Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([OH:6])(=[O:5])[C:2]([CH3:4])=[O:3].[CH2:7](O)[CH2:8][CH2:9][CH3:10]>O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>[C:1]([O:6][CH2:7][CH2:8][CH2:9][CH3:10])(=[O:5])[C:2]([CH3:4])=[O:3]
Reactant: CC(=O)C(=O)O
Reactant: CCCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: CCCCOC(=O)C(C)=O
Temperature: 25 °C
Yield: 70.1 %

Procedure:
First, a toluene (1 L) solution of pyruvic acid (440 g, 5.0 mol), n-butanol (371 g, 5.0 mol) and p-toluenesulfonic acid monohydrate (2.5 g) was heated and refluxed for 16 hours while removing water under a nitrogen gas stream, whereby a first reaction solution was obtained. Next, the first reaction solution was cooled to room temperature (25° C.). Thereafter, toluene was removed under reduced pressure (40 mmHg) using an evaporator, and the residue was purified by reduced pressure distillation (40 mmHg, 93 to 100° C.), whereby butyl pyruvate (505 g, yield 70%) was obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[C:9]([O:15][CH2:16][CH2:17][CH2:18][NH2:19])=[C:8]3[NH:20][C:21]4[CH:22]=[CH:23][C:24]([Cl:27])=[CH:25][C:26]=4[C:7]3=[CH:6][C:5]2=1.[NH:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:30]([CH:37]=O)=[CH:29]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CC(O)=O>ClCCCl>[NH:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:30]([CH2:37][NH:19][CH2:18][CH2:17][CH2:16][O:15][C:9]2[C:8]3[NH:20][C:21]4[C:26](=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=4)[C:7]=3[CH:6]=[C:5]3[C:4]4[CH:3]=[C:2]([Cl:1])[CH:14]=[CH:13][C:12]=4[NH:11][C:10]=23)=[CH:29]1
Reactant: O=Cc1c[nH]c2ccccc12
Reactant: NCCCOc1c2[nH]c3ccc(Cl)cc3c2cc2c1[nH]c1ccc(Cl)cc12
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Solvent: CC(=O)O
Product: Clc1ccc2[nH]c3c(OCCCNCc4c[nH]c5ccccc45)c4[nH]c5ccc(Cl)cc5c4cc3c2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 50 %

Procedure:
To a solution of 3-(2,10-dichloro-5,7-dihydroindolo[2,3-b]carbazol-6-yloxy)propan-1-amine (1 equiv) in 1,2-dichloroethane (10 mL/mmol), under an atmosphere of argon, was added 1H-indole-3-carbaldehyde (1 equiv), NaBH(OAc)3 (2 equiv), and then HOAc (2-3 equiv). The resulting mixture was stirred at RT overnight, and then partitioned between dichloromethane and 2 M Na2CO3. The organic layer was washed with brine, dried over Na2SO4, and concentrated. The residue was subjected to chromatography on silica gel, eluting with CH2Cl2/MeOH (10% cNH3.H2O) to the expected product in 50-80% yield. 1H NMR (400 MHz, CD3CN) δ 11.0 (br s, 2H), 9.25 (br s, 1H), 8.31 (s, 1H), 7.99 (d, J=2.4 Hz, 2H), 7.64 (d, J=7.6 Hz, 1H), 7.44 (dt, J=8.4, 0.8 Hz, 1H), 7.21 (d, J=2.4 Hz, 1H), 7.19-7.10 (m, 3H), 7.00 (ddd, J=7.2, 6.8, 0.8 Hz, 1H), 6.93 (d, J=8.4 Hz, 1H), 4.29 (t, J=5.6 Hz, 2H), 4.09 (s, 2H), 3.07 (t, J=6.0 Hz, 2H), 2.00 (pentalet, J=5.8 Hz, 2H).
Reaction SMILES: [CH2:1]([C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].OO.[I:18]I>CO>[I:18][C:14]1[CH:15]=[C:9]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH:10]=[CH:11][C:12]=1[NH2:13]
Reactant: CCCCCCCCc1ccc(N)cc1
Reactant: II
Agent: OO
Solvent: CO
Product: CCCCCCCCc1ccc(N)c(I)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 173.6 %

Procedure:
To a stirred mixture of 4-octyl aniline (0.33 g, 1.6 mmol) and H2O2 (30%, 0.5 ml) in CH3OH (1.5 nil) was added I2 (0.2 g, 0.8 mmol) and the mixture was stirred overnight at room temperature. The solvent was distilled off and the residue was diluted to 10 ml with CH2Cl2, washed with H2O, dried over MgSO4 and filtered. The filtrate was evaporated to dryness to give the title compound (0.46 g, 86%) as yellow paste. 1H NMR (CDCl3) 7.44 (d, 1H, J=1.83 Hz); 6.93 (dd, 1H, J=8.07, 1.86 Hz); 6.65 (d, 1H, J=8.1 Hz); 4.1 (b, 2H); 2.43 (t, 2H, J=7.5 Hz); 1.54-1.49 (m, 2H); 1.26 (b, 10H); 0.87 (t, 3H, J=6.39 Hz).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:22])/[CH:5]=[CH:6]/[CH:7]1[CH2:12][CH2:11][CH:10]([CH:13]2[CH2:18][CH2:17][CH:16]([CH2:19][CH2:20][CH3:21])[CH2:15][CH2:14]2)[CH2:9][CH2:8]1)[CH3:2].[H][H]>C1COCC1.[Pd]>[CH2:1]([O:3][C:4](=[O:22])[CH2:5][CH2:6][CH:7]1[CH2:12][CH2:11][CH:10]([CH:13]2[CH2:14][CH2:15][CH:16]([CH2:19][CH2:20][CH3:21])[CH2:17][CH2:18]2)[CH2:9][CH2:8]1)[CH3:2]
Reactant: [H][H]
Reactant: CCCC1CCC(C2CCC(/C=C/C(=O)OCC)CC2)CC1
Agent: [Pd]
Solvent: C1CCOC1
Product: CCCC1CCC(C2CCC(CCC(=O)OCC)CC2)CC1

Procedure:
(E)-3-(4′-Propyl-bicyclohexyl-4-yl)acrylic acid ethyl ester is hydrogenated in THF in the presence of palladium on charcoal. After 1 eq. of hydrogen has been consumed the catalyst is filtered off, the solvent is evaporated and the residue is filtered through silica yielding 3-(4′-propyl-bicyclohexyl-4-yl)-propionic acid ethyl ester as a colourless oil.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([CH3:13])=[CH:7][C:8](=[O:12])[O:9]2)=[CH:4][CH:3]=1.[C:14](Cl)(=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.CCN(CC)CC>C1COCC1>[C:14]([O:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([CH3:13])=[CH:7][C:8](=[O:12])[O:9]2)=[CH:4][CH:3]=1)(=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: Cc1cc(=O)oc2cc(O)ccc12
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Cc1cc(=O)oc2cc(OC(=O)c3ccccc3)ccc12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 7-hydroxy-4-methyl-chromen-2-one (0.5210 g, 3.0 mmol) and benzoyl chloride (0.4844 g, 0.4 mL, d=1.211 g/mL, 3.4 mmol) in THF (40 mL) was added Et3N (1 mL) at room temperature. The reaction mixture was stirred at room temperature overnight and filtered. The filtrate was concentrated to give the crude product 7-benzoyloxy-4-methyl-coumarin.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])/[C:4](/[NH:10][NH2:11])=[CH:5]\[C:6](OC)=[O:7].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C(C)=CC=CC=1>[CH3:1][O:2][C:3]([C:4]1[NH:10][N:11]=[C:6]([OH:7])[CH:5]=1)=[O:12]
Reactant: COC(=O)/C=C(/NN)C(=O)OC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1C
Product: COC(=O)c1cc(O)n[nH]1
Temperature: 25 °C
Reaction time: 8 h
Yield: 69.4 %

Procedure:
To a solution of (E)-2-hydrazino-but-2-enedioic acid dimethyl ester (500 mg, 2.87 mmol) in xylene (10 mL) was added para-toluenesulfonic acid (45 mg, 0.24 mmol) and the resulting mixture heated at reflux for 4 h. After cooling to room temperature the mixture was stirred overnight and the resulting solid was filtered off and dried to afford the title compound (283 mg, 69%) as a white solid after trituration with dichloromethane. MS: m/e=141.1 [M+H]+.
Reaction SMILES: Br[C:2]1[S:6][C:5]([CH:7]=[O:8])=[CH:4][CH:3]=1.[F:9][C:10]([F:19])([F:18])[C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1.C(=O)([O-])[O-].[K+].[K+].Cl>CN(C)C=O>[F:9][C:10]([F:18])([F:19])[C:11]1[CH:16]=[CH:15][C:14]([O:17][C:2]2[S:6][C:5]([CH:7]=[O:8])=[CH:4][CH:3]=2)=[CH:13][CH:12]=1
Reactant: O=Cc1ccc(Br)s1
Reactant: Oc1ccc(C(F)(F)F)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=Cc1ccc(Oc2ccc(C(F)(F)F)cc2)s1
Temperature: 100 °C
Reaction time: 68 h
Yield: 29 %

Procedure:
To a solution of 5-bromothiophene-2-carbaldehyde (0.12 mL, 1.0 mmol) and 4-trifluoromethylphenol (195 mg, 1.20 mmol) in 3 mL dimethylformamide was added potassium carbonate (276 mg, 2.00 mmol). The resulting suspension was stirred at 100° C. for 68 h before being cooled to room temperature and poured into 20 mL 0.2 N hydrochloric acid. Organics were extracted with ether (3×25 mL), washed with 2 N NaOH (2×30 mL), 0.2 N hydrochloric acid and brine (30 mL each), dried over magnesium sulfate, filtered and concentrated. The crude residue was subjected to chromatography on silica gel with gradient elution (5-10% ethyl acetate in hexanes+2% triethylamine) to give 5-(4-(trifluoromethyl)phenoxy)thiophene-2-carbaldehyde (79 mg, 29%) as an off-white solid. Used without further characterization.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.[C:7]([O:11][C:12](=[O:20])[NH:13][C:14]([CH3:19])([CH3:18])[CH2:15][CH2:16][OH:17])([CH3:10])([CH3:9])[CH3:8].C(N(CC)CC)C>ClCCl>[C:7]([O:11][C:12]([NH:13][C:14]([CH3:19])([CH3:18])[CH2:15][CH:16]=[O:17])=[O:20])([CH3:10])([CH3:9])[CH3:8]
Reactant: CC(C)(CCO)NC(=O)OC(C)(C)C
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(CC=O)NC(=O)OC(C)(C)C
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 63.6 %

Procedure:
Dimethylsufoxide (1.22 ml, 17.2 mmol) was added to a solution of oxalyl chloride (1.1 ml, 12.9 mmol) at −78° C. in dichloromethane (15 ml). The mixture was stirred for 15 min at −78° C. A solution of 3hydroxy-1,1-dimethylpropylcarbamic acid tert-butyl ester (1.75 g, 8.6 mmol) in dichloromethane (10 ml) was added dropwise over a period of 15 min. The solution was stirred at −78° C. for another 15 min. Triethylamine (6.0 ml, 43 mmol) was added. The solution was stirred at −78° C. for 5 min and then warmed to room temperature. The solution was diluted with dichloromethane (100 ml) and extracted with 1N hydrochloric acid (100 ml). The aqueous phase was extracted with dichloromethane (50 ml). The combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by column chromatography on silica (140 g) with ethyl acetate/heptane (1:3) to give 1.10 g of 3-(tert-butoxycarbonylamino)-3-methylbutanal.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]([CH3:14])([CH3:13])[C:10]([OH:12])=[O:11])=[CH:5][CH:4]=1)[CH3:2].[I:15]N1C(=O)CCC1=O.S(=O)(=O)(O)O.S([O-])(O)=O.[Na+]>C(O)(=O)C.O>[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]([CH3:13])([CH3:14])[C:10]([OH:12])=[O:11])=[CH:5][C:4]=1[I:15])[CH3:2]
Reactant: O=C1CCC(=O)N1I
Reactant: CCc1ccc(C(C)(C)C(=O)O)cc1
Agent: O=S(=O)(O)O
Agent: O=S([O-])O
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: CCc1ccc(C(C)(C)C(=O)O)cc1I
Temperature: 25 °C
Reaction time: 2 h

Procedure:
2-(4-Ethylphenyl)-2-methylpropanoic acid (58.1 g, 302.2 mmol) was dissolved in acetic acid (175 ml), added with N-iodosuccinimide (71.4 g, 317.3 mmol, 1.05 eq.) and conc. sulfuric acid (75 ml) at 0° C. Thereafter, the mixture was stirred at room temperature for 2 hrs. After cooling the reaction solution to 0° C., 10% aqueous solution of sodium hydrogen sulfite (100 ml) was added and the mixture was stirred for 1 hr. H2O (450 ml) was added to the mixture and the precipitated solid was filtered to obtain the title compound as a crude product. Ethanol (150 ml) and 10% aqueous solution of sodium hydrogen sulfite (50 ml) were added to the crude product, and the mixture was dissolved under heating at 50° C. After confirming the dissolution, the solution was cooled to room temperature, added with H2O (300 ml), and then stirred at 0° C. for 1 hr. The precipitated solid was filtered to obtain the title compound (95.8 g, 99%).
Reaction SMILES: C[Si]([C:5]#[C:6][C:7]1[CH:8]=[C:9]([CH:13]([O:23][CH:24]2[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]2)[C:14]2[NH:18][C:17]3[CH:19]=[CH:20][CH:21]=[CH:22][C:16]=3[N:15]=2)[CH:10]=[CH:11][CH:12]=1)(C)C.C(=O)([O-])[O-].[K+].[K+]>CO>[C:6]([C:7]1[CH:8]=[C:9]([CH:13]([O:23][CH:24]2[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]2)[C:14]2[NH:18][C:17]3[CH:19]=[CH:20][CH:21]=[CH:22][C:16]=3[N:15]=2)[CH:10]=[CH:11][CH:12]=1)#[CH:5]
Reactant: CN1CCC(OC(c2cccc(C#C[Si](C)(C)C)c2)c2nc3ccccc3[nH]2)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: C#Cc1cccc(C(OC2CCN(C)CC2)c2nc3ccccc3[nH]2)c1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of 2-[(3-trimethylsilylethynylphenyl)(1-methylpiperidin-4-yloxy)methyl]-1H-benzimidazole (205 mg) in methanol (2 mL) is added potassium carbonate (81 mg). The reaction mixture is stirred at room temperature for 4 hours, then methanol is removed under reduced pressure. The residue is dissolved in water and extracted with ethyl acetate. The organic phase is dried on magnesium sulphate and solvent is removed under reduced pressure to give 2-[(3-ethynylphenyl)(1-methylpiperidin-4-yloxy)methyl]-1H-benzimidazole
Reaction SMILES: [C:1]1([CH2:7][CH2:8][N:9]2[CH2:14][CH2:13][C:12]([CH3:18])([CH:15]=[N:16]O)[CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl>[Pt](=O)=O.CO>[C:1]1([CH2:7][CH2:8][N:9]2[CH2:14][CH2:13][C:12]([CH3:18])([CH2:15][NH2:16])[CH2:11][CH2:10]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC1(C=NO)CCN(CCc2ccccc2)CC1
Agent: O=[Pt]=O
Agent: Cl
Solvent: CO
Product: CC1(CN)CCN(CCc2ccccc2)CC1
Reaction time: 2 h
Yield: 78.9 %

Procedure:
A mixture containing 0.58 g (2.4 mmol) of 1-(2-phenylethyl)-4-methyl-4-oximinomethylpiperidine, 100 mL of methanol, 80 mg of platinum (IV) oxide and 0.75 mL of concentrated hydrochloric acid was hydrogenated at 40 p.s.i. for 2 hours. The mixture was filtered and evaporated. The residue was dissolved in water and made alkaline with aqueous potassium carbonate. The aqueous mixture was extracted with methylene chloride. The organic extracts were dried and evaporated to give 0.44 g of 1-(2-phenylethyl) -4-methyl-4-aminomethylpiperidine. NMR (CDCl3) δ7.18-7.28 (m, 5H); 5.22- 5.45 (br, 2H); 2.89 (s, 2H); 2.78-2.88 (m, 2H); 2.55-2.67 (m, 2H); 2.19 (t, 2H); 1.51-1.78 (m, 4H); 1.27-1.49 (m, 2H); 0.98 (s, 3H).
Reaction SMILES: [Cl-].[CH3:2][O:3][CH2:4][PH3+].[Li]CCCC.[CH3:11][O:12][C@H:13]1[C@@H:18]([CH3:19])[CH2:17][O:16][C@@H:15]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[C:14]1=O>O1CCCC1.C(OCC)(=O)C>[CH3:2][O:3][C@H:4]1[C@@H:18]([CH3:19])[CH2:17][O:16][C@@H:15]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[C:14]1=[CH:13][O:12][CH3:11]
Reactant: COC[PH3+]
Reactant: CCCCCCCCC[C@@H]1OC[C@H](C)[C@H](OC)C1=O
Agent: [Cl-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCCCCCCCC[C@@H]1OC[C@H](C)[C@H](OC)C1=COC
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 82.6 %

Procedure:
To a stirred suspension of methoxymethylphosphonium chloride (1,130 mg) in dry tetrahydrofuran (3 ml) there was added n-BuLi (1.9 ml, 1.6M in n-hexane) at 0° C. After the mixture was stirred at 0° C. for 30 min, a solution of (2S,4S,5S)-4-methoxy-5-methyl-2-nonyltetrahydro-2H-pyran-3-one (273 mg) in dry tetrahydrofuran (3 ml) was added to the resulting deep orange solution. After 30 min, the mixture was allowed to warm to room temperature, and stirred for an additional 2 hrs. The reaction was quenched by addition of saturated aqueous ammonium chloride solution. The mixture was extracted with diethyl ether, and the combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. Purification of the residue by silica gel chromatography (n-hexane: ethyl acetate=10:1 as an eluent) gave (2S,4S,5S)-4-methoxy-5-methyl-3-methoxymethylene-2-nonyltetrahydro-2H-pyran (249 mg, 83% yield).
Reaction SMILES: [OH:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][CH:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.Cl.Cl[CH2:24][CH2:25][N:26]([CH2:29][CH3:30])[CH2:27][CH3:28].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:25]([N:26]([CH2:29][CH3:30])[CH2:27][CH2:28][O:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[CH2:9][CH2:8]2)=[CH:20][CH:21]=1)[CH3:24]
Reactant: CC(C)(C)OC(=O)N1CCC(Oc2ccc(O)cc2)CC1
Reactant: CCN(CC)CCCl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCN(CC)CCOc1ccc(OC2CCN(C(=O)OC(C)(C)C)CC2)cc1
Reaction time: 4 h
Yield: 95.5 %

Procedure:
7.9 g tert-butyl 4-(4-hydroxyphenoxy)-piperidine-1-carboxylate (see WO2006/64218), 5.2 g (2-chloroethyl)-diethylamine hydrochloride and 16.6 g potassium carbonate are placed in 250 ml acetone. The reaction mixture is stirred at reflux temperature. After 4 hours the inorganic salts are suction filtered and the mixture is evaporated to dryness. The residue is combined with ethyl acetate. The organic phase is washed with a saturated NaHCO3 solution, dried and evaporated to dryness. 10.1 g of the product are obtained as an oil.
Reaction SMILES: O1CC[O:3][CH:2]1[C:6]1[CH:15]=[CH:14][C:9]([C:10]([O:12]C)=O)=[CH:8][CH:7]=1.[CH2:16]([NH:18][CH2:19][CH2:20][OH:21])[CH3:17]>>[CH2:16]([N:18]([CH2:19][CH2:20][OH:21])[C:2](=[O:3])[C:6]1[CH:7]=[CH:8][C:9]([CH:10]=[O:12])=[CH:14][CH:15]=1)[CH3:17]
Reactant: COC(=O)c1ccc(C2OCCO2)cc1
Reactant: CCNCCO
Product: CCN(CCO)C(=O)c1ccc(C=O)cc1
Reaction time: 1 h
Yield: 50.3 %

Procedure:
A solution of methyl 4-(1,3-dioxolan-2-yl)benzoate (0.63 g, 3.0 mmol) in 2-(ethylamino)ethanol (2.93 mL, 30.0 mmol) was heated in a microwave at 130° C. for 2 hours. The reaction mixture was partitioned between DCM and 1M aqueous hydrochloric acid and stirred vigorously for 1 hour. The organic phase was removed, washed with brine and passed through a hydrophobic frit. The solvent was evaporated at reduced pressure to afford the title compound (0.334 g, 50%).
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:30])[C@H:10]([CH:27]([CH3:29])[CH3:28])[NH:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[C:25]#[N:26])=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:31](Cl)(=[O:36])[CH2:32][CH2:33][CH2:34][CH3:35]>C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:30])[C@H:10]([CH:27]([CH3:28])[CH3:29])[N:11]([CH2:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[C:25]#[N:26])=[CH:17][CH:18]=1)[C:31](=[O:36])[CH2:32][CH2:33][CH2:34][CH3:35])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)[C@H](NCc1ccc(-c2ccccc2C#N)cc1)C(=O)OCc1ccccc1
Reactant: CCCCC(=O)Cl
Solvent: ClCCl
Product: CCCCC(=O)N(Cc1ccc(-c2ccccc2C#N)cc1)[C@H](C(=O)OCc1ccccc1)C(C)C

Procedure:
6.2 g (15.5 mmol) of N-[(2'-cyanobiphenyl-4-yl)methyl]-(L)-valine benzyl ester and 8.0 ml of Huinig base, dissolved in 50 ml of methylene chloride, are treated with 2.3 ml of valeryl chloride with stirring and further processed analogously to Example 29b. The title compound is thus obtained as a yellow oil which is further used in crude form (Rf 0.51, toluene-methanol 19:1)
Reaction SMILES: [CH3:1][N:2]([C:11](SC)=[C:12]([C:15]#[N:16])[C:13]#[N:14])[N:3]=[CH:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH3:19][NH:20][CH3:21]>C(O)C>[CH3:1][N:2]([C:11]([N:20]([CH3:21])[CH3:19])=[C:12]([C:15]#[N:16])[C:13]#[N:14])[N:3]=[CH:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: CSC(=C(C#N)C#N)N(C)N=Cc1ccccc1
Reactant: CNC
Solvent: CCO
Product: CN(C)C(=C(C#N)C#N)N(C)N=Cc1ccccc1
Temperature: 0 °C

Procedure:
The product of stage (a) (26 g), aqueous dimethylamine (6.6 g) and ethanol (250 ml) were heated under reflux for 4 hours and then cooled to 0° C. Benzaldehyde N-methyl-N-[2,2-dicyano-1-(dimethylamino)ethenyl]hydrazone (19.8 g) precipitated, m.p. 127°-128° C.
Reaction SMILES: [CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH:26]([CH3:28])[CH3:27])[CH2:23][CH2:22][C:21]([C:29]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([S:38][CH2:39][C:40]5[N:41]([CH3:45])[CH:42]=[N:43][CH:44]=5)=[CH:34][CH:33]=4)=[O:30])=[CH:20][C:19]=3[CH:46]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].ClC1C=CC=C(C(OO)=[O:55])C=1.S([O-])([O-])(=O)=S.[Na+].[Na+]>ClCCl>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH:26]([CH3:27])[CH3:28])[CH2:23][CH2:22][C:21]([C:29]([NH:31][C:32]4[CH:33]=[CH:34][C:35]([S:38]([CH2:39][C:40]5[N:41]([CH3:45])[CH:42]=[N:43][CH:44]=5)=[O:55])=[CH:36][CH:37]=4)=[O:30])=[CH:20][C:19]=3[CH:46]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH3:4]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(SCc4cncn4C)cc2)CCN3CC(C)C)cc1
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClCCl
Product: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(S(=O)Cc4cncn4C)cc2)CCN3CC(C)C)cc1
Temperature: -78 °C
Reaction time: 1 h
Yield: 66.3 %

Procedure:
7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[4-[(3-methylimidazol-4-yl)methylthio]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (0.53 g) was dissolved in dichloromethane (5 ml), and the mixture was cooled to −78° C. 3-chloroperbenzoic acid (0.31 g) in dichloromethane solution (5 ml) was added dropwise to the solution. The mixture was stirred for 1 hour at −78° C., and then, sodium thiosulfate solution was added to the mixture. The mixture was concentrated, and extracted with ethyl acetate. The organic layer was washed with aqueous sodium bicarbonate solution, water and saturated brine, and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off. The residue was purified by silica gel column chromatography (elution solvent: triethylamine/methanol/ethyl acetate), to give 7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[4-[(3-methylimidazol-4-yl)methylsulfinyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 72) (0.36 g) as yellow amorphous.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:21]=[CH:20][C:12]([C:13]([NH:15][CH2:16][CH2:17][CH2:18]Cl)=[O:14])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:22]([C:29]1([OH:35])[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+].CC(=O)CC>O>[CH2:22]([C:29]1([OH:35])[CH2:34][CH2:33][N:32]([CH2:18][CH2:17][CH2:16][NH:15][C:13](=[O:14])[C:12]2[CH:20]=[CH:21][C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:10][CH:11]=2)[CH2:31][CH2:30]1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: O=C(NCCCCl)c1ccc(OCc2ccccc2)cc1
Reactant: OC1(Cc2ccccc2)CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Solvent: O
Product: O=C(NCCCN1CCC(O)(Cc2ccccc2)CC1)c1ccc(OCc2ccccc2)cc1
Yield: 24.6 %

Procedure:
A mixture of 4-benzyloxy-N-(3-chloro-propyl)-benzamide (0.5 g, 1.64 mmol), ), 4-benzyl-4-hydroxy-piperidine (0.315 g, 1.65 mmol), potassium carbonate (0.45 g, 3.29 mmol) and 2-butanone (10 ml) was stirred at 60° C. for 48 h. After the addition of water, the mixture was extracted with ethyl acetate. The organic layer was dried (Na2SO4), filtered and evaporated. The residue was purified by chromatography (silica gel, methylene chloride-methanol from 95:5 to 9:1) to give N-[3-(4-benzyl-4-hydroxy-piperidin-1-yl)-propyl]-4-benzyloxy-benzamide (185 mg, 25%) as a light yellow solid. MS: me/e=459 (M+H)+.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[C:3]1[C:7]1[CH:17]=[CH:16][C:10]([O:11][CH:12]2[O:15][CH:13]2[CH3:14])=[CH:9][CH:8]=1.[CH3:18][O:19][C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][C:28]=1[O:29][CH3:30])[CH2:23][CH2:24][NH2:25]>C(O)(C)C>[CH3:18][O:19][C:20]1[CH:21]=[C:22]([CH2:23][CH2:24][NH:25][CH2:14][CH:13]([OH:15])[CH2:12][O:11][C:10]2[CH:16]=[CH:17][C:7]([C:3]3[N:2]([CH3:1])[CH:6]=[CH:5][N:4]=3)=[CH:8][CH:9]=2)[CH:26]=[CH:27][C:28]=1[O:29][CH3:30]
Reactant: CC1OC1Oc1ccc(-c2nccn2C)cc1
Reactant: COc1ccc(CCN)cc1OC
Solvent: CC(C)O
Product: COc1ccc(CCNCC(O)COc2ccc(-c3nccn3C)cc2)cc1OC
Temperature: 70 °C
Reaction time: 18 h

Procedure:
Compound 7 was dissolved in isopropanol (45 ml) and a solution of 3,4-dimethoxyphenethylamine (4.5 g., 0.025 ml.) was added dropwise. After the addition the solution was heated with stirring at 70° C. After 18 hours, the solution was concentrated to dryness. The residue was chromatographed on silica gel and the product eluted with CHCl3 saturated with NH3. The product was crystallized from HCl/EtOH and recrystallized from isopropanol to yield 2.7 g. of 8, mp 192°-194° C.; 'H NMR (DMSO-6) 3.05 (6H, m), 3.7 (6H, d), 3.85 (3H, s), 4.3 (3H, m), 6.8 (3H, m), 7.2 (2H, d), 7.8 (4H, m).