Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([Li])CCC.[CH2:6]([OH:9])[C:7]#[CH:8].Cl[C:11]([N:13]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[C:17](=[O:24])[NH:16][C:15]2[CH:25]=[CH:26][CH:27]=[N:28][C:14]1=2)=[O:12]>CCCCCC.O1CCCC1>[CH2:6]([O:9][C:11]([N:13]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[C:17](=[O:24])[NH:16][C:15]2[CH:25]=[CH:26][CH:27]=[N:28][C:14]1=2)=[O:12])[C:7]#[CH:8]
Reactant: O=C1Nc2cccnc2N(C(=O)Cl)c2ccccc21
Reactant: C#CCO
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: C#CCOC(=O)N1c2ccccc2C(=O)Nc2cccnc21
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
At 15° to 20° C., 3.08 g (0.048 mol) of n-butyl-lithium in 30 ml of n-hexane are added dropwise to a solution of 2.24 g (0.04 mol) of propargyl alcohol in 120 ml of tetrahydrofuran. After it has all been added, the mixture is stirred for a further 30 minutes at ambient temperature and then mixed with a suspension of 10.9 g (0.04 mol) of 11-chlorocarbonyl-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one in 250 ml of tetrahydrofuran. In order to complete the reaction the mixture is stirred for a further hour. It is evaporated to dryness in vacuo and the residue is crystallised by stirring in water. After recrystallisation from ethyl acetate, 7.5 g (64% of theory) of the desired product are obtained, m.p. 213° C.
Reaction SMILES: [CH2:1]([N:3]([CH2:31][CH3:32])[C:4]([C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:14]=1[NH:13][CH:12]=[C:11]2[CH2:15][C@H:16]([N:18]1[CH2:22][C@@H:21]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=2)[O:20][C:19]1=[O:30])[CH3:17])=[O:5])[CH3:2].CI.[C:35](=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:31]([N:3]([CH2:1][CH3:2])[C:4]([C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:14]=1[N:13]([CH3:35])[CH:12]=[C:11]2[CH2:15][C@H:16]([N:18]1[CH2:22][C@@H:21]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=2)[O:20][C:19]1=[O:30])[CH3:17])=[O:5])[CH3:32]
Reactant: CCN(CC)C(=O)c1cccc2c(C[C@@H](C)N3C[C@@H](c4cccc(Cl)c4)OC3=O)c[nH]c12
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CI
Product: CCN(CC)C(=O)c1cccc2c(C[C@@H](C)N3C[C@@H](c4cccc(Cl)c4)OC3=O)cn(C)c12
Yield: 29.1 %

Procedure:
A solution of 3-{(2 R)-2-[(5R)-5-(3-chlorophenyl)-2-oxooxazolidin-3-yl]propyl}-1H-indole-7-carboxylic acid diethylamide (10 mg, 0.022 mmol), methyl iodide (21 μL, 0.33 mmol), potassium carbonate (90 mg, 0.66 mmol) in acetone (2 mL) is refluxed for 24 hours. After cooling, the insoluble materials are removed by filtration, and the filtrate is concentrated under reduced pressure. The residue is purified by preparative TLC (silica gel, 0.5 mm, 20×20 cm, methanol/chloroform=1/30) to give 3-{(2R)-2-[(5R)-5-(3-chlorophenyl)-2-oxooxazolidin-3-yl]-propyl}-1-methyl-1H-indole-7-carboxylic acid diethylamide (3 mg). A solution of 3-{(2R)-2-[(5R)-5-(3-chlorophenyl)-2-oxooxazolidin-3-yl]-propyl}-1-methyl-1H-indole-7-carboxylic acid diethylamide (3 mg, 0.0064 mmol) and potassium hydroxide (0.6 g) in water (1 mL) and ethanol (1 mL) is stirred at 70° C. for 7 hours. After cooling, ethanol is removed by distillation, and water is added thereto. The mixture is extracted with ethyl acetate, and the organic layer is washed with a saturated aqueous sodium hydrogen carbonate solution, dried over sodium sulfate, and concentrated. The residue is purified by silica gel column chromatography (60, 2 g, a saturated ammonia solution in chloroform) to give 3-{(2R)-2-[2-(3-chlorophenyl)-(2R)-2-hydroxyethyl-amino]propyl}-1-methyl-1H-indole-7-carboxylic acid diethylamide (2 mg, yield: 71%).
Reaction SMILES: [CH2:1]([S:3]([C:6]1[CH:7]=[CH:8][C:9]2[O:13][C:12](S)=[N:11][C:10]=2[CH:15]=1)(=[O:5])=[O:4])[CH3:2].S(Cl)([Cl:18])=O>CN(C)C=O>[Cl:18][C:12]1[O:13][C:9]2[CH:8]=[CH:7][C:6]([S:3]([CH2:1][CH3:2])(=[O:5])=[O:4])=[CH:15][C:10]=2[N:11]=1
Reactant: O=S(Cl)Cl
Reactant: CCS(=O)(=O)c1ccc2oc(S)nc2c1
Solvent: CN(C)C=O
Product: CCS(=O)(=O)c1ccc2oc(Cl)nc2c1
Reaction time: 0.75 h

Procedure:
8 mmol of 5-Ethanesulfonyl-benzooxazole-2-thiol were dissolved in 10 ml of thionyl chloride. 1 drop of N,N-dimethylformamide is added and the reaction mixture hold at 65° for 45 min. Evaporation of the solvent yields the title compound as brownish solid.
Reaction SMILES: [NH2:1][C:2]1[C:3]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.Cl[C:16](Cl)([O:18]C(=O)OC(Cl)(Cl)Cl)Cl>CC#N>[C:9]1([N:8]2[C:3]3=[N:4][CH:5]=[CH:6][CH:7]=[C:2]3[NH:1][C:16]2=[O:18])[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: Nc1cccnc1Nc1ccccc1
Solvent: CC#N
Product: O=c1[nH]c2cccnc2n1-c1ccccc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To a stirred mixture of 3-amino-N-phenylpyridin-2-amine from Step B (258 mg, 1.39 mmol) in CH3CN (15 mL) was added triphosgene (413 mg, 1.39 mmol) and the reaction mixture was stirred for 10 min at ambient temperature. The mixture was concentrated in vacuo and the crude solid was quenched with H2O (10 mL) and saturated aqueous NaHCO3 (10 mL). The precipitate was filtered, washed with water and air-dried to yield the title compound as a brown solid, which was of sufficient purity for use in the next step. MS: m/z=212 (M+1).
Reaction SMILES: [O:1]1[CH2:6][CH:5]=[C:4]([C:7]2[CH:15]=[CH:14][C:13]([F:16])=[C:12]3[C:8]=2[CH2:9][CH2:10][C:11]3=[O:17])[CH2:3][CH2:2]1>O1CCCC1.[Pd]>[F:16][C:13]1[CH:14]=[CH:15][C:7]([CH:4]2[CH2:5][CH2:6][O:1][CH2:2][CH2:3]2)=[C:8]2[C:12]=1[C:11](=[O:17])[CH2:10][CH2:9]2
Reactant: O=C1CCc2c(C3=CCOCC3)ccc(F)c21
Agent: [Pd]
Solvent: C1CCOC1
Product: O=C1CCc2c(C3CCOCC3)ccc(F)c21
Reaction time: 12 h

Procedure:
To a solution of 4-(3,6-dihydro-2H-pyran-4-yl)-7-fluoro-2,3-dihydro-1H-inden-1-one (100 mg) in tetrahydrofurane (10 mL) is added 10% palladium on activated carbon (30 mg) and the mixture is hydrogenated at a pressure of 2 bar for 12 hours. The catalyst is filtered off and washed with methanol. The combined mother liquors are concentrated and the residue is chromatographed on silica gel (petrole ether/ethyl acetate 80:20→50:50) to give the title compound. Yield: 55 mg; LC (method 8): tR=0.36 min; Mass spectrum (ESI+): m/z=339 [M+H]+.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]3[S:12][CH:13]=[C:14]([C:16]([OH:19])([CH3:18])[CH3:17])[N:15]=3)[S:10][C:3]=12.[CH3:20][N:21]1[C:25]([C:26]([F:29])([F:28])[F:27])=[CH:24][C:23]([OH:30])=[N:22]1>>[CH3:20][N:21]1[C:25]([C:26]([F:27])([F:28])[F:29])=[CH:24][C:23]([O:30][C:2]2[CH:7]=[CH:6][N:5]=[C:4]3[CH:8]=[C:9]([C:11]4[S:12][CH:13]=[C:14]([C:16]([OH:19])([CH3:18])[CH3:17])[N:15]=4)[S:10][C:3]=23)=[N:22]1
Reactant: CC(C)(O)c1csc(-c2cc3nccc(Cl)c3s2)n1
Reactant: Cn1nc(O)cc1C(F)(F)F
Product: Cn1nc(Oc2ccnc3cc(-c4nc(C(C)(C)O)cs4)sc23)cc1C(F)(F)F
Yield: 8 %

Procedure:
The title compound (11 mg, 8%) was prepared from 2-[2-(7-chloro-thieno[3,2-b]pyridin-2-yl)-thiazol-4-yl]-propan-2-ol and 1-methyl-5-trifluoromethyl-1H-pyrazol-3-ol by a procedure analogous to Example 16. C18H15F3N4O2S2: APCI m/z 441.3 (pos.); 1H NMR (CD3OD): δ 8.53 (d, 1H, J=5.6 Hz), 7.91 (s, 1H), 7.48 (s, 1H), 7.07 (d, 1H, J=5.6 Hz), 6.68 (s, 1H), 3.98 (s, 3H), 1.61 (s, 6H) ppm.
Reaction SMILES: S([N:11]1[C:15]2[N:16]=[CH:17][C:18]3[N:19]([C:20]([C:23]45[CH2:30][CH2:29][C:26]([NH:31][S:32]([CH:35]6[CH2:37][CH2:36]6)(=[O:34])=[O:33])([CH2:27][CH2:28]4)[CH2:25][CH2:24]5)=[N:21][N:22]=3)[C:14]=2[CH:13]=[CH:12]1)(C1C=CC(C)=CC=1)(=O)=O.[OH-].[Na+].O1CCOCC1>CN(C=O)C>[C:20]1([C:23]23[CH2:24][CH2:25][C:26]([NH:31][S:32]([CH:35]4[CH2:37][CH2:36]4)(=[O:33])=[O:34])([CH2:27][CH2:28]2)[CH2:29][CH2:30]3)[N:19]2[C:14]3[CH:13]=[CH:12][NH:11][C:15]=3[N:16]=[CH:17][C:18]2=[N:22][N:21]=1
Reactant: Cc1ccc(S(=O)(=O)n2ccc3c2ncc2nnc(C45CCC(NS(=O)(=O)C6CC6)(CC4)CC5)n23)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: CN(C)C=O
Product: O=S(=O)(NC12CCC(c3nnc4cnc5[nH]ccc5n34)(CC1)CC2)C1CC1
Temperature: 60 °C
Reaction time: 2 h
Yield: 56.9 %

Procedure:
A round bottom flask was charged with N-(4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)cyclopropanesulfonamide (0.27 g, 0.50 mmol), aqueous NaOH (1N, 1.0 mL, 1.0 mmol), and 1,4-dioxane (8 mL). The reaction mixture was stirred at about 60° C. for about 2 h. NH4OAc (50 mM aqueous buffer, 2 mL) and DMF (7 mL) were added and insoluble material was removed via filtration. The filtrate was purified by RP-HPLC (Table 2, Method c). The appropriate fractions were combined, the organic solvent was concentrated under reduced pressure, the resulting solid was collected by filtration, washed with water (20 mL), and lyophilized to give N-(4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)cyclopropanesulfonamide as a solid (0.11 g, 56%): LC/MS (Table 2, Method a) Rt=1.53 min; MS m/z 387 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]([CH2:9][CH2:10][C:11](OC)=O)[CH:4]=1.[NH2:15][C:16]1[C:21]([NH2:22])=[CH:20][CH:19]=[CH:18][N:17]=1.[OH-].[Na+]>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][N:6]=[C:5]([CH2:9][CH2:10][C:11]2[NH:15][C:16]3=[N:17][CH:18]=[CH:19][CH:20]=[C:21]3[N:22]=2)[CH:4]=1
Reactant: COC(=O)CCc1cc(OC)ccn1
Reactant: Nc1cccnc1N
Agent: [Na+]
Agent: [OH-]
Product: COc1ccnc(CCc2nc3cccnc3[nH]2)c1
Temperature: 160 °C
Yield: 43 %

Procedure:
With stirring, a mixture of 0.643 g of methyl 3-(4-methoxypyridin-2-yl)propionate (starting material A2), 0.359 g of 2,3-diaminopyridine and 10 g of polyphosphoric acid (PPA) is heated at 160° C. for 1 h. After cooling, the mixture is poured into about 50 ml of ice-water and then neutralized (pH 7–8) using 6N aqueous sodium hydroxide solution. The mixture is extracted three times with dichloromethane/methanol 9:1, the combined organic phases are evaporated to dryness and the residue is chromatographed on a silica gel column (dichloromethane/methanol 15:1). Concentration of the chromatographically pure fractions gives 0.36 g of an oil, which crystallizes on standing. The product is recrystallized from ethyl acetate/petroleum ether, giving 0.278 g of the title compound as a light-beige powder of m.p. 116–117° C.; the mass spectrum shows the molecular peaks MH+ and 2MNa+ at 255.3 and 530.9 Da.
Reaction SMILES: [CH3:1][N:2]=[C:3]=[S:4].[Cl:5][C:6]1[CH:28]=[CH:27][C:9]([C:10]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[C:14]([CH2:23][NH:24][OH:25])=[C:13]2[CH3:26])=[O:11])=[CH:8][CH:7]=1>O1CCOCC1.O>[Cl:5][C:6]1[CH:28]=[CH:27][C:9]([C:10]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[C:14]([CH2:23][N:24]([OH:25])[C:3]([NH:2][CH3:1])=[S:4])=[C:13]2[CH3:26])=[O:11])=[CH:8][CH:7]=1
Reactant: CN=C=S
Reactant: COc1ccc2c(c1)c(CNO)c(C)n2C(=O)c1ccc(Cl)cc1
Solvent: O
Solvent: C1COCCO1
Product: CNC(=S)N(O)Cc1c(C)n(C(=O)c2ccc(Cl)cc2)c2ccc(OC)cc12
Reaction time: 8 h
Yield: 54.1 %

Procedure:
A solution of methyl isothiocyanate (1.36 g, 18.56 mmol) in 2 ml of dioxane is added dropwise to a suspension of 1-(4-chlorobenzoyl)-N-hydroxy-5-methoxy-2-methyl-1H-indole-3-methanamine (2.01 g, 5.84 mmol) in 60 ml of dioxane and 60 ml of H2O at 0° C. The ice bath is removed. After one hour 0.5 g (6.84 mmol) additional methyl isothiocyanate is added and the reaction mixture is stored in a freezer overnight. The solids are collected by filtration and recrystallized from THF/hexane, rinsed with ether, and dried under high vacuum over P2O5 to give pure 1-(4-chlorobenzoyl)-N-hydroxy-5-methoxy-2-methyl-N-[(methylamino)thioxomethyl]-1H-indole-3- methanamine (1.32 g, 54%); mp 198°-198.5° C. (dec).
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]1[CH:8]=[C:7]([CH2:9][NH:10][C:11](=[O:21])[CH2:12][N:13]2[CH:17]=[CH:16][N:15]=[C:14]2[N+:18]([O-:20])=[O:19])[N:6]=[N:5]1.[O:22](S(C1C=CC(C)=CC=1)(=O)=O)[S:23]([C:26]1[CH:32]=[CH:31][C:29]([CH3:30])=[CH:28][CH:27]=1)(=O)=[O:24]>C(Cl)Cl>[CH3:30][C:29]1[CH:31]=[CH:32][C:26]([S:23]([O:1][CH2:2][CH2:3][N:4]2[CH:8]=[C:7]([CH2:9][NH:10][C:11](=[O:21])[CH2:12][N:13]3[CH:17]=[CH:16][N:15]=[C:14]3[N+:18]([O-:20])=[O:19])[N:6]=[N:5]2)(=[O:24])=[O:22])=[CH:27][CH:28]=1
Reactant: O=C(Cn1ccnc1[N+](=O)[O-])NCc1cn(CCO)nn1
Reactant: Cc1ccc(S(=O)(=O)OS(=O)(=O)c2ccc(C)cc2)cc1
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)OCCn2cc(CNC(=O)Cn3ccnc3[N+](=O)[O-])nn2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 34.1 %

Procedure:
To a round bottom flask was added the alcohol 20 (106 mg, 0.359 mmol), TEA (36.3 mg, 0.359 mmol) and DCM (10 mL). Ts2O (117 mg, 0.359 mmol) was added in one portion. The reaction was stirred at RT for 4 hrs. The reaction was then concentrated to dryness and purified on a silica gel cartridge using EtOAc:Hex as the eluent to afford 55 mg (34% yield) of 21 as a white solid. Mass Spec (lo-res): Calc'd for C17H19N7O6S: 449.11; found: 450.1 (M+H).
Reaction SMILES: [OH-].[K+].[OH:3][C:4]1[CH:19]=[CH:18][C:7]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])=[CH:6][CH:5]=1.Br[CH2:21][CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25]>CS(C)=O>[CH2:11]([O:10][C:8](=[O:9])[C:7]1[CH:18]=[CH:19][C:4]([O:3][CH2:21][CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])=[CH:5][CH:6]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CC(C)CCCBr
Reactant: O=C(OCc1ccccc1)c1ccc(O)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CS(C)=O
Product: CC(C)CCCOc1ccc(C(=O)OCc2ccccc2)cc1
Yield: 57.5 %

Procedure:
To a mixture of KOH (0.74 g) in DMSO(15 ml) were added benzyl 4-hydroxybenzoate(1.5 g) and 1-bromo-4-methylpentane(2.78 ml), then the mixture was refluxed for an hour. Then the reaction mixture was partitioned between a mixture of ethyl acetate and water. The separated organic layer was washed in turn water, 20% aqueous sodium carbonate solution and brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by a silica gel column chromatography eluting with a mixture of ethyl acetate and n-hexane (1:30) to give benzyl-4-isohexyloxybenzoate(1.18 g, 57.5%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH:10]([CH3:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[I:15][C:16]1[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][C:17]=1[C:18](O)=[O:19].C(N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:18](=[O:19])[C:17]2[CH:21]=[C:22]([S:25]([CH3:28])(=[O:27])=[O:26])[CH:23]=[CH:24][C:16]=2[I:15])[CH:10]([CH3:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CS(=O)(=O)c1ccc(I)c(C(=O)O)c1
Reactant: CC1CN(C(=O)OC(C)(C)C)CCN1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC1CN(C(=O)OC(C)(C)C)CCN1C(=O)c1cc(S(C)(=O)=O)ccc1I
Temperature: 25 °C
Reaction time: 16 h
Yield: 47.1 %

Procedure:
To a solution of rac-3-Methyl-piperazine-1-carboxylic acid tert-butyl ester (350 mg, 1.75 mmol) in dimethylformamide (3 ml) were added 2-Iodo-5-methanesulfonyl-benzoic acid (540 mg, 1.67 mmol), N-ethyldiisopropylamine (1.8 ml, 10.5 mmol), and TBTU (630 mg, 1.92 mmol). The reaction mixture was then allowed to stir at room temperature for 16 hours. The reaction mixture was then concentrated in vacuo and the residue was purified by column chromatography (SiO2, 20 g, Heptane/EtOAc 0-100%) to give the title compound (400 mg, 45%). MS (m/e): 526.2 (M+NH4+).
Reaction SMILES: [OH:1][C:2]1[C:19]([OH:20])=[CH:18][C:17]2[C:16]3[C:11](=[CH:12][C:13]([OH:22])=[C:14]([OH:21])[CH:15]=3)[C:10]3[C:5](=[CH:6][C:7]([OH:24])=[C:8]([OH:23])[CH:9]=3)[C:4]=2[CH:3]=1.[C:25](Cl)(=[O:35])[O:26][C@H:27]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH3:28].Cl>N1C=CC=CC=1>[CH3:28][C@H:27]([O:26][C:25]([O:1][C:2]1[C:19]([O:20][C:25]([O:26][C@H:27]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH3:28])=[O:35])=[CH:18][C:17]2[C:16]3[C:11](=[CH:12][C:13]([O:22][C:25]([O:26][C@H:27]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH3:28])=[O:35])=[C:14]([O:21][C:25]([O:26][C@H:27]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH3:28])=[O:35])[CH:15]=3)[C:10]3[C:5](=[CH:6][C:7]([O:24][C:25]([O:26][C@H:27]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH3:28])=[O:35])=[C:8]([O:23][C:25]([O:26][C@H:27]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH3:28])=[O:35])[CH:9]=3)[C:4]=2[CH:3]=1)=[O:35])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]
Reactant: CCCCCC[C@H](C)OC(=O)Cl
Reactant: Oc1cc2c3cc(O)c(O)cc3c3cc(O)c(O)cc3c2cc1O
Agent: Cl
Solvent: c1ccncc1
Product: CCCCCC[C@H](C)OC(=O)Oc1cc2c3cc(OC(=O)O[C@@H](C)CCCCCC)c(OC(=O)O[C@@H](C)CCCCCC)cc3c3cc(OC(=O)O[C@@H](C)CCCCCC)c(OC(=O)O[C@@H](C)CCCCCC)cc3c2cc1OC(=O)O[C@@H](C)CCCCCC
Temperature: 25 °C
Yield: 69 %

Procedure:
A TFT solution of 4.86 g (15 mmol) of 2,3,6,7,10,11-hexahydroxytriphenylene and 135 mmol of (s)-2-octyl chlorocarbonate was stirred while chilled with ice. After 40 ml of pyridine was slowly and dropwise added, the liquid was heated for 50 minutes to the room temperature. The solution was poured into diluted hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The organic phase was collected, washed with diluted hydrochloric acid, water and saturated aqueous solution of sodium chloride, and then dried with anhydrous magnesium sulfate. After the solvent was distilled off, the obtained brown oily product (26.2 g) was purified through silica-gel chromatography (hexane:ethyl acetate =10:1) to prepare 13.75 g of the titled optically active triphenylene compound (5) [colorless oily product at room temperature, yield: 69%].
Reaction SMILES: [NH2:1][CH2:2][CH:3]([OH:11])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][CH:5]=1.N([C:16]1[NH:17][CH2:18][CH2:19][N:20]=1)[N+]([O-])=O.C1(C)C(C)=CC=CC=1>CC(C)=O>[NH:20]1[CH2:19][CH2:18][N:17]=[C:16]1[NH:1][CH2:2][CH:3]([OH:11])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][CH:5]=1
Reactant: O=[N+]([O-])NC1=NCCN1
Reactant: Cc1ccc(C(O)CN)cc1
Solvent: CC(C)=O
Solvent: Cc1ccccc1C
Product: Cc1ccc(C(O)CNC2=NCCN2)cc1
Temperature: 160 °C
Reaction time: 0.5 h

Procedure:
A mixture of 9.06 parts of α-(aminomethyl)-p-methylbenzyl alcohol, 7.8 parts of 2-(nitramino)-2-imidazoline and 8 parts of xylene is stirred for 30 minutes at 160°C (oil-bath). The reaction mixture is cooled and acetone is added. The precipitated product is filtered off, washed with acetone and dried, yielding α-(2-imidazolin-2-ylaminomethyl)-p-methylbenzyl alcohol; 163.7°C.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[C:8]([S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)(=[O:12])=[O:11])[CH:7]=[CH:6][C:5]=1[Cl:19])([O-])=O.ClCCl>C(O)C>[Cl:19][C:5]1[C:4]([NH2:1])=[CH:9][C:8]([S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)(=[O:11])=[O:12])=[CH:7][CH:6]=1
Reactant: O=[N+]([O-])c1cc(S(=O)(=O)c2ccccc2)ccc1Cl
Solvent: CCO
Solvent: ClCCl
Product: Nc1cc(S(=O)(=O)c2ccccc2)ccc1Cl
Temperature: 75 °C
Yield: 82.8 %

Procedure:
2-Nitro-4-(phenylsulfonyl)chlorobenzene (9.8 g) and stannous chloride dihydrate (33.5 g) were suspended in absolute ethanol (200 mL) and heated to 75° C. for 40 minutes. The solution was evaporated and the resulting material was cooled to 0° C. Water (100 mL) was added, and the pH was adjusted to 8.0 with aqueous sodium hydroxide. The resulting solids were removed by filtration and the aqueous filtrate was extracted with ethyl acetate. The combined ethyl acetate solutions were evaporated to give a brown solid. Chromatography, with dichloromethane as the eluent yielded the aniline as an orange solid (7.3 g); mp: 105°-107° C.; 250 MHz NMR: 5.96 (s,2), 7.02 (dd,1 J=8, 2), 7.34 (d,1, J=2), 7.41 (d,1, J=8), 7.61 (m,3), 7.88 (d,2, J=7); MS: m/z=268(M+1).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:17]=[CH:16][CH:15]=[CH:14][C:6]=1[C:7]([C:9]1[S:10][CH:11]=[CH:12][CH:13]=1)=O)(=[O:3])[CH3:2].CC[O-].[Na+]>C(O)C.O>[S:10]1[CH:11]=[CH:12][CH:13]=[C:9]1[C:7]1[C:6]2[C:5](=[CH:17][CH:16]=[CH:15][CH:14]=2)[NH:4][C:1](=[O:3])[CH:2]=1
Reactant: CC(=O)Nc1ccccc1C(=O)c1cccs1
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: O=c1cc(-c2cccs2)c2ccccc2[nH]1

Procedure:
To a solution of 2-(2-acetylaminobenzoyl)thiophene (4.8 g) in ethanol (60 cc) is added sodium ethylate (3.2 g). The reaction mixture is refluxed for 9 hours, treated again with sodium ethylate (0.5 g) and then allowed to reflux for 10 hours. The mixture is poured in iced water (200 cc). The precipitate formed is filtered, washed with distilled water until neutrality and then with acetone (3×50 cc) and dried at 40° C. under reduced pressure. The residue thus obtained is recrystallized in ethanol to obtain the product as a yellow solid. (m.p.=262°-264° C.)
Reaction SMILES: C(OO)(=[O:3])C.[C:6]([O:9][C@@H:10]1[C@@H:15]([O:16][C:17](=[O:19])[CH3:18])[C@H:14]([O:20][C:21](=[O:23])[CH3:22])[C@@H:13]([S:24][CH3:25])[O:12][C@H:11]1[C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[C:28]([CH2:33][C:34]2[CH:39]=[CH:38][C:37]([CH2:40][CH2:41][CH2:42][C:43]([O:45][CH3:46])=[O:44])=[CH:36][CH:35]=2)[CH:27]=1)(=[O:8])[CH3:7]>CC(O)=O.CC#N>[C:6]([O:9][C@@H:10]1[C@@H:15]([O:16][C:17](=[O:19])[CH3:18])[C@H:14]([O:20][C:21](=[O:23])[CH3:22])[C@@H:13]([S@:24]([CH3:25])=[O:3])[O:12][C@H:11]1[C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[C:28]([CH2:33][C:34]2[CH:35]=[CH:36][C:37]([CH2:40][CH2:41][CH2:42][C:43]([O:45][CH3:46])=[O:44])=[CH:38][CH:39]=2)[CH:27]=1)(=[O:8])[CH3:7]
Reactant: COC(=O)CCCc1ccc(Cc2cc([C@@H]3O[C@H](SC)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]3OC(C)=O)ccc2C)cc1
Reactant: CC(=O)OO
Solvent: CC(=O)O
Solvent: CC#N
Product: COC(=O)CCCc1ccc(Cc2cc([C@@H]3O[C@H]([S@](C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]3OC(C)=O)ccc2C)cc1
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 58.6 %

Procedure:
Peracetic acid (32% in dilute HOAc, 0.12 mL, 0.512 mmol) was added to a solution of (2S,3S,4R,5S,6R)-2-(3-(4-(4-methoxy-4-oxobutyl)benzyl)-4-methylphenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triyl triacetate (9, 100 mg, 0.170 mmol) in 1 mL of HOAc and 2 mL of CH3CN at 0° C. The reaction was stirred for 20 min at 0° C. The reaction was quenched with 1N aqueous NaOH, then extracted twice with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered, and the solvents were removed in vacuo to provide a 2:1 diastereomeric mixture of sulfoxides 60 (60 mg, 58% yield) that was carried to the next step without further purification. 1H NMR (400 MHz, CHLOROFORM-d, 2:1 mixture of diastereomers at S, designated as major Ha and minor Hb) δ ppm 7.11-7.17 (m, 2 H), 7.05-7.09 (m, 2 H), 6.97-7.02 (m, 3 H), 5.59 (t, J=9.3 Hz, 1 Hb), 5.46 (t, J=9.3 Hz, 1 Hb), 5.41 (t, J=9.6 Hz, 1 Ha), 5.21 (t, J=9.9 Hz, 1 Ha), 5.17 (t, J=9.3 Hz, 1 Hb), 5.13 (t, J=9.9 Hz, 1 Ha), 4.50 (t, J=10.4 Hz, 1 Ha), 4.48 (d, J=9.9 Hz, 1 Ha), 4.46 (d, J=10.1 Hz, 1 Hb), 4.31 (d, J=10.1 Hz, 1 Hb), 3.93 (m, 2 Hb), 3.92 (m, 2 Ha), 3.66 (s, 3 H), 2.67 (s, 3 Ha), 2.64 (s, 3 Hb), 2.61 (t, J=7.8 Hz, 2 H), 2.33 (t, J=7.3 Hz, 2 H), 2.23 (s, 3 H), 2.09 (s, 3 Ha), 2.08 (s, 3 Hb), 2.02 (s, 3 Hb), 2.01 (s, 3 Ha), 1.93 (quin, J=7.3 Hz, 2 H), 1.75 (s, 3 Ha), 1.74 (s, 3 Hb). MS (ES+) [M+H]+=603.
Reaction SMILES: [C:1]([CH:3]([CH:8]([C:10]1[CH:15]=[CH:14][C:13]([N:16]2[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]2)=[CH:12][CH:11]=1)[CH3:9])C(OC)=O)#[N:2].[Cl-].[Na+].CS(C)=O>O>[CH3:22][N:19]1[CH2:20][CH2:21][N:16]([C:13]2[CH:14]=[CH:15][C:10]([CH:8]([CH3:9])[CH2:3][C:1]#[N:2])=[CH:11][CH:12]=2)[CH2:17][CH2:18]1
Reactant: COC(=O)C(C#N)C(C)c1ccc(N2CCN(C)CC2)cc1
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: CC(CC#N)c1ccc(N2CCN(C)CC2)cc1
Temperature: 162.5 °C
Yield: 79.7 %

Procedure:
A mixture of methyl 2-cyano-3-(4-(4-methylpiperazin-1-yl)phenyl)butanoate (700 mg, 2.32 mmol), sodium chloride (405 mg, 6.90 mmol), DMSO (5 ml) and water (2 ml, 3 vol %) and heated at 160-165° C. for 12 h. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford 450 mg (79.6%) of 3-(4-(4-methylpiperazin-1-yl)phenyl)butanenitrile as a colorless liquid.