Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]([NH:13][C:14](=[O:23])[C:15]2[C:20]([F:21])=[CH:19][CH:18]=[CH:17][C:16]=2[F:22])=[O:12])[CH:5]=[C:6]([Cl:9])[C:7]=1[OH:8].C(N(CC)CC)C.[C:31]([Si:35](Cl)([CH3:37])[CH3:36])([CH3:34])([CH3:33])[CH3:32]>CN(C)C=O.C(OCC)(=O)C>[O:8]([C:7]1[C:2]([Cl:1])=[CH:3][C:4]([NH:10][C:11]([NH:13][C:14](=[O:23])[C:15]2[C:16]([F:22])=[CH:17][CH:18]=[CH:19][C:20]=2[F:21])=[O:12])=[CH:5][C:6]=1[Cl:9])[Si:35]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:37])[CH3:36]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: O=C(NC(=O)c1c(F)cccc1F)Nc1cc(Cl)c(O)c(Cl)c1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)(C)[Si](C)(C)Oc1c(Cl)cc(NC(=O)NC(=O)c2c(F)cccc2F)cc1Cl
Reaction time: 0.08 h
Yield: 65.8 %

Procedure:
Into a homogeneous solution of 1-(3,5-dichloro-4-hydroxyphenyl)-3-(2,6-difluorobenzoyl)urea (3.13 grams, 8.66 mmol) in dimethylformamide (25 milliliters) was added triethylamine (1.75 grams, 17.3 mmol), and the resulting mixture was stirred for 5 minutes. Tertiary-butyldimethylsilyl chloride (3.92 grams, 26.0 mmol) was then added, and a thick precipitate formed immediately. This heterogeneous mixture was then diluted with ethyl acetate (200 milliliters), washed with saturated sodium bicarbonate (twice with 150 milliliters) and then washed with a brine solution (150 milliliters). The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure to give a brown solid. The solid was washed with cold ether and vacuum dried to afford 1-(4-tert-butyldimethylsiloxy-3,5-dichlorophenyl)-3-(2,6-difluorobenzoyl)urea (2.71 grams, 5.70 mmol) having a melting point of 184° C.-186° C. Elemental analysis of the product indicated the following:
Reaction SMILES: [C:1]([O-:4])(=[S:3])[CH3:2].[K+].CS(O[CH:11]1[CH2:20][CH2:19][C:14]2([O:18][CH2:17][CH2:16][O:15]2)[CH2:13][CH2:12]1)(=O)=O>CS(C)=O.[Cl-].[Na+].O>[C:1](=[S:3])([O:4][CH:11]1[CH2:20][CH2:19][C:14]2([O:18][CH2:17][CH2:16][O:15]2)[CH2:13][CH2:12]1)[CH3:2]
Reactant: CS(=O)(=O)OC1CCC2(CC1)OCCO2
Reactant: CC([O-])=S
Agent: [Cl-]
Agent: [K+]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: CC(=S)OC1CCC2(CC1)OCCO2
Temperature: 40 °C
Yield: 64.8 %

Procedure:
Potassium thioacetate (21.39 g, 187 mmol) was added to a stirred mixture of 1,4-dioxaspiro[4.5]dec-8-yl methanesulfonate (29.5 g, 125 mmol) in DMSO (31.2 ml) and the mixture was heated at 40° C. for 24 h. The mixture was cooled, brine was added and the mixture was extracted with ethyl acetate. The combined organic fractions were washed with brine, dried, and evaporated. The residue was purified by column chromatography on silica gel using a Biotage 65i cartridge, eluting with EtOAc/isohexane to give 1,4-dioxaspiro[4.5]dec-8-yl ethanethioate (17.5 g, 81 mmol, 64.8% yield) as a red oil. 1H NMR (500 MHz, CDCl3): δ 3.92 (4H, s), 3.53 (1H, s), 2.29 (3H, s), 2.00-1.93 (2H, m), 1.77-1.63 (6H, m).
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]([N+:28]([O-])=O)[C:5]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]3[CH:19]=[N:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=3)=[C:12]([O:26][CH3:27])[CH:11]=2)=[N:6][CH:7]=1>C(O)(=O)C.C(OCC)(=O)C.[Fe]>[I:1][C:2]1[CH:3]=[C:4]([NH2:28])[C:5]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]3[CH:19]=[N:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=3)=[C:12]([O:26][CH3:27])[CH:11]=2)=[N:6][CH:7]=1
Reactant: COc1ccc(COc2ccc(CNc3ncc(I)cc3[N+](=O)[O-])cc2OC)cn1
Agent: [Fe]
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: COc1ccc(COc2ccc(CNc3ncc(I)cc3N)cc2OC)cn1
Temperature: 85 °C
Yield: 84.4 %

Procedure:
To a stirred suspension of 5-iodo-N-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-3-nitropyridin-2-amine (14.67 g, 28.09 mmol) in acetic acid (130 mL) was added iron powder (10.98 g, 196.6 mmol). The bright yellow mixture was warmed to ˜85° C. After 15 min of heating, the reaction mixture became a gray-brown suspension and was allowed to cool to room temperature. The mixture was diluted with ethyl acetate (400 mL), and the thick mixture was filtered through Celite with the aid of additional ethyl acetate (100 mL). The filtrate was washed with water (2×150 mL) and 5N ammonium hydroxide solution (4×125 mL). The organic phase was dried over magnesium sulfate, filtered, and concentrated to provide 11.67 g (84%) of 5-iodo-N2-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)pyridine-2,3-diamine as a tan solid.
Reaction SMILES: [CH2:1]([N:8]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH:9]1[CH2:15][CH2:14][CH:13]2[CH2:16][CH:10]1[C:11](=[O:24])[N:12]2[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>C1COCC1.O>[CH2:25]([N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C@H:9]1[CH2:15][CH2:14][C@@H:13]([NH:12][C:17](=[O:18])[O:19][C:20]([CH3:22])([CH3:23])[CH3:21])[CH2:16][C@H:10]1[CH2:11][OH:24])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: CC(C)(C)OC(=O)N1C(=O)C2CC1CCC2N(Cc1ccccc1)Cc1ccccc1
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N[C@@H]1CC[C@H](N(Cc2ccccc2)Cc2ccccc2)[C@H](CO)C1
Temperature: 25 °C
Reaction time: 6 h
Yield: 72.4 %

Procedure:
Examples 11p and 11q, Step 3: To a solution of tert-butyl 2-(dibenzylamino)-7-oxo-6-aza-bicyclo[3.2.1]octane-6-carboxylate (3.12 g, 7.42 mmoles) in 50 ml of THF and 10 ml of water was added sodium borohydride (1.4 g, 37.1 mmoles), and the mixture was stirred for 6 hours at room temperature. The reaction was quenched with saturatedd sodium bicarbonate, and the product was extracted with EtOAc three times. The combined extracts were washed with brine, dried over Na2SO4 and evaporated to give an oily residue. It was purified by column chromatography (silica gel, 3:7 EtOAc and hexane) to give 2.28 g of tert-butyl (1R,3R,4S)-4-(dibenzylamino)-3-(hydroxymethyl)cyclohexylcarbamate as an oil.
Reaction SMILES: Cl.[P:2]([O-:13])([O:8][CH2:9][CH2:10][CH2:11][CH3:12])[O:3][CH2:4][CH2:5][CH2:6][CH3:7].[CH3:14][C:15]([CH3:17])=[O:16]>C(N(CC)CC)C.[Cl-].[Mg+2].[Cl-]>[CH2:4]([O:3][P:2]([C:15]([OH:16])([CH3:17])[CH3:14])(=[O:13])[O:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH2:5][CH2:6][CH3:7]
Reactant: CC(C)=O
Reactant: CCCCOP([O-])OCCCC
Agent: Cl
Agent: [Cl-]
Agent: [Mg+2]
Solvent: CCN(CC)CC
Product: CCCCOP(=O)(OCCCC)C(C)(C)O
Temperature: 80 °C
Yield: 91.7 %

Procedure:
Next, into a two-liter four-necked flask provided with a stirrer, a thermometer, a dropping device, a hydrochloric-acid-recovering device and a condenser, 213.4 g (1.1 moles) of dibutyl phosphite, 5.6 g (0.06 moles) of triethylamine and 1.9 g (0.020 moles) of magnesium chloride were fed. While stirring the resulting mixed solution at 40° C., 70.2 g (1.2 moles) of acetone was added thereto in an hour. The mixed solution was further stirred for 1 hour at the same temperature (40° C.) to complete the reaction. Thereafter, the resulting reaction solution was washed with a 1% dilute hydrochloric acid aqueous solution and a saturated sodium carbonate aqueous solution successively and rinsed with water twice to remove the triethylamine and the magnesium chloride. Then, while heating the reaction mixture to 80° C., water was recovered under a reduced pressure of about 2.7 kPa. Further, nitrogen topping was carried out under the same conditions to remove the low-boiling point portions, thereby obtaining 254.6 g of dibutyl(1-hydroxy-1-methylethyl)phosphonate (raw material 2).
Reaction SMILES: Cl.[NH2:2][CH2:3][CH2:4][C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].C(N(CC)CC)C.Cl[C:20](=[O:27])[CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23]>O1CCCC1>[C:8]([O:7][C:5](=[O:6])[CH2:4][CH2:3][NH:2][C:20](=[O:27])[CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])([CH3:11])([CH3:10])[CH3:9]
Reactant: CC(C)(C)OC(=O)CCN
Reactant: CCOC(=O)CC(=O)Cl
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CCOC(=O)CC(=O)NCCC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 18 h

Procedure:
10 g (55.05 mmol) tert.-butyl β-alaninate hydrochloride are dissolved in 50 ml tetrahydrofuran, and 11.14 g (110.1 mmol) triethylamine and 5.53 g (36.7 mmol) ethyl 3-chloro-3-oxopropanoate are added at 0° C. The reaction mixture is stirred at room temperature for 18 hours. The solvent is removed in vacuo and the product is isolated by column chromatography (silica, eluent dichloromethane/methanol 100:1→50:1).
Reaction SMILES: [CH3:1][C:2]([CH3:17])([CH3:16])[C:3]#[C:4][C:5]1[O:9][N:8]=[C:7]([C:10]([O:12]CC)=[O:11])[C:6]=1[CH3:15].[OH-].[Na+].Cl.O>C1COCC1.CO>[CH3:1][C:2]([CH3:17])([CH3:16])[C:3]#[C:4][C:5]1[O:9][N:8]=[C:7]([C:10]([OH:12])=[O:11])[C:6]=1[CH3:15]
Reactant: CCOC(=O)c1noc(C#CC(C)(C)C)c1C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: Cc1c(C(=O)O)noc1C#CC(C)(C)C

Procedure:
Ethyl 5-(3,3-dimethylbut-1-yn-1-yl)-4-methylisoxazole-3-carboxylate (101 mg, 0.429 mmol) in THF (3 mL) and MeOH (1.800 mL) was treated at room temperature with 2M NaOH (aq) (0.429 mL, 0.859 mmol) for 1 hour. 2M HCl (aq) (0.6 mL) and water were added and the aqueous was extracted with EtOAc. The combined organic extracts were dried over MgSO4 and filtered. The solvent was removed under reduced pressure to afford the title compound;
Reaction SMILES: [C:1]([O:9]CC)([O:6][CH2:7][CH3:8])(OCC)[CH3:2].[Cl:12][C:13]([Cl:24])([C:20]([F:23])([F:22])[F:21])[CH:14](O)[CH:15]=[C:16]([CH3:18])[CH3:17].C(O)(=O)C(C)C>>[Cl:12][C:13]([Cl:24])([C:20]([F:21])([F:22])[F:23])[CH:14]=[CH:15][C:16]([CH3:18])([CH3:17])[CH2:2][C:1]([O:6][CH2:7][CH3:8])=[O:9]
Reactant: CC(C)=CC(O)C(Cl)(Cl)C(F)(F)F
Reactant: CCOC(C)(OCC)OCC
Solvent: CC(C)C(=O)O
Product: CCOC(=O)CC(C)(C)C=CC(Cl)(Cl)C(F)(F)F

Procedure:
A mixture of triethyl orthoacetate (25 ml), 5,5-dichloro-4-hydroxy-2-methyl-6,6,6-trifluorohex-2-ene (3.5 g), and isobutyric acid (0.11 g) was heated at the reflux temperature. The refluxing volatiles were condensed and collected in a Dean & Stark apparatus containing molecular sieves (4A) to collect the by-product ethanol and separate it from the orthoacetate which was returned to the mixture. After 30 minutes the more volatile components were removed by evaporation under reduced pressure and the residual oil (consisting principally of 5,5-dichloro-4-(1,1-diethoxyethoxy)-2-methyl-6,6,6-trifluorohex-2-ene, 3.8 g) collected. This was then heated with isobutyric acid (10 μl ) at the reflux temperature for 16 hours under a condenser containing molecular sieves (4A) to remove ethanol from the condensate. The residual oil was subjected to purification by column chromatography using a 15:1 (by volume) mixture of hexane:ethyl acetate as eluant and a silica gel column (230-400 mesh, 60 Å) to obtain ethyl 6,6-dichloro-3,3-dimethyl-7,7,7-trifluorohept-enoate, identified by nuclear magnetic resonance, and gas chromatographic mass-spectroscopy.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH:11]([CH2:14][OH:15])[CH2:12][OH:13])=[C:6]([CH3:16])[CH:5]=1)([O-])=O.C1(N)C(F)=C(F)C(F)=C(N)C=1F.[ClH:29].Cl>[Zn].[Cl-].[NH4+].O.C(O)C>[ClH:29].[ClH:29].[NH2:1][C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH:11]([CH2:12][OH:13])[CH2:14][OH:15])=[C:6]([CH3:16])[CH:5]=1
Reactant: Cc1cc([N+](=O)[O-])ccc1NC(CO)CO
Agent: Cl
Agent: Nc1c(F)c(N)c(F)c(F)c1F
Agent: [Cl-]
Solvent: CCO
Solvent: O
Product: Cc1cc(N)ccc1NC(CO)CO

Procedure:
The 2-(4-nitro-2-methylphenylamino)propane-1,3-diol (13) obtained above was reduced with a boiling zinc/ammonium chloride/water/ethanol mixture. The corresponding amine was isolated in dihydrochloride form.
Reaction SMILES: [C:1]1([S:7](Cl)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]#[N:28])=[CH:23][CH:22]=2)[C:13]=1[CH3:29]>N1C=CC=CC=1>[C:27]([C:24]1[CH:25]=[CH:26][C:21]([CH2:20][CH2:19][O:18][C:14]2[C:13]([CH3:29])=[C:12]([NH:11][S:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)(=[O:9])=[O:8])[CH:17]=[CH:16][CH:15]=2)=[CH:22][CH:23]=1)#[N:28]
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: Cc1c(N)cccc1OCCc1ccc(C#N)cc1
Solvent: c1ccncc1
Product: Cc1c(NS(=O)(=O)c2ccccc2)cccc1OCCc1ccc(C#N)cc1
Reaction time: 8 h
Yield: 70.4 %

Procedure:
Benzenesulfonyl chloride (0.24 mL; 1.9 mmol) was added to a stirred solution of amino-3-[2-(4-cyanophenyl)ethoxy]-2-methylbenzene (0.42 g; 1.7 mmol; from step (iii) above) in dry pyridine (20 mL) under nitrogen. The reaction was left overnight at room temperature. After evaporation of the solvent the residue was partitioned between 10% aqueous HCl and EtOAc. The organic layer was washed with brine, dried (MgSO4) and the solvent removed in vacuo. Purification by flash chromatography afforded 0.47 g (72%) of the sub-title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][NH:7][C:8](SC)=[CH:9][N+:10]([O-:12])=[O:11])=[CH:4][CH:3]=1.[CH3:17][NH:18][CH3:19]>CCO>[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][NH:7][C:8]([N:18]([CH3:19])[CH3:17])=[CH:9][N+:10]([O-:12])=[O:11])=[CH:4][CH:3]=1
Reactant: CNC
Reactant: CSC(=C[N+](=O)[O-])NCc1ccc(Cl)cc1
Solvent: CCO
Product: CN(C)C(=C[N+](=O)[O-])NCc1ccc(Cl)cc1
Yield: 47.3 %

Procedure:
In 100 ml of EtOH was dissolved 2.59 g (0.01 mole) of 1-(4-chlorobenzyl)amino-1-methylthio-2-nitroethylene with heating. Then, with refluxing and stirring, a solution of 2.25 g of 50% aqueous dimethylamine solution in 10 ml of EtOH was added dropwise over a period of 35 minutes. After completion of dropwise addition, the mixture was further stirred and refluxed for 2.5 hours. The solvent was then distilled off and the residue was diluted with ether and triturated, whereupon crystals separated. After addition of EtOH and ether (about 1:5), the crystals were collected by filtration, washed with ether and dried. The procedure gave 1.21 g of the title compound as white crystals.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([Cl:9])[C:3]=1[N:10]1[C:14](=[O:15])[CH:13]=[C:12]([NH:16][C:17]2[CH:22]=[C:21]([NH2:23])[CH:20]=[CH:19][C:18]=2[Cl:24])[NH:11]1.C(#N)C.[C:28]([C:36]1[CH:46]=[CH:45][C:39]([O:40][CH2:41][C:42](Cl)=[O:43])=[CH:38][CH:37]=1)([CH2:31][C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:30])[CH3:29]>N1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([Cl:9])[C:3]=1[N:10]1[C:14](=[O:15])[CH:13]=[C:12]([NH:16][C:17]2[CH:22]=[C:21]([NH:23][C:42](=[O:43])[CH2:41][O:40][C:39]3[CH:45]=[CH:46][C:36]([C:28]([CH2:31][C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:29])[CH3:30])=[CH:37][CH:38]=3)[CH:20]=[CH:19][C:18]=2[Cl:24])[NH:11]1
Reactant: Nc1ccc(Cl)c(Nc2cc(=O)n(-c3c(Cl)cc(Cl)cc3Cl)[nH]2)c1
Reactant: CC(C)(C)CC(C)(C)c1ccc(OCC(=O)Cl)cc1
Solvent: CC#N
Solvent: c1ccncc1
Product: CC(C)(C)CC(C)(C)c1ccc(OCC(=O)Nc2ccc(Cl)c(Nc3cc(=O)n(-c4c(Cl)cc(Cl)cc4Cl)[nH]3)c2)cc1
Yield: 854.2 %

Procedure:
Forty point four grams of 1-(2,4,6-trichlorophenyl)-3-(2-chloro-5-aminoanilino)-5-pyrazolone were dissolved into 250 ml of acetonitrile, and to the solution were added 9.4 grams of pyridine. To this mixture, while being refluxed by heating, were dropwise added 28.3 g of 4-t-octylphenoxyacetyl chloride, and the reflux was further continued for another hour. The acetonitrile was distilled off from the reaction liquid under reduced pressure, then 500 ml of water and ethyl acetate were added to the liquid, and then the reaction product was extracted by ethyl acetate. The residuum that has been obtained by distilling off the ethyl acetate phase under reduced pressure was recrystallized from 300 ml of ethanol, whereby 55 g of objective 1-(2,4,6-trichlorophenyl)-3-[2-chloro-5-(4-t-octylphenoxyacetamido)anilino]-5-pyrazolone were obtained. Melting point: 126° to 128° C. The structure was confirmed through the procedures of NMR, IR and MASS.
Reaction SMILES: [CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[C:19]1([CH:25]([CH3:29])[C:26](Cl)=[O:27])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(=O)(O)[O-].[Na+]>C1COCC1>[C:2]1([CH2:1][C@H:8]2[CH2:12][O:11][C:10](=[O:13])[N:9]2[C:26](=[O:27])[CH:25]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH3:29])[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1N[C@@H](Cc2ccccc2)CO1
Reactant: CC(C(=O)Cl)c1ccccc1
Agent: O=C([O-])O
Agent: [Li]CCCC
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1)c1ccccc1
Reaction time: 0.83 h

Procedure:
A mixture of (4S)-(-)-4-benzyl-2-oxazolidinone (3.903 g, 22.0 mmol) in THF (23 ml) is cooled at -78° and butyl lithium (1.6M in hexane, 14.7 ml, 23.5 mmol) is added. The mixture is stirred for 50 min and then the portion of 2-phenylpropionic acid chloride (XL) from above, in THF (8 ml) is added dropwise to the mixture. The mixture is stirred for 1 hr at -78° and then allowed to warm to 20°-25°. Saturated aqueous sodium bicarbonate solution (100 ml) is added and the phases separated. The aqueous phase is washed with ether and the combined organic phases are then washed several times with saturated aqueous sodium bicarbonate followed by a saline wash. The organic phase is dried over magnesium sulfate and concentrated. The resulting diastereomers are separated on silica gel eluting with ethyl acetate/hexane (7/93) followed by ethyl acetate/hexane (12/88). The appropriate fractions are pooled and concentrated to give (4S)-4-(phenylmethyl)-3-(2-phenylpropionyl)-2-oxazolidinone (XLI, Isomer I, less polar isomer), NMR (CDCl3) 1.55, 2.79, 3.35, 4.09, 4.58, 5.12 and 7.30 δ; and (4S)-4-(phenylmethyl)-3-(2-phenylpropionyl)-2-oxazolidinone (XLII, Isomer II, more polar isomer), NMR (CDCl3) δ1.52, 2.58, 3.09, 4.08, 4.19, 4.75, 5.11, 6.95 and 7.31 δ.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[C:11](=[O:22])[NH:12][C:13](=[O:21])[C:14]=2[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:5][CH:4]=1.[C:23]([O:27][CH2:28][CH3:29])(=[O:26])[CH2:24]O.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1COCC1.CC#N.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10]2[C:11](=[O:22])[N:12]([CH2:24][C:23]([O:27][CH2:28][CH3:29])=[O:26])[C:13](=[O:21])[C:14]=2[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:7][CH:8]=1
Reactant: COc1ccc(NC2=C(c3ccccc3)C(=O)NC2=O)cc1
Reactant: CCOC(=O)CO
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: C1CCOC1
Solvent: CC#N
Solvent: O
Product: CCOC(=O)CN1C(=O)C(Nc2ccc(OC)cc2)=C(c2ccccc2)C1=O
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 41 %

Procedure:
To a solution of 3-[(4-methoxyphenyl)amino]-4-phenyl-1H-pyrrole-2,5-dione (0.34 mmol, 100 mg) in dry THF (1.0 mL) under an atmosphere of N2 at room temperature was added ethyl glycolate (0.34 mmol, 35 mg). The reaction mixture was cooled to 0° C. and tributylphosphine (0.17 mmol, 34 mg) was added followed by 1,1′-(azodicarbonyl)dipiperidine (0.36 mmol, 84 mg). After stirring at 0° C. for 10 min., the reaction mixture was brought to room temperature and the stirring was continued for 26 h. The reaction mixture was diluted with CH3CN:water 1:1 (2 mL) and purified using HPLC (95% 0.1M ammonium acetate buffer:5% CH3CN→100% CH3CN, 38.5 min., 25 mL/min.) to give 53 mg (41%) of the title compound. 1H NMR (400 MHz, CDCl3) δ 7.22-7.17 (bs, 1H), 7.15-7.05 (m, 3H), 7.01-6.96 (m, 2H), 6.63-6.52 (m, 4H), 4.36 (s, 2H), 4.24 (q, J=7.1 Hz, 2H), 3.69 (s, 3H), 1.30 (t, J=7.1 Hz, 3H).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([NH:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[N:15]([C:19]1[N:27]=[C:26]([NH:28][C@H:29]3[CH2:34][CH2:33][C@H:32]([NH:35]C(OC(C)(C)C)=O)[CH2:31][CH2:30]3)[N:25]=[C:24]3[C:20]=1[N:21]=[CH:22][N:23]3C(OC(C)(C)C)=O)[CH2:14][CH2:13]2)=[O:8].Cl>CO>[NH2:35][C@H:32]1[CH2:31][CH2:30][C@H:29]([NH:28][C:26]2[N:25]=[C:24]3[C:20]([N:21]=[CH:22][NH:23]3)=[C:19]([N:15]3[C:16]4[C:12](=[CH:11][C:10]([NH:9][C:7](=[O:8])[CH2:6][C:2]5[S:1][CH:5]=[CH:4][CH:3]=5)=[CH:18][CH:17]=4)[CH2:13][CH2:14]3)[N:27]=2)[CH2:34][CH2:33]1
Reactant: CC(C)(C)OC(=O)N[C@H]1CC[C@H](Nc2nc(N3CCc4cc(NC(=O)Cc5cccs5)ccc43)c3ncn(C(=O)OC(C)(C)C)c3n2)CC1
Agent: Cl
Solvent: CO
Product: N[C@H]1CC[C@H](Nc2nc(N3CCc4cc(NC(=O)Cc5cccs5)ccc43)c3nc[nH]c3n2)CC1
Reaction time: 48 h

Procedure:
The product obtained in stage 5 is dissolved in 2 ml of methanol. 2 ml of a 2N solution of hydrochloric acid in methanol are added. Stirring is carried out for 48 hours at ambient temperature, followed by evaporation to dryness. The residue is chromatographed on an Xterra LCMSprep column, eluting with acetonitrile/ammonium hydrogen carbonate buffer at 0.2% as a gradient. 6 mg of expected product, example 41, are thus recovered.
Reaction SMILES: [NH2:1][C:2]1[C:18]([Cl:19])=[CH:17][C:5]([C:6]([NH:8][CH:9]2[CH:14]3[CH2:15][CH2:16][N:11]([CH2:12][CH2:13]3)[CH2:10]2)=[O:7])=[C:4]([OH:20])[CH:3]=1.[H-].[Na+].Cl[CH2:24][C:25](=[O:27])[CH3:26]>CN(C=O)C>[NH2:1][C:2]1[C:18]([Cl:19])=[CH:17][C:5]([C:6]([NH:8][CH:9]2[CH:14]3[CH2:13][CH2:12][N:11]([CH2:16][CH2:15]3)[CH2:10]2)=[O:7])=[C:4]([O:20][CH2:24][C:25](=[O:27])[CH3:26])[CH:3]=1
Reactant: CC(=O)CCl
Reactant: Nc1cc(O)c(C(=O)NC2CN3CCC2CC3)cc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(=O)COc1cc(N)c(Cl)cc1C(=O)NC1CN2CCC1CC2
Reaction time: 5 h

Procedure:
When the starting benzamide intermediate from Example 74 is first reacted with one equivalent of sodium hydride in DMF and then to this is added on equivalent of chloroacetone and the mixture stirred for 5 h followed by heating to 50° for 30 min and workup, the title compound is isolated.
Reaction SMILES: [OH:1][NH:2][C:3]([N:5]1[CH2:10][CH2:9][CH:8]([CH:11]2[O:29][C:14]3=[CH:15][N:16]=[C:17]([C:19]4[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][CH:20]=4)[CH:18]=[C:13]3[CH2:12]2)[CH2:7][CH2:6]1)=[NH:4].[C:30](Cl)(=O)[CH2:31][CH2:32][CH3:33]>>[CH3:28][S:25]([C:22]1[CH:23]=[CH:24][C:19]([C:17]2[CH:18]=[C:13]3[CH2:12][CH:11]([CH:8]4[CH2:7][CH2:6][N:5]([C:3]5[N:4]=[C:30]([CH2:31][CH2:32][CH3:33])[O:1][N:2]=5)[CH2:10][CH2:9]4)[O:29][C:14]3=[CH:15][N:16]=2)=[CH:20][CH:21]=1)(=[O:27])=[O:26]
Reactant: CCCC(=O)Cl
Reactant: CS(=O)(=O)c1ccc(-c2cc3c(cn2)OC(C2CCN(C(=N)NO)CC2)C3)cc1
Product: CCCc1nc(N2CCC(C3Cc4cc(-c5ccc(S(C)(=O)=O)cc5)ncc4O3)CC2)no1

Procedure:
The title compound is prepared from N-hydroxy-4-[5-(4-methanesulfonyl-phenyl)-2,3-dihydro-furo[2,3-c]pyridin-2-yl]-piperidine-1-carboxamidine and butyryl chloride following a procedure analogous to that described in Example 8. LC (method 5): tR=1.30 min; Mass spectrum (ESI+): m/z=469 [M+H]+.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][CH:10]([C:13]([N:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)=[O:14])[CH2:9][CH2:8]2)=[CH:3][CH:2]=1.[CH:21]1[C:29]2[C:28]3[CH:30]=[CH:31][CH:32]=[CH:33][C:27]=3[O:26][C:25]=2[CH:24]=[C:23]([S:34](Cl)(=[O:36])=[O:35])[CH:22]=1>>[CH:21]1[C:29]2[C:28]3[CH:30]=[CH:31][CH:32]=[CH:33][C:27]=3[O:26][C:25]=2[CH:24]=[C:23]([S:34]([N:18]2[CH2:17][CH2:16][N:15]([C:13]([CH:10]3[CH2:11][CH2:12][N:7]([C:4]4[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=4)[CH2:8][CH2:9]3)=[O:14])[CH2:20][CH2:19]2)(=[O:35])=[O:36])[CH:22]=1
Reactant: O=C(C1CCN(c2ccncc2)CC1)N1CCNCC1
Reactant: O=S(=O)(Cl)c1ccc2c(c1)oc1ccccc12
Product: O=C(C1CCN(c2ccncc2)CC1)N1CCN(S(=O)(=O)c2ccc3c(c2)oc2ccccc23)CC1
Yield: 75 %

Procedure:
Using an analogous procedure to that described in Example 2, 1-[1-(4-pyridyl)piperidin-4-ylcarbonyl]piperazine was reacted with dibenzofuran-3-sulphonyl chloride to give 1-(dibenzofuran-3-ylsulphonyl)-4-[1-(4-pyridyl)piperidin-4-ylcarbonyl]piperazine as a glassy solid in 75% yield;