Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([C:3]1[CH:7]=[CH:6][NH:5][CH:4]=1)=[O:2].[H-].[Na+].[C:10](Cl)(=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>O1CCCC1.O>[C:10]([N:5]1[CH:6]=[CH:7][C:3]([CH:1]=[O:2])=[CH:4]1)(=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: O=Cc1cc[nH]c1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: O=Cc1ccn(C(=O)c2ccccc2)c1
Reaction time: 0.25 h

Procedure:
500 mg of 3-formyl-pyrrole were dissolved in 10 ml of tetrahydrofuran and then, at +20° C., 227 mg of sodium hydride dispersed at 55% in vaseline oil were added all at once. Gas evolved and after stirring for 15 minutes, a solution of 0.58 ml of benzoyl chloride in 2 ml of tetrahydrofuran was introduced dropwise at +5° C. The mixture was stirred for 2 hours at 20° C. and diluted with water. Extracting with ether, concentrating to dryness by distillation under reduced pressure and chromatographing the residue over silica and eluting with a mixture of hexane and ethyl acetate (7-3) yielded 558 mg of 1-benzoyl-3-formyl-pyrrole.
Reaction SMILES: [CH3:1][C:2]1[C:3](=[O:11])[C:4]([CH3:10])([CH3:9])[CH2:5][C:6](=[O:8])[CH:7]=1.[Se](=O)=[O:13]>O1CCOCC1.O>[CH3:9][C:4]1([CH3:10])[C:3](=[O:11])[C:2]([CH3:1])=[CH:7][C:6](=[O:8])[C:5]1=[O:13]
Reactant: O=[Se]=O
Reactant: CC1=CC(=O)CC(C)(C)C1=O
Solvent: O
Solvent: C1COCCO1
Product: CC1=CC(=O)C(=O)C(C)(C)C1=O

Procedure:
129.4 g of 2,6,6-trimethylcyclohex-2-ene-1,4-dione (from Example 1) were added to a solution of 100 g of selenium dioxide in a mixture of 800 ml of dioxane and 50 ml of water, and the mixture was refluxed for 9 hours with stirring. The precipitate of elemental selenium was then filtered off with suction, and then all the low boilers were removed in a rotary evaporator. The residue was distilled at 125° C./20 mbar. The distillate was melted, mortared with n-hexane and then extracted with 600 ml of n-hexane. The target product crystallized out in the form of yellow needles.
Reaction SMILES: [CH2:1]([Li])[CH2:2][CH2:3][CH3:4].C1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)C=C1.IC>C1(C)C=CC=CC=1.C1COCC1>[CH3:4][CH:3]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:1]=[CH:2]1
Reactant: C1=Cc2ccccc2C1
Reactant: [Li]CCCC
Solvent: CI
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CC1C=Cc2ccccc21
Temperature: 25 °C
Reaction time: 24 h
Yield: 63 %

Procedure:
140 ml (0.35 mol) of a 2.5 M solution of n-butyllithium in toluene were added dropwise to a solution of 45.0 g of indene (0.35 mol) in 200 ml of THF at 0° C. in the course of 30 min in a 500 ml four-necked flask having a dropping funnel. After warming up to room temperature, the solution was stirred for a further hour. Thereafter, it was again cooled to 0° C., and 99.4 g (0.70 mol) of iodomethane were added dropwise in the course of 2 h. After warming up to room temperature, stirring was effected for a further 24 h. The solvents were distilled off on a rotary evaporator at a bath temperature of 40° C. and 100 mbar. The black residue was extracted by shaking three times with 200 ml of pentane each time. After concentration of the combined pentane fractions on a rotary evaporator, the crude product was fractionated over a 25 cm Vigreux column. 28.6 g (0.22 mol; 63% yield) of colorless methylindene were obtained under a vacuum from a diaphragm pump at 19 mbar and a top temperature of 71-73° C. The 1H-NMR spectrum shows an isomer mixture of 1- and 3-methylindene in the ratio of 1:1.
Reaction SMILES: [C:1]([NH:4][C:5]1[C:6]([I:17])=[C:7]([C:11]([I:16])=[C:12]([NH2:15])[C:13]=1[I:14])[C:8]([OH:10])=[O:9])(=[O:3])[CH3:2].[O-][CH2:19]C.[Na+].[Na].CI>>[NH2:15][C:12]1[C:11]([I:16])=[C:7]([C:6]([I:17])=[C:5]([N:4]([CH3:19])[C:1](=[O:3])[CH3:2])[C:13]=1[I:14])[C:8]([OH:10])=[O:9]
Reactant: CC(=O)Nc1c(I)c(N)c(I)c(C(=O)O)c1I
Reactant: CC[O-]
Agent: [Na+]
Agent: [Na]
Solvent: CI
Product: CC(=O)N(C)c1c(I)c(N)c(I)c(C(=O)O)c1I
Temperature: 22 °C
Reaction time: 0.17 h
Yield: 82.6 %

Procedure:
3-Acetamido-5-amino-2,4,6-triiodobenzoic acid (I; 228.76 g., 0.4 mole) was added to an anhydrous ethanolic solution of sodium ethoxide (prepared from 18.4 g. (0.8 g. atom) of sodium) at 45° C. After 10 minutes, the homogeneous solution was cooled to 22° C. and methyl iodide (62.48 g.; 0.44 mole) was added. The reaction mixture was heated at 50°-55° C. for 30 minutes, at 62° C. for 30 minutes and finally at 68°-70° C. for 15 minutes. The reaction mixture was now pH 8. Methyl iodide (1 ml.) was added and heating was continued at 70° C. for 15 minutes after which the solution was neutral. The ethanol was removed under reduced pressure and water (1300 ml.) was added to the residue. The solid which dropped out of solution was collected; the filtrate was basified (~pH 10) with 50% sodium hydroxide and was washed with a 3:1 chloroform-isopropyl alcohol mixture (800 ml.). The aqueous layer was acidified to pH 5 with acetic acid and treated with activated charcoal marketed under the trade designation "Darco G-60" (5 g.) for 1 hour. The filtered solution was added to 6N hydrochloric acid (700 ml.) at room temperature to precipitate the product. The precipitate was digested for 10 minutes and was then collected, washed with water (500 ml.), and dried at 60° C. overnight to yield 193.5 g. of 3-amino-2,4,6-triiodo-5-(N-methylacetamido)-benzoic acid (82.6% yield). The product was homogeneous by thin-layer chromatography (chloroform-ethyl acetate-acetic acid, 30:20:1) and the structure of the product was confirmed by nuclear magnetic resonance spectroscopy.
Reaction SMILES: [NH2:1][C:2]1[NH:3][C:4](=[O:12])[C:5]2[S:10][C:9](=[O:11])[NH:8][C:6]=2[N:7]=1.[C:13]([O:21][CH:22]([C@@H:25]1[CH2:29][C@@H:28]([O:30][C:31](=[O:33])[CH3:32])[CH:27](OC(=O)C)[O:26]1)[CH2:23][CH3:24])(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C>C(#N)C>[C:13]([O:21][CH:22]([C@@H:25]1[CH2:29][C@@H:28]([O:30][C:31](=[O:33])[CH3:32])[C@H:27]([N:8]2[C:6]3[N:7]=[C:2]([NH2:1])[NH:3][C:4](=[O:12])[C:5]=3[S:10][C:9]2=[O:11])[O:26]1)[CH2:23][CH3:24])(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: CCC(OC(=O)c1ccccc1)[C@@H]1C[C@@H](OC(C)=O)C(OC(C)=O)O1
Reactant: Nc1nc2[nH]c(=O)sc2c(=O)[nH]1
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: CC#N
Product: CCC(OC(=O)c1ccccc1)[C@@H]1C[C@@H](OC(C)=O)[C@H](n2c(=O)sc3c(=O)[nH]c(N)nc32)O1
Temperature: 70 °C
Reaction time: 0.5 h
Yield: 79.3 %

Procedure:
To a suspension of 5-amino-3,6-dihydrothiazolo[4,5-d]pyrimidine-2,7-dione (2.82 g, 16.8 mmol) in ACN (100 mL) was added BSA (10.4 mL, 42 mmol). The resulting reaction mixture was then stirred at 70° C. under argon for 0.5 hour to form a clear solution. After the solution was cooled to room temperature, 1-[(2S,4R)-4,5-diacetoxytetrahydrofuran-2-yl]propyl benzoate (compound 26b, 4.9 g, 14.0 mmol) and TMSOTf (4.7 mL, 2.3 21 mmol) were added in sequence. After being heated with stirring at 70° C. for 14 hours, the solvent was removed in vacuo. The residue was partitioned between EtOAc and saturated NaHCO3 solution (30 mL). The organic layer was separated and the aqueous phase was extracted with EtOAc (30 mL) twice. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 1:200 methanol in DCM) to afford 5.27 g crude product of 1-[(2S,4R,5R)-4-acetoxy-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)tetrahydrofuran-2-yl]propyl benzoate (compound 26c) as a light yellow solid. MS obsd. (ESI+) [(M+H)+]: 475.
Reaction SMILES: [N+:1]([C:4]1[NH:5][CH:6]=[CH:7][N:8]=1)([O-:3])=[O:2].C(=O)([O-])[O-].[K+].[K+].[CH2:15]([CH:17]1[O:19][CH2:18]1)[Cl:16]>>[N+:1]([C:4]1[N:5]([CH2:18][CH:17]([OH:19])[CH2:15][Cl:16])[CH:6]=[CH:7][N:8]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ncc[nH]1
Reactant: ClCC1CO1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: O=[N+]([O-])c1nccn1CC(O)CCl

Procedure:
Epichlorohydrin (100 mL) was added to a mixture of 2-nitroimidazole (11.3 g, 0.1 mol) and 1 g of potassium carbonate and the solution refluxed for 15-20 min until all 2-nitroimidazole was dissolved. The hot solution was filtered and the yellow crystal was collected to give compound (5, 17 g, 83%). 1H NMR (DMSO-d6, δppm): 3.61 (m, 2H, Cl—CH2—), 4.06 (m, 1H, HO—CH—), 4.32 (dd, 1H, N—CHa—, J=13.8 Hz, 8.4 Hz), 4.63 (dd, 1H, N—CHb—, J=13.8 Hz, 3.6 Hz), 5.67 (d, 1H, OH, J=5.7 Hz), 7.15 (s, 1H, —CH═), 7.56 (s, 1H, —CH═). 13C NMR (DMSO-d6, δppm): 46.81, 52.27, 68.75, 127.40, 128.45, 144.98.
Reaction SMILES: [CH3:1][C@H:2]([NH2:6])[C:3]([OH:5])=[O:4].C(OC([NH:17][CH2:18][CH2:19][CH2:20][CH2:21][C@@H:22]([C:24]([OH:26])=[O:25])[NH2:23])=O)C1C=CC=CC=1.FC(F)(F)C(O)=O.C1(SC)C=CC=CC=1.C(N[C@H](C(OC(=O)[C@H](CCCCNC(OCC1C=CC=CC=1)=O)NC(O)=O)=O)CCCCNC(OCC1C=CC=CC=1)=O)(O)=O>>[CH3:1][C@H:2]([NH2:6])[C:3]([OH:5])=[O:4].[NH2:23][C@H:22]([C:24]([OH:26])=[O:25])[CH2:21][CH2:20][CH2:19][CH2:18][NH2:17]
Reactant: N[C@@H](CCCCNC(=O)OCc1ccccc1)C(=O)O
Agent: C[C@H](N)C(=O)O
Agent: O=C(O)N[C@@H](CCCCNC(=O)OCc1ccccc1)C(=O)OC(=O)[C@H](CCCCNC(=O)OCc1ccccc1)NC(=O)O
Solvent: O=C(O)C(F)(F)F
Solvent: CSc1ccccc1
Product: NCCCC[C@H](N)C(=O)O

Procedure:
To the poly-L-alanine/Nε-benzyloxycarbonyl-L-lysine copolymer (9/1) obtained in Production Example 16 were added 270 equivalents and 5 equivalents of trifluoroacetic acid (manufactured by TOKYO CHEMICAL INDUSTRY CO., LTD.) and thioanisole (manufactured by TOKYO CHEMICAL INDUSTRY CO., LTD.), respectively, relative to the number of moles of N-carboxy-N′-benzyloxycarbonyl-L-lysine anhydride, and the mixture was reacted at room temperature to give a poly-L-alanine/L-lysine copolymer. This was dissolved in a dichloromethane-trifluoroacetic acid mixed solvent (50:70 (v/v)) to give a 4.4 wt % poly-L-alanine/L-lysine copolymer solution. A fiber structure made of a poly-L-alanine/L-lysine copolymer was obtained from this solution in the same manner as in Production Example 1.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH:9]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:10][C:11](=O)[CH:12]([CH3:14])[CH3:13])=[CH:4][CH:3]=1.[NH2:23][CH2:24][CH2:25][C@H:26]1[O:31][B:30]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([N+:38]([O-:40])=[O:39])[CH:33]=2)[O:29][C@@H:28]([CH2:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:27]1>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:23]([CH2:24][CH2:25][C@H:26]3[O:31][B:30]([C:32]4[CH:37]=[CH:36][CH:35]=[C:34]([N+:38]([O-:40])=[O:39])[CH:33]=4)[O:29][C@@H:28]([CH2:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:27]3)[C:11]([CH:12]([CH3:14])[CH3:13])=[CH:10][C:9]=2[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)C[C@H]1C[C@@H](CCN)OB(c2cccc([N+](=O)[O-])c2)O1
Reactant: CC(C)C(=O)CC(C(=O)c1ccc(F)cc1)c1ccccc1
Product: CC(C)c1cc(-c2ccccc2)c(-c2ccc(F)cc2)n1CC[C@@H]1C[C@H](CC(=O)OC(C)(C)C)OB(c2cccc([N+](=O)[O-])c2)O1

Procedure:
According to the same method as in Example 4-1, the title compound was synthesized using 1-(4-fluorophenyl)-5-methyl-2-phenyl-1,4-hexanedione and t-butyl 2-((4R,6R)-6-(2-aminoethyl)-2-(3-nitrophenyl)-1,3,2-dioxaborinan-4-yl)acetate.
Reaction SMILES: [NH2:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([F:11])=[CH:8][CH:9]=2)[NH:4][C:3]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13].[CH2:17](N(CC)CC)C.[C:24](Cl)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(OCC)(=O)C>C(Cl)Cl>[CH2:17]([NH:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([F:11])=[CH:8][CH:9]=2)[NH:4][C:3]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:24]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:31]
Reactant: CCN(CC)CC
Reactant: O=C(Cl)c1ccccc1
Reactant: CCOC(=O)c1[nH]c2cc(F)ccc2c1N
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CCOC(=O)c1[nH]c2cc(F)ccc2c1NCC(=O)c1ccccc1

Procedure:
Suspend 3-Amino-2-carbethoxy-6-fluoroindole (1.1 eq) in methylene chloride and add triethylamine (1.1 eq). Add benzoyl chloride (1.1 eq) and stir for 30 minutes at room temperature to produce a precipitate. Dilute the reaction with ethyl acetate, rinse with water, dry over magnesium sulfate, filter and concentrate in vacuo to yield the title compound (1.26 g).
Reaction SMILES: C([O:3][C:4]([C:6]1[C:7]([O:12][C:13]2[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=2[Cl:20])=[N:8][CH:9]=[N:10][CH:11]=1)=[O:5])C.[OH-].[Na+]>O1CCCC1.O>[Cl:20][C:14]1[CH:15]=[CH:16][C:17]([Cl:19])=[CH:18][C:13]=1[O:12][C:7]1[C:6]([C:4]([OH:5])=[O:3])=[CH:11][N:10]=[CH:9][N:8]=1
Reactant: CCOC(=O)c1cncnc1Oc1cc(Cl)ccc1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)c1cncnc1Oc1cc(Cl)ccc1Cl
Temperature: 80 °C
Yield: 82.3 %

Procedure:
To a solution of 515 mg (1.64 mmol) 4-(2,5-dichloro-phenoxy)-pyrimidine-5-carboxylic acid ethyl ester in 10 mL tetrahydrofuran/water (2/1 v/v) was added 3.29 mL (3.28 mmol) 1M aqueous sodium hydroxide solution and the resulting solution was heated by microwave irradiation (Emrys Optimizer, Personal Chemistry) 30 minutes at 80° C. Solvents were evaporated under vacuum and the residue extracted three times with ethyl acetate and 1M aqueous hydrochloric acid. The combined organic layers were dried over magnesium sulfate, filtered and evaporated to give 385 mg (57%) of the desired compound as an off-white powder. MS (ESI): m/z=238.8 [M−H]−.
Reaction SMILES: Cl.Cl.[CH3:3][CH:4]1[CH2:9][CH2:8][CH2:7][CH2:6][N:5]1[CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[CH2:20][NH:19][CH2:18][CH2:17]2.[CH3:24][C:25]([CH3:27])=O.[BH3-]C#N.[Na+]>CO.O>[CH:25]([N:19]1[CH2:18][CH2:17][C:16]2[C:21](=[CH:22][CH:23]=[C:14]([O:13][CH2:12][CH2:11][CH2:10][N:5]3[CH2:6][CH2:7][CH2:8][CH2:9][CH:4]3[CH3:3])[CH:15]=2)[CH2:20]1)([CH3:27])[CH3:24]
Reactant: CC(C)=O
Reactant: CC1CCCCN1CCCOc1ccc2c(c1)CCNC2
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CC(C)N1CCc2cc(OCCCN3CCCCC3C)ccc2C1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a flask equipped with a stir bar is placed 6-[3-(2-Methyl-piperidin-1-yl)-propoxy]-1,2,3,4-tetrahydro-isoquinoline dihydrochloride (300 mg, 0.83 mmol), acetone (excess), NaCNBH3 (155 mg, 2.5 mmol) in MeOH (8 mL) and the mixture stirred at room temperature for 2 h. The reaction mixture is diluted with water, and extracted with CH2Cl2. The organic phase is dried over Na2SO4 and concentrated. M+1 331, LCMS >98% @ 230 nm and ELSD.
Reaction SMILES: [CH2:1]([S:3][C:4]1[C@:5]2([CH2:22][C@H:21]([OH:23])[C@@:20]3([F:24])[C@@H:10]([CH2:11][CH2:12][C:13]4[C@:18]3([CH3:19])[CH:17]=[CH:16][C:15](=[O:25])[CH:14]=4)[C@@H:7]2[CH2:8][CH:9]=1)[CH3:6])[CH3:2].[SH2:26].B(F)(F)F.CCOCC>ClCCl.C(Cl)(Cl)Cl>[CH3:2][CH2:1][S:3][C@@:4]1([SH:26])[CH2:9][CH2:8][C@H:7]2[C@H:10]3[C@:20]([F:24])([C@@H:21]([OH:23])[CH2:22][C@:5]12[CH3:6])[C@:18]1([CH3:19])[C:13](=[CH:14][C:15](=[O:25])[CH:16]=[CH:17]1)[CH2:12][CH2:11]3
Reactant: CCSC1=CC[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@]12C
Reactant: S
Agent: FB(F)F
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Solvent: CCOCC
Product: CCS[C@@]1(S)CC[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@@]21C
Temperature: -40 °C
Reaction time: 3.75 h

Procedure:
A solution of 2.0 g of 17-ethylthio-9-fluoro-11β-hydroxyandrosta-1,4,16-triene-3-one in dry dichloromethane (120 ml) was cooled and stirred in a bath at about -40° C. and a slow stream of hydrogen sulfide gas was passed into the solution while boron trifluoride etherate (1.2 ml) was added. After about 3.5 to 4.0 hours, the mixture was diluted with chloroform, warmed to room temperature and washed successively with a dilute sodium bicarbonate solution and water. The soluiton was dried (anhydrous magnesium sulfate), evaporated and the solid residue crystallized from ethyl acetate to afford 1.4. g of the title compound, melting point 239°-242° C.
Reaction SMILES: S(Cl)([Cl:3])=O.[CH2:5]([OH:13])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[CH:14]12[CH2:21][CH2:20][CH:17]([CH2:18][CH2:19]1)[C@@H:16]([C:22](O)=[O:23])[NH:15]2.CCOCC>O.CCOCC>[ClH:3].[CH2:5]([O:13][C:22]([C@@H:16]1[CH:17]2[CH2:20][CH2:21][CH:14]([CH2:19][CH2:18]2)[NH:15]1)=[O:23])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCO
Reactant: O=C(O)[C@H]1NC2CCC1CC2
Reactant: O=S(Cl)Cl
Solvent: O
Solvent: CCOCC
Product: CCCCCCCCOC(=O)[C@H]1NC2CCC1CC2
Product: Cl
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 81 %

Procedure:
9.6 ml of thionyl chloride are added dropwise into a 250 ml round-bottomed flask containing 60 ml of n-octanol cooled to 0° C. After stirring for 10 min at 0° C., 18.6 g of (3S)-2-azabicyclo[2.2.2]octane-3-carboxylic acid (described in Patent FR 2,585,709) are added slowly. The reaction mixture is left stirring overnight at room temperature, then heated for 6 hours at 80° C. and again left overnight at room temperature. After adding 100 ml of anhydrous ether and filtering off the unreacted hydrochloride, the filtrate is condensed and then taken up with a water/ether mixture (50:50). The expected product is obtained after concentration of the aqueous phase and then drying under vacuum.
Reaction SMILES: [CH2:1]([O:8][CH:9]1[CH2:14][CH2:13][CH2:12][C:11]2(OCC[O:15]2)[C:10]1([CH3:26])[CH2:19][CH2:20][CH2:21][CH:22]([CH3:25])[CH2:23][OH:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)=O.S(=O)(=O)(O)O>O>[CH2:1]([O:8][CH:9]1[CH2:14][CH2:13][CH2:12][C:11](=[O:15])[C:10]1([CH3:26])[CH2:19][CH2:20][CH2:21][CH:22]([CH3:25])[CH2:23][OH:24])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(CO)CCCC1(C)C(OCc2ccccc2)CCCC12OCCO2
Agent: O=S(=O)(O)O
Solvent: CC(C)=O
Solvent: O
Product: CC(CO)CCCC1(C)C(=O)CCCC1OCc1ccccc1
Yield: 99.8 %

Procedure:
A mixture of (2S*, 3R*)-3-benzyloxy-1,1-ethylenedioxy-2-methyl-2-(4'-methyl-5'-hydroxypentyl)-cyclohexane (13.9 g, 0.0384 mol), acetone (150 ml), water (20 ml) and 0.002 N sulfuric acid (50 ml) is refluxed for 18 hours under a nitrogen atmosphere. The reaction mixture is cooled, the acetone evaporated under reduced pressure and the aqueous layer extracted with ether (3×500 ml). The combined organic layers are washed with saturated sodium bicarbonate (100 ml), saturated sodium chloride (2×200 ml) and dried (MgSO4). The solvents are removed to afford (2S*, 3R*)-3-benzyloxy-2-methyl-2-(4'-methyl-5'-hydroxypentyl)-cyclohexanone (crude product, 12.2 g, 100%): ir (neat) 3484 (OH), 1709 cm-1 (CO); nmr (CDCl3)δ 0.88 (d, J=6 Hz, 3H, --CH--CH3), 1.08 (s, 3H, CH3), 3.42 (m, 4 H, ##STR56## 4.50 (d of d, J=10 Hz, 2H, Ph--CH2 --O--), 7.2 (s, 5H, aromatic).
Reaction SMILES: [CH3:1][N:2]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]2[CH:16]=[CH:15][C:12]([C:13]#N)=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.C(O)=[O:18]>[Ni]>[CH3:1][N:2]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]2[CH:16]=[CH:15][C:12]([CH:13]=[O:18])=[CH:11][CH:10]=2)[CH2:4][CH2:3]1
Reactant: O=CO
Reactant: CN1CCCN(c2ccc(C#N)cc2)CC1
Agent: [Ni]
Product: CN1CCCN(c2ccc(C=O)cc2)CC1

Procedure:
4-(4-Methylhomopiperazin-1-yl)benzonitrile (15 g) was dissolved in formic acid (225 ml) and Raney nickel (15.5 g) was added. The mixture was refluxed under heating for 2.5 hr. After the reaction, the catalyst was filtered off and the mixture was concentrated under reduced pressure. The residue was neutralized with saturated aqueous potassium carbonate solution and extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure to give the objective 4-(4-methylhomopiperazin-1-yl)benzaldehyde as an oil (16.1 g).
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]([C:12](=O)[CH3:13])[C:9]([N:15]2[CH2:20][CH2:19][N:18]([C:21]([C:23]3[CH:27]=[CH:26][N:25]([CH3:28])[N:24]=3)=[O:22])[CH2:17][CH2:16]2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.C([O-])(=O)C.[NH4+].C([BH3-])#[N:35].[Na+].O1CCCC1>CO.C(#N)C>[Cl:1][C:2]1[CH:11]=[C:10]([CH:12]([NH2:35])[CH3:13])[C:9]([N:15]2[CH2:20][CH2:19][N:18]([C:21]([C:23]3[CH:27]=[CH:26][N:25]([CH3:28])[N:24]=3)=[O:22])[CH2:17][CH2:16]2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2
Reactant: [BH3-]C#N
Reactant: CC(=O)c1cc(Cl)c2cccnc2c1N1CCN(C(=O)c2ccn(C)n2)CC1
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CO
Solvent: CC#N
Solvent: C1CCOC1
Product: CC(N)c1cc(Cl)c2cccnc2c1N1CCN(C(=O)c2ccn(C)n2)CC1
Temperature: 65 °C

Procedure:
A mixture of 1-(5-chloro-8-{4-[(1-methyl-1H-pyrazol-3-yl)carbonyl]piperazin-1-yl}quinolin-7-yl)ethanone (0.032 g, 0.080 mmol) and ammonium acetate (0.0620 g, 0.804 mmol) in methanol (0.3 mL,) and acetonitrile (0.3 mL) was heated at 65° C. in a sealed tube for 1 hour. After cooling to room temperature, to the resulting mixture was added 1.0 M sodium cyanoborohydride in tetrahydrofuran (0.20 mL, 0.20 mmol). The reaction was heated at 65° C. overnight. The mixture was cooled to room temperature, quenched with sat. NaHCO3 solution, extracted with dichloromethane, dried over MgSO4 and concentrated to give the crude product. LCMS calculated for C20H24ClN6O (M+H)+: m/z=399.2; Found: 399.2.
Reaction SMILES: [Cl-].C([C@H:9]1[CH2:13][O:12][C:11](=[O:14])[N:10]1[C:15](=[O:36])[CH2:16]P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)C1C=CC=CC=1.[CH:37]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH:40]=[CH:39][C:38]=1[CH:47]=O.C(N(CC)CC)C>CN(C)C1C=CN=CC=1.C(#N)C>[CH:37]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH:40]=[CH:39][C:38]=1/[CH:47]=[CH:16]/[C:15]([N:10]1[CH2:9][CH2:13][O:12][C:11]1=[O:14])=[O:36]
Reactant: O=Cc1ccc2ccccc2c1
Reactant: O=C(C[PH](c1ccccc1)(c1ccccc1)c1ccccc1)N1C(=O)OC[C@@H]1Cc1ccccc1
Agent: CN(C)c1ccncc1
Agent: [Cl-]
Solvent: CC#N
Solvent: CCN(CC)CC
Product: O=C(/C=C/c1ccc2ccccc2c1)N1CCOC1=O
Yield: 69.8 %

Procedure:
A mixture of (4S)-4-benzyl-3-[(triphenylphosphino) acetyl]-1,3-oxazolidin-one chloride (10 mg, 0.193 mmol), 2-naphthaldehyde (30 mg, 0.193 mmol), triethylamine (0.030 ml, 0.212 mmol) and 4-(dimethylamino)pyridine in acetonitrile (5 ml) was heated under reflux for 24 h. After evaporation, the residue was dissolved in hexaneetherdichloromethane and chromatographed on flash silica eluting with hexane:ether 3:2 to give a white solid (36 mg, 52%) of 3-[(E)-3-Naphthalen-2-ylprop-2-enoyl]-1,3-oxazolidin-2-one. M/e 358 (MH+).
Reaction SMILES: [CH3:1][C:2]1[C:3]([CH2:14][S:15][C:16]2[NH:20][C:19]3[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=3[N:17]=2)=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11].[O-:25]S([O-])(=S)=O.[Na+].[Na+].C(O)(=O)C>C(O)C.OO.O>[CH3:1][C:2]1[C:7]([O:8][CH2:9][C:10]([F:12])([F:11])[F:13])=[CH:6][CH:5]=[N:4][C:3]=1[CH2:14][S+:15]([O-:25])[C:16]1[NH:20][C:19]2[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=2[N:17]=1
Reactant: Cc1c(OCC(F)(F)F)ccnc1CSc1nc2ccccc2[nH]1
Reactant: O=S([O-])([O-])=S
Agent: OO
Agent: [Na+]
Solvent: CCO
Solvent: O
Solvent: CC(=O)O
Product: Cc1c(OCC(F)(F)F)ccnc1C[S+]([O-])c1nc2ccccc2[nH]1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 63 %

Procedure:
0.5 g of 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]thio]-1H-benzimidazole was suspended in 7 ml of ethanol at room temperature. 0.025 g of Na2WO4·2H2O oxidation catalyst was dissolved in 0.141 g H2O2 (35% aqueous solution), and further diluted with 2 ml of water. The oxidant/catalyst solution was added to the reactant suspension dropwise so that the addition was completed in about 30 minutes while stirring at room temperature. The reaction was continued for additional 8 hours while stirring. 2 ml of 10% Na2S2O3 aqueous solution was then added, and the resulting mixture was subjected to a reduced pressure to remove ethanol therefrom. Finally, a precipitate was formed after adding a diluted acetic acid aqueous solution to a pH value of about 8, which was filtered, water washed, and dried in vacuo to obtain Lansoprazole with a yield of about 63% (LC purity>80%).