Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]([C:26]4[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=4)(O)[C:19]4[N:23]([CH3:24])[CH:22]=[N:21][N:20]=4)[CH:16]=3)[N:11]([CH3:33])[C:10](=[O:34])[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.S(Cl)([Cl:37])=O>>[Cl:37][C:18]([C:26]1[CH:27]=[CH:28][C:29]([Cl:32])=[CH:30][CH:31]=1)([C:19]1[N:23]([CH3:24])[CH:22]=[N:21][N:20]=1)[C:15]1[CH:16]=[C:17]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH3:33])[C:10](=[O:34])[CH:9]=[C:8]2[C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=1
Reactant: Cn1cnnc1C(O)(c1ccc(Cl)cc1)c1ccc2c(c1)c(-c1cccc(Cl)c1)cc(=O)n2C
Reactant: O=S(Cl)Cl
Product: Cn1cnnc1C(Cl)(c1ccc(Cl)cc1)c1ccc2c(c1)c(-c1cccc(Cl)c1)cc(=O)n2C
Temperature: 25 °C
Reaction time: 4 h

Procedure:
4-(3-chlorophenyl)-6-[(4-chlorophenyl)hydroxy(4-methyl-4H-1,2,4-triazol-3-yl)methyl]-1-methyl-2(1H)-quinolinone (0.012 mol) (described in Example B13) was added portionwise at 5° C. to thionyl chloride (6 ml). The mixture was stirred at room temperature for 4 hours. The solvent was evaporated till dryness. The product was used without further purification in the next reaction step, yielding 6-[chloro(4-chlorophenyl)(4-methyl-4H-1,2,4-triazol-3-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone.
Reaction SMILES: [NH2:1][C:2]1[C:3]([NH:14][CH2:15][C:16]([N:18]([CH3:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:17])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N:6][CH:7]=1.[C:26](OC(=O)C)(=[O:28])[CH3:27].N1C=CC=CC=1>C(Cl)(Cl)Cl>[C:26]([NH:1][C:2]1[C:3]([NH:14][CH2:15][C:16]([N:18]([CH3:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:17])=[N:4][C:5]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[N:6][CH:7]=1)(=[O:28])[CH3:27]
Reactant: CC(=O)OC(C)=O
Reactant: CN(C(=O)CNc1nc(-c2ccccc2)ncc1N)c1ccccc1
Solvent: ClC(Cl)Cl
Solvent: c1ccncc1
Product: CC(=O)Nc1cnc(-c2ccccc2)nc1NCC(=O)N(C)c1ccccc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A mixture of 2-(5-amino-2-phenyl-4-pyrimidinylamino)-N-methyl-N-phenylacetamide (3.6 g) obtained in Example 124, acetic anhydride (10 ml) and pyridine (7 ml) is stirred at room temperature for four hours. To the reaction mixture is added chloroform, and the mixture is washed with 1N hydrochloric acid, then washed with a saturated aqueous sodium hydrogen carbonate solution. The chloroform layer is collected, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (eluent; chloroform), and recrystallized from ethanol to give the desired compound (4.0 g), m.p. 200-201° C.
Reaction SMILES: [CH3:1][O:2][C:3]([C@@:5]1([CH3:9])[CH2:8][CH2:7][NH:6]1)=[O:4].[CH2:10](Br)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>C1COCC1>[CH3:1][O:2][C:3]([C@@:5]1([CH3:9])[CH2:8][CH2:7][N:6]1[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:4]
Reactant: COC(=O)[C@@]1(C)CCN1
Reactant: BrCc1ccccc1
Solvent: C1CCOC1
Product: COC(=O)[C@@]1(C)CCN1Cc1ccccc1
Temperature: 50 °C

Procedure:
To a solution of (R)-2-methyl-azetidine-2-carboxylic acid methyl ester (1 eq.) in THF were added TEA (2 eq.) and benzyl bromide (1 eq.). The reaction was heated at 50° C. for 15 h. The solvent was concentrated under reduced pressure, the crude was purified by chromatography on silica gel (elution with heptane/EtOAc 1/0 to 1/1) to afford (R)-1-benzyl-2-methyl-azetidine-2-carboxylic acid methyl ester.
Reaction SMILES: CO[C:3](=[O:31])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[C:13]([C:15]3[C:16]([C:24]4[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=4)=[N:17][O:18][C:19]=3[C:20]([F:23])([F:22])[F:21])[N:12]=[CH:11]2)=[N:6][CH:5]=1.[CH:32]1([NH2:35])[CH2:34][CH2:33]1>>[Cl:30][C:27]1[CH:26]=[CH:25][C:24]([C:16]2[C:15]([C:13]3[N:12]=[CH:11][N:10]([C:7]4[CH:8]=[CH:9][C:4]([C:3]([NH:35][CH:32]5[CH2:34][CH2:33]5)=[O:31])=[CH:5][N:6]=4)[CH:14]=3)=[C:19]([C:20]([F:22])([F:23])[F:21])[O:18][N:17]=2)=[CH:29][CH:28]=1
Reactant: COC(=O)c1ccc(-n2cnc(-c3c(-c4ccc(Cl)cc4)noc3C(F)(F)F)c2)nc1
Reactant: NC1CC1
Product: O=C(NC1CC1)c1ccc(-n2cnc(-c3c(-c4ccc(Cl)cc4)noc3C(F)(F)F)c2)nc1
Yield: 76 %

Procedure:
As described for Example 48b, 6-{4-[3-(4-chloro-phenyl)-5-trifluoromethyl-isoxazol-4-yl]-imidazol-1-yl}-nicotinic acid methyl ester (100 mg, 0.23 mmol), was converted, using cyclopropylamine instead of cyclopropanemethylamine, to the title compound (80 mg, 76%) which was obtained as a white solid. MS: m/e=474.1 [M+H]+.
Reaction SMILES: [Cl:1][S:2]([C:5]1[CH:6]=[C:7]([CH:11]=[CH:12][CH:13]=1)[C:8](Cl)=[O:9])(=[O:4])=[O:3].[CH3:14][C:15]([NH2:23])([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH3:16].N1C(C)=CC=CC=1C>C(Cl)Cl.CCOC(C)=O>[CH3:14][C:15]([NH:23][C:8]([C:7]1[CH:6]=[C:5]([S:2]([Cl:1])(=[O:4])=[O:3])[CH:13]=[CH:12][CH:11]=1)=[O:9])([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH3:16]
Reactant: CC(C)(N)c1ccccc1
Reactant: O=C(Cl)c1cccc(S(=O)(=O)Cl)c1
Solvent: Cc1cccc(C)n1
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CC(C)(NC(=O)c1cccc(S(=O)(=O)Cl)c1)c1ccccc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 106.7 %

Procedure:
3-Chlorosulfonyl-benzoyl chloride (1 g, 4.2 mmol) was dissolved in DCM (10 mL) and cooled in an ice bath. To the solution was added 1-methyl-1-phenyl-ethylamine (0.9 g, 3.8 mmol) and 2,6-lutidine (1 mL, 8.4 mmol). The mixture was allowed to warm up to RT and stirred for 4 h. The reaction mixture was diluted with EtOAc (100 mL) and washed with 1 N HCl (2×75 mL) and brine. The organic layer was dried (MgSO4) and evaporated in vacuo to provide 1.37 g (98%) of 3-(1-methyl-1-phenyl-ethylcarbamoyl)-benzenesulfonyl chloride as a tan solid. 1H-NMR (CDCl3): δ 8.40 (t, 1H, J=1.7 Hz), 8.15-8.18 (m, 2H), 7.72 (t, 1H, J=7.8 Hz), 7.46-7.50 (m, 2H), 7.36-7.41 (m, 2H), 7.27-7.32 (m, 1H), 6.56 (br s, 1H), and 1.87 (s, 6H).
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[CH2:11][C:10]([CH3:13])([CH3:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7](Br)[CH:8]=2)[S:3]1.C([Li])(C)(C)C.[C:21](=[O:23])=[O:22].O>CCOCC.CCCCC>[CH3:1][C:2]1([CH3:15])[CH2:11][C:10]([CH3:13])([CH3:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:21]([OH:23])=[O:22])[CH:8]=2)[S:3]1
Reactant: CC1(C)CC(C)(C)c2cc(Br)ccc2S1
Reactant: O=C=O
Agent: [Li]C(C)(C)C
Solvent: CCCCC
Solvent: O
Solvent: CCOCC
Product: CC1(C)CC(C)(C)c2cc(C(=O)O)ccc2S1
Temperature: -78 °C
Reaction time: 2 h

Procedure:
To a stirred solution of 240 mg (0.84 minol) of 2,2,4,4-tetramethyl-6-bromothiochroman in 1 ml of dry ether at -78° C. was added, dropwise under nitrogen, 1 ml of 1.7M (1.7 mmol) tert-butyl lithium in pentane. The reaction mixture was stirred at -78° C. for a further 2 h and then treated quickly with an excess of dry ice. The reaction mixture was warmed to room temperature and treated with 1 ml of water and 1 ml of ether. The aqueous layer was separated and the organic layer was extracted with 4×5 ml of water. The aqueous extracts were combined, acidified with HCl to a pH of 2 and then extracted with 2×15 ml of ether. The ether extracts were combined, washed with water and saturated NaCl solution and then dried (MgSO4). The ether solution was filtered and the solvent removed in-vacuo to give the title compound as a white solid. PMR (CDCl3): δ1.42 (6H, s), 1.43 (6H, s), 2.03 (2H, s), 7.50 (1H, d, J~8.4 Hz), 7.81 (1H, dd, J~8.4 Hz, 1.8 Hz), 7.89 (1H, d, J~1.8 Hz).
Reaction SMILES: [CH2:1]([N:5]1[C:9](=[O:10])[C:8]2=[CH:11][CH:12]=[CH:13][CH:14]=[C:7]2[C:6]1=[O:15])[CH2:2][C:3]#[CH:4].O1CCCC1.[CH2:21]([C:28]1[S:29][CH:30]=[C:31](Br)[N:32]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu](I)I.C(N(CC)CC)C>[CH2:21]([C:28]1[S:29][CH:30]=[C:31]([C:4]#[C:3][CH2:2][CH2:1][N:5]2[C:9](=[O:10])[C:8]3[C:7](=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:6]2=[O:15])[N:32]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: C#CCCN1C(=O)c2ccccc2C1=O
Reactant: Brc1csc(Cc2ccccc2)n1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: I[Cu]I
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=C1c2ccccc2C(=O)N1CCC#Cc1csc(Cc2ccccc2)n1
Temperature: 25 °C
Yield: 66.9 %

Procedure:
To 143 mg of dichlorobis(triphenylphosphine)palladium, 38 mg of copper iodide, and 0.80 g of N-(3-butynyl)phthalimide were added 9 ml of tetrahydrofuran, 1.02 g of the 2-benzyl-4-bromothiazole obtained in the foregoing stage, and 2.3 ml of triethylamine in a nitrogen atmosphere, and the mixture was stirred under reflux for 4 hours. After the stirring, the reaction mixture was cooled to room temperature and the solids were filtered. After concentrating the filtrate, the residue was purified by column chromatography (Wakogel C-200; toluene:ethyl acetate=9:1) to give 1.00 g of a phthalimide compound.
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1I.[S:22]1[CH:26]=[CH:25][CH:24]=[C:23]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].CCOCC>C(COC)OC.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>[NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[C:23]1[S:22][CH:26]=[CH:25][CH:24]=1
Reactant: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1I
Reactant: OB(O)c1cccs1
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: O
Solvent: COCCOC
Solvent: CCOCC
Product: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1-c1cccs1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-iodopyrazole (0.45 g) in dimethoxyethane (4 ml) containing tetrakis(triphenylphosphine)palladium(0) (0.035 g) was stirred at room temperature for 30 minutes and then heated to 80° C. Thiophene-2-boronic acid (0.14 g) and aqueous sodium carbonate solution (2 ml, 1M) were added and the mixture heated under reflux for 3 hours. The cooled reaction was poured into ether and water. The organic layer was separated, dried (MgSO4) and evaporated. The residue was taken up the minimum amount of dichloromethane and silica gel (10 g) added. The solvent was removed and the residue applied to a column of silica gel (75 g) which was eluted with hexane containing increasing proportions of dichloromethane. Combination and evaporation of suitable fractions gave the title compound as a white solid. A sample recrystallised form methanol had m.p. 206-7° C.
Reaction SMILES: FC(F)(F)C(O)=O.[CH2:8]([O:10][CH2:11][CH2:12][O:13][C:14]1[N:22]=[C:21]2[C:17]([N:18]=[C:19]([O:23][CH3:24])[NH:20]2)=[C:16]([NH2:25])[N:15]=1)[CH3:9].C(=O)([O-])[O-].[K+].[K+].CS(O[CH2:37][CH:38]1[CH2:43][CH2:42][CH2:41][O:40][CH2:39]1)(=O)=O>CN(C)C=O.C(OCC)(=O)C>[CH2:8]([O:10][CH2:11][CH2:12][O:13][C:14]1[N:22]=[C:21]2[C:17]([N:18]=[C:19]([O:23][CH3:24])[N:20]2[CH2:37][CH:38]2[CH2:43][CH2:42][CH2:41][O:40][CH2:39]2)=[C:16]([NH2:25])[N:15]=1)[CH3:9]
Reactant: CS(=O)(=O)OCC1CCCOC1
Reactant: CCOCCOc1nc(N)c2nc(OC)[nH]c2n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: O=C(O)C(F)(F)F
Product: CCOCCOc1nc(N)c2nc(OC)n(CC3CCCOC3)c2n1
Temperature: 60 °C
Reaction time: 1.5 h

Procedure:
To a solution of 2-{[2-(ethyloxy)ethyl]oxy}-8-(methoxy)-9H-purin-6-amine trifluoroacetic acid salt (500 mg) in dry N,N-dimethylformamide (6.0 ml) at room temperature and under nitrogen was added potassium carbonate (0.75 g) in one go. The reaction was stirred at 60° C. for 1.5 hours. A solution of tetrahydro-2H-pyran-3-ylmethyl methanesulfonate (0.29 g) in dry N,N-dimethylformamide (1.0 ml) was added in one go and the reaction heated at 90° C. for 2 hours. The reaction was cooled to room temperature and then diluted with ethyl acetate (20 ml) and washed with water (10 ml). The organic layer was concentrated in vacuo. The product was purified by C18 reverse phase chromatography using water (containing 0.1% formic acid)-acetonitrile (containing 0.05% formic acid) as eluant (10-60%) to afford the title compound as a clear viscous oil that crystallises at room temperature (245 mg).
Reaction SMILES: C([Li])CCC.[CH:6]([C@H:9]1[CH2:13][O:12][C:11](=[O:14])[NH:10]1)([CH3:8])[CH3:7].[C:15]1([CH2:21][CH2:22][C:23](Cl)=[O:24])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[Cl-].[NH4+]>CCCCCC.O1CCCC1>[CH:6]([C@H:9]1[CH2:13][O:12][C:11](=[O:14])[N:10]1[C:23](=[O:24])[CH2:22][CH2:21][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([CH3:8])[CH3:7]
Reactant: CC(C)[C@H]1COC(=O)N1
Reactant: O=C(Cl)CCc1ccccc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CC(C)[C@H]1COC(=O)N1C(=O)CCc1ccccc1
Reaction time: 0.5 h
Yield: 84.6 %

Procedure:
68.3 ml (0.11 mol) of butyllithium (as a 1.6M solution in hexane) were added dropwise, at -78° C. and under an atmosphere of nitrogen, to a solution of 11.75 g (91.0 mmole) of 4(S)-isopropyl-2-oxazolidinone in 200 ml of anhydrous tetrahydrofuran; the mixture was then stirred for 30 minutes, after which a solution of 18.41 g (0.11 mole) of phenylpropionyl chloride in 100 ml of anhydrous tetrahydrofuran was added to it over a period of 10 minutes. The mixture was then stirred for 1 hour, after which it was mixed with a saturated aqueous solution of ammonium chloride and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and the solvent was then removed by distillation under reduced pressure. The residue was purified by medium pressure column chromatography through silica gel (using a 1:3 by volume mixture of ethyl acetate and hexane as the eluent), followed by recrystallization from diisopropyl ether, to afford 20.12 g (yield 85%) of the title compound as white crystals, melting at 62°-63° C.
Reaction SMILES: [Cl:1][C:2]1[C:3]([N+:9]([O-])=O)=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].C(O)(=O)C>C(O)(C)C.O.[Ni]>[Cl:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:4]([NH2:5])[C:3]=1[NH2:9]
Reactant: Nc1cccc(Cl)c1[N+](=O)[O-]
Agent: [Ni]
Solvent: O
Solvent: CC(C)O
Solvent: CC(=O)O
Product: Nc1cccc(Cl)c1N
Temperature: 25 °C
Reaction time: 5 h
Yield: 66.6 %

Procedure:
3-Chloro-2-nitro-aniline (0.345 g, 2 mmol) was dissolved in iso-propanol (10 ml) and water (2 ml). Catalytic acetic acid (0.1 ml) was added, followed by Raney nickel (0.02 g, as 50% slurry in H2O) under a flow of nitrogen. The reaction mixture was then shaken under an atmosphere of hydrogen at ambient temperature for 5 hours and the catalyst was removed by filtration under a nitrogen atmosphere. The filtrate was reduced in vacuo, partitioned between ethyl acetate and water, and the organic layer reduced in vacuo to give 3-chloro-benzene-1,2-diamine as a brown oil (0.190 g, 67%). (LC/MS: Rt 1.84, [M+H]+ 143.07).
Reaction SMILES: C(O[Na])C.[OH:5][C:6]1[CH:13]=[CH:12][C:9]([CH:10]=[O:11])=[CH:8][CH:7]=1.Br[C:15]([CH3:22])([CH3:21])[C:16]([O:18][CH2:19][CH3:20])=[O:17]>C(O)C>[CH:10]([C:9]1[CH:12]=[CH:13][C:6]([O:5][C:15]([CH3:22])([CH3:21])[C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:7][CH:8]=1)=[O:11]
Reactant: CCOC(=O)C(C)(C)Br
Reactant: O=Cc1ccc(O)cc1
Agent: CCO[Na]
Solvent: CCO
Product: CCOC(=O)C(C)(C)Oc1ccc(C=O)cc1
Yield: 41.9 %

Procedure:
In an ethanol solvent, 1 N ethoxy sodium (NaOEt) (1.1 eq.) was added dropwise to 4-hydroxybenzaldehyde (1.0 eq.) and ethyl α-bromoisobutyrate (1.1 eq.), and the reaction mixture was refluxed. After the ethanol was evaporated, the residual was distributed between ethyl acetate and water, and an organic layer was dried by using MgSO4, filtered, and evaporated. The residual was purified by silica gel column chromatography using hexane and ethyl acetate (8:1) to obtain Compound 97a.
Reaction SMILES: Cl[C:2]1[CH:11]=[N:10][C:9]2[C:4](=[C:5]3[CH:19]=[CH:18][CH:17]=[CH:16][C:6]3=[C:7]3[CH:15]=[CH:14][CH:13]=[CH:12][C:8]3=2)[N:3]=1.[CH:20]1[C:28]2[C:27]3[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=3[S:25][C:24]=2[C:23]([C:33]2[CH:34]=[C:35](B(O)O)[CH:36]=[C:37]([C:39]3[C:44]4[S:45][C:46]5[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=5[C:43]=4[CH:42]=[CH:41][CH:40]=3)[CH:38]=2)=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1>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.C(O)C.O>[CH:20]1[C:28]2[C:27]3[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=3[S:25][C:24]=2[C:23]([C:33]2[CH:34]=[C:35]([C:2]3[CH:11]=[N:10][C:9]4[C:4](=[C:5]5[CH:19]=[CH:18][CH:17]=[CH:16][C:6]5=[C:7]5[CH:15]=[CH:14][CH:13]=[CH:12][C:8]5=4)[N:3]=3)[CH:36]=[C:37]([C:39]3[C:44]4[S:45][C:46]5[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=5[C:43]=4[CH:42]=[CH:41][CH:40]=3)[CH:38]=2)=[CH:22][CH:21]=1
Reactant: OB(O)c1cc(-c2cccc3c2sc2ccccc23)cc(-c2cccc3c2sc2ccccc23)c1
Reactant: Clc1cnc2c3ccccc3c3ccccc3c2n1
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: [K+]
Solvent: CCO
Solvent: O
Solvent: Cc1ccccc1
Product: c1ccc2c(c1)sc1c(-c3cc(-c4cnc5c6ccccc6c6ccccc6c5n4)cc(-c4cccc5c4sc4ccccc45)c3)cccc12
Temperature: 320 °C
Yield: 31.1 %

Procedure:
Into a 200-mL three-neck flask were put 1.2 g (4.5 mmol) of 2-chlorodibenzo[f,h]quinoxaline, 2.2 g (4.5 mmol) of 3,5-bis(dibenzothiophen-4-yl)phenylboronic acid, and 1.2 g (9.0 mmol) of potassium carbonate. To this mixture were added 23 mL of toluene, 4.5 mL of water, and 5 mL of ethanol, and this mixture was degassed by being stirred under reduced pressure. To the mixture was added 104 mg (0.09 mmol) of tetrakis(triphenylphosphine)palladium(0), and this mixture was stirred under a nitrogen stream at 100° C. for 3.5 hours. After the stirring, the obtained mixture was filtrated, and the solid was washed with water and then with ethanol. To the obtained solid was added toluene, and the mixture was suction-filtered through Celite, alumina, and Florisil. The filtrate was concentrated to give a solid. This solid was recrystallized from toluene, so that 1.4 g of a white solid was obtained in a yield of 46%. By a train sublimation method, 1.3 g of the obtained solid was purified. In the purification by sublimation, 2DBT2PDBq-II was heated at 320° C. under a pressure of 2.8 Pa with a flow rate of argon gas of 5 mL/min. After the purification by sublimation, 0.94 g of a white solid was obtained at a collection rate of 72%. The synthesis scheme of Step 3 is shown in (b-3).
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][C@H:6]([OH:25])/[CH:7]=[CH:8]/[C@@H:9]1[C@@H:14]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]([OH:23])=[O:22])[C:12](=[O:13])[CH2:11][C@H:10]1[OH:24].[CH:26](Cl)(Cl)Cl.C(O)(=O)C.O>CO>[CH3:26][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][C@H:6]([OH:25])/[CH:7]=[CH:8]/[C@@H:9]1[C@@H:14]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]([OH:23])=[O:22])[C:12](=[O:13])[CH2:11][C@H:10]1[OH:24]
Reactant: CCCCC[C@H](O)/C=C/[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)O
Reactant: ClC(Cl)Cl
Solvent: O
Solvent: CO
Solvent: CC(=O)O
Product: CCCCCC[C@H](O)/C=C/[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)O

Procedure:
A mixture of heneicosa-8c, 11c,14c-trienoic acid (24 mg), glutathione (120 mg), hydroquinone (12 mg) and protein (600 mg) from the particulate enzyme fraction of the vesicular glands of sheep (obtained as described by Struyk et al., loc.cit.) suspended in aqueous 0.2 M tris(hydroxymethyl)aminomethane hydrochloride buffer solution, pH 8.0, to a total volume of 300 ml, was incubated aerobically by stirring the mixture in a large beaker open to the air at 30° for 20 minutes. The enzymic reaction was then terminated by acidification with citric acid to pH 4 and the mixture was extracted with two portions of ether (300 ml). The residue from evaporation of the extract was dissolved in chloroform and the solution chromatographed on a column of silica gel (25 g) using as successive eluants chloroform (150 ml), chloroform containing 3% methanol (150 ml), and chloroform containing 5% methanol (150 ml), and 10 ml fractions of eluate were collected. Small samples of the fractions (0.1 ml) were tested for the presence of a prostaglandin by treatment with 0.5 ml 3N potassium hydroxide in 75% aqueous methanol and examination for an ultraviolet absorption peak at 278 nm. The last fractions of the 3% methanol eluant and the first fractions of the 5% methanol eluant were found to contain the substance required: they were evaporated to give 12 mg of product. This was then purified further by RPPC using as support a diatomaceous earth (2.5 g) that had been made water-repellent by the action of a methylchlorosilane, as stationary phase a mixture (1.8 ml) of equal volumes of iso-octanol and chloroform, and as eluant aqueous methanol containing 9 volumes of methanol to 10 of water, and collecting 2 ml fractions. All those fractions shown to give the alkali reaction referred to above, except the first and the last, were combined and evaporated and the residue recrystallised from a mixture of ether and light petroleum to give 1α-(6-carboxyhexyl)-4α-hydroxy-5β-(3S-hydroxynon-1t-enyl)cyclopentan-2-one (ω-homo-PGE1, 7.2 mg), m.p. 92°-3°, showing an optical rotation in methanol (1 g/liter) at 20° of -69°. Comparison with PGE1 by TLC on silica gel using a mixture of chloroform, methanol, acetic acid and water in the respective proportions by volume 90:8:1:0.75, gave an Rf value for ω-homo-PGE1 of 0.34 as compared with 0.32 for PGE1, the two substances being just separated.
Reaction SMILES: [NH3:1].[Br:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([CH2:13]Br)=[CH:5][CH:4]=1.[ClH:15]>C(Cl)Cl>[ClH:15].[Br:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([CH2:13][NH2:1])=[CH:5][CH:4]=1
Reactant: BrCc1ccc(Br)c2ccccc12
Reactant: N
Agent: Cl
Solvent: ClCCl
Product: NCc1ccc(Br)c2ccccc12
Temperature: -40 °C
Reaction time: 18 h
Yield: 80 %

Procedure:
A mixture of 1-bromo-4-methylnaphthaline (25 g, 0.113 mol), NBS (22.2 g, 0.123 mol) and benzoylperoxide (5 g) in CCl4 (750 mL) was refluxed for 5 h. The reaction mixture was cooled, filtered off the succinimide and concentrated to give crude bromide (34 g) and used for the next reaction without any purification. To a cold (−40° C.) solution of liquid ammonia (2 L) was added 1-bromo-4-bromomethyl naphthaline (crude 34 g) dissolved in 200 mL of CH2Cl2 over a period of 45 min. The reaction mixture was then stirred at −40° C. for 18 h. The reaction mixture was then allowed to stir at RT and concentrated under vacuum to give yellow residue. The residue was then treated with 3N HCl (250 mL), filtered off the solid obtained and washed with CH2Cl2 (2×250 mL). The solid was dried under vacuum to give (4-bromo-1-naphthyl)methylamine hydrochloride (25 g, 80%). HPLC purity: 96.6%
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=1.C([Li])CCC.[C:14](=[S:16])=[S:15].Br[CH:18]([CH3:23])[C:19]([O:21][CH3:22])=[O:20]>C1COCC1>[CH3:1][N:2]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=1)[C:14]([S:16][CH:18]([CH3:23])[C:19]([O:21][CH3:22])=[O:20])=[S:15]
Reactant: CNc1ccccn1
Reactant: COC(=O)C(C)Br
Reactant: S=C=S
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: COC(=O)C(C)SC(=S)N(C)c1ccccn1
Temperature: -10 °C
Reaction time: 1 h

Procedure:
To a cold (−10° C.) solution of 2-(methylamino)pyridine (1.71 g; 15.8 mmol) in dry THF (50 mL) was added n-butyl lithium (1.6M in hexane) (10 mL, 16 mmol) over 30 minutes under an inert atmosphere. The resultant pale yellow mixture was allowed to stir at −10° C. for one hour and then warmed to 0° C. before the dropwise addition of carbon disulfide (1.58 g, 20.8 mmol); the resultant solution was allowed to stir at room temperature for one hour. Methyl 2-bromopropionate (2.84 g, 17 mmol) was added dropwise and allowed to stir for 2 hours. THF was removed in vacuo, the mixture was suspended in ethyl acetate and filtered. After in vacuo elimination of the ethyl acetate the crude product was purified by column chromatography using 20% ethyl acetate in n-hexane as eluent to afford the title product (6), an off-white solid (2.32 g, 54.3% yield). 1H nmr (CDCl3) δ (ppm) 1.50 (d, 3H, CHCH3); 3.70 (s, 3H, COOCH3 or N—CH3); 3.75 (s, 3H, COOCH3 or N—CH3); 4.70 (q, 1H, CHCH3); 7.30-7.40 (m, 2H, ArH); 7.80 (m, 1H, ArH); 8.60 (m, 1H, ArH).