Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [ClH:1].[CH:2]1([N:14]2[CH2:30][CH2:29][C:17]3([N:21]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH2:20][NH:19][C:18]3=[O:28])[CH2:16][CH2:15]2)[C:12]2=[C:13]3[C:8](=[CH:9][CH:10]=[CH:11]2)[CH:7]=[CH:6][CH:5]=[C:4]3[CH2:3]1.[CH3:31]I>>[ClH:1].[CH:2]1([N:14]2[CH2:15][CH2:16][C:17]3([N:21]([C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[CH2:20][N:19]([CH3:31])[C:18]3=[O:28])[CH2:29][CH2:30]2)[C:12]2=[C:13]3[C:8](=[CH:9][CH:10]=[CH:11]2)[CH:7]=[CH:6][CH:5]=[C:4]3[CH2:3]1
Reactant: CI
Reactant: O=C1NCN(c2ccccc2)C12CCN(C1Cc3cccc4cccc1c34)CC2
Agent: Cl
Product: CN1CN(c2ccccc2)C2(CCN(C3Cc4cccc5cccc3c45)CC2)C1=O

Procedure:
The title compound, light brown solid, m.p.>185° C. (dec.) and MS: m/e=398.3 (M+H+) was prepared in accordance with the general method of example 4 from (RS)-8-(acenaphthen-1-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one hydrochloride (1:1) and methyl iodide.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:12][CH:11]([CH2:13][NH:14][C:15]([C:17]3[S:18][C:19]([Cl:22])=[CH:20][CH:21]=3)=[O:16])[O:10][N:9]=2)=[CH:4][CH:3]=1.[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[Sn](CCCC)(CCCC)CCCC>C1(C)C=CC=CC=1>[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:12][CH:11]([CH2:13][NH:14][C:15]([C:17]3[S:18][C:19]([Cl:22])=[CH:20][CH:21]=3)=[O:16])[O:10][N:9]=2)=[CH:4][CH:3]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccccn1
Reactant: O=C(NCC1CC(c2ccc(Br)cc2)=NO1)c1ccc(Cl)s1
Solvent: Cc1ccccc1
Product: O=C(NCC1CC(c2ccc(-c3ccccn3)cc2)=NO1)c1ccc(Cl)s1

Procedure:
Combined the bromide from Example 1 (50 mg, 0.13 mmol) with 2-pyridyltributyl stannane (55 mg, 0.15 mmol) and 5 mL of toluene. The mixture was degassed for three minutes then treated with tetrakistriphenylphosphine palladium (14 mg, 0.013 mmol) and stirred at reflux overnight. The following day the reaction was checked by TLC which showed consumption of the starting bromide and a more polar spot. The reaction was partitioned with aqueous sodium fluoride and ethyl acetate, separated and dried over magnesium sulfate. After filtration and concentration the crude residue was purified by preparative HPLC affording the desired product as a white solid. MS found for C20H16ClN3O2S as (M+H)+ 398.1, 400.1
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[NH:10][C:11]2[C:16]([CH:17]=1)=[CH:15][CH:14]=[C:13]([C:18](O)=[O:19])[CH:12]=2.[C:21]([C:25]1[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=1)([CH3:24])([CH3:23])[CH3:22].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(OCC)(=O)C>CN(C=O)C>[C:21]([C:25]1[CH:26]=[CH:27][C:28]([NH:29][C:18]([C:13]2[CH:12]=[C:11]3[C:16]([CH:17]=[C:9]([C:3]4[C:4]([CH3:8])=[CH:5][CH:6]=[CH:7][C:2]=4[CH3:1])[NH:10]3)=[CH:15][CH:14]=2)=[O:19])=[CH:30][CH:31]=1)([CH3:24])([CH3:22])[CH3:23]
Reactant: Cc1cccc(C)c1-c1cc2ccc(C(=O)O)cc2[nH]1
Reactant: CC(C)(C)c1ccc(N)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cc1cccc(C)c1-c1cc2ccc(C(=O)Nc3ccc(C(C)(C)C)cc3)cc2[nH]1
Reaction time: 18 h

Procedure:
A mixture of 2-(2,6-dimethylphenyl)-1H-indole-6-carboxylic acid. (17 mg, 60 μmol), 4-tert.-butylaniline (10 μL, 9.4 mg, 63 μmol) and HATU (33 mg, 87 μmol) in DMF (3 mL) was stirred, initially at ambient temperature, then at 60° C. for 18 h. The mixture was poured into ethyl acetate and extracted once with water and five times with brine. The organic layer was dried, filtered, and solvent was removed under reduced pressure. The residual material was chromatographed using a gradient of 20-60% heptane/ethyl acetate to give 2-(2,6-dimethylphenyl)-1H-indole-6-carboxylic acid (4-tert-butylphenyl)-amide. 1H NMR (CDCl3, 400 MHz) δ 8.54 (s, broad, 1H), 8.12 (s, 1H), 7.89 (s, 1H), 7.70 (d, J=8.3 Hz, 1H), 7.56 (m, 3H), 7.37 (d, J=8.7 Hz, 2H), 7.15 (d, J=7.6 Hz, 2H), 6.46 (s, 1H), 2.18 (s, 6H), 1.33 (s, 9H). MS (m/z) 397.2 (M+1).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]([CH:24]=O)=[C:16]2[CH3:26])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH2:28][OH:29].CO>N1C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]([CH:24]=[N:28][OH:29])=[C:16]2[CH3:26])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1c(C=O)c2ccccc2n1-c1ccc(OCc2ccccc2)cc1
Reactant: NO
Agent: Cl
Solvent: CO
Solvent: c1ccncc1
Product: Cc1c(C=NO)c2ccccc2n1-c1ccc(OCc2ccccc2)cc1
Yield: 53 %

Procedure:
A solution of 1-(4-benzyloxyphenyl)-2-methyl-1H-indole-3-carbaldehyde (0.64 g, 1.9 mmol), hydroxylamine hydrochloride (0.25 g, 3.6 mmol), methanol (25 mL) and pyridine (1 mL) was heated to reflux for 30 min. The mixture was cooled, the methanol removed by evaporation. The product was extracted into ethyl acetate (2×50 mL) and the organic layer was washed with water and brine and dried over MgSO4. The solvent was evaporated, and the product was purified by silica gel chromatography (25% ethyl acetate-hexanes) to provide a white solid (53%): mp 171-173° C.; 1H NMR (DMSO-d6): δ 2.31 (3H, s), 5.20 (2H, s), 6.94-7. J01 (1H, m), 7.10-7.14 (2H, m), 7.23 (2H, d, J=8.9 Hz), 7.37-7.47 (5H, m), 7.52 (2H, d, J=7.4 Hz), 8.01-8.03 (1H, m), 8.41 (1 H, s), 10.66 (1H, s); MS m/z (M+H)+357. Anal. for C23H20N2O2·0.5H2O: Calc'd: C, 75.60; H, 5.79; N, 7.67. Found: C, 75.12; H, 5.53; N, 7.34.
Reaction SMILES: [CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12](=O)[C:13]([Cl:19])=[C:14]([Cl:18])[C:15]([OH:17])=[O:16])=[C:4]1[CH3:21])[CH3:2].[CH3:22][C:23]1[NH:24][C:25]2[C:30]([CH:31]=1)=[CH:29][CH:28]=[CH:27][CH:26]=2>C(OC(=O)C)(=O)C>[CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]2([C:31]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[NH:24][C:23]=3[CH3:22])[O:17][C:15](=[O:16])[C:14]([Cl:18])=[C:13]2[Cl:19])=[C:4]1[CH3:21])[CH3:2]
Reactant: CCn1c(C)c(C(=O)C(Cl)=C(Cl)C(=O)O)c2ccccc21
Reactant: Cc1cc2ccccc2[nH]1
Solvent: CC(=O)OC(C)=O
Product: CCn1c(C)c(C2(c3c(C)[nH]c4ccccc34)OC(=O)C(Cl)=C2Cl)c2ccccc21
Temperature: 25 °C

Procedure:
A mixture of 10.0 g (0.047 mole) of 4-(1-ethyl-2-methyl-3-indolyl)-2,3-dichloro-4-oxo-2-butenoic acid, 4.0 g (0.030 mole) of 2-methylindole and 150 ml of acetic anhydride was stirred at ambient temperature in an atmosphere of air for approximately seventeen hours and the solid which formed was collected by filtration. After drying in vacuo at 60° C. there was obtained 5-(1-ethyl-2-methyl-3-indolyl)-5-(2-methyl-3-indolyl)-3,4-dichloro-2(5H)-furanone (Formula V: R=CH3CH2 ; R1 =R3 =CH3 ; R2 =Y=Y1 =H) as a blue-colored solid which melted over the range of 282°-285° C.
Reaction SMILES: [CH3:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4].C([Li])CCC.[C:13](OC)(=[O:19])[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].C(O)(=O)C>O1CCCC1>[O:19]=[C:13]([CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH2:1][P:2](=[O:7])([O:5][CH3:6])[O:3][CH3:4]
Reactant: CCCCCC(=O)OC
Reactant: COP(C)(=O)OC
Agent: [Li]CCCC
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CCCCCC(=O)CP(=O)(OC)OC
Temperature: -78 °C

Procedure:
A solution of 100 g. of dimethyl methylphosphonate in 670 ml. of anhydrous tetrahydrofuran is cooled to -78°C. under an argon atmosphere. To the cold solution are added dropwise under stirring and under argon atmosphere, 495 ml. of a 0.1M solution of n-butyllithium in tetrahydrofuran, maintaining the temperature at -70°C. When the addition is complete the reaction mixture is maintained under the same conditions for 10 additional minutes, a solution of 58 ml. of methyl caproate dissolved in 187 ml. of tetrahydrofuran is then carefully added, maintaining the temperature at -78°C. The reaction mixture is stirred at -78°C. for 2 hours followed by stirring for 4 hours at room temperature. The excess base is neutralized with acetic acid and the solvent is evaporated under high vacuo. The residue is dissolved in ether-water (1:1, 950 ml. each), the ethereal phase is separated, washed with water and dried over magnesium sulfate. The ether is evaporated and the residue is purified by vacuum distillation, thus obtaining the pure dimethyl 2-oxoheptylphosphonate.
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[NH2:13])=[CH:4][CH:3]=1.[CH:16]1([C:21]([N:23]2[CH2:28][CH2:27][C:26](=O)[CH2:25][CH2:24]2)=[O:22])[CH2:20][CH2:19][CH2:18][CH2:17]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[NH:13][CH:26]2[CH2:27][CH2:28][N:23]([C:21]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:22])[CH2:24][CH2:25]2)=[CH:4][CH:3]=1
Reactant: Nc1ccccc1Oc1ccc(Cl)cc1
Reactant: O=C1CCN(C(=O)C2CCCC2)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Solvent: CC(=O)O
Product: O=C(C1CCCC1)N1CCC(Nc2ccccc2Oc2ccc(Cl)cc2)CC1
Temperature: 100 °C
Yield: 45.7 %

Procedure:
To a solution of 2-(4-chlorophenoxy)phenylamine (100 mg, 0.45 mmol), 1-cyclopentylcarbonyl-4-piperidone (144 mg, 0.735 mmol) and acetic acid (147 mg, 2.45 mmol) in DCE (1.5 ml) was added sodium triacetoxyborohydride (260 mg, 1.23 mmol). This solution was then heated at 100° C. for 15 minutes in a CEM discover microwave (fixed hold time set to on). The reaction mixture was then quenched with saturated aqueous sodium bicarbonate solution (5 ml) and extraction with ethyl acetate (3×5 ml) followed. The combined organics were concentrated in vacuo and purification by flash chromatography proceeded (eluant: 8:2 hexane:ethyl acetate) to provide the title compound as a transparent oil (82 mg, 43%). 1H NMR (300 MHz, CDCl3): δ 1.16-1.36 (2H, m, 2×CH), 1.47-1.56 (2H, m, 2×CH), 1.59-1.78 (6H, m, 6×CH), 1.93-2.08 (2H, m, 2×CH), 2.76-2.87 (2H, m, 2×CH), 3.07-3.18 (1H, m, CH), 3.43-3.52 (1H, sept, J=3.9 Hz, CH), 3.78-3.89 (1H, bd, J=13.8 Hz, CH), 3.97-4.10 (1H, m, CH), 4.31-4.42 (1H, bd, J=13.5 Hz, NH), 6.55-6.62 (1H, td, J=1.5, 1.2, 1.2, 7.7 Hz, ArH), 6.68-6.71 (1H, dd, J=1.5, 8.1 Hz, ArH), 6.73-6.77 (1H, dd, J=1.5, 8.1 Hz, ArH), 6.79-6.84 (2H, m, ArH), 6.95-7.01 (1H, td, J=1.5, 0.6, 1.5, 7.7 Hz, ArH), 7.16-7.22 ppm (2H, m, ArH). 13C NMR (67.93 MHz, CDCl3): δ 19.5, 19.6, 30.2, 32.2, 33.2, 40.6, 44.1, 49.9, 112.2, 117.2, 118.8, 119.6, 125.3, 127.9, 129.8, 138.9, 143.1, 156.1, 175.4 ppm LCMS: M+H, 421.46 HPLC: 98.41% (3.124 min, isocratic 90% acetonitrile, 10% water at 1 ml/min).
Reaction SMILES: [Si:1]([CH:18]([OH:25])[C@@H:19]1[O:23][C:22](=[O:24])[CH2:21][CH2:20]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Si](Cl)(C)(C)C.[C:41]1([Se:47]Br)[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>C1COCC1.CCOCC>[Si:1]([CH:18]([OH:25])[C@@H:19]1[O:23][C:22](=[O:24])[C@@H:21]([Se:47][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH2:20]1)([C:14]([CH3:17])([CH3:15])[CH3:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Br[Se]c1ccccc1
Reactant: CC(C)(C)[Si](c1ccccc1)(c1ccccc1)C(O)[C@H]1CCC(=O)O1
Agent: C[Si](C)(C)Cl
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: CC(C)(C)[Si](c1ccccc1)(c1ccccc1)C(O)[C@H]1C[C@H]([Se]c2ccccc2)C(=O)O1
Temperature: -78 °C
Reaction time: 1 h
Yield: 57 %

Procedure:
To a solution of 4 (5 g, 14.1 mmol) in anhydrous THF (50 mL) at −78° C. was added lithium bis(trimethylsilyl)amide (1 M solution in THF, 15.8 mL, 15.8 mmol) over a period of 10 min. After being stirred at −78° C. for 1 h, Me3SiCl (1.918 g, 17.65 mmol) was added dropwise, and the reaction mixture was allowed to warm to room temperature. After being stirred at room temperature for 30 min, the mixture was cooled to −78° C., and a solution of PhSeBr (5 g, 21.19 mmol) in anhydrous THF (25 mL) was added rapidly. The mixture was diluted with ether (50 mL), washed with water until the color of organic layer changed from dark brown to light yellow, dried (Na2SO4), filtered, and evaporated. The resulting oily residue [containing 3S (α, 5) and 3R (β) isomers; TLC: hexane/EtOAc, 10:1; Rf=0.42 and 0.28, respectively] was purified by flash chromatography on silica gel, eluting with hexane/EtOAc (99:1 to 95:5) to give the title compound 5 as a light yellow oil (4.093 g, 57%). 1H NMR (CDCl3) δ 7.69-7.60 (m, 6H, arom.), 7.46-7.30 (m, 9H, arom.), 4.37-4.34 (m, 1H, H-5), 4.12-4.08 (m, 1H, H-3), 3.86-3.82 (dd, J=3 & 11 Hz, 1H, CH2OH), 3.62-3.59 (dd, J=3 & 11 Hz, 1H, CH2OH), 2.73-2.67 (m, 1H, H-4), 2.32-2.28 (m, 1H, H-4), 1.02 (s, 9H, t-Bu).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)=[CH:4][C:3]=1[N+:18]([O-:20])=[O:19].[OH:21][C:22]1[CH:27]=[CH:26][C:25]([SH:28])=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl>CN(C)C=O>[CH3:17][O:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:9][O:8][C:5]2[CH:6]=[CH:7][C:2]([S:28][C:25]3[CH:26]=[CH:27][C:22]([OH:21])=[CH:23][CH:24]=3)=[C:3]([N+:18]([O-:20])=[O:19])[CH:4]=2)=[CH:11][CH:12]=1
Reactant: COc1ccc(COc2ccc(Cl)c([N+](=O)[O-])c2)cc1
Reactant: Oc1ccc(S)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: COc1ccc(COc2ccc(Sc3ccc(O)cc3)c([N+](=O)[O-])c2)cc1
Temperature: 25 °C
Yield: 100.2 %

Procedure:
A solution of the product of Example 10C (0.812 g, 2.76 mmol), 4-hydroxythiophenol (0.419, 3.32 mmol) and cesium carbonate (2.16 g, 6.64 mmol) in N,N-dimethylformamide (5 mL) was heated to 100° C. for 16 hours. After cooling to room temperature the mixture was poured into ice water (20 mL) and the resultant solution acidified with 1N aqueous hydrochloric acid. The solution was then extracted with ethyl acetate (3×10 mL), the combined extracts dried over magnesium sulfate, filtered and concentrated under vacuum to provide the title compound (1.06 g, 100%).
Reaction SMILES: [Cl:1][C:2]([Cl:9])([Cl:8])[CH:3]1[NH:7][CH2:6][CH2:5][O:4]1.[C:10](=[S:12])=[S:11].C([O-])(=O)C.[Zn+2:17].C([O-])(=O)C>C(O)(C)C.O>[Cl:1][C:2]([Cl:9])([Cl:8])[CH:3]1[N:7]([C:10]([S-:12])=[S:11])[CH2:6][CH2:5][O:4]1.[Cl:1][C:2]([Cl:9])([Cl:8])[CH:3]1[N:7]([C:10]([S-:12])=[S:11])[CH2:6][CH2:5][O:4]1.[Zn+2:17]
Reactant: ClC(Cl)(Cl)C1NCCO1
Reactant: S=C=S
Agent: CC(=O)[O-]
Agent: [Zn+2]
Solvent: O
Solvent: CC(C)O
Product: S=C([S-])N1CCOC1C(Cl)(Cl)Cl
Temperature: 25 °C

Procedure:
Ninety-five and two-tenths g. of 2-trichloromethyloxazolidine (preparation described by W. Ruske and I. Hartmann J. Prakt, Chem. 18 146 (1962) was dissolved in a mixture of 300 ml isopropanol, and 50.5 g. (0.50 mole) of carbon disulfide was added dropwise followed by 43.9 g. (0.25 mole) of anhydrous zinc acetate. The reaction mixture was heated for two hours at 45°- 50°C, cooled to room temperature, and diluted with 1 liter water; the precipitated product was filtered, washed thoroughly with water and dried in vacuo to give 86.3 g. of the crude product, melting at 193°-195°C (decomp.). Hot benzene extractions of the crude product gave 38 g. of the desired carbodithioate sintering at 208°C, and melting 213°- 216°C (decomp.). It had the following analysis: Found: C, 20.19; H, 2.08; N, 4.67; S, 20.96%. Calcd for C10H10Cl6N2O2S4Zn: C, 20.12; H, 1,68; N, 4.69; S, 21.46%.
Reaction SMILES: Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH3:22])([CH3:21])[CH2:7][N:8]2[Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])=[CH:4][C:3]=1[F:23].[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29]([S:32](F)(=[O:34])=[O:33])=[CH:28][CH:27]=1>>[F:23][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:2]=1[S:32]([C:29]1[CH:28]=[CH:27][C:26]([O:25][CH3:24])=[CH:31][CH:30]=1)(=[O:34])=[O:33])[N:8]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH2:7][C:6]2([CH3:22])[CH3:21]
Reactant: CC(C)[Si](C(C)C)(C(C)C)N1CC(C)(C)c2cc(F)c(Br)cc21
Reactant: COc1ccc(S(=O)(=O)F)cc1
Product: COc1ccc(S(=O)(=O)c2cc3c(cc2F)C(C)(C)CN3[Si](C(C)C)(C(C)C)C(C)C)cc1
Yield: 54.9 %

Procedure:
The title compound was prepared starting from 6-bromo-5-fluoro-3,3-dimethyl-1-triisopropylsilanyl-2,3-dihydro-1H-indole (400 mg, 1.0 mmol) and 4-methoxy-benzenesulfonyl fluoride (190 mg, 1.0 mmol) following similar methods to those Preparation 77 to give the title compound (270 mg) as a yellow oil. 1H NMR (CDCl3): 7.92 (2H, dd), 7.20 (1H, d), 7.01-6.94 (2H, m), 6.67 (1H, d), 3.87 (3H, s), 3.49 (2H, s), 1.56-1.43 (3H, m), 1.25-1.21 (6H, m), 1.17 (18H, d).
Reaction SMILES: [N+:1]([C:4]1[CH:21]=[CH:20][C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[O:16][CH:17]=[CH:18][N:19]=3)=[CH:11][CH:10]=2)=[CH:6][CH:5]=1)([O-])=O>C(OCC)(=O)C.CO.[Pd]>[O:16]1[CH:17]=[CH:18][N:19]=[C:15]1[C:12]1[CH:13]=[CH:14][C:9]([O:8][C:7]2[CH:20]=[CH:21][C:4]([NH2:1])=[CH:5][CH:6]=2)=[CH:10][CH:11]=1
Reactant: O=[N+]([O-])c1ccc(Oc2ccc(-c3ncco3)cc2)cc1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CO
Product: Nc1ccc(Oc2ccc(-c3ncco3)cc2)cc1
Reaction time: 3 h
Yield: 103.4 %

Procedure:
A slurry of 2-[4-(4-nitrophenoxy)phenyl]oxazole (2.6 g, 9.2 mmol) in a mixture of ethyl acetate (20 mL) and methanol (100 mL) was placed under a nitrogen atmosphere before the addition of catalyst palladium (10% on C, 0.65 g). The reaction mixture was placed under a hydrogen atmosphere at atmospheric pressure. After 3 hours, the reaction mixture was filtered through a pad of Celite and washed with methanol. The filtrate was concentrated to give the 2.4 g of 4-[4-(2-oxazolyl)phenoxy]benzenamine.
Reaction SMILES: N[C:2]1[CH:3]=[C:4]([CH2:12][OH:13])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[CH3:14][S:15]SC.N(OC(C)(C)C)=O.O>C(Cl)(Cl)Cl>[CH3:14][S:15][C:2]1[CH:3]=[C:4]([CH2:12][OH:13])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1
Reactant: CSSC
Reactant: Nc1cc(CO)cc(C(F)(F)F)c1
Agent: CC(C)(C)ON=O
Solvent: ClC(Cl)Cl
Solvent: O
Product: CSc1cc(CO)cc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of [3-amino-5-(trifluoromethyl)phenyl]methanol (319 mg, 1.67 mmol) (Step A, Example 24) in CHCl3 (5 mL) was added dimethyl disulfide (296 μL, 3.34 mmol). Next, t-butyl nitrite (285 μL, 2.4 mmol) was added dropwise by syringe. The reaction was stirred at room temperature for two hours and then poured into H2O (15 mL). The mixture was extracted with EtOAc (50 mL), washed with brine (15 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography with 0% to 50% EtOAc/hexanes afforded [3-(methylthio)-5-(trifluoromethyl)phenyl]-methanol. The [3-(methylthio)-5-(trifluoromethyl)phenyl]methanol was contaminated with minor impurities that were removed after the next step. Rf=0.53 (50% EtOAc/hexanes). 1H NMR (CDCl3, 500 MHz) δ 7.63 (s, 1H), 7.40 (s, 1H), 7.35 (s, 1H), 4.71 (s, 2H), 2.51 (s, 3H).
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([CH:8]([CH3:10])[CH3:9])[C:5]([F:11])=[CH:4][C:3]=1[O:12][CH3:13].C([Li])CCC.[B:19](OC(C)C)([O:24]C(C)C)[O:20]C(C)C.CN(CCN(C)C)C>C1(C)C=CC=CC=1>[F:11][C:5]1[C:6]([CH:8]([CH3:10])[CH3:9])=[CH:7][C:2]([B:19]([OH:24])[OH:20])=[C:3]([O:12][CH3:13])[CH:4]=1
Reactant: COc1cc(F)c(C(C)C)cc1Br
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: CN(C)CCN(C)C
Agent: [Li]CCCC
Solvent: Cc1ccccc1
Product: COc1cc(F)c(C(C)C)cc1B(O)O
Reaction time: 0.17 h
Yield: 83 %

Procedure:
A solution of 2-bromo-4-isopropyl-5-fluoroanisole (88 wt % in toluene, 10.44 g, 37.2 mmol) in anhydrous toluene was cooled to −10° C. under N2 atmosphere, and 2.5 M, n-butyllithium solution in hexanes (16.36 ml, 40.69 mmol) was added slowly. After stirring at the same temperature for 10 minutes, the resulting solution was transferred to a cooled solution of triisopropyl borate (14.53 ml, 61.3 mmol) and TMEDA (2.80 ml, 18.59 mmol) in toluene slowly at −20° C. After stirring for 30 minutes, the reaction mixture was quenched with 3M H2SO4 (45 ml), and the resulting mixture was worked up as described in Step 4a to provide the title compound in 83% yield (6.62 g, 98.5 wt %).
Reaction SMILES: [C:1]([C:3]1[CH:11]=[CH:10][C:6]2[O:7][CH2:8][O:9][C:5]=2[CH:4]=1)#[CH:2].[C:12]([O:16][C:17](N1C2C(=CC=C(CCOC3C=C4C(=CC=3)NC=C4)N=2)CCC1)=[O:18])(C)(C)[CH3:13]>>[CH2:12]([O:16][C:17](=[O:18])[C:2]#[C:1][C:3]1[CH:11]=[CH:10][C:6]2[O:7][CH2:8][O:9][C:5]=2[CH:4]=1)[CH3:13]
Reactant: C#Cc1ccc2c(c1)OCO2
Reactant: CC(C)(C)OC(=O)N1CCCc2ccc(CCOc3ccc4[nH]ccc4c3)nc21
Product: CCOC(=O)C#Cc1ccc2c(c1)OCO2
Yield: 54 %

Procedure:
The title compound was synthesized from 5-ethynyl-benzo[1,3]dioxole and 7-[2-(1H-indol-5-yloxy)-ethyl]-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester using the procedure described in Example 23, step (c), in 54% yield. 1H NMR (CDCl3) δ 7.16 (dd, 1H, J=1.6, 8.1 Hz), 7.00 (d, 1H, J=1.6 Hz,), 6.80 (d, 1H, J=8.1 Hz,), 6.02 (s, 2H), 4.29 (q, 2H, J=7.2 Hz,), 1.35 (t, 3H, J=7.2 Hz).
Reaction SMILES: [C:1](Cl)(=[O:5])[CH:2]([CH3:4])[CH3:3].CCN(CC)CC.[Cl:14][C:15]1[CH:20]=[C:19]([N+:21]([O-:23])=[O:22])[CH:18]=[CH:17][C:16]=1[N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1>C(Cl)Cl>[Cl:14][C:15]1[CH:20]=[C:19]([N+:21]([O-:23])=[O:22])[CH:18]=[CH:17][C:16]=1[N:24]1[CH2:29][CH2:28][N:27]([C:1](=[O:5])[CH:2]([CH3:4])[CH3:3])[CH2:26][CH2:25]1
Reactant: CC(C)C(=O)Cl
Reactant: O=[N+]([O-])c1ccc(N2CCNCC2)c(Cl)c1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)C(=O)N1CCN(c2ccc([N+](=O)[O-])cc2Cl)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 100 %

Procedure:
According to Scheme 4 Step 1: Isobutyryl chloride (1.24 mmol, 0.13 mL) and Et3N (2.48 mmol, 0.35 mL) were added to a solution of 1-(2-chloro-4-nitrophenyl)piperazine (0.83 mmol, 200 mg) in DCM (5 mL) at 0° C. The reaction mixture was stirred at room temperature for 2 hours. The organic phase was washed with a saturated solution of NaHCO3. The aqueous phase was extracted with AcOEt. The organic phase was washed with brine, was dried over Na2SO4, was filtered and was concentrated under reduced pressure to afford 1-(4-(2-chloro-4-nitrophenyl)piperazin-1-yl)-2-methylpropan-1-one (0.83 mmol, 261 mg, 100%). The product was used without further purification.
Reaction SMILES: [Cl:1]C1C=CC=C(C(OO)=[O:9])C=1.[CH3:12][C:13]1[CH:36]=[CH:35][C:16]([CH2:17][S:18][CH:19]([S:26][CH2:27][C:28]2[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=2)[CH2:20][N:21]2[CH:25]=[CH:24][N:23]=[CH:22]2)=[CH:15][CH:14]=1.CCOCC.Cl>C(Cl)(Cl)Cl>[ClH:1].[CH3:12][C:13]1[CH:14]=[CH:15][C:16]([CH2:17][S:18]([CH:19]([S:26][CH2:27][C:28]2[CH:29]=[CH:30][C:31]([CH3:34])=[CH:32][CH:33]=2)[CH2:20][N:21]2[CH:25]=[CH:24][N:23]=[CH:22]2)=[O:9])=[CH:35][CH:36]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Cc1ccc(CSC(Cn2ccnc2)SCc2ccc(C)cc2)cc1
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: CCOCC
Product: Cc1ccc(CSC(Cn2ccnc2)S(=O)Cc2ccc(C)cc2)cc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A solution of 85% m-chloroperbenzoic acid (1.66 g, 9.63 mmoles) in chloroform (80 ml) was added dropwise during 1 hour to a stirred, cooled (ice/water) solution of 1-[2,2-bis(4-methylbenzylthio)ethyl]-1H-imidazole (3.55 g, 9.63 mmoles) in chloroform (125 ml). The solution was stirred for 18 hours at ambient temperature and then washed successively with aqueous Na2CO3 (2×), H2O and brine. The solution was dried over Na2SO4 and concentrated to leave a mixture of the diastereoisomeric mono-sulfoxides as a cloudy oil. Trituration of the oil with ether afforded the free base of diastereomer A (1.45 g), mp 86°-92° which was converted into the hydrochloride salt, mp 167°-170° with ethereal hydrogen chloride. Hydrogen chloride was bubbled into the ethereal mother liquor from the trituration step to give a mixture of the hydrochloride salts which after recrystallization from acetonitrile provided additional diastereomer A, mp 164°-168° (0.42 g) and 0.57 g of diastereomer B, mp 141°-146°.