Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[C:22]([CH3:32])=[CH:23][C:24]([O:30][CH3:31])=[C:25]([CH:29]=4)[C:26](O)=[O:27])=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:4][CH:3]=1.[N:33]1[CH:38]=[CH:37][N:36]=[CH:35][C:34]=1[C:39]1([NH2:42])[CH2:41][CH2:40]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>ClCCl.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[CH:29]=[C:25]([C:26](=[O:27])[NH:42][C:39]5([C:34]6[CH:35]=[N:36][CH:37]=[CH:38][N:33]=6)[CH2:41][CH2:40]5)[C:24]([O:30][CH3:31])=[CH:23][C:22]=4[CH3:32])=[CH:17][C:11]=3[C:12]=2[C:13]([NH:14][CH3:15])=[O:16])=[CH:4][CH:3]=1
Reactant: CNC(=O)c1c(-c2ccc(F)cc2)oc2ccc(-c3cc(C(=O)O)c(OC)cc3C)cc12
Reactant: NC1(c2cnccn2)CC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: ClCCl
Product: CNC(=O)c1c(-c2ccc(F)cc2)oc2ccc(-c3cc(C(=O)NC4(c5cnccn5)CC4)c(OC)cc3C)cc12
Temperature: 25 °C
Reaction time: 18 h

Procedure:
5-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-2-methoxy-4-methylbenzoic acid (0.16 g, 0.369 mmol, 1 eq), 1-(pyrazin-2-yl)cyclopropanamine (0.05 g, 0.369 mmol, 1 eq), EDCI.HCl (0.07 g, 0.369 mmol, 1 eq), HOBT (0.05 g, 0.369 mmol, 1.0 eq) and TEA (0.15 ml, 1.107 mmol, 3 eq) were dissolved in dichloromethane and the above mixture was stirred at room temperature for 18 h. The mixture was then added with water, and organic layer separated and washed with water. The organic layer was dried over Na2SO4 and concentrated. The crude product obtained was purified by Prep. HPLC. 1H NMR (400 MHz, CD3OD): δ 1.43-1.46 (m, 2H), 1.72-1.75 (m, 2H), 2.37 (s, 3H), 2.95 (s, 3H), 4.08 (s, 3H), 7.161 (s, 1H), 7.25-7.30 (m, 2H), 7.35 (dd, J=2, 8.4 Hz, 1H), 7.59 (d, J=1.2 Hz, 1H), 7.64 (d, J=8.4 Hz, 1H), 7.76 (s, 1H), 7.96-7.99 (m, 2H), 8.36 (d, J=2.8 Hz, 1H), 8.520-8.531 (m, 1H), 8.72 (d, J=1.2 Hz, 1H). LCMS: (ES+) m/z=551.2 (M+H)+
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][CH2:15][CH2:16][O:17][CH3:18])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[S:19]1[CH:23]=[CH:22][N:21]=[C:20]1[CH:24]=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([N:14]([CH2:15][CH2:16][O:17][CH3:18])[CH2:24][C:20]2[S:19][CH:23]=[CH:22][N:21]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: O=Cc1nccs1
Reactant: COCCNC1CCN(C(=O)OC(C)(C)C)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCCl
Solvent: ClCCl
Product: COCCN(Cc1nccs1)C1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Amine preparation: 4-(2-Methoxy-ethylamino)-piperidine-1-carboxylic acid tert-butyl ester (465 mg) and 2-thiazolecarboxaldehyde (190 ul) were stirred in dry 1,2-dichloroethane (5 mL) for 1 h. Next were added acetic acid (1 eq.) and sodium triacetoxyborohydride (458 mg). The reaction mixture was stirred at room temperature overnight, diluted with DCM, washed with brine, dried (MgSO4) and the solvent removed in vacuo. The residue was purified using flash chromatography to yield 4-[(2-methoxy-ethyl)-thiazol-2-ylmethyl-amino]-piperidine-1-carboxylic acid tert-butyl ester (574 mg). Treatment of this compound with HCl in DCM/MeOH and basic wash with sodium hydrogen carbonate yielded the desired amine.
Reaction SMILES: [CH3:1][CH:2]=[CH:3][SiH:4](Cl)Cl.[NH:7]1[CH2:11][CH2:10][CH2:9][CH2:8]1>CCCCCC>[N:7]1([CH:1]([CH:2]=[CH:3][SiH3:4])[N:7]2[CH2:11][CH2:10][CH2:9][CH2:8]2)[CH2:11][CH2:10][CH2:9][CH2:8]1
Reactant: CC=C[SiH](Cl)Cl
Reactant: C1CCNC1
Solvent: CCCCCC
Product: [SiH3]C=CC(N1CCCC1)N1CCCC1
Temperature: 25 °C
Reaction time: 12 h
Yield: 72.9 %

Procedure:
Over a 1.5 hour period, 145 grams (1.03 mol) of methylvinyldichlorosilane was added with stirring to a mixture under nitrogen at 0.C of 1 L of dry hexane and 293 grams (4.12 mols) of pyrrolidine. The resulting mixture was allowed to stir for about 12 hours while warming to room temperature. A solid white precipitate was filtered and washed with dry hexane under nitrogen. The solvent was removed under reduced pressure and the product was distilled giving 158 grams (73% yield) of bis(pyrrolidinyl)methylvinylsilane, having a boiling point of 50°-52° C. at less than 1 torr. There was added dropwise to 28.4 grams (135 millimoles) of bis(pyrrolidinyl) methylvinylsilane, which was stirring under nitrogen at 0° C., 26.7 grams (270 millimoles) of butylisocyanate. The reaction was stirred at 0° C. for a period of 12 hours. The mixture was then allowed to warm to room temperature over a 60 minute period. There was obtained a quantitative yield of bis(1,1-tetramethylene-3-butylureidomethylvinylsilane in the form of a clear viscous oil. Its identity was confirmed by IR and NMR. It is referred to hereinafter as the "bis(uriedo) coupler".
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([NH2:11])[O:9][CH:10]=1)=[O:5])[CH3:2].[CH3:12][C:13]([CH3:15])=O.S(C)C.B>C1COCC1.CC(O)=O>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([NH:11][CH:13]([CH3:15])[CH3:12])[O:9][CH:10]=1)=[O:5])[CH3:2]
Reactant: CC(C)=O
Reactant: CCOC(=O)c1coc(N)n1
Agent: B
Solvent: CC(=O)O
Solvent: CSC
Solvent: C1CCOC1
Product: CCOC(=O)c1coc(NC(C)C)n1
Temperature: 25 °C
Reaction time: 72 h
Yield: 63.1 %

Procedure:
A mixture of 2-aminooxazole-4-carboxylic acid ethyl ester (500 mg, 3.2 mmol) and acetone (2.4 mL, 32 mmol) in THF (6 mL) was stirred at rt. BH3.SMe2 (10M in THF, 0.64 mL, 6.4 mmol) was added slowly via syringe (exotherm and gas evolution were observed). AcOH (0.36 mL, 6.4 mmol) was subsequently added in the same manner. Two additional equivalents of borane and AcOH were added 18 h later. After 3 days at rt, the reaction mixture was concentrated in vacuo. The resulting residue was dissolved in EtOAc (100 mL), washed with saturated NH4Cl solution, 0.1 M NH4OH and brine. The organic phase was dried over Na2SO4 and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel, eluting with EtOAc/hexane to give 2-isopropylamino-oxazole-4-carboxylic acid ethyl ester (0.40 g, 64% yield). LCMS found 199 [M+H]+.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[Mg]Br.[C:13](=[S:15])=[S:14].Br[CH:17]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:18]#[N:19]>O>[C:1]1([C:13]([S:15][CH:17]([C:18]#[N:19])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[S:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: Br[Mg]c1ccc2ccccc2c1
Reactant: N#CC(Br)c1ccccc1
Reactant: S=C=S
Solvent: O
Product: N#CC(SC(=S)c1cccc2ccccc12)c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a 100 ml round bottom flask was added 20 ml 2-naphthylmagnesium bromide (0.5M solution in THF). 0.76 g carbon disulfide was added dropwise to this mixture and stirred for ½ h at room temperature. Then to the dark red solution was added 2 g α-bromobenzeneacetonitrile dropwise and the mixture stirred for another 2 h. Water was added to the mixture and the organic product was extracted with diethyl ether (3×50 ml), dried with magnesium sulfate overnight and filtered. After removal of solvent and column chromatography (10:3 mixture of hexane and ethyl ether), pure α-cyanobenzyl dithionaphthalate was obtained as an orange odorless solid (63% yield). Proton and carbon NMR spectra were consistent with the expected structure, CTA-CP-2.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH2:20][N:21]2[CH:25]=[CH:24][N:23]=[CH:22]2)=[CH:9][C:10]2[CH:19]=[CH:18][C:13]([C:14]([O:16]C)=[O:15])=[CH:12][CH:11]=2)=[CH:4][CH:3]=1.[OH-].[Na+]>CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH2:20][N:21]2[CH:25]=[CH:24][N:23]=[CH:22]2)=[CH:9][C:10]2[CH:19]=[CH:18][C:13]([C:14]([OH:16])=[O:15])=[CH:12][CH:11]=2)=[CH:4][CH:3]=1
Reactant: COC(=O)c1ccc(C=C(Cn2ccnc2)c2ccc(F)cc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)c1ccc(C=C(Cn2ccnc2)c2ccc(F)cc2)cc1

Procedure:
A solution of the product from step B (E and Z isomers) (2.3 g, 6.8 mmol) in methanol (50 ml) was treated with 2N aqueous sodium hydroxide solution (7 ml, 14 mmol) for 1 hour. Methanol was then evaporated and the solution was acidified to pH 5.5 with 6N HCl. The resulting precipitate was triturated in ether and filtered to give 4-(-2-(4-fluorophenyl)-3-(imidazol-1-yl)-prop-1-en-1-yl)benzoic acid as a mixture of E and Z isomers 1.4 g (65%).
Reaction SMILES: [F:1][C:2]1[CH:19]=[CH:18][CH:17]=[CH:16][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][C:11]([CH3:14])=[N:12][CH:13]=[C:8]2[C:7](I)=[N:6]1.[Cu][C:21]#[N:22]>CS(C)=O>[F:1][C:2]1[CH:19]=[CH:18][CH:17]=[CH:16][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][C:11]([CH3:14])=[N:12][CH:13]=[C:8]2[C:7]([C:21]#[N:22])=[N:6]1
Reactant: N#C[Cu]
Reactant: Cc1ncc2c(I)nn(Cc3ccccc3F)c2n1
Solvent: CS(C)=O
Product: Cc1ncc2c(C#N)nn(Cc3ccccc3F)c2n1
Temperature: 150 °C

Procedure:
1.485 g (4.03 mmol) of 1-(2-fluorobenzyl)-3-iodo-6-methyl-1H-pyrazolo[3,4-d]pyrimidine and 397 mg (4.44 mmol) of copper(I) cyanide were put in 11 ml of absolute DMSO and heated for 2 h at 150° C. After cooling, the reaction mixture was filtered on Celite and then washed with ethyl acetate and THF. The organic phase was washed with 25% aqueous ammonia solution, saturated aqueous ammonium chloride solution and saturated aqueous sodium chloride solution, dried over sodium sulphate and concentrated in a rotary evaporator. 994 mg (purity 81%, 75% of theor.) of the target compound was obtained.
Reaction SMILES: [CH3:1][O:2][CH:3]([O:14][CH3:15])[CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH3:13])[CH:9]=[C:10]([OH:12])[CH:11]=1.[CH3:16][N:17]=[C:18]=[O:19]>C(N(CC)CC)C.C1C=CC=CC=1>[CH3:16][NH:17][C:18](=[O:19])[O:12][C:10]1[CH:9]=[C:8]([CH3:13])[CH:7]=[C:6]([O:5][CH2:4][CH:3]([O:2][CH3:1])[O:14][CH3:15])[CH:11]=1
Reactant: CN=C=O
Reactant: COC(COc1cc(C)cc(O)c1)OC
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: CNC(=O)Oc1cc(C)cc(OCC(OC)OC)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
3-(2,2-Dimethoxyethoxy)-5-hydroxytoluene (2.50 grams), benzene (50 ml) and triethylamine (4 drops) were charged into a glass reaction vessel equipped with a mechanical stirrer. Methyl isocyanate (1.0 ml) was added to the vessel, and the resulting mixture was stirred at room temperature for a period of about 2 hours. The mixture was then allowed to stand at ambient temperature over the weekend. After this time the reaction mixture was stripped of benzene, leaving a viscous liquid residue. This residue was distilled under vacuum to yield the desired product O-[3-(2,2-dimethoxyethoxy)-5-methylphenyl] N-methylcarbamate as an oil.
Reaction SMILES: [H-].[Na+].[CH2:3]([O:5][C:6]1[C:10]([CH2:11][CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:9][N:8]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=2)[N:7]=1)[CH3:4].Cl[CH2:27][N:28]1[C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=2[N:30]=[N:29]1.O>CN(C)C=O>[N:28]1([CH2:27][O:25][C:22]2[CH:21]=[CH:20][C:19]([CH2:18][N:8]3[CH:9]=[C:10]([CH2:11][CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:6]([O:5][CH2:3][CH3:4])=[N:7]3)=[CH:24][CH:23]=2)[C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=2[N:30]=[N:29]1
Reactant: CCOC(=O)CCc1cn(Cc2ccc(O)cc2)nc1OCC
Reactant: ClCn1nnc2ccccc21
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)CCc1cn(Cc2ccc(OCn3nnc4ccccc43)cc2)nc1OCC
Temperature: 25 °C
Reaction time: 1 h
Yield: 96.9 %

Procedure:
Sodium hydride (60%, oily, 60.0 mg) was added to a solution of ethyl 3-[3-ethoxy-1-(4-hydroxybenzyl)-1H-pyrazol-4-yl]propionate (478 mg) and 1-chloromethyl-1H-benzotriazole (251 mg) in N,N-dimethylformamide (10 ml) at, 0° C., and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into water, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated. The residue was subjected to silica gel column chromatography to obtain ethyl 3-[1-[4-(1H-benzotriazol-1-ylmethoxy)benzyl]-3-ethoxy-1H-pyrazol-4-yl]propionate (652 mg, yield: 97%) as a colorless oily substance from the fraction eluted with ethyl acetate-hexane (1:1, volume ratio).
Reaction SMILES: [CH:1]([O:4][C@H:5]1[CH2:22][C@@:21]2([CH3:23])[C@@H:8]([CH2:9][CH2:10][C@@H:11]3[C@@H:20]2[CH2:19][CH2:18][C@@:16]2([CH3:17])[C@H:12]3[CH2:13][CH2:14][C:15]2=O)[CH2:7][C@@H:6]1[OH:25])([CH3:3])[CH3:2].[BH3-]C#N.[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1.S1(CCCC1)(=O)=O>O.CN(C=O)C>[CH:1]([O:4][C@H:5]1[CH2:22][C@@:21]2([CH3:23])[C@@H:8]([CH2:9][CH2:10][C@@H:11]3[C@@H:20]2[CH2:19][CH2:18][C@@:16]2([CH3:17])[C@H:12]3[CH2:13][CH2:14][CH2:15]2)[CH2:7][C@@H:6]1[OH:25])([CH3:3])[CH3:2]
Reactant: CC(C)O[C@H]1C[C@@]2(C)[C@@H](CC[C@@H]3[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]32)C[C@@H]1O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Solvent: O=S1(=O)CCCC1
Product: CC(C)O[C@H]1C[C@@]2(C)[C@@H](CC[C@H]3[C@@H]4CCC[C@@]4(C)CC[C@@H]32)C[C@@H]1O
Temperature: 110 °C

Procedure:
To a mixture of 2β-isopropoxy-3α-hydroxy-5α-androstan-17-one tosylhydazone (300 mg), NaBH3CN (144 mg) and p-toluenesulfonic acid (30 mg) was added DMF and sulfolane (1:1, 3 mL) and the mixture obtained was heated to 110° C. for 3 h. Then additional amount of NaBH3CN (144 mg) and p-toluenesulfonic acid (30 mg) was added and it was heated for another hour. Water was then added and the mixture was extracted with EtOAc (2×45 mL). The combined extracts were dried over Na2SO4 and the crude product obtained by removal of the solvent was purified by flash chromatography over silica gel to yield the pure 2β-isopropoxy-3α-hydroxy-5α-androstane (37 mg); TLC Rf (EtOAc:hexane 1:9)=0.17.
Reaction SMILES: [CH3:1][C:2]1([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[C@@H:18]4[CH2:19][CH2:20][CH2:21][CH2:22][C@H:17]4[NH:16][C:15]3=[O:23])[CH2:10][CH2:9]2)[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[CH:24]1([C:27](O)=[O:28])[CH2:26][CH2:25]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH:24]1([C:27]([N:5]2[CH2:6][CH2:7][C:2]([N:8]3[CH2:13][CH2:12][CH:11]([N:14]4[C@@H:18]5[CH2:19][CH2:20][CH2:21][CH2:22][C@H:17]5[NH:16][C:15]4=[O:23])[CH2:10][CH2:9]3)([CH3:1])[CH2:3][CH2:4]2)=[O:28])[CH2:26][CH2:25]1
Reactant: O=C(O)C1CC1
Reactant: CC1(N2CCC(N3C(=O)N[C@@H]4CCCC[C@H]43)CC2)CCNCC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC1(N2CCC(N3C(=O)N[C@@H]4CCCC[C@H]43)CC2)CCN(C(=O)C2CC2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 27.8 %

Procedure:
To the solution (3aR,7aR)-1-[1-(4-methyl-4-piperidyl)-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-3H-benzoimidazol-2-one (HCl salt, 99 mg, 0.25 mmol) in dry DMF (3 mL) was added cyclopropanecarboxylic acid (26 mg, 0.3 mmol) followed by HATU (114 mg, 0.3 mmol) and diisopropylethylamine (0.10 mL, 0.5 mmol) and the mixture was stirred at room temperature for 1 h. The solvent was removed in vacuo, the residue dissolved in dichloromethane (15 mL), washed with saturated NaHCO3 (10 mL) and brine (10 mL), dried over Na2SO4 and concentrated in vacuo. The residue was purified with preparative LC/MS (high pH) to afford the title compound (27 mg, 28%) as white powder. 1H NMR (400 MHz, METHANOL-D4) δ ppm 0.63-0.81 (m, 4H), 0.97 (s, 3H), 1.23-1.43 (m, 5H), 1.51-1.82 (m, 9H), 1.83-1.95 (m, 3H), 2.06-2.29 (m, 2H), 2.81-3.00 (m, 2H), 2.98-3.14 (m, 2H), 3.33-3.64 (m, 4H), 3.70-3.88 (m, 1H). MS (M+1): 389.2.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([N+:11]([O-:13])=[O:12])[CH:10]=1)[C:5]([OH:7])=[O:6].S(=O)(=O)(O)O.[CH3:19]O>>[OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([N+:11]([O-:13])=[O:12])[CH:10]=1)[C:5]([O:7][CH3:19])=[O:6]
Reactant: O=C(O)c1cc(O)cc([N+](=O)[O-])c1
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)c1cc(O)cc([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a clean, dry 100 mL round bottom flask is added 3-hydroxy-5-nitrobenzoic acid (1 g, 5.5 mmole, 1 eq) followed by 10 mL methanol and 2 mL of concentrated sulfuric acid. The exothermic reaction mixture reached 60° C. prior to cooling to room temperature. The reaction mixture was stirred for 18 h prior to partitioning between ethyl acetate and water. After extraction, the organic layer was dried over magnesium sulfate, filtered and evaporated. A white solid product was obtained (1 g, 100%). Calc'd for C8H7NO5; m/z (M+H+)=198; found 198.
Reaction SMILES: [C:1]([O:9][C@H:10]1[CH2:34][CH2:33][C@@:32]2([CH3:35])[C@@H:12]([CH2:13][CH2:14][C:15]3[C:16]4[C@:28]([CH3:36])([CH2:29][CH2:30][C:31]=32)[C@@H:19]([C@H:20]([CH3:27])[CH2:21][CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])[CH2:18][CH:17]=4)[C:11]1([CH3:38])[CH3:37])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC1C=CC=C(C(OO)=[O:47])C=1>C(OCC)C.C(=O)(O)[O-].[Na+]>[C:1]([O:9][C@H:10]1[CH2:34][CH2:33][C@@:32]2([CH3:35])[C@H:12]([CH2:13][CH2:14][C:15]3[C@H:16]4[C@:28]([CH3:36])([CH2:29][CH2:30][C:31]=32)[C@@H:19]([C@H:20]([CH3:27])[CH2:21][CH2:22][CH2:23][CH:24]([CH3:26])[CH3:25])[CH2:18][C:17]4=[O:47])[C:11]1([CH3:38])[CH3:37])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)CCC[C@@H](C)[C@H]1CC=C2C3=C(CC[C@@]21C)[C@@]1(C)CC[C@H](OC(=O)c2ccccc2)C(C)(C)[C@@H]1CC3
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOCC
Product: CC(C)CCC[C@@H](C)[C@H]1CC(=O)[C@H]2C3=C(CC[C@@]21C)[C@@]1(C)CC[C@H](OC(=O)c2ccccc2)C(C)(C)[C@H]1CC3
Reaction time: 0.5 h
Yield: 75.4 %

Procedure:
To a solution of 3β-benzoyloxy-4,4-dimethyl-5α-cholest-8,14-diene (5.0 g, 10.2 mmol) in diethyl ether solution (300 mL) and 0.5M aqueous sodium bicarbonate (300 mL) was added meta-chloro-perbenzoic acid (2.44 g, 11.3 mmol) (Aldrich). After 30 min, the ether fraction was separated from the sodium bicarbonate layer and the aqueous fraction was repeatedly extracted with diethyl ether (5×500 mL). The organic fractions were combined, washed with brine (1×100 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to about 150 ml. This ether solution of 38a was promptly cooled (0°) and treated dropwise with boron trifluoride etherate (26 mL, 22.5 mmol (Aldrich). After 30 min, the reaction was quenched with ice water (200 mL) and the aqueous phase was reextracted with ether (3×100 mL). The combined ether fractions were extracted with saturated sodium bicarbonate solution (1×200 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was crystallized from isopropanol (75 mL) to afford 4.10 g of 3β-benzoyloxy-4,4-dimethyl-5β-cholest-8-en-15-one (Compound 40a) in 75% yield.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([OH:16])[CH:12]=[C:13]([CH3:15])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[C:26]1([S:36](Cl)(=[O:38])=[O:37])[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH:29]=[CH:28][CH:27]=1>C(Cl)Cl.O>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([O:16][S:36]([C:26]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH:29]=[CH:28][CH:27]=2)(=[O:38])=[O:37])[CH:12]=[C:13]([CH3:15])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=S(=O)(Cl)c1cccc2ccccc12
Reactant: Cc1cc(O)cc(OCc2ccccc2)c1
Solvent: O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cc(OCc2ccccc2)cc(OS(=O)(=O)c2cccc3ccccc23)c1
Temperature: 0 °C
Reaction time: 2 h
Yield: 86.5 %

Procedure:
A solution of 3-benzyloxy-5-methylphenol (600 mg, 3.0 mmol), as prepared in step a of Example 3, in methylene chloride (15 mL) at 0° C. was treated with N,N-diisopropylethylamine (0.5 mL) and 1-naphthalenesulfonyl chloride (670 mg, 3.0 mmol). The reaction mixture was stirred at 0° C. for 2 h and at room temperature for 2 h. The reaction mixture was diluted with methylene chloride (200 mL) and water (50 mL). The organic extract was washed sequentially with saturated NaHCO3 (2×50 mL) and brine (2×50 mL), dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography (1:1 hexane:methylene chloride) to give the title compound as a colorless liquid (1.05 g, 87%). 1H-NMR (300 MHz, CDCl3) δ 2.16 (s, 3H), 4.73 (s, 2H), 6.23 (t, 1H), 6.37 (dd, 1H), 6.61 (dd, 1H), 7.28 (m, 5H), 7.48 (t, 1H), 7.67 (t, 1H), 7.77 (t, 1H), 7.97 (t, 1H), 8.12 (dt, 2H), 8.19 (dd, 1H).
Reaction SMILES: [OH-].[Na+].O.C[O:5][C:6](=[O:42])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([CH2:38][CH3:39])([C:23]3[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][CH:31]([OH:36])[C:32]([CH3:35])([CH3:34])[CH3:33])=[C:25]([CH3:37])[CH:24]=3)[CH2:21][CH3:22])=[CH:16][C:15]=2[CH3:40])=[CH:10][C:9]=1[F:41].Cl>CO>[CH2:21]([C:20]([C:17]1[CH:18]=[CH:19][C:14]([C:11]2[CH:12]=[CH:13][C:8]([CH2:7][C:6]([OH:42])=[O:5])=[C:9]([F:41])[CH:10]=2)=[C:15]([CH3:40])[CH:16]=1)([C:23]1[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][CH:31]([OH:36])[C:32]([CH3:34])([CH3:35])[CH3:33])=[C:25]([CH3:37])[CH:24]=1)[CH2:38][CH3:39])[CH3:22]
Reactant: CCC(CC)(c1ccc(CCC(O)C(C)(C)C)c(C)c1)c1ccc(-c2ccc(CC(=O)OC)c(F)c2)c(C)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CCC(CC)(c1ccc(CCC(O)C(C)(C)C)c(C)c1)c1ccc(-c2ccc(CC(=O)O)c(F)c2)c(C)c1
Temperature: 25 °C
Reaction time: 6 h
Yield: 96.4 %

Procedure:
A mixed solution of a 6 N sodium hydroxide aqueous solution (0.011 mL) with water (0.032 mL) was added to a solution of (4′-{1-ethyl-1-[4-(3-hydroxy-4,4-dimethyl-pentyl)-3-methyl-phenyl]-propyl}-3-fluoro-2′-methyl-biphenyl-4-yl)acetic acid methyl ester (Example 60-(2); 8.5 mg, 0.016 mmol) in methanol (0.22 mL) at room temperature, and the mixture was stirred at room temperature for six hours. The mixture was acidified with dilute hydrochloric acid aqueous solution, followed by extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to give the title compound (8 mg, 100%).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7](=O)[CH2:8][C:9](=O)[CH3:10])[CH:2]=1.O.[NH2:14][NH2:15]>CO>[CH3:10][C:9]1[CH:8]=[C:7]([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[NH:14][N:15]=1
Reactant: NN
Reactant: CC(=O)CC(=O)c1cccnc1
Solvent: O
Solvent: CO
Product: Cc1cc(-c2cccnc2)[nH]n1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
1-Pyridin-3-yl-butane-1,3-dione (step 1) (500 mg, 3.06 mmol) was dissolved in MeOH (20 ml). Hydrazine monohydrate (230 mg, 223 μl, 4.60 mmol) was added and the resulting mixture was stirred at RT for 1 hour. After cooling to RT, the solvent was removed in vacuo. The crude residue was dissolved in DCM, dried over (MgSO4) filtered and concentrated in vacuo to afford the title compound which was used without further purification.
Reaction SMILES: [C:1]1([CH:7]2[O:11][N:10]=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([N:18]4[CH2:22][CH:21]([CH2:23][N:24]5[CH2:29][CH2:28][N:27]([CH:30]([C:37]([O:39][CH2:40][CH3:41])=[O:38])[CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:26][CH2:25]5)[O:20][C:19]4=[O:42])=[CH:14][CH:13]=3)[NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(OCC)(=O)C>CO>[C:7]([NH:8][C:9]([C:12]1[CH:13]=[CH:14][C:15]([N:18]2[CH2:22][CH:21]([CH2:23][N:24]3[CH2:29][CH2:28][N:27]([CH:30]([C:37]([O:39][CH2:40][CH3:41])=[O:38])[CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:26][CH2:25]3)[O:20][C:19]2=[O:42])=[CH:16][CH:17]=1)=[NH:10])(=[O:11])[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCOC(=O)CC(C(=O)OCC)N1CCN(CC2CN(c3ccc(C4=NOC(c5ccccc5)N4)cc3)C(=O)O2)CC1
Solvent: CO
Solvent: CCOC(C)=O
Product: CCOC(=O)CC(C(=O)OCC)N1CCN(CC2CN(c3ccc(C(=N)NC(=O)c4ccccc4)cc3)C(=O)O2)CC1

Procedure:
1,3 g 3-[4-(5-phenyl-1,2,4-oxadiazolin-3-yl)phenyl]-5-[4-(1,2-diethoxycarbonyl-ethyl)-piperazinomethyl]-oxazolidin-2-one [obtainable as described in Ex. 14] are dissolved in 50 ml methanol and hydrogenated on Raney nickel. The reaction mixture is then filtered and the filtrate is concentrated in vacuo. The product obtained is treated with 20 ml of ethyl acetate in the presence of heat and filtered off with suction after cooling. 3-[4-(N-benzoylamidino)-phenyl]-5-[4-(1,2-diethoxycarbonylethyl)-piperazinomethyl]-oxazolidin-2-one, m.p. 136°, is obtained.