Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8](Cl)([Cl:10])[Cl:9])[N:3]=1.CO.Cl.ClC1C=CC=C(CCl)N=1>[Fe].C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH:8]([Cl:10])[Cl:9])[N:3]=1
Reactant: Clc1cccc(C(Cl)(Cl)Cl)n1
Agent: [Fe]
Agent: Cl
Agent: ClCc1cccc(Cl)n1
Solvent: CO
Solvent: ClCCl
Product: Clc1cccc(C(Cl)Cl)n1
Temperature: 70 °C
Reaction time: 0.08 h
Yield: 90.1 %

Procedure:
Into a 250 milliliter (ml) flask fitted with a condenser, magnetic stirrer and dropping funnel were added 46.2 grams (g) (0.20 mole) of 2-chloro-6(trichloromethyl)pyridine, 30 g of methanol and 9.1 g (0.16 mole) of 20 mesh iron filings. The mixture was heated to 70° C. and 30 g of concentrated hydrochloric acid was added thereto over a 5 minute period. A slight exotherm occurred and the mixture was heated and maintained under reflux (83°-86° C.) for 1 hour. The reaction mixture was cooled to 45° C., and 50 ml of methylene chloride was added thereto. The mixture was filtered through diatomaceous earth and the filter cake washed thoroughly with water and then with methylene chloride. The filtrates were combined and the methylene chloride phase separated from the water phase. The product from a second run was combined with the above product mix and the mixture concentrated to a pot temperature of 95° C. at 15 millimeters of mercury (mm Hg). This residue was present in an amount of 74.5 g and melted at 48°-52° C. Analysis by gas-liquid chromatography (glc) showed a yield of 90.1 percent 2-chloro-6-(dichloromethyl)pyridine, 3.7 percent 2-chloro-6-(chloromethyl)pyridine and 1.7 percent 2 -chloro-6-(trichloromethyl)pyridine. The 2-chloro-6-(dichloromethyl)pyridine was recovered by recrystallization from heptane and melted at 53.3°-54.0° C.
Reaction SMILES: [CH:1]1([N:7]([C:9]2[CH:14]=[CH:13][C:12]([C@@H:15]3[O:20][CH2:19][CH2:18][NH:17][CH2:16]3)=[CH:11][CH:10]=2)[CH3:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.Cl[C:29]1[N:34]([CH3:35])[C:33](=[O:36])[CH:32]=[C:31]([C:37]2[CH:42]=[CH:41][N:40]=[CH:39][CH:38]=2)[N:30]=1.ClC1C=CNC(=O)N=1>O1CCCC1>[CH:1]1([N:7]([C:9]2[CH:14]=[CH:13][C:12]([C@@H:15]3[O:20][CH2:19][CH2:18][N:17]([C:29]4[N:34]([CH3:35])[C:33](=[O:36])[CH:32]=[C:31]([C:37]5[CH:38]=[CH:39][N:40]=[CH:41][CH:42]=5)[N:30]=4)[CH2:16]3)=[CH:11][CH:10]=2)[CH3:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: Cn1c(Cl)nc(-c2ccncc2)cc1=O
Reactant: CN(c1ccc([C@H]2CNCCO2)cc1)C1CCCCC1
Agent: O=c1nc(Cl)cc[nH]1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CN(c1ccc([C@H]2CN(c3nc(-c4ccncc4)cc(=O)n3C)CCO2)cc1)C1CCCCC1
Yield: 75.6 %

Procedure:
To a solution of (2S)-2-(4-(N-cyclohexyl-N-methylamino)phenyl)morpholine (4.47 g, 16.30 mmol) and triethylamine (3.1 ml, 22.2 mmol) in tetrahydrofuran (50 ml) was added 2-chloro-3-methyl-6-(4-pyridyl)-3H-pyrimidin-4-one (3.28 g, 14.82 mmol) portionwise. Upon disappearance of the chloropyrimidone, the reaction mixture was condensed under reduced pressure. The residue was partitioned between 1 N sodium hydroxide and dichloromethane. The organic layer was washed with water, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give a pale yellow solid, which was recrystallized from ethanol to afford 2-((2S)-2-(4-(N-cyclohexyl-N-methylamino)-phenyl)morpholin-4-yl)-3-methyl-6-(4-pyridyl)-pyrimidin-4-one (5.15 g, 75.7%) as white crystals.
Reaction SMILES: [N:1]([CH:4]([C:6]1[N:7]=[C:8]2[S:21][CH:20]=[C:19]([CH3:22])[N:9]2[C:10](=[O:18])[C:11]=1[C:12]1[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=1)[CH3:5])=[N+]=[N-].CP(C)C.C(OCC)(=O)C>O1CCCC1.O>[NH2:1][CH:4]([C:6]1[N:7]=[C:8]2[S:21][CH:20]=[C:19]([CH3:22])[N:9]2[C:10](=[O:18])[C:11]=1[C:12]1[CH:13]=[CH:14][N:15]=[CH:16][CH:17]=1)[CH3:5]
Reactant: Cc1csc2nc(C(C)N=[N+]=[N-])c(-c3ccncc3)c(=O)n12
Agent: CP(C)C
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: Cc1csc2nc(C(C)N)c(-c3ccncc3)c(=O)n12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred solution of 7-(1-azidoethyl)-3-methyl-6-pyridin-4-yl-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one (0.050 g, 0.16 mmol) in tetrahydrofuran (0.5 mL) and water (0.12 mL) was added 1.00 M of trimethylphosphine in tetrahydrofuran (0.19 mL, 0.19 mmol) at room temperature and the mixture was stirred at room temperature for 1 hour. To the mixture was added ethyl acetate (EtOAc) and the mixture was extracted with 1N HCl two times. The combined extracts were neutralized with solid sodium bicarbonate, and extracted with dichloromethane. The combined organic layers were washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue, shown two peaks with same desired mass, was used directly in next step. LCMS calculated for C14H15N4OS (M+H)+: m/z=287.1. Found: 287.0.
Reaction SMILES: Br[C:2]([F:19])([F:18])[S:3]([C:6]1[N:10]=[CH:9][N:8]([C:11](=[O:17])[N:12]([CH2:15][CH3:16])[CH2:13][CH3:14])[N:7]=1)(=[O:5])=[O:4].[CH2:20]([S:22]SCC)[CH3:21].P([O-])([O-])(O)=O.[Na+].[Na+].S(S([O-])=O)([O-])=O.[Na+].[Na+]>CN(C)C=O.O>[CH2:13]([N:12]([CH2:15][CH3:16])[C:11]([N:8]1[CH:9]=[N:10][C:6]([S:3]([C:2]([F:19])([F:18])[S:22][CH2:20][CH3:21])(=[O:5])=[O:4])=[N:7]1)=[O:17])[CH3:14]
Reactant: CCN(CC)C(=O)n1cnc(S(=O)(=O)C(F)(F)Br)n1
Reactant: CCSSCC
Agent: O=P([O-])([O-])O
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCSC(F)(F)S(=O)(=O)c1ncn(C(=O)N(CC)CC)n1
Reaction time: 2 h
Yield: 56.8 %

Procedure:
To a stirred solution of 10 g (0.028 mol) 3-(bromodifluoromethylsulfonyl)-1-(N,N-diethylcarbamoyl)-1,2,4-triazole (as prepared in Example 1) and 6.81 ml (0.055 mol) diethyl disulfide in a mixture of 30 ml N,N-dimethylformamide and 20 ml water at 0° C. was added 5.9 g (0.042 mol) sodium hydrogen phosphate and 7.23 g (0.042 mol) sodium dithionite. After 2 h, the reaction mixture was diluted with 100 ml water and extracted with ethyl acetate (3×100 ml). The combined resulting organic layers were washed with saturated sodium chloride solution, dried over MgSO4 and evaporated. Preparative LC purification of the residue with 40% ethyl acetate-hexane gave 5.45 g (57% yield) of the desired 1-(N,N-diethylcarbamoyl)-3-[difluoro(ethylthio)methylsulfonyl]-1,2,4-triazole as a colorless oil having n D 25 = 1.5063 .
Reaction SMILES: [CH2:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17].ClC1C=CC=C(C(OO)=[O:26])C=1>ClCCl>[O:26]1[CH:2]([CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH2:1]1
Reactant: C=CCCCCCCCCCCCCCCC
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CCCCCCCCCCCCCCCC1CO1
Temperature: 25 °C
Reaction time: 8 h
Yield: 57.2 %

Procedure:
In 100 ml of dichloromethane was dissolved 26.2 g (0.11 mole) of 1-heptadecene, and a solution of 24.5 g of m-chloroperbenzoic acid in 250 ml of dichloromethane was added dropwise to the solution. The mixture was stirred at room temperature overnight. The resulting crystalline precipitate was filtered off and the filtrate was washed with water, aqueous sodium sulfite, aqueous sodium hydrogen carbonate and aqueous sodium chloride, dried and concentrated. The residue was purified by silica gel column chromatography [eluent: hexane-ethyl acetate (30:1)] to give 16 g of the desired compound as a colorless oil.
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[CH2:7][CH2:6]2.[Cl-].[Al+3].[Cl-].[Cl-].O>C1(C)C=CC=CC=1>[OH:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[CH2:7][CH2:6]2
Reactant: COc1ccc2c(c1)CCC2=O
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: Cc1ccccc1
Product: O=C1CCc2cc(O)ccc21
Temperature: 25 °C

Procedure:
A suspension of 5-methoxy-1-indanone (10.3 g, 63.5 mmol) in toluene (150 mL) was ice-cooled, and aluminum chloride (16.9 g, 127 mmol) was added by small portions, and the mixture was heated under reflux under nitrogen atmosphere for 4 hr. The reaction mixture was allowed to cool to room temperature and poured into iced water. The organic product was extracted with a mixed solvent of ethyl acetate and tetrahydrofuran. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 5-hydroxy-1-indanone as yellow crystals.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:17]3[C:12](=[CH:13][C:14]([F:20])=[C:15](F)[C:16]=3[Br:18])[C:11](=[O:21])[C:10]([C:22]([OH:24])=[O:23])=[CH:9]2)[C:5]([F:25])=[CH:4][C:3]=1[F:26].[CH3:27][NH2:28]>N1C=CC=CC=1>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:17]3[C:12](=[CH:13][C:14]([F:20])=[C:15]([NH:28][CH3:27])[C:16]=3[Br:18])[C:11](=[O:21])[C:10]([C:22]([OH:24])=[O:23])=[CH:9]2)[C:5]([F:25])=[CH:4][C:3]=1[F:26]
Reactant: Nc1nc(-n2cc(C(=O)O)c(=O)c3cc(F)c(F)c(Br)c32)c(F)cc1F
Reactant: CN
Solvent: c1ccncc1
Product: CNc1c(F)cc2c(=O)c(C(=O)O)cn(-c3nc(N)c(F)cc3F)c2c1Br
Temperature: 25 °C
Reaction time: 2 h

Procedure:
1-(6-Amino-3,5-difluoropyridin-2-yl)-8-bromo-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (200 mg) and a 40% aqueous solution (230 mg) of methylamine were added to pyridine (620 mag), and the mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure, and ethanol (2 ml) was added to the residue. Deposits were collected by filtration and washed successively with ethanol and diisopropyl ether to obtain the title compound (103 mg) as a colorless powder.
Reaction SMILES: [CH:1]1([C:4]2[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([CH3:14])[CH:5]=2)[CH2:3][CH2:2]1.[I:15]I.S(=O)(=O)(O)O.O>CC(O)=O>[CH:1]1([C:4]2[C:13]([I:15])=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([CH3:14])[CH:5]=2)[CH2:2][CH2:3]1
Reactant: II
Reactant: COC(=O)c1ccc(C2CC2)cc1C
Agent: O=S(=O)(O)O
Solvent: CC(=O)O
Solvent: O
Product: COC(=O)c1cc(I)c(C2CC2)cc1C
Temperature: 110 °C
Reaction time: 8 h
Yield: 47.2 %

Procedure:
To a solution of methyl 4-cyclopropyl-2-methylbenzoate (compound 86.1, 2.68 g, 13.4 mmol, 95%) in AcOH (50 mL) were added NaIO4 (1.51 g, 7.08 mmol), iodine (3.58 g, 14.1 mmol), and sulfuric acid (106 μL, 2.0 mmol, 0.15 equiv). The reaction mixture was stirred overnight at 110° C. After cooling to ambient temperature, water (100 mL) was slowly added and the mixture was extracted with ethyl acetate (100 mL). The organic layer was washed with Na2S2O3 (aq., sat., 3×30 mL) and brine (30 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1/50) as the eluent to yield 2.0 g (45%) of the title compound as a colorless oil.
Reaction SMILES: C(OC([NH:11][CH:12]([CH2:23][CH2:24][P:25]([O:29][C:30]1[CH:35]=[CH:34][C:33]([CH2:36][C:37]([O:39]CC2C=CC=CC=2)=[O:38])=[CH:32][CH:31]=1)([O:27][CH3:28])=[O:26])[C:13]([O:15]CC1C=CC=CC=1)=[O:14])=O)C1C=CC=CC=1.[H][H]>C(O)(=O)C.[C].[Pd]>[NH2:11][CH:12]([CH2:23][CH2:24][P:25]([O:29][C:30]1[CH:31]=[CH:32][C:33]([CH2:36][C:37]([OH:39])=[O:38])=[CH:34][CH:35]=1)([O:27][CH3:28])=[O:26])[C:13]([OH:15])=[O:14]
Reactant: COP(=O)(CCC(NC(=O)OCc1ccccc1)C(=O)OCc1ccccc1)Oc1ccc(CC(=O)OCc2ccccc2)cc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CC(=O)O
Product: COP(=O)(CCC(N)C(=O)O)Oc1ccc(CC(=O)O)cc1
Yield: 63.8 %

Procedure:
Next, 1.25 g (1.94 mmol) of benzyl 2-(N-benzyloxycarbonylamino)-4-{[4-(benzyloxycarbonylmethyl)phenyl] (methyl)phosphono}butanoate was dissolved in 20 mL of acetic acid and mixed with 200 mg of 5% palladium-carbon and hydrogen gas was introduced at room temperature for 3.5 hours. Thereafter, the palladium-carbon was removed by Celite filtration and the filtrate was vacuum-concentrated and the residue was purified by medium pressure reversed-phase chromatography (ODS-S-50B). The column was eluted with a linear gradient of 30 to 60% methanol at a flow rate of 6 mL/min and the fractions of the compound eluted with 60% methanol were collected. The elution and purity of the compound were confirmed by TLC (BuOH/AcOH/H2O=5:2:2, ninhydrin coloration). After vacuum concentration, freeze drying from water were carried out to obtain 2-amino-4-{[4-(carboxymethyl)phenyl](methyl)phosphono}butanoic acid (0.41 g, yield 64%) as a colorless solid.
Reaction SMILES: [CH:1]1[C:14]2[C:5](=[CH:6][C:7]3[C:12]([CH:13]=2)=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH:4]=[CH:3][CH:2]=1.[CH2:15]([Cl:18])[CH:16]=[CH2:17]>C1C=CC=CC=1>[Cl:18][CH2:15][CH:16]1[CH:6]2[C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:12]=3[CH:13]([C:14]3[C:5]2=[CH:4][CH:3]=[CH:2][CH:1]=3)[CH2:17]1
Reactant: C=CCCl
Reactant: c1ccc2cc3ccccc3cc2c1
Solvent: c1ccccc1
Product: ClCC1CC2c3ccccc3C1c1ccccc12
Temperature: 220 °C

Procedure:
Anthracene (75 gm) was combined with allyl chloride (150 gm) and benzene (375 gm) in a Parr bomb and heated to 220° C. for 13 hours. The contents were filtered and the benzene was removed on a rotary evaporator. The residue was recrystallized from ethanol to provide the product as a white solid (mp=108-111° C.).
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([CH2:14][O:15][C:16](=[O:18])[CH3:17])[O:7][C@H:6]1[N:19]1[CH:27]=[N:26][C:25]2[C:20]1=[N:21][C:22](N)=[N:23][C:24]=2[Cl:28])(=[O:3])[CH3:2].C(ON=O)CC(C)C.[CH3:38][S:39]SC>C(#N)C>[C:1]([O:4][C@@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([CH2:14][O:15][C:16](=[O:18])[CH3:17])[O:7][C@H:6]1[N:19]1[CH:27]=[N:26][C:25]2[C:20]1=[N:21][C:22]([S:39][CH3:38])=[N:23][C:24]=2[Cl:28])(=[O:3])[CH3:2]
Reactant: CSSC
Reactant: CC(=O)OC[C@H]1O[C@@H](n2cnc3c(Cl)nc(N)nc32)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: CC(C)CCON=O
Solvent: CC#N
Product: CSc1nc(Cl)c2ncn([C@@H]3O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H]3OC(C)=O)c2n1
Temperature: 100 °C
Yield: 72.6 %

Procedure:
9-(2',3',5'-Tri-O-acetyl-β-D-ribofuranosyl)-2-amino-6-chloro-9H-purine (see Example 9) (4.0 g, 9.3 mmol) was dissolved in acetonitrile (100 ml). Isoamylnitrite (10.84 g, 93 mmol) was introduced followed by methyl disulphide (4.14 ml, 46 mmol) and the reaction mixture was heated at an oil bath temperature of 100° C. for 2h. The evolved gas was removed via a hypochlorite scrubber. The reaction mixture was cooled, evaporated and purified by flash chromatography on silica gel. Elution initially with dichloromethane, followed by dichloro-methane/methanol (100/1) provided 9-(2',3',5'-tri-O-acetyl-β-D-ribofuranosyl)-6-chloro-2-methylthio-9H-purine (3.1 g, 72%) as a foam, 1H NMR (CDCl3) δ 2.12, 2.14, 2.18 (9H, 3s, 2', 3' and 5'-O-acetyl CH3), 2.66 (3H, s, --SCH3), 4.28-4.51 (3H, m, H-5'a, H-5'b and H-4'), 5.66 (1H, t, H-3'), 6.0 (1H, t, H-2'), 6.13 (1H, d, H-1'), 8.11 (1H, s, H-8).
Reaction SMILES: [F:1][C:2]1[CH:60]=[CH:59][C:58]([F:61])=[CH:57][C:3]=1[O:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:22])[CH2:17][CH:16]2[O:31][CH2:32][C:33]2[CH:34]=[CH:35][C:36]3[O:41][CH2:40][C:39](=[O:42])[N:38]([CH2:43][CH2:44][O:45][Si](C(C)C)(C(C)C)C(C)C)[C:37]=3[CH:56]=2)=[CH:11][CH:10]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[F:1][C:2]1[CH:60]=[CH:59][C:58]([F:61])=[CH:57][C:3]=1[O:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][CH2:24][C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)=[O:22])[CH2:17][CH:16]2[O:31][CH2:32][C:33]2[CH:34]=[CH:35][C:36]3[O:41][CH2:40][C:39](=[O:42])[N:38]([CH2:43][CH2:44][OH:45])[C:37]=3[CH:56]=2)=[CH:11][CH:10]=1
Reactant: CC(C)[Si](OCCN1C(=O)COc2ccc(COC3CN(C(=O)OCc4ccccc4)CCC3c3ccc(OCCCOc4cc(F)ccc4F)cc3)cc21)(C(C)C)C(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: O=C(OCc1ccccc1)N1CCC(c2ccc(OCCCOc3cc(F)ccc3F)cc2)C(OCc2ccc3c(c2)N(CCO)C(=O)CO3)C1
Temperature: 60 °C
Reaction time: 0.5 h

Procedure:
The solution of 2.0 g of benzyl 4-{4-[3-(2,5-difluorophenoxy)propoxy]phenyl}-3-[3-oxo-4-(2-triisopropylsilanyloxyethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate in 30 ml of tetrahydrofuran is admixed with 2.30 ml of tetrabutylammonium fluoride solution (1M in tetrahydrofuran) and stirred at 60° C. over 30 minutes. The reaction mixture is cooled, poured onto water (100 ml) and extracted with tert-butyl methyl ether (2×100 ml). The organic phases are washed with brine (1×100 ml), dried over sodium sulphate, filtered and concentrated by evaporation. The title compound is obtained as a white foam from the residue by means of flash chromatography (SiO2 60F). Rf=0.10 (1:1 EtOAc-heptane); Rt=5.43.
Reaction SMILES: CC1C=CC([N+]([O-])=[O:9])=CC=1O.CN(C)CCO.[C:18]1([P:24]([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:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CCOC(/N=N/C(OCC)=O)=O.C1(C)C=CC=CC=1>C1COCC1>[C:31]1([P:24](=[O:9])([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: Cc1ccc([N+](=O)[O-])cc1O
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: CN(C)CCO
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: O=P(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
As another non-limiting example, 2-methyl-5-nitrophenol (2.00 g, 13.07 mmol), N,N-dimethylethanolamine (1.31 mL, 13.07 mmol) and triphenylphosphine (4.46 g, 16.99 mmol) were placed in a 100 mL round-bottomed flask under nitrogen. 40 mL of anhydrous THF were added via syringe at 0° C. After stirring the reaction mixture at this temperature for 10 minutes, 7.32 mL of a solution of diethylazodicarboxylate 40% in toluene (2.93 g, 16.99 mmol) were added via syringe. The reaction was warmed to room temperature and stirred under nitrogen for two hours. The solvents were removed under vacuum. Triphenylphosphine oxide formed during the reaction was precipitated in a mixture of ethyl acetate/hexane and filtrated. The crude was then purified by flash chromatography (0 to 2% of MeOH in DCM) to afford 10 (2.11 g, 70%) as a yellow oil.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[Cl:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10]([C:16]3[C:24]4[C:19](=[CH:20][CH:21]=[C:22]([NH:25]S(C)(=O)=O)[CH:23]=4)[N:18]([CH2:30][C:31]([OH:33])=[O:32])[C:17]=3[CH3:34])=[CH:11][CH:12]=[N:13]2)=[CH:8][CH:7]=1.C(N(CC)CC)C.O>ClCCl>[C:1]([NH:25][C:22]1[CH:23]=[C:24]2[C:19](=[CH:20][CH:21]=1)[N:18]([CH2:30][C:31]([OH:33])=[O:32])[C:17]([CH3:34])=[C:16]2[C:10]1[C:9]2[C:14](=[CH:15][C:6]([Cl:5])=[CH:7][CH:8]=2)[N:13]=[CH:12][CH:11]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Cl
Reactant: Cc1c(-c2ccnc3cc(Cl)ccc23)c2cc(NS(C)(=O)=O)ccc2n1CC(=O)O
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)Nc1ccc2c(c1)c(-c1ccnc3cc(Cl)ccc13)c(C)n2CC(=O)O
Temperature: 20 °C
Reaction time: 1 h

Procedure:
Acetyl chloride (60 μl) was added to a solution of the product from Example 46 step a) and triethylamine (0.13 ml) in dichloromethane (3 ml) at 0° C. and stirred at 20° C. for 1 hour. Water was added and the mixture was extracted with dichloromethane. The organic extracts were dried (MgSO4), evaporated and purified by chromatography (silica, ethyl acetate as eluent) to give the sub-title compound (290 mg). M.p. 281-4° C.
Reaction SMILES: BrC1C=CC=CC=1CBr.[Br:10][C:11]1[CH:20]=[CH:19][CH:18]=[C:17]2[C:12]=1[CH2:13][CH2:14][CH2:15][C:16]2=[O:21].[Se](=O)=[O:23]>>[Br:10][C:11]1[CH:20]=[CH:19][CH:18]=[C:17]2[C:12]=1[CH:13]=[CH:14][C:15](=[O:23])[C:16]2=[O:21]
Reactant: O=C1CCCc2c(Br)cccc21
Reactant: O=[Se]=O
Agent: BrCc1ccccc1Br
Product: O=C1C=Cc2c(Br)cccc2C1=O

Procedure:
2-Bromobenzyl bromide was converted into 5-bromotetralone according to the literature (J. Org. Chem. 1984, p4226). Treatment of 5-bromotetralone with selenium dioxide as described in Referene Example 1A yielded 5-bromo-[1,2]naphthoquinone, which was coupled with 2,3-diamino-benzoic acid, diacetate salt, as described in Reference Example 1A to yield the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:23]=[CH:22][C:5]2[N:6]([C:18]([CH3:21])([CH3:20])[CH3:19])[C:7]([C:9]3[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=3[C:11]([NH2:13])=[O:12])=[N:8][C:4]=2[CH:3]=1>COC(OC)N(C)C>[Br:1][C:2]1[CH:23]=[CH:22][C:5]2[N:6]([C:18]([CH3:19])([CH3:20])[CH3:21])[C:7]([C:9]3[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=3[C:11](/[N:13]=[CH:5]/[N:6]([CH3:18])[CH3:7])=[O:12])=[N:8][C:4]=2[CH:3]=1
Reactant: CC(C)(C)n1c(-c2ccccc2C(N)=O)nc2cc(Br)ccc21
Agent: COC(OC)N(C)C
Product: CN(C)/C=N/C(=O)c1ccccc1-c1nc2cc(Br)ccc2n1C(C)(C)C
Temperature: 110 °C
Reaction time: 3 h
Yield: 200.3 %

Procedure:
To a round bottom flask is added 2-(5-bromo-1-tert-butyl-1H-benzimidazol-2-yl)-benzamide (400 mg, 1.075 mmol) in N,N-dimethylformamide dimethyl acetal (8 mL). The reaction mixture is stirred at 110° C. for 3 hours. The reaction mixture is concentrated to remove all volatile material to afford 2-(5-bromo-1-tert-butyl-1H-benzimidazol-2-yl)-N-[1-dimethylamino-meth-(E)-ylidene]-benzamide (460 mg, 100%) ready for the next step. LCMS (ESMS): m/z 427.68, 429.64 (M++1)
Reaction SMILES: [C:1](#[N:4])[CH:2]=[CH2:3].C[Si]([CH2:9][N:10]=[C:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[SH-]C)(C)C>C1COCC1>[C:14]1([C:11]2[CH2:3][CH:2]([C:1]#[N:4])[CH2:9][N:10]=2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: C=CC#N
Reactant: C[SH-]C(=NC[Si](C)(C)C)c1ccccc1
Solvent: C1CCOC1
Product: N#CC1CN=C(c2ccccc2)C1
Temperature: -5 °C
Reaction time: 0.5 h

Procedure:
A solution of acrylonitrile (0.65 mL; 0.01 mol) and N-(trimethylsilyl)methyl-S-methyl-benzenethioimidate (2.4 g; 0.01 mol) in THF (100 mL) is cooled to -5° C. in an ice-acetone bath. Under a nitrogen purge, a solution of tetrabutylammonium fluoride (1.0 mL of a 1 N solution in THF) and THF (20 mL) is added dropwise over 30 minutes. The solution is stirred another 30 minutes at -5° C., and then allowed to warm slowly to ambient. Stirring is continued another 18 hours, and then solvent is removed under reduced pressure. The residue is partitioned between ether/water and the water layer extracted with fresh ether. The combined organic layer is washed with water, then saturated sodium chloride. The solution is dried over MgSO4, and cooling the filtrate causes precipitation of an off-white solid (1.2 g; 70% theoretical yield) whose spectral characteristics are identical to the material described by Tsuge [J. Org. Chem. 52, 2523 (1987)].
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([Si:11]([CH3:14])([CH3:13])[CH3:12])[C:3]=1[C:4](Cl)=[O:5].[CH2:15]([O:17][CH2:18][CH2:19][NH2:20])[CH3:16]>C1(C)C=CC=CC=1>[CH2:15]([O:17][CH2:18][CH2:19][NH:20][C:4](=[O:5])[C:3]1[C:7]([Si:11]([CH3:14])([CH3:13])[CH3:12])=[CH:8][CH:9]=[CH:10][C:2]=1[Cl:1])[CH3:16]
Reactant: C[Si](C)(C)c1cccc(Cl)c1C(=O)Cl
Reactant: CCOCCN
Solvent: Cc1ccccc1
Product: CCOCCNC(=O)c1c(Cl)cccc1[Si](C)(C)C
Yield: 66.2 %

Procedure:
The compound of Example b (4.94 g, 20 mmol), 2-ethoxyethyl amine (3.92 g, 44 mmol), and toluene (35 mL) were combined according to General Method E1. The crude product was recrystallized from aq ethanol to afford 3.97 g of N-(2-ethoxyethyl)-2-chloro-6-(trimethylsilyl)benzamide as white solid, a 66% yield. m.p. 71-73° C.