Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[C:2]([NH2:5])(=[NH:4])[CH3:3].C([O:8][CH:9]=[C:10]([C:16](OCC)=O)[C:11]([O:13][CH2:14][CH3:15])=[O:12])C>[O-]CC.[Na+].C(O)C.ClCCl>[CH3:3][C:2]1[NH:4][C:9](=[O:8])[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:16][N:5]=1
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Reactant: CC(=N)N
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: ClCCl
Product: CCOC(=O)c1cnc(C)[nH]c1=O
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 26.4 %

Procedure:
Acetamidine hydrochloride (37.16 g, 0.39 mole) was stirred in sodium ethoxide in ethanol (73 mL of a 21% solution, 0.20 mole) for 5 minutes. Diethyl ethoxymethylenemalonate (31.5 mL, 0.15 mole) was added, and the reaction mixture was refluxed for 5 hours. The reaction mixture was allowed to cool to room temperature overnight, and diluted with dichloromethane (100 mL). The solution was filtered, washing the solid cake with dichloromethane. The filtrate was concentrated at reduced pressure. The residue was dissolved in dichloromethane (150 mL) and 2.0N HCl (30 mL). The pH of the aqueous layer was 1. The organic layer was washed with water, saturated sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was dissolved in hot dichloromethane (50 mL). Ethyl acetate was added (50 mL). The product precipitated. The solution was boiled for 5 minutes, cooled to room temperature, and hexanes were added (50 mL). The resulting crystals were filtered, then washed with ethyl acetate (20 mL) followed by hexanes (50 mL) to yield the title compound (7.22 g, 27%) as off-white crystals. Rf =0.27 (silica gel, 10% isopropanol in dichloromethane). The title compound also was prepared by the route described in Example 102.
Reaction SMILES: [C:1]([OH:13])(=O)[CH2:2][NH:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5].C1CCC([N:20]=[C:21]=[N:22]C2CCCCC2)CC1.ON1C(=O)CCC1=O.N#CN.[Na]>C(#N)C.O.CCOC(C)=O.CC(O)=O>[C:4]([NH:3][CH2:2][C:1]([NH:22][C:21]#[N:20])=[O:13])(=[O:5])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: O=C(O)CNC(=O)c1ccccc1
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Agent: N#CN
Agent: O=C1CCC(=O)N1O
Agent: [Na]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Solvent: CC#N
Product: N#CNC(=O)CNC(=O)c1ccccc1
Reaction time: 8 h
Yield: 56.1 %

Procedure:
Hippuric acid (3.58 g, 0.020 mol), DCC (4.13 g, 0.020 mol), and N-hydroxysuccinimide (2.3 g, 0.020 mol) were stirred in 100 ml of acetonitrile at ice bath temperature for 2 hours. The reaction mixture was filtered to remove the bulk of by-product DCU. The filtrate was evaporated in vacuo to dryness, the residue was redissolved in THF and the mixture was filtered to remove any residual DCU. The filtrate (70 ml) was added drop-wise to a solution of sodium cyanamide (3.84 g, 0.060 mol) in 100 ml of distilled water with vigorous stirring at ice bath temperature. The reaction was allowed to proceed at room temperature overnight. The reaction mixture (pH 11) was extracted with ethyl acetate (2×60 ml) and the separated aqueous layer was acidified to pH 1.5 with 10% HCl. The resulting solid suspension was filtered to give 2.28 g (56.1% yield) of white crystalline 10. It was recrystallized from THF/acetonitrile/petroleum ether to yield 0.78 g (crop 1) of white crystalline product. The filtrate was concentrated to yield 0.9 g (crop 2) of additional crystals. Mp dec. > 155° C. (turns to brown oil at 160° C.); TLC: Rf =0.36 in EtOAc/AcOH (100:1), detected by UV quenching and orange color with ferricyanide spray reagent; IR (Nujol, cm-1) 3400 (NH), 3080 (C6H5), 2220 (C≡N), 1710 and 1620 (C=O); NMR (Silanor C and DMSO (1:1), δ from TMS) 8.2-8.4 (broad, NH); 7.3-8.0 (m, C6H5 --), 4.1-4.2 (d, --NH--CH2 --CO). Anal. Calcd for C10H9N3O2 : C, 59.11; H, 4.46; N, 20.68. Found: C, 59.26; H, 4.46; N, 20.84 (crop 1) and C, 59.03; H, 4.20; N, 20.80 (crop 2).
Reaction SMILES: S1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1([N:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1.CN[C@@H:20](C([O-])=O)[CH2:21]C([O-])=O>>[CH:5]1[CH:4]=[CH:3][C:2]([C:6]2([N:12]3[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]3)[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]2)=[CH:20][CH:21]=1
Reactant: CN[C@H](CC(=O)[O-])C(=O)[O-]
Reactant: c1csc(C2(N3CCCCC3)CCCCC2)c1
Product: c1ccc(C2(N3CCCCC3)CCCCC2)cc1

Procedure:
N[1-(2-thienyl)cyclohexyl]piperidine (TCP); N-methyl-D-aspartate (NMDA); D(-)2-amino-5-phosphovaleric acid (AP-5); (+) 5 methyl-10,11 dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (dibenzocycloalkenimine) (MK-801).
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:6]([S:8]([C:11]2[CH:12]=[C:13]([CH:18]=[CH:19][CH:20]=2)[C:14]([O:16][CH3:17])=[O:15])(=[O:10])=[O:9])[CH:7]=1)=O.CO.[CH3:29][NH2:30].[BH4-].[Na+]>>[CH3:29][NH:30][CH2:1][C:3]1[CH:4]=[C:5]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:6]([S:8]([C:11]2[CH:12]=[C:13]([CH:18]=[CH:19][CH:20]=2)[C:14]([O:16][CH3:17])=[O:15])(=[O:10])=[O:9])[CH:7]=1
Reactant: COC(=O)c1cccc(S(=O)(=O)n2cc(C=O)cc2-c2ccccc2)c1
Reactant: CN
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CNCc1cc(-c2ccccc2)n(S(=O)(=O)c2cccc(C(=O)OC)c2)c1
Yield: 48.6 %

Procedure:
Using methyl 3-[(4-formyl-2-phenyl-1H-pyrrol-1-yl)sulfonyl]benzoate (1.32 g), 40% methylamine methanol solution (416 mg) and sodium borohydride (100 mg), a procedure as in Reference Example 145 was performed to give the title compound as a pale-yellow oil (yield 668 mg, 49%).
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:7](Br)=[CH:6][C:3]=1[C:4]#[N:5].C(=O)([O-])[O-].[Na+].[Na+].[C:17]1(B(O)O)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(OCC)(=O)C>O1CCOCC1.O>[NH2:1][C:2]1[CH:9]=[CH:8][C:7]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:6][C:3]=1[C:4]#[N:5]
Reactant: OB(O)c1ccccc1
Reactant: N#Cc1cc(Br)ccc1N
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: N#Cc1cc(-c2ccccc2)ccc1N
Temperature: 100 °C
Reaction time: 3 h
Yield: 73.8 %

Procedure:
A mixture of 2-amino-5-bromo-benzonitrile (4.0 g, 0.0203 mole) in 55 mL of dioxane was treated with sodium carbonate (7.1 g) in 55 mL of water, phenyl boronic acid (2.72 g, 0.0223 mole), and tetrakistriphenylphosphine palladium (0) (0.235 g). the mixture was heated to 100° C. with stirring under an atmosphere of argon for 3 h., cooled to room temperature, poured into ethyl acetate, washed with 1M HCl, then brine, dried, evaporated and purified by chromatography to give 2.91 g of 4-amino-biphenyl-3-carbonitrile as a yellow solid.
Reaction SMILES: Br[C:2]1[S:6][C:5]([C:7]2[C:12]([C:13]#[N:14])=[CH:11][N:10]=[C:9]([NH:15][CH2:16][CH2:17][N:18]3[CH2:22][CH2:21][NH:20][C:19]3=[O:23])[N:8]=2)=[CH:4][CH:3]=1.[S:24]1[CH:28]=[CH:27][CH:26]=[C:25]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C(O)C>ClCCl.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>[O:23]=[C:19]1[NH:20][CH2:21][CH2:22][N:18]1[CH2:17][CH2:16][NH:15][C:9]1[N:8]=[C:7]([C:5]2[S:6][C:2]([C:25]3[S:24][CH:28]=[CH:27][CH:26]=3)=[CH:3][CH:4]=2)[C:12]([C:13]#[N:14])=[CH:11][N:10]=1
Reactant: OB(O)c1cccs1
Reactant: N#Cc1cnc(NCCN2CCNC2=O)nc1-c1ccc(Br)s1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: ClCCl
Product: N#Cc1cnc(NCCN2CCNC2=O)nc1-c1ccc(-c2cccs2)s1
Temperature: 130 °C

Procedure:
4-(5-Bromothiophen-2-yl)-2-(2-(2-oxoimidazolidin-1-yl)ethylamino)pyrimidine-5-carbonitrile (0.08 g, 0.2 mmol), thiophen-2-ylboronic acid (0.052 g, 04 mmol), sodium carbonate (1.5 mL of 2 M solution, 1 mmol) were added to a microwave tube containing ethanol (1.5 mL). The tube was flushed with nitrogen and tetrakis(triphenylphosphine)palladium (0.06 g, 0.054 mmol) was added. The tube was capped and heated to 130° C. for 30 min in a Personal Chemistry microwave. The reaction was diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate, water and brine. The organic layer was then dried with sodium sulfate, reduced in vacuo and purified by flash chromatography on silica gel using a gradient of 0 to 10% methanol in dichloromethane to afford a yellow solid which recrystallized from ethyl acetate. Yield=0.066 g. MS (M+H)+ 397.
Reaction SMILES: [CH2:1]([O:3][CH2:4][CH2:5][O:6][C:7]1[CH:22]=[CH:21][C:10]([CH2:11][CH2:12][NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[CH:9][CH:8]=1)[CH3:2].[CH3:23]I>CN(C)C=O>[CH2:1]([O:3][CH2:4][CH2:5][O:6][C:7]1[CH:22]=[CH:21][C:10]([CH2:11][CH2:12][N:13]([CH3:23])[C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[CH:9][CH:8]=1)[CH3:2]
Reactant: CI
Reactant: CCOCCOc1ccc(CCNC(=O)OC(C)(C)C)cc1
Solvent: CN(C)C=O
Product: CCOCCOc1ccc(CCN(C)C(=O)OC(C)(C)C)cc1
Temperature: 0 °C

Procedure:
3.2 g of a 55% sodium hydride dispersion in oil were washed with hexane and covered with 190 ml of dimethylformamide. Thereafter, 19.0 g (61.6 mmol) of t-butyl [4-(2-ethoxyethoxy)phenethyl]carbamate in solid form were added while cooling with ice and stirring, the reaction mixture was stirred at room temperature for 15 minutes and subsequently treated dropwise with 5.7 ml of methyl iodide in 10 ml of dimethylformamide within 5 minutes. After completion of the addition the reaction mixture was stirred at room temperature for 18 hours and subsequently poured into ice-water and extracted with methylene chloride. The methylene chloride extracts were dried over magnesium sulfate and evaporated under reduced pressure, and the residue was chromatographed on 240 g of silica gel with a mixture of hexane and ethyl acetate as the eluting agent, whereby 19.5 g of t-butyl [4-(2-ethoxyethoxy) phenethyl]-methylcarbamate were obtained as an oil which was used directly in the next step.
Reaction SMILES: [H-].[Na+].[F:3][C:4]([F:8])([CH3:7])[CH2:5][OH:6].Cl[C:10]1[C:15]([C:16]#[N:17])=[CH:14][N:13]=[CH:12][N:11]=1>C1COCC1>[F:3][C:4]([F:8])([CH3:7])[CH2:5][O:6][C:10]1[C:15]([C:16]#[N:17])=[CH:14][N:13]=[CH:12][N:11]=1
Reactant: N#Cc1cncnc1Cl
Reactant: CC(F)(F)CO
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(F)(F)COc1ncncc1C#N
Temperature: 25 °C
Reaction time: 1 h
Yield: 51.2 %

Procedure:
To a suspension of sodium hydride (60% dispersed in mineral oil, 1.84 g, 46 mmol) in a THF (30.0 mL) was added 2,2-difluoropropan-1-ol (4.42 g, 46.0 mmol) at 0° C. The resulting mixture was stirred at room temperature for 1 hour, then 4-chloropyrimidine-5-carbonitrile (6 g, 43.2 mmol) was added in portions at 0° C. After addition, the reaction mixture was stirred at room temperature for 30 min. The reaction was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated to give the crude product, which was purified by silica gel column chromatography (10% ethyl acetate in petroleum ether) to afford the title compound (4.40 g, 22.1 mmol, 51% yield) as a yellow solid. MS (ESI) m/z 200.0 [M+H]+.
Reaction SMILES: [C:1]1([C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N+]=[N-])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:16]([C:18]1[CH:23]([C:24]([OH:26])=[O:25])[N:22]2[C:27](=[O:38])[CH:28]([NH:29][C:30](=[O:37])[CH2:31][C:32]3[S:33][CH:34]=[CH:35][CH:36]=3)[C@H:21]2[S:20][CH:19]=1)=[O:17]>O1CCCC1>[CH:16]([C:18]1[CH:23]([C:24]([O:26][CH:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[O:25])[N:22]2[C:27](=[O:38])[CH:28]([NH:29][C:30](=[O:37])[CH2:31][C:32]3[S:33][CH:34]=[CH:35][CH:36]=3)[C@H:21]2[S:20][CH:19]=1)=[O:17]
Reactant: [N-]=[N+]=C(c1ccccc1)c1ccccc1
Reactant: O=CC1=CS[C@@H]2C(NC(=O)Cc3cccs3)C(=O)N2C1C(=O)O
Solvent: C1CCOC1
Product: O=CC1=CS[C@@H]2C(NC(=O)Cc3cccs3)C(=O)N2C1C(=O)OC(c1ccccc1)c1ccccc1
Reaction time: 2 h

Procedure:
A solution of diphenyldiazomethane (0.213 g, 1.1. mmol) in dry tetrahydrofuran (2 ml) was added dropwise with stirring to the 3-formyl-7-(2-thienylacetamido)-2-cephem-4-carboxylic acid (0.352 g., 1 mmol) in dry tetrahydrofuran (10 ml) at 40°. The reagent was allowed to completely react as noted by the color changes between each addition. The reaction was stirred at 40° for two hours after the addition was completed and then the solvent was removed in vacuo. The residual oil was dissolved in chloroform, washed with 5% NaHCO3, dried over MgSO4 and concentrated to half volume. The product was precipitated by the addition of hexane.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([CH2:10][OH:11])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.O1CCCC1>C(Cl)Cl.[O-2].[Mn+4].[O-2]>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([CH:10]=[O:11])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1
Reactant: OCc1ccc2[nH]ccc2c1
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCl
Solvent: C1CCOC1
Product: O=Cc1ccc2[nH]ccc2c1

Procedure:
51.1 g (0.347 mole) of 6c are stirred analogously to Example 1b in 1,900 ml of CH2Cl2 and 200 ml of tetrahydrofuran with 190 g (2.18 moles) of manganese(IV) oxide at 20° C. overnight.
Reaction SMILES: Cl[C:2]1[N:6]=[C:5]([CH:7]2[CH2:12][CH:11]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=3)[CH2:10][N:9]([C:23]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[O:24])[CH2:8]2)[O:4][N:3]=1.[NH:31]1[CH2:35][CH2:34][C@H:33]([OH:36])[CH2:32]1>C(O)C>[OH:36][C@H:33]1[CH2:34][CH2:35][N:31]([C:2]2[N:6]=[C:5]([CH:7]3[CH2:12][CH:11]([C:13]4[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=4)[CH2:10][N:9]([C:23]([N:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[O:24])[CH2:8]3)[O:4][N:3]=2)[CH2:32]1
Reactant: O[C@H]1CCNC1
Reactant: O=C(N1CCOCC1)N1CC(c2ccc(C(F)(F)F)cc2)CC(c2nc(Cl)no2)C1
Solvent: CCO
Product: O=C(N1CCOCC1)N1CC(c2ccc(C(F)(F)F)cc2)CC(c2nc(N3CC[C@H](O)C3)no2)C1
Reaction time: 2 h

Procedure:
To a solution of 150 mg (0.337 mmol) of the oxadiazole from Example 23A in 2.25 ml of ethanol were added 588 mg (6.74 mmol) of (3S)-pyrrolidin-3-ol, and then the reaction mixture was stirred in the microwave at 80 for 2 h. The solvent was removed under reduced pressure and the crude product was purified by means of preparative
Reaction SMILES: [F:1][C:2]1[CH:25]=[CH:24][CH:23]=[CH:22][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:19]=[C:18]([NH2:20])[C:17]([NH2:21])=[CH:16][CH:15]=2)=[N:6]1.O[CH:27]1[CH:32](O)OCCO1>C(O)C>[F:1][C:2]1[CH:25]=[CH:24][CH:23]=[CH:22][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[CH:15]=[CH:16][C:17]3[C:18]([N:19]=2)=[N:20][CH:27]=[CH:32][N:21]=3)=[N:6]1
Reactant: Nc1ccc(-c2nn(Cc3ccccc3F)c3ncccc23)nc1N
Reactant: OC1OCCOC1O
Solvent: CCO
Product: Fc1ccccc1Cn1nc(-c2ccc3nccnc3n2)c2cccnc21
Temperature: 25 °C
Reaction time: 5 h

Procedure:
200 mg (0.598 mmol) of the compound from example 43A were initially charged in ethanol (10 ml), then 144 mg (1.20 mmol) of 2,3-dihydroxy-1,4-dioxane were added and the reaction mixture was stirred at RT for 5 h. The solid formed was filtered off, washed with ethanol and dried under high vacuum. This gave 90 mg (41% of theory) of the title compound in solid form.
Reaction SMILES: [NH2:1][CH2:2][C:3]([N:5]([CH:12]([CH3:23])[C:13]([N:15]([CH3:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:14])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:4].[CH3:24][C:25]1[CH:26]=[C:27]([N:31]=[C:32]=[O:33])[CH:28]=[CH:29][CH:30]=1>>[CH3:22][N:15]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:13](=[O:14])[CH:12]([N:5]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:3](=[O:4])[CH2:2][NH:1][C:32]([NH:31][C:27]1[CH:28]=[CH:29][CH:30]=[C:25]([CH3:24])[CH:26]=1)=[O:33])[CH3:23]
Reactant: Cc1cccc(N=C=O)c1
Reactant: CC(C(=O)N(C)c1ccccc1)N(C(=O)CN)c1ccccc1
Product: Cc1cccc(NC(=O)NCC(=O)N(c2ccccc2)C(C)C(=O)N(C)c2ccccc2)c1
Yield: 35.7 %

Procedure:
The procedure is analogous to that described in Example 1, but 1.0 g of (RS)-2-(2-amino-N-phenylacetamido)-N-methyl-N-phenylpropionamide and 0.42 g of 3-methylphenyl isocyanate are used as the starting material. After recrystallization from a mixture of acetonitrile and dimethylformamide (93-7 by volume), 0.5 g of (RS)-N-methyl-2-{2-[3-(3-methylphenyl)ureido]-N-phenylacetamido}-N-phenylpropionamide melting at 214° C. is obtained.
Reaction SMILES: [N:1]([CH2:4][CH:5]1[CH2:9][C:8]2[CH:10]=[CH:11][C:12]([Cl:21])=[C:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[Cl:20])[C:7]=2[O:6]1)=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[Cl:21][C:12]1[CH:11]=[CH:10][C:8]2[CH2:9][CH:5]([CH2:4][NH2:1])[O:6][C:7]=2[C:13]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[Cl:20]
Reactant: [N-]=[N+]=NCC1Cc2ccc(Cl)c(-c3ccccc3Cl)c2O1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: NCC1Cc2ccc(Cl)c(-c3ccccc3Cl)c2O1
Yield: 28.5 %

Procedure:
Treatment of 1-bromo-2-chlorobenzene (5.0 g, 26.88 mmol) with (2-chloro-6-methyoxyphenyl)boronic acid (15.6 g, 80.64 mol) generally according to the procedure described for Intermediate 37 afforded 5.0 g (73%) of 6-chloro-2′-chlorobiphenyl-2-yl methyl ether. Treatment of 6-chloro-2′-methylbiphenyl-2-yl methyl ether with hydrogen bromide (60 mL, 30 wt. % in acetic acid) generally according to the procedure described for Example 395 afforded a brown oil. The oil was reacted with sodium hydride (1.05 g, 26.35 mmol) and allyl bromide (3.19 g, 26.35 mmol) followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 provided 3-allyl-6-chloro-2′-chlorobiphenyl-2-ol. Treatment of 3-allyl-6-chloro-2′-chlorobiphenyl-2-ol (2.8 g, 10.03 mmol) with m-chloroperoxybenzoic acid (4.6 g, 15.0 mmol, 77%) and potassium carbonate (1.6 g, 12.0 mmol) generally according to the procedure described for Intermediate 9 afforded 2.2 g (74%) of (±)-[7-(2-chlorophenyl)-6-chloro-2,3-dihydro-1-benzofuran-2-yl]methanol. Treatment (±)-[7-(2-chlorophenyl)-6-chloro-2,3-dihydro-1-benzofuran-2-yl]methanol (1.6 g, 5.42 mmol) with p-toluenesulfonyl chloride (1.55 g, 8.13 mmol) generally according to the procedure described for Intermediate 10 gave 2.1 g (86%) of (±)-[6-chloro-7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a colorless oil. Treatment of (±)-[6-chloro-7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.2 g, 0.44 mmol) with sodium azide (0.2 g, 3.08 mmol) generally according to the procedure described for Intermediate 98 afforded 0.14 g, (99%) of (±)-2-(azidomethyl)-7-(2-chlorophenyl)-6-chloro-2,3-dihydro-1-benzofuran. Treatment of (±)-2-(azidomethyl)-7-(2-chlorophenyl)-6-chloro-2,3-dihydro-1-benzofuran (0.14 g, 0.43 mmol) in tetrahydrofuran (10 mL) with polymer-supported triphenylphosphine (0.3 g, 1.14 mmol) generally according to the procedure described for Example 154 provided 0.036 g (24%) of (±)-{[6-chloro-7-(2-chlorophenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl}amine as a white solid, hydrochloride salt. mp 221-223° C.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][S:8][CH2:9][CH2:10][OH:11])[CH:2]=1.ClC1C=C(C=CC=1)C(OO)=[O:17]>ClCCl>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][S:8]([CH2:9][CH2:10][OH:11])=[O:17])[CH:2]=1
Reactant: OCCSCc1cccnc1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: O=S(CCO)Cc1cccnc1
Temperature: 0 °C
Reaction time: 3 h

Procedure:
A stirred solution of 2-(3-pyridylmethylthio)ethanol (3.38 g, 20 mmol) in dichloromethane (50 ml) at 0° C. was treated dropwise with a solution of m-chloroperoxybenzoic acid in dichloromethane (50 ml). The mixture was stirred at 0° C. for 1 hr and at room temperature for 3 hrs. The mixture was evaporated in vacuo and purified by flash chromatography on silica eluting with 20% methanol in ethyl acetate to give 2-(3-pyridylmethylsulphinyl)ethanol (3.5 g), as colourless crystals, m.p. 84°-86° C.;
Reaction SMILES: [SH:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[NH3:11].O=O>CO>[CH:8]1[CH:7]=[C:5]2[N:6]=[C:2]([S:1][S:1][C:2]3[S:3][C:4]4[C:5](=[CH:7][CH:8]=[CH:9][CH:10]=4)[N:11]=3)[S:3][C:4]2=[CH:10][CH:9]=1
Reactant: Sc1nc2ccccc2s1
Reactant: N
Agent: O=O
Solvent: CO
Product: c1ccc2sc(SSc3nc4ccccc4s3)nc2c1

Procedure:
A solution of 40 g (0.24 mol) of 2-mercaptobenzothiazole, 22.4 mg (0.1×10-3 mol) of Mn(OAc)2. 4H2O and 4.08 g (0.24 mol) of ammonia in 120 g of methanol is in the manner and reaction equipment described in Example 1 reacted with oxygen at an oxygen pressure of 4 bar and a reaction temperature of 55° C. After a reaction time of 3 hours, one obtains dibenzo thiazyl disulfide at a yield of 35.9 g, corresponding to 90.3% of theoretical. The conversion rate is determined to be 92.1%.
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:33])[NH:10][CH:11]([CH2:31][OH:32])[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[C:15]([C:27]([CH3:30])([CH3:29])[CH3:28])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:34]1([CH3:44])[C:35]([S:40](Cl)(=[O:42])=[O:41])=[CH:36][CH:37]=[CH:38][CH:39]=1.O>N1C=CC=CC=1>[CH2:1]([O:8][C:9](=[O:33])[NH:10][CH:11]([CH2:31][O:32][S:40]([C:35]1[C:34]([CH3:44])=[CH:39][CH:38]=[CH:37][CH:36]=1)(=[O:42])=[O:41])[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[C:15]([C:27]([CH3:30])([CH3:28])[CH3:29])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)c1cc(CC(CO)NC(=O)OCc2ccccc2)ccc1OCc1ccccc1
Reactant: Cc1ccccc1S(=O)(=O)Cl
Solvent: O
Solvent: c1ccncc1
Product: Cc1ccccc1S(=O)(=O)OCC(Cc1ccc(OCc2ccccc2)c(C(C)(C)C)c1)NC(=O)OCc1ccccc1
Reaction time: 6.5 h
Yield: 88.3 %

Procedure:
To a solution of 2-(4-benzyloxy-3-t-butylphenyl)-1-hydroxymethylethylcarbamic acid benzyl ester (2.07 g, 4.63 mmol) in pyridine (46 ml), toluenesulfonyl chloride (6.79 g, 35.6 mmol) was added under cooling with ice. After stirring for 6.5 hours, the mixture was mixed with water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated to remove the solvent under reduced pressure; the thus obtained residue was subjected to silica gel column chromatography (developing solvent: n-hexane:ethyl acetate=2:1), giving the titled compound (2.46 g, 88%).
Reaction SMILES: [CH2:1]([C:5]1[N:6]([CH2:18][CH2:19][CH2:20][CH:21]=[O:22])[C:7]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:17]=1)[CH2:2][CH2:3][CH3:4].[C:23]1([Mg]Br)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C1COCC1>[CH2:1]([C:5]1[N:6]([CH2:18][CH2:19][CH2:20][CH:21]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[OH:22])[C:7]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:17]=1)[CH2:2][CH2:3][CH3:4]
Reactant: Br[Mg]c1ccccc1
Reactant: CCCCc1nc2cnc3ccccc3c2n1CCCC=O
Solvent: C1CCOC1
Product: CCCCc1nc2cnc3ccccc3c2n1CCCC(O)c1ccccc1
Reaction time: 0.5 h

Procedure:
To a stirred solution of 4-(2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)butyraldehyde (8.0 g, 27.1 mmol) in anhydrous THF (270 mL) was added dropwise a solution of phenylmagnesium bromide (27.08 mL of a 1 M solution in THF). After 30 minutes, the solution was quenched with saturated ammonium chloride (100 mL), diluted with ethyl acetate (300 mL), and the layers separated. The organic solution was washed successively with a saturated aqueous sodium bicarbonate solution (100 mL) and brine (100 mL), dried over sodium sulfate, filtered, and concentrated to a light orange oil. Chromatography on silica gel (elution with 5% methanol in dichloromethane) provided 4-(2-butyl-1H-imidazo[4,5-c]quinolin-1-yl)-1-phenylbutan-1-ol (4.3 g) as a light orange, gummy solid.