Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([Li])CCC.[C:6]1([CH:12]([CH3:28])[CH2:13][C:14]2([CH2:19][CH:20]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH3:21])[CH:18]=[CH:17][CH:16]=[CH:15]2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.S(C1C=CC(C)=CC=1)(O[CH2:33][CH2:34][N:35]([CH3:37])[CH3:36])(=O)=O.O>CCCCCC.O1CCCC1.O1CCCC1.CCCCCC>[CH3:36][N:35]([CH2:34][CH2:33][C:15]1[C:14]([CH2:19][CH:20]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH3:21])([CH2:13][CH:12]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH3:28])[CH:18]=[CH:17][CH:16]=1)[CH3:37]
Reactant: CC(CC1(CC(C)c2ccccc2)C=CC=C1)c1ccccc1
Reactant: Cc1ccc(S(=O)(=O)OCCN(C)C)cc1
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CC(CC1(CC(C)c2ccccc2)C=CC=C1CCN(C)C)c1ccccc1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
12.5 mL of a 1.6 molar solution of n-butyllithium in hexane was added dropwise to a cooled (0° C.) solution of di-(2-phenyl-propyl)-cyclopentadiene (6.05 g; 20.0 mmol) in dry tetrahydrofuran (100 ml) under a nitrogen atmosphere in a 250 mL three-necked round-bottomed flask provided with a magnetic stirrer and a dropping funnel. After 24 hours of stirring at room temperature, a solution of 2-dimethylaminoethyl tosylate (20.0 mmol) prepared in situ in tetrahydrofuran/hexane was added. After 18 hours of stirring, the conversion was found to be 90%, and water (100 ml) was carefully added dropwise to the reaction mixture and the tetrahydrofuran was then distilled off. The crude product was extracted with ether, and the combined organic phase was then dried with sodium sulphate, and boiled down. The residue was purified on a silica gel column, which resulted in 5.98 grams (80%) of (dimethyl-aminoethyl)di(2-phenyl-propyl)cyclopentadiene.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:26])[CH2:5][C:6]1[CH:7]=[N:8][CH:9]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:13]=2[CH2:22][NH:23][CH2:24][CH3:25])[CH:11]=1)[CH3:2].[CH2:27]([O:29][CH2:30][C:31](O)=[O:32])[CH3:28]>>[CH2:1]([O:3][C:4](=[O:26])[CH2:5][C:6]1[CH:7]=[N:8][CH:9]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:19])([F:21])[F:20])=[CH:14][C:13]=2[CH2:22][N:23]([C:31](=[O:32])[CH2:30][O:29][CH2:27][CH3:28])[CH2:24][CH3:25])[CH:11]=1)[CH3:2]
Reactant: CCOCC(=O)O
Reactant: CCNCc1cc(C(F)(F)F)ccc1-c1cncc(CC(=O)OCC)c1
Product: CCOCC(=O)N(CC)Cc1cc(C(F)(F)F)ccc1-c1cncc(CC(=O)OCC)c1

Procedure:
[5-(2-ethylaminomethyl-4-trifluoromethyl-phenyl)-pyridin-3-yl]-acetic acid ethyl ester and ethoxyacetic acid were reacted as described in Example 8, Step 6 to provide [5-(2-{[N-(2-ethoxy-acetyl)-N-ethyl-amino]-methyl}-4-trifluoromethyl-phenyl)-pyridin-3-yl]-acetic acid ethyl ester. The ester was hydrolyzed to the acid as described in Example 30, Step 2.
Reaction SMILES: [N+:1]([C:4]1[S:5][CH:6]=[CH:7][CH:8]=1)([O-:3])=[O:2].[C:9]1([NH:15]SC2C=CC=CC=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.Cl>CN(C)C=O>[C:9]1([NH:15][C:6]2[S:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:8][CH:7]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[C:9]1([NH:15][C:8]2[CH:7]=[CH:6][S:5][C:4]=2[N+:1]([O-:3])=[O:2])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: c1ccc(NSc2ccccc2)cc1
Reactant: O=[N+]([O-])c1cccs1
Agent: Cl
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1ccc(Nc2ccccc2)s1
Product: O=[N+]([O-])c1sccc1Nc1ccccc1
Reaction time: 0.25 h
Yield: 15 %
Yield: 42 %

Procedure:
2.9 g of 2-nitrothiophene and 4 g of N-phenylbenzenesulphenamide, dissolved in 10 ml of dimethylformamide, are added dropwise to a stirred solution of 6 g of potassium tert.-butylate in 60 ml of dimethylformamide, while the temperature is kept at about -20° C. The mixture is stirred for a further 15 minutes; then an excess of dilute hydrochloric acid is added to the mixture, after which it is treated in the same way as described in Example 1. The crude product is separated by column chromatography; N-phenyl-5-nitro-2-thienylamine (melting point 186° C., yield 1.8 g, 42%) and N-phenyl-2-nitro-3-thienylamine (melting point 105° C., yield 0.7 g, 15%) are obtained.
Reaction SMILES: [CH2:1]([N:8]1[CH:12]=[C:11]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][OH:19])[N:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.I([O-])(=O)(=O)=[O:21].[Na+].C(#N)C>O.C(OCC)(=O)C.[Ru](Cl)(Cl)Cl>[CH2:1]([N:8]1[CH:12]=[C:11]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]([OH:21])=[O:19])[N:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: OCCCCCCc1cn(Cc2ccccc2)nn1
Agent: Cl[Ru](Cl)Cl
Agent: [Na+]
Solvent: O
Solvent: CC#N
Solvent: CCOC(C)=O
Product: O=C(O)CCCCCc1cn(Cc2ccccc2)nn1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
6-(1-Benzyl-1H-1,2,3-triazol-4-yl)hexan-1-ol (100 mg, 0.386 mmol), sodium periodate (330 mg, 1.542 mmol), and ruthenium trichloride (1.6 mg, 7.7 μmol) were taken up in water (640 μl), ethyl acetate (320 μl) and acetonitrile (320 μl) to give a brown suspension. The reaction was stirred overnight at room temperature under nitrogen. The mixture was diluted with ethyl acetate and water and the black precipitate formed was removed by filtration. The organics were dried with MgSO4, filtered and concentrated under reduced pressure to give the crude title product.
Reaction SMILES: [CH3:1][C:2]([CH3:19])([CH3:18])[CH2:3][O:4][C:5]1[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][C:6]=1[C:7]([OH:9])=O.Cl.[CH3:21][S:22]([C:25]1[S:29][C:28]([N:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)=[N:27][CH:26]=1)(=[O:24])=[O:23]>>[CH3:18][C:2]([CH3:1])([CH3:19])[CH2:3][O:4][C:5]1[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][C:6]=1[C:7]([N:33]1[CH2:34][CH2:35][N:30]([C:28]2[S:29][C:25]([S:22]([CH3:21])(=[O:24])=[O:23])=[CH:26][N:27]=2)[CH2:31][CH2:32]1)=[O:9]
Reactant: CS(=O)(=O)c1cnc(N2CCNCC2)s1
Reactant: CC(C)(C)COc1ccc(S(C)(=O)=O)cc1C(=O)O
Agent: Cl
Product: CC(C)(C)COc1ccc(S(C)(=O)=O)cc1C(=O)N1CCN(c2ncc(S(C)(=O)=O)s2)CC1
Yield: 36 %

Procedure:
Prepared in analogy to example 1 (b) from 2-(2,2-dimethyl-propoxy)-5-methanesulfonyl-benzoic acid (Example A11) and 1-(5-methanesulfonyl-thiazol-2-yl)-piperazine hydrochloride (Example 21(c)). The crude material was purified by chromatography (SiO2, ethyl acetate/heptane) followed by trituration in ether to yield the title compound as a white crystalline solid (yield 36%). MS (m/e): 516.2 (M+H+, 100%).
Reaction SMILES: OC(COCCCCCCCC)CNC(C)(C)CC1C=CC(OC)=CC=1.[ClH:27].[OH:28][CH:29]([CH2:44][O:45][C:46]1[CH:51]=[CH:50][C:49]([Cl:52])=[CH:48][CH:47]=1)[CH2:30][NH:31][C:32]([CH3:43])([CH3:42])[CH2:33][C:34]1[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=1.Cl.OC(COC1C=CC(C(C)(C)C)=CC=1)CNC(C)(C)CC1C=CC(OC)=CC=1>>[ClH:52].[OH:28][CH:29]([CH2:44][O:45][C:46]1[CH:47]=[CH:48][C:49]([Cl:52])=[CH:50][C:51]=1[Cl:27])[CH2:30][NH:31][C:32]([CH3:43])([CH3:42])[CH2:33][C:34]1[CH:35]=[CH:36][C:37]([O:40][CH3:41])=[CH:38][CH:39]=1
Reactant: COc1ccc(CC(C)(C)NCC(O)COc2ccc(Cl)cc2)cc1
Agent: CCCCCCCCOCC(O)CNC(C)(C)Cc1ccc(OC)cc1
Agent: COc1ccc(CC(C)(C)NCC(O)COc2ccc(C(C)(C)C)cc2)cc1
Agent: Cl
Product: COc1ccc(CC(C)(C)NCC(O)COc2ccc(Cl)cc2Cl)cc1

Procedure:
GC/EI-MS, m/z (rel. int.) 382 (M-15,1), 280 (11), 279 (9), 278 (65), 277 (5), 276 (100), 163 (10), 161 (6), 132 (5).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@@H:9]([CH2:13][CH2:14][CH3:15])[CH2:10][CH2:11][OH:12])[C:5]([CH2:16][C:17]2[CH:35]=[CH:34][C:20]([CH2:21][N:22]3[CH2:26][CH2:25][CH2:24][C@@H:23]3[C:27]([O:29]C(C)(C)C)=[O:28])=[CH:19][C:18]=2[O:36][CH3:37])=[C:4]([CH3:38])[N:3]=1.FC(F)(F)C(O)=O.CO>C(Cl)(Cl)Cl>[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@@H:9]([CH2:13][CH2:14][CH3:15])[CH2:10][CH2:11][OH:12])[C:5]([CH2:16][C:17]2[CH:35]=[CH:34][C:20]([CH2:21][N:22]3[CH2:26][CH2:25][CH2:24][C@@H:23]3[C:27]([OH:29])=[O:28])=[CH:19][C:18]=2[O:36][CH3:37])=[C:4]([CH3:38])[N:3]=1
Reactant: CCC[C@@H](CCO)Nc1nc(N)nc(C)c1Cc1ccc(CN2CCC[C@@H]2C(=O)OC(C)(C)C)cc1OC
Solvent: ClC(Cl)Cl
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Product: CCC[C@@H](CCO)Nc1nc(N)nc(C)c1Cc1ccc(CN2CCC[C@@H]2C(=O)O)cc1OC
Temperature: 25 °C
Reaction time: 12 h
Yield: 79.9 %

Procedure:
To a solution of the product of step (ii) (70 mg) in chloroform (1.5 mL) was added trifluoroacetic acid (1.5 mL) and the mixture was stirred at RT. After 12 h, methanol (10 mL) was stirred at room temperature. After 12 h, the mixture was concentrated under reduced pressure. 10% aqueous potassium dicarbonate was added and the resulting mixture was extracted with chloroform/EtOH (3/1). The combined organic layer was dried and concentrated under reduced pressure to afford the sub-title compound (50 mg) as a white solid; 1H NMR (methanol-d4); 7.23 (1H, d), 7.02-6.97 (2H, m), 4.47 (1H, m), 4.34 (2H, s), 3.97 (3H, s), 3.85-3.80 (3H, m), 3.64 (1H, m), 3.45-3.41 (2H, m), 2.44 (1H, m), 2.28 (3H, s), 2.11 (2H, m), 1.96 (1H, m), 1.74-1.20 (7H, m), 0.87 (3H, t); LC-MS: m/z 472.
Reaction SMILES: [C:1]([O:5][C:6](=[O:29])[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14](=[O:28])[C:15]2[CH:20]=[C:19]([N+:21]([O-])=O)[C:18]([NH:24][CH3:25])=[C:17]([O:26][CH3:27])[CH:16]=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH2:30]([N:32]1[C:36]2=[N:37][CH:38]=[CH:39][CH:40]=[C:35]2[CH:34]=[C:33]1[CH:41]=O)[CH3:31].S(S([O-])=O)([O-])=O.[Na+].[Na+]>C(O)C.O.C(Cl)Cl>[C:1]([O:5][C:6](=[O:29])[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]([C:15]2[CH:16]=[C:17]([O:26][CH3:27])[C:18]3[N:24]([CH3:25])[C:41]([C:33]4[N:32]([CH2:30][CH3:31])[C:36]5=[N:37][CH:38]=[CH:39][CH:40]=[C:35]5[CH:34]=4)=[N:21][C:19]=3[CH:20]=2)=[O:28])[CH2:9]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CNc1c(OC)cc(C(=O)N2CCC[C@@H](NC(=O)OC(C)(C)C)C2)cc1[N+](=O)[O-]
Reactant: CCn1c(C=O)cc2cccnc21
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: CCO
Solvent: ClCCl
Solvent: O
Product: CCn1c(-c2nc3cc(C(=O)N4CCC[C@@H](NC(=O)OC(C)(C)C)C4)cc(OC)c3n2C)cc2cccnc21
Temperature: 100 °C
Yield: 75 %

Procedure:
To a solution of (R)-tert-butyl(1-(3-methoxy-4-(methylamino)-5-nitrobenzoyl)piperidin-3-yl)carbamate (4.5 g, 11.02 mmol) and 1-ethyl-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde (2.015 g, 11.57 mmol) in ethanol (100 mL) was added portionwise a solution of sodium dithionite (4.25 g, 20.75 mmol) in water (50 mL). The mixture was flushed with nitrogen then heated at 100° C. overnight (16 hours). The reaction mixture was concentrated under vacuum then diluted with DCM (150 ml) and water (150 ml). The organic layer was collected and the aqueous layer washed with DCM (3×100 ml). Organic layers were combined and back washed with water (3×150 ml), collected, dried with Na2SO4, filtered through a hydrophobic frit and concentrated under vacuum to yield 5.5 g of crude product as white solid. The crude product was dissolved in a minimum volume of DCM and purified using Biotage SP4 on a SNAP 100 g silica cartridge. The column was eluted with a gradient of 70-100% ethyl acetate in DCM for 10CV. Appropriate fractions were collected and concentrated in vacuo to afford the title compound as a white solid (4.40 g).
Reaction SMILES: [C:1](Cl)(=[O:5])[C:2]([CH3:4])=[CH2:3].[C:7]1([NH:13][S:14]([C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(N(CC)CC)C>C(Cl)Cl>[C:7]1([NH:13][S:14]([C:17]2[CH:18]=[CH:19][C:20]([O:23][C:1](=[O:5])[C:2]([CH3:4])=[CH2:3])=[CH:21][CH:22]=2)(=[O:15])=[O:16])[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: O=S(=O)(Nc1ccccc1)c1ccc(O)cc1
Reactant: C=C(C)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=C(C)C(=O)Oc1ccc(S(=O)(=O)Nc2ccccc2)cc1
Reaction time: 2 h

Procedure:
A solution of 3.31 g (0.03169 mol) of methacryloyl chloride in 60 ml of methylene chloride was added to a solution of 7.9 (0.03169 mol) of N-phenyl-4-hydroxybenzenesulfonamide, 7.06 g (0.0697 mol) of triethylamine and 60 ml of methylene chloride at -5° C. over a period of 15 minutes. The reaction mixture was stirred at reduced temperature for another 2 hours, after which the solution was washed once with 2 percent hydrochloric acid and twice with water. The solution was dried over sodium sulfate, and concentrated in vacuo with warm bath-heating. The resultant oil crystallized on cooling. This solid was recrystallized from ethanol:water (3:2), collected and dried in vacuo. The yield of N-phenyl-4-methacryloyloxybenzenesulfonamide was 7.05 g; m.p.=101° to 102° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:13]=1[O:14][CH3:15])[CH:6]=[CH:7][C:8]([OH:10])=O.P(Cl)(OCC)(OCC)=O.C(N(CC)CC)C.[CH3:32][N:33]([CH3:44])[CH2:34][CH2:35][NH:36][C@H:37]1[CH2:42][CH2:41][C@H:40]([CH3:43])[CH2:39][CH2:38]1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH3:32][N:33]([CH3:44])[CH2:34][CH2:35][N:36]([C@H:37]1[CH2:38][CH2:39][C@H:40]([CH3:43])[CH2:41][CH2:42]1)[C:8](=[O:10])[CH:7]=[CH:6][C:5]1[CH:11]=[CH:12][C:13]([O:14][CH3:15])=[C:3]([O:2][CH3:1])[CH:4]=1
Reactant: COc1ccc(C=CC(=O)O)cc1OC
Reactant: CN(C)CCN[C@H]1CC[C@H](C)CC1
Agent: CCOP(=O)(Cl)OCC
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccc(C=CC(=O)N(CCN(C)C)[C@H]2CC[C@H](C)CC2)cc1OC

Procedure:
Using 2.7 g of 3,4-dimethoxycinnamic acid, 2.8 ml of diethyl chlorophosphate, 2.7 ml of triethylamine, 100 ml of methylene chloride, 3.0 ml of N-(2-dimethylaminoethyl)-trans-4-methylcyclohexylamine (Example 78), and 0.5 g of 4-dimethylaminopyridine, a reaction similar to that conducted in Example 81 was carried out. As a result, 1.53 g of N-(2-dimethylaminoethyl)-N-(trans-4-methylcyclohexyl)-3,4-dimethoxycinnamamide (a compound of the present invention) was obtained as white crystal, which had the following physiochemical properties:
Reaction SMILES: [CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][CH2:5][OH:6].[C:8]([C:12]1[CH:13]=[C:14]([CH:18]=[C:19]([C:22]([CH3:25])([CH3:24])[CH3:23])[C:20]=1[OH:21])[C:15](Cl)=[O:16])([CH3:11])([CH3:10])[CH3:9].[OH-].[Na+]>C(Cl)Cl.O>[C:22]([C:19]1[CH:18]=[C:14]([CH:13]=[C:12]([C:8]([CH3:11])([CH3:10])[CH3:9])[C:20]=1[OH:21])[C:15]([O:6][CH2:5][CH2:4][CH2:3][N:2]([CH3:7])[CH3:1])=[O:16])([CH3:25])([CH3:24])[CH3:23]
Reactant: CN(C)CCCO
Reactant: CC(C)(C)c1cc(C(=O)Cl)cc(C(C)(C)C)c1O
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Product: CN(C)CCCOC(=O)c1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 68.8 %

Procedure:
A solution of 41.3 g (400 mmol) of 3-dimethylaminopropanol in 200 ml of methylene chloride was added to a solution of 107.3 g (400 mmol) of 3,5-di-tert-butyl-4-hydroxybenzoyl chloride prepared as described in Example 1 in 400 ml of methylene chloride over a period of seven minutes. The reaction was exothermic. The reaction mixture was stirred for 90 minutes at room temperature and then washed with a solution of 16.0 g (400 mmol) of NaOH in 600 ml of water and then with water. The solution was dried over magnesium sulfate and concentrated to a residue on a rotary evaporator. The residue was then heated to reflux in 800 ml of heptane and filtered through supercel. The filtrate was cooled and the white solid was collected, washed with heptane and dried to give 92.3 g (68.8% of theory) of 3-dimethylaminopropyl 3,5-di-tert-butyl-4-hydroxybenzoate.
Reaction SMILES: [C:1]([NH:5][C:6]([C:8]1[CH:13]=[N:12][CH:11]=[CH:10][N:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl-]>CO>[C:1]([NH:5][C:6]([C@@H:8]1[CH2:13][NH:12][CH2:11][CH2:10][NH:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)NC(=O)c1cnccn1
Agent: [Cl-]
Solvent: CO
Product: CC(C)(C)NC(=O)[C@@H]1CNCCN1
Reaction time: 20 h

Procedure:
0.5 g (2.7 mmol) of pyrazinecarboxylic acid tert-butylamide (prepared according to Example 3), 26.9 mg (58 μmol) of bicyclo[2.2.1]hepta-2,5-dienerhodium(I) chloride dimer and 72 mg (121 μmol) of 1-[1 (R)-(dicyclohexylphosphino)ethyl]-2(S)-(diphenylphosphino)ferrocene were placed in an autoclave under argon. After the addition of 10 ml of degassed methanol, the autoclave was flushed three times with argon and twice with hydrogen. A hydrogen pressure of 50 bar was then applied. Hydrogenation was carried out at 70° C. for 20 hours. The autoclave was depressurized and flushed with nitrogen. The solvent was completely distilled off. The yield of the title compound was 0.50 g. A conversion of 80 percent was determined by NMR. The enantiomeric excess (ee) was 77.6 percent according to GC analysis.
Reaction SMILES: [Cl:1][C:2]1[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH:11][S:12]([C:15]1[CH:27]=[CH:26][C:18]([C:19]([NH:21][CH2:22][C:23]([OH:25])=O)=[O:20])=[CH:17][CH:16]=1)(=[O:14])=[O:13].C(OC([N:40]1[CH2:46][CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1)=O)(C)(C)C>>[ClH:1].[N:40]1([C:23](=[O:25])[CH2:22][NH:21][C:19](=[O:20])[C:18]2[CH:17]=[CH:16][C:15]([S:12](=[O:14])(=[O:13])[NH:11][C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=3[O:4][C:3]3[CH:28]=[CH:29][C:30]([Cl:32])=[CH:31][C:2]=3[Cl:1])=[CH:27][CH:26]=2)[CH2:46][CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1
Reactant: O=C(O)CNC(=O)c1ccc(S(=O)(=O)Nc2ccccc2Oc2ccc(Cl)cc2Cl)cc1
Reactant: CC(C)(C)OC(=O)N1CCCNCC1
Product: Cl
Product: O=C(NCC(=O)N1CCCNCC1)c1ccc(S(=O)(=O)Nc2ccccc2Oc2ccc(Cl)cc2Cl)cc1

Procedure:
The title compound was prepared from {4-[2-(2,4-dichloro-phenoxy)-phenylsulfamoyl]-benzoylamino}-acetic acid (Example 1.1/e) and [1,4]diazepane-1-carboxylic acid tert-butyl ester (Fluka) according to the method described in Example 11.1. MS (EI) 578.2 (MH+).
Reaction SMILES: [NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:31][CH2:32][CH2:33][CH3:34])[N:14]([CH2:15][CH2:16][CH2:17][NH:18][CH2:19][C:20]3[CH:25]=[CH:24][C:23]([CH2:26][C:27]([O:29][CH3:30])=[O:28])=[CH:22][CH:21]=3)[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.C(Cl)Cl.Cl.[CH3:39][N:40]([CH3:45])[CH2:41][C:42](Cl)=[O:43].CCN(CC)CC>CN(C=O)C>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:31][CH2:32][CH2:33][CH3:34])[N:14]([CH2:15][CH2:16][CH2:17][N:18]([CH2:19][C:20]3[CH:21]=[CH:22][C:23]([CH2:26][C:27]([O:29][CH3:30])=[O:28])=[CH:24][CH:25]=3)[C:42](=[O:43])[CH2:41][N:40]([CH3:45])[CH3:39])[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1
Reactant: CCCCc1nc2c(N)nc3ccccc3c2n1CCCNCc1ccc(CC(=O)OC)cc1
Reactant: CN(C)CC(=O)Cl
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CCCCc1nc2c(N)nc3ccccc3c2n1CCCN(Cc1ccc(CC(=O)OC)cc1)C(=O)CN(C)C
Reaction time: 72 h

Procedure:
The product from example 1 (15 mg) was dissolved in a mixture of DMF:DCM, 1:1 (5 mL) and N,N-dimethylglycyl chloride hydrochloride salt (8 mg) and Et3N (0.01 mL) were added. The reaction mixture was stirred for 72 h. More N,N-dimethylglycyl chloride hydrochloride salt (0.050 g) and Et3N (0.06 mL) were added, the mixture was stirred for a further 16 h. The product was purified via RPHPLC.
Reaction SMILES: [CH2:1]([C:3]1([CH3:14])[CH:8]([CH3:9])[C:7](=O)[CH2:6][C:5]([CH2:12][CH3:13])([CH3:11])[NH:4]1)[CH3:2].[NH3:15].[H][H]>CO.[Ni]>[CH2:1]([C:3]1([CH3:14])[CH:8]([CH3:9])[CH:7]([NH2:15])[CH2:6][C:5]([CH2:12][CH3:13])([CH3:11])[NH:4]1)[CH3:2]
Reactant: CCC1(C)CC(=O)C(C)C(C)(CC)N1
Reactant: N
Reactant: [H][H]
Agent: [Ni]
Solvent: CO
Product: CCC1(C)CC(N)C(C)C(C)(CC)N1
Reaction time: 24 h

Procedure:
197.3 g of 2,6-diethyl-2,3,6-trimethylpiperidin-4-one are dissolved in 1.5 liters of methanol which is saturated with ammonia. This solution is hydrogenated in a 3 liter-autoclave at a hydrogen pressure of 100 bar in the presence of 30 g of Raney nickel. After 24 hours, the solution is filtered and the solvent evaporated. The residue is distilled in vacuo yielding 162 g 2,6-diethyl-2,3,6-trimethyl-4-aminopiperidine (compound no. 1) distilling at 133°-35° C. at 23 mm Hg. Using a methanolic solution of methylamine, n-butylamine, n-hexylamine, n-dodecylamine, benzylamine and 2-amino-ethanol, respectively, instead of the ammonia solution while otherwise following the procedure described above, there are obtained:
Reaction SMILES: [CH2:1]([C:5]1[O:6][C:7]2[CH:13]=[CH:12][C:11]([NH:14][S:15]([CH3:18])(=[O:17])=[O:16])=[CH:10][C:8]=2[CH:9]=1)[CH2:2][CH2:3][CH3:4].[CH2:19]([N:23]([CH2:36][CH2:37][CH2:38][CH3:39])[CH2:24][CH2:25][CH2:26][O:27][C:28]1[CH:35]=[CH:34][C:31]([CH:32]=[O:33])=[CH:30][CH:29]=1)[CH2:20][CH2:21][CH3:22].O>FC(F)(F)C(O)=O>[CH2:1]([C:5]1[O:6][C:7]2[CH:13]=[CH:12][C:11]([NH:14][S:15]([CH3:18])(=[O:16])=[O:17])=[CH:10][C:8]=2[C:9]=1[CH:32]([C:31]1[CH:30]=[CH:29][C:28]([O:27][CH2:26][CH2:25][CH2:24][N:23]([CH2:36][CH2:37][CH2:38][CH3:39])[CH2:19][CH2:20][CH2:21][CH3:22])=[CH:35][CH:34]=1)[OH:33])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCN(CCCC)CCCOc1ccc(C=O)cc1
Reactant: CCCCc1cc2cc(NS(C)(=O)=O)ccc2o1
Solvent: O=C(O)C(F)(F)F
Solvent: O
Product: CCCCc1oc2ccc(NS(C)(=O)=O)cc2c1C(O)c1ccc(OCCCN(CCCC)CCCC)cc1
Temperature: 40 °C
Reaction time: 10 h
Yield: 32.9 %

Procedure:
5.34 g of N-(2-butyl-1-benzofuran-5-yl)methanesulfonamide (II) (0.02 mol, 1 eq) is dissolved in 40 mL of trifluoroacetic acid and 8.7 g of 4-(3-dibutylamino-propoxy)-benzaldehyde (V) (0.03 mol, 1.5 eq) is added to the solution. The reaction mixture is heated to 40° C. and stirred for 10 hours at this temperature. The mixture is cooled to room temperature and 100 mL of water is added. After 15 min of stirring, the product is extracted with 2×50 mL of dichloromethane. The organic phase is concentrated and the crude product is purified by column chromatography (spheric silica; eluent:toluene:MTBE:methanol=50:40:10) to obtain 3.68 g of compound (VI) (33%).
Reaction SMILES: [N:1](OCCCC)=[O:2].[CH3:8][C:9]1[C:14]([CH3:15])=[C:13]([S:16]([CH3:19])(=[O:18])=[O:17])[CH:12]=[CH:11][C:10]=1[Cl:20].CC(C)([O-])C.[K+].O>CN(C)C=O.C(O)(=O)C>[Cl:20][C:10]1[C:9]([CH3:8])=[C:14]([C:13]([S:16]([CH3:19])(=[O:17])=[O:18])=[CH:12][CH:11]=1)[CH:15]=[N:1][OH:2]
Reactant: CCCCON=O
Reactant: Cc1c(Cl)ccc(S(C)(=O)=O)c1C
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(=O)O
Solvent: O
Solvent: CN(C)C=O
Product: Cc1c(Cl)ccc(S(C)(=O)=O)c1C=NO
Temperature: 0 °C

Procedure:
A solution of 12.7 g (119 mmol) of n-butyl nitrite (97%) and 20 g (92 mmol) of 2,3-dimethyl-4-methylsulfonylchlorobenzene in 100 ml of dimethylformamide is cooled to from −55 to −60° C., and a solution of 16.8 g (147 mmol) of potassium tert-butoxide in 70 ml of dimethylformamide is added dropwise at this temperature, over a period of 30 minutes. The reaction is monitored by HPLC. For work-up, initially 50 ml of water are added, and the mixture is then adjusted to pH 5-6 using about 30 ml of glacial acetic acid. The mixture is then poured onto 0.7 kg of ice-water and the aqueous phase is extracted with methylene chloride. The organic phase is washed with sodium bicarbonate solution, dried over magnesium sulfate and concentrated. This gives 18.4 g of a light-beige crude product which is purified by recrystallization from about 30 ml of toluene.