Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(N(CC)CC)C.Br.Br[CH:10]([C:21]1[CH:26]=[CH:25][N:24]=[C:23]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:22]=1)[C:11]([C:13]1[CH:18]=[C:17]([CH3:19])[CH:16]=[C:15]([CH3:20])[CH:14]=1)=O.[NH2:35][C:36]([NH2:38])=[S:37]>C(#N)C>[CH3:20][C:15]1[CH:14]=[C:13]([C:11]2[N:35]=[C:36]([NH2:38])[S:37][C:10]=2[C:21]2[CH:26]=[CH:25][N:24]=[C:23]([O:27][CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH:22]=2)[CH:18]=[C:17]([CH3:19])[CH:16]=1
Reactant: Cc1cc(C)cc(C(=O)C(Br)c2ccnc(OCc3ccccc3)c2)c1
Reactant: NC(N)=S
Agent: Br
Solvent: CC#N
Solvent: CCN(CC)CC
Product: Cc1cc(C)cc(-c2nc(N)sc2-c2ccnc(OCc3ccccc3)c2)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 53.1 %

Procedure:
Triethylamine (1.4 mL, 10 mmol) was added dropwise to a solution of 2-bromo-1-(3,5-dimethylphenyl)-2-(2-phenylmethyloxy-4-pyridyl)ethanone hydrobromide (4.8 g, 9.8 mmol) and thiourea (0.77 g, 11 mmol) in acetonitrile (40 mL) and the mixture was stirred at room temperature for 3 hours. The solvent was removed under reduced pressure, a saturated aqueous solution of sodium hydrogencarbonate was added to the residue and extracted with ethyl acetate. The organic layer was washed with water, dried and the solvent was distilled off. The resulting crude crystals were recrystallized from ethyl acetate to obtain 2.0 g (5.2 mmol, yield 53%) of the title compound.
Reaction SMILES: C([O:4][C@@H:5]1[C@@H:10]([O:11]C(=O)C)[C@H:9]([O:15]C(=O)C)[C@@H:8]([CH2:19][O:20]C(=O)C)[O:7][C@H:6]1[N:24]1C(=O)C(=CC2C=CC=CC=2)S[C:25]1=[S:37])(=O)C.[CH3:38][O:39][C:40]1[CH:47]=[CH:46][C:43]([CH2:44][NH2:45])=[CH:42][CH:41]=1>CO>[C@@H:6]1([NH:24][C:25]([NH:45][CH2:44][C:43]2[CH:46]=[CH:47][C:40]([O:39][CH3:38])=[CH:41][CH:42]=2)=[S:37])[O:7][C@H:8]([CH2:19][OH:20])[C@@H:9]([OH:15])[C@H:10]([OH:11])[C@H:5]1[OH:4]
Reactant: CC(=O)OC[C@H]1O[C@@H](N2C(=O)C(=Cc3ccccc3)SC2=S)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: COc1ccc(CN)cc1
Solvent: CO
Product: COc1ccc(CNC(=S)N[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)cc1
Temperature: 25 °C
Reaction time: 19 h

Procedure:
N-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl)-5-benzylidenerhodanine(1.102 g., 0.002 mole) was added to a solution of p-methoxybenzylamine(3.5 g., 0.024 mole) in 50 ml. of methanol in a pressure bottle. The reaction mixture was stirred for 19 hours at room temperature in the pressure bottle with the stopper well closed. The mixture was filtered and the filtrate was evaporated to a sticky syrup in vacuo. The residual syrup was dissolved in the minimum amount of acetone, and anhydrous ether was added to the solution to give a sticky yellow solid. The supernatent was decanted, and the residual sticky solid was dissolved in the minimum amount of actone. Ethyl acetate was added to the solution to give a precipitate. The solid was filtered, partially dissolved in ethyl acetate, and then chromatographed on a column of silica gel (1×20 cm) using ethyl acetate as the first solvent, and acetone as the second solvent. Fifty ml. of ethyl acetate effluent was collected in the first Erlenmeyer flask, and 75 ml. of actone effluent was collected in the second Erlenmeyer flask. The volume of the acetone effluent was reduced to ca. 25 ml. and was set aside at 5° for 24 hours. The straw crystals were filtered, washed with ethyl acetate, and dried in vacuo at room temperature, yielding 0.525 g. (73.2%); m.p. 83°-85°(dec.).
Reaction SMILES: [CH2:1]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1Br)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].[Mg].CN(C)[CH:20]=[O:21].[Cl-].[NH4+]>O1CCCC1.C(Cl)(Cl)(Cl)Cl>[CH2:1]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH:20]=[O:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: CCCCCCCCCc1ccccc1Br
Reactant: CN(C)C=O
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: ClC(Cl)(Cl)Cl
Solvent: C1CCOC1
Product: CCCCCCCCCc1ccccc1C=O
Reaction time: 1 h

Procedure:
A third of a solution of 22 g of 2-nonylbromobenzene in 35 ml of tetrahydrofuran is added to a mixture, stirred under an argon atmosphere, of 3.4 g of magnesium turnings, 25 ml of tetrahydrofuran and 3 drops of carbon tetrachloride and the whole is heated at the boil under reflux for 30 minutes. The remainder of the 2-nonylbromobenzene solution is then added dropwise over a period of one hour and the reaction mixture is maintained under reflux for 2 hours. After dilution with 40 ml of tetrahydrofuran the whole is cooled in an ice bath to approximately 5° and a solution of 11.6 ml of dimethylformamide in 20 ml of tetrahydrofuran is added dropwise over a period of 15 minutes. After stirrin9 for one hour at room temperature, 250 ml of saturated ammonium chloride solution are added to the reaction mixture, the organic layer is separated off and the aqueous layer is extracted three times with ether. The residue that remains after the combined ethereal extracts have been dried and concentrated by evaporation is purified by chromatography on silica gel with mixtures of petroleum ether with an increasing amount of methylene chloride, yielding the desired 2-nonylbenzaldehyde in the form of a pale yellow liquid.
Reaction SMILES: C(OC(=O)[CH:5]([N:7]([CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[C:8](=[O:32])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][NH:14]C(OCC1C2C=CC=CC=2C2C1=CC=CC=2)=O)[CH3:6])C>N1CCCCC1.CN(C)C=O>[CH2:37]([O:36][C:34](=[O:35])[CH2:6][CH2:5][N:7]([C:8](=[O:32])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][NH2:14])[CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH3:38]
Reactant: CCOC(=O)CN(C(=O)CCCCCNC(=O)OCC1c2ccccc2-c2ccccc21)C(C)C(=O)OCC
Solvent: CN(C)C=O
Solvent: C1CCNCC1
Product: CCOC(=O)CCN(CC(=O)OCC)C(=O)CCCCCN
Reaction time: 1 h

Procedure:
3-{(Ethoxycarbonylmethyl-[6-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoyl]-amino}-propionic acid ethyl ester AB (11.5 g, 21.3 mmol) was dissolved in 20% piperidine in dimethylformamide at 0° C. The solution was continued stirring for 1 h. The reaction mixture was concentrated under vacuum, water was added to the residue, and the product was extracted with ethyl acetate. The crude product was purified by conversion into its hydrochloride salt.
Reaction SMILES: C[O:2][C:3]([C:5]1[S:6][C:7]([C:27]#[C:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:8][C:9]=1[N:10]1[C@H:15]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:14][O:13][C@@:12]([CH2:23][CH:24]=[CH2:25])([CH3:22])[C:11]1=[O:26])=[O:4].B1C2CCCC1CCC2.[OH-:42].[Na+].OO>C1COCC1.CCO>[CH:16]1([C@H:15]2[N:10]([C:9]3[CH:8]=[C:7]([C:27]#[C:28][C:29]([CH3:32])([CH3:30])[CH3:31])[S:6][C:5]=3[C:3]([OH:2])=[O:4])[C:11](=[O:26])[C@:12]([CH2:23][CH2:24][CH2:25][OH:42])([CH3:22])[O:13][CH2:14]2)[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]1
Reactant: [OH-]
Reactant: C=CC[C@@]1(C)OC[C@@H](C2CCCCC2)N(c2cc(C#CC(C)(C)C)sc2C(=O)OC)C1=O
Agent: B1C2CCCC1CCC2
Agent: OO
Agent: [Na+]
Solvent: CCO
Solvent: C1CCOC1
Product: CC(C)(C)C#Cc1cc(N2C(=O)[C@@](C)(CCCO)OC[C@H]2C2CCCCC2)c(C(=O)O)s1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 3-((2R,5R)-2-allyl-5-cyclohexyl-2-methyl-3-oxo-morpholin-4-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (50 mg, 0.11 mmol, 1.0 equiv) in THF (1.0 mL) was added 9-BBN (0.5 M solution in THF, 0.55 ml, 0.27 mmol, 2.5 equiv) at 0° C. The reaction mixture was then stirred at room temperature for 2 hours. To the solution was then cooled in an ice water bath and was added EtOH, followed by aq. NaOH solution and H2O2 aq. solution. During addition the reaction internal temperature was kept between 5° C. and 10° C. The reaction mixture was then heated to reflux for 90 minutes. After cooled at room temperature, the reaction mixture was extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by prep-HPLC to give the product 26 mg. MW: 462.2 [M+H]+. 1H-NMR (400 MHz, MeOD): δ 6.91 (s, 1H), 4.23 (d, 1H), 3.94 (d, 1H), 3.62 (m, 1H), 3.55 (m, 2H), 1.96-1.52 (m, 10H), 1.45 (s, 3H), 1.32 (s, 9H), 1.21 (m, 4H), 1.05 (m, 1H).
Reaction SMILES: [O:1]=[C:2]1[N:6]([CH2:7][CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[C:5](=[CH:14][C:15]([C:17]2[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=2)=[O:16])[NH:4][C:3]1([CH2:32][C:33]1[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=1)[CH2:25][C:26]1[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=1.[CH3:39][N:40]([CH3:45])[S:41](Cl)(=[O:43])=[O:42]>>[CH3:39][N:40]([CH3:45])[S:41]([N:11]1[CH2:12][CH2:13][CH:8]([CH2:7][N:6]2[C:2](=[O:1])[C:3]([CH2:25][C:26]3[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=3)([CH2:32][C:33]3[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=3)[NH:4][C:5]2=[CH:14][C:15]([C:17]2[CH:18]=[CH:19][C:20]([C:21]#[N:22])=[CH:23][CH:24]=2)=[O:16])[CH2:9][CH2:10]1)(=[O:43])=[O:42]
Reactant: CN(C)S(=O)(=O)Cl
Reactant: N#Cc1ccc(C(=O)C=C2NC(Cc3ccncc3)(Cc3ccncc3)C(=O)N2CC2CCNCC2)cc1
Product: CN(C)S(=O)(=O)N1CCC(CN2C(=O)C(Cc3ccncc3)(Cc3ccncc3)NC2=CC(=O)c2ccc(C#N)cc2)CC1

Procedure:
According to the procedure of Example 13, the title compound of 40B (50 mg, 0.099 mmol) and N,N-dimethylsulfamyl chloride (0.025 ml, 0.237 mmol) were reacted to generate the title compound as a white solid (14 mg, 0.023 mmol, 19% yield).
Reaction SMILES: [F:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][C:7]([CH2:11][C:12]3[CH:17]=[C:16]([O:18][CH3:19])[C:15]([O:20][CH3:21])=[CH:14][C:13]=3[I:22])=[N:8]2)=[C:4]([NH2:23])[N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].S(C1C=CC(C)=CC=1)(O[CH2:34][CH2:35][CH2:36][C:37]#[CH:38])(=O)=O>CN(C=O)C>[F:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:11][C:12]3[CH:17]=[C:16]([O:18][CH3:19])[C:15]([O:20][CH3:21])=[CH:14][C:13]=3[I:22])[N:8]2[CH2:38][CH2:37][CH2:36][C:35]#[CH:34])=[C:4]([NH2:23])[N:3]=1
Reactant: C#CCCCOS(=O)(=O)c1ccc(C)cc1
Reactant: COc1cc(I)c(Cc2nc3nc(F)nc(N)c3[nH]2)cc1OC
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: C#CCCCn1c(Cc2cc(OC)c(OC)cc2I)nc2c(N)nc(F)nc21

Procedure:
A solution of 2-fluoro-8-(2-iodo-4,5-dimethoxy-benzyl)adenine (12 mg, 0.028 mmol), Cs2CO3 (9 mg, 0.028 mmol), pent-4-ynyl tosylate (8.6 mg, 7 L, 0.036 mmol) in anhydrous DMF (80 L) was stirred at 50° C. for 1 h. Following solvent removal, the product (13.7 mg, 99%) was collected through silica gel column purification (CHC13:EtOAc:hexanes:i-PrOH at 20:10:20:1). 1H NMR (400 MHz, CDC13) 7.27 (s, 1H), 6.65 (s, 1H), 5.94 (bs, 2H), 4.29 (s, 2H), 4.13 (t, J=7.3 Hz, 2H), 3.87 (s, 3H), 3.73 (s, 3H), 2.26-2.22 (m, 2H), 2.00 (t, J=2.6 Hz, 1H), 1.97-1.90 (m, 2H); 13C NMR (100 MHz, CDC13) 156.5, 153.2, 151.3, 150.0, 149.1, 130.9, 121.9, 112.6, 88.5, 82.5, 70.0, 56.4, 56.2, 42.6, 39.2, 28.4, 16.1; MS m/z 496.2 (M+H)+. HPLC: (a) 99.9% (60% water-40% acetonitrile); (b) 96.8% (35% to 55% acetonitrile).
Reaction SMILES: COC(/C=C/[C:7]1[CH:12]=[C:11](O)[C:10]2[O:14][CH:15](C3C=CC(O)=C(O)C=3)[CH:16](C(OC)=O)[C:9]=2[CH:8]=1)=O.[Br:29]N1C(=O)CCC1=O>C(#N)C>[Br:29][C:7]1[CH:12]=[CH:11][C:10]2[O:14][CH2:15][CH2:16][C:9]=2[CH:8]=1
Reactant: COC(=O)/C=C/c1cc(O)c2c(c1)C(C(=O)OC)C(c1ccc(O)c(O)c1)O2
Reactant: O=C1CCC(=O)N1Br
Solvent: CC#N
Product: Brc1ccc2c(c1)CCO2
Temperature: 25 °C
Reaction time: 3 h
Yield: 331.3 %

Procedure:
Dihydrobenzofuran (9.34 g) was dissolved in 130 ml of acetonitrile, 13.9 g of N-bromosuccinimide was added thereto and the mixture was stirred at room temperature for 3 hours. The solvent was evaporated, then the residue was dissolved in ethyl acetate and successively washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate and the solvent was removed, to give 15.94 g of the title compound.
Reaction SMILES: [CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[Br:11][C:12]1[CH:17]=[C:16](F)[CH:15]=[C:14]([F:19])[CH:13]=1>CC(N(C)C)=O>[Br:11][C:12]1[CH:17]=[C:16]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:15]=[C:14]([F:19])[CH:13]=1
Reactant: OCc1ccccc1
Reactant: Fc1cc(F)cc(Br)c1
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: Fc1cc(Br)cc(OCc2ccccc2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 75 %

Procedure:
A mixture of benzyl alcohol (10 g), sodium hydride (4.44 g of a 50% w/w dispersion in mineral oil) and dimethylacetamide (180 ml) was stirred at ambient temperature for 1 hour, 1-bromo-3,5-difluorobenzene (10.65 ml) was added and the exothermic reaction mixture was stirred for 2 hours. The mixture was evaporated and the organic layer was separated, washed with water, dried (MgSO4) and evaporated. The residue was purified by column chromatography using a 20:1 v/v mixture of petroleum ether (b.p. 60°-80° C.) and ethyl acetate as eluent. There was thus obtained, as a liquid, benzyl 3-bromo-5-fluorophenyl ether (19.5 g, 75%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[O:9][CH2:10][CH2:11][N:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[CH:4][CH:3]=1.Cl[CH2:26][CH2:27][CH2:28][C:29]([C:31]1[S:32][CH:33]=[CH:34][CH:35]=1)=[O:30].C(=O)([O-])[O-].[K+].[K+]>CC(CC(C)C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:18]2[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=2)[O:9][CH2:10][CH2:11][N:12]2[CH2:17][CH2:16][N:15]([CH2:26][CH2:27][CH2:28][C:29](=[O:30])[C:31]3[S:32][CH:33]=[CH:34][CH:35]=3)[CH2:14][CH2:13]2)=[CH:6][CH:7]=1
Reactant: O=C(CCCCl)c1cccs1
Reactant: Fc1ccc(C(OCCN2CCNCC2)c2ccc(F)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)CC(C)C
Product: O=C(CCCN1CCN(CCOC(c2ccc(F)cc2)c2ccc(F)cc2)CC1)c1cccs1

Procedure:
A mixture of 1.67 g (0.005 mol) 1-(2-[bis(4-fluorophenyl)-methoxy]ethyl)piperazine, (U.S. Pat. No. 1545094), 1.89 g (0.010 mol) 3-chloropropyl-2-thienyl ketone, 1.52 g (0.011 mol) potassium carbonate and 30 ml methylisobutyl ketone was stirred and heated to reflux for 45 h. The reaction mixture was then evaporated in vacuo. The residue was redissolved in dichloromethane (1 00 ml) and washed twice with water (100 ml). The organic layer was then separated and dried with sodium sulfate. Evaporation in vacuo left a brown syrup. This was redissolved in dry ether and precipitated as the dihydrochloride with gaseous hydrogen chloride. The precipitate was collected by filtration and recrystallized from isopropanol. White crystals, m.p. 185°-88° C. (0.98 g=35%).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.[F:11][C:12]([F:22])([F:21])[C:13]1[CH:20]=[CH:19][C:16]([CH:17]=O)=[CH:15][CH:14]=1.COC(OC)OC.[BH4-].[Na+]>CO>[F:11][C:12]([F:21])([F:22])[C:13]1[CH:20]=[CH:19][C:16]([CH2:17][NH:1][CH2:2][CH2:3][C:4]2[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=2)=[CH:15][CH:14]=1
Reactant: O=Cc1ccc(C(F)(F)F)cc1
Reactant: NCCc1ccc(O)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: COC(OC)OC
Solvent: CO
Product: Oc1ccc(CCNCc2ccc(C(F)(F)F)cc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 77.6 %

Procedure:
A suspension of tyramine (1 g; 7.29 mmol) in MeOH (8 ml) was treated with 4-trifluoromethyl benzaldehyde (1.27 g; 7.29 mmol) and trimethylorthoformate (5 ml). The reaction mixture was stirred at rt overnight and then treated with sodium borohydride (0.69 g; 18.23 mmol) in small portions. After stirring for 30 minutes, it was concentrated and partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated. Crystallization from ethyl ether-hexane provided the title compound as a white crystalline solid (1.67 g; 78% yield). 1H NMR (CDCl3) δ 7.54 (d, 2H, J=8.0), 7.37 (d, 2H, J=8.0), 7.00 (d, 2H, J=8.4), 6.68 (d, 2H, J=8.4), 4.50 (bs, 2H), 3.86 (s, 2H), 2.88 (t, 2H, J=6.9), 2.77 (t, 2H, J=6.9).
Reaction SMILES: Cl.[N:2]1[C:6]2[CH2:7][CH2:8][CH:9]([C:11](N3CCCC3)=[O:12])[CH2:10][C:5]=2[NH:4][CH:3]=1.ClC(Cl)C.[NH:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=[CH:23]1.P(Cl)(Cl)(Cl)=O>C(=O)([O-])[O-].[K+].[K+]>[NH:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]([C:11]([CH:9]2[CH2:8][CH2:7][C:6]3[N:2]=[CH:3][NH:4][C:5]=3[CH2:10]2)=[O:12])=[CH:23]1
Reactant: O=C(C1CCc2nc[nH]c2C1)N1CCCC1
Reactant: c1ccc2[nH]ccc2c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O=P(Cl)(Cl)Cl
Solvent: CC(Cl)Cl
Product: O=C(c1c[nH]c2ccccc12)C1CCc2nc[nH]c2C1
Reaction time: 7 h
Yield: 43.9 %

Procedure:
4 g of N-[(4,5,6,7-tetrahydrobenzimidazol-5-yl)carbonyl]pyrrolidine hydrochloride obtained in Example 5 were added to 40 ml of dichloroethane, and 2.74 g of indole and 4.4 ml of phosphorus oxychloride were added thereto. The mixture was stirred at 80° to 85° C. for 7 hours and then at room temperature overnight. To the mixture was added 40 ml of a cold potassium carbonate aqueous solution, followed by extraction with chloroform. The extract was dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was subjected to column chromatography using chloroform/methanol as an eluent to obtain 1.82 g of 5-[(indol-3-yl)carbonyl]-4,5,6,7-tetrahydrobenzimidazole as a foam-like substance. In 1 ml of methanol were dissolved 0.16 g of the resulting product and 0.06 g of fumaric acid, and 5 ml of acetonitrile was added to the solution. The formed crystal was collected by filtration to obtain 0.13 g of 5-[(indol- 3-yl)carbonyl]-4,5,6,7-tetrahydrobenzimidazole fumarate.
Reaction SMILES: [C:1]([CH:4]([CH2:10][C:11]([C:13]1[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][CH:14]=1)=O)[C:5]([O:7][CH2:8][CH3:9])=[O:6])(=O)[CH3:2].[NH2:20][C:21]1[CH:26]=[CH:25][C:24]([S:27]([NH2:30])(=[O:29])=[O:28])=[CH:23][CH:22]=1>C(O)(=O)C>[NH2:30][S:27]([C:24]1[CH:23]=[CH:22][C:21]([N:20]2[C:11]([C:13]3[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][CH:14]=3)=[CH:10][C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])=[C:1]2[CH3:2])=[CH:26][CH:25]=1)(=[O:28])=[O:29]
Reactant: CCOC(=O)C(CC(=O)c1ccc(Br)cc1)C(C)=O
Reactant: Nc1ccc(S(N)(=O)=O)cc1
Solvent: CC(=O)O
Product: CCOC(=O)c1cc(-c2ccc(Br)cc2)n(-c2ccc(S(N)(=O)=O)cc2)c1C

Procedure:
A mixture of Example 1A (3.3 g, 10.1 mmol) and 4-aminobenzenesulfonamide (1.74 g, 10.1 mmol) in glacial acetic acid (75 mL) was heated to 100° C. for 48 hours. After cooling the mixture was concentrated under reduced pressure. Ether (50 mL) was added to the residue and the precipitate was isolated by filtration. The pale yellow solid was washed with ether and dried. 1H NMR (CDCl3) δ ppm 1.32 (3H), 2.20 (3H), 3.50 (2H), 4.27 (2H), 6.85 (1H), 7.30-7.90 (8H); MS (ESI) m/z m/z 462/464.
Reaction SMILES: [C:1]([O:5][C:6](=[O:26])[NH:7][C:8]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:12][CH2:11][N:10](CC2C=CC=CC=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[H][H]>CO.[Pd]>[C:1]([O:5][C:6](=[O:26])[NH:7][C:8]1([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:12][CH2:11][NH:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)NC1(c2ccccc2)CCN(Cc2ccccc2)C1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)NC1(c2ccccc2)CCNC1
Yield: 99.9 %

Procedure:
(1-Benzyl-3-phenylpyrrolidin-3-yl)carbamic acid tert-butyl ester (Hagen S. E., Domagala J. M., Heifetz C. L., Sanchez J. P., Solomon M., J. Med. Chem., 1990; 33(2):849-854) (2.79 g, 7.9 mmol) in 100 mL of methanol is treated with 1.0 g of 20% Pd/C and shaken for 17 hours under 50 psi of hydrogen. The solution is filtered and concentrated to afford 2.07 g of the title compound as a foam; MS EI+: m/z 263 (MH+).
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([NH2:15])=[N:12][O:13][N:14]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:23][C:24](=[O:33])[CH:25]=[CH:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CN(C=O)C.C(OCC)(=O)C>[NH2:15][C:11]1[C:10]([C:2]2[N:1]([CH2:23][C:24](=[O:33])/[CH:25]=[CH:26]/[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=2)=[N:14][O:13][N:12]=1
Reactant: Nc1nonc1-c1nc2ccccc2[nH]1
Reactant: O=C(C=Cc1ccccc1)CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Nc1nonc1-c1nc2ccccc2n1CC(=O)/C=C/c1ccccc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A suspension of 4-(1H-benzimidazol-2-yl)-furazan-3-ylamine (0.275 g, 1.37 mmol), potassium carbonate (0.472 g, 3.42 mmol) and 1-chloro-4-phenyl-but-3-en-2-one (0.297 g, 1.64 mmol) in DMF (5 ml) is stirred at room temperature for 16 hours. The reaction mixture is diluted with ethyl acetate, washed with water and dried over sodium sulphate. Filtration of the sodium sulphate, concentration of the filtrate under reduced pressure and chromatography of the residue on silicagel using hexane-ethyl acetate as eluent gives the title compound as a yellowish solid, m.p. 176-180° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[CH:4]([NH:15][CH:16]=[O:17])[CH:5](O)[C:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[CH2:7].S(Br)(Br)=O.[P:23]([O:30]CC)([O:27][CH2:28][CH3:29])[O:24][CH2:25][CH3:26]>C(OCC)(=O)C.CCCCCC>[CH3:1][O:2][C:3](=[O:18])[CH:4]([NH:15][CH:16]=[O:17])/[CH:5]=[C:6](\[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)/[CH2:7][P:23]([O:27][CH2:28][CH3:29])([O:24][CH2:25][CH3:26])=[O:30]
Reactant: CCOP(OCC)OCC
Reactant: C=C(c1ccccc1)C(O)C(NC=O)C(=O)OC
Agent: O=S(Br)Br
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CCOP(=O)(C/C(=C/C(NC=O)C(=O)OC)c1ccccc1)OCC

Procedure:
By reaction of the 2-formylamino-3-hydroxy-4-phenyl-4-pentenoic acid methyl ester with thionyl bromide and subsequent treatment with triethyl phosphite in a manner analogous to that described in Example 1, and after chromatography (silica gel; ethyl acetate/hexane 4:1), E-2-formylamino-4-phenyl-5-diethylphosphono-3-pentenoic acid methyl ester is obtained in the form of a colourless oil. 1H-NMR (CDCl3): 2.98 (d, 2H,C(5)-H); 5.03 (dd, 1H, C(2)-H); 5.77 (dd, 1H, C(3)-H).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=2[S:16]([N:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)(=[O:18])=[O:17])[C:5]([Cl:24])=[CH:4][N:3]=1.[CH3:25][N:26]1[CH2:31][CH2:30][N:29]([CH2:32][C:33]2[CH:39]=[CH:38][C:36]([NH2:37])=[CH:35][CH:34]=2)[CH2:28][CH2:27]1>C(Cl)Cl.CO>[Cl:24][C:5]1[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=2[S:16]([N:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)(=[O:18])=[O:17])=[N:7][C:2]([NH:37][C:36]2[CH:35]=[CH:34][C:33]([CH2:32][N:29]3[CH2:28][CH2:27][N:26]([CH3:25])[CH2:31][CH2:30]3)=[CH:39][CH:38]=2)=[N:3][CH:4]=1
Reactant: CN1CCN(Cc2ccc(N)cc2)CC1
Reactant: O=S(=O)(c1cc(O)ccc1Nc1nc(Cl)ncc1Cl)N1CCCC1
Solvent: ClCCl
Solvent: CO
Product: CN1CCN(Cc2ccc(Nc3ncc(Cl)c(Nc4ccc(O)cc4S(=O)(=O)N4CCCC4)n3)cc2)CC1
Yield: 27 %

Procedure:
The title compound was prepared according to synthesis procedure B described above from 4-((2,5-dichloropyrimidin-4-yl)amino)-3-(pyrrolidin-1-ylsulfonyl)phenol and 4-((4-methylpiperazin-1-yl)methyl)aniline in 27% yield (yellow solid) after flash chromatography (CH2Cl2/CH3OH 99:1 gradually increasing to 95:5). 1H NMR (400 MHz, CDCl3): δ 8.08 (s, 1H), 7.87 (d, 1H, J=8.4 Hz), 7.67 (s, 1H), 7.44 (d, 2H, J=8.1 Hz), 7.26 (1H), 7.23 (d, 2H, J=8.4 Hz), 7.10 (d, 1H, J=8.8 Hz), 3.53 (s, 2H), 3.33 (m, 4H), 2.63 (bs, 8H), 2.43 (s, 3H), 1.83 (m, 4H); MS (ESI): 558.1 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]=O)=[CH:7][CH:8]=1.[C:11]([C:14]1[CH:19]=[CH:18][C:17]([S:20]([NH2:23])(=[O:22])=[O:21])=[CH:16][CH:15]=1)([OH:13])=[O:12].CC1C=CC(S(O)(=O)=O)=CC=1>ClC1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]=[N:23][S:20]([C:17]2[CH:16]=[CH:15][C:14]([C:11]([OH:13])=[O:12])=[CH:19][CH:18]=2)(=[O:21])=[O:22])=[CH:5][CH:4]=1
Reactant: COc1ccc(C=O)cc1
Reactant: NS(=O)(=O)c1ccc(C(=O)O)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Clc1ccccc1
Product: COc1ccc(C=NS(=O)(=O)c2ccc(C(=O)O)cc2)cc1

Procedure:
In a similar manner to Example 2, 1.28 g (9 mmol) of anisaldehyde, 1.89 g (9 mmol) of 4-carboxybenzenesulfonamide and 20 mg of TsOH in 150 mL of chlorobenzene and under nitrogen were heated for 4.5 hours to yield 2.86 g (96%) of SULF-8 as a white powder: IR (Nujol) 3300-2700 (br), 1693, 1601, 1584, 1155 cm-1 ; 1H NMR (DMSO-d6, TMS ext std) δ 8.91 (s, 1), 8.4-7.7 (m, 8), 3.92 (s, 3).