Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [I-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[H][H].[F:11][C:12]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:13]=1[CH2:14][CH:15]1[CH2:19][CH2:18][CH2:17][C:16]1=[O:20]>CS(C)=O>[F:11][C:12]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:13]=1[CH2:14][CH:15]1[CH2:19][CH2:18][CH2:17][C:16]21[O:20][CH2:2]2
Reactant: O=C1CCCC1Cc1ccc(F)cc1F
Reactant: [H][H]
Reactant: C[S+](C)(C)=O
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: CS(C)=O
Product: Fc1ccc(CC2CCCC23CO3)c(F)c1
Temperature: 25 °C

Procedure:
Trimethylsulfoxonium iodide (4.86 g, 22.1 mmol, 1.3 eq) was dissolved in DMSO (25 ml) and sodium hydride (0.49 g, 20.4 mmol, 1.2 eq) was added at 100° C. while being stirred. The solution was warmed to room temperature and stirred for 45 min while being stirred; thereafter, the solution became transparent. After terminal evolution of hydrogen had been confirmed, the solution was again heated at 10° C. and 2-(2,4-difluorobenzyl)cyclopentanone (3.56 g, 17.0 mmol, 1.0 eq) was dripped into the solution.
Reaction SMILES: [O:1]=[C:2]1[C:7]([CH2:8][N:9]2C(=O)C3C(=CC=CC=3)C2=O)=[N:6][N:5]=[CH:4][NH:3]1.NN>C(Cl)Cl.CCO>[NH2:9][CH2:8][C:7]1[C:2](=[O:1])[NH:3][CH:4]=[N:5][N:6]=1
Reactant: O=C1c2ccccc2C(=O)N1Cc1nnc[nH]c1=O
Agent: NN
Solvent: ClCCl
Solvent: CCO
Product: NCc1nnc[nH]c1=O
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A slurry of 2-(5-oxo-4,5-dihydro-[1,2,4]triazin-6-ylmethyl)isoindole-1,3-dione (4 g, 15.6 mmol) in DCM/EtOH (1:1) (150 mL) was charged with anhydrous hydrazine (1.23 mL, 39.0 mmol) and stirred at rt for 18 h. The reaction mixture was concentrated in vacuo and the off-white solid was triturated with warm CHCl3 and filtered through a fritted funnel. The solid was then triturated with hot boiling methanol (MeOH) and filtered through a fritted funnel resulting in an off-white solid. The material was triturated a second time as before and dried overnight resulting in the title compound as a white solid, which was taken on to the next step without further purification; 1H NMR (DMSO-d6, 400 MHz) δ 3.88 (s, 2H), 8.31 (2, 1H); MS (ES+): m/z 127.07 (100) [MH+], HPLC: tR=0.34 min (MicromassZQ, polar—5 min).
Reaction SMILES: Cl.N[CH2:3][CH2:4][SH:5].[NH2:6][C:7]1[N:11]([C:12]2[C:17]([Cl:18])=[CH:16][C:15]([C:19]([F:22])([F:21])[F:20])=[CH:14][C:13]=2[Cl:23])[N:10]=[C:9]([C:24]#[N:25])[C:8]=1[S:26]([CH3:28])=[O:27]>CO>[NH2:6][C:7]1[N:11]([C:12]2[C:17]([Cl:18])=[CH:16][C:15]([C:19]([F:20])([F:21])[F:22])=[CH:14][C:13]=2[Cl:23])[N:10]=[C:9]([CH:24]2[NH:25][CH:3]=[CH:4][S:5]2)[C:8]=1[S:26]([CH3:28])=[O:27]
Reactant: NCCS
Reactant: CS(=O)c1c(C#N)nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c1N
Agent: Cl
Solvent: CO
Product: CS(=O)c1c(C2NC=CS2)nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c1N
Temperature: 25 °C
Yield: 16.1 %

Procedure:
A solution of 0.297 gram (0.00261 mole) of 2-aminoethanethiol hydrochloride in 2.5 milliliters of methanol was added to 1.0 gram (0.00261 mole) of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl) phenyl]-4-methylsulfinyl-1H-pyrazole-3-carbonitrile, and the mixture was stirred at room temperature for an approximately 17-hour period The mixture was partitioned between water and dichloromethane and the organic layer was separated, dried over Na2SO4 and filtered. Solvent was evaporated leaving a residue which was purified by preparative thin-layer chromatography to give 0.186 gram (0.00042 mole) of 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-3-(dihydro-2-thiazolyl)-4-methylsulfinyl-1H-pyrazole having a melting point of 189.5° C. (with decomposition). This compound is referred to hereinafter as Compound 1.
Reaction SMILES: N(C(C)C)C(C)C.[Li]CCCC.CCCCCC.[Cl:19][C:20]1[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=1[CH2:27][C:28]([O:30][CH3:31])=[O:29].I[CH2:33][CH2:34][CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37]>C1COCC1>[CH3:31][O:30][C:28](=[O:29])[CH:27]([C:21]1[CH:22]=[CH:23][C:24]([Cl:26])=[CH:25][C:20]=1[Cl:19])[CH2:33][CH2:34][CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37]
Reactant: CCOC(=O)CCCI
Reactant: COC(=O)Cc1ccc(Cl)cc1Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Solvent: CCCCCC
Product: CCOC(=O)CCCC(C(=O)OC)c1ccc(Cl)cc1Cl
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
To a solution of i-Pr2NH (0.921 mL, 1.2 eq) in anh. THF (22 mL), at 0° C., under N2, was added a 1.6 M solution of BuLi in hexane (3.42 mL, 1 eq) and the mixture was stirred at 0° C. for 10 min. It was then cooled to −78° C. and a solution of methyl 2,4-dichlorophenylacetate (1.2 g, 5.478 mmol) in anh. THF (3.3 mL) was added dropwise. The mixture was stirred at −78° C. for 45 min before the addition of a solution of ethyl 4-iodobutyrate (1.72 g, 1.3 eq) in anh. THF (2 mL). The cooling bath was then removed and the mixture was stirred at r.t. for 4 hr. The solvents were evaporated under reduced pressure. The residue was dissolved in CH2Cl2, washed with water (2×25 mL) and brine (1×25 mL) and dried over anh. Na2SO4. The solids were filtered and the solvent evaporated. The crude product was purified by flash chromatography (silica gel, cHex/EtOAc 9:1). Mixed fractions were repurified with the same eluent. The title compound was obtained as a pale yellow oil (1.36 g, 4.088 mmol, 75%).
Reaction SMILES: [C:1]([C:4]1[S:8][C:7]([NH2:9])=[N:6][C:5]=1[C:10]([O:12][CH2:13][CH3:14])=[O:11])(=[O:3])[CH3:2].[BrH:15].Br.[NH+]1C=CC=CC=1.O>C(O)(=O)C>[NH2:9][C:7]1[S:8][C:4]([C:1](=[O:3])[CH2:2][Br:15])=[C:5]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[N:6]=1
Reactant: CCOC(=O)c1nc(N)sc1C(C)=O
Reactant: Br
Agent: c1cc[nH+]cc1
Solvent: CC(=O)O
Solvent: O
Product: CCOC(=O)c1nc(N)sc1C(=O)CBr
Reaction time: 1 h

Procedure:
To a solution of ethyl 5-acetyl-2-amino-4-thiazolecarboxylate (12.9 g) in a mixture of 30% solution of hydrogen bromide in acetic acid (50 ml) and acetic acid (50 ml) was added pyridinium hydrobromide perbromide (21.1 g) at ambient temperature and stirred for one hour. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, and evaporatec in vacuo. The residue was washed with diisopropyl ether to give ethyl 2-amino-5-(2-bromoacetyl)-4-thiazolecarboxylate (14.86 g). mp 164°-166° C. (dec.)
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][N:9]2[C:14]([O:15][C:16]3[CH:21]=[C:20]([CH3:22])[CH:19]=[C:18]([CH:23]4OCC[O:24]4)[CH:17]=3)=[C:13]([CH:28]([CH3:30])[CH3:29])[C:12](=[O:31])[NH:11][C:10]2=[O:32])[CH:5]=[C:4]([NH:33][CH2:34][C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)[N:3]=1.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1>O.CC(C)=O>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][N:9]2[C:14]([O:15][C:16]3[CH:17]=[C:18]([CH:19]=[C:20]([CH3:22])[CH:21]=3)[CH:23]=[O:24])=[C:13]([CH:28]([CH3:29])[CH3:30])[C:12](=[O:31])[NH:11][C:10]2=[O:32])[CH:5]=[C:4]([NH:33][CH2:34][C:35]2[CH:36]=[CH:37][C:38]([O:41][CH3:42])=[CH:39][CH:40]=2)[N:3]=1
Reactant: COc1ccc(CNc2cc(Cn3c(Oc4cc(C)cc(C5OCCO5)c4)c(C(C)C)c(=O)[nH]c3=O)cc(Cl)n2)cc1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: O
Solvent: CC(C)=O
Product: COc1ccc(CNc2cc(Cn3c(Oc4cc(C)cc(C=O)c4)c(C(C)C)c(=O)[nH]c3=O)cc(Cl)n2)cc1
Temperature: 25 °C
Yield: 41.7 %

Procedure:
A mixture of 1-[2-chloro-6-(4-methoxy-benzylamino)-pyridin-4-ylmethyl]-6-(3-[1,3]dioxolan-2-yl-5-methyl-phenoxy)-5-isopropyl-1 H-pyrimidine-2,4-dione (908 mg, 1.53 mmol), PPTS (77 mg, 0.31 mmol), and water (7 drops) in acetone (10 ml) was heated under reflux for 3 hr. After cooling to room temperature, the mixture was evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, EA:hexanes (1:2)) to afford 350 mg (50%) of a white foam. 1H NMR (200 MHz, CDCl3) δ 1.11 (6H, d, J=6.8 Hz), 2.40 (3H, s), 2.68 (1H, m), 3.80 (3H, s), 4.29 (2H, d, J=5.4 Hz), 4.72 (2H, s), 5.02 (1H, t, J=5.4 Hz), 6.01 (1H, s), 6.26 (1H, s), 6.85-6.89 (3H, m), 7.09 (1H, s), 7.21-7.27 (2H, m), 7.40 (1H, s), 8.98 (1H, s), 9.89 (1H, s).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][C:8]([NH2:11])=[CH:7][CH:6]=1)[CH3:2].[Cl:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][C:21]=1[F:22])[CH:17]=O>C1(C)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][C:8]([N:11]=[CH:17][C:16]2[CH:19]=[CH:20][C:21]([F:22])=[C:14]([Cl:13])[CH:15]=2)=[CH:7][CH:6]=1)[CH3:2]
Reactant: CCOC(=O)c1ccc(N)cc1
Reactant: O=Cc1ccc(F)c(Cl)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: CCOC(=O)c1ccc(N=Cc2ccc(F)c(Cl)c2)cc1
Temperature: 25 °C
Yield: 100.7 %

Procedure:
A mixture solution of 4-amino-benzoic acid ethyl ester (16.5 g, 100 mmol), 3-chloro-4-fluoro-benzaldehyde (16.1 g, 100 mmol) and p-toluenesulfonic acid (384 mg, 2.0 mmol) in toluene (200 mL) was heated to reflux for 12 hours. Then the reaction mixture was cooled to room temperature. The solvent was removed in vacuo and the residue was washed with ether to afford 4-[(3-chloro-4-fluoro-benzylidene)-amino]-benzoic acid ethyl ester (30.8 g, quant.) as a pale-white solid: MS calcd. for C16H13ClFNO2 306.74, obsd. (ESI+) [(M+H)+] 306.1.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([CH2:9][CH:10]=O)=[CH:7][CH:6]=[CH:5][N:4]=1.[F:12][C:13]1[CH:14]=[C:15]([CH:27]=[CH:28][CH:29]=1)[CH2:16][NH:17][C:18](=[O:26])[CH2:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][NH:21]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C1COCC1.C(O)(=O)C>[F:12][C:13]1[CH:14]=[C:15]([CH:27]=[CH:28][CH:29]=1)[CH2:16][NH:17][C:18](=[O:26])[CH2:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][N:21]1[CH2:10][CH2:9][C:8]1[C:3]([O:2][CH3:1])=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(CC1CCCCN1)NCc1cccc(F)c1
Reactant: COc1ncccc1CC=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: COc1ncccc1CCN1CCCCC1CC(=O)NCc1cccc(F)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 72.5 %

Procedure:
200 mg of 2-(2-methoxy-3-pyridyl)acetaldehyde, 400 mg of N1-(3-fluorobenzyl)-2-(2-piperidyl)acetamide, 440 mg of sodium triacetoxyborohydride and 0.12 ml of acetic acid were suspended in THF, followed by stirring at room temperature for 1 hour. An aqueous sodium bicarbonate was added thereto, and the mixture was extracted with ethyl acetate. The extract was dried over sodium sulfate. After filtering off the drying agent, the solvent was evaporated. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=8:1, subsequently 4:1), to give 370 mg of a yellow oil.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][CH:3]=1.C([Li])CCC.[CH:14](=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=1>O1CCCC1.CCCCCC>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([CH:14]([OH:23])[C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=2)=[CH:3][CH:4]=1
Reactant: Clc1ccc(Br)cc1
Reactant: COc1cccc(C=O)c1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: COc1cccc(C(O)c2ccc(Cl)cc2)c1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 99.3 %

Procedure:
A solution of 35.0 g (183 mmole) of 4-bromochlorobenzene in 300 ml of dry tetrahydrofuran was cooled to -78° C. under nitrogen and 115 ml (183 mmole) of 1.59 M n-butyllithium in hexane was added dropwise at a rate to maintain temperature below -60° C. After stirring an additional 15 minutes, 23.0 ml (183 mmole) of m-anisaldehyde was added dropwise and the reaction was stirred for 15 minutes. The reaction was quenched at -78° C. with saturated aqueous ammonium chloride and allowed to warm to room temperature. The reaction solution was diluted with 300 ml of diethyl ether and washed with three 150 ml portions of 1.0 M sodium bisulfite, followed by 100 ml of 1.0 M sodium hydroxide, 100 ml of water, and 50 ml of saturated sodium chloride. After drying over magnesium sulfate, the solvent was removed to give 45.2 g (99%) of crude 4-chloro-α-(3-methoxyphenyl)benzyl alcohol as a pale yellow oil.
Reaction SMILES: Cl.Cl.Cl.[NH:4]([C:6]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:9]=[C:8]([CH3:18])[N:7]=1)[NH2:5].[C:19]([C:22]1[CH:27]=[CH:26][C:25]([NH:28][C:29](=[O:31])[CH3:30])=[CH:24][CH:23]=1)(=O)[CH3:20]>C(O)C>[CH3:18][C:8]1[N:7]=[C:6]([NH:4][N:5]=[C:19]([C:22]2[CH:27]=[CH:26][C:25]([NH:28][C:29](=[O:31])[CH3:30])=[CH:24][CH:23]=2)[CH3:20])[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:9]=1
Reactant: Cc1nc(NN)cc(-c2ccccc2)n1
Reactant: CC(=O)Nc1ccc(C(C)=O)cc1
Agent: Cl
Solvent: CCO
Product: CC(=O)Nc1ccc(C(C)=NNc2cc(-c3ccccc3)nc(C)n2)cc1

Procedure:
The title compound was prepared from 4-hydrazino-2-methyl-6-phenylpyrimidine trihydrochloride (300 mg, 0.97 mmol) and N-(4-acetyl-phenyl)acetamide (515 mg, 2.91 mmol) in ethanol (10.0 mL) by a procedure similar to example 1, step 4 yielding 43 mg (12%) of a brown solid. HPLC Purity: 95%.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][CH2:12][N:13]([CH2:16][CH3:17])[CH2:14][CH3:15])[N:6]=[C:5]3[C:18]4[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=4[S:20][C:3]=1[C:4]=23.Cl.[Br:26][CH2:27][CH2:28][NH2:29]>CCO>[BrH:26].[CH2:14]([N:13]([CH2:16][CH3:17])[CH2:12][CH2:11][N:7]1[C:8]2[CH:9]=[CH:10][C:2]([NH:1][CH2:27][CH2:28][NH2:29])=[C:3]3[S:20][C:19]4[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=4[C:5]([C:4]=23)=[N:6]1)[CH3:15]
Reactant: NCCBr
Reactant: CCN(CC)CCn1nc2c3c(c(N)ccc31)Sc1ccccc1-2
Agent: Cl
Solvent: CCO
Product: Br
Product: CCN(CC)CCn1nc2c3c(c(NCCN)ccc31)Sc1ccccc1-2
Temperature: 25 °C
Yield: 37.5 %

Procedure:
A solution of 5.0 g (0.015 mol) of 5-amino-N,N-diethyl-2H[1]benzothiopyrano[4,3,2-cd]indazole-2-ethanamine and 9.2 g (0.045 mol) of 2-bromoethylamine, hydrochloride in 50 ml of EtOH was heated under reflux for four days and allowed to cool to room temperature. The solid was collected and recrystallized from MeOH to give 2.6 g of product, mp 263° C. dec.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH2:22]=[O:23].[OH-].[Na+]>O>[CH2:1]([N:8]1[CH2:9][CH:10]=[C:11]([C:14]2[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=2)[CH:12]([CH2:22][OH:23])[CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Fc1ccc(C2=CCN(Cc3ccccc3)CC2)cc1
Reactant: C=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: OCC1CN(Cc2ccccc2)CC=C1c1ccc(F)cc1
Temperature: 100 °C
Reaction time: 5 h
Yield: 78.3 %

Procedure:
4.5 g (16.8 mmol) of 1-benzyl-4-(4-fluoro-phenyl)-1,2,3,6-tetrahydro-pyridine were suspended in 55 ml of water, then partially dissolved by the addition of 70 ml of concentrated hydrochloric acid, 1.36 g (45.3 mmol) of paraformaldehyde were added and the mixture was stirred at 100° C. for 5 hours. After cooling to room temperature the mixture was adjusted to pH 5-6 with sodium hydroxide solution and the product was extracted twice with 100 ml of ethyl acetate. The organic phases were washed once with 100 ml of water, dried over magnesium sulphate, filtered and concentrated in a water-jet vacuum. The thus-obtained crude product was chromatographed on silica gel with hexane and ethyl acetate as the eluent (sic). There were obtained 3.91 g (78% of theory) of (RS)-[1-benzyl-4-(4-fluoro-phenyl)-1,2,3,6-tetrahydro-pyridin-3-yl]-methanol; MS: 297 (M)+.
Reaction SMILES: C(O[C:9]([N:11]1C=CC=[C:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[N:12]1[C:24](=[O:49])[CH:25]([N:38]1[C:42](=[O:43])[C:41]2=[CH:44][CH:45]=[CH:46][CH:47]=[C:40]2[C:39]1=[O:48])[CH2:26]NC(OCC1C=CC=CC=1)=O)=O)C1C=CC=CC=1.C=O>CO.[Pd]>[O:49]=[C:24]1[N:12]2[C@@H:13]([C:17]([O:19][C:20]([CH3:22])([CH3:23])[CH3:21])=[O:18])[NH:12][CH2:24][CH2:25][CH2:26][N:11]2[CH2:9][CH2:26][C@@H:25]1[N:38]1[C:42](=[O:43])[C:41]2=[CH:44][CH:45]=[CH:46][CH:47]=[C:40]2[C:39]1=[O:48]
Reactant: CC(C)(C)OC(=O)C1=CC=CN(C(=O)OCc2ccccc2)N1C(=O)C(CNC(=O)OCc1ccccc1)N1C(=O)c2ccccc2C1=O
Agent: [Pd]
Agent: C=O
Solvent: CO
Product: CC(C)(C)OC(=O)[C@H]1NCCCN2CC[C@H](N3C(=O)c4ccccc4C3=O)C(=O)N12
Reaction time: 24 h
Yield: 94.6 %

Procedure:
A solution of ester 267 (50 mg, 0.074 mmol) in methanol (15 ml) was treated with 10% palladium on carbon (50 mg) and hydrogenated at room temperature and atmospheric pressure for 24 h. The mixture was evacuated thoroughly to remove hydrogen then treated with 37% aqueous formaldehyde (18 mg, 0.22 mmol) and stirred under nitrogen for 2 h. The mixture was filtered, evaporated to dryness and the product purified by flash chromatography (4-100% ethyl acetate/dichloromethane) to afford 268 14.5 mg (48%) as an oil: 1H NMR (CDCl3) δ 7.85 (2H, m), 7.71 (2H, m), 5.78 (1H, dd, J=10, 5), 4.99 (1H, dd, J=6.1, 1.5), 4.07 (1H, d, J=10.6), 3.49 (1H, dd, J=14, 5), 3.39 (1H, d, J=10.3), 3.24 (1H, dd, J=14, 10.2), 3.17 (2H, m), 2.39 (1H, m), 1.84-1.46 (3H), 1.51 (9H, s); MS (ES+), 415 (M+1), 437 (M+Na)
Reaction SMILES: NC1N(C(OC(C)(C)C)=O)N=C(C2C=CC(OCC3C=CC(C4SC(N5CCC6C(=C(C(=O)N(C7SC8C=CC=CC=8N=7)COCC[Si](C)(C)C)C=CC=6)C5)=NC=4C(OCC)=O)=CC=3)=CC=2)C=1C#N.NC1N(C(OC(C)(C)C)=O)N=C(C2C=CC(O)=CC=2)C=1C#N.O[CH2:93][C:94]1[S:98][C:97]([N:99]2[CH2:108][CH2:107][C:106]3[C:101](=[C:102]([C:109](=[O:128])/[N:110]=[C:111]4/[S:112][C:113]5[CH:127]=[CH:126][CH:125]=[CH:124][C:114]=5[N:115]/4[CH2:116][O:117][CH2:118][CH2:119][Si:120]([CH3:123])([CH3:122])[CH3:121])[CH:103]=[CH:104][CH:105]=3)[CH2:100]2)=[N:96][C:95]=1[C:129]([O:131][CH3:132])=[O:130].[OH:133][C:134]1[CH:139]=[CH:138][C:137]([C:140]2[C:141]([C:145]#[N:146])=[CH:142][S:143][CH:144]=2)=[CH:136][CH:135]=1>>[C:145]([C:141]1[C:140]([C:137]2[CH:136]=[CH:135][C:134]([OH:133])=[C:139]([CH:138]=2)[CH2:93][C:94]2[S:98][C:97]([N:99]3[CH2:108][CH2:107][C:106]4[C:101](=[C:102]([C:109](=[O:128])/[N:110]=[C:111]5/[S:112][C:113]6[CH:127]=[CH:126][CH:125]=[CH:124][C:114]=6[N:115]/5[CH2:116][O:117][CH2:118][CH2:119][Si:120]([CH3:121])([CH3:123])[CH3:122])[CH:103]=[CH:104][CH:105]=4)[CH2:100]3)=[N:96][C:95]=2[C:129]([O:131][CH3:132])=[O:130])=[CH:144][S:143][CH:142]=1)#[N:146]
Reactant: COC(=O)c1nc(N2CCc3cccc(C(=O)/N=c4/sc5ccccc5n4COCC[Si](C)(C)C)c3C2)sc1CO
Reactant: N#Cc1cscc1-c1ccc(O)cc1
Agent: CC(C)(C)OC(=O)n1nc(-c2ccc(O)cc2)c(C#N)c1N
Agent: CCOC(=O)c1nc(N2CCc3cccc(C(=O)N(COCC[Si](C)(C)C)c4nc5ccccc5s4)c3C2)sc1-c1ccc(COc2ccc(-c3nn(C(=O)OC(C)(C)C)c(N)c3C#N)cc2)cc1
Product: COC(=O)c1nc(N2CCc3cccc(C(=O)/N=c4/sc5ccccc5n4COCC[Si](C)(C)C)c3C2)sc1Cc1cc(-c2cscc2C#N)ccc1O

Procedure:
The title compound 60A was prepared in a similar manner to the synthesis of compound 35A by substituting compound 34D and compound 31F with compound 45D and compound 51A, respectively: ESI (+)/LC/MS: 892 (M+NH4—H2O)+: 1H NMR (DMSO-d6): δ 9.99 (s, 1H), 8.58 (s, 1H), 8.21 (d, J=6.71 Hz, 1H), 7.92 (d, J=7.32 Hz, 1H), 7.66-7.68 (m, 2H), 7.52-7.55 (m, 1H), 7.32-7.41 (m, 5H), 6.92 (d, J=8.24 Hz, 1H), 5.97 (s, 2H), 5.08 (s, 2H), 4.35 (s, 2H), 3.78 (s, 3H), 3.64-3.68 (m, 2H), 2.98 (t, J=5.8 Hz, 2H), 0.84-0.87 (m, 2H), −0.22 (s, 9H). ESI (+)/MS: 794 (M+H)+.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:30])[C:5]([CH3:29])([O:7][C:8]1[CH:16]=[C:15]2[C:11]([CH:12]=[C:13]([C:20]3[CH:25]=[CH:24][C:23]([N+:26]([O-])=O)=[CH:22][CH:21]=3)[N:14]2[CH2:17][CH2:18][CH3:19])=[CH:10][CH:9]=1)[CH3:6])[CH3:2].[H][H].[C:33](OC(=O)C)(=[O:35])[CH3:34]>[Ni]>[CH2:1]([O:3][C:4](=[O:30])[C:5]([O:7][C:8]1[CH:16]=[C:15]2[C:11]([CH:12]=[C:13]([C:20]3[CH:25]=[CH:24][C:23]([NH:26][C:33](=[O:35])[CH3:34])=[CH:22][CH:21]=3)[N:14]2[CH2:17][CH2:18][CH3:19])=[CH:10][CH:9]=1)([CH3:29])[CH3:6])[CH3:2]
Reactant: [H][H]
Reactant: CC(=O)OC(C)=O
Reactant: CCCn1c(-c2ccc([N+](=O)[O-])cc2)cc2ccc(OC(C)(C)C(=O)OCC)cc21
Agent: [Ni]
Product: CCCn1c(-c2ccc(NC(C)=O)cc2)cc2ccc(OC(C)(C)C(=O)OCC)cc21

Procedure:
An amount of 5.4 g (13 m mole) of 2-methyl-2-[2-(4-nitro-phenyl)-1-propyl-1H-indole-6-yloxy]-propanoic acid ethylester and 2.5 g of Raney-Nickel were suspended in 150 ml of acetic anhydride and hydrogenated at a pressure of 5 bar with hydrogen at 20° C. Subsequently the catalyst was filtered off and the filtrate was evaporated. The resulting residue was chromatographed on silicagel (solvent: toluene/acetone (3:1)), the eluates were evaporated, and the residue was triturated with petroleum ether/ether and suction filtered.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:16]=[C:17]([O:21][CH3:22])[C:18]=1[O:19][CH3:20])[CH2:6][N:7]1[CH2:12][CH2:11][N:10]([C:13]([S-:15])=[S:14])[CH2:9][CH2:8]1.[Na+].[CH:24](I)([CH3:26])[CH3:25]>C(O)C>[CH3:22][O:21][C:17]1[CH:16]=[C:5]([CH:4]=[C:3]([O:2][CH3:1])[C:18]=1[O:19][CH3:20])[CH2:6][N:7]1[CH2:8][CH2:9][N:10]([C:13]([S:15][CH:24]([CH3:26])[CH3:25])=[S:14])[CH2:11][CH2:12]1
Reactant: COc1cc(CN2CCN(C(=S)[S-])CC2)cc(OC)c1OC
Reactant: CC(C)I
Agent: [Na+]
Solvent: CCO
Product: COc1cc(CN2CCN(C(=S)SC(C)C)CC2)cc(OC)c1OC
Temperature: 25 °C
Reaction time: 8 h
Yield: 70.3 %

Procedure:
In 2 ml of ethanol was suspended 364 mg of sodium 4-(3,4,5-trimethoxybenzyl)-1-piperazinecarbodithioate, and to the suspension was added 204 mg of isopropyl iodide. The resulting homogeneoussolution was stirred overnight at room temperature. Ethanol was distilled off from the solution, and to the residue were added ether and water. The ether portion was taken out, washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and placed under reduced pressure to evaporate the solvent. The residue was purified by silica gel column chromatography to give 270 mg of the desired compound asa colorless oil, yield 70.3%).
Reaction SMILES: [C:1]1(C2C=CC=CC=2)[CH:6]=[CH:5][C:4]([CH:7]([N:14]2[CH:18]=[CH:17][N:16]=[CH:15]2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:3][CH:2]=1.[C:25]1([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[CH:31]([Cl:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C(#N)C>[Cl-:38].[C:25]1([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[CH:31]([N+:16]1[CH:17]=[CH:18][N:14]([CH:7]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=2[C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:4]2[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=2)[CH:15]=1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1
Reactant: ClC(c1ccccc1)c1ccccc1-c1ccccc1
Reactant: c1ccc(-c2ccc(C(c3ccccc3)n3ccnc3)cc2)cc1
Solvent: CC#N
Product: [Cl-]
Product: c1ccc(-c2ccccc2C(c2ccccc2)n2cc[n+](C(c3ccccc3)c3ccccc3-c3ccccc3)c2)cc1
Yield: 122.2 %

Procedure:
31 g (0.1 mol) of 1-[α-(4-biphenylyl)-benzyl]-imidazole and 27.9 g (0.1 mol) of α-biphenylyl-benzyl chloride are suspended in 200 ml of acetonitrile. The mixture is heated under reflux for 18 hours. The reaction mixture is then concentrated by distilling off the solvent and the residue, in 500 ml of toluene, is heated under reflux. The gel thereby formed is separated off and caused to crystallise by trituration with diisopropyl ether. 36 g (62% of theory) of 1,3-bis-[α-(-biphenylyl)-benzyl]-imidazolium chloride of melting point 150° C. (with decomposition) are obtained.
Reaction SMILES: O=[C:2]([CH2:11][CH2:12][CH3:13])[CH2:3][C:4]([O:6]CCC#N)=[O:5].[NH2:14]/[C:15](/[CH3:21])=[CH:16]\[C:17]([O:19][CH3:20])=[O:18].[N+:22]([C:25]1[CH:32]=[CH:31][C:28]([CH:29]=O)=[CH:27][CH:26]=1)([O-:24])=[O:23]>C(O)(C)C>[CH3:20][O:19][C:17]([C:16]1[CH:29]([C:28]2[CH:31]=[CH:32][C:25]([N+:22]([O-:24])=[O:23])=[CH:26][CH:27]=2)[C:3]([C:4]([OH:6])=[O:5])=[C:2]([CH2:11][CH2:12][CH3:13])[NH:14][C:15]=1[CH3:21])=[O:18]
Reactant: CCCC(=O)CC(=O)OCCC#N
Reactant: COC(=O)/C=C(/C)N
Reactant: O=Cc1ccc([N+](=O)[O-])cc1
Solvent: CC(C)O
Product: CCCC1=C(C(=O)O)C(c2ccc([N+](=O)[O-])cc2)C(C(=O)OC)=C(C)N1
Reaction time: 0.5 h

Procedure:
A mixture of 2-cyanoethyl 3-oxohexanoate (11.9 mmol), methyl 3-aminocrotonate (11.9 mmol), and 4-nitrobenzaldehyde in 25 mL of isopropanol were heated at reflux temperature for 16 h, cooled, and the solvent was removed under reduced pressure. The residue was dissolved in 15 mL of dioxane (slightly warmed with a heat gun to dissolve the product) and 626 mg of NaOH in 15 mL of water was added to the reaction mixture. After 0.5 hrs, the maroon solution was concentrated to a small volume under reduced pressure, partitioned between 50 mL of water and 50 mL of ethyl acetate, separated, and the aqueous solution was washed with 2×20 mL of ethyl acetate. The aqueous extract was acidified with concentrated HCl (pH=2), and the precipitated oil was extracted with ethyl acetate (2×40 mL). The combined organic extracts were dried (MgSO4), and the solvent was removed in vacuo to give the desired product as a foamy yellow solid. The acid was used in the next step without further purification.