Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: S(Cl)([Cl:3])=O.[CH2:5]([O:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[O:21][CH3:22])[CH2:16]O)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>ClCCl>[CH2:5]([O:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][C:20]=1[O:21][CH3:22])[CH2:16][Cl:3])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: O=S(Cl)Cl
Reactant: COc1ccc(CO)cc1OCc1ccccc1
Solvent: ClCCl
Product: COc1ccc(CCl)cc1OCc1ccccc1
Yield: 105.5 %

Procedure:
Thionyl chloride (64 ml) was added over 10 minutes to a stirred solution of the above alcohol in dichloromethane (500 ml). After 20 minutes the mixture was evaporated to dryness, in vacuo, toluene (2×75 ml) added, and evaporation in vacuo repeated to give crude 3-benzyloxy-4-methoxy-benzyl chloride (97.85 g, 105.5%). The chloride (353 mmole) was dissolved in acetone, (400 ml) treated with sodium thiocyanate, (57.22 g ,706 mmole) homogenized and heated under reflux for 1.5 hours. The solid was filtered off at room temperature and the solvent evaporated in vacuo. The residue was suspended in water (600 ml) to give a solution of pH 2, and neutralized with sodium bicarbonate solution. After crystallization the solid was collected, dried, dissolved in dichloromethane (300 ml) , dried (Na2SO4), treated with charcoal, filtered and evaporated to dryness. The residue was crystallized from petroleum ether (400 ml) to give 3-benzyloxy-4-methoxy-benzyl thiocyanate (95.65 g, 95.0%), mp 70-74° C. The thiocyanate (335 mmole) was heated under reflux in n-valeronitrile (280ml) for 2 hours and evaporated to dryness to give 98.4 g of crude product. This was dissolved in THF (200 ml) and treated with 32% aqueous ammonia solution (101 ml) at room temperature. After 3 hours the thiourea was collected at 10° C. and washed with diethyl ether to give 1-(3-benzyloxy-4-methoxy-benzyl)-2-thiourea (63.08 g, 62.2%), mp 179-181° C. The filtrate was evaporated to dryness and the residue crystallized from dichloromethane to give 11.51 g (11.3%) as a second crop.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[OH:9].[CH:10](=O)/[CH:11]=[CH:12]/[CH3:13].[NH4+].[OH-]>Cl>[F:8][C:5]1[CH:6]=[C:7]2[C:2](=[C:3]([OH:9])[CH:4]=1)[N:1]=[C:12]([CH3:13])[CH:11]=[CH:10]2
Reactant: Nc1ccc(F)cc1O
Reactant: C/C=C/C=O
Agent: Cl
Agent: [NH4+]
Agent: [OH-]
Product: Cc1ccc2cc(F)cc(O)c2n1
Yield: 82.5 %

Procedure:
To 2-amino-5-fluorophenol (5.0 g, 39 mmol) in refluxing 6N HCl (50 mL) was added dropwise over 10 minutes (E)-but-2-enal (5.5 g, 79 mmol). The reaction was heated to reflux for 3 hours then cooled down and neutralized (pH=7-8) by addition of NH4OH. The aqueous phase was extracted with DCM. The combined organic phases were dried over MgSO4, filtered and concentrated to yield 6-fluoro-2-methylquinolin-8-ol (5.7 g, 82% yield) as a dark oil which solidified upon standing.
Reaction SMILES: [Cl:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:11]=[N:12][C:13]3[C:18]([C:19]=2[OH:20])=[CH:17][C:16](I)=[CH:15][CH:14]=3)=[O:9])=[CH:4][CH:3]=1.CN(C=O)C.[CH2:29]([OH:32])[C:30]#[CH:31]>N(CC)CC.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:11]=[N:12][C:13]3[C:18]([C:19]=2[OH:20])=[CH:17][C:16]([C:31]#[C:30][CH2:29][OH:32])=[CH:15][CH:14]=3)=[O:9])=[CH:4][CH:3]=1
Reactant: C#CCO
Reactant: O=C(NCc1ccc(Cl)cc1)c1cnc2ccc(I)cc2c1O
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCNCC
Solvent: CN(C)C=O
Product: O=C(NCc1ccc(Cl)cc1)c1cnc2ccc(C#CCO)cc2c1O
Temperature: 25 °C
Reaction time: 48 h
Yield: 79 %

Procedure:
To a mixture of N-(4-chlorobenzyl)-4-hydroxy-6-iodo-3-quinolinecarboxamide from Preparation No. 4 (0.494 g) in Et2NH (12.9 mL) is added CuI (10.8 mg) and (Ph3P)2PdCl2 (39.7 mg). DMF (2 mL) is added to solubilize the reactants. To this solution is added propargyl alcohol (0.066 mL) and the reaction is stirred at room temperature for 2 days. The reaction mixture is concentrated to remove Et2NH. The resulting residue is partitioned between CH2Cl2 (3×) and H2O. A brown solid precipitated from the CH2Cl2 layer is filtered and collected to obtain pure product as indicated by NMR. The organic layers are combined, dried over Na2SO4, and concentrateed to obtain a brown residue. The residue is placed under high vac to remove residual DMF. The residue is adsorbed onto silica and chromatographed eluting with 2% MeOH in CH2C12 and 3% MeOH in CH2Cl2. Fractions homogenous by TLC are combined, condensed and recrystallized with EtOAc/hexanes to obtain a creme solid. The two crops yielded 325.4 mg (79%) of the desired product as a tan solid.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.N1C=CN=C1.[Si:14](Cl)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15].O>C1COCC1>[Si:14]([O:8][C:5]1[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: Nc1ccc(O)cc1
Agent: c1c[nH]cn1
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)Oc1ccc(N)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 67.1 %

Procedure:
To a solution of 4-aminophenol (11 g, 100 mmol) and imidazole (10 g, 150 mmol) in THF (250 mL) was added tert-butyldimethylsilyl chloride (18 g, 120 mmol) and the reaction was stirred at room temperature for 18 h. The reaction mixture was poured into water and extracted with diethyl ether. The combined organic layers were dried over Na2SO4, filtered, concentrated and the residue was purified by column chromatography to afford the desired product (15 g, 67%): ESI MS m/z 224 [C12H21NOSi+H]+.
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][C:6]([CH3:9])([CH3:8])[N:5]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[C:4]([CH3:20])([CH3:19])[CH2:3]1.[C:21]([C:26]([C:55]([O:57]CC)=O)=[C:27]1[NH:32][C:31](=[C:33]([C:39](OCC)=[O:40])[C:34](OCC)=[O:35])[NH:30][C:29](=[C:44]([C:50](OCC)=[O:51])[C:45](OCC)=[O:46])[NH:28]1)(OCC)=[O:22]>>[CH2:11]([O:10][N:5]1[C:6]([CH3:8])([CH3:9])[CH2:7][CH:2]([NH:1][C:21]([C:26]([C:55]([NH:1][CH:2]2[CH2:7][C:6]([CH3:8])([CH3:9])[N:5]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[C:4]([CH3:19])([CH3:20])[CH2:3]2)=[O:57])=[C:27]2[NH:28][C:29](=[C:44]([C:45]([NH:1][CH:2]3[CH2:7][C:6]([CH3:8])([CH3:9])[N:5]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[C:4]([CH3:19])([CH3:20])[CH2:3]3)=[O:46])[C:50]([NH:1][CH:2]3[CH2:7][C:6]([CH3:8])([CH3:9])[N:5]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[C:4]([CH3:19])([CH3:20])[CH2:3]3)=[O:51])[NH:30][C:31](=[C:33]([C:39]([NH:1][CH:2]3[CH2:7][C:6]([CH3:8])([CH3:9])[N:5]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[C:4]([CH3:19])([CH3:20])[CH2:3]3)=[O:40])[C:34]([NH:1][CH:2]3[CH2:7][C:6]([CH3:8])([CH3:9])[N:5]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[C:4]([CH3:19])([CH3:20])[CH2:3]3)=[O:35])[NH:32]2)=[O:22])[CH2:3][C:4]1([CH3:19])[CH3:20])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCCON1C(C)(C)CC(N)CC1(C)C
Reactant: CCOC(=O)C(C(=O)OCC)=C1NC(=C(C(=O)OCC)C(=O)OCC)NC(=C(C(=O)OCC)C(=O)OCC)N1
Product: CCCCCCCCON1C(C)(C)CC(NC(=O)C(C(=O)NC2CC(C)(C)N(OCCCCCCCC)C(C)(C)C2)=C2NC(=C(C(=O)NC3CC(C)(C)N(OCCCCCCCC)C(C)(C)C3)C(=O)NC3CC(C)(C)N(OCCCCCCCC)C(C)(C)C3)NC(=C(C(=O)NC3CC(C)(C)N(OCCCCCCCC)C(C)(C)C3)C(=O)NC3CC(C)(C)N(OCCCCCCCC)C(C)(C)C3)N2)CC1(C)C

Procedure:
The title compound is prepared from 4-amino-1-octyloxy-2,2,6,6-tetramethylpiperidine and 2,4,6-tris(dicarbethoxymethylene) hexahydro-1,3,5-triazine according to the general procedure of Example 1.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=1)#[CH:2].C([Mg]Br)C.[CH3:13][C:14]1([CH3:23])[CH2:19][C:18]([CH3:21])([CH3:20])[CH2:17][C:16](=[O:22])[CH2:15]1.C(OCC)(=O)C>C1COCC1>[CH3:20][C:18]1([CH3:21])[CH2:19][C:14]([CH3:23])([CH3:13])[CH2:15][C:16]([C:2]#[C:1][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][N:4]=2)([OH:22])[CH2:17]1
Reactant: C#Cc1ccccn1
Reactant: CC1(C)CC(=O)CC(C)(C)C1
Agent: CC[Mg]Br
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC1(C)CC(C)(C)CC(O)(C#Cc2ccccn2)C1
Temperature: 25 °C
Yield: 9.7 %

Procedure:
To a solution of 2-ethynylpyridine (1.0 g, 10 mmol) in TMF at −78° C. was added a 1.0 M solution of ethyl magnesium bromide in THF (10 mL, 10 mmol). After stirring at reduced temperature for 30 minutes a solution of 3,3,5,5-tetramethylcyclohexanone (1.5 g, 10 mmol) in THF was added rapidly. The mixture was allowed to warm to ambient temperature over 16 hours, then partitioned between water and ethyl acetate. The organic layer was dried over anhydrous Na2SO4, and concentrated in vacuo. The resultant product was purified by flash column chromatography on silica gel eluting with 1:1 hexane:ethyl acetate to afford 3,3,5,5-tetramethyl-1-(2-pyridinylethynyl)cyclohexanol (250 mg, 10% yield) as a white solid. M.p. 126-127° C. 1H NMR (DMSO-d6, 300 MHz) δ 8.57 (m, 1H), 7.64 (m, 1H), 7.39 (d, J=5 Hz, 1H), 7.22 (m, 1H), 1.91 (d, J=9 Hz, 2H), 1.71 (d, J=9 Hz, 2H), 1.26 (s, 2H), 1.14 (s, 6H), 1.09 (s, 6H).
Reaction SMILES: [CH3:1][N:2]([CH2:6][CH2:7][N:8]([CH3:21])[C:9]1[S:10][C:11]2[CH:17]=[C:16]([N+:18]([O-])=O)[CH:15]=[CH:14][C:12]=2[N:13]=1)[C:3](=[O:5])[CH3:4]>C(O)C.C1COCC1.[Pd]>[NH2:18][C:16]1[CH:15]=[CH:14][C:12]2[N:13]=[C:9]([N:8]([CH3:21])[CH2:7][CH2:6][N:2]([CH3:1])[C:3](=[O:5])[CH3:4])[S:10][C:11]=2[CH:17]=1
Reactant: CC(=O)N(C)CCN(C)c1nc2ccc([N+](=O)[O-])cc2s1
Agent: [Pd]
Solvent: CCO
Solvent: C1CCOC1
Product: CC(=O)N(C)CCN(C)c1nc2ccc(N)cc2s1
Yield: 77.2 %

Procedure:
Shake a mixture of N-methyl-N-{2-[methyl-(6-nitro-benzothiazol-2-yl)-amino]-ethyl}-acetamide (0.30 g, mmol) and Pd/C (5%, 0.1515 g) in absolute ethanol (50 mL) and anhydrous THF (20 mL) under 60 psi H2(g) at room temperature for 18 h. Filter the mixture and concentrate in vacuo. Residue re-subjected to hydrogenation using Pd/C (0.2101 g) in absolute ethanol (50 mL) and THF (10 mL) to yield the desired product (0.209 g). Adsorb onto silica gel and subject to silica gel flash column chromatography (12 g column, eluting with 1-5% MeOH/CH2Cl2). Adsorbed on a Silicycle cartridge (Si-Tosic Acid, 35 mL, 10 g) washing with MeOH and eluted with 2N NH3 in MeOH. The product is 70% pure by LC-MS (0.146 g, %). mass spectrum (m/e): 279.0 (M+1). Used without further purification.
Reaction SMILES: [C:1]1([CH2:7][C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:11][C:12]1(C)[O:17]C(=O)[CH2:15][C:14](=O)[O:13]1.N1C=CC=CC=1>C(Cl)Cl>[O:9]=[C:8]([CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH2:11][C:12]([O:13][CH2:14][CH3:15])=[O:17]
Reactant: CC1(C)OC(=O)CC(=O)O1
Reactant: O=C(Cl)Cc1ccccc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCOC(=O)CC(=O)Cc1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 38.5 %

Procedure:
To a solution of phenylacetyl chloride (1 mL, 7.56 mmol) was added dropwise a solution of 2,2-dimethyl-1,3-dioxane-4,6-dione (1.09 g, 7.56 mmol) and pyridine (1.3 mL) in CH2Cl2 (20 mL) at 0° C. The solution was stirred for 30 min at 0° C., then allowed to warm slowly to rt and stirred overnight. The reaction mixture was then washed with 10% aqueous HCl (2×10 mL). The organic layer was dried (MgSO4), filtered, and concentrated under reduced pressure. The crude residue was dissolved in EtOH (20 mL) and heated under reflux conditions for 4 h. The mixture was cooled to rt and then concentrated under reduced pressure. The resulting oil was purified by flash column chromatography (PE/EA=1/4) to afford the title compound (600 mg, 38%) as a yellow oil. [M+H] Calc'd for C12H14O3, 207. Found, 207.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[NH:9][C:10]([NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:25][CH2:26][CH:27]3[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]3)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][N:14]=1)=S.[NH2:34][CH2:35][CH2:36][OH:37].C(Cl)(Cl)Cl>CO>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[NH:9][C:10]([NH:34][CH2:35][CH2:36][OH:37])=[N:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:25][CH2:26][CH:27]3[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]3)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][N:14]=1
Reactant: NCCO
Reactant: COc1cc2c(NC(=S)Nc3c(C)cccc3Cl)ncnc2cc1OCC1CCN(C)CC1
Solvent: CO
Solvent: ClC(Cl)Cl
Product: COc1cc2c(N=C(NCCO)Nc3c(C)cccc3Cl)ncnc2cc1OCC1CCN(C)CC1

Procedure:
Mercuric(II) oxide (0.107 g) was added to a mixture of 1-(2-chloro-6-methylphenyl)-3-[6-methoxy-7-(N-methylpiperidin-4-ylmethoxy)quinazolin-4-yl]thiourea (0.118 g), 2-aminoethanol (0.03 ml), chloroform (5 ml) and methanol (5 ml) and the resultant mixture was stirred at ambient temperature for 2 hours. The reaction mixture was filtered and the filtrate was evaporated. The residue was purified by column chromatography on silica using increasingly polar mixtures of methylene chloride and a 2M solution of ammonia gas in methanol as eluent. There was thus obtained the title compound (0.128 g); NMR Spectrum: (DMSOd6+CD3CO2D) 1.47–1.62 (m, 2H), 1.85–2.11 (m, 5H), 2.29 (s, 3H), 2.67 (s, 3H), 2.87 (t, 2H), 3.33 (d, 2H), 3.59 (t, 4H), 3.79 (s, 3H), 4.0 (d, 2H), 7.08 (s, 1H), 7.19–7.32 (m, 3H), 7.4 (d, 1H), 8.43 (s, 1H), 10.5 (br s, 1H); Mass Spectrum: M+H+ 513 and 515.
Reaction SMILES: [CH:1]([NH:4][C:5]1[CH:12]=[CH:11][CH:10]=[CH:9][C:6]=1[CH:7]=O)([CH3:3])[CH3:2].[C:13](OCC)(=[O:20])[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16].C(=O)(O)[O-].[Na+]>C(OC(=O)C)(=O)C>[CH:1]([N:4]1[C:5]2[C:6](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:13]1=[O:20])([CH3:3])[CH3:2]
Reactant: CC(C)Nc1ccccc1C=O
Reactant: CCOC(=O)CC(=O)OCC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)OC(C)=O
Product: CCOC(=O)c1cc2ccccc2n(C(C)C)c1=O
Temperature: 100 °C
Yield: 61.3 %

Procedure:
A solution of 7.5 g of 2-isopropylaminobenzaldehyde, 11.0 g of diethyl malonate and 11.6 g of sodium bicarbonate in 800 ml of acetic anhydride was stirred under heating at 100° C. for 15 hours. After evaporation of the solvent under reduced pressure, water was added, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium bicarbonate solution and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting oily substance was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1) to give 7.3 g of ethyl 1-isopropyl-2(1H)-quinolone-3-carboxylate.
Reaction SMILES: O[CH:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[C:12]([CH3:13])[C:7]=2[CH:6]=[CH:5][C:4]2[CH:14]=[CH:15][CH:16]=[CH:17][C:3]1=2.S(Cl)([Cl:20])=O>C1C=CC=CC=1>[Cl:20][CH:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[C:12]([CH3:13])[C:7]=2[CH:6]=[CH:5][C:4]2[CH:14]=[CH:15][CH:16]=[CH:17][C:3]1=2
Reactant: O=S(Cl)Cl
Reactant: Cc1cccc2c1C=Cc1ccccc1C2O
Solvent: c1ccccc1
Product: Cc1cccc2c1C=Cc1ccccc1C2Cl

Procedure:
23 g. of 5-Hydroxy-1-methyl-5H-dibenzo[a,d]cycloheptene in 200 ml. of absolute benzene are heated with 45 ml. of thionylchloride for two hours under reflux conditions. The mixture is subsequently evaporated under reduced pressure. The resulting, white crystalline residue is recrystallized from carbon tetrachloride. 5-Chloro-1-methyl-5H-dibenzo[a,d]cycloheptene, melting at 158°-160°C., is obtained.
Reaction SMILES: [CH2:1]([C:4]1([CH3:15])[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][CH2:6][C:5]1=[O:14])[CH:2]=[CH2:3].[CH3:16]OC(OC)OC.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[CH3:16][O:14][C:5]1[C:4]([CH2:1][CH:2]=[CH2:3])([CH3:15])[C:13]2[C:8]([CH2:7][CH:6]=1)=[CH:9][CH:10]=[CH:11][CH:12]=2
Reactant: C=CCC1(C)C(=O)CCc2ccccc21
Reactant: COC(OC)OC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Solvent: O
Product: C=CCC1(C)C(OC)=CCc2ccccc21
Temperature: 25 °C
Yield: 73 %

Procedure:
To a solution of Example 123A (10.1 g, 50.5 mmol), trimethylorthoformate (20 mL), p-toluenesulfonic acid monohydrate (60 mg, 0.315 mmol) in methanol (100 mL) was heated at 60 C for 2 hours. After cooling to room temperature, the solution was concentrated in vacuo, and the resultant residue was purified by column chromatography employing 70-230 mesh silica gel eluting with hexane to provide the title compound as a colorless oil (7.8 g, 73%). 1H NMR (300 MHz, DMSO-d6): δ 1.38 (s, 3 H), 2.44 (dd, J=13.8, 7.4 Hz, 1H), 2.65 (dd, J=13.6, 7.0 Hz, 1 H), 3.41 (d, J=3.7 Hz, 2 H), 3.54 (s, 3 H), 4.75 m, 2 H), 4.90 (t, J=3.7 Hz, 1 H), 5.24 m, 1 H), 7.10 m, 2 H), 7.19 m, 1 H), 7.40 (d, J=7.8 Hz, 1 H).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([CH:18]([C:37]2[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][CH:38]=2)[N:19]2[CH2:22][C:21](=[CH:23][S:24]([CH2:27][C:28]3[CH:29]=[C:30]([CH:34]=[CH:35][CH:36]=3)[C:31](O)=[O:32])(=[O:26])=[O:25])[CH2:20]2)=[CH:14][CH:13]=1>ClCCl>[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([CH:18]([C:37]2[CH:38]=[CH:39][C:40]([Cl:43])=[CH:41][CH:42]=2)[N:19]2[CH2:22][C:21](=[CH:23][S:24]([CH2:27][C:28]3[CH:29]=[C:30]([CH:34]=[CH:35][CH:36]=3)[C:31]([NH:1][CH2:2][CH2:3][CH2:4][N:5]3[CH2:10][CH2:9][O:8][CH2:7][CH2:6]3)=[O:32])(=[O:26])=[O:25])[CH2:20]2)=[CH:14][CH:13]=1
Reactant: NCCCN1CCOCC1
Reactant: O=C(O)c1cccc(CS(=O)(=O)C=C2CN(C(c3ccc(Cl)cc3)c3ccc(Cl)cc3)C2)c1
Solvent: ClCCl
Product: O=C(NCCCN1CCOCC1)c1cccc(CS(=O)(=O)C=C2CN(C(c3ccc(Cl)cc3)c3ccc(Cl)cc3)C2)c1
Reaction time: 1.5 h

Procedure:
0.0388 cm3 of N-(3-aminopropyl)morpholine is added, at the same temperature, to a suspension of 150 mg of 3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}methanesulfonylmethyl)benzoic acid activated on TFP resin (165 μM) in 3 cm3 of dichloromethane, pre-stirred for 90 minutes at a temperature close to 20° C. The suspension is stirred at a temperature close to 20° C. for 22 hours and then filtered on sintered glass. The solid residue is rewashed with twice 1.5 cm3 of dichloromethane. The filtrates are combined and concentrated to dryness under reduced pressure (2.7 kPa) at a temperature close to 40° C. 60 mg of 3-({1-[bis(4-chlorophenyl)methyl]azetidin-3-ylidene}methanesulfonylmethyl)-N-(3-morpholin-4-ylpropyl)benzamide are thus obtained in the form of a pale yellow foam.
Reaction SMILES: [CH3:1][C:2]([CH3:9])([CH3:8])[C:3]#[C:4][CH2:5][CH2:6]O.C(N(CC)CC)C.CS(Cl)(=O)=O.[CH3:22][NH:23][CH2:24][C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=[CH:27][CH:26]=1>CN(C)C=O>[CH3:22][N:23]([CH2:24][C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=[CH:27][CH:26]=1)[CH2:6][CH2:5][C:4]#[C:3][C:2]([CH3:9])([CH3:8])[CH3:1]
Reactant: CNCc1cccc2ccccc12
Reactant: CC(C)(C)C#CCCO
Agent: CS(=O)(=O)Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CN(CCC#CC(C)(C)C)Cc1cccc2ccccc12

Procedure:
To a solution of 540 mg 5,5-dimethyl-3-hexyn-1-ol in dimethylformamide (DMF) are added, at 0° 1.2 ml triethylamine. Then are added, dropwise, with stirring, 0.335 ml methanesulfonylchloride. After 2 hours of stirring at room temperature are added 740 mg N-methyl-1-naphthylmethylamine and the mixture is heated overnight at 80°. The solvent is evaporated in vacuum, the residue distributed between saturated aqueous NaHCO3 solution and ethyl acetate, the organic phase washed, dried and evaporated. The crude residue is chromatographed over silicagel (with toluene/ethylacetate 9/1) and the title compound (Compound 1) obtained as an oil.
Reaction SMILES: [NH2:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[O:4][CH2:5][CH2:6][CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9].[CH:17]([S:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][C:32](O)=[O:33])([CH3:19])[CH3:18].C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl.CN(C)C1C=CN=CC=1>[CH:17]([S:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][C:32]([NH:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[O:4][CH2:5][CH2:6][CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])=[O:33])([CH3:19])[CH3:18]
Reactant: CC(C)SCCCCCCCCCCCC(=O)O
Reactant: CCOC(=O)CCCOc1ccccc1N
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CCOC(=O)CCCOc1ccccc1NC(=O)CCCCCCCCCCCSC(C)C
Reaction time: 48 h
Yield: 45.9 %

Procedure:
To a solution of (4) (0.25 g, 1.14 mM) and (6) (0.274 g, 1.0 mM) in dry methylene chloride (10 mL) at room temperature was added 4-dimethylamino-pyridine (0.122 g, 1.0 mM) followed within one minute by a solution of N,N'-dicyclohexylcarbodiimide (0.22 g, 1.06 mM) in methylene chloride (1 mL), 3×1 mL rinses with methylene chloride. After 2 days, the filtered mixture was concentrated in vacuo and the residue flash chromatographed on silica gel using 15-20% ethyl acetate in hexane as eluant to give product 7 (0.22 g) as an oil that solidified readily in a short time.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C@@H:12](/[CH:13]=[CH:14]/[C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-])=O)=[CH:17][CH:16]=2)[CH2:11][O:10][C:9]1([CH3:25])[CH3:24])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])=O.[NH4+]>CO.[Pd]>[C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH2:13][CH2:14][C:15]2[CH:16]=[CH:17][C:18]([NH2:21])=[CH:19][CH:20]=2)[CH2:11][O:10][C:9]1([CH3:25])[CH3:24])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1[C@@H](/C=C/c2ccc([N+](=O)[O-])cc2)COC1(C)C
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CO
Product: CC(C)(C)OC(=O)N1[C@@H](CCc2ccc(N)cc2)COC1(C)C
Temperature: 60 °C
Yield: 82.6 %

Procedure:
To a stirred suspension of (S)-2,2-dimethyl-4-[(E)-2-(4-nitro-phenyl)-vinyl]-oxazolidine-3-carboxylic acid tert-butyl ester (2.08 g) in methanol (140 ml) were added ammonium formate (5.66 g) and palladium on charcoal (0.51 g, 10 wt %) and the mixture was heated at 60° C. for 90 min. The mixture was then cooled to room temperature, filtered through celite and the filtrate was concentrated in vacuo. The residue was purified by column chromatography (SiO2; gradient: heptane/EtOAc) to give (S)-4-[2-(4-amino-phenyl)-ethyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (1.58 g, 82%) as a yellow oil. MS (ISP): 321.4 ([M+H]+).
Reaction SMILES: [O:1]=[C:2]1[NH:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:16]=[CH:15][C:10]([C:11]([O:13][CH3:14])=[O:12])=[CH:9][CH:8]=1.[H-].[Na+].Br[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([CH3:30])([CH3:29])[CH3:28])=[CH:23][CH:22]=1>CN(C)C=O>[C:27]([C:24]1[CH:23]=[CH:22][C:21]([CH2:20][N:6]2[CH2:5][CH2:4][N:3]([C:7]3[CH:8]=[CH:9][C:10]([C:11]([O:13][CH3:14])=[O:12])=[CH:15][CH:16]=3)[C:2]2=[O:1])=[CH:26][CH:25]=1)([CH3:30])([CH3:28])[CH3:29]
Reactant: COC(=O)c1ccc(N2CCNC2=O)cc1
Reactant: CC(C)(C)c1ccc(CBr)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(N2CCN(Cc3ccc(C(C)(C)C)cc3)C2=O)cc1
Reaction time: 1 h
Yield: 80.9 %

Procedure:
To a solution of methyl 4-(2-oxoimidazolidin-1-yl)benzoate (440 mg, 2.0 mmol) in N,N-dimethylformamide (10 ml) at 0° C. was added sodium hydride (96 mg-60% in oil, 2.4 mmole). The resulting mixture was stirred for 1 hour followed by addition of 1-(bromomethyl)-4-tert-butylbenzene (545 mg, 2.4 mmol). After stirring 24 hours at room temperature, the mixture was quenched with 1 ml water and the solvents were removed under reduced pressure. The residue was diluted with ethyl acetate (50 ml) and washed with water (50 ml) and brine (50 ml). Removal of the solvent gave the residue which was purified on ISCO system (1% methanol in dichloromethane) to give a pure product as a white solid (593 mg, 81%): 1H NMR (400 MHz, CDCl3) δ 8.25 (d, 2H), 7.68 (d, 2H), 7.36 (d, 2H), 7.23 (d, 2H), 4.46 (s, 2H), 3.90 (s, 3H), 3.83 (dd, 2H), 3.43 (dd, 2H), 1.31 (s, 9H). MS (ESI) m/z: Calculated: 366.19; Observed: 367.1 (M++1).