Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]12[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:10][CH:4]([CH2:5]3)[CH2:3]1)[CH2:9]2>C1C=CC=CC=1.O.FC(F)(F)S([O-])(=O)=O.[Ag+]>[C:2]1([C:2]23[CH2:11][CH:6]4[CH2:7][CH:8]([CH2:10][CH:4]([CH2:5]4)[CH2:3]2)[CH2:9]3)[CH:11]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: BrC12CC3CC(CC(C3)C1)C2
Agent: [Ag+]
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: c1ccccc1
Solvent: O
Product: c1ccc(C23CC4CC(CC(C4)C2)C3)cc1
Reaction time: 0.5 h
Yield: 82 %

Procedure:
Silver trifluoromethanesulfonate (5 g) and 50 ml of benzene were mixed, 4.2 g of 1-bromoadamantane dissolved in 50 ml of benzene was added thereto over 30 minutes, and the resulting mixture was stirred for 12 hours in a dark place. The obtained reaction solution was poured in 300 ml of water and extracted with hexane, and the organic phase was washed with water and saturated saline, dried and concentrated to obtain a crude product. This crude product was purified by column chromatography, as a result, 1.7 g of 1-phenyladamantane was obtained.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[I:9]N1C(=O)CCC1=O.S(=O)(=O)(O)O.O>C(O)(=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([I:9])[CH:3]=1
Reactant: O=C1CCC(=O)N1I
Reactant: Oc1ccc(Br)cc1
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CC(=O)O
Product: Oc1ccc(Br)cc1I

Procedure:
4-Bromophenol (51.9 g, 0.30 mol) and N-iodosuccinimide (67.5 g, 0.30 mol) were combined in acetic acid (360 mL). The mixture was stirred briefly, treated with concentrated sulfuric acid (5 mL, 0.09 mol) and stirred at about 22° C. overnight. The mixture was poured into water (about 800 mL) with stirring to precipitate the product. The suspension was stirred for about 1 hour and filtered. The wet cake was washed with water (50 mL, 2×) and dried under reduced pressure at about 50° C. (80.9 g, 90%). MS-DEI (M+H)+ m/z at 298; 1H NMR (CDCl3 at 400 MHz) δ 5.28 (s,1H), 6.86 (d, 1H), 7.33 (dd, 1H), 7.75 (d, 1H); 13C NMR (CDCl3 at 100 MHz) δ 86.0, 112.8, 116.0, 132.7, 139.4, 153.7.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>C(O)C>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][N:25]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=2)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]
Reactant: Clc1ccnc(Cl)n1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Product: CC(C)(C)OC(=O)N1CCN(c2ccnc(Cl)n2)CC1
Temperature: 25 °C
Yield: 77.1 %

Procedure:
To a solution of 2,4-dichloropyrimidine (3.00 g, 20.1 mmol) in 100 mL of ethanol was added powdered sodium carbonate (2.1 g, 20.1 mmol) and piperazine-1-carboxylic acid tert-butyl ester (3.75 g, 20.1 mmol). The reaction was heated to reflux for 5 hours, then cooled to room temperature and concentrated in vacuo. The residue was taken up in 400 mL of ethyl acetate and extracted with water (100 mL) and brine (100 mL). The organic phase was then dried over sodium sulfate, filtered, and concentrated in vacuo to a clear oil. Flash column chromatography (silica gel, gradient elution from 10% ethyl acetate-hexanes to 50% ethyl acetate-hexanes) yielded 4.63 g of the title compound (I-1a).
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH+]1C=CC=CC=1.[O:28]1[CH:33]=[CH:32][CH2:31][CH2:30][CH2:29]1>C(OCC)C>[O:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH:29]1[O:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1
Reactant: C1=COCCC1
Reactant: O=C(O)c1ccc(O)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: c1cc[nH+]cc1
Solvent: CCOCC
Product: O=C(O)c1ccc(OC2CCCCO2)cc1
Temperature: 0 °C
Reaction time: 4 h

Procedure:
To an ice-cooled mixture of 4-hydroxybenzoic acid (13.81 g) in 250 ml of diethylether containing 1.98 g of pyridinium p-toluenesulphonic acid, 3,4-dihydro-2H-pyran (16 g) was drop wise added. After complete addition stirring was continued at temperature below +8° C. for 4 h and the white precipitate was filtered off, washed twice with 100 ml of +4° C. pre-cooled diethylether and dried to give nearly pure 4-(tetrahydro-2H-pyran-2-yloxy)benzoic acid as white powder.
Reaction SMILES: [OH:1][C:2]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:3]=1[C:4]([C:6]1[CH:11]=[C:10]([Cl:12])[CH:9]=[CH:8][C:7]=1[OH:13])=[O:5].I[CH2:20]I>CN(C)C=O>[Cl:18][C:15]1[CH:16]=[CH:17][C:2]2[O:1][CH2:20][O:13][C:7]3[CH:8]=[CH:9][C:10]([Cl:12])=[CH:11][C:6]=3[C:4](=[O:5])[C:3]=2[CH:14]=1
Reactant: O=C(c1cc(Cl)ccc1O)c1cc(Cl)ccc1O
Reactant: ICI
Solvent: CN(C)C=O
Product: O=C1c2cc(Cl)ccc2OCOc2ccc(Cl)cc21
Temperature: 105 °C
Reaction time: 8 h
Yield: 96 %

Procedure:
2,2'-Dihydroxy-5,5'-dichlorobenzophenone (12.1 g, 0.042 mol, prepared similarly as described in Journal of the American Chemical Society 77, 543 (1955)) and diiodomethane (11.9 g, 0.044 mol) were dissolved in dry N,N-dimethylformamide (226 ml). Dried and powdered potassium carbonate (8.3 g) was added and the mixture was heated at 105° C. for 5 h and left overnight at room temperature. The reaction mixture was poured on ice (220 g). The precipitate was collected by filtration after 0.5 h and dissolved in diethyl ether (500 ml). The organic layer was washed with 5% sodium hydroxide (50 ml), dried over MgSO4 and evaporated in vacuo, affording 12 g (96%) of 2,10-dichloro-12H-dibenzo[d,g][1,3]-dioxocin-12-one as a solid.
Reaction SMILES: [CH2:1]([O:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18]O)=[CH:16][CH:15]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].S(Cl)([Cl:24])=O>C1C=CC=CC=1>[CH2:1]([O:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18][Cl:24])=[CH:16][CH:15]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: O=S(Cl)Cl
Reactant: CCCCCCCCCCCCOc1ccc(CO)cc1
Solvent: c1ccccc1
Product: CCCCCCCCCCCCOc1ccc(CCl)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of 4-dodecyloxybenzyl alcohol (Preparation 1, 2.92 g, 0.0010 M) in benzene (40 mL) is added dropwise to a stirred solution of thionyl chloride (3.0 mL, 4.97 g, 0.04 M) over a period of 20 minutes. The solution is stirred at room temperature for 0.5 hr and then is heated at reflux temperature for 3 hours (monitoring of the reaction by TLC may be deceptive since the product is hydrolyzed to starting alcohol when placed on a silica gel plate; the plate must be developed immediately after the sample is applied). Benzene and excess thionyl chloride are removed under reduced pressure. The crude product is used in Example 1 without further purification.
Reaction SMILES: Cl.Cl.[CH2:3]([NH:10][CH2:11][CH2:12][CH2:13][S:14][C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:21](Cl)(=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C(Cl)Cl>[CH2:3]([N:10]([CH2:11][CH2:12][CH2:13][S:14][C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1)[C:21](=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: c1ccc(CNCCCSc2ccncc2)cc1
Agent: Cl
Solvent: ClCCl
Product: O=C(c1ccccc1)N(CCCSc1ccncc1)Cc1ccccc1
Yield: 50.2 %

Procedure:
To a solution of 400 mg (1.21 mmol) of 4-[3-(N-benzylamino)propylthio]pyridine dihydrochloride and 0.55 ml (4.00 mmol) of triiethylamine in 5 ml of methylene chloride, 0.17 ml (1.45 mmol) of benzoyl chloride was added under ice-cooling with stirring. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was washed with a saturated aqueous solution of sodium bicarbonate and water and dried, and then the solvent was distilled off. The residue was purified by column chromatography (eluent: ethyl acetate) to obtain 0.22 g of the desired compound (yield: 50.4%, yellow oil).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].B(F)(F)F.CCOCC.[N+](=[CH:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[N-].C(=O)([O-])[O-].[K+].[K+]>CCOCC>[CH2:30]([O:29][C:27]([CH:26]1[C:11](=[O:14])[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH2:13][CH2:12]1)=[O:28])[CH3:31]
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: CCOC(=O)C=[N+]=[N-]
Agent: FB(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOCC
Product: CCOC(=O)C1CCN(C(=O)OC(C)(C)C)CCC1=O
Temperature: 25 °C

Procedure:
To 10.0 g (50.18 mmol) 4-oxo-piperidine-1-carboxylic acid tert-butyl ester in 60 mL anhydrous ether maintained between −25° C. and −30° C. were added, over 20 minutes, solutions of 8.2 mL (65.23 mmol) boron trifluoride diethyl etherate in 17 mL anhydrous ether, followed by 6.85 mL (65.23 mmol) ethyl diazoacetate in 17 mL anhydrous ether, and the reaction was maintained between −25° C. and −30° C. for 1 hour. The mixture was allowed to warm to room temperature, 30 mL 30% potassium carbonate solution was added and the mixture extracted with EtOAc (3×30 mL), the organic layers were combined and dried with MgSO4. After filtration, the solvent was evaporated to give the desired product.
Reaction SMILES: [O:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.B(F)(F)F.CCOCC.[N+](=[CH:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[N-].O>CCOCC>[O:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9])[CH2:4][CH2:3][CH:26]1[C:27]([O:29][CH2:30][CH3:31])=[O:28]
Reactant: CCOC(=O)C=[N+]=[N-]
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Agent: FB(F)F
Solvent: O
Solvent: CCOCC
Product: CCOC(=O)C1CCN(C(=O)OC(C)(C)C)CCC1=O
Temperature: -50 °C
Reaction time: 8 h
Yield: 87.6 %

Procedure:
To a solution of tert-butyl 4-oxopiperidine-1-carboxylate (3.2 g, 16 mmol, 1.0 equiv) in Et2O (20 mL) at −50° C. were added BF3.Et2O (2.3 g, 16 mmol, 1.0 equiv) in dropwise. After completion of addition of BF3.Et2O, ethyl 2-diazoacetate (2 g, 17.6 mmol, 1.1 equiv) was added dropwise. The reaction was then stirred at −50° C. for an hour and kept at room temperature overnight. Then the reaction mixture was poured into water (100 mL), extracted with ethyl acetate (3×100 mL), combined of the organic layers and dried over Na2SO4. The solvent was removed under reduced pressure to give the desired product (4 g), which was purified by silica gel chromatography. MS (ESI): 286 (MH+).
Reaction SMILES: [O-:1][Mn](=O)(=O)=O.[K+].[Br:7][C:8]1[C:9]([Cl:16])=[CH:10][C:11]([CH2:14][OH:15])=[N:12][CH:13]=1>O.C([O-])([O-])=O.[Na+].[Na+]>[Br:7][C:8]1[C:9]([Cl:16])=[CH:10][C:11]([C:14]([OH:1])=[O:15])=[N:12][CH:13]=1
Reactant: O=[Mn](=O)(=O)[O-]
Reactant: OCc1cc(Cl)c(Br)cn1
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na+]
Solvent: O
Product: O=C(O)c1cc(Cl)c(Br)cn1
Reaction time: 2 h

Procedure:
KMnO4 (174 mg, 1.1 mmol) in H2O was added dropwise to a solution of (5-bromo-4-chloro-2-pyridinyl)methanol (187 mg, 0.846 mmol) in 10% Na2CO3 (1 mL). After 2 h, the solution was filtered through Celite®, adjusted to pH ˜4 and the resulting precipitate was filtered then azeotropically dried with toluene affording the title compound (135 mg, 68%) as a white powder: LCMS (ES) m/z=237 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.[CH2:12]([OH:16])[CH2:13][C:14]#[CH:15]>C(N(CC)CC)C.ClCCl.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>[N:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:11]=[C:2]([C:15]#[C:14][CH2:13][CH2:12][OH:16])[CH:3]=1
Reactant: C#CCCO
Reactant: Brc1cnc2ccccc2c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: OCCC#Cc1cnc2ccccc2c1
Yield: 136.9 %

Procedure:
A solution of 3-bromoquinoline (13.57 mL, 0.10 mol) and 3-butyn-1-ol (9.0 mL, 0.12 mol) in 40 mL of triethylamine and 75 mL of dichloromethane is degassed by bubbling in dry nitrogen for 15 minutes, and 0.7 g (0.001 mol) of bis(triphenylphosphine)palladium chloride and 0.013 g of cuprous iodide are added. The flask is flushed with nitrogen and the mixture is heated to reflux for 5 hours. The cooled mixture is diluted with dichloromethane and washed with water, dried (sodium sulfate), and concentrated to give 27 g of an oil. The oil is triturated with diethyl ether to give 18.2 g of the title compound as a tan solid; mp 95.7°-96.7° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)(O)[CH:9]2[S:14][CH2:13][S:12][CH2:11][S:10]2)=[CH:4][CH:3]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1C=CC=CC=1>C1CCCCC1>[F:22][C:19]1[CH:20]=[CH:21][C:16]([C:8](=[C:9]2[S:10][CH2:11][S:12][CH2:13][S:14]2)[C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)=[CH:17][CH:18]=1
Reactant: OC(c1ccc(F)cc1)(c1ccc(F)cc1)C1SCSCS1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Solvent: C1CCCCC1
Product: Fc1ccc(C(=C2SCSCS2)c2ccc(F)cc2)cc1
Yield: 89.5 %

Procedure:
A mixture of 2.0 g of 2-{bis(4-fluorophenyl)hydroxymetyl}-1,3,5-trithiane, 0.2 g of p-toluenesulfonic acid and 50 ml of benzene was refluxed with heating for 15 minutes by means of a Dean-Stark reflux condenser. After being cooled, the mixture was extracted with ethyl acetate and the extract was washed with a saturated aqueous sodium hydrogencarbonate solution. The washed extract was dried over anhydrous magnesium sulfate and the solvent was removed by distillation under reduced pressure to obtain a material, which was recrysallized from cyclohexane to give 1.7 g of the desired compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)[C:9](O)=[O:10])=[CH:4][CH:3]=1.O=S(Cl)[Cl:25]>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)[C:9]([Cl:25])=[O:10])=[CH:4][CH:3]=1
Reactant: O=C(O)C(Oc1cccc(C(F)(F)F)c1)c1ccc(Cl)cc1
Reactant: O=S(Cl)Cl
Solvent: ClC(Cl)Cl
Product: O=C(Cl)C(Oc1cccc(C(F)(F)F)c1)c1ccc(Cl)cc1
Temperature: 70 °C
Yield: 107.6 %

Procedure:
A 3-L evaporation flask with magnetic stirrer, Claissen adapter, pot thermometer and a reflux condenser routed to a gas scrubber was charged with (+) 4-chlorophenyl-(3-trifluoromethylphenoxy)-acetic acid (131 g, 0.37 mole) and CHCl3 (152 ml) and heated to boiling in order to dissolve. SOCl2 (35 ml, 56.5 g, 0.48 mole) was added. The mixture was heated to reflux (70° C. final) for 4 hours and then stripped of volatiles to obtain 139 g liquid. The material was used in the next step without further purification.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[C:4]([Cl:9])[CH:3]=1.[Br:10]N1C(=O)CCC1=O>ClC1C=CC=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][Br:10])=[C:4]([Cl:9])[CH:3]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ccc(Br)cc1Cl
Solvent: Clc1ccccc1
Product: Clc1cc(Br)ccc1CBr
Yield: 27.3 %

Procedure:
4-Bromo-2-chlorotoluene (7.02 g) and N-bromosuccinimide (6.07 g) was stirred in chlorobenzene (50 ml) under ultraviolet light at 100° C. for 18 h. The reaction mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by medium-pressure liquid chromatography, eluting with iso-hexane, to give a colourless oil (2.65 g).
Reaction SMILES: [C:1]([S:5]([CH2:8][CH:9]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10]([O:12]CC)=[O:11])(=[O:7])=[O:6])([CH3:4])([CH3:3])[CH3:2].O.[OH-].[Na+]>CS(C)=O.[OH-].[Ca+2].[OH-]>[C:1]([S:5]([CH2:8][C@@H:9]([CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[C:10]([OH:12])=[O:11])(=[O:6])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)C(Cc1ccccc1)CS(=O)(=O)C(C)(C)C
Agent: [Ca+2]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CS(C)=O
Product: CC(C)(C)S(=O)(=O)C[C@@H](Cc1ccccc1)C(=O)O
Yield: 48 %

Procedure:
A solution of 79 g (0.25 mol) of ethyl (RS)-α-[(tert-butylsulfonyl)methyl]hydrocinnamate in 105 ml of dimethyl sulfoxide was added dropwise while stirring vigorously to 6.2 l of water at 30° C. The pH value was adjusted to 7.5 with 0.1N sodium hydroxide solution. The hydrolysis was started by the addition of 1.05 g of α-chymotrypsin. The pH value was held constant at 7.5 using automatic titration by dosing-in 0.043N calcium hydroxide solution of 30° C. After a consumption of 2.67 l of 0.043N calcium hydroxide solution (after 19.5 hours), the reaction mixture was extracted three times with 2 l of ethyl acetate. The aqueous phase was acidified to pH 2.5 with 5% hydrochloric acid and extracted twice with 2 l of ethyl acetate. The organic phases were filtered over DICALITE Speedex, combined and dried over magnesium sulfate. After evaporating the solvent and drying the residue in a high vacuum, there were obtained 35 g (0.12 mol, 48.3%, 96.9% of theory) of (S)-α-[(tert-butylsulfonyl)methyl]hydrocinnamic acid in the form of white crystals, which had an enantiomeric excess of >98%. In order to determine the purity by gas chromatography, the compound obtained was silylated and had a purity of >99%.
Reaction SMILES: [CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:16][CH2:17][Si:18]([CH2:21][CH2:22]Br)([CH3:20])[CH3:19].O>ClCCl>[CH2:1]([N:8]1[CH2:22][CH2:21][Si:18]([CH3:20])([CH3:19])[CH2:17][CH2:16]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NCc1ccccc1
Reactant: C[Si](C)(CCBr)CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: ClCCl
Product: C[Si]1(C)CCN(Cc2ccccc2)CC1
Yield: 58.4 %

Procedure:
Benzylamine (17.56 g, 0.16 mol) and K2CO3 (3.4 g, 24.6 mmol) are added to a solution of bis(2-bromoethyl)dimethylsilane 2(4.0 g, 16.4 mmol) in Dichloromethane (DCM). The mixture is then refluxed for 16 h. Water is added and the aqueous layer is extracted with DCM. It is then washed with 5% sodiumhydroxide (NaOH) solution, dried and concentrated. The product is purified by column chromatography on silica using hexane-ethylacetate mixtures to obtain the product as a colorless liquid 3 (2.1 g) in 59% yield.
Reaction SMILES: S(=O)(=O)(O)O.[N+:6]([O-:9])(O)=[O:7].[CH3:10][C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][N+:12]=1[O-:18].C(=O)([O-])[O-].[Na+].[Na+]>>[CH3:10][C:11]1[CH:16]=[C:15]([N+:6]([O-:9])=[O:7])[C:14]([CH3:17])=[CH:13][N+:12]=1[O-:18]
Reactant: Cc1ccc(C)[n+]([O-])c1
Reactant: O=[N+]([O-])O
Agent: O=C([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Product: Cc1c[n+]([O-])c(C)cc1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 85.4 %

Procedure:
To a nitrating mixture of sulphuric acid (24 mL) and nitric acid (12 mL) cooled to 0° C. was added 2,5-dimethyl-1-oxido-pyridin-1-ium (CAS: 4986-05-4) (8.4 g, 68.21 mmol). The solution was allowed to warm to room temperature and stirred over 30 mins then heated to 110° C. and stirred over 5 hrs. The reaction mixture was cooled and poured onto ice. The aqueous solution was made basic with solid sodium carbonate, giving a precipitate. The aqueous was extracted into DCM (3x), and the combined extracts were dried over magnesium sulphate, filtered and evaporated to yield a yellow solid, 2,5-dimethyl-4-nitro-1-oxido-pyridin-1-ium (D135) (9.8 g, 58.3 mmol, 85.4% yield);
Reaction SMILES: [Br:1][C:2]1[N:7]2[N:8]=[CH:9][N:10]=[C:6]2[C:5](Br)=[N:4][CH:3]=1.[NH2:12][C:13]1[CH:14]=[C:15]([CH:21]=[CH:22][CH:23]=1)[C:16]([O:18][CH2:19][CH3:20])=[O:17].Br>C(O)CC>[CH2:19]([O:18][C:16](=[O:17])[C:15]1[CH:21]=[CH:22][CH:23]=[C:13]([NH:12][C:5]2[C:6]3[N:7]([N:8]=[CH:9][N:10]=3)[C:2]([Br:1])=[CH:3][N:4]=2)[CH:14]=1)[CH3:20]
Reactant: Brc1ncc(Br)n2ncnc12
Reactant: CCOC(=O)c1cccc(N)c1
Agent: Br
Solvent: CCCO
Product: CCOC(=O)c1cccc(Nc2ncc(Br)n3ncnc23)c1
Temperature: 85 °C
Yield: 98 %

Procedure:
5,8-Dibromo-[1,2,4]triazolo[1,5-a]pyrazine (1.39 g, 5.00 mmol) and ethyl 3-aminobenzoate (0.93 g, 5.60 mmol) are stirred in PrOH (10 mL) and HBr (48% aq., 1.14 mL, 10 mmol) is added. The mixture is heated at 85° C. for 4 h and then cooled to rt and quenched with NaHCO3 (sat. aq., 25 mL). The resulting suspension is cooled to 0° C. and the white solid is collected by suction filtration and washed with water (10 mL). The crude product is taken up in EtOH and the solvent evaporated to afford the title compound as an off-white solid (1.79 g, 4.9 mmol) which is used without further purification.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[N:4][C:5]([CH2:11][S+:12]([O-:24])[C:13]2[N-:14][C:15]3[CH:16]=[CH:17][C:18]([O:22][CH3:23])=[CH:19][C:20]=3[N:21]=2)=[C:6]([CH3:10])[C:7]=1[O:8][CH3:9].[K+].O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Mg+2:38]>CO>[CH3:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([CH3:10])[C:5]([CH2:11][S@@:12]([C:13]2[N-:14][C:15]3[CH:16]=[CH:17][C:18]([O:22][CH3:23])=[CH:19][C:20]=3[N:21]=2)=[O:24])=[N:4][CH:3]=1.[Mg+2:38]
Reactant: COc1ccc2[n-]c([S+]([O-])Cc3ncc(C)c(OC)c3C)nc2c1
Agent: O=S(=O)([O-])[O-]
Agent: [K+]
Agent: [Mg+2]
Solvent: CO
Solvent: O
Product: COc1ccc2[n-]c([S@@](=O)Cc3ncc(C)c(OC)c3C)nc2c1
Temperature: 2.5 °C
Reaction time: 1.75 h
Yield: 45 %

Procedure:
To a solution of esomeprazole potassium salt (100 g, 0.261 mole) in methanol (500 ml) kept in a round bottom flask, was added magnesium sulphate heptahydrate (64.1 g, 0.26 mole) at 25-30° C. and stirred for 1.5-2 hrs. The insoluble material formed was filtered off and the filtrate was passed through a 0.45 micron membrane filter. To the filtrate, water (1300 ml) was added and stirred at 25-30° C. for 1-1.5 hrs, cooled to 0-5° C., and stirred for a further period of 1-1.5 hrs. The solid formed was collected by filtration and washed with water and dried under reduced pressure at 40-45° C. to obtain the esomeprazole magnesium salt.
Reaction SMILES: [Cl:1][CH:2]([CH2:6][C:7]1[CH:12]=[C:11]([N:13]2[C:17](=[O:18])[N:16]([CH:19]([F:21])[F:20])[C:15]([CH3:22])=[N:14]2)[C:10]([F:23])=[CH:9][C:8]=1[Cl:24])[C:3]([OH:5])=[O:4].[CH2:25](O)[CH3:26]>C1C=CC=CC=1>[CH3:25][CH2:26][O:4][C:3]([CH:2]([Cl:1])[CH2:6][C:7]1[CH:12]=[C:11]([N:13]2[N:14]=[C:15]([CH3:22])[N:16]([CH:19]([F:20])[F:21])[C:17]2=[O:18])[C:10]([F:23])=[CH:9][C:8]=1[Cl:24])=[O:5]
Reactant: Cc1nn(-c2cc(CC(Cl)C(=O)O)c(Cl)cc2F)c(=O)n1C(F)F
Reactant: CCO
Solvent: c1ccccc1
Product: CCOC(=O)C(Cl)Cc1cc(-n2nc(C)n(C(F)F)c2=O)c(F)cc1Cl

Procedure:
adding 1 mol of the 2-chloro-3-{2-chloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorophenyl}propionic acid of the step (1), 4˜10 mol of ethanol and 0.03˜0.2 mol of an acid catalyst into 6˜12 mol of the solvent of benzene class; refluxing the reaction mixture until an esterification is completed; washing successively with water, with aqueous alkali base and then with water; and removing the solvent totally from the organic layer, to give a product carfentrazone-ethyl.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[C:4]([NH:16][C:17]2[N:22]=[C:21](SC#N)[C:20]([N+:26]([O-:28])=[O:27])=[CH:19][N:18]=2)[CH:3]=1.Cl.[F:30][C:31]1[CH:32]=[CH:33][CH:34]=[C:35]2[C:40]=1[O:39][CH2:38][CH2:37][C@H:36]2[NH2:41].C(N(CC)C(C)C)(C)C>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:13])([CH3:14])[CH3:12])=[C:4]([NH:16][C:17]2[N:22]=[C:21]([NH:41][C@H:36]3[C:35]4[C:40](=[C:31]([F:30])[CH:32]=[CH:33][CH:34]=4)[O:39][CH2:38][CH2:37]3)[C:20]([N+:26]([O-:28])=[O:27])=[CH:19][N:18]=2)[CH:3]=1
Reactant: CC(C)(C)OC(=O)Nc1ccc(F)cc1Nc1ncc([N+](=O)[O-])c(SC#N)n1
Reactant: N[C@@H]1CCOc2c(F)cccc21
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)Nc1ccc(F)cc1Nc1ncc([N+](=O)[O-])c(N[C@@H]2CCOc3c(F)cccc32)n1
Temperature: 25 °C
Reaction time: 6 h
Yield: 94 %

Procedure:
tert-Butyl 4-fluoro-2-(5-nitro-4-thiocyanatopyrimidin-2-ylamino)phenylcarbamate (2.0 g) was added to a solution of (R)-8-fluorochroman-4-amine hydrochloride (1.1 gram) and N,N-diisopropylethylamine (2.2 mL) in THF (anhydrous, 50 mL). The mixture was stirred for 6 hr at room temperature then partitioned between water and EtOAc and separated. The aq. layer was washed with additional EtOAc and the combined organics were dried over Na2SO4 and concentrated in vacuo to give the title product in 94% yield. MH+=515, 459 (-tBu).