Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[CH3:12])[C:5]([O:7][CH3:8])=[O:6].[Br:13]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Br:13][CH2:12][C:11]1[CH:10]=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]=1[F:1]
Reactant: COC(=O)c1ccc(C)c(F)c1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1ccc(CBr)c(F)c1
Yield: 47.9 %

Procedure:
To a mixture of methyl 3-fluoro-4-methylbenzoate (0.630 g; 3.75 mmol) in carbon tetrachloride (30 mL) was added N-bromosuccinimide (0.840 g, 4.67 mmol) and benzoyl peroxide (0.094 g; 0.375 mmol). The mixture was refluxed for 18 hours and the resulting suspension was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent 1 to 12% ethyl acetate in heptane) to give 0.444 g (48%) of methyl 4-(bromomethyl)-3-fluorobenzoate as an oily residue which was directly used in the next step.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:8]=[C:9]([CH:13]=[CH:14][CH:15]=2)[C:10](O)=[O:11])[CH2:3][CH2:2]1.C(Cl)(=O)C([Cl:19])=O>O1CCOCC1>[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:8]=[C:9]([CH:13]=[CH:14][CH:15]=2)[C:10]([Cl:19])=[O:11])[CH2:3][CH2:2]1
Reactant: O=C(O)c1cccc(N2CCOCC2)c1
Reactant: O=C(Cl)C(=O)Cl
Solvent: C1COCCO1
Product: O=C(Cl)c1cccc(N2CCOCC2)c1
Reaction time: 1 h
Yield: 81.8 %

Procedure:
The above reagents, including 25 g of 3-morpholinobenzoic acid and 15.2 g of oxalyl chloride, were mixed in dioxane at 0° C. under argon gas. The reaction proceeded for about 2 hours, one hour at 0° C. and one hour at room temperature. The solvent was then removed under reduced pressure to yield 22.1 g of 3-morpholinobenzoyl chloride, which was used without further purification.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][CH:5]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C:31]([Si:33]([CH3:36])([CH3:35])[CH3:34])#[CH:32].CCN(CC)CC>C1COCC1.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.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7]([C:32]#[C:31][Si:33]([CH3:36])([CH3:35])[CH3:34])=[CH:6][CH:5]=1
Reactant: COC(=O)c1ccc(Br)cc1
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc(C#C[Si](C)(C)C)cc1
Reaction time: 0.33 h
Yield: 54 %

Procedure:
4-Bromobenzoic acid methyl ester (1.124 g, 5.22 mmol), PdCl2(PPh3)2 (192 mg, 27.4 mmol), and PPh3 (37 mg, 14.1 mmol) were suspended in THF (25.0 mL). Ethynyltrimethylsilane (1.14 mL, 8.1 mmol) and Et3N (1.14 mL, 7.8 mmol) were added and the reaction was allowed to stir for 20 min. CuI (14 mg, 0.075 mmol) was added and the reaction color changed from orange to red. Reaction was allowed to proceed overnight. After overnight reaction, the solution was brown in color and TLC analysis indicated the reaction was complete. The reaction mixture was concentrated to a brown residue, redissolved in DCM and filtered through Celite. The filtrate and rinses were evaporated to dryness and purification via Silica in 15:1 cyclohexane: EtOAc afforded 4-(trimethylsilyl)ethynyl-benzoic acid methyl ester (656 mg, 2.82 mmol, 54%) as an orange solid. H-NMR (CD3C1, 500 MHz) δ (ppm): 0.239 (s, 9H); 3.89 (s, 3H); 7.49 (d, J=16.84 Hz, 2H); 7.94 (d, J=16.4 Hz, 2H).
Reaction SMILES: [C:1]([Si:3]([CH3:6])([CH3:5])[CH3:4])#[CH:2].Br[C:8]1[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=1>[Cu]I>[CH3:4][Si:3]([C:1]#[C:2][C:8]1[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=1)([CH3:6])[CH3:5]
Reactant: COC(=O)c1ccc(Br)cc1
Reactant: C#C[Si](C)(C)C
Agent: [Cu]I
Product: COC(=O)c1ccc(C#C[Si](C)(C)C)cc1
Temperature: 90 °C
Reaction time: 0.5 h
Yield: 95.9 %

Procedure:
Ethynyltrimethylsilane (82.4 g, 0.84 mol) was added dropwise over 10 min under a nitrogen atmosphere to a solution of methyl 4-bromobenzoate (150 g, 0.7 mol), PdCl2 (PPh3)2 (15 g, 0.021 mol) and CuI (13 g, 0.07 mol) in TEA (1.5 L) and the reaction was stirred at 90° C. for 30 minutes. Solids were collected by filtration and washed with EtOAc (5×500 mL). The filtrate was concentrated under reduced pressure to give a residue, which was distilled under reduced pressure to yield methyl 4-((trimethylsilyl)ethynyl)benzoate (INT-1.2) as an off-white solid (156 g, 96%).
Reaction SMILES: N1C=CC=CC=1.C1(CC([NH:16][CH:17]2[C:42](=[O:43])[N:19]3[C:20]([C:26]([O:28][CH:29]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[O:27])=[C:21]([CH2:24]O)[CH2:22][S:23][C@H:18]23)=O)C=CC=CC=1.P(Cl)(Cl)(Cl)(Cl)[Cl:45].CO>C(Cl)Cl>[NH2:16][CH:17]1[C:42](=[O:43])[N:19]2[C:20]([C:26]([O:28][CH:29]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[O:27])=[C:21]([CH2:24][Cl:45])[CH2:22][S:23][C@H:18]12
Reactant: O=C(Cc1ccccc1)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(CO)CS[C@H]12
Reactant: ClP(Cl)(Cl)(Cl)Cl
Solvent: CO
Solvent: c1ccncc1
Solvent: ClCCl
Product: NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(CCl)CS[C@H]12
Temperature: -20 °C
Reaction time: 0.08 h

Procedure:
19.64 ml (0.242 mol) of pyridine are added to a suspension of 50 g (0.0972 mol) of benzhydryl 7-phenylacetamido-3-hydroxymethyl-3-cephem-4-carboxylate in 500 ml of methylene chloride at room temperature. After cooling to -20° C., 40.48 g (0.0972 mol) of phosphorus pentachloride are added and the mixture is stirred at -20° C. for 5 minutes. The mixture is warmed to 0° C. with an icebath and stirred for 10 minutes, and is then warmed to 15° C. with a waterbath and stirred for 1 hour. Thereafter, the mixture is cooled to -70° C. and 720 ml of cold methanol are quickly added The mixture is then stirred at -70° C. for 5 minutes, at 0° C. for 10 minutes and at +15° C. for 25 minutes. The solution is subsequently concentrated to a high degree in vacuo and 1,400 ml of saturated sodium bicarbonate solution are added. The solution is extracted three times with methylene chloride and the organic phase is dried with sodium sulphate and concentrated in vacuo. The crude product is chromatographed on 500 g of silica gel 60 (0.04-0.063 mm) with methylene chloride.
Reaction SMILES: O1CCCC1.B.N1CCCCC1.CS(O)(=O)=O.[O:18]=[C:19]([N:33]1[CH2:38][CH2:37][N:36]2[C:39]([C:42]([F:45])([F:44])[F:43])=[N:40][N:41]=[C:35]2[CH2:34]1)[CH:20]=[C:21]([NH2:32])[CH2:22][C:23]1[CH:28]=[C:27]([F:29])[C:26]([F:30])=[CH:25][C:24]=1[F:31].N>O>[O:18]=[C:19]([N:33]1[CH2:38][CH2:37][N:36]2[C:39]([C:42]([F:45])([F:44])[F:43])=[N:40][N:41]=[C:35]2[CH2:34]1)[CH2:20][CH:21]([NH2:32])[CH2:22][C:23]1[CH:28]=[C:27]([F:29])[C:26]([F:30])=[CH:25][C:24]=1[F:31]
Reactant: NC(=CC(=O)N1CCn2c(nnc2C(F)(F)F)C1)Cc1cc(F)c(F)cc1F
Agent: B
Agent: CS(=O)(=O)O
Agent: N
Solvent: C1CCNCC1
Solvent: O
Solvent: C1CCOC1
Product: NC(CC(=O)N1CCn2c(nnc2C(F)(F)F)C1)Cc1cc(F)c(F)cc1F
Temperature: -10 °C
Reaction time: 1 h

Procedure:
In a 250 mL round bottom flask 1.0 M Borane tetrahydrofuran (37 mL) was taken. It was cooled to −10° C. and piperidine (3.14 g) was added dropwise at −10 to 5° C. After 30 min. methanesulfonic acid (6.0 mL) was added dropwise at −10 to 5° C. over a period of 15-30 min. Separately, 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)but-2-en-2-amine (5.0 g) was added in small portions into the reaction mixture, keeping the temperature between −10 to −5° C. It was stirred for 1 h at −10 to −5° C. Reaction mixture was poured into cold water. It was basified by adding aq. ammonia solution. Product was extracted in an ethyl acetate. The organic layer was collected. It was washed with water and dried over anhydrous sodium sulfate. Solvent was evaporated at reduced pressure to obtain the product. (Wt.-4.1 g, % Y-81.0%, % Purity by HPLC-84.5%).
Reaction SMILES: [CH2:1]([N:3]1[C:9](=[O:10])[C:8]([CH3:12])([CH3:11])[C:7](=[O:13])[N:6]([CH3:14])[C:5]2[CH:15]=[C:16]([O:19]CC3C=CC=CC=3)[CH:17]=[CH:18][C:4]1=2)[CH3:2]>[C].[Pd].C(O)C>[CH2:1]([N:3]1[C:9](=[O:10])[C:8]([CH3:12])([CH3:11])[C:7](=[O:13])[N:6]([CH3:14])[C:5]2[CH:15]=[C:16]([OH:19])[CH:17]=[CH:18][C:4]1=2)[CH3:2]
Reactant: CCN1C(=O)C(C)(C)C(=O)N(C)c2cc(OCc3ccccc3)ccc21
Agent: [Pd]
Solvent: CCO
Product: CCN1C(=O)C(C)(C)C(=O)N(C)c2cc(O)ccc21
Reaction time: 1 h
Yield: 96 %

Procedure:
10% palladium carbon (1.66 g, water content: 54.8%) was added to an ethanol (150 mL) solution of 1-ethyl-7-benzyloxy-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (15.0 g, 42.6 mmol), and catalytic hydrogenation reaction was performed at 40-50° C., at 3 atm. The reaction solution was filtered to remove a catalyst, and ethanol was distilled off. Methanol (105 mL) and water (105 mL) were added to the resulting residue, and the mixture was heated while stirring. After the dissolution was confirmed, stirring under ice cooling was conducted for 1 hour, and precipitated crystals were collected by filtration. The resulting crystals were washed with 50% methanol (30 mL), and dried at 60° C., thereby obtaining 10.7 g of a white, powdery target compound (yield: 96%).
Reaction SMILES: [CH3:1][CH:2]([N:4]1[C:12](/[CH:13]=[CH:14]/[C@H:15]([OH:24])[CH2:16][C@H:17]([OH:23])[CH2:18][C:19]([O:21]C)=[O:20])=[C:11]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH3:3].[OH-].[Na+:33]>CC(C)=O>[CH3:3][CH:2]([N:4]1[C:12](/[CH:13]=[CH:14]/[CH:15]([OH:24])[CH2:16][CH:17]([OH:23])[CH2:18][C:19]([O-:21])=[O:20])=[C:11]([C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]1=2)[CH3:1].[Na+:33]
Reactant: COC(=O)C[C@@H](O)C[C@@H](O)/C=C/c1c(-c2ccc(F)cc2)c2ccccc2n1C(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)=O
Product: CC(C)n1c(/C=C/C(O)CC(O)CC(=O)[O-])c(-c2ccc(F)cc2)c2ccccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 75.6 %

Procedure:
Fluvastatin methyl ester (3.0 g) was dissolved in acetone (30 ml) and NaOH (0.29 g) partially dissolved in acetone (0.75 ml) was added. The mixture was stirred at room temperature overnight. The product was isolated by filtration under nitrogen, washed with acetone (40 ml) and dried at 50° C. in a vacuum oven for 24 h to obtain 2.31 g (76.2%) of fluvastatin sodium crystal Form I.
Reaction SMILES: [CH3:1][CH:2]([N:4]1[C:12](/[CH:13]=[CH:14]/[C@H:15]([OH:24])[CH2:16][C@H:17]([OH:23])[CH2:18][C:19]([O:21]C)=[O:20])=[C:11]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH3:3].[OH-].[Na+:33].CC(OC)(C)C>O.C(O)C>[CH3:3][CH:2]([N:4]1[C:12](/[CH:13]=[CH:14]/[CH:15]([OH:24])[CH2:16][CH:17]([OH:23])[CH2:18][C:19]([O-:21])=[O:20])=[C:11]([C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]1=2)[CH3:1].[Na+:33]
Reactant: COC(=O)C[C@@H](O)C[C@@H](O)/C=C/c1c(-c2ccc(F)cc2)c2ccccc2n1C(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: COC(C)(C)C
Solvent: CCO
Product: CC(C)n1c(/C=C/C(O)CC(O)CC(=O)[O-])c(-c2ccc(F)cc2)c2ccccc21
Temperature: 25 °C
Yield: 72.3 %

Procedure:
Fluvastatin methyl ester (3.0 g) was added to a solution of NaOH (1 eq.) in water (0.75 ml) and ethanol (7.5 ml). The mixture was heated to reflux and stirred until the starting material was no longer detectable by HPLC. Then, 58 ml of MTBE was dripped into the solution over 1.5 h. Turbidity appeared in the solution. The mixture was cooled slowly to room temperature and stirred overnight. The product was isolated by filtration under nitrogen, washed with MTBE (50 ml) and dried at 50° C. in a vacuum oven for 24 h to obtain 2.21 g (72.3%) of fluvastatin sodium Form XIV.
Reaction SMILES: [NH2:1][OH:2].[CH3:3][O:4][C:5]1[CH:12]=[CH:11][CH:10]=[CH:9][C:6]=1[C:7]#[N:8]>CCO>[OH:2][N:1]=[C:7]([C:6]1[CH:9]=[CH:10][CH:11]=[CH:12][C:5]=1[O:4][CH3:3])[NH2:8]
Reactant: COc1ccccc1C#N
Reactant: NO
Solvent: CCO
Product: COc1ccccc1C(N)=NO
Temperature: 25 °C
Reaction time: 16 h
Yield: 100.8 %

Procedure:
Hydroxylamine (Fluka 55458; 50% in water; 11.28 mL; 187.76 mmol; 5 eq.) was added to a solution of 2-methoxybenzonitrile (Alrich 231231; 4.59 mL; 37.55 mmol; 1 eq.) in EtOH (50 mL) and the resulting mixture was stirred at room temperature for 16 hours then at 55° C. for 24 hours. The solvent was then evaporated and the resulting colourless oil was further dried under high vacuum to give a white solid. The latter was triturated in n-hexane, filtered and dried to afford the title compound (6.29 g, quantitative) as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[CH:6][C:5]=1[Cl:11].CO[CH:15]1[CH2:19][CH2:18][CH:17](OC)O1>CC(O)=O.O>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:15]=[CH:19][CH:18]=[CH:17]2)=[CH:6][C:5]=1[Cl:11]
Reactant: COC1CCC(OC)O1
Reactant: COC(=O)c1ccc(N)cc1Cl
Solvent: CC(=O)O
Solvent: O
Product: COC(=O)c1ccc(-n2cccc2)cc1Cl
Temperature: 25 °C

Procedure:
A mixture of 4-amino-2-chlorobenzoic acid methyl ester (0.46 g) and 2,5-dimethoxytetrahydrofuran (0.33 mL) in AcOH (16 mL) was heated under reflux for 2 h. The mixture was cooled to room temperature, diluted with water and extracted with EtOAc. The extract was washed with satd. NaHCO3 and brine, dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography (silica gel; eluent: hexane/EtOAc 5/1) to yield 0.48 g of 2-chloro-4-(1-pyrrolyl)benzoic acid methyl ester. ESMS: m/z 236 (MH+).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH2:22][CH2:23][OH:24])[CH:10]=[C:11]([C:13]3[N:17]([CH:18]([CH3:20])[CH3:19])[N:16]=[C:15]([CH3:21])[N:14]=3)[N:12]=2)=[C:4](F)[CH:3]=1.C1(C)C=CC=CC=1.[OH-].[K+]>CN1C=CN=C1.[Cl-].C[N+](CCCC)(CCCC)CCCC>[Br:1][C:2]1[CH:7]=[CH:6][C:5]2[C:8]3[N:9]([CH:10]=[C:11]([C:13]4[N:17]([CH:18]([CH3:20])[CH3:19])[N:16]=[C:15]([CH3:21])[N:14]=4)[N:12]=3)[CH2:22][CH2:23][O:24][C:4]=2[CH:3]=1
Reactant: Cc1nc(-c2cn(CCO)c(-c3ccc(Br)cc3F)n2)n(C(C)C)n1
Agent: CCCC[N+](C)(CCCC)CCCC
Agent: Cn1ccnc1
Agent: [Cl-]
Solvent: Cc1ccccc1
Product: Cc1nc(-c2cn3c(n2)-c2ccc(Br)cc2OCC3)n(C(C)C)n1
Temperature: 65 °C
Reaction time: 18 h
Yield: 112575.1 %

Procedure:
To a solution of 2-(2-(4-Bromo-2-fluorophenyl)-4-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-1H-imidazol-1-yl)ethanol (7.55 mmol) 14 in N-methylimidazole(12 L) at 35° C. was added methyl tributylammonium chloride (115 g, 0.453 mol), toluene (27.5 L) and 35% potassium hydroxide solution (10.6 kg, 25 mol in 22 L of water). The biphasic solution was stirred vigorously at 65° C. for 18 h when it was judged complete by HPLC. Stirring was stopped but heating was continued and the bottom aqueous layer was removed. Added isopropyl acetate (13.8 L) and the organic phase was washed twice with water (13.8 L and 27.5 L). The solvent was removed via vacuum distillation and after 30 L had been removed, isopropanol (67.6 L) was added. Vacuum distillation was resumed until an additional 30 L of solvent had been removed. Added additional isopropanol (28.8 L) and continued vacuum distillation until the volume was reduced by 42 L. Added isopropanol (4 L) and the temperature was increased to >50° C. Added water (28 L) such that the internal temperature was maintained above 50° C., then heated to 75° C. to obtain a clear solution. The mixture was allowed to cool slowly and the product crystallized out of solution. The resulting suspension was cooled to 0° C., held for 1 h then filtered and the cake was washed with water (5.5 L). The cake was dried at 45° C. under a nitrogen sweep to give III as a tan solid (3.30 kg, 71.6 wt %, 80.6% yield).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:8](OC(=O)C)(=[O:10])[CH3:9]>>[C:8]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)(=[O:10])[CH3:9]
Reactant: CC(=O)OC(C)=O
Reactant: Nc1ccccc1
Product: CC(=O)Nc1ccccc1

Procedure:
The aminophenyl-β-sulfatoethylsulfone has been produced by reacting aniline with acetic anhydride to produce acetoanilide, followed by chlorosulfonating the latter with a largely excessive quantity of chlorosulfonic acid to produce acetylaminobenzenesulfonyl chloride, reducing the latter with sodium sulfite to produce the corresponding sulfinic acid, reacting the latter with ethylene oxide or ethylene chlorohydrin to produce acetylaminophenyl-β-hydroxyethylsulfone, and then subjecting the latter to hydrolysis and esterification in sulfuric acid to obtain the desired sulfuric ester.
Reaction SMILES: C[O:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19]C)[CH:14]=3)[CH:9]=2)[CH:4]=1.B(Br)(Br)Br>>[OH:19][C:15]1[CH:14]=[C:13]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[CH:4]=[C:3]([OH:2])[CH:12]=[CH:11]3)[CH:18]=[CH:17][CH:16]=1
Reactant: COc1cccc(-c2ccc3cc(OC)ccc3c2)c1
Agent: BrB(Br)Br
Product: Oc1cccc(-c2ccc3cc(O)ccc3c2)c1
Yield: 52 %

Procedure:
The compound is prepared by reaction of 2-methoxy-6-(3-methoxyphenyl)-naphthalene (51 mg, 0.19 mmol, 1 eq) with boron tribromide (0.6 ml, 0.60 mmol, 3 eq) according to method G. Purification by column chromatography with dichloromethane/methanol 98/2 as the eluent yields the desired product in a yield of 52%, 23 mg.
Reaction SMILES: [CH3:1][N:2]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[S:3]([C:6]1[CH:25]=[CH:24][C:9]2[N:10]([CH3:23])[C:11]([CH2:13][O:14][C:15]3[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[CH:17][CH:16]=3)=[N:12][C:8]=2[CH:7]=1)(=[O:5])=[O:4].[ClH:32].C(=O)([O-])[O-].[NH4+:37].[NH4+]>C(O)C>[ClH:32].[CH3:1][N:2]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[S:3]([C:6]1[CH:25]=[CH:24][C:9]2[N:10]([CH3:23])[C:11]([CH2:13][O:14][C:15]3[CH:16]=[CH:17][C:18]([C:21](=[NH:37])[NH2:22])=[CH:19][CH:20]=3)=[N:12][C:8]=2[CH:7]=1)(=[O:4])=[O:5]
Reactant: CN(c1ccccc1)S(=O)(=O)c1ccc2c(c1)nc(COc1ccc(C#N)cc1)n2C
Reactant: [NH4+]
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CCO
Product: CN(c1ccccc1)S(=O)(=O)c1ccc2c(c1)nc(COc1ccc(C(=N)N)cc1)n2C
Yield: 46 %

Procedure:
Prepared analogously to Example 32 from 1-methyl-2-[(4-cyanophenyl)-oxymethyl]-benzimidazol-5-yl-sulphonic acid-N-methyl-N-phenyl-amide and ethanolic hydrochloric acid, ethanol and ammonium carbonate. Yield: 46% of theory, C23H23N5O3S (449.5) ##EQU14##
Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4]>O>[OH:1][CH2:2][C:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])=[O:4]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Solvent: O
Product: O=C(CO)[C@@H](O)[C@H](O)[C@H](O)CO

Procedure:
A water white, clear dextrose liquor 40 having a D.E. of over 95 is recovered from the ion exchange treatment. This dextrose liquor 40 is concentrated to about 45% dissolved solids in an evaporator 41. Its pH is then adjusted to within the range of about 8 to about 8.5 with active magnesium oxide in a mixing tank 42. Ideally, the ratio of dissolved magnesium to calcium is adjusted to at least 20:1 in the tank 42. The resulting liquor 43 is then ready for treatment with a glucose isomerase (such as that marketed by Novo Enzyme Corporation under the trade name "Sweetzyme") to produce a high fructose sweetener.
Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4].S([O-])([O-])(=O)=O.[Mg+2].S([O-])([O-])=O.[Na+].[Na+]>>[OH:1][CH2:2][C:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])=[O:4]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: O=S(=O)([O-])[O-]
Agent: O=S([O-])[O-]
Agent: [Mg+2]
Product: O=C(CO)[C@@H](O)[C@H](O)[C@H](O)CO
Temperature: 37 °C
Reaction time: 1 h

Procedure:
[One unit of glucose isomerase is defined as the enzymatic activity which produces one micromole of fructose by reaction with glucose at 37° C. at pH 7.0 for one minute. The reaction with glucose is conducted by adding 2 g of the immobilized glucose isomerase preparation to 20 ml of an aqueous 0.1 M glucose solution (pH 7.0) containing 0.01 M of magnesium sulfate, 1 mM cobaltous chloride and 0.1 M sodium sulfite, and then shaking the mixture at 37° C. for one hour. The amount of fructose produced is measured by the cysteinecarbazole-sulfuric acid method.]
Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4].[O-]S([O-])(=O)=O.[Mg+2].C(O)C(N)(CO)CO.C([O-])(=O)/C=C\C([O-])=O>>[OH:1][CH2:2][C:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])=[O:4]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: NC(CO)(CO)CO
Agent: O=C([O-])/C=C\C(=O)[O-]
Agent: O=S(=O)([O-])[O-]
Product: O=C(CO)[C@@H](O)[C@H](O)[C@H](O)CO
Temperature: 85 °C

Procedure:
The conditions used for the bioconversion are the following: To a 5 ml solution of 0.8 M glucose, 10 mM MgSO4, 1 mM CoCl2, 50 mM Tris/maleate pH 6.4 was added 200 μl of the enzyme preparation. The temperature is maintained at 85° C. for 120 min to effectuate the bioconversion. Subsequently, the amount of fructose formed is determined chromatographically by HPLC.
Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4].C(O)[C@H]1O[C@H](O[C@]2(CO)O[C@H](CO)[C@@H](O)[C@@H]2O)[C@H](O)[C@@H](O)[C@@H]1O>>[OH:1][CH2:2][C:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])=[O:4]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: OC[C@H]1O[C@@](CO)(O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@@H](O)[C@@H]1O
Product: O=C(CO)[C@@H](O)[C@H](O)[C@H](O)CO

Procedure:
The experiment of Example 1 was repeated, except that the resins were washed with increasing volumes (2, 4, 6, or 8 bed volumes) of a dilute (4 mM) solution of NaOH. Fructose retention on the column was extended, but fructose still eluted as a distinct peak within reasonable times (at about 4.5, 5, 5.5, and 6 minutes, respectively). By contrast, retention of myo-inositol was not affected, and still left the column at about 3 minutes, as was observed in Example 1. Results for other mono-and di-saccharides that have been tested in comparable experiments (to date, glucose and sucrose) were similar to the results for fructose.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:14]=[CH:15][CH:16]=1)[CH2:7][N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)([O-])=O.C(O)C.O.NN>C1COCC1.[Ni]>[N:8]1([CH2:7][C:6]2[CH:5]=[C:4]([NH2:1])[CH:16]=[CH:15][CH:14]=2)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1
Reactant: O=[N+]([O-])c1cccc(CN2CCCCC2)c1
Agent: [Ni]
Agent: NN
Solvent: O
Solvent: CCO
Solvent: C1CCOC1
Product: Nc1cccc(CN2CCCCC2)c1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 79.5 %

Procedure:
To a solution of 1-(3-nitrobenzyl)piperidine (263 mg; 1.19 mmol) in THF:ethanol mixture (1:1) (15 mL) was added a catalytical amount of Raney-Nickel and hydrazine hydrate (6.0 mmol) and the mixture was stirred for 15 minutes at ambient temperature, filtered through a Celite-pad and the filtrate was evaporated to provide the title compound (180 mg, 95%), which was used in futher reactions without purification.
Reaction SMILES: [CH2:1]1[CH:7](O)[NH:6][P:4]([N:9]([CH2:13][CH2:14][Cl:15])[CH2:10][CH2:11][Cl:12])(=[O:5])[O:3][CH2:2]1.[CH:16]1([NH3+:22])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1.[SH:23][CH2:24][CH2:25][S:26]([O-:29])(=[O:28])=[O:27].ClC(Cl)(Cl)C(O)=O>CO>[CH:16]1([NH3+:22])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1.[Cl:12][CH2:11][CH2:10][N:9]([CH2:13][CH2:14][Cl:15])[P:4]1(=[O:5])[NH:6][CH:7]([S:23][CH2:24][CH2:25][S:26]([O-:29])(=[O:28])=[O:27])[CH2:1][CH2:2][O:3]1
Reactant: O=P1(N(CCCl)CCCl)NC(O)CCO1
Reactant: O=S(=O)([O-])CCS
Agent: O=C(O)C(Cl)(Cl)Cl
Agent: [NH3+]C1CCCCC1
Solvent: CO
Product: O=P1(N(CCCl)CCCl)NC(SCCS(=O)(=O)[O-])CCO1
Reaction time: 8 h

Procedure:
1.4 g (5 mmol) of 4-hydroxycyclophosphamide and 1.2 g (5 mmol) of cyclohexylammonium-2-mercaptoethanesulphonate were dissolved together with a trace of trichloroacetic acid in 25 ml of methanol and were left to stand overnight in a refrigerator at -25° C. The reaction solution was then concentrated to about 5 ml, ether was added until clouding commensed and the mixture was triturated. The crystallised material was filtered with suction after standing for 20 hours at 0° C., and was washed and dried.