Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:10]([N:11]2[C:15](=[O:16])[N:14]([CH3:17])[N:13]=[N:12]2)=[C:9]([Cl:18])[CH:8]=[CH:7][C:3]=1[C:4](Cl)=[O:5].[C:19]1(=[O:26])[CH2:24][CH2:23][CH2:22][C:21](=[O:25])[CH2:20]1.C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[C:10]([N:11]2[C:15](=[O:16])[N:14]([CH3:17])[N:13]=[N:12]2)=[C:9]([Cl:18])[CH:8]=[CH:7][C:3]=1[C:4]([CH:20]1[C:21](=[O:25])[CH2:22][CH2:23][CH2:24][C:19]1=[O:26])=[O:5]
Reactant: O=C1CCCC(=O)C1
Reactant: Cn1nnn(-c2c(Cl)ccc(C(=O)Cl)c2Cl)c1=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cn1nnn(-c2c(Cl)ccc(C(=O)C3C(=O)CCCC3=O)c2Cl)c1=O
Temperature: 25 °C
Reaction time: 6 h
Yield: 51.1 %

Procedure:
A dichloromethane solution of the crude 2,4-dichloro-3-(4,5-dihydro-4-methyl-5-oxo-1H-tetrazol-1-yl)benzoyl chloride (1.10 g) was added drop by drop to the solution of 1,3-cyclohexanedione (0.44 g) and triethylamine (0.43 g) in dichloromethane (8 ml) at 5° C. and the mixture was stirred at room temperature for 6 hours. After completion of the reaction it was extracted with dichloromethane (150 ml), washed with diluted hydrochloric acid and aqueous solution of sodium hydrogen carbonate and then dried with anhydrous magnesium sulfate. The residue, obtained by distilling off the dichloromethane, was dissolved in acetonitrile (7 ml), added with triethylamine (0.43 g) and acetonecyanohydrin (18 mg) and stirred at room temperature for 8 hours. After the solvent was distilled off, the residue was acidified by addition of diluted hydrochloric acid and extracted with ethyl acetate (150 ml). The organic layer was washed with saturated salt water and dried with anhydrous magnesium sulfate. By distilling off the ethyl acetate, the objective 2-[2,4-dichloro-3-(4,5-dihydro-4-methyl-5-oxo-1H-tetrazol-1-yl)benzoyl]cyclohexan-1,3-dione (0.70 g, 51% yield from 2,4-dichloro-3-(4,5-dihydro4-methyl-5-oxo-1H-tetrazol-1-yl)benzoic acid) was obtained. mp 138-140° C.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH2:9])=[O:8])=[CH:5][CH:4]=1.[P:12]([O:19]CC)([O:16][CH2:17][CH3:18])[O:13][CH2:14][CH3:15].[I-].[K+].C(#N)C>O>[C:7]([C:6]1[CH:10]=[CH:11][C:3]([CH2:2][P:12](=[O:19])([O:16][CH2:17][CH3:18])[O:13][CH2:14][CH3:15])=[CH:4][CH:5]=1)(=[O:8])[NH2:9]
Reactant: CCOP(OCC)OCC
Reactant: NC(=O)c1ccc(CCl)cc1
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Product: CCOP(=O)(Cc1ccc(C(N)=O)cc1)OCC
Yield: 93.3 %

Procedure:
The compound (44.83 g, 0.264 mol) obtained in Example 1, triethyl phosphite (53.21 g, 0.320 mol), potassium iodide (39.4 g, 0.237 mol) and acetonitrile (224 mL) were charged and stirred under reflux for 4 hrs. The reaction mixture was allowed to return to room temperature, and water (336 mL) was added. The mixture was concentrated under reduced pressure, and the residue (315 g) was stirred at room temperature for 1 hr. and under ice-cooling for 1 hr. The crystals were collected by filtration, washed with cold water (20 mL) and dried in vacuo at 40° C. for 7 hrs. to give the title compound (66.79 g, yield 93.2%) as slightly yellow crystals.
Reaction SMILES: [SH:1][CH2:2][CH:3]([CH3:14])[C:4]([N:6]1[CH2:13][CH2:12][CH2:11][C@H:7]1[C:8]([NH2:10])=[O:9])=[O:5].[CH2:15](OC(=O)[C@@H]1CCCN1C(=O)CCS)C>>[CH3:15][S:1][CH2:2][CH:3]([CH3:14])[C:4]([N:6]1[CH2:13][CH2:12][CH2:11][C@H:7]1[C:8]([NH2:10])=[O:9])=[O:5]
Reactant: CC(CS)C(=O)N1CCC[C@H]1C(N)=O
Reactant: CCOC(=O)[C@@H]1CCCN1C(=O)CCS
Product: CSCC(C)C(=O)N1CCC[C@H]1C(N)=O

Procedure:
By substituting 1-(3-mercapto-2-methylpropanoyl)-L-proline amide for the 1-(3-mercaptopropanoyl)-L-proline ethyl ester in the Procedure B of Example 80 and eliminating the saponification step, 1-(3-methylthio-2-methylpropanoyl)-L-proline amide is obtained.
Reaction SMILES: [CH3:1][C:2](C)([O-:4])C.[K+].Cl[C:8]1[N:16]=[CH:15][CH:14]=[CH:13][C:9]=1[C:10]([OH:12])=[O:11]>C(O)C>[CH2:2]([O:4][C:8]1[C:9]([C:10]([OH:12])=[O:11])=[CH:13][CH:14]=[CH:15][N:16]=1)[CH3:1]
Reactant: CC(C)(C)[O-]
Reactant: O=C(O)c1cccnc1Cl
Agent: [K+]
Solvent: CCO
Product: CCOc1ncccc1C(=O)O
Temperature: 170 °C
Yield: 86.3 %

Procedure:
A solution of potassium t-butoxide (44.9 g, 0.40 mol) in absolute ethanol (300 ml) was added slowly to a solution of 2-chloronicotinic acid (30 g, 0.19 mol) in absolute ethanol (100 ml) and the reaction mixture heated in a sealed vessel at 170° C. for 20 hours, then allowed to cool. The resulting mixture was evaporated under reduced pressure, the residue dissolved in water (200 ml) and the solution acidified to pH 3 with hydrochloric acid and extracted with dichloromethane (4×200 ml). The combined extracts were dried (Na2SO4) and evaporated under reduced pressure to give the title compound (27.4 g, 41%) as a white solid. δ (CDCl3): 1.53 (3H, t), 4.69 (2H, q), 7.13 (1H, m), 8.37 (1H, d), 8.48 (1H, d).
Reaction SMILES: [C:1]([C@@H:9]1[CH2:13][CH:12]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:17][CH:16]=2)[N:11](/[CH:27]=[CH:28]/[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:10]1=[O:35])(=O)C1C=CC=CC=1.N1CCOCC1.C=O.Cl>CO>[C:18]1([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:17]=[CH:16][C:15]([CH2:14][C@H:12]2[N:11](/[CH:27]=[CH:28]/[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:10](=[O:35])[C:9](=[CH2:1])[CH2:13]2)=[CH:20][CH:19]=1
Reactant: O=C(c1ccccc1)[C@@H]1CC(Cc2ccc(-c3ccccc3)cc2)N(/C=C/c2ccccc2)C1=O
Agent: C=O
Agent: Cl
Solvent: C1COCCN1
Solvent: CO
Product: C=C1C[C@@H](Cc2ccc(-c3ccccc3)cc2)N(/C=C/c2ccccc2)C1=O

Procedure:
(S)-3-Benzoyl-5-biphenyl-4-ylmethyl-1-((E)-styryl)-pyrrolidin-2-one (4a, R1=styryl, R4=phenyl) (0.50 g, 1.1 mmol) is dissolved in 2 mL of methanol, add morpholine (125 mg, 1.4 mmol) and paraformaldehyde (66 mg, 2.2 mmol) in one portion, reflux for 2 h under nitrogen atmosphere. The reaction mixture is added 10 mL of 5% HCl(aq), extract with toluene, the organic extracts are washed with saturated Na2CO3 aqueous solution and brine, dry over anhydrous Na2SO4, evaporate the solvent under vacuum, the residue is purified by column chromatography to obtain (R)-5-Biphenyl-4-ylmethyl-3-methylene-1-((E)-styryl)-pyrrolidin-2-one (1a, R1=styryl). Spectroscopic data as Example 23, Method 1.
Reaction SMILES: Br[C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][CH:3]=1.[N:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[C:19]1[C:20](B(O)O)=[C:21]2[CH2:26][CH2:25][CH2:24][N:22]2[N:23]=1>>[C:7]1([C:5]2[O:6][C:2]([C:20]3[C:19]([C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][N:13]=4)=[N:23][N:22]4[CH2:24][CH2:25][CH2:26][C:21]=34)=[CH:3][N:4]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: Brc1cnc(-c2ccccc2)o1
Reactant: OB(O)c1c(-c2ccccn2)nn2c1CCC2
Product: c1ccc(-c2ncc(-c3c(-c4ccccn4)nn4c3CCC4)o2)cc1
Yield: 11.7 %

Procedure:
In a similar fashion to Example 1, react 5-bromo-2-phenyloxazole (Combi-Blocks; 120 mg, 0.52 mmol) with 2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acid (Preparation 5; 120 mg, 0.52 mmol) to provide the title compound (20 mg, 12%) as a white solid. MS ESI+ m/e 329 (M+1). 1H NMR (CDCl3) δ 8.78-8.70 (m, 1H), 8.05-7.99 (m, 2H), 7.95-7.89 (m, 1H), 7.82 (s, 1H), 7.81-7.70 (m, 1H), 7.50-7.41 (m, 3H), 7.30-7.25 (m, 1H), 4.31-4.21 (m, 2H), 3.38-3.24 (m, 2H), 2.82-2.66 (m, 2H). HPLC: 97.2%, Rt=16.67 min. TLC (SiO2): Rf0.3 (1:3 [80:18:2 chloroform/methanol/concentrated aqueous ammonium hydroxide]/dichloromethane).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:37])[C@H:4]([CH2:28][S:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[NH:5][C:6](=[O:27])[C@H:7]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH2:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:10](O)=[O:11].[NH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:37])[C@H:4]([CH2:28][S:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[NH:5][C:6](=[O:27])[C@H:7]([CH2:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[CH2:8][C@H:9]([C:10]([NH:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=1)=[O:11])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: COC(=O)[C@H](CSCc1ccccc1)NC(=O)[C@H](Cc1ccccc1)C[C@@H](Cc1ccccc1)C(=O)O
Reactant: Nc1ccccn1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Product: COC(=O)[C@H](CSCc1ccccc1)NC(=O)[C@H](Cc1ccccc1)C[C@@H](Cc1ccccc1)C(=O)Nc1ccccn1

Procedure:
A solution of 2.1 g of N-[(S,S)-2,4-dibenzyl-4-carboxybutyryl]-S-benzyl-(L)-cysteine methyl ester 0.60 g of 2-aminopyridine and 1.2 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in 25 ml of methylene chloride is stirred at room temperature overnight. The mixture is concentrated, ethyl acetate is added and washed with water, sodium bicarbonate, dried (Na2SO4), filtered and concentrated. The residue is chromatographed on silica gel eluting with ethyl acetatemethylene chloride (1:9) to give N-[4-(2-pyridylaminocarbonyl)-(S,S)-2,4-dibenzylbutyryl]-S-benzyl-(L)-cysteine methyl ester (oil).
Reaction SMILES: [F:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:25])[N:12]([CH2:21][CH2:22][NH:23][CH3:24])[C:13]3[C:18]([C:19]=2[OH:20])=[N:17][CH:16]=[CH:15][CH:14]=3)=[O:9])=[C:4]([S:28]([CH3:31])(=[O:30])=[O:29])[CH:3]=1.[CH3:32][N:33]([CH3:38])[S:34](Cl)(=[O:36])=[O:35].CCN(C(C)C)C(C)C>>[CH3:32][N:33]([CH3:38])[S:34]([N:23]([CH3:24])[CH2:22][CH2:21][N:12]1[C:13]2[C:18](=[N:17][CH:16]=[CH:15][CH:14]=2)[C:19]([OH:20])=[C:10]([C:8]([NH:7][CH2:6][C:5]2[CH:26]=[CH:27][C:2]([F:1])=[CH:3][C:4]=2[S:28]([CH3:31])(=[O:30])=[O:29])=[O:9])[C:11]1=[O:25])(=[O:36])=[O:35]
Reactant: CN(C)S(=O)(=O)Cl
Reactant: CNCCn1c(=O)c(C(=O)NCc2ccc(F)cc2S(C)(=O)=O)c(O)c2ncccc21
Solvent: CCN(C(C)C)C(C)C
Product: CN(C)S(=O)(=O)N(C)CCn1c(=O)c(C(=O)NCc2ccc(F)cc2S(C)(=O)=O)c(O)c2ncccc21
Temperature: 25 °C

Procedure:
A solution of N-[4-fluoro-2-(methylsulfonyl)benzyl]-4-hydroxy-1-[2-(methylamino)ethyl]-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide (0.07 g, 0.16 mmol) in DM (3 mL) was treated with dimethylsulfamoyl chloride (0.44 g, 0.31 mmol) and Hunig's base (0.11 mL, 0.62 mmol) and stirred at room temperature for several hours. Additional dimethylsulfamoyl chloride was added after an hour. The reaction was injected directly onto a reverse phase HPLC column and the compound collected after eluting with a gradient of 95% water/acetonitrile to 5% water acetonitrile. The fractions were combined, evaporated and the crude oil was lyophilized from acetonitrile and water to give the product as a fluffy solid.
Reaction SMILES: Cl.[NH2:2][CH2:3][CH2:4][O:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9](=[O:16])[NH:8][C:7]=1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[CH2:23]=O>C(O)=O>[CH3:23][NH:2][CH2:3][CH2:4][O:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9](=[O:16])[NH:8][C:7]=1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: NCCOc1c(-c2ccccc2)[nH]c(=O)c2ccccc12
Reactant: C=O
Agent: Cl
Solvent: O=CO
Product: CNCCOc1c(-c2ccccc2)[nH]c(=O)c2ccccc12
Yield: 51.6 %

Procedure:
To a solution of 25 mg (0.079 mmol) of 4-(2-amino-ethoxy)-3-phenyl-2H-isoquinolin-1-one hydrochloride (cmpd. 1) in formic acid (0.1 mL), 8 μL (0.08 mmol) of formaldehyde (37% in water) were added and the mixture was refluxed for 1 hour. The solvent was concentrated under reduced pressure and the resulting crude was purified by preparative HPLC affording 12 mg of the title compound (51%).
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][CH:11]([NH2:14])[CH2:10][CH2:9]1)C1C=CC=CC=1.CC(OC(OC(OC(C)(C)C)=O)=O)(C)C.Cl[C:31]1[N:40]=[C:39]([N:41]([CH3:43])[CH3:42])[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[N:32]=1>C1COCC1.CC(O)C>[NH2:14][CH:11]1[CH2:12][CH2:13][N:8]([C:31]2[N:40]=[C:39]([N:41]([CH3:43])[CH3:42])[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[N:32]=2)[CH2:9][CH2:10]1
Reactant: CN(C)c1nc(Cl)nc2ccccc12
Reactant: NC1CCN(Cc2ccccc2)CC1
Agent: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Solvent: C1CCOC1
Solvent: CC(C)O
Product: CN(C)c1nc(N2CCC(N)CC2)nc2ccccc12
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 60.1 %

Procedure:
To a solution of 1-benzyl-piperidin-4-ylamine (2.00 g, 10.5 mmol) in THF (20 mL) was added (Boc)2O (2.52 g, 11.5 mmol). The mixture was stirred at ambient temperature for 40 min, and concentrated. To a solution of the residue in MeOH (20 mL) was added 20% Pd(OH)2 (400 mg). The mixture was stirred at ambient temperature under hydrogen atmosphere for 20 hr. Additionally, 20% Pd(OH)2 (400 mg) was added and the mixture was stirred at ambient temperature under hydrogen atmosphere for 7 hr, at 50° C. for 4.5 hr, and at ambient temperature for 12 hr, filtered through a pad of celite, and concentrated to give a white solid. A mixture of (2-chloro-quinazolin-4-yl)-dimethyl-amine obtained in step B of example 1 (1.10 g, 5.30 mmol) and the above solid (1.27 g, 6.34 mmol) in 2-propanol (11 mL) was stirred at reflux for 20 hr. The precipitate was collected by filtration, washed with 2-propanol, dissolved in 50% MeOH in CHCl3 (60 mL). The solution was poured into saturated aqueous NaHCO3, and the aqueous layer was extracted with CHCl3 (three times). The combined organic layer was dried over MgSO4, filtered, concentrated, and purified by flash chromatography (NH-silica gel, EtOAc to CHCl3) to give [2-(4-amino-piperidin-1-yl)-quinazolin-4-yl]-dimethyl-amine (864 mg, 68%) as a colorless oil.
Reaction SMILES: O.[Na].[N+:3]([CH:6]([CH:9]=O)[CH:7]=O)([O-:5])=[O:4].[NH2:11][C:12]1[NH:16][N:15]=[C:14]([O:17][CH2:18][CH2:19][OH:20])[CH:13]=1>C(O)(=O)C.O>[N+:3]([C:6]1[CH:7]=[N:11][C:12]2[N:16]([N:15]=[C:14]([O:17][CH2:18][CH2:19][OH:20])[CH:13]=2)[CH:9]=1)([O-:5])=[O:4]
Reactant: O=CC(C=O)[N+](=O)[O-]
Reactant: Nc1cc(OCCO)n[nH]1
Agent: [Na]
Solvent: O
Solvent: CC(=O)O
Product: O=[N+]([O-])c1cnc2cc(OCCO)nn2c1
Temperature: 90 °C
Yield: 36.9 %

Procedure:
Nitromalonaldehyde sodium salt monohydrate (1.46 g, 9.29 mmol) was added to crude 2-(5-amino-1H-pyrazol-3-yloxy)ethanol (3.28 g) with salts (1.33 g, 9.29 mmol theoretical) in acetic acid (10 mL). This was heated at 90° C. for 2 hours. The cooled reaction mixture was diluted with water, and the mixture was extracted twice with DCM containing 25% IPA. The organic extracts were dried over magnesium sulfate, filtered, and evaporated to yield regioisomer 2-(6-nitropyrazolo[1,5-a]pyrimidin-2-yloxy)ethanol (0.77 g, 3.43 mmol) as a solid. The 2-(6-nitropyrazolo[1,5-a]pyrimidin-2-yloxy)ethanol (460 mg, 2.9 mmol) was suspended in water (40 mL), treated with saturated aqueous sodium bicarbonate (2 mL), and the mixture was refluxed for 2 hours. The cooled reaction mixture was extracted three times with DCM containing 25% IPA. The organic extracts were dried over magnesium sulfate, filtered, and evaporated to an oil. The crude material was purified by column chromatography with ethyl acetate to provide 2-(5-nitro-1H-pyrazolo[3,4-b]pyridin-3-yloxy)ethanol (60 mg, 0.27 mmol, 2.9% yield) as a solid.
Reaction SMILES: [CH3:1][N:2]1[CH2:6][CH2:5][C:4]2([CH2:11][CH2:10][N:9](C(OC(C)(C)C)=O)[CH2:8][CH2:7]2)[C:3]1=[O:19].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:1][N:2]1[CH2:6][CH2:5][C:4]2([CH2:11][CH2:10][NH:9][CH2:8][CH2:7]2)[C:3]1=[O:19]
Reactant: CN1CCC2(CCN(C(=O)OC(C)(C)C)CC2)C1=O
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CN1CCC2(CCNCC2)C1=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 89.6 %

Procedure:
To a solution of tert-butyl 2-methyl-1-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate (315 mg, 1.174 mmol) in DCM (5 mL) was added TFA (1.718 mL, 22.30 mmol) and the mixture was stirred at room temperature for 2 h. The reaction was concentrated under reduced pressure to obtain crude and purified by SCX cartridge, loading with MeOH, washed with additional MeOH. Product was recovered eluting with 2M NH3 in MeOH. Solvent evaporation gave 2-methyl-2,8-diazaspiro[4.5]decan-1-one (177 mg).
Reaction SMILES: [CH2:1](Cl)[CH:2]=[CH2:3].Cl[SiH:6]1[CH2:11][CH2:10][CH:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][CH3:26])=[CH:20][CH:19]=3)=[CH:14][CH:13]=2)[CH2:8][CH2:7]1>>[CH:3]([Si@H:6]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[CH:20][C:21]([CH2:24][CH2:25][CH3:26])=[CH:22][CH:23]=3)=[CH:14][CH:13]=2)[CH2:8][CH2:7]1)=[CH:2][CH3:1]
Reactant: C=CCCl
Reactant: CCCc1ccc(-c2ccc(C3CC[SiH](Cl)CC3)cc2)cc1
Product: CC=C[Si@H]1CC[C@H](c2ccc(-c3ccc(CCC)cc3)cc2)CC1

Procedure:
Preparation was conducted in the same manner as in Example 1 except for the fact that allyl chloride was used instead of n-propylbromide and that 4'-(4-chloro-4-silacyclohexyl)-4-n-propylbiphenyl was used instead of 4'-(4-chloro-4-silacyclohexyl)-4-fluorobiphenyl.
Reaction SMILES: [CH2:1]([C:4]1[C:19]([O:20][CH2:21][CH2:22][CH2:23][O:24][C:25]2[CH:30]=[C:29]([OH:31])[C:28]([C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=3)=[CH:27][C:26]=2[CH2:39][CH3:40])=[CH:18][CH:17]=[CH:16][C:5]=1[S:6][C:7]1[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=1[C:9]([OH:11])=[O:10])[CH2:2][CH3:3].ClC1C=C(C=CC=1)C(OO)=[O:46]>C(Cl)Cl>[CH2:1]([C:4]1[C:19]([O:20][CH2:21][CH2:22][CH2:23][O:24][C:25]2[CH:30]=[C:29]([OH:31])[C:28]([C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=3)=[CH:27][C:26]=2[CH2:39][CH3:40])=[CH:18][CH:17]=[CH:16][C:5]=1[S:6]([C:7]1[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=1[C:9]([OH:11])=[O:10])=[O:46])[CH2:2][CH3:3]
Reactant: CCCc1c(OCCCOc2cc(O)c(-c3ccc(F)cc3)cc2CC)cccc1Sc1ccccc1C(=O)O
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CCCc1c(OCCCOc2cc(O)c(-c3ccc(F)cc3)cc2CC)cccc1S(=O)c1ccccc1C(=O)O
Yield: 82.4 %

Procedure:
To a solution of 2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]propoxy]thiophenoxy]benzoic acid (450 mg, 0.803 mmol) in methylene chloride (10 mL) at −78° C. was added a solution of 85% m-chloroperoxybenzoic acid (138 mg) in methylene chloride (2 mL). After 40 minutes the mixture was concentrated in vacuo. Purification of the residue via silica gel chromatography (95% chloroform/4.5% methanol/0.5% acetic acid) provided 380 mg (80%) of the title product as an off-white solid: mp >100° C. (dec); NMR (CDCl3) 8.53 (d, J=8 Hz, 1H), 8.14 (d, J=8 Hz, 1H), 7.93 (t, J=8 Hz, 1H), 7.63 (t, J=8 Hz, 1H), 7.43 (m, 2H), 7.13 (m, 2H), 6.94-7.06 (m, 2H), 6.88 (d, J=8 Hz, 1H), 6.50 (d, J=8 Hz, 1H), 7.46 (s, 1H), 6.38 (bs, 1H, —OH), 4.15 (m, 4H), 3.32 (m, 1H), 3.08 (m, 1H), 2.57 (q, J=7.5 Hz, 2H), 2.29 (quintet, J=6 Hz, 2H), 1.75 (m, 2H), 1.17 (t, J=7.5 Hz, 3H), 1.05 (t, J=7.3 Hz, 3H); MS (high resolution) calc 577.202642 (MH+), found 577.203800; IR (CHCl3, cm−1) 2969, 1708, 1497, 1455, 1266, 1146, 1018.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([O:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([OH:28])=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][CH:17]=2)[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:6][C:7]=1[CH3:8].C(=O)([O-])[O-].[K+].[K+].[CH2:35]([CH:37]1[O:39][CH2:38]1)Br.O>CN(C)C=O>[CH3:1][C:2]1[CH:3]=[C:4]([O:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:28][CH2:35][CH:37]4[CH2:38][O:39]4)=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][CH:17]=2)[C:5]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[N:6][C:7]=1[CH3:8]
Reactant: COc1cc2c(Oc3cc(C)c(C)nc3-c3ccccc3)ccnc2cc1O
Reactant: BrCC1CO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1cc2c(Oc3cc(C)c(C)nc3-c3ccccc3)ccnc2cc1OCC1CO1
Temperature: 25 °C
Reaction time: 8 h
Yield: 82 %

Procedure:
4-(5,6-Dimethyl-2-phenyl-pyridin-3-yloxy)-6-methoxy-quinolin-7-ol (compound 332) (150 mg) was dissolved in N,N-dimethylformamide (4 ml) to prepare a solution, potassium carbonate (167 mg) and epibromohydrin (0.1 ml) were added to the solution, and the mixture was stirred at room temperature overnight. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using chloroform-methanol to give the title compound (140 mg, yield 82%).
Reaction SMILES: C([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15](/[C:18](/[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[C:19](\[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)/[CH2:20][CH2:21][Cl:22])=[CH:14][CH:13]=1)C1C=CC=CC=1>C(OCC)(=O)C.C(O)C.[Pd]>[Cl:22][CH2:21][CH2:20]/[C:19](/[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)=[C:18](/[C:15]1[CH:14]=[CH:13][C:12]([O:11][CH2:10][CH2:9][OH:8])=[CH:17][CH:16]=1)\[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1
Reactant: ClCC/C(=C(\c1ccccc1)c1ccc(OCCOCc2ccccc2)cc1)c1ccccc1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCO
Product: OCCOc1ccc(/C(=C(/CCCl)c2ccccc2)c2ccccc2)cc1

Procedure:
Z-1-[4-(2-benzyloxyethoxy)-phenyl]-4-chloro-1,2-diphenyl-but-1-ene (36 g, 0.08 mol) was dissolved in the mixture of ethyl acetate (350 ml) and ethanol (350 ml). Palladium on carbon (5%, 0.28 g) was added and the solution was flushed with hydrogen gas until there was not any starting compound left (thin layer chromatography). Palladium on carbon was filtered off through siliceous earth and the filtrate was evaporated. The residue was crystallized from the mixture of ethanol (155 ml) and water (65 ml). Yield 20 g.
Reaction SMILES: [O:1]=[C:2]1[NH:6][C:5]([CH2:18][S:19](Cl)(=[O:21])=[O:20])([CH2:7][N:8]2[C:12](=[O:13])[C:11]([CH3:15])([CH3:14])[N:10]([CH3:16])[C:9]2=[O:17])[C:4](=[O:23])[NH:3]1.[Cl:24][C:25]1[CH:26]=[CH:27][C:28]([O:31][CH:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)=[N:29][CH:30]=1>>[Cl:24][C:25]1[CH:26]=[CH:27][C:28]([O:31][CH:32]2[CH2:37][CH2:36][N:35]([S:19]([CH2:18][C:5]3([CH2:7][N:8]4[C:12](=[O:13])[C:11]([CH3:15])([CH3:14])[N:10]([CH3:16])[C:9]4=[O:17])[NH:6][C:2](=[O:1])[NH:3][C:4]3=[O:23])(=[O:21])=[O:20])[CH2:34][CH2:33]2)=[N:29][CH:30]=1
Reactant: Clc1ccc(OC2CCNCC2)nc1
Reactant: CN1C(=O)N(CC2(CS(=O)(=O)Cl)NC(=O)NC2=O)C(=O)C1(C)C
Product: CN1C(=O)N(CC2(CS(=O)(=O)N3CCC(Oc4ccc(Cl)cn4)CC3)NC(=O)NC2=O)C(=O)C1(C)C

Procedure:
The title compound was prepared as described in Example 12 from racemic {2,5-dioxo-4-[(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)methyl]imidazolidin-4-yl}methanesulfonyl chloride and 5-chloro-2-(piperidin-4-yloxy)-pyridine.
Reaction SMILES: [CH3:1][C:2]1([CH3:10])[O:6][C@H:5]([CH2:7][CH2:8][OH:9])[CH2:4][O:3]1.O[N:12]1C(=O)C2C(=CC=CC=2)C1=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.O.NN>C(Cl)Cl>[CH3:1][C:2]1([CH3:10])[O:6][C@H:5]([CH2:7][CH2:8][O:9][NH2:12])[CH2:4][O:3]1
Reactant: CC1(C)OC[C@@H](CCO)O1
Reactant: O=C1c2ccccc2C(=O)N1O
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: NN
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: ClCCl
Product: CC1(C)OC[C@@H](CCON)O1
Yield: 43.4 %

Procedure:
The title compound was prepared using the procedure described for Example 2K by using (R)-2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethanol (4.28 mL, 30 mmol), CH2Cl2 (100 mL), 2-hydroxyisoindoline-1,3-dione (4.9 g, 30 mmol), triphenylphosphine (11.8 g, 45 mmol), diisopropylazodicarboxylate (8.8 ml, 45 mmol) and hydrazine hydrate (6.0 mL, 60 mmol) to afford 2.1 g (43%, over two steps) of (R)—O-(2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl)hydroxylamine (2X) as a pale yellow oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.13 (s, 3H), 1.18 (s, 3H), 1.53-1.71 (m, 2H), 3.53 (m, 2H), 3.79-3.89 (m, 1H), 3.89-4.01 (m, 1H), 4.63-4.81 (m, 1H). MS (ES) [M+H] calculated for C2H16NO3, 162.11; found 162.0.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[CH:4][NH:5][C:6]=1[CH2:7][S:8][CH2:9][CH2:10][NH2:11].CS[C:14]1[NH:15][S:16](=[O:21])(=[O:20])[CH2:17][CH2:18][N:19]=1>>[CH3:1][C:2]1[N:3]=[CH:4][NH:5][C:6]=1[CH2:7][S:8][CH2:9][CH2:10][NH:11][C:14]1[NH:15][S:16](=[O:21])(=[O:20])[CH2:17][CH2:18][N:19]=1
Reactant: Cc1nc[nH]c1CSCCN
Reactant: CSC1=NCCS(=O)(=O)N1
Product: Cc1nc[nH]c1CSCCNC1=NCCS(=O)(=O)N1
Yield: 31.1 %

Procedure:
A mixture of 4-methyl-5-((2-aminoethyl)thiomethyl)imidazole (4.0 g.) and 3-methylthio-5,6-dihydro-1,2,4-thiadiazine-1,1-dioxide (4.2 g.) was heated in an oil bath at 140° for 4 hours. The product was chromatographed on a column of silica gel with ethyl acetate-ethanol (3:2) as eluant and finally recrystallized from ethanol-ether to give 3-[2-((4-methyl-5-imidazolyl)methylthio)ethylamino]-5,6-dihydro-1,2,4-thiadiazine-1,1-dioxide (2.2 g.) m.p. 146°-147°.