Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]1[C:6]([NH:7][CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][N:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)[CH:13]=2)=[N:5][C:4]([CH2:25][S:26][CH2:27][C:28](OCC)=[O:29])=[N:3]1.[CH3:33][NH2:34]>>[CH3:33][NH:34][C:28](=[O:29])[CH2:27][S:26][CH2:25][C:4]1[N:5]=[C:6]([NH:7][CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][N:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)[CH:13]=2)[N:2]([CH3:1])[N:3]=1
Reactant: CCOC(=O)CSCc1nc(NCCCOc2cccc(CN3CCCCC3)c2)n(C)n1
Reactant: CN
Product: CNC(=O)CSCc1nc(NCCCOc2cccc(CN3CCCCC3)c2)n(C)n1

Procedure:
A solution of ethyl [[[1-methyl-5-[[3-[3-(1-piperidinylmethyl)phenoxy]propyl]amino]-1H-1,2,4-triazol-3-yl]methyl]thio]acetate (0.4 g) in ethanolic methylamine (33%, 20 ml) under nitrogen, was heated under reflux for 30 h, cooled, evaporated in vacuo, the residue dissolved in 2N hydrochloric acid (20 ml), and washed with ethyl acetate. The acidic layer was basified with potassium carbonate extracted with ethyl acetate and the extract was dried and evaporated to give an oil (0.28 g) which was chromatographed using System E as eluent to give the title compound (0.13 g) as an oil.
Reaction SMILES: [N:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:2]=1C.ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O.O.[OH-].[K+].[CH:27]([Cl:30])(Cl)[Cl:28]>>[Cl:28][CH:27]([C:2]1[CH:4]=[CH:5][C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[N:1]=1)[Cl:30]
Reactant: ClC(Cl)Cl
Reactant: Cc1ccc2ccccc2n1
Agent: O=c1n(Cl)c(=O)n(Cl)c(=O)n1Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: ClC(Cl)c1ccc2ccccc2n1
Temperature: 60 °C
Reaction time: 2.92 h
Yield: 24.5 %

Procedure:
A solution of 143.19 g (1 mole) of quinaldine in 350 ml of chloroform was heated to 60° C. and 83 g (0.36 mole) of trichloroisocyanuric acid (min. 90% available chlorine) were added thereto in portions over 175 minutes. The mixture was stirred for another 45 minutes at 60° C. and then cooled. 700 ml of water and 200 ml of 50% potassium hydroxide were added with stirring until two clear layers have formed. The decanted aqueous phase was extracted twice with 150 ml of chloroform and the combined chloroform phases were covered with a layer of 350 ml of 10% HCl to thoroughly extract any 2-monochloromethyl-quinoline from the chloroform solution. The decanted chloroform phase was dried over MgSO4 and evaporated to dryness on a rotary evaporator to obtain 52 g (24.5%) of crude dichloromethyl-quinoline. After recrystallization from isopropanol, there were 16 g (7.5%) of product melting at 80° to 81° C. with a chlorine content of 33.02% (theory 33.4%). The acid aqueous phase was covered with 300 ml of ethyl acetate and the pH was adjusted to 3 with 50% sodium hydroxide. The mixture was well stirred and the decanted aqueous phase was extracted with 100 ml of ethyl acetate again. The combined acetic ester phases were dried over MgSO4 and evaporated to dryness to obtain 95 g (53.5%) of crystalline 2-chloromethylquinoline melting at 53° C. with a chlorine content of 19.87% (theory 19.96%). The aqueous phase was made alkaline with sodium hydroxide and was extracted with 200 ml of ethyl acetate. After drying and evaporating the organic phase, 23 g of quinaline were recovered. The yield of 2-chloromethyl-quinoline calculated for reacted quinaldine was 63.7%.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[Cl:22])[CH2:5][CH:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:16][CH3:17])[CH:14]=2)[CH2:9][CH2:8][C:7]1=O.[NH:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1.CO.C#N.[Na]>C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[Cl:22])[CH2:5][CH:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:16][CH3:17])[CH:14]=2)[CH2:9][CH2:8][CH:7]1[N:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1
Reactant: C1CCNC1
Reactant: COc1ccc2c(c1)C(Cc1ccc(Cl)c(Cl)c1)C(=O)CC2
Agent: C#N
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Na]
Solvent: Cc1ccccc1
Solvent: CO
Solvent: O
Product: COc1ccc2c(c1)C(Cc1ccc(Cl)c(Cl)c1)C(N1CCCC1)CC2
Temperature: 25 °C
Reaction time: 96 h
Yield: 25 %

Procedure:
1-(3,4-Dichlorobenzyl)-7-methoxy-3,4-dihydronaphthalen-2(1H)-one (5.5 g, 16.4 mmol, example 1), pyrrolidine (1.40 g, 19.7 mmol), and p-toluenesulfonic acid monohydrate (31.0 mg, 0.164 mmol) were dissolved in toluene (100 ml) and refluxed for 2 h using a Dean-Stark condenser. The solvent was removed and after addition of MeOH (50 ml) and sodium cyanohydride (1.57 g, 24.6 mmol) the mixture was stirred for 4 d at room temperature under nitrogen. Water was added, the organic phase separated and the aqueous phase extracted with ethyl acetate. The combined organic layers were washed with saturated NaCl solution, dried over MgSO4, and concentrated to afford a residue that was purified by flash chromatography (silica gel, MeOH/CH2Cl23:97→5:95). The beige solid product (1.6 g, 25%) was obtained from precipitation in ethyl acetate/diisopropylether (1:1).
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]([CH3:41])=[C:5]([C:21]([O:23][CH2:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH:34]3[CH2:38][O:37]C(C)(C)[O:35]3)=[CH:28][CH:27]=2)=[O:22])[CH:6]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[C:7]=1[C:8]([O:10][CH3:11])=[O:9].Cl>CC(C)=O.O>[CH3:1][C:2]1[NH:3][C:4]([CH3:41])=[C:5]([C:21]([O:23][CH2:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH:34]([OH:35])[CH2:38][OH:37])=[CH:28][CH:27]=2)=[O:22])[CH:6]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[C:7]=1[C:8]([O:10][CH3:11])=[O:9]
Reactant: COC(=O)C1=C(C)NC(C)=C(C(=O)OCCc2ccc(OCC3COC(C)(C)O3)cc2)C1c1cccc([N+](=O)[O-])c1
Agent: Cl
Solvent: CC(C)=O
Solvent: O
Product: COC(=O)C1=C(C)NC(C)=C(C(=O)OCCc2ccc(OCC(O)CO)cc2)C1c1cccc([N+](=O)[O-])c1
Yield: 61.5 %

Procedure:
A solution of 21 g of 2,6-dimethyl-3-methoxycarbonyl-4-(3-nitrophenyl)-5-(2-[4-(2,2-dimethyl-1,3-dioxolan-4-yl)methoxyphenyl]ethoxycarbonyl)-1,4-dihydropyridine (6) in 150 mL of acetone and 50 mL of water was treated with 10 mL of hydrochloric acid and the mixture heated at reflux for 6 h. Water (500 mL) was added and the mixture was extracted with ether. The ether layer was dried over Na2SO4 and evaporated to an oil which was purified by medium pressure chromatography on silica gel (90% ethyl acetate-hexane) to give 12 g of 2,6-dimethyl-3-methoxycarbonyl-4-(3-nitrophenyl)-5-(2-[4-(2,3-dihydroxypropoxy)phenyl]ethoxycarbonyl)-1,4-dihydropyridine (1) as a thick oil which crystallized upon trituration with ethyl acetate, m.p. 117°-118° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([N+:13]([O-])=O)[C:5]2[N:9]=[C:8]([CH3:10])[N:7]([CH3:11])[C:6]=2[CH:12]=1.C.O.NN.CCCCCCC>CO.[Fe](Cl)(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([NH2:13])[C:5]2[N:9]=[C:8]([CH3:10])[N:7]([CH3:11])[C:6]=2[CH:12]=1
Reactant: Cc1nc2c([N+](=O)[O-])cc(Br)cc2n1C
Agent: Cl[Fe](Cl)Cl
Agent: NN
Solvent: O
Solvent: CO
Solvent: CCCCCCC
Product: Cc1nc2c(N)cc(Br)cc2n1C
Temperature: 80 °C
Yield: 79.1 %

Procedure:
To a solution of 19 g (70 mmol) 6-bromo-1,2-dimethyl-4-nitro-1H-benzimidazole in 250 ml methanol were added 13.7 g (84 mmol) iron(III) chloride and 6 g activated charcoal. The reaction mixture was heated to 80° C. and 17 ml hydrazine hydrate (95%) were slowly added. After refluxing for 3 h, the hot reaction mixture was filtered through celite and the precipitate was washed with methanol and dichloromethane. The filtrate was evaporated to give a suspension, which was treated with n-heptane. The precipitate was collected, washed with n-heptane and dried in vacuo to give 13.3 g (79%) of the title compound as a white solid. m.p. 206-209° C.
Reaction SMILES: [OH:1][C@@H:2]([C@H:8]([OH:25])[C:9](=[O:24])[NH:10][C@H:11]([C:16](=[O:23])[NH:17][CH2:18][CH2:19][CH:20]([CH3:22])[CH3:21])[CH2:12][CH:13]([CH3:15])[CH3:14])[C:3]([O:5]CC)=[O:4].[OH-].[K+]>CO>[OH:1][C@@H:2]([C@H:8]([OH:25])[C:9](=[O:24])[NH:10][C@H:11]([C:16](=[O:23])[NH:17][CH2:18][CH2:19][CH:20]([CH3:21])[CH3:22])[CH2:12][CH:13]([CH3:14])[CH3:15])[C:3]([OH:5])=[O:4]
Reactant: CCOC(=O)[C@@H](O)[C@H](O)C(=O)N[C@@H](CC(C)C)C(=O)NCCC(C)C
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: CC(C)CCNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](O)[C@H](O)C(=O)O
Temperature: 0 °C
Reaction time: 2 h
Yield: 92.6 %

Procedure:
Ethyl (2S,3S)-2,3-dihydroxy-3-[(S)-3-methyl-1-(3-methylbutylcarbamoyl)butylcarbamoyl]propionate (309 mg) obtained in Example 2 was dissolved in methanol. 2N KOH (472 μl) was added to the resultant solution, and the solution was stirred at 0° C. for two hours. Thereafter, the solvent was distilled off under reduced pressure, sodium bicarbonate solution was added to adjust the pH to be about 8, and the aqueous layer was washed with ethyl acetate. Subsequently, the pH was adjusted to about 2 with dilute hydrochloric acid, sodium chloride was added until the solution was saturated, and the aqueous layer was extracted with ethyl acetate. The extracted organic layer was washed with sodium chloride solution and dried with magnesium sulfate, and the solvent was distilled off under reduced pressure, thereby obtaining 264 mg of a target compound. NMR data of the compound were as follows.
Reaction SMILES: [C:1]([NH:5][CH2:6][C:7]1[N:8]=[C:9]([C:12]2[O:13][C:14]3[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][C:15]=3[CH:16]=2)[S:10][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[C:22](OC(=O)C)(=[O:24])[CH3:23]>C(OCC)(=O)C>[C:22]([N:5]([CH2:6][C:7]1[N:8]=[C:9]([C:12]2[O:13][C:14]3[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][C:15]=3[CH:16]=2)[S:10][CH:11]=1)[C:1]([CH3:4])([CH3:2])[CH3:3])(=[O:24])[CH3:23]
Reactant: CC(C)(C)NCc1csc(-c2cc3cc(O)ccc3o2)n1
Reactant: CC(=O)OC(C)=O
Solvent: CCOC(C)=O
Product: CC(=O)N(Cc1csc(-c2cc3cc(O)ccc3o2)n1)C(C)(C)C
Yield: 99.6 %

Procedure:
A mixture of 4-(tert-butylaminomethyl)-2-(5-hydroxybenzofuran-2-yl)thiazole (0.82 g) and acetic anhydride (0.75 g) in ethyl acetate (10 ml) was stirred under reflux for 4 hours. After being cooled, the resulting mixture was concentrated under reduced pressure. A solution of the resulting mixture in methanol (3 ml) and conc. ammonia water (1 ml) was stirred for 2 hours at ambient temperature, poured into brine, extracted with ethyl acetate, dried over magnesium sulfate and concentrated under reduced pressure to give 4-(N-acetyl-tert-butylaminomethyl)-2-(5-hydroxybenzofuran-2-yl)thiazole (0.93 g).
Reaction SMILES: [CH2:1]([CH2:8][NH:9][CH2:10][CH2:11][C:12]([OH:14])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:15][NH:16][CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[N:26]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:27][CH2:28][N:29]=2)=[CH:21][CH:20]=1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>O1CCCC1>[CH2:1]([CH2:8][NH:9][CH2:10][CH2:11][C:12]([CH2:15][NH:16][CH2:17][CH2:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]2[N:26]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:27][CH2:28][N:29]=2)=[CH:23][CH:24]=1)=[O:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CNCCc1ccc(C2=NCCN2C(=O)OC(C)(C)C)cc1
Reactant: O=C(O)CCNCCc1ccccc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCN=C1c1ccc(CCNCC(=O)CCNCCc2ccccc2)cc1

Procedure:
A solution of 2.08 g (9.06 mmol) of 3-(benzylmethylamino)propionic acid, 2.72 g (8.96 mmol) of tert.-butyl 2-[4-(2-methylaminoethyl)phenyl]-4,5-dihydroimidazole-1-carboxylate (see procedure 1 g), 5.05 ml (36.24 mmol) of triethylamine and 2.91 g (9.06 mmol) of TBTU in 350 ml of tetrahydrofuran was stirred at room temperature overnight. The mixture was then evaporated to dryness, and the residue was purified by column chromatography (mobile phase: dichloromethane/methanol/aqueous ammonia solution 9:1:0.1).
Reaction SMILES: [NH2:1][C:2]([NH2:4])=[O:3].N[C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([OH:11])=[O:10].Cl>CN(C)C=O.O>[C:9]([C:8]1[CH:7]=[C:6]([NH:1][C:2]([NH2:4])=[O:3])[CH:14]=[CH:13][CH:12]=1)([OH:11])=[O:10]
Reactant: NC(N)=O
Reactant: Nc1cccc(C(=O)O)c1
Agent: Cl
Solvent: O
Solvent: CN(C)C=O
Product: NC(=O)Nc1cccc(C(=O)O)c1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 19 %

Procedure:
Urea (17.5 g, 0.292 mol), m-aminobenzoic acid (Aldrich, 10.0 g, 0.073 mol), water (30 mL), and concentrated HCl (3 mL) were added to a 125-mL Erlenmeyer flask and boiled for 45 min. The brown suspension became a purple solution on boiling and a brown precipitate formed after 15 min. The pH of the solution was 7 after 45 min. The mixture was cooled on ice and a mauve solid was collected by filtration, slurried with water, and again collected by filtration. The solid was added to 50 mL boiling ethanol and dimethylformamide (DMF, 25 mL) was added by drop until the solid dissolved. No precipitate formed on cooling. Water was added with stirring until turbidity and then a few drops of DMF were added to give a clear solution. The solution was cooled on ice and a light-purple solid was collected by filtration. Water was added to the filtrate to precipitate a tan solid which was also collected by filtration. The tan solid was dissolved in 5% sodium bicarbonate and neutralized with a 10% solution of potassium bisulfate. The tan solid was collected by filtration, washed with water, and dried in vacuo. The tan solid was then recrystallized from 700 mL methanol and 300 mL water. After cooling, a purple solid was collected by filtration. The product was precipitated from the filtrate with the addition of 1 L of water. This light-tan solid was collected on a filter and dried in vacuo. The product was dissolved in 175 mL boiling ethanol and the volume was reduced to 75 mL and filtered while hot. This was slowly cooled to room temperature and then on ice to give an off-white solid. This solid was collected on a filter, washed with cold ethanol, and dried in vacuo to give 2.5 g (20%) of the title compound, mp 276°-280° C.
Reaction SMILES: [C:1]1(=[O:7])[O:6][CH:4]([CH3:5])[CH2:3][CH2:2]1.[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17]2[N:27]=[CH:26][CH:25]=[CH:24][C:18]=2[C:19](OCC)=[O:20])[CH:12]=[CH:13][C:14]=1[Cl:15].CC(C)([O-])C.[K+].[OH-].[K+]>>[Cl:8][C:9]1[CH:10]=[C:11]([N:16]2[C:17]3[C:18](=[CH:24][CH:25]=[CH:26][N:27]=3)[C:19]([OH:20])=[C:2]([CH2:3][CH:4]([OH:6])[CH3:5])[C:1]2=[O:7])[CH:12]=[CH:13][C:14]=1[Cl:15]
Reactant: CCOC(=O)c1cccnc1Nc1ccc(Cl)c(Cl)c1
Reactant: CC1CCC(=O)O1
Agent: CC(C)(C)[O-]
Agent: [K+]
Agent: [OH-]
Product: CC(O)Cc1c(O)c2cccnc2n(-c2ccc(Cl)c(Cl)c2)c1=O
Temperature: 110 °C
Reaction time: 5 h

Procedure:
A stirred mixture of gamma-valerolactone (40 g.), ethyl 2-(3,4-dichlorophenylamino)-nicotinate (20 g.) and potassium t-butoxide (30 g.) was warmed in an atmosphere of nitrogen to 110° C. and kept there for 5 hr. After cooling somewhat the product was poured into 1000 ml. of 5% KOH solution and was allowed to stir overnight. The basic solution was extracted with ether (2×500 ml.) and the aqueous solution was acidified to pH 5 with conc. HCl. The solid was filtered off, washed with water, dried in air then recrystallized from methanol/charcoal to yield the desired product, m.p. 232°-234° C.
Reaction SMILES: [Cl:1][C:2]1[C:13]([Cl:14])=[CH:12][C:5]2[O:6][C@@H:7]([CH2:10][OH:11])[CH2:8][O:9][C:4]=2[CH:3]=1.[H-].[Na+].[S:17](Cl)(=[O:20])(=[O:19])[NH2:18]>CN(C=O)C.O>[S:17](=[O:20])(=[O:19])([O:11][CH2:10][CH:7]1[O:6][C:5]2[CH:12]=[C:13]([Cl:14])[C:2]([Cl:1])=[CH:3][C:4]=2[O:9][CH2:8]1)[NH2:18]
Reactant: OC[C@H]1COc2cc(Cl)c(Cl)cc2O1
Reactant: NS(=O)(=O)Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: NS(=O)(=O)OCC1COc2cc(Cl)c(Cl)cc2O1
Reaction time: 0.5 h

Procedure:
(2S)-6,7 dichloro-2,3-dihydro-benzo[1,4]dioxin-2-ylmethanol (2.0 g, 8.5 mmol), prepared according to the procedure described in Example 11 above, in DMF (20 mL) was cooled in an ice bath. Then, 95% sodium hydride (0.28 g, 11 mmol) was added under argon and the reaction mixture was stirred 30 min. Sulfamoyl chloride (1.97 g, 17 mmol) was added and the reaction mixture was stirred with ice bath cooling. After 1 h, the reaction mixture was diluted with water (50 mL) and extracted three times with ethyl acetate. The combined ethyl acetate was washed with brine, dried (Na2SO4) and evaporated in vacuo to an oil, which was purified by flash column chromatography (ethyl acetate/heptane 1:1) to yield a white solid. The white solid was recrystallized from benzene to yield the title compound as a white solid.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6](Cl)=[O:7].[C:9]1([CH2:15][CH2:16][CH2:17][N:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH:19]2[CH3:24])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C(Cl)(Cl)Cl>[C:9]1([CH2:15][CH2:16][CH2:17][N:18]2[CH2:23][CH2:22][N:21]([C:6]([C:2]3[O:1][CH:5]=[CH:4][CH:3]=3)=[O:7])[CH2:20][CH:19]2[CH3:24])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CC1CNCCN1CCCc1ccccc1
Reactant: O=C(Cl)c1ccco1
Solvent: ClC(Cl)Cl
Product: CC1CN(C(=O)c2ccco2)CCN1CCCc1ccccc1

Procedure:
2-Furoyl chloride (1.5 g) was added dropwise with stirring to a solution of 1-(3-phenylpropyl)-2-methylpiperazine [b.p. 138° - 140°C (8 mmHg)] (2.2 g) and CHCl3 (100 ml).
Reaction SMILES: [CH:1](=[C:8](/[CH2:12][C:13]([N:15]1[CH2:24][CH2:23][C@H:22]2[C@@H:17]([CH2:18][CH2:19][CH2:20][CH2:21]2)[CH2:16]1)=[O:14])\[C:9]([OH:11])=[O:10])/[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(O)C.[Pd]>[CH2:1]([CH:8]([CH2:12][C:13]([N:15]1[CH2:24][CH2:23][C@H:22]2[C@@H:17]([CH2:18][CH2:19][CH2:20][CH2:21]2)[CH2:16]1)=[O:14])[C:9]([OH:11])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)/C(=C/c1ccccc1)CC(=O)N1CC[C@@H]2CCCC[C@H]2C1
Agent: [Pd]
Solvent: CCO
Product: O=C(O)C(CC(=O)N1CC[C@@H]2CCCC[C@H]2C1)Cc1ccccc1
Reaction time: 16 h
Yield: 93.4 %

Procedure:
To a suspension of (E)-2-benzylidene-3-(trans-decahydro- 2-isoquinolylcarbonyl)propionic acid (200 mg) in ethanol (2 ml) was added 10% Pd-C (20 mg) and the mixture was hydrogenated at room temperature and atmospheric pressure for 16 hours. After the catalyst was filtered off, the solvent was evaporated under reduced pressure to give 188 mg of 2-benzyl-3-(trans-decahydro-2-isoquinolylcarbonyl)propionic acid as a colorless viscous oil.
Reaction SMILES: [CH:1]1([N:8]2[CH:16]=[N:15][C:14]3[C:9]2=[N:10][CH:11]=[N:12][C:13]=3Cl)[S:5][C@H:4]([CH2:6][OH:7])[CH2:3][CH2:2]1.[C@@H]1(N2C3N=CN=C(N)C=3N=C2)O[C@H](CO)[C@@H](O)[C@H]1[OH:20]>CC[N+](CC)(CC)CC.[Br-]>[C@@H:1]1([N:8]2[C:9]3[N:10]=[CH:11][N:12]=[C:13]([OH:20])[C:14]=3[N:15]=[CH:16]2)[S:5][C@H:4]([CH2:6][OH:7])[CH2:3][CH2:2]1
Reactant: Nc1ncnc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Reactant: OC[C@@H]1CCC(n2cnc3c(Cl)ncnc32)S1
Agent: CC[N+](CC)(CC)CC
Agent: [Br-]
Product: OC[C@@H]1CC[C@H](n2cnc3c(O)ncnc32)S1
Reaction time: 34 h
Yield: 79 %

Procedure:
To a solution of the α/β anomers of 20 (82 mg, 0.3 mmol) in 20 mL of a 0.75 M TEAB buffer was added 3 μL adenosine deaminase. The reaction was stirred 34 h followed by lyophilization. The residue was purified by preparative TLC with 6:1 chloroform-methanol containing 1% acetic acid. The crude product was recrystallized from methanol/carbontetrachloride to give 30.5 mg (79%) of 21; mp. 195°-197° C.; [α]D25 -13.9° (c=0.1, H2O); FAB MS 253 (M+H+ ; 1H NMR (D20) δ 8.5 (s, 1, H-2), 8.2 (s, 1, H-8), 6.2 (m, 1, 1'-H), 3.95 (m, 1, 5'-H), 3.8 (m, 2, 4'-H, 5'-H), 2.5 (m, 2, 2'-H's), 2.3 (m, 1, 3'-H), 1.9 (m, 1, 3'-H).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2(O)[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:17]([C:25]#[C:26][C:27]3[CH:32]=[CH:31][C:30]([Br:33])=[CH:29][CH:28]=3)(O)[C:16]3[C:11]2=[CH:12][CH:13]=[CH:14][CH:15]=3)=[CH:4][CH:3]=1.O.O.[Sn](Cl)Cl>CC(C)=O.O.C(O)(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]#[C:9][C:10]2[C:23]3[C:18]([C:17]([C:25]#[C:26][C:27]4[CH:28]=[CH:29][C:30]([Br:33])=[CH:31][CH:32]=4)=[C:16]4[C:11]=2[CH:12]=[CH:13][CH:14]=[CH:15]4)=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:6][CH:7]=1
Reactant: OC1(C#Cc2ccc(Br)cc2)c2ccccc2C(O)(C#Cc2ccc(Br)cc2)c2ccccc21
Agent: Cl[Sn]Cl
Solvent: CC(C)=O
Solvent: CC(=O)O
Solvent: O
Product: Brc1ccc(C#Cc2c3ccccc3c(C#Cc3ccc(Br)cc3)c3ccccc23)cc1
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
To a suspension of 9,10-bis-(4-bromo-phenylethynyl)-9,10-dihydro-anthracene-9,10-diol (2.0 g, 3.5 mmol) in aceton (25 ml), a solution of tin(II)chloride dihydrate (1.82 g, 8.05 mmol) in a mixture of water (15 ml) and acetic acid (15 ml) is added within 15 minutes. The obtained suspension is stirred for another 2.5 hours at ambient temperature, and then the solid is filtered off to give a first crop the title compound. Over night another crop of product crystallizes from the mother liquors, and the combined crops are recrystallized from anisol (30 ml) to give the title compound as orange needles. DSC: mp=305° C. MS: 534 (correct isotope pattern). Elementary analysis: C, 67.45; (calcd. 67.19); H, 3.23; (calcd. 3.01).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[O:10])[N:8]3[CH2:11][CH2:12][NH:13][C:7]3([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][OH:21])=[CH:16][CH:15]=3)[CH2:6][N:5]2[CH:22]=1.[N:23]1[CH:28]=[CH:27][CH:26]=[C:25](B(O)O)[CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+].C(O)C>COCCOC.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.O>[OH:21][CH2:20][C:17]1[CH:16]=[CH:15][C:14]([C:7]23[NH:13][CH2:12][CH2:11][N:8]2[C:9](=[O:10])[C:4]2[N:5]([CH:22]=[C:2]([C:25]4[CH:24]=[N:23][CH:28]=[CH:27][CH:26]=4)[CH:3]=2)[CH2:6]3)=[CH:19][CH:18]=1
Reactant: OB(O)c1cccnc1
Reactant: O=C1c2cc(Br)cn2CC2(c3ccc(CO)cc3)NCCN12
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Solvent: COCCOC
Product: O=C1c2cc(-c3cccnc3)cn2CC2(c3ccc(CO)cc3)NCCN12
Temperature: 120 °C
Reaction time: 0.75 h
Yield: 96.5 %

Procedure:
7-bromo-10a-[4-(hydroxymethyl)phenyl]-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]-pyrazin-5-one (84 mg, 0.23 mmol), dichlorobis(triphenylphosphine)palladium(II) (6.5 mg, 9.3 μmol), 3-pyridine boronic acid (34 mg, 0.28 mmol) and an aqueous solution of sodium carbonate (2M) (58 mg, 28.8 μl, 0.41 mmol) were suspended in a mixture of 1,2-dimethoxyethane (2.5 mL), ethanol (200 μL) and water (300 μL). The reaction vessel was flushed with argon and heated at 120° C. After 45 minutes the reaction was complete. The mixture was diluted with CH2Cl2 (5 mL) then washed with H2O. The aqueous was extracted with CH2Cl2 (2×5 mL). The combined organic was evaporated to dryness to give crude 10a-[4-(hydroxymethyl)phenyl]-7-(pyridin-3-yl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (80 mg) that was used in the next step without further purification. ESI-MI m/z [M+H]+ 361.9.
Reaction SMILES: CS(O)(=O)=O.CS(O)(=O)=O.[NH2:11][C:12]1[C:19](=[O:20])[N:15]2[CH2:16][CH2:17][CH2:18][N:14]2[C:13]=1[NH2:21].[NH2:22][C:23]1[C:24]([Cl:31])=[C:25]([OH:30])[C:26]([CH3:29])=[CH:27][CH:28]=1.N.OO>O.C(O)C>[NH2:21][C:13]1[N:14]2[CH2:18][CH2:17][CH2:16][N:15]2[C:19](=[O:20])[C:12]=1/[N:11]=[C:28]1/[C:23]([NH2:22])=[C:24]([Cl:31])[C:25](=[O:30])[C:26]([CH3:29])=[CH:27]/1
Reactant: Nc1c(N)n2n(c1=O)CCC2
Reactant: Cc1ccc(N)c(Cl)c1O
Agent: CS(=O)(=O)O
Agent: N
Agent: OO
Solvent: O
Solvent: CCO
Product: CC1=C/C(=N\c2c(N)n3n(c2=O)CCC3)C(N)=C(Cl)C1=O

Procedure:
0.58 mmol of 2,3-diamino-6,7-dihydro-1H,5H-pyrazolo[1,2-a]pyrazol-1-one dimethane sulphonate was dissolved in a mixture of water and ethanol (7.5 ml/1.5 ml). This solution was admixed with 0.58 mmol of 3-amino-2-chloro-6-methylphenol, then with 1.8 ml of concentrated aqueous ammonia, then with 9 ml of hydrogen peroxide.