Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[N:3]([CH3:26])[C:4](=[O:25])[C:5]([C:17]2[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=2)[CH:20]=O)([C:7]2[CH:12]=[CH:11][C:10]([O:13][CH:14]([F:16])[F:15])=[CH:9][CH:8]=2)[N:6]=1.[CH3:27][NH:28][CH3:29].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>C1COCC1.C(O)(=O)C.ClCCCl>[NH2:1][C:2]1[N:3]([CH3:26])[C:4](=[O:25])[C:5]([C:7]2[CH:8]=[CH:9][C:10]([O:13][CH:14]([F:15])[F:16])=[CH:11][CH:12]=2)([C:17]2[CH:24]=[CH:23][CH:22]=[C:19]([CH2:20][N:28]([CH3:29])[CH3:27])[CH:18]=2)[N:6]=1
Reactant: CNC
Reactant: CN1C(=O)C(c2ccc(OC(F)F)cc2)(c2cccc(C=O)c2)N=C1N
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: C1CCOC1
Solvent: ClCCCl
Product: CN(C)Cc1cccc(C2(c3ccc(OC(F)F)cc3)N=C(N)N(C)C2=O)c1
Yield: 43 %

Procedure:
A small vial (10 ml) was charged with 3-[2-Amino-4-(4-difluoromethoxy-phenyl)-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl]-benzaldehyde (69 mg, 192 μmol) and 1,2-dichloroethane (DCE, 1 ml). To this was added a 2M solution of dimethylamine in THF (1 ml). After stirring overnight at room temperature sodium triacetoxyborohydride (58 mg, 270 μmol) was added followed by 1 drop of glacial acetic acid (˜12 mg), then after another 20 hours 1N sodium hydroxide (1 ml) was added and the mixture extracted with diethyl ether. The ethereal layer was concentrated by rotary evaporation, diluted with methanol and re-concentrated (repeated three times). Finally the oily residue was redissolved in diethylether/hexanes and concentrated, twice then placed under vacuum to give a white foam 32 mg (43%) 1H NMR (400 MHz, DMSO-d6) δ ppm 2.04 (s, 6H) 2.93 (s, 3H) 3.26 (s, 2H, partially obscured by solvent) 6.62 (br. s., 4H) 7.04-7.09 (m, 3H) 7.12 (t, J=74.18 Hz 1H) 7.18 (t, J=7.6 Hz, 1H) 7.27 (d, J=7.9 Hz, 1H) 7.35 (s, 1H) 7.40 (d, J=8.8 Hz, 2H); MS (APPI) m/z 389 [M+H]+
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.CS(O[CH2:14][CH:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)(=O)=O.C1(O)C=CC=CC=1.O[C@@H](C1C=CC=C(O)C=1)CCNC(=O)OC(C)(C)C>>[Br:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[O:8][CH2:14][CH:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1
Reactant: CS(=O)(=O)OCC1CCOCC1
Reactant: Oc1cccc(Br)c1
Agent: CC(C)(C)OC(=O)NCC[C@@H](O)c1cccc(O)c1
Solvent: Oc1ccccc1
Product: Brc1cccc(OCC2CCOCC2)c1

Procedure:
Alkylation of 3-bromophenol with (tetrahydro-2H-pyran-4-yl)methyl methanesulfonate following the method used in preparation of phenol (7, Intermediate I) gave 4-((3-bromophenoxy)methyl)tetrahydro-2H-pyran as a white solid which was used in the next step without additional purification. Yield (quant.).
Reaction SMILES: [H-].[Na+].[CH:3]1([SH:8])[CH2:7][CH2:6][CH2:5][CH2:4]1.Br[CH2:10][CH2:11][CH2:12][OH:13].O>CN(C=O)C.C(OCC)C>[CH:3]1([S:8][CH2:10][CH2:11][CH2:12][OH:13])[CH2:7][CH2:6][CH2:5][CH2:4]1
Reactant: SC1CCCC1
Reactant: OCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CCOCC
Solvent: CN(C)C=O
Solvent: O
Product: OCCCSC1CCCC1
Temperature: 80 °C

Procedure:
To a suspension of sodium hydride (commercially available, for example, from Aldrich) (60% dispersion in mineral oil; 800 mg, 20 mmol) in dry DMF (30 ml) was carefully added cyclopentyl mercaptan (commercially available, for example, from Aldrich and/or Alfa Aesar) (2.14 ml, 20 mmol). The resultant suspension was stirred at room temperature, under nitrogen for 15 min before adding 3-bromopropanol (commercially available, for example, from Aldrich) (1.81 ml, 20 mmol). The mixture was then stirred under nitrogen and heated to 80° C. overnight. Water (20 ml) was cautiously added to the reaction mixture, followed by diethyl ether (50 ml). The aqueous solution was extracted with diethyl ether (2×50 ml). The combined organic solutions were washed with water (100 ml) and brine (100 ml) and concentrated in vacuo to leave a yellow oil, which was purified by flash chromatography on silica eluting with cyclohexane-EtOAc (3:1) increasing to (1:1). The solvents were removed in vacuo to afford the title compound (2.18 g). LCMS RT=2.61 min, ES+ve m/z 161 (M+H)+.
Reaction SMILES: C([N:5]1[C:12](=O)[N:11]2[C:7](=[N:8][C:9]3[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=32)[S:6]1)CCC.[C:18](C#N)(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>ClCCl>[O:25]=[C:18]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:12]1[N:11]2[C:7](=[N:8][C:9]3[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=32)[S:6][N:5]=1
Reactant: N#CC(=O)c1ccccc1
Reactant: CCCCn1sc2nc3ccccc3n2c1=O
Solvent: ClCCl
Product: O=C(c1ccccc1)c1nsc2nc3ccccc3n12
Temperature: 25 °C
Reaction time: 24 h
Yield: 95.5 %

Procedure:
A mixture of 2-butyl-1,2,4-thiadiazolo[4,5-a]benzimidazole-3(2H)-one (6.0 g, 24.3 mmole) and benzoyl cyanide (6.36 g, 48.5 mmole) in 80 mL of dichloromethane was stirred at room temperature for 24 h. The precipitate was filtered and washed with dichloromethane. The crude product was recrystallized from acetone to give 6.48 g (96%) of 3-(oxophenylmethyl)-1,2,4-thiadiazolo[4,5-a]benzimidazole as yellow crystals: mp 190-191° C.; 1H NMR (CDCl3) δ 8.35 (d, 3H), 7.82 (d, 1H), 7.73 (t, 1H), 7.59 (t, 2H), 7.50 (t, 1H), 7.36 (t, 1H) ppm; 13C NMR (CDCl3) δ180.86, 163.69, 150.82, 146.70, 134.79, 134.34, 131.22 (2C), 129.46 (2C), 128.74, 125.82, 122.27, 119.49, 115.23 ppm; IR (KBr) ν 1671 cm-1 ; HRMS calcd for C15H9N3OS: 279.0466, found: 279.0475. Anal. Calcd for C15H9N3OS: C, 64.50; H, 3.25; N, 15.04. Found: C, 63.93; H, 3.10; N, 14.53.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[Cl:10][C:11]1[CH:18]=[C:17](F)[CH:16]=[CH:15][C:12]=1[C:13]#[N:14].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[Cl:10][C:11]1[CH:18]=[C:17]([O:1][C:2]2[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=2)[CH:16]=[CH:15][C:12]=1[C:13]#[N:14]
Reactant: N#Cc1ccc(F)cc1Cl
Reactant: O=Cc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: N#Cc1ccc(Oc2ccc(C=O)cc2)cc1Cl
Temperature: 25 °C

Procedure:
4-Hydroxy benzaldehyde (1 equiv), 2-chloro-4-fluorobenzonitrile (1 equiv) and K2CO3 (2.5 equiv) in anhydrous DMF (0.2 M) were heated at 110° C. under nitrogen during 1 hour (the reaction can be monitored by tlc). After cooling down to room temperature, the reaction mixture was poured into water and extracted with ethyl acetate (3×50 mL). The combined organic layer was dried over Na2SO4, filtered and concentrated under vacuum (toluene was added to aid DMF evaporation). The crude mixture was purified by flash chromatography using hexanes/ethyl acetate (4:1) as eluent.
Reaction SMILES: C(OC([N:11]1[CH2:23][CH2:22][CH2:21][C@H:12]1[C:13]([N:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[O:14])=O)C1C=CC=CC=1.[H][H]>C(O)C.[C].[Pd]>[NH:11]1[CH2:23][CH2:22][CH2:21][C@H:12]1[C:13]([N:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[O:14]
Reactant: O=C([C@@H]1CCCN1C(=O)OCc1ccccc1)N1CCOCC1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: O=C([C@@H]1CCCN1)N1CCOCC1
Yield: 98.7 %

Procedure:
In 100 ml of ethanol was suspended 4.9 g of compound (83) and after adding thereto 250 mg of 10% palladium carbon, the mixture was stirred for 4 hours in a hydrogen stream. After filtering off 10% palladium-carbon, ethanol was distilled off under reduced pressure from the filtrate to provide 2.8 g of crude N-(L-prolyl)morpholine (84).
Reaction SMILES: [CH3:1][C:2]1[C:3]2[N:4]([C:8]([C:11]3[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=3)=[CH:9][CH:10]=2)[CH2:5][CH2:6][N:7]=1.[BH4-].[Na+].[C:23]([OH:30])(=[O:29])/[CH:24]=[CH:25]/[C:26]([OH:28])=[O:27]>CO.O.C(O)C>[C:23]([OH:30])(=[O:29])/[CH:24]=[CH:25]/[C:26]([OH:28])=[O:27].[CH3:1][CH:2]1[NH:7][CH2:6][CH2:5][N:4]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:18])[F:19])=[CH:13][CH:12]=3)=[CH:9][CH:10]=[C:3]12
Reactant: CC1=NCCn2c1ccc2-c1ccc(C(F)(F)F)cc1
Agent: O=C(O)/C=C/C(=O)O
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Solvent: CCO
Product: CC1NCCn2c(-c3ccc(C(F)(F)F)cc3)ccc21
Yield: 70 %

Procedure:
3,4-Dihydro-1-methyl-6-[4-(trifluoromethyl)-phenyl]pyrrolo[1,2-a]pyrazine (2.5 g) was dissolved in a mixture of 130 ml of methanol and 13 ml of water under argon. The solution was treated portionwise with 1.0 g of sodium borohydride while stirring and stirred at room temperature overnight. Thereafter, the methanol was removed in a vacuum, the residue was taken up in 100 ml of methylene chloride and washed with 80 ml of 10% ammonia solution. The phases were separated and the aqueous phase was extracted twice with 50 ml of methylene chloride each time. The organic phases were combined, dried with MgSO4 and freed from solvent. The crude product, 2.5 g of yellow-brown solid, was dissolved in a 20-fold amount of ethanol, treated with 1.1 equivalents of a saturated solution of fumaric acid in ethanol and concentrated to 40 ml. There were obtained 2.5 g (70%) of 1,2,3,4-tetrahydro-1-methyl-6-[4-(trifluoromethyl)phenyl]pyrrolo[1,2-a]pyrazine fumarate (1:1); m.pt.: 180°-183° C. (dec.).
Reaction SMILES: Cl.Cl.[NH:3]1[CH2:8][CH2:7][CH:6]([CH2:9][CH2:10][NH:11][C:12]([C:14]2[S:24][C:23]3[N:25]4[C:16](=[CH:17][N:18]=[C:19]4[CH:20]=[CH:21][CH:22]=3)[CH:15]=2)=[O:13])[CH2:5][CH2:4]1.C(N(CC)CC)C.[C:33]1([CH2:39][CH2:40][CH2:41]Br)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C(O)C>[C:33]1([CH2:39][CH2:40][CH2:41][N:3]2[CH2:8][CH2:7][CH:6]([CH2:9][CH2:10][NH:11][C:12]([C:14]3[S:24][C:23]4[N:25]5[C:16](=[CH:17][N:18]=[C:19]5[CH:20]=[CH:21][CH:22]=4)[CH:15]=3)=[O:13])[CH2:5][CH2:4]2)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1
Reactant: O=C(NCCC1CCNCC1)C1=Cc2cnc3cccc(n23)S1
Reactant: BrCCCc1ccccc1
Agent: Cl
Solvent: CCO
Solvent: CCN(CC)CC
Product: O=C(NCCC1CCN(CCCc2ccccc2)CC1)C1=Cc2cnc3cccc(n23)S1

Procedure:
To a solution of 0.60 g (1.49 mM) of N-[2-(4-piperidyl)ethyl]-5-thia-1,8b-diazaacenaphthylene-4-carboxamide dihydrochloride and 1.0 ml (7.17 mM) of triethylamine in ethanol (6 ml) was added 0.27 ml (1.78 mM) of 3-phenyl-1-bromopropane at room temperature and the mixture was refluxed under nitrogen for 24 hours. The solvent was then distilled off under reduced pressure and the residue was diluted with water and extracted with chloroform. The organic layer was washed with saturated aqueous solution of sodium chloride, dried over MgSO4, and purified by column chromatography (methanol/ethyl acetate 30-50-80%) to provide the title compound.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7]([Cl:16])=[N:8][C:9]2[C:14]([N:15]=1)=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:5])[CH3:2].[CH3:17][NH:18][C:19]([NH2:21])=[S:20]>CC(C)=O>[ClH:16].[CH2:1]([O:3][C:4]([C:6]1[C:7]([S:20][C:19](=[NH:21])[NH:18][CH3:17])=[N:8][C:9]2[C:14]([N:15]=1)=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1nc2ccccc2nc1Cl
Reactant: CNC(N)=S
Solvent: CC(C)=O
Product: CCOC(=O)c1nc2ccccc2nc1SC(=N)NC
Product: Cl

Procedure:
2-Chloro-3-quinoxalinecarboxylic acid ethyl ester (4.733 g., 0.02 mole) and 1.803 g. (0.02 mole) of monomethylthiourea were dissolved in 100 ml. of acetone and the solution as stirred at reflux for 11/2 hours, cooled, and filtered to give 5.62 g. of crude solid. Extraction of the crude solid with boiling acetonitrile left 3.14 g. of insoluble product, m.p. 180° (dec.).
Reaction SMILES: [CH3:1][NH:2][CH2:3][CH2:4][C:5]1[C:13]2[C:8](=CC=[CH:11][CH:12]=2)[NH:7][CH:6]=1.Cl.[Cl:15]CCCN1CCCCC1.Cl.ClCCC[N:30]1C[CH2:34][CH2:33][CH:32]([C:36]2[CH:41]=[CH:40][C:39](OC)=[CH:38][CH:37]=2)[CH2:31]1>>[ClH:15].[NH:30]1[C:37]2[C:36](=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:32]([CH2:33][CH2:34][N:2]([CH3:1])[CH2:3][CH2:4][CH2:5][CH:13]2[CH2:12][CH2:11][CH2:6][NH:7][CH2:8]2)=[CH:31]1
Reactant: CNCCc1c[nH]c2ccccc12
Reactant: COc1ccc(C2CCCN(CCCCl)C2)cc1
Reactant: ClCCCN1CCCCC1
Agent: Cl
Product: CN(CCCC1CCCNC1)CCc1c[nH]c2ccccc12

Procedure:
Using 3-(2-methylaminoethyl)indole (123 mg, 0.70 mmol) and 1-(3-chloropropyl)piperidine hydrochloride (198 mg, 1.0 mmol) instead of 4-(3-indolyl)piperidine and 1-(3-chloropropyl)-3-(4-methoxyphenyl)piperidine hydrochloride respectively, reaction and concentration were carried out in the same procedure as Example 2. The resulting crude product was purified by column chromatography on a silica gel (silica gel NH-DM 1020 produced by Fuji Silysia Chemical Ltd., eluent; hexane:ethyl acetate=1:1) to afford a free form (166 mg) of the title compound as a pale yellow viscous oil. After adding hydrochloric acid/methanol to a solution of the free form in methanol, the mixture was concentrated and was then reprecipitated with methanol/ether to afford the title compound (167 mg, yield: 64%) as a pale yellow crystalline powder.
Reaction SMILES: [NH2:1][C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C:7]([O:9][CH3:10])=[O:8].[C:11]([C:15]1[CH:20]=[CH:19][C:18]([S:21](Cl)(=[O:23])=[O:22])=[CH:17][CH:16]=1)([CH3:14])([CH3:13])[CH3:12]>N1C=CC=CC=1.ClCCl>[C:11]([C:15]1[CH:20]=[CH:19][C:18]([S:21]([NH:1][C:2]2[CH:6]=[CH:5][S:4][C:3]=2[C:7]([O:9][CH3:10])=[O:8])(=[O:23])=[O:22])=[CH:17][CH:16]=1)([CH3:14])([CH3:12])[CH3:13]
Reactant: COC(=O)c1sccc1N
Reactant: CC(C)(C)c1ccc(S(=O)(=O)Cl)cc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: COC(=O)c1sccc1NS(=O)(=O)c1ccc(C(C)(C)C)cc1
Temperature: 40 °C
Reaction time: 48 h
Yield: 66 %

Procedure:
To a solution of methyl 3-aminothiophene-2-carboxylate (0.55 g; 3.5 mmol) in pyridine (2 mL) and dichloromethane (2 mL) was added 4-tert-butylbenzenesulfonyl chloride (0.98 g; 4.2 mmol). The resulting mixture was warmed to 40° C. to aid in solubility, then stirred at room temperature for 48 hours. The reaction mixture was diluted with dichloromethane and washed with aqueous hydrochloric acid (2N). The aqueous layer was separated and extracted with dichloromethane. The organic layers were combined, dried over anhydrous sodium sulfate, decanted, and filtered through a and of silica. The silica was washed with dichloromethane. The eluant was combined with hexanes and allowed to stand. After 24 hours the resulting solid product was collected by filtration to give the desired product as a white solid (817 mg).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]#[C:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:8][C:9]=1[NH2:10])=[O:4].[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][C:27](=O)[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18].C1([SiH3])C=CC=CC=1>C1COCC1.C(Cl)Cl.C([Sn](Cl)(Cl)CCCC)CCC>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]#[C:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:8][C:9]=1[NH:10][CH:27]1[CH2:28][CH2:29][N:24]([C:22]([O:21][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:23])[CH2:25][CH2:26]1)=[O:4]
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: COC(=O)c1sc(C#CC(C)(C)C)cc1N
Agent: CCCC[Sn](Cl)(Cl)CCCC
Agent: [SiH3]c1ccccc1
Solvent: ClCCl
Solvent: C1CCOC1
Product: COC(=O)c1sc(C#CC(C)(C)C)cc1NC1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 204.8 %

Procedure:
To a solution of 5-(3,3-dimethyl-but-1-ynyl)-3-amino-thiophene-2-carboxylic acid methyl ester (1.512 g, 5.97 mmol) and N-tert-butoxycarbonyl-piperidin-4-one (1.189 g, 5.97 mmol) in 2 mL of dry THF is added dibutyltin dichloride (181 mg, 0.60 mmol), and the mixture is stirred for 10 min at room temperature under nitrogen. Then phenylsilane (810 μL, 6.57 mmol) is added, and the mixture is stirred for 24 h at room temperature. Additional 595 mg of N-tert-butoxycarbonyl-piperidin-4-one, 90 mg of dibutyltin dichloride and 405 μL of phenylsilane are added, and the mixture is stirred for another 24 h. Then the mixture is diluted with CH2Cl2, washed with brine, organic fraction is separated, dried over Na2SO4, and concentrated to give 5.142 g of crude 5-(3,3-dimethyl-but-1-ynyl)-3-(N-tert-butoxycarbonyl-piperidin-4-yl)amino-thiophene-2-carboxylic acid methyl ester.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][C:10]([O:12][CH3:13])=[O:11].[CH2:14](Br)[CH:15]=[CH2:16]>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]([CH2:16][CH:15]=[CH2:14])[C:10]([O:12][CH3:13])=[O:11]
Reactant: COC(=O)Cc1ccc(F)cc1Cl
Reactant: C=CCBr
Solvent: C1CCOC1
Product: C=CCC(C(=O)OC)c1ccc(F)cc1Cl
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a chilled (−78° C.) solution of lithium hexamethydisilylazide (27.1 mL, 1 M in THF, 27.1 mmol) in THF (30 mL) was added methyl 2-(2-chloro-4-fluorophenyl)acetate (5 g, 24.7 mmol) in THF (10 mL). After stirring for 0.5 hour, allyl bromide (2.4 mL, 27.1 mmol) was added in a single portion, the cooling bath removed and the reaction allowed to warm to room temperature (0.5 hour). The reaction was diluted with ethyl acetate, washed with water, brine, and the organic phase was dried with sodium sulfate and the solvent was evaporated in vacuo. The residue was purified by column chromatography on silica gel using n-heptane/ethyl acetate (v/v 1:0 to 9:1) as eluent. The title compound was obtained as a colourless liquid (6.0 g, 100%).
Reaction SMILES: [CH3:1][N:2]([CH3:29])[C:3]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:8][CH2:7][CH:6]([C:9]2[NH:10][C:11]3[C:16]([C:17]=2[CH:18](O)[CH2:19][CH2:20][CH3:21])=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH2:5][CH2:4]1.[Si]([Cl:34])(C)(C)C.C(OCC)(=[O:37])C>>[ClH:34].[CH3:29][N:2]([CH3:1])[C:3]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:8][CH2:7][CH:6]([C:9]2[NH:10][C:11]3[C:16]([C:17]=2[CH2:18][CH2:19][CH2:20][CH2:21][OH:37])=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH2:5][CH2:4]1
Reactant: CCOC(C)=O
Reactant: CCCC(O)c1c(C2CCC(c3ccccc3)(N(C)C)CC2)[nH]c2ccccc12
Reactant: C[Si](C)(C)Cl
Product: CN(C)C1(c2ccccc2)CCC(c2[nH]c3ccccc3c2CCCCO)CC1
Product: Cl
Reaction time: 1 h

Procedure:
4-[(2-(4-Dimethylamino-4-phenylcyclohexyl)-1H-indol-3-yl)butan-1-ol (less polar diastereomer) (170 mg, 0.43 mmol) was dissolved in ethyl acetate (50 ml). Me3SiCl (108 μl, 0.86 mmol) was then added dropwise at RT and the mixture was stirred for 1 h. A white precipitate precipitated out. The precipitate was filtered off with suction, washed with ethyl acetate (2×5 ml) and then dried. Example 173 (170 mg, m.p. 223-226° C., 91%) was obtained as a white solid.
Reaction SMILES: CO.C(=O)=O.[F:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]([CH3:29])[C:14]([N:16]2[CH:20]=[C:19]([C:21]3[CH:26]=[CH:25][C:24]([O:27]C)=[CH:23][CH:22]=3)[N:18]=[CH:17]2)=[O:15])=[CH:9][CH:8]=1.O>ClCCl>[F:6][C:7]1[CH:8]=[CH:9][C:10]([N:13]([CH3:29])[C:14]([N:16]2[CH:20]=[C:19]([C:21]3[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=3)[N:18]=[CH:17]2)=[O:15])=[CH:11][CH:12]=1
Reactant: COc1ccc(-c2cn(C(=O)N(C)c3ccc(F)cc3)cn2)cc1
Agent: O=C=O
Solvent: ClCCl
Solvent: CO
Solvent: O
Product: CN(C(=O)n1cnc(-c2ccc(O)cc2)c1)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To an methanol-dry ice cooled solution of N-(4-fluorophenyl)-4-(4-methoxyphenyl)-N-methyl-1H-imidazole-1-carboxamide (0.283 g, 0.870 mmol) in dichloromethane (8 ml) was added borontribromide (0.164 ml, 1.740 mmol). The dark reaction mixture was allowed to warm up to room temperature and stirred for 2 hours. TLC showed the reaction to be completed, then was poured into a mixture of ice and water and stirred for 30 min. There was no precipitation. The mixture was extracted with DCM:IPA (70:30), the organic phase was dried over MgSO4 and filtered. DCM was removed by vacuum and the product precipitated from IPA, filtered and dried under vacuum. (Yield: 210 mg, 78%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:56]=[CH:55][CH:54]=[CH:53][C:4]=1[CH2:5][O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH:18]2[O:30][CH2:31][CH2:32][O:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[CH2:40][CH2:41]OS(C2C=CC(C)=CC=2)(=O)=O)=[CH:13][CH:12]=1.[N-:57]=[N+:58]=[N-:59].[Na+]>CN(C)C=O.C(=O)([O-])O.[Na+]>[N:57]([CH2:41][CH2:40][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=1[O:33][CH2:32][CH2:31][O:30][CH:18]1[CH:17]([C:14]2[CH:13]=[CH:12][C:11]([O:10][CH2:9][CH2:8][CH2:7][O:6][CH2:5][C:4]3[CH:53]=[CH:54][CH:55]=[CH:56][C:3]=3[O:2][CH3:1])=[CH:16][CH:15]=2)[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:24])[CH2:19]1)=[N+:58]=[N-:59]
Reactant: COc1ccccc1COCCCOc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2OCCOc2ccccc2CCOS(=O)(=O)c2ccc(C)cc2)cc1
Reactant: [N-]=[N+]=[N-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccccc1COCCCOc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2OCCOc2ccccc2CCN=[N+]=[N-])cc1

Procedure:
A solution of 2.0 g of tert-butyl 4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}-3-(2-{2-[2-(toluene-4-sulphonyloxy)ethyl]phenoxy}ethoxy)piperidine-1-carboxylate (Example 26b) and 1.32 g of sodium azide in 20 ml of N,N-dimethylformamide is stirred at 65° C. over 90 minutes. The reaction mixture is diluted with semisaturated aqueous sodium hydrogencarbonate solution and extracted with tert-butyl methyl ether (3×). The combined organic phases are dried over sodium sulphate and concentrated by evaporation. The crude title compound is obtained as a colourless oil from the residue. Rf=0.43 (1:1 EtOAc-heptane); Rt=6.40.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=1.[C:16](Cl)(Cl)=[S:17]>O1CCOCC1.O>[CH3:15][O:14][C:11]1[CH:12]=[CH:13][C:8]([C:3]2[C:2]([N:1]=[C:16]=[S:17])=[CH:7][CH:6]=[CH:5][CH:4]=2)=[CH:9][CH:10]=1
Reactant: S=C(Cl)Cl
Reactant: COc1ccc(-c2ccccc2N)cc1
Solvent: O
Solvent: C1COCCO1
Product: COc1ccc(-c2ccccc2N=C=S)cc1

Procedure:
Reaction of 2-amino-4'-methoxybiphenyl (10 g) with thiophosgene (8.7 g) in dioxane (25 ml) and water (80 ml) at 0° C. for 3 hours gave 4'-methoxy-2-biphenylylisothiocyanate as a pale yellow oil.
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:3]=1[CH2:4][O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]([CH3:14])=[CH2:13].[Br:20]N1C(=O)CCC1=O.O>C(Cl)(Cl)(Cl)Cl.N(C(C)(C)C#N)=NC(C)(C)C#N>[Cl:1][C:2]1[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:3]=1[CH2:4][O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]([CH2:14][Br:20])=[CH2:13]
Reactant: O=C1CCC(=O)N1Br
Reactant: C=C(C)c1ccccc1OCc1ccc(Cl)cc1Cl
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Solvent: O
Product: C=C(CBr)c1ccccc1OCc1ccc(Cl)cc1Cl
Reaction time: 12 h
Yield: 41 %

Procedure:
2-[2-(2,4-Dichlorobenzyloxy)phenyl]-1-propene (1.0 g, 3.41 mmole), N-bromosuccinimide (0.61 g, 3.41 mmole) and azobisisobutyronitrile (2.8 mg, 0.017 mmole) were suspended in carbon tetrachloride (4 ml) and the suspension was refluxed with stirring for 12 hours. Then, the mixture was poured into water (30 ml) and extracted with ethyl acetate (50 ml). The extract was washed with water (50 ml) and dried over anhydrous soidum sulfate. After distilling off the solvent under reduced pressure, the residue was subjected to chromatography on a silica gel column and eluted with n-hexane to obtain the title compound (0.52 g, 41.0%). 1H-NMR (CDCl3, δ): 4.50 (s, 2H, CH2Br), 5.20 (s, 2H, ##STR49## 5.33 (d, 1H, =CH), 5.57 (d, 1H, =CH), 6.80-7.57 (m, 7H, aromatic).
Reaction SMILES: [OH:1][CH:2]1[CH2:20][CH:19]2[N:4]([C:5](=[O:39])[CH:6]([NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:7][CH2:8][CH2:9][O:10][CH2:11][CH:12]=[CH:13][CH:14]3[C:16]([C:22]([NH:24][S:25]([CH:28]4[CH2:30][CH2:29]4)(=[O:27])=[O:26])=[O:23])([NH:17][C:18]2=[O:21])[CH2:15]3)[CH2:3]1.[CH3:40][O:41][C:42]1[CH:43]=[C:44]([CH:48]=[CH:49][CH:50]=1)[C:45](Cl)=[O:46]>>[CH3:40][O:41][C:42]1[CH:43]=[C:44]([CH:48]=[CH:49][CH:50]=1)[C:45]([O:1][CH:2]1[CH2:20][CH:19]2[N:4]([C:5](=[O:39])[CH:6]([NH:31][C:32]([O:34][C:35]([CH3:36])([CH3:38])[CH3:37])=[O:33])[CH2:7][CH2:8][CH2:9][O:10][CH2:11][CH:12]=[CH:13][CH:14]3[C:16]([C:22]([NH:24][S:25]([CH:28]4[CH2:29][CH2:30]4)(=[O:26])=[O:27])=[O:23])([NH:17][C:18]2=[O:21])[CH2:15]3)[CH2:3]1)=[O:46]
Reactant: CC(C)(C)OC(=O)NC1CCCOCC=CC2CC2(C(=O)NS(=O)(=O)C2CC2)NC(=O)C2CC(O)CN2C1=O
Reactant: COc1cccc(C(=O)Cl)c1
Product: COc1cccc(C(=O)OC2CC3C(=O)NC4(C(=O)NS(=O)(=O)C5CC5)CC4C=CCOCCCC(NC(=O)OC(C)(C)C)C(=O)N3C2)c1
Yield: 45.4 %

Procedure:
Prepared by way of method I using 18-hydroxy-14-tert-butoxycarbonylamino-4-cyclopropylsulfonylaminocarbonyl-2,15-dioxo-3,16-diaza-10-oxatricyclo[14.3.0.04,6]-nonadec-7-ene (100 mg, 0.175 mmol) and 3-methoxybenzoyl chloride (74 μL, 0.53 mmol). The final trituration (diethyl ether/hexane) and filtration gave 56 mg (45%) of 18-(3-methoxybenzoyloxy)-14-tert-butoxycarbonylamino-4-cyclopropylsulfonylaminocarbonyl-2,15-dioxo-3,16-diaza-10-oxatricyclo-[14.3.0.04,6]-nonadec-7-ene as a white powder: 98.7% pure (HPLC), MS m/z 703 (M−H)−, HRMS: calcd. 705.2806 and found 705.2782 (M+H)+, mp 149-151° C.