Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Si]([O:8][C@@H:9]1[CH2:14][CH2:13][C@H:12]([N:15]2[C:23]3[CH:22]=[CH:21][N:20]=[C:19]([O:24]C)[C:18]=3[C:17]([C:26]3[CH:31]=[CH:30][C:29]([S:32]([NH2:35])(=[O:34])=[O:33])=[CH:28][CH:27]=3)=[CH:16]2)[CH2:11][CH2:10]1)(C(C)(C)C)(C)C.[I-].[Na+].Cl[Si](C)(C)C.C(=O)([O-])O.[Na+]>C(#N)C>[OH:8][C@@H:9]1[CH2:14][CH2:13][C@H:12]([N:15]2[C:23]3[CH:22]=[CH:21][NH:20][C:19](=[O:24])[C:18]=3[C:17]([C:26]3[CH:31]=[CH:30][C:29]([S:32]([NH2:35])(=[O:34])=[O:33])=[CH:28][CH:27]=3)=[CH:16]2)[CH2:11][CH2:10]1
Reactant: COc1nccc2c1c(-c1ccc(S(N)(=O)=O)cc1)cn2[C@H]1CC[C@@H](O[Si](C)(C)C(C)(C)C)CC1
Agent: C[Si](C)(C)Cl
Agent: O=C([O-])O
Agent: [I-]
Solvent: CC#N
Product: NS(=O)(=O)c1ccc(-c2cn([C@H]3CC[C@@H](O)CC3)c3cc[nH]c(=O)c23)cc1
Temperature: 50 °C
Reaction time: 8 h

Procedure:
To a solution of 4-(1-(cis-4-((tert-butyl(dimethyl)silyl)oxy)cyclohexyl)-4-methoxy-1H-pyrrolo[3,2-c]pyridin-3-yl)benzenesulfonamide (20.0 mg) in acetonitrile (2 mL) were added sodium iodide (14.5 mg) and chloro(trimethyl)silane (0.049 mL), and the mixture was stirred overnight at 50° C. To the reaction mixture was added saturated aqueous sodium hydrogencarbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (basic silica gel, ethyl acetate to ethyl acetate/methanol) to give the title compound (12.3 mg).
Reaction SMILES: [F:1][CH:2]([F:5])[CH2:3]Cl.[CH2:6]([NH2:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(N(CC)CC)C.Cl>CN1CCCC1=O>[CH2:6]([NH:13][CH2:3][CH:2]([F:5])[F:1])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: FC(F)CCl
Reactant: NCc1ccccc1
Agent: Cl
Solvent: CN1CCCC1=O
Solvent: CCN(CC)CC
Product: FC(F)CNCc1ccccc1
Yield: 92.7 %

Procedure:
An amount of 10 g (92 mmol) of 2,2-difluoro-1-chloroethane, 5 g (46 mmol) of benzylamine and 5.2 g (51 mmol) of triethylamine are heated in 20.6 g of N-methylpyrrolidone in an autoclave at an internal temperature of 120° C. for 6 hours. Subsequently, 100 g of 1N hydrochloric acid are added and the solvent is removed under vacuum. The residue is taken up in 30 ml of dichloromethane and adjusted to pH 8 with solid sodium hydrogencarbonate. The phases are subsequently separated and the aqueous phase is again extracted with 20 ml of dichloromethane. The organic phase is distilled. An amount of 7.3 g of N-benzyl-2,2-difluoroethanamine is obtained, which corresponds to a yield of 93%, based on benzylamine.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8](=O)[C:9](=[CH:18][N:19](C)C)[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:11])[CH:5]=[CH:6][CH:7]=1.O.[NH2:24]N>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:9]([C:10](=[O:11])[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:18][NH:19][N:24]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: NN
Reactant: CN(C)C=C(C(=O)c1ccccc1)C(=O)c1cccc(Cl)c1
Solvent: CCO
Solvent: O
Product: O=C(c1ccccc1)c1c[nH]nc1-c1cccc(Cl)c1

Procedure:
1-(3-Chlorophenyl)-2-(N,N-dimethylaminomethylene)-3-phenyl-1,3-propanedione (11.25 g) synthesized in accordance with Example 1 was dissolved in ethanol (150 ml) and added with hydrazine hydrate (1.98 g). After heating at reflux temperature for 3 hours, the solvent was distilled off, and then the resulting residue was added with diisopropyl ether and stirred. The resulting solid was then filtered off, recrystallized from acetonitrile to give the compound of interest (3.0 g). M.P.: 161.3-164.1° C.
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[OH-].[Na+].[CH2:11](Br)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]>CS(C)=O.O>[CH2:11]([O:8][C:5]1[CH:6]=[CH:7][C:2]([I:1])=[CH:3][CH:4]=1)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: CCCCCCCCCCBr
Reactant: Oc1ccc(I)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: O
Product: CCCCCCCCCCOc1ccc(I)cc1
Yield: 88.3 %

Procedure:
To 34.0 g of p-iodo-phenol dissolved in 350 ml of DMSO, were added 7.4 g of sodium hydroxide dissolved in 50 ml of water and stirred to obtain a homogeneous solution. Then, 32.4 g of n-decyl bromide were added and stirred at room temperature for 3 days. The resulting solution was introduced into 1 l of iced water, and extracted three times with hexane. The hexane phase was washed with water, followed by distilling off the hexane to obtain 46.6 g of oily p-n-decyloxy-iodobenzene.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[N:13][OH:14])[C:9]([F:12])([F:11])[F:10])=[C:4](F)[CH:3]=1.N12CCCN=C1CCCCC2.C1COCC1>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]2[C:8]([C:9]([F:12])([F:11])[F:10])=[N:13][O:14][C:4]=2[CH:3]=1
Reactant: ON=C(c1ccc(Br)cc1F)C(F)(F)F
Solvent: ClCCl
Solvent: C1CCOC1
Solvent: C1CCC2=NCCCN2CC1
Product: FC(F)(F)c1noc2cc(Br)ccc12
Temperature: 150 °C
Yield: 67.3 %

Procedure:
A solution consisting of 1-(4-bromo-2-fluoro-phenyl)-2,2,2-trifluoro-ethanone oxime (3.2 g, 11 mmol), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (1.1 mL, 7.4 mmol) and THF (42 mL) was heated at 150° C. via microwave irradiation for 30 min. The reaction mixture was diluted with CH2Cl2 (25 mL) and washed with HCl (1 N aq., 25 mL). The organic layer was then dried (Na2SO4), concentrated and purified (FCC) to yield the title compound (1.97 g, 66%).
Reaction SMILES: [CH2:1]([S:5]([NH:8][C:9](=[O:20])[C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[C:12]([NH2:19])[CH:11]=1)(=[O:7])=[O:6])[CH2:2][CH2:3][CH3:4].[I-].[Na+].C(=O)([O-])[O-].[K+].[K+].[Cl:29][C:30]1[CH:37]=[C:36]([Cl:38])[CH:35]=[CH:34][C:31]=1[CH2:32]Cl>C(OCC)(=O)C.CO>[CH2:1]([S:5]([NH:8][C:9](=[O:20])[C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[C:12]([NH:19][CH2:32][C:31]2[CH:34]=[CH:35][C:36]([Cl:38])=[CH:37][C:30]=2[Cl:29])[CH:11]=1)(=[O:7])=[O:6])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCS(=O)(=O)NC(=O)c1ccc([N+](=O)[O-])c(N)c1
Reactant: ClCc1ccc(Cl)cc1Cl
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CO
Solvent: CCOC(C)=O
Product: CCCCS(=O)(=O)NC(=O)c1ccc([N+](=O)[O-])c(NCc2ccc(Cl)cc2Cl)c1
Temperature: 60 °C
Reaction time: 24 h
Yield: 52.7 %

Procedure:
A solution containing 1.10 g of N-1-butanesulfonyl-3-amino-4-nitrobenzamide, 0.273 g of sodium iodide, 1.54 g of potassium carbonate, 2.17 g of 2,4-dichlorobenzyl chloride and 10 ml of methanol was stirred at 60° C. for 24 hours. Further, 2.00 g of 2,4-dichlorobenzyl chloride were added thereto, and the mixture was heated at 60° C. for 36 hours. To the reaction solution were added ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate, and N-1-butanesulfonyl-3-(2,4-dichlorobenzylamino)-4-nitrobenzamide was extracted in the aqueous layer. The organic layer was concentrated to give 0.885 g of N-1-butanesulfonyl-3-(2,4-dichlorobenzylamino)-4-nitrobenzamide.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:14])[CH:4]([O:6][C:7]1[CH:12]=[CH:11][C:10]([NH2:13])=[CH:9][CH:8]=1)[CH3:5].C(N(CC)CC)C.Cl[C:23](Cl)([O:25]C(=O)OC(Cl)(Cl)Cl)Cl>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:14])[CH:4]([O:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]=[C:23]=[O:25])=[CH:9][CH:8]=1)[CH3:5]
Reactant: COC(=O)C(C)Oc1ccc(N)cc1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: COC(=O)C(C)Oc1ccc(N=C=O)cc1
Temperature: 75 °C
Yield: 143.8 %

Procedure:
To a mixture of 2-(4-aminophenoxy)-propionic acid methyl ester 10 (15 g, 76.9 mmol) and triethylamine (15.6 g, 154.16 mmol) in toluene (210 ml) under nitrogen atmosphere was added triphosgene (8.4 g, 28.3 mmol) in one lot. Later the reaction mixture was heated to 75° C. over a period of one hour and maintained at this temperature for 26 hours. The reaction mixture was cooled to room temperature, the solids filtered off, and the toluene was distilled off under vacuum to get crude 11, which was vacuum distilled to get pure 11 (9 grams, 52.9%) as a light yellow syrup.
Reaction SMILES: [N:1]1([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:5][CH:4]=[CH:3][CH2:2]1.F[B-](F)(F)F.[Cl:18][C:19]1[CH:20]=[CH:21][C:22]([F:27])=[C:23]([N+]#N)[CH:24]=1.N1C(C)=CC=CC=1C.FC(F)(F)C(OC(=O)C(F)(F)F)=O>O.C(Cl)(Cl)(Cl)Cl.C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([F:27])=[C:21]([CH:3]2[CH:4]=[CH:5][N:1]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:2]2)[CH:20]=1
Reactant: CC(C)(C)OC(=O)N1CC=CC1
Reactant: N#[N+]c1cc(Cl)ccc1F
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: F[B-](F)(F)F
Solvent: Cc1cccc(C)n1
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1C=CC(c2cc(Cl)ccc2F)C1
Temperature: 23 °C
Reaction time: 5 h

Procedure:
Palladium(II) acetate (106 mg, 0.473 mmol, 0.020 equiv) was added to a vigorously stirred, deoxygenated mixture of tert-butyl 2,5-dihydro-1H-pyrrole-1-carboxylate (4.00 g, 23.6 mmol, 1 equiv) and 5-chloro-2-fluorobenzenediazonium tetrafluoroborate (10.4 g, 42.5 mmol, 1.80 equiv) in water and carbon tetrachloride (1:1, 150 mL) at 23° C., and the resulting mixture was stirred for 20 hours. The reaction mixture was partitioned between saturated aqueous sodium bicarbonate solution (200 ml) and dichloromethane (2×200 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was dissolved in toluene (200 mL), and the resulting solution concentrated in vacuo to facilitate azeotropic removal of residual water. 2,6-Lutidine (5.51 mL, 47.3 mmol, 2.00 equiv) and trifluoroacetic anhydride (1.67 mL, 11.8 mmol, 0.500 equiv) were then sequentially added to a solution of the residue in toluene (150 mL) at −20° C. The resulting mixture was kept at −20° C. for 5 hours, then allowed to slowly warm to 23° C. After 16 hours at 23° C., the reaction mixture was heated at reflux for 30 minutes. The reaction mixture was allowed to cool to 23° C., then partitioned between ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate solution (100 mL). The organic layer was dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (hexanes initially, grading to 30% EtOAc in hexanes) to give tert-butyl 3-(5-chloro-2-fluorophenyl)-2,3-dihydro-1H-pyrrole-1-carboxylate (17-1) as an orange oil. LRMS m/z (M+H CH3) 283.0 found, 283.1 required.
Reaction SMILES: [CH3:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][CH:5]=[C:4]([CH3:11])[C:3]=1[NH:12][C:13](=[O:15])[CH3:14]>CO.CCO.C(O)(=O)C.[Pd]>[NH2:8][C:7]1[C:2]([CH3:1])=[C:3]([NH:12][C:13](=[O:15])[CH3:14])[C:4]([CH3:11])=[CH:5][CH:6]=1
Reactant: CC(=O)Nc1c(C)ccc([N+](=O)[O-])c1C
Agent: [Pd]
Solvent: CCO
Solvent: CO
Solvent: CC(=O)O
Product: CC(=O)Nc1c(C)ccc(N)c1C
Temperature: 25 °C
Reaction time: 36 h
Yield: 19.3 %

Procedure:
N-(2,6-dimethyl-3-nitro-phenyl)acetamide (12 g, 58 mmol, 1.0 eq) was dissolved in a mixture of MeOH (60 mL), EtOH (30 mL) and acetic acid (60 mL). Pd/C (1.6 g, 10%) was added and the reaction stirred at room temperature under H2 for 36 h. The catalyst was removed by filtration through celite and the filtrate collected. Water was added and the pH adjusted to pH 8 by addition of aqueous NaHCO3. The solution was concentrated in vacuo to remove methanol and ethanol. The aqueous layer was extracted with EtOAc and the combined organic extracts were dried (Na2SO4) filtered and evaporated in vacuo. The crude product was purified by column chromatography (EtOAc:petroleum ether, 1:10 to 1:1) to give the title compound as a yellow solid (2 g, 19%).
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7]O[C:9]2=[O:14])([O-:3])=[O:2].CO.Cl.[NH2:18][C@H:19]([CH3:23])[C:20]([NH2:22])=[O:21].C(N(CC)CC)C>>[N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][N:18]([C@H:19]([CH3:23])[C:20]([NH2:22])=[O:21])[C:9]2=[O:14])([O-:3])=[O:2]
Reactant: C[C@@H](N)C(N)=O
Reactant: O=c1occc2c([N+](=O)[O-])cccc12
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CO
Product: C[C@H](C(N)=O)n1ccc2c([N+](=O)[O-])cccc2c1=O
Temperature: 52 °C
Reaction time: 3 h

Procedure:
To a solution of 5-nitro-isochromen-1-one (2 g, 0.01 mol) in methanol (40 mL, 1 mol) was added (R)-2-aminopropanamide hydrochloride (2.0 g, 0.016 mol) and triethylamine (2.6 mL, 0.019 mol) and stirred at 52° C. for 3 hr. The product (yellow solid) precipitated out and was filtered and carried on to the next reaction. MS m/z=262.1 (M+1).
Reaction SMILES: C([Li])CCC.[CH3:6][N:7]1[CH:11]=[CH:10][N:9]=[CH:8]1.[Cu]C#N.[Cl-].[Li+].[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:33]=[C:32]([CH:34]=[CH:35][CH2:36]Br)[CH:31]=[CH:30][C:25]=2[C:26]([O:28][CH3:29])=[O:27])=[CH:20][CH:19]=1.C(N(CC(O)=O)CC(O)=O)CN(CC(O)=O)CC(O)=O>C1COCC1.O.[I-].[Zn+2].[I-]>[CH3:6][N:7]1[CH:11]=[CH:10][N:9]=[C:8]1[CH2:36][CH:35]=[CH:34][C:32]1[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[C:24]([C:21]2[CH:20]=[CH:19][C:18]([F:17])=[CH:23][CH:22]=2)[CH:33]=1
Reactant: Cn1ccnc1
Reactant: COC(=O)c1ccc(C=CCBr)cc1-c1ccc(F)cc1
Agent: N#C[Cu]
Agent: O=C(O)CN(CCN(CC(=O)O)CC(=O)O)CC(=O)O
Agent: [Cl-]
Solvent: C1CCOC1
Solvent: O
Product: COC(=O)c1ccc(C=CCc2nccn2C)cc1-c1ccc(F)cc1
Temperature: -78 °C
Reaction time: 0.75 h
Yield: 71 %

Procedure:
1H NMR (CDCl3, 400 MHz) δ: 3.65 (3H, m); 4.15 (2H, m); 6.1-6.2 and 6.4-6.7 (2H, m); 7-7.95 (7H, m). n-Butyl lithium (1.6 M solution in ether, 30 ml) was added at −78° C. and under argon atmosphere to a solution of N-methylimidazole (3.2 ml; 40 mmol). After stirring at −78° C. for 45 minutes, zinc iodide (14 g; 44 mmol) in solution in THF (100 ml) was added. The mixture was allowed to warm to ambient temperature for 1 hour, cooled down to −78° C., and a solution of copper (I) cyanide (0.72 g; 8 mmol) and lithium chloride (0.68 g; 1.6 mmol) in THF (10 ml) was then added at −78° C. followed by a solution of methyl 2-(4-fluorophenyl)-4-(3-bromoprop-1-en-1-yl)benzoate (7 g; 20 mmol) in THF (50 ml). The mixture was stirred at −78° C., for 30 minutes and for 1 hour 30 minutes at room temperature. After evaporation of the solvent, the residue was treated with EDTA (17 g; 44 mmol) in distilled water (50 ml) and extracted with dichloromethane. The organic layer was evaporated and purified by flash chromatography eluting with dichloromethane/ethanol (98/2) to give methyl 4-[3-(1-methylimidazol-2-yl)prop-1-en-1-yl]-2-(4-fluorophenyl)benzoate as a mixture of E and Z isomers. Yield: 71%
Reaction SMILES: C(N(CC)CC)C.[CH3:8][S:9](Cl)(=O)=O.O[C@H]1[CH2:18][N:17]([C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=2)=[O:20])[C@H:16]([C:32]([N:34]2[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][O:42][C:43]([O:45][CH2:46][C:47]3[CH:52]=[CH:51][C:50]([N+:53]([O-:55])=[O:54])=[CH:49][CH:48]=3)=[O:44])[CH2:36][CH2:35]2)=[O:33])[CH2:15]1>O1CCCC1>[SH:9][C@@H:8]1[CH2:18][N:17]([C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=2)=[O:20])[C@H:16]([C:32]([N:34]2[CH2:35][CH2:36][N:37]([CH2:40][CH2:41][O:42][C:43]([O:45][CH2:46][C:47]3[CH:48]=[CH:49][C:50]([N+:53]([O-:55])=[O:54])=[CH:51][CH:52]=3)=[O:44])[CH2:38][CH2:39]2)=[O:33])[CH2:15]1
Reactant: CS(=O)(=O)Cl
Reactant: O=C(OCCN1CCN(C(=O)[C@@H]2C[C@@H](O)CN2C(=O)OCc2ccc([N+](=O)[O-])cc2)CC1)OCc1ccc([N+](=O)[O-])cc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=C(OCCN1CCN(C(=O)[C@@H]2C[C@H](S)CN2C(=O)OCc2ccc([N+](=O)[O-])cc2)CC1)OCc1ccc([N+](=O)[O-])cc1
Reaction time: 0.5 h

Procedure:
89 μl of triethylamine and 50 μl of methanesulfonyl chloride were added, whilst ice-cooling, to a solution of 321 mg of (2S,4R)-4-hydroxy-2-{4-[2-(4-nitrobenzyloxycarbonyl)oxyethyl]-1-piperazinylcarbonyl}-1-(4-nitrobenzyloxycarbonyl)pyrrolidine in 3.2 ml of dry tetrahydrofuran, and the resulting mixture was stirred at between 0° C. and 5° C. for 30 minutes and then at room temperature for a further 1 hour. At the end of tis time, the reaction mixture was concentrated by evaporation under reduced pressure, and the resulting residue was mixed with an aqueous solution of sodium hydrogencarbonate; the mixture was then extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, to give 345 mg of the title compound as a powder.
Reaction SMILES: C[O:2][C:3](=[O:30])[C:4](=[O:29])[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][CH2:13][O:14][C:15]2[CH:28]=[CH:27][C:26]3[C:17](=[CH:18][C:19]4[C:24]([CH:25]=3)=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH:16]=2)=[CH:7][CH:6]=1.[OH-].[Na+]>O1CCCC1.O>[CH:16]1[C:17]2[C:26](=[CH:25][C:24]3[C:19]([CH:18]=2)=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:27]=[CH:28][C:15]=1[O:14][CH2:13][CH2:12][O:11][C:8]1[CH:9]=[CH:10][C:5]([C:4](=[O:29])[C:3]([OH:30])=[O:2])=[CH:6][CH:7]=1
Reactant: COC(=O)C(=O)c1ccc(OCCOc2ccc3cc4ccccc4cc3c2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)C(=O)c1ccc(OCCOc2ccc3cc4ccccc4cc3c2)cc1
Yield: 75.8 %

Procedure:
A mixture of 4-[[2-(2-anthracenyloxy)ethyl]oxy]-alpha-oxobenzeneacetic acid methyl ester (0.615 g) in hot tetrahydrofuran (100 mL) was treated with 1N sodium hydroxide (4 mL) and diluted with water. The resulting solids were recovered by filtration and stirred in a mixture of dichloromethane and excess 2N hydrochloric acid until the solids dissolved. The organic layer was separated, dried (Na2SO4), filtered, and evaporated to give crude product. Crystallization from acetone-hexane gave 0.45 g of 4-[[2-(2-anthracenyloxy) ethyl]oxy]-alpha-oxobenzene-acetic acid as a colorless solid, mp 213°-214° C.
Reaction SMILES: Cl[C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[NH:4][CH:5]=[N:6]2.[Cl:11][C:12]1[CH:13]=[C:14](/[CH:18]=[CH:19]/[C@H:20]2[CH2:24][CH2:23][CH2:22][NH:21]2)[CH:15]=[CH:16][CH:17]=1.C(N(CC)CC)C>C(O)CCC>[Cl:11][C:12]1[CH:13]=[C:14](/[CH:18]=[CH:19]/[C@H:20]2[CH2:24][CH2:23][CH2:22][N:21]2[C:2]2[N:10]=[CH:9][N:8]=[C:7]3[C:3]=2[N:4]=[CH:5][NH:6]3)[CH:15]=[CH:16][CH:17]=1
Reactant: Clc1ncnc2nc[nH]c12
Reactant: Clc1cccc(/C=C/[C@H]2CCCN2)c1
Solvent: CCCCO
Solvent: CCN(CC)CC
Product: Clc1cccc(/C=C/[C@H]2CCCN2c2ncnc3[nH]cnc23)c1
Yield: 16.5 %

Procedure:
695 mg of 6-chloropurine and 850 mg of (R)-2-[(E)-2-(3-chlorophenyl)vinyl]-pyrrolidine are dissolved in 20 ml of 1-butanol and warmed at 130° C. in the microwave for 6 h with 3.1 ml of triethylamine. For work-up, the batch is partitioned between ethyl acetate and water, the organic phase is dried over sodium sulfate, filtered off and evaporated in vacuo. The residue is purified by chromatography, giving 220 mg of 6-[(R)-2-((E)-2-(3-chlorophenyl)vinyl)pyrrolidin-1-yl]-9H-purine (“A11”); Rt: 1.778 min; [M+H]+326.2; m.p. 194-196°;
Reaction SMILES: Br[CH:2]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:15]1([N:21]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:22][C:23]([N:25]([CH3:31])[C@@H:26]2[CH2:30][CH2:29][NH:28][CH2:27]2)=[O:24])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C([O-])([O-])=O.[K+].[K+]>CC(=O)CC>[CH:2]([N:28]1[CH2:29][CH2:30][C@@H:26]([N:25]([CH3:31])[C:23](=[O:24])[CH2:22][N:21]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:27]1)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CN(C(=O)CN(c1ccccc1)c1ccccc1)[C@@H]1CCNC1
Reactant: BrC(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Product: CN(C(=O)CN(c1ccccc1)c1ccccc1)[C@@H]1CCN(C(c2ccccc2)c2ccccc2)C1

Procedure:
To a solution of bromodiphenylmethane (0.3 g, 1.23 mmol) in butanone (10 ml) was added (R)-2-diphenylamino-N-methyl-N-pyrrolidin-3-yl-acetamide (0.46 g, 1.5 mmol), K2CO3 (0.17 g, 1.23 mmol) and KI (0.2 g, 1.23 mmol). The mixture was heated under reflux for 18 hours, then filtered and the solvent was removed in vacuo. The residue was dissolved in CH2Cl2, (50 ml) and washed with water (10 ml). Drying over MgSO4 and removal of solvent under reduced pressure followed by column chromatography using Hex:EtOAc (3:1) gave the desired product.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[CH2:9][C:8](=[O:10])[N:7]([C@@H]2CCCC[C@H]2O)[C:6]1=[O:18])(=[O:3])[CH3:2].C(OC1C=C(CCN=C([O-])C(Cl)(Cl)Cl)C=CC=1OC)C1C=CC=CC=1>ClCCl>[C:1]([O:4][C@@H:5]1[CH2:9][C:8](=[O:10])[NH:7][C:6]1=[O:18])(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@@H]1CC(=O)N([C@@H]2CCCC[C@H]2O)C1=O
Agent: COc1ccc(CCN=C([O-])C(Cl)(Cl)Cl)cc1OCc1ccccc1
Solvent: ClCCl
Product: CC(=O)O[C@@H]1CC(=O)NC1=O
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 271.1 %

Procedure:
To a chilled (0° C.) solution of (3R)-1-((1R,2R)-2-hydroxylcyclohex-1-yl)-2,5-dioxopyrrolidin-3-yl acetate (15.0 g, 58.7 mmol) in anhydrous dichloromethane (100 mL) was added tetrafluoroboric acid diethyl ether complex (3.2 mL). The resultant reaction mixture was stirred at 0° C. for 20 minutes before adding a solution of 2-(3-benzyloxy-4-methoxy-phenyl)-ethyl-2,2,2-trichloroacetimidate (24.8 g, 61.6 mmol, 1.05 equiv.) in dichloromethane (100 mL) via an addition funnel over 30 minutes. The reaction mixture was stirred at 0° C. until the reaction was judged complete by HPLC analysis. The reaction mixture was quenched with water (250 mL). The organic layer was separated from the aqueous layer and subsequently washed with dilute NaHCO3 (5% wt solution, 2×100 mL), and water (5×100 mL). The organic layer was dried (anhydrous MgSO4), filtered, and concentrated under reduced pressure to ˜100 mL solution. The solution was cooled at −20° C. for 24 hours and the precipitate (trichloroacetamide) was removed by filtration. The filtrate was further concentrated to a volume of ˜40 mL. This process was repeated three times until the bulk of the by-product (trichloroacetamide) was removed. After the third filtration, the filtrate was concentrated in vacuo to give (1R, 2R)-12-[2-(3-benzyloxy-4-methoxy-phenyl)ethoxy]cyclohexyl}-2,5-dioxopyrrolidin-3-(R)-yl acetate as a pale yellow syrup (25 g, 86% yield).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]([Cl:11])([Cl:10])[Cl:9])[CH:5]=[C:4]([Cl:12])[N:3]=1.[Na].[CH3:14][O:15][CH2:16][CH2:17][OH:18]>>[Cl:12][C:4]1[CH:5]=[C:6]([C:8]([Cl:11])([Cl:10])[Cl:9])[CH:7]=[C:2]([O:18][CH2:17][CH2:16][O:15][CH3:14])[N:3]=1
Reactant: Clc1cc(C(Cl)(Cl)Cl)cc(Cl)n1
Reactant: COCCO
Agent: [Na]
Product: COCCOc1cc(C(Cl)(Cl)Cl)cc(Cl)n1
Reaction time: 5 h

Procedure:
To a solution of 26.54 grams (0.10 mole) of 2,6-dichloro-4-(trichloromethyl)pyridine dissolved in 150 milliliters (ml) of 2-methoxyethanol was added over a 35 minute period, a solution composed of 2.53 grams (0.11 mole) of sodium metal dissolved in 100 ml of 2-methoxyethanol. The mixture was stirred for 5 hours at 65°-75° C. The insoluble by-products were removed by filtration and the 2-methoxyethanol was removed by evaporation under reduced pressure. The resulting oily product was diluted with water and extracted with methylene chloride and dried with sodium sulfate. The methylene chloride was then removed leaving the 2-chloro-6-(2-methoxyethoxy)-4-(trichloromethyl)pyridine as an oil. The product was recovered in a yield of 25.6 grams (84 percent of theoretical) and had a refractive index of n 25/d = 1.5440. Upon analysis, the compound was found to have carbon, hydrogen and nitrogen contents of 35.48, 2.99 and 4.72 percent, respectively, as compared with the theoretical contents of 35.44, 2.97 and 4.59 percent, respectively, as calculated for the above named structure.