Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([Li])CCC.[F:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[S:14][CH:15]=[CH:16][C:17]=2[C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=2)=[CH:9][CH:8]=1.CN(C)[CH:30]=[O:31].Cl>CCCCCC.O1CCCC1>[F:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[S:14][C:15]([CH:30]=[O:31])=[CH:16][C:17]=2[C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=2)=[CH:11][CH:12]=1
Reactant: CS(=O)(=O)c1ccc(-c2ccsc2-c2ccc(F)cc2)cc1
Reactant: CN(C)C=O
Agent: Cl
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CS(=O)(=O)c1ccc(-c2cc(C=O)sc2-c2ccc(F)cc2)cc1
Reaction time: 0.5 h

Procedure:
n-Butyl lithium (1.6M) in hexane (36 ml) was added dropwise to a stirred solution of 2-(4-fluorophenyl)-3-[4-(methylsulfonyl)phenyl]thiophene (8.0 g) in tetrahydrofuran (80 ml) at -60° C. The mixture was stirred for 30 minutes, and N,N-dimethylformamide (3.7 ml) was added dropwise over ten minutes to the mixture. The mixture was stirred at -70° to -20° C. for 2 hours. 1N Hydrochloric acid (70 ml) was added dropwise, and the solution was extracted with ethyl acetate. The extract was washed with brine, dried and concentrated. The residual syrup was purified by column chromatography on silica gel eluting with a mixture of toluene and ethyl acetate (9:1). The obtained crystals (4.5 g) were recrystallized from ethyl acetate to give pale yellow crystals of 5-(4-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]thiophene-2-carbaldehyde (3.7 g).
Reaction SMILES: C[O:2][C:3](=[O:24])[C:4]1[CH:9]=[C:8]([CH3:10])[CH:7]=[C:6](Br)[C:5]=1[NH:12][S:13]([C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1)(=[O:15])=[O:14].[Cu][C:26]#[N:27].O.Cl>N1C=CC=CC=1>[C:26]([C:6]1[C:5]([NH:12][S:13]([C:16]2[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=2)(=[O:15])=[O:14])=[C:4]([CH:9]=[C:8]([CH3:10])[CH:7]=1)[C:3]([OH:2])=[O:24])#[N:27]
Reactant: COC(=O)c1cc(C)cc(Br)c1NS(=O)(=O)c1ccc(OC)cc1
Reactant: N#C[Cu]
Agent: Cl
Solvent: c1ccncc1
Solvent: O
Product: COc1ccc(S(=O)(=O)Nc2c(C#N)cc(C)cc2C(=O)O)cc1
Yield: 72.2 %

Procedure:
To a solution of 4.0 g (10 mmol) of the product of Example 135 in 60 ml of pyridine was added 2.0 g (22 mmol) of copper (I) cyanide and the mixture was refluxed for 48 h. The reaction mixture was then cooled to room tempera and poured over cold water. The resulting mixture was stirred for sixteen hours and carefully acidified with concentted HCl solution. The resulting precipitate was filtered and washed with water, dissolved in chloroform, filtered and concentrated. The residue was triturated with ether, filtered and dried to provide 2.5 g (72%) of the desired product as a white solid. m.p. 162° C.; Electrospray Mass Spec 347 (M+H).
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[C:8]([N+:10]([O-])=O)[CH:7]=[CH:6][C:5]=1[O:13][CH3:14])([CH3:3])[CH3:2]>CO.[Pd]>[CH:1]([C:4]1[CH:9]=[C:8]([CH:7]=[CH:6][C:5]=1[O:13][CH3:14])[NH2:10])([CH3:3])[CH3:2]
Reactant: COc1ccc([N+](=O)[O-])cc1C(C)C
Agent: [Pd]
Solvent: CO
Product: COc1ccc(N)cc1C(C)C
Yield: 108.2 %

Procedure:
2-Isopropyl-1-methoxy-4-nitro-benzene (4.53 g, 23.6 mmol) was dissolved in 100 mL of methanol in presence of 0.4 g of 10% Pd/C in a Parr bottle, and then subjected to 40 psi of H2 overnight at room temperature. The mixture was purged with nitrogen for 10 minutes and filtered over Celite. The filtrate was concentrated to give 4.22 g 3-isopropyl-4-methoxyaniline.
Reaction SMILES: [CH2:1]([NH:8][C:9]1[CH:14]=[C:13](F)[CH:12]=[CH:11][C:10]=1[N+:16]([O-:18])=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:19][N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1.O>C(#N)C>[CH2:1]([NH:8][C:9]1[CH:14]=[C:13]([N:23]2[CH2:24][CH2:25][N:20]([CH3:19])[CH2:21][CH2:22]2)[CH:12]=[CH:11][C:10]=1[N+:16]([O-:18])=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CN1CCNCC1
Reactant: O=[N+]([O-])c1ccc(F)cc1NCc1ccccc1
Solvent: CC#N
Solvent: O
Product: CN1CCN(c2ccc([N+](=O)[O-])c(NCc3ccccc3)c2)CC1
Temperature: 160 °C
Reaction time: 0.67 h

Procedure:
Benzyl-(5-fluoro-2-nitro-phenyl)-amine E-1.1″ (2.000 g; 6.579 mmol) is dissolved in acetonitril (10.000 ml). N-Methylpiperazine (1.460 ml; 13.158 mmol) is then added. The reaction mixture is stirred for 40 min at 160° C. in a Biotage XP Sixty microwave. The reaction mixture is poured into water and extracted with 3×50 ml DCM. The combined organic layer is dried over MgSO4 and concentrated under reduced pressure. The residue is used in the next step without further purification.
Reaction SMILES: [NH2:1](=S)[NH2:2].[C:4]([OH:7])(=O)[CH3:5].[C:8]1(C)[CH:13]=[CH:12]C=[CH:10][CH:9]=1>C1(C)C(C)=CC=CC=1>[NH:1]1[C:10]2[CH:5]([CH2:12][CH2:13][CH2:8][CH:9]=2)[C:4](=[O:7])[NH:2]1
Reactant: Cc1ccccc1
Reactant: CC(=O)O
Solvent: Cc1ccccc1C
Product: O=C1NNC2=CCCCC12

Procedure:
The aminosulfide (IV) is then reacted with concentrated hydrochloric acid at a temperature of 0° to 40° C., followed by reacting the resultant hydrochloride with 1.0 to 1.5 equivalents of sodium nitrite at -10° to 5° C. to form the diazonium salt. The diazonium salt is reduced with 3.0 to 10 equivalents (in regard to the aminosulfide (IV)) of stannous chloride at 0° to -40° C. to obtain the hydrazine hydrochloride, which is neutralized with an aqueous alkaline solution (e.g. sodium hydroxide, potassium hydroxide, potassium carbonate) to obtain the hydrazine sulfide (V). The thus obtained hydrazine sulfide (V) is reacted with 1.0 to 1.2 equivalents of 2-alkoxycarbonylcyclohexanone in a solvent (e.g. acetic acid, toluene, xylene) at a temperature of 50° to 200° C. (preferably 80° to 150° C.) optionally while dehydration by azeotropic distillation or in the presence of molecular sieve is conducted to give the hexahydroindazol-3-one (II).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:10](=[O:11])[O:9][CH2:8][C:5]2=[N:6][CH:7]=1.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1.C[O-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>>[Cl:1][C:2]1[CH:7]=[N:6][C:5]([CH2:8][O:19][C:16]2[CH:17]=[CH:18][C:13]([Cl:12])=[CH:14][CH:15]=2)=[C:4]([CH:3]=1)[C:10]([OH:9])=[O:11]
Reactant: Oc1ccc(Cl)cc1
Reactant: O=C1OCc2ncc(Cl)cc21
Agent: C[O-]
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [Na+]
Product: O=C(O)c1cc(Cl)cnc1COc1ccc(Cl)cc1
Temperature: 130 °C
Yield: 58.3 %

Procedure:
A mixture of 3-chlorofuro[3,4-b]pyridin-5(7H)-one (step 1, 110 mg, 0.65 mmol) and 4-chloro phenol (416 mg, 3.24 mmol) was heated to 130° C. under N2, then sodium methoxide (28% methanol solution, 250 mg, 1.30 mmol) was added dropwise to the mixture at 130° C. The mixture was heated at the same temperature for 4 hours. After cooling, to the mixture was added 10% aqueous citric acid and the mixture was extracted with ethyl acetate. The extracts were dried over sodium sulfate and evaporated. The residue was purified by flash column chromatography on silica gel to afford 113 mg of the title compound:
Reaction SMILES: [CH2:1]([CH:5]1[CH2:11][C:10](=[O:12])[O:9][C:7](=[O:8])[CH2:6]1)[CH:2]([CH3:4])[CH3:3].[CH:13]1([SH:19])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1>>[CH:13]1([S:19][C:10]([CH2:11][C@H:5]([CH2:1][CH:2]([CH3:3])[CH3:4])[CH2:6][C:7]([OH:9])=[O:8])=[O:12])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1
Reactant: SC1CCCCC1
Reactant: CC(C)CC1CC(=O)OC(=O)C1
Product: CC(C)C[C@H](CC(=O)O)CC(=O)SC1CCCCC1

Procedure:
A schematic of the catalytic enantioselective thiolysis of 3-isobutylglutaric anhydride using cyclohexane thiol to afford (R)-3-cyclohexylsulfanylcarbonylmethyl-5-methyl-hexanoic acid is provided in FIG. 1. Thiolysis of 3-isobutylglutaric anhydride in methyltertbutylether (MTBE), at room temperature (rt) in the presence of catalytic quantities of C1 affords 3-cyclohexylsulfanylcarbonylmethyl-5-methyl-hexanoic acid in quantitative yield with the (R) enantiomer obtained in 93% ee.
Reaction SMILES: [CH3:1][N:2]([CH3:35])[CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:34])/[C:14](/[C:24]2[CH:29]=[CH:28][C:27]([O:30]COC)=[CH:26][CH:25]=2)=[C:15](/[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)\[CH2:16][CH3:17])=[CH:8][CH:7]=1.Cl.C([O-])(O)=O.[Na+]>CO.O1CCOCC1.O>[CH3:35][N:2]([CH3:1])[CH2:3][CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]([NH:12][C:13](=[O:34])/[C:14](/[C:24]2[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=2)=[C:15](/[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)\[CH2:16][CH3:17])=[CH:10][CH:11]=1
Reactant: CC/C(=C(\C(=O)Nc1ccc(OCCN(C)C)cc1)c1ccc(OCOC)cc1)c1ccccc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Solvent: CO
Product: CC/C(=C(\C(=O)Nc1ccc(OCCN(C)C)cc1)c1ccc(O)cc1)c1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 89 %

Procedure:
To a solution of 4 (2.89 g, 6.09 mmol) in MeOH (40 ml) was added 4N HCl in 1,4-dioxane (15.2 ml) under ice cooling, and the mixture was stirred at room temperature for 2 h. A solution of NaHCO3 in H2O was poured into the reaction mixture under ice cooling, and the whole was extracted with AcOEt. The organic layer was washed with brine, dried over Na2SO4, and then concentrated. The residual solid was triturated with AcOEt to give 5 (89%).
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[C:5]([C:7]([N:9]2[CH2:14][C@H:13]3[C@H:11]([CH2:12]3)[C@H:10]2[CH2:15][NH2:16])=[O:8])[N:6]=1.[CH3:24][N:25]1[C:29]([C:30](O)=[O:31])=[CH:28][C:27]([CH3:33])=[N:26]1>>[NH2:1][C:2]1[S:3][C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[C:5]([C:7]([N:9]2[CH2:14][C@H:13]3[C@H:11]([CH2:12]3)[C@H:10]2[CH2:15][NH:16][C:30]([C:29]2[N:25]([CH3:24])[N:26]=[C:27]([CH3:33])[CH:28]=2)=[O:31])=[O:8])[N:6]=1
Reactant: Cc1cc(C(=O)O)n(C)n1
Reactant: NC[C@@H]1[C@H]2C[C@H]2CN1C(=O)c1nc(N)sc1-c1cccc(F)c1
Product: Cc1cc(C(=O)NC[C@@H]2[C@H]3C[C@H]3CN2C(=O)c2nc(N)sc2-c2cccc(F)c2)n(C)n1

Procedure:
prepared by reaction of [2-Amino-5-(3-fluoro-phenyl)-thiazol-4-yl]-((1S,2S,5R)-2-aminomethyl-3-aza-bicyclo[3.1.0]hex-3-yl)-methanone with 2,5-Dimethyl-2H-pyrazole-3-carboxylic acid. LC-MS (basic): tR=0.73 min; [M+H]+=455.3.
Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@H:5]([C@H:7]([C@@H:9]([C:11]([OH:13])=[O:12])[OH:10])[OH:8])[OH:6])[OH:4].[O:14]=C[C@@H]([C@H]([C@H]([C@@H](C(O)=O)O)O)O)O.O=C[C@@H]([C@H]([C@H]([C@@H](C(O)=O)O)O)O)O>>[C@H:5]([OH:6])([C@H:3]([OH:4])[C:2]([OH:14])=[O:1])[C@H:7]([OH:8])[C@@H:9]([OH:10])[C:11]([OH:13])=[O:12]
Reactant: O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(=O)O
Product: O=C(O)[C@@H](O)[C@H](O)[C@H](O)[C@@H](O)C(=O)O

Procedure:
Since D-galacturonic acid is a cheap raw material, which is enriched in sugar beet pulp and citrus fruit peel, a method for catabolizing D-galacturonic acid (D-galacturonate) is needed. In particular, a cheap method for producing mucic acid is needed.
Reaction SMILES: C[O:2][C:3](=[O:32])[C:4]1[C:5](=[CH:10][C:11]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[C:12]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=2[O:23][CH3:24])[CH:13]=1)[C:6]([O:8]C)=[O:7].CO.O.[OH-].[Li+].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>O>[NH:25]([C:11]1[CH:10]=[C:5]([C:6]([OH:8])=[O:7])[C:4](=[CH:13][C:12]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=1[O:23][CH3:24])[C:3]([OH:32])=[O:2])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: COC(=O)c1cc(Nc2ccccc2)c(Nc2ccc(OC)cc2OC)cc1C(=O)OC
Agent: O=C1O[C@H]([C@@H](O)CO)C([O-])=C1O
Agent: [Li+]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: COc1ccc(Nc2cc(C(=O)O)c(C(=O)O)cc2Nc2ccccc2)c(OC)c1
Temperature: 25 °C

Procedure:
A steady stream of argon is passed through a suspension of 479 mg (1.09 mmol) of 4-anilino-5-(2,4-dimethoxy-anilino)phthalic acid dimethylester in3.6 ml of methanol, and a solution of 205 mg (4.905 mmol, 4.5 eq) of lithium hydroxide monohydrate and 10 mg sodium ascorbate in 1.7 ml of water is added. The reaction mixture is heated to reflux for 4 hours, cooled to RT, and the methanol is removed by evaporation. The resulting mixture is poured onto 20 ml of 4N hydrochloric acid, the red suspension is filtered and the crystals are washed with washed with isopropanol/hexane 1:5 to yield the title compound in the form of red crystals, TLC (dichloromethane/methanol 7:3) Rf =0.33.
Reaction SMILES: [CH3:1][N:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][NH:20][C:21](=[O:23])[CH3:22])[O:16][C:15]3=[O:24])=[CH:10][CH:9]=2)=[CH:4][C:3]1=[O:25]>CO.[Pd]>[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[CH2:18][C@H:17]([CH2:19][NH:20][C:21](=[O:23])[CH3:22])[O:16][C:15]3=[O:24])=[CH:10][CH:9]=2)[CH2:4][C:3]1=[O:25]
Reactant: CC(=O)NC[C@H]1CN(c2ccc(-c3ccn(C)c(=O)c3)cc2)C(=O)O1
Agent: [Pd]
Solvent: CO
Product: CC(=O)NC[C@H]1CN(c2ccc(C3CCN(C)C(=O)C3)cc2)C(=O)O1
Reaction time: 16 h
Yield: 97.5 %

Procedure:
To a mixture of N-({(5S)-3-[4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide (0.170 g. 0.49 mmol) in 20 mL of MeOH is added 0.05 g of 10% palladium on activated charcoal. The mixture is hydrogenated at 50 psi for 16 hours. The reaction mixture is filtered through celite, silica is added and the mixture is concentrated to dryness. The residue is loaded onto a SIM and purified on a Biotage 12S column with 2% MeOH in CH2Cl2 to yield the desired compound (0.165 g, 96%). 1H-NMR (DMSO) δ: 8.25, 7.48, 7.28, 4.70, 4.10, 3.72, 3.40, 3.29, 3.05, 2.84, 2.39, 1.93, 1.83.
Reaction SMILES: [C:1]([CH:3]([C:9]1[C:14]([N+:15]([O-])=O)=[CH:13][CH:12]=[C:11]([O:18][CH3:19])[N:10]=1)[CH2:4][C:5]([O:7][CH3:8])=[O:6])#N.C1CC=CCC=1>[Pd].CO>[CH3:19][O:18][C:11]1[N:10]=[C:9]2[C:3]([CH2:4][C:5]([O:7][CH3:8])=[O:6])=[CH:1][NH:15][C:14]2=[CH:13][CH:12]=1
Reactant: COC(=O)CC(C#N)c1nc(OC)ccc1[N+](=O)[O-]
Agent: [Pd]
Solvent: C1=CCC=CC1
Solvent: CO
Product: COC(=O)Cc1c[nH]c2ccc(OC)nc12
Temperature: 120 °C

Procedure:
A 2 mL microwave process vial with a stir bar was charged with crude methyl 3-cyano-3-(6-methoxy-3-nitropyridin-2-yl)propanoate (50 mg, 0.19 mmol), 10% Pd/C (5 Mol %, 20 mg, 0.01 mmol), and methanol (1.5 mL). An excess of 1,4-cyclohexadiene (91 mg, 1.13 mmol) was added and the vessel flooded with argon, capped and heated under microwave conditions at 120° C. for 5 min. The reaction was filtered through CELITE® and the solvent was evaporated in vacuo. The crude material was purified by flash chromatography (SiO2, ethyl acetate/hexane gradient) to yield the product as colorless oil. C11H12N2O3, Mr=220.22; 1H NMR (400 MHz, DMSO-d6) d: 3.61 (s, 3H), 3.72 (s, 2H), 3.83 (s, 3H), 6.53 (d, J=8.8 Hz, 1H), 7.38 (d, J=2.8 Hz, 1H), 7.66 (d, J=8.4 Hz, 1H), 11.01 (bs, 1H); 13C NMR (100 MHz, DMSO-d6) d: 29.41 (s, —CH2—), 51.86 (s, —C(O)OCH3), 52.83 (s, —OCH3), 104.86 (s, C6′), 107.19 (s, C3′), 122.78 (s, C2′), 124.60 (s, C7a′), 126.80 (s, C7′), 141.29 (s, C3a′), 159.16 (s, C5′), 172.47 (s, >C═O); LCMS (ESI) tR: 0.69 min (>97%, UV220, ELSD), m/z: 221.2 [M+1]+.
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].C(=O)(OC)[O:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:8]=1[CH3:14]>S(=O)(=O)(O)O>[F:13][C:10]1[C:11]([N+:1]([O-:4])=[O:2])=[CH:12][C:7]([OH:6])=[C:8]([CH3:14])[CH:9]=1
Reactant: COC(=O)Oc1ccc(F)cc1C
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Product: Cc1cc(F)c([N+](=O)[O-])cc1O
Temperature: 0 °C
Reaction time: 2 h
Yield: 22 %

Procedure:
A mixture of concentrated nitric acid (6 ml) and concentrated sulphuric acid (6 ml) was added slowly to a solution of 4-fluoro-2-methylphenyl methyl carbonate (11.34 g, 62 mmol) in concentrated sulphuric acid (6 ml) such that the temperature of the mixture was kept below 50° C. The mixture was stirred for 2 hours, then ice/water was added and the precipitated product collected by filtration. The crude product was purified by chromatography on silica eluting with methylene chloride/hexane progressing through increasingly polar mixtures to methanol/methylene chloride (1:19) to give 4-fluoro-2-methyl-5-nitrophenol (2.5 g, 22%) as a solid.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[N+:9]([C:12]1[CH:20]=[CH:19][C:15]([C:16](O)=[O:17])=[CH:14][CH:13]=1)([O-:11])=[O:10]>>[N+:9]([C:12]1[CH:13]=[CH:14][C:15]([C:16]([NH:6][C:5]2[CH:7]=[CH:8][C:2]([Cl:1])=[CH:3][CH:4]=2)=[O:17])=[CH:19][CH:20]=1)([O-:11])=[O:10]
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Reactant: Nc1ccc(Cl)cc1
Product: O=C(Nc1ccc(Cl)cc1)c1ccc([N+](=O)[O-])cc1
Yield: 98.7 %

Procedure:
Using 4-chloroaniline (1.42 g, 11.0 mmol) and 4-nitrobenzoic acid (1.76 g, 10.4 mmol), the procedure of Reference Example 16 was repeated to obtain 2.84 g (98.5%) of the title compound in the form of yellow crystals.
Reaction SMILES: [SH:1][C:2]1[NH:3][C:4]2[CH:10]=[C:9]([O:11][C:12]([F:15])([F:14])[F:13])[CH:8]=[CH:7][C:5]=2[N:6]=1.[H-].[Na+].[N+]([C:21]1[O:25][C:24]([CH:26]=[O:27])=[CH:23][CH:22]=1)([O-])=O>O1CCCC1>[F:14][C:12]([F:15])([F:13])[O:11][C:9]1[CH:8]=[CH:7][C:5]2[NH:6][C:2]([S:1][C:21]3[O:25][C:24]([CH:26]=[O:27])=[CH:23][CH:22]=3)=[N:3][C:4]=2[CH:10]=1
Reactant: O=Cc1ccc([N+](=O)[O-])o1
Reactant: FC(F)(F)Oc1ccc2nc(S)[nH]c2c1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=Cc1ccc(Sc2nc3cc(OC(F)(F)F)ccc3[nH]2)o1
Temperature: 25 °C
Reaction time: 2 h
Yield: 62.3 %

Procedure:
A solution of 2-mercapto-5-trifluoromethoxy-benzimidazole (1.26 g, 5.38 mmol) in tetrahydrofuran (10 ml) is added dropwise to a mixture of sodium hydride (60% dispersion in mineral oil, 0.344 g, 8.61 mmol) and tetrahydrofuran (5 ml) at 0° C. The mixture is stirred at room temperature for 2 hours. A solution of 5-nitro-2-furaldehyde (0.76 g, 5.38 mmol) in tetrahydrofuran (15 ml) is then added dropwise over a 15 minute period and the mixture is stirred for 16 hours at room temperature. The reaction mixture is concentrated under reduced pressure and the residue is dissolved in 10 ml of dichloromethane and filtered through a silica gel plug (40 ml). The silica gel plug is eluted with 800 ml of cylohexane/ethyl acetate (7/3, v/v). The organic filtrates are combined and concentrated under reduced pressure to yield 1.1 g of 5-(5-trifluoromethoxy-1H-benzoimidazol-2-ylsulfanyl)-furan-2-carbaldehyde as an oil. Yield=62%. Analytical LC/MS (method B): retention time=3.77 min., m/z=329.0 (positive ion mode).
Reaction SMILES: [CH3:1][S:2]([CH2:5][CH2:6][CH2:7][CH2:8][C:9]([O:11][CH3:12])=[O:10])(=[NH:4])=[O:3].[I:13][C:14]1[C:15]([NH2:23])=[N:16][CH:17]=[C:18]([CH:22]=1)[C:19](O)=[O:20].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[NH2:23][C:15]1[N:16]=[CH:17][C:18]([C:19]([N:4]=[S:2]([CH2:5][CH2:6][CH2:7][CH2:8][C:9]([O:11][CH3:12])=[O:10])([CH3:1])=[O:3])=[O:20])=[CH:22][C:14]=1[I:13]
Reactant: Nc1ncc(C(=O)O)cc1I
Reactant: COC(=O)CCCCS(C)(=N)=O
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COC(=O)CCCCS(C)(=O)=NC(=O)c1cnc(N)c(I)c1
Temperature: 70 °C
Yield: 50.3 %

Procedure:
A solution of methyl 5-(S-methylsulfonimidoyl)pentanoate (2.32 g) was dissolved in anhydrous DMF (30 mL) and to this solution was added 5-iodo-6-amino-nicotinic acid (3.17 g, ˜1 eq), diisopropylethylamine (4.2 mL, 2 eq), and BOP (5.85 g, 1.1 eq). The reaction mixture was heated at 70° C. for 1 hour and then partitioned between EtOAc and aq NH4Cl. The organic layer was separated, washed sequentially with aq NH4Cl (1×), saturated aq NaHCO3 (1×), brine (1×), and dried with anhydrous Na2SO4 overnight. The upper solution layer was decanted, concentrated, and the brown oily reside was subject to column chromatography (acetone-CHCl3 1:100 to MeOH-acetone-CHCl3 1:2:50). Concentration of the product eluting fractions provided the title compound as a slight yellow colored foam (2.65 g).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6](Cl)[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1.[Na].[CH2:13]([OH:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>>[NH2:1][C:2]1[N:7]=[C:6]([O:20][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1
Reactant: Nc1ncc([N+](=O)[O-])c(Cl)n1
Reactant: OCc1ccccc1
Agent: [Na]
Product: Nc1ncc([N+](=O)[O-])c(OCc2ccccc2)n1
Temperature: 130 °C
Reaction time: 0.17 h

Procedure:
2-Amino-4-chloro-5-nitropyrimidine (0.70 g, 4.0 mmol) was added to a solution of sodium (0.12 g, 5.2 mmol) in benzyl alcohol (8 mL) under argon. The solution was heated in a 130° C. oil bath for 3 h, and approximately half of the benzyl alcohol was evaporated under reduced pressure. The residue was poured into water (50 mL) with constant stirring for 10 min. After neutralization with glacial acetic acid, a brown precipitate formed which was collected by filtration and washed with water. This solid was crystallized from benzene to give 5a as a golden crystalline solid: yield, 126 mg (13%); mp 164-167° C.; UV (pH 1) λmax 262 nm (ε=0.879×104), 295 (sh) (0.571×104); (pH 6.9) 235 (sh) (0.448×104), 273 (0.360×104), 326 (1.085×104); (pH 13) 273 (0.404×104), 327 (1.055×104); 1H NMR δ 5.51 (s, 2H, ArCH2), 7.35-7.54 (m, 5H, ArH), 8.05 (d, 2H, NH2, exchange with D2O), 8.92 (s, 1H, H-6); MS (EI) calcd. m/z for C11H10N4O3 246.0752, found 246.075; Anal. (C11H10N4O3) C, H, N.
Reaction SMILES: [C:1]([O:4][CH:5]([CH2:7][CH2:8][CH2:9][OH:10])[CH3:6])(=[O:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC([O-])=O.[F:40][C:41]([F:62])([F:61])[C:42]([C:51]1[CH:56]=[CH:55][C:54](O)=[C:53]([CH2:58][CH2:59][CH3:60])[CH:52]=1)([O:47][CH2:48][O:49][CH3:50])[C:43]([F:46])([F:45])[F:44]>O1CCCC1>[C:1]([O:4][CH:5]([CH2:7][CH2:8][CH2:9][O:10][C:54]1[CH:55]=[CH:56][C:51]([C:42]([O:47][CH2:48][O:49][CH3:50])([C:43]([F:46])([F:45])[F:44])[C:41]([F:40])([F:61])[F:62])=[CH:52][C:53]=1[CH2:58][CH2:59][CH3:60])[CH3:6])(=[O:3])[CH3:2]
Reactant: CC(=O)OC(C)CCCO
Reactant: CCCc1cc(C(OCOC)(C(F)(F)F)C(F)(F)F)ccc1O
Agent: CCOC(=O)N=NC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCCc1cc(C(OCOC)(C(F)(F)F)C(F)(F)F)ccc1OCCCC(C)OC(C)=O
Yield: 84.7 %

Procedure:
5-Hydroxypent-2-yl acetate (58.5 mg), triphenylphosphine (131 mg) and ethyl azodicarboxylate (2.2 mol/L, 200 μL) were added to a mixed solution of 4-[1,1,1,3,3,3-hexafluoro-2-(methoxymethyl)oxypropan-2-yl]-2-propylphenol (69.3 mg, 200 μmol) in tetrahydrofuran (2 mL) at room temperature. After completion of the reaction, the solvent was evaporated, and the residue was purified by silica gel preparative thin-layer chromatography (hexane:ethyl acetate=5:1) to obtain 80.4 mg of the title compound (yield: 85%) as a colorless oil.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[C:5]#[N:6].[F:10][C:11]1[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][C:12]=1B1OC(C)(C)C(C)(C)O1>>[F:10][C:11]1[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][C:12]=1[C:2]1[CH:9]=[CH:8][CH:7]=[C:4]([C:5]#[N:6])[CH:3]=1
Reactant: CC1(C)OB(c2cc([N+](=O)[O-])ccc2F)OC1(C)C
Reactant: N#Cc1cccc(Br)c1
Product: N#Cc1cccc(-c2cc([N+](=O)[O-])ccc2F)c1

Procedure:
3-Bromobenzonitrile and 2-(2-fluoro-5-nitrophenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane were coupled using the procedure described in Example 1 to afford 2′-fluoro-5′-nitrobiphenyl-3-carbonitrile as a brown solid: δH (360 MHz, DMSO) 7.33-7.40 (2H, m), 7.46-7.55 (2H, m), 7.61 (1H, ddd, J 8, 8 and 2), 7.96-8.01 (1H, m), 8.61 (1H, dd, J 5 and 2), 8.77 (1H, s).