CH3:2]
Reactant: CCOC(=O)c1ccc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)cc1[N+](=O)[O-]
Solvent: O
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CCOC(=O)c1ccc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)cc1N
Temperature: 75 °C
Reaction time: 2 h
Yield: 106.7 %

Procedure:
In a solution of 0.60 g of 4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-nitro benzoic acid ethyl ester synthesized in Steps 1 to 3 of Synthetic Example 5 in 6 ml of ethyl acetate, 2.0 ml of water, 0.6 ml of acetic acid and 0.46 g of reduced iron were added, and stirred at 75° C. for 2 hours. After the completion of the reaction, the organic phase was collected, and the aqueous phase was extracted with ethyl acetate (10 ml×2). The organic phases together were washed with water, dehydrated with saturated sodium chloride aqueous solution and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain 0.60 g of crude aimed product as brown oily substance. The resulting product was used as such without purification for the next step.
Reaction SMILES: S(Cl)([Cl:3])=O.[NH2:5][C:6]([CH3:11])([CH3:10])[C:7]([OH:9])=[O:8].[CH3:12]O>>[ClH:3].[NH2:5][C:6]([CH3:11])([CH3:10])[C:7]([O:9][CH3:12])=[O:8]
Reactant: CO
Reactant: CC(C)(N)C(=O)O
Reactant: O=S(Cl)Cl
Product: COC(=O)C(C)(C)N
Product: Cl
Temperature: 50 °C
Yield: 96 %

Procedure:
A 500 mL round bottomed flask equipped with nitrogen inlet, thermometer adapter, solids addition funnel, and magnetic stirrer was placed in an ice salt bath and charged with 100 mL of methanol. To this solution was added thionyl chloride(18.0 mL, 0.25 mol) via syringe at such a rate that the internal temperature was maintained at less than 0° C. This solution was then treated with aminoisobutyric acid (19.6g, 0.19 mol) portion wise from the addition funnel at such a rate that the temperature did not rise above 5° C. The ice bath was removed and replaced with an oil bath and the solution warmed to 50° C. for 1 h and then concentrated in vacuo. The salt was thoroughly dried under vacuum to give the desired product as a white solid 28 g, 96%, mp 185° C. 1H nmr (CDCl3) 300 MHz 8.87(brs, 3H), 3.74(s, 3H), 1.65(s, 6H).
Reaction SMILES: [CH2:1]([S:6][C:7]1[N:12]=[C:11]([C:13]2[S:14][C:15]3[CH:23]=[CH:22][CH:21]=[CH:20][C:16]=3[C:17](=[O:19])[N:18]=2)[CH:10]=[CH:9][CH:8]=1)[CH2:2][CH2:3][CH2:4][CH3:5].ClC1C=CC=C(C(OO)=[O:32])C=1>C(Cl)(Cl)Cl>[CH2:1]([S:6]([C:7]1[N:12]=[C:11]([C:13]2[S:14][C:15]3[CH:23]=[CH:22][CH:21]=[CH:20][C:16]=3[C:17](=[O:19])[N:18]=2)[CH:10]=[CH:9][CH:8]=1)=[O:32])[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCCCCSc1cccc(-c2nc(=O)c3ccccc3s2)n1
Solvent: ClC(Cl)Cl
Product: CCCCCS(=O)c1cccc(-c2nc(=O)c3ccccc3s2)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 47.5 %

Procedure:
2-[6-(n-Pentylthio)-2-pyridyl]-4H-1,3-benzothiazine-4-one (0.15 g, 0.44 mmol) was dissolved in chloroform (50 ml), and a solution of 3-chloroperbenzoic acid (ca. 77%, 0.10 g, 0.46 mmol) in chloroform (10 ml) was added dropwise thereto. The reaction mixture was stirred at room temperature for 1 hr. The solvent was evaporated, and the residue was recrystallized from ethanol to give the titled compound (0.075 g, 48%) as white crystals.
Reaction SMILES: O1CCOCC1.[CH2:7]([O:9][CH:10]1[CH2:15][CH2:14][C:13](OS(C(F)(F)F)(=O)=O)=[CH:12][CH2:11]1)[CH3:8].[CH3:24][N:25]1[CH2:33][C:32]2[C:27](=[C:28]([N+:43]([O-:45])=[O:44])[CH:29]=[CH:30][C:31]=2B2OC(C)(C)C(C)(C)O2)[C:26]1=[O:46].C(=O)([O-])[O-].[Cs+].[Cs+]>O>[CH2:7]([O:9][CH:10]1[CH2:15][CH2:14][C:13]([C:31]2[CH:30]=[CH:29][C:28]([N+:43]([O-:45])=[O:44])=[C:27]3[C:32]=2[CH2:33][N:25]([CH3:24])[C:26]3=[O:46])=[CH:12][CH2:11]1)[CH3:8]
Reactant: CN1Cc2c(B3OC(C)(C)C(C)(C)O3)ccc([N+](=O)[O-])c2C1=O
Reactant: CCOC1CC=C(OS(=O)(=O)C(F)(F)F)CC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: C1COCCO1
Product: CCOC1CC=C(c2ccc([N+](=O)[O-])c3c2CN(C)C3=O)CC1
Temperature: 60 °C

Procedure:
Dioxane (20 mL) and water (5 mL) were taken in a three necked RB flask equipped with a nitrogen inlet and a thermometer. The solvents were deoxygenated for 15 min using nitrogen gas. Trifluoro-methanesulfonic acid 4-ethoxy-cyclohex-1-enyl ester (Compound 166D, 300 mg, 1.1 mmol), 2-methyl-7-nitro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,3-dihydro-isoindol-1-one (Compound 205E, 630 mg, 1.64 mmol), tetrakis triphenyl phosphine palladium catalyst (114 mg, 0.01 mmol) and cesium carbonate (889 mg, 2.7 mmol) were added. The reaction mixture was heated to 60° C. for 3 hrs. The solvents were evaporated and the residue was purified over silica gel column using (methanol:methylene chloride: 1:99). Yield: 300 mg (86%). 1H NMR (CDCl3, 400 MHz): δ 1.2 (t, 3H, J=7 Hz), 1.8-2.4 (m, 6H), 3.15 (s, 3H), 3.50-3.64 (m, 3H), 4.36 (s, 2H), 5.79 (m, 1H), 7.4 (d, 1H, J=8.1 Hz), 7.63 (d, 1H, J=8.1 Hz).
Reaction SMILES: I(C1C=CC=CC=1C(O)=O)(=O)=[O:2].[C:13]1(C)[CH:18]=[CH:17][C:16]([S:19][C:20]2C=CC(C)=CC=2)=[CH:15][CH:14]=1>[Br-].C([N+](CC)(CC)CC)C.C(Cl)(Cl)Cl.O>[C:16]1([S:19]([CH3:20])=[O:2])[CH:17]=[CH:18][CH:13]=[CH:14][CH:15]=1
Reactant: Cc1ccc(Sc2ccc(C)cc2)cc1
Reactant: O=C(O)c1ccccc1I(=O)=O
Agent: CC[N+](CC)(CC)CC
Agent: [Br-]
Solvent: ClC(Cl)Cl
Solvent: O
Product: CS(=O)c1ccccc1
Yield: 99.9 %

Procedure:
To a stirred suspension of iodoxybenzoic acid (3.7 g, 13.2 mmol, 1.1 eq) in 100:1 CHCl3/H2O (25 mL) was added tetraethylammonium bromide (TEAB) (126 mg, 5 mol %), followed by the addition of p-tolyl sulfide (1.66 g, 12 mmol) in one portion. The mixture was stirred at room temperature for approximately 30 minutes until consumption of sulfide was observed (TLC, hexanes/EtOAc 1/1). The residual solids were removed by filtration and washed with CHCl3 (40 mL). The combined filtrate was washed successively with saturated aq. NaHCO3 (30 mL), saturated aq. NaCl (30 mL), dried over sodium sulfate, and concentrated to provide the crude product. Purification by silica gel column chromatography (50% hexanes/EtOAc elution) afforded the title compound (1.68 g, yield 91%). 1H NMR (300 MHz, CDCl3) δ 7.52 (d, J=8.4 Hz, 2H), 7.32 (d, J=8.4 Hz, 2H), 2.71 (s, 3H), 2.42 (s, 3H); ESI-MS m/z 154.7 (M+H)+.
Reaction SMILES: FC(F)(F)C(O)=O.[NH2:8][CH2:9]/[CH:10]=[CH:11]/[C:12]([O:14][CH2:15][CH3:16])=[O:13].ClC(Cl)(Cl)[C:19]([C:21]1[NH:22][CH:23]=[C:24]([I:26])[CH:25]=1)=[O:20].C(N(CC)C(C)C)(C)C>ClCCl>[I:26][C:24]1[CH:25]=[C:21]([C:19]([NH:8][CH2:9]/[CH:10]=[CH:11]/[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[O:20])[NH:22][CH:23]=1
Reactant: O=C(c1cc(I)c[nH]1)C(Cl)(Cl)Cl
Reactant: CCOC(=O)/C=C/CN
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)/C=C/CNC(=O)c1cc(I)c[nH]1
Temperature: 25 °C
Reaction time: 8 h
Yield: 68.9 %

Procedure:
Ethyl (2E)-4-aminobut-2-enoate trifluoroacetate (IV) (0.97 g, 4 mmol) was added to a solution of 2,2,2-trichloro-1-(4-iodo-1H-pyrrol-2-yl)ethanone (IX) (0.68 g, 2 mmol) and N,N-diisopropylethylamine (DIPEA) (2.7 mL, 16 mmol) in dichloromethane (20 mL) and the reaction mixture was stirred at room temperature overnight. The solvent was evaporated under vacuum and the residue purified by flash chromatography (SiO2, hexane-EtOAc 1:1) to obtain compound ethyl (2E)-4-{[(4-iodo-1H-pyrrol-2-yl)carbonyl]amino}but-2-enoate (X, where R1=OCH2CH3) as an off-white solid (0.48 g, 68% yield).
Reaction SMILES: [C:1]1([CH3:8])[C:6]([OH:7])=[CH:5]C=[CH:3][CH:2]=1.[N+]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([O-])=O.[Cl-].[Al+3].[Cl-].[Cl-].C(Cl)(=[O:27])CCCC>Cl>[OH:7][CH:6]([CH3:5])[CH:1]([CH3:8])[CH2:2][C:3]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:27]
Reactant: Cc1ccccc1O
Reactant: CCCCC(=O)Cl
Reactant: O=[N+]([O-])c1ccccc1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Product: CC(O)C(C)CC(=O)c1ccccc1
Temperature: 0 °C
Reaction time: 12 h

Procedure:
108 g (1 mole) of orthocresol are added to a liter of nitrobenzene. The solution is cooled to 0° C. and 280 g (2.1 moles) of powdered aluminium chloride are added over a period of one hour (while stirring). While still stirring and at 0° C., 120.5 g (1 mole) of valeryl chloride are added over a period of one hour 30 minutes. The temperature of the solution is left for about 12 hours at this temperature. The solution is then poured into a mixture of 1 kg of ice and 500 ml of 37% hydrochloric acid. The mixture is stirred for one hour and the organic phase is decanted. It is whashed with 5 N hydrochloric acid and then with deionized water.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:16][CH3:17])=[C:6]([NH:8][C:9](=[S:15])[NH:10][CH2:11][C:12](N)=[O:13])[CH:7]=1.[CH2:18](I)[CH3:19]>C(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:16][CH3:17])=[C:6]([N:8]2[C:12](=[O:13])[CH2:11][N:10]=[C:9]2[S:15][CH2:18][CH3:19])[CH:7]=1
Reactant: CCI
Reactant: COc1ccc(Cl)cc1NC(=S)NCC(N)=O
Solvent: CCO
Product: CCSC1=NCC(=O)N1c1cc(Cl)ccc1OC
Yield: 53.3 %

Procedure:
A mixture of 2-[3-(5-chloro-2-methoxyphenyl)-thioureido]-acetamide (11.0 g) and ethyl iodide (12.5 g) in ethanol (400 mL) was heated at reflux for 4.5 hours. The solvent was evaporated. The residue was dissolved in chloroform (500 mL) and washed with water. The organic phase was dried over anhydrous MgSO4, then evaporated to dryness. The residue was crystallized from ethanol to give the title compound (6.1 g) as a tan solid, m.p. 113°-115° C. Anal. Calcd. for. C12H13Cl N2O2S: C, 50.61; H, 4.60; N,9.84. Found: C, 50.32; H, 4.59; N, 9.77. Mass spectrum (ESI+, [M+H]+) m/z 285/287. 1H-NMR (DMSO-d6; 400 MHz) 15 7.53 (m, 1H), 7.41 (d, 1H), 7.22 (d, 1H), 4.31 (dd, 2H), 3.77 (s, 3H), 3.05 (m, 2H), and 1.26 ppm (t, 3H).
Reaction SMILES: [C:1]([O:4][C:5]1[CH:10]=[CH:9][C:8](I)=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[C:12]1([C:18]#[CH:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C.O>C(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:19]#[C:18][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:7][CH:6]=1)(=[O:3])[CH3:2]
Reactant: C#Cc1ccccc1
Reactant: CC(=O)Oc1ccc(I)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)Oc1ccc(C#Cc2ccccc2)cc1
Reaction time: 2 h
Yield: 108.6 %

Procedure:
4-Iodophenyl acetate (50.00 g, 0.191 mol), phenylacetylene (23.40 g, 0.229 mol), and triethylamine (54 mL) are added to a 250-mL round bottom flask fitted with a condenser/nitrogen inlet, a thermometer, and a stopper. PdCl2(PPh3)2 (0.200 g, 0.286 mmol) and PPh3 (1.50 g, 5.73 mmol) are then added and the mixture heated to reflux. When the reaction mixture reaches 40° C., CuI (0.054 g, 0.286 mmol) is added. After 2 hours, the reaction is allowed to cool. The mixture is diluted with methylene chloride and poured into water (500 mL). The aqueous layer is extracted with methylene chloride (100 mL). The combined organic layers are washed with three 300-mL portions of water, dried (MgSO4), and filtered. The solvent is removed in vacuo to give 49 g of a yellow solid. The material is recrystallized from hexanes to give light yellow crystals, mp 104.5° C. to 105.5° C.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([CH:8]2[CH2:10][CH2:9]2)[N:5]=[C:4]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[C:17]([F:20])([F:19])[F:18])[N:3]=1.[NH:21]1[C:25]2=[N:26][CH:27]=[CH:28][CH:29]=[C:24]2[C:23]([NH2:30])=[N:22]1.O.C(=O)(O)[O-].[Na+]>CN1CCCC1=O>[CH:8]1([C:6]2[N:5]=[C:4]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[C:17]([F:20])([F:19])[F:18])[N:3]=[C:2]([NH:30][C:23]3[C:24]4[C:25](=[N:26][CH:27]=[CH:28][CH:29]=4)[NH:21][N:22]=3)[CH:7]=2)[CH2:10][CH2:9]1
Reactant: FC(F)(F)c1ccccc1-c1nc(Cl)cc(C2CC2)n1
Reactant: Nc1n[nH]c2ncccc12
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CN1CCCC1=O
Product: FC(F)(F)c1ccccc1-c1nc(Nc2n[nH]c3ncccc23)cc(C2CC2)n1
Temperature: 130 °C
Yield: 56.6 %

Procedure:
A mixture of 4-chloro-6-cyclopropyl-2-(2-trifluoromethyl-phenyl)-pyrimidine (7.00 g, 23.4 mmol, prepared as described above in example 8) and 1H-pyrazolo[3,4-b]pyridin-3-ylamine (9.43 g, 70.3 mmol) in N-methylpyrrolidinone (50 mL) was heated at 130° C. for 12 hours. The residue was cooled, dissolved in N-methyl-pyrrolidinone (2 mL), poured into water (500 mL) and sodium bicarbonate (15 mL) then filtered, washing with water. Purification by flash chromatography [SiO2, ethyl acetate:hexanes (35:65)] provided the title compound (5.25 g, 57% yield) as a white solid. 1H-NMR (500 MHz, DMSO-d6) δ 13.1 (br s, 1H), 10.5 (br s, 1H), 8.50 (m, 2H), 7.82 (d, J=7.8 Hz, 1H), 7.73 (m, 3H), 7.66 (t, J=7.7 Hz, 1H), 7.12 (m, 1H), 2.07 (m, 1H), 1.02 (m, 2H), 0.97 (m, 2H) ppm; LC-MS 397.22 (M+H); Rt (Method A) 3.412 minutes.
Reaction SMILES: F[C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][N:3]=1.[NH2:9][C:10]1[CH:15]=[CH:14][C:13]([S:16]([NH2:19])(=[O:18])=[O:17])=[CH:12][CH:11]=1>O.C(#N)C>[I:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([S:16]([NH2:19])(=[O:17])=[O:18])=[CH:12][CH:11]=2)[CH:7]=1
Reactant: Nc1ccc(S(N)(=O)=O)cc1
Reactant: Fc1cc(I)ccn1
Solvent: O
Solvent: CC#N
Product: NS(=O)(=O)c1ccc(Nc2cc(I)ccn2)cc1
Temperature: 150 °C

Procedure:
A mixture of 2-fluoro-4-iodopyridine (1.0 g, 4.48 mmol) and 4-aminobenzenesulfonamide (772 mg, 4.48 mmol) was heated with an oil bath for 3 hours at 150° C. The title compound A4 was obtained from the residue by preparative HPLC (water/ACN gradient). Yield: 135 mg (8%). MS (ES) C11H10IN3O2S requires: 375. found: 376 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([O:12][CH3:13])[CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.C(N(CC)CC)C.Cl.[CH3:34][NH:35][O:36][CH3:37]>CN(C=O)C.O>[CH3:37][O:36][N:35]([CH3:34])[C:6](=[O:8])[C:5]1[CH:9]=[C:10]([Cl:11])[C:2]([NH2:1])=[CH:3][C:4]=1[O:12][CH3:13]
Reactant: CNOC
Reactant: COc1cc(N)c(Cl)cc1C(=O)O
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: COc1cc(N)c(Cl)cc1C(=O)N(C)OC
Reaction time: 0.25 h
Yield: 82 %

Procedure:
4-Amino-5-chloro-2-methoxybenzoic acid (10.1 g, 50 mmol) was dissolved in DMF (50 mL). Carbonyldiimidazole (8.9 g, 55 mmol) was added to the solution and the mixture was stirred for 15 minutes. Triethylamine (7 mL, 5.1 g, 50 mmol) and N,O-dimethylhydroxylamine hydrochloride (6.3 g, 65 mmol) were added and the mixture was stirred for 12 hours. The mixture was then diluted with water and extracted into ethyl acetate. The ethyl acetate extract was washed with 5% HCl, with water, and then with brine. The extract was dried over sodium sulfate and then evaporated. Crystallization from ethyl acetate gave N-methoxy-N-methyl-4-amino-5-chloro-2-methoxybenzamide (10 g, 41 mmol), m.p. 134°-135° C.
Reaction SMILES: CO.[OH-].[Na+].[C:5]1([C:11]2[CH:23]=[CH:22][C:14]([C:15]([O:17]C(C)(C)C)=[O:16])=[C:13]([NH:24][C:25](=[O:37])[C:26]3[CH:31]=[CH:30][C:29]([N:32]4[CH:36]=[CH:35][CH:34]=[CH:33]4)=[CH:28][CH:27]=3)[CH:12]=2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.Cl>C(OCC)(=O)C.O1CCOCC1>[C:5]1([C:11]2[CH:23]=[CH:22][C:14]([C:15]([OH:17])=[O:16])=[C:13]([NH:24][C:25](=[O:37])[C:26]3[CH:31]=[CH:30][C:29]([N:32]4[CH:33]=[CH:34][CH:35]=[CH:36]4)=[CH:28][CH:27]=3)[CH:12]=2)[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1
Reactant: CC(C)(C)OC(=O)c1ccc(-c2ccccc2)cc1NC(=O)c1ccc(-n2cccc2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Solvent: CO
Product: O=C(Nc1cc(-c2ccccc2)ccc1C(=O)O)c1ccc(-n2cccc2)cc1
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 86 %

Procedure:
1.0 mL of methanol and 0.5 mL of 2.0 mol/L aqueous sodium hydroxide were added to 1.0 mL of dioxane solution containing 20 mg of tert-butyl 4-phenyl-2-(4-(1H-pyrrol-1-yl)benzamido)benzoate at room temperature and stirred at 50° C. for 30 minutes. Ethyl acetate and 1.0 mol/L hydrochloric acid were added after the reaction mixture was cooled to room temperature. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with a saturated sodium chloride aqueous solution, and the solvent was evaporated under reduced pressure, Diisopropyl ether were added to toe obtained residue and a solid substance was separated by filtration to obtain 15 mg of 4-phenyl-2-(4-(1H-pyrrol-1-yl)benzamido)benzoic acid as white solid.
Reaction SMILES: C[Si](C)(C)Cl.[C:6]1([CH:12]=[CH:13][C:14](=[O:18])[CH2:15][CH2:16][CH3:17])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C(=O)C1C=CC=CC=1.CC(=O)CCC.Br[CH2:34][C:35]([O:37][CH3:38])=[O:36].Cl>C(OCC)(=O)C.[Zn]>[OH:18][C:14]([CH:13]=[CH:12][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([CH2:15][CH2:16][CH3:17])[CH2:34][C:35]([O:37][CH3:38])=[O:36]
Reactant: COC(=O)CBr
Reactant: CCCC(=O)C=Cc1ccccc1
Agent: C[Si](C)(C)Cl
Agent: Cl
Agent: [Zn]
Solvent: O=Cc1ccccc1
Solvent: CCCC(C)=O
Solvent: CCOC(C)=O
Product: CCCC(O)(C=Cc1ccccc1)CC(=O)OC
Temperature: 65 °C
Reaction time: 0.5 h

Procedure:
At room temperature, a three-necked flask fitted with reflux condenser, internal thermometer, dropping funnel and stirrer was charged, under nitrogen protective gas, with 8.5 g of zinc powder (129 mmol) in 55 ml of ethyl acetate. After 2.4 ml of trimethylchlorosilane (19 mmol) had been added, the mixture was heated at 65° C. for 30 min, then left to cool to 50° C. Over the course of 8 min, a mixture of 15 g of 1-phenylhex-1-en-3-one, prepared by base-catalyzed aldol condensation of benzaldehyde and pentan-2-one, and 15.8 g of methyl bromoacetate (103 mmol) was added dropwise, the temperature being maintained at 50° C. by external cooling. The mixture was then stirred at 50° C. for 30 min, and following cooling to 0° C., acidified with 60 ml of 2 N hydrochloric acid to a pH of 1 and stirred for 30 min. Excess zinc was then removed by filtration and the organic phase separated. The organic phase was then stirred at 0° C. with 60 ml of 0.5 N hydrochloric acid and finally washed with 20 ml of saturated sodium hydrogen carbonate solution. Following phase separation and drying over sodium sulfate, the solvent was removed by distillation under reduced pressure. Methyl 3-hydroxy-3-(2′-phenylethenyl)caproate was obtained in a yield of 20.4 g (95% of theory) and a purity of greater than 97% (HPLC). The compound had a melting point of 43° C. following recrystallization from petroleum ether.
Reaction SMILES: [CH:1]([O:4][N:5]=[C:6]([N:14]1[CH:18]=[N:17][CH:16]=[N:15]1)[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([OH:13])[CH:8]=1)([CH3:3])[CH3:2].Cl[Si:20]([CH3:23])([CH3:22])[CH3:21].[C:24](=O)([O-])[O-].[K+].[K+].CN(C=O)C>[I-].[K+].O>[CH:1]([O:4][N:5]=[C:6]([N:14]1[CH:18]=[N:17][CH:16]=[N:15]1)[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH2:21][Si:20]([CH3:23])([CH3:24])[CH3:22])[CH:8]=1)([CH3:3])[CH3:2]
Reactant: CC(C)ON=C(c1cccc(O)c1)n1cncn1
Reactant: C[Si](C)(C)Cl
Reactant: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)ON=C(c1cccc(OC[Si](C)(C)C)c1)n1cncn1
Temperature: 90 °C
Yield: 87.8 %

Procedure:
2.7 g of 1-(O-isopropyl-3-hydroxybenzohydroximoyl)-1H-1,2,4-triazole, 1.5 g of chlorotrimethylsilane, 1.8 g of potassium carbonate, and a small amount of potassium iodide catalyst were added to 100 ml of DMF. The mixture was stirred for at 90° C. 2 hours. After the resultant mixture was allowed to sit and cool naturally, it was poured into water. The organic layer was extracted with ethyl acetate and dried over magnesium sulfate. The solvent in the organic layer was removed under reduced pressure. The residue was purified by column chromatography (eluate: hexane/ethyl acetate=4/1), thus yielding 3.2 g (yield: 89%) of the desired product (transparent viscous liquid) having a refractive index of [nD20 ] 1.5310 at 20° C.