Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([NH:8][NH:9][C:10]([C@@H:12]1[CH2:16][C@@H:15]([S:17][C:18]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:14][N:13]1[S:37]([C:40]1[CH:49]=[CH:48][C:47]2[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH:41]=1)(=[O:39])=[O:38])=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[CH3:59][O:60][C:61]1[CH:66]=[CH:65][C:64]([S:67](Cl)(=[O:69])=[O:68])=[CH:63][CH:62]=1>C(Cl)Cl>[CH2:1]([N:8]([S:67]([C:64]1[CH:63]=[CH:62][C:61]([O:60][CH3:59])=[CH:66][CH:65]=1)(=[O:69])=[O:68])[NH:9][C:10]([C@@H:12]1[CH2:16][C@@H:15]([S:17][C:18]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:14][N:13]1[S:37]([C:40]1[CH:49]=[CH:48][C:47]2[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH:41]=1)(=[O:39])=[O:38])=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(NNCc1ccccc1)[C@@H]1C[C@@H](SC(c2ccccc2)(c2ccccc2)c2ccccc2)CN1S(=O)(=O)c1ccc2ccccc2c1
Reactant: COc1ccc(S(=O)(=O)Cl)cc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(S(=O)(=O)N(Cc2ccccc2)NC(=O)[C@@H]2C[C@@H](SC(c3ccccc3)(c3ccccc3)c3ccccc3)CN2S(=O)(=O)c2ccc3ccccc3c2)cc1
Temperature: 25 °C
Reaction time: 72 h
Yield: 59.3 %

Procedure:
(step 12) To 200 mg (0.3 mmol) (2S,4R)-1-(Naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carboxylic acid N′-benzyl-hydrazide in 3 ml CH2Cl2 were added 60 μl (0.35 mmol, 1.2 eq) N,N-diisopropylethylamine, 72.5 mg (0.35 mmol, 1.2 eq) 4-methoxybenzene sulfonylchloride and 22.5 mg (0.12 eq) DMAP-poly at 0° C. The suspension was shaken at RT for 3 days, additional 25 μl (0.15 mmol, 0.5 eq) N,N-diisopropylethylamine, 31 mg (0.15 mmol, 0.5 eq) 4-methoxybenzene sulfonylchloride and 22.5 mg (0.12 eq) DMAP-poly were added and the reaction was continued for a day. After filtration and washing of the resin with CH2Cl2, the organic phase was concentrated and the crude material purified by flash chromatography yielding 152 mg (61%) (2S,4R)-1-(Naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carboxylic acid N′-benzyl-N′-(4-methoxy-benzenesulfonyl)-hydrazide which was directly subjected to the following reaction.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[NH:17][C:18]3[C:23]([CH:24]=2)=[CH:22][C:21]([Cl:25])=[CH:20][CH:19]=3)=[O:15])[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:25][C:21]1[CH:22]=[C:23]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:16]([C:14]([N:11]1[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1)=[O:15])=[CH:24]2
Reactant: CC(C)(C)OC(=O)N1CCN(C(=O)c2cc3cc(Cl)ccc3[nH]2)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=C(c1cc2cc(Cl)ccc2[nH]1)N1CCNCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 95.3 %

Procedure:
The product from Step A (11 g) was suspended in CH2Cl2 (75 mL), and TFA was added dropwise (75 mL). The resulting solution was stirred overnight at ambient temperature. The reaction solution was concentrated under reduced pressure, and the resulting residue was dissolved in CH2Cl2 (100 mL). Saturated aqueous NaHCO3 (100 mL) was added slowly with stirring. After 20 min the organic layer was separated, washed with water (10 mL) and then brine (30 mL), and dried over Na2SO4. The organic layer was then concentrated under reduced pressure and purified via silica gel chromatography (0-35% methanol/dichloromethane) to give the title compound (7.6 g). MS (electrospray): exact mass calculated for C13H14ClN3O, 263.08; m/z found, 264.1 [M+H]+.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C:10](=[O:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:14]([O:16][C:17](=[O:26])[CH2:18][N:19]1[CH:23]=[C:22]([CH:24]=O)[CH:21]=[N:20]1)[CH3:15].N1CCCC1>C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12]/[C:11](=[CH:24]\[C:22]2[CH:21]=[N:20][N:19]([CH2:18][C:17]([O:16][CH2:14][CH3:15])=[O:26])[CH:23]=2)/[C:10](=[O:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)Cn1cc(C=O)cn1
Reactant: CC(C)(C)OC(=O)N1CCC(=O)C1
Solvent: CCO
Solvent: C1CCNC1
Product: CCOC(=O)Cn1cc(/C=C2\CN(C(=O)OC(C)(C)C)CC2=O)cn1
Temperature: 80 °C
Reaction time: 0.75 h
Yield: 34.8 %

Procedure:
To a solution of 1-(t-butoxycarbonyl)pyrrolidin-3-one (6.8 g) in ethanol (200 ml) were added ethyl(4-formyl-1H-pyrazol-1-yl)acetate (8.0 g) and pyrrolidine (600 μl). The resulting mixture was stirred at 80° C. for 45 minutes, cooled to room temperature, and the solvent was evaporated in vacuo. The residue was purified by chromatography on silica gel using a mixture of hexane, ethyl acetate and dichloromethane (2:1:1) as the eluent to afford the title compound as a yellow amorphous solid (4.47 g, yield: 35%).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:14]=[C:13](Cl)[C:12]2[C:7](=[CH:8][C:9]([Cl:16])=[CH:10][CH:11]=2)[N:6]=1)=[O:4].[C:17]([N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1)([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]>C(N(C(C)C)CC)(C)C>[CH3:1][O:2][C:3]([C:5]1[CH:14]=[C:13]([N:27]2[CH2:26][CH2:25][N:24]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:29][CH2:28]2)[C:12]2[C:7](=[CH:8][C:9]([Cl:16])=[CH:10][CH:11]=2)[N:6]=1)=[O:4]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: COC(=O)c1cc(Cl)c2ccc(Cl)cc2n1
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1cc(N2CCN(C(=O)OC(C)(C)C)CC2)c2ccc(Cl)cc2n1
Reaction time: 3 h
Yield: 80 %

Procedure:
The mixture of 4,7-dichloro-2-quinolinecarboxylic acid methyl ester (90.2 g, 379 mmol) and N-boc-piperazine (60.1 g, 387 mmol) in dry diisopropylethyl amine (300 mL) was kept at 140 degrees C. for 3 h. After the removal of diisopropylethyl amine in vacuo, ethyl ether was added to precipitate the product. The crude solid was collected by filtration and was purified by re-crystallization from EtOAc (500 mL) to afford 123 g (80%) of 7-chloro-4-[4-[(1,1-dimethylethoxy)carbonyl]-1-piperazinyl]-2-quinolinecarboxylic acid methyl ester as an off-white solid. 1H NMR (DMSO-d6): δ 1.42 (s, 18H), 3.18 (m, 4H), 3.61 (m, 4H), 3.92 (s, 3H), 7.47 (s, 1H), 7.63 (d, 1H), 8.04 (d, 1H), 8.1 (s, 1H).
Reaction SMILES: [NH2:1][CH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([C:9]([OH:11])=[O:10])[CH2:5][CH2:4]1.[OH-].[Na+].[C:14]1([S:20](Cl)(=[O:22])=[O:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>O>[C:14]1([S:20]([NH:1][CH2:2][C@H:3]2[CH2:4][CH2:5][C@H:6]([C:9]([OH:11])=[O:10])[CH2:7][CH2:8]2)(=[O:22])=[O:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: NC[C@H]1CC[C@H](C(=O)O)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(O)[C@H]1CC[C@H](CNS(=O)(=O)c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
trans-4-(Aminomethyl)cyclohexane carboxylic acid (15.2 g, 0.097 mol) was dissolved in a 2N NaOH solution (96.5 mL, 2 equivalents). The solution was brought to 10° C., benzenesulfonyl chloride (17.1 g, 0.097 mol) was added dropwise and then the mixture was stirred overnight at room temperature. The mixture was diluted with water, the solution was washed with ether, and then the aqueous portion was acidified with 12N HCl to give an oily precipitate. The precipitate was extracted with CH2Cl2, and the extracts were dried (Na2SO4) and concentrated under reduced pressure to give trans-4-(Benzenesulfonylamino-methyl)-cyclohexanecarboxylic acid as a white solid.
Reaction SMILES: [CH3:1][C:2]1[C:6]2[CH:7]=[C:8]3[C:13]4([C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[NH:15][C:14]4=[O:22])[CH2:12][O:11][C:9]3=[CH:10][C:5]=2[O:4][N:3]=1.[H-].[Na+].Br[CH2:26][C:27]1[O:28][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:30][CH:31]=1>CN(C)C=O.C(OCC)(=O)C>[CH3:1][C:2]1[C:6]2[CH:7]=[C:8]3[C:13]4([C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[N:15]([CH2:26][C:27]5[O:28][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:30][CH:31]=5)[C:14]4=[O:22])[CH2:12][O:11][C:9]3=[CH:10][C:5]=2[O:4][N:3]=1
Reactant: Cc1noc2cc3c(cc12)C1(CO3)C(=O)Nc2ccccc21
Reactant: FC(F)(F)c1ccc(CBr)o1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Cc1noc2cc3c(cc12)C1(CO3)C(=O)N(Cc2ccc(C(F)(F)F)o2)c2ccccc21
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 79.5 %

Procedure:
To a stirred solution of 3-methylspiro[furo[3,2-f][1,2]benzisoxazole-5,3′-indol]-2′(1′H)-one (0.29 g, 1.00 mmol) in N,N-dimethylformamide (10 mL) was added sodium hydride (0.05 g, 1.25 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 30 min, then 2-(bromomethyl)-5-(trifluoromethyl)furan (0.25 mL, 1.80 mmol) was added. The mixture was stirred at ambient temperature for 20 h, diluted with ethyl acetate, washed with water and brine, and dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuum. The residue was purified by column chromatography with ethyl acetate in hexanes (10% to 40% gradient) to afford 3-methyl-1′-{[5-(trifluoromethyl)furan-2-yl]methyl}spiro[furo[3,2-f][1,2]benzisoxazole-5,3′-indol]-2′(1′H)-one (0.35 g, 80%): mp 111-112° C. (diethyl ether/hexanes); 1H NMR (300 MHz, CDCl3) δ 7.46 (d, J=9.0 Hz, 1H), 7.33-7.27 (m, 1H), 7.15-7.12 (m, 1H), 7.06-7.01 (m, 3H), 6.77-6.76 (m, 1H), 6.55-6.52 (m, 1H), 5.20-4.85 (m, 4H), 2.44 (s, 3H); 13C NMR (75 MHz, CDCl3) δ175.7, 163.9, 158.1, 154.9, 151.6, 141.4, 130.2, 129.5, 123.9, 123.1, 120.7, 117.9, 117.1, 112.9, 109.3, 108.9, 108.8, 107.9, 81.2, 56.2, 37.5, 9.8; MS (ES+) m/z 462.9 (M+23).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[C:7]([Cl:17])[C:8]([O:12][CH2:13]COC)=[CH:9][CH:10]=2)[N:5]=[C:4]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([CH:24]([CH3:26])[CH3:25])[N:19]=2)[CH:3]=1.NC1C(Cl)=C(OC)C=CC=1C(=O)C>>[Cl:1][C:2]1[C:11]2[C:6](=[C:7]([Cl:17])[C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([CH:24]([CH3:26])[CH3:25])[N:19]=2)[CH:3]=1
Reactant: COCCOc1ccc2c(Cl)cc(-c3cccc(C(C)C)n3)nc2c1Cl
Agent: COc1ccc(C(C)=O)c(N)c1Cl
Product: COc1ccc2c(Cl)cc(-c3cccc(C(C)C)n3)nc2c1Cl

Procedure:
4,8-Dichloro-2-(6-isopropyl-pyridin-2-yl)-7-methoxy-quinoline was prepared in a similar fashion as 4,8-dichloro-2-(6-isopropyl-pyridin-2-yl)-7-(2-methoxy-ethoxy)-quinoline except that 1-(2-amino-3-chloro-4-methoxy-phenyl)-ethanone was used instead of 1-[2-amino-3-chloro-4-(2-methoxy-ethoxy)-phenyl]-ethanone.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([N:13]3[CH2:18][CH2:17][CH:16]([N:19]4[C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[CH2:21][C:20]4=[O:28])[CH2:15][CH2:14]3)=[O:12])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.Cl.Cl[CH2:31][CH2:32][N:33]([CH3:35])[CH3:34].C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C.[OH-].[Na+]>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([N:13]3[CH2:18][CH2:17][CH:16]([N:19]4[C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[CH2:21][C:20]4=[O:28])[CH2:15][CH2:14]3)=[O:12])=[CH:7][N:8]2[CH2:31][CH2:32][N:33]([CH3:35])[CH3:34])=[CH:4][CH:3]=1
Reactant: O=C(c1c[nH]c2cc(Cl)ccc12)N1CCC(N2C(=O)Cc3ccccc32)CC1
Reactant: CN(C)CCCl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC#N
Product: CN(C)CCn1cc(C(=O)N2CCC(N3C(=O)Cc4ccccc43)CC2)c2ccc(Cl)cc21
Temperature: 50 °C
Yield: 38.7 %

Procedure:
A suspension of 0.40 g (1.0 mmol) 1-[1-(6-chloro-1H-indole-3-carbonyl)-piperidin-4-yl]-1,3-dihydro-indol-2-one, 0.16 g (1.1 mmol) 1-chloro-2-dimethylaminoethane hydrochloride and 0.69 g (2.1 mmol) cesium carbonate in 10 ml acetonitrile was heated at 50° C. over night. After cooling to room temperature the reaction mixture was diluted with a 0.5 M aqueous solution of sodium hydroxide and extracted with three portions of ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated in vacuo. Flash chromatography gave 0.18 g (39%) of the title compound.
Reaction SMILES: [SH:1][C:2]1[N:7]2[CH:8]=[C:9]([CH3:11])[N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.Br[CH2:20][CH2:21][CH2:22][CH2:23][Cl:24]>>[Cl:24][CH2:23][CH2:22][CH2:21][CH2:20][S:1][C:2]1[N:7]2[CH:8]=[C:9]([CH3:11])[N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1
Reactant: Cc1cn2c(S)cccc2n1
Reactant: ClCCCCBr
Solvent: CCN(CC)CC
Product: Cc1cn2c(SCCCCCl)cccc2n1

Procedure:
Using 657 mg (4.0 mmol) of 5-mercapto-2-methylimidazo-[1,2-a]pyridine, 0.70 ml (5.0 mmol) of triethylamine and 0.58 ml (5.0 mmol) of 1-bromo-4-chlorobutane, the same procedure as in Reference Example 1 was followed, to yield 838 mg (82.3%, light orange solid) of the desired product.
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][C:16]=1[Cl:17])[C:13](=[O:18])[N:12]([C:19]1[CH:20]=[N:21][CH:22]=[CH:23][C:24]=1[CH3:25])[CH2:11][CH2:10]2)(=O)=O.CO.C([O-])([O-])=O.[Na+].[Na+].[CH3:36][N:37](C=O)C>C(Cl)(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].[C-]#N.[C-]#N.[Zn+2]>[Cl:17][C:16]1[CH:15]=[C:14]2[C:9]([CH2:10][CH2:11][N:12]([C:19]3[CH:20]=[N:21][CH:22]=[CH:23][C:24]=3[CH3:25])[C:13]2=[O:18])=[CH:8][C:7]=1[C:36]#[N:37]
Reactant: CN(C)C=O
Reactant: Cc1ccncc1N1CCc2cc(OS(=O)(=O)C(F)(F)F)c(Cl)cc2C1=O
Agent: [Fe+2]
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CO
Solvent: ClC(Cl)Cl
Product: Cc1ccncc1N1CCc2cc(C#N)c(Cl)cc2C1=O
Temperature: 80 °C
Reaction time: 18 h
Yield: 10.6 %

Procedure:
Pd2(dba)3 (17.4 mg, 0.018 mmol), dppf (42.2 mg, 0.076 mmol) and Zn(CN)2 (65 mg, 0.6 mmol) were added to previously degassed 7-chloro-2-(4-methylpyridin-3-yl)-1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl trifluoromethane sulfonate (I-87a: 200 mg, 0.476 mmol) in DMF (3 mL). The resulting mixture was stirred for 18 hours at 80° C. The reaction was monitored by TLC (5% methanol in CHCl3). The reaction mixture was cooled to room temperature, poured into saturated Na2CO3 solution and extracted with ethyl acetate. The organic layer was dried over Na2SO4 and concentrated under reduced pressure to afford the crude product. Purification by column chromatography on silica gel (2% methanol in CHCl3), followed by preparative HPLC afforded 5 mg of the product (10.6% yield).
Reaction SMILES: [NH2:1][CH:2]([CH2:5][OH:6])[CH2:3][OH:4].C(N(CC)CC)C.[Cl:14][CH2:15][C:16](Cl)=[O:17]>C(#N)C.CO>[Cl:14][CH2:15][C:16]([NH:1][CH:2]([CH2:5][OH:6])[CH2:3][OH:4])=[O:17]
Reactant: O=C(Cl)CCl
Reactant: NC(CO)CO
Solvent: CC#N
Solvent: CCN(CC)CC
Solvent: CO
Product: O=C(CCl)NC(CO)CO
Temperature: 25 °C
Reaction time: 8 h
Yield: 86.1 %

Procedure:
2-Amino-1,3-propanediol (5.24 g, 57.5 mmol) was dissolved in a mixed solvent (220 mL) of acetonitrile/methanol (6/1). To this, triethylamine (9.60 mL, 69.6 mmol) and chloroacetyl chloride (5.10 mL, 63.3 mmol) were successively added under ice-cooling, and the mixture was stirred at room temperature overnight. After completion of the reaction, the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/methanol=90/10) to give 2-chloro-N-(2-hydroxy-1-hydroxymethylethyl)acetamide (8.30 g, yield: 86%).
Reaction SMILES: [CH2:1]([C:5]1[N:10]=[C:9](Cl)[C:8]([CH2:12][CH3:13])=[C:7]([CH3:14])[N:6]=1)[CH2:2][CH2:3][CH3:4].[NH3:15]>>[NH2:15][C:9]1[C:8]([CH2:12][CH3:13])=[C:7]([CH3:14])[N:6]=[C:5]([CH2:1][CH2:2][CH2:3][CH3:4])[N:10]=1
Reactant: CCCCc1nc(C)c(CC)c(Cl)n1
Reactant: N
Product: CCCCc1nc(C)c(CC)c(N)n1

Procedure:
The title compound prepared from 2-butyl-4-chloro-5-ethyl-6-methylpyrimidine (from Example 18) upon treatment with alcoholic ammonia as described by Marshall and Walker (J. Chem. Soc., 1951, 1004).
Reaction SMILES: ClC1C=C(C=CC=1)C(OO)=[O:6].[F:12][C:13]([F:34])([F:33])[C:14]1[C:22]2[N:21]=[C:20]([S:23][CH2:24][C:25]3[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=[CH:27][N:26]=3)[NH:19][C:18]=2[CH:17]=[CH:16][CH:15]=1>C(Cl)Cl>[F:34][C:13]([F:33])([F:12])[C:14]1[C:22]2[N:21]=[C:20]([S:23]([CH2:24][C:25]3[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=[CH:27][N:26]=3)=[O:6])[NH:19][C:18]=2[CH:17]=[CH:16][CH:15]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COc1ccnc(CSc2nc3c(C(F)(F)F)cccc3[nH]2)c1
Solvent: ClCCl
Product: COc1ccnc(CS(=O)c2nc3c(C(F)(F)F)cccc3[nH]2)c1
Reaction time: 1 h

Procedure:
2.3 g of commercially available 85% strength m-chloroperoxybenzoic acid, dissolved in 30 ml of methylene chloride, are added dropwise to a solution, cooled to -30° C., of 3.0 g (0.0088 mole) of 4-trifluoromethyl-2-[(4-methoxy-2-pyridylmethyl)thio]-(1H)-benzimidazole in 50 ml of methylene chloride over the course of 45 minutes. The resulting mixture is then stirred for a further 60 minutes, and the temperature is subsequently allowed to rise to 0° C. After the mixture is washed with saturated aqueous sodium carbonate solution (30 ml), it is dried over sodium sulfate, and the solvent is stripped off in vacuo. The solid residue which remains is recrystallized successively from isopropanol and acetonitrile. Yield: 1.6 g of title compound, m.p. 150° to 151° C.
Reaction SMILES: Cl[CH2:2][Si:3]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH3:14])=[CH:8][CH:7]=1)([CH3:5])[CH3:4].[C:15]([O-:18])(=[O:17])[CH3:16].[Na+].C(Cl)(Cl)(Cl)Cl>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)C>[C:15]([O:18][CH2:2][Si:3]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH3:14])=[CH:8][CH:7]=1)([CH3:5])[CH3:4])(=[O:17])[CH3:16]
Reactant: CCOc1ccc([Si](C)(C)CCl)cc1
Reactant: CC(=O)[O-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Agent: [Na+]
Solvent: ClC(Cl)(Cl)Cl
Solvent: CCOCC
Product: CCOc1ccc([Si](C)(C)COC(C)=O)cc1
Temperature: 25 °C
Yield: 105.4 %

Procedure:
In a flask under nitrogen were placed 10.1 g (0.044 mole) of (chloromethyl)(4-ethoxyphenyl)dimethylsilane, 4.0 g (0.049 mole) of sodium acetate, 1.2 g (0.0043 mole) of tetrabutylammonium chloride, and 75 ml of carbon tetrachloride. This mixture was refluxed for four days. After cooling to room temperature, 2.0 g (0.024 mole) of sodium acetate and 0.60 g (0.0022 mole) of tetrabutylammonium chloride was added, and the reaction mixture was refluxed for five more days. This mixture was then diluted with diethyl ether, filtered through silica gel, and the solvent was evaporated under reduced pressure, leaving 11.7 g of 2-(4-ethoxyphenyl)-2-methyl-2-silapropyl acetate as a clear, light brown oil. The nmr spectrum was consistent with the proposed structure.
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]([Cl:12])[C:5]2[C:6](=[O:9])[O:7][CH2:8][C:4]=2[CH:3]=1.BrC1[C:19]2[C:20](=O)[O:21]CC=2C=C(Cl)C=1.[Cl-].[Li+].CSC>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.C1(C)C=CC=CC=1>[Cl:12][C:10]1[C:5]2[C:6](=[O:9])[O:7][CH2:8][C:4]=2[CH:3]=[C:2]([CH2:19][CH:20]=[O:21])[CH:11]=1
Reactant: O=C1OCc2cc(Cl)cc(Br)c21
Reactant: O=C1OCc2cc(Br)cc(Cl)c21
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: [Cl-]
Solvent: ClCCl
Solvent: Cc1ccccc1
Solvent: CSC
Product: O=CCc1cc(Cl)c2c(c1)COC2=O
Temperature: 120 °C

Procedure:
To a round bottom flask charged with a mixture of 5-bromo-7-chloro-2-benzofuran-1(3H)-one and 7-bromo-5-chloro-2-benzofuran-1(3H)-one (120 mg, 0.48 mmol) and a stir bar was added PdCl2(dppf)-DCM complex (40 mg, 0.048 mmol) allyl tri-n-butyltin (241 mg, 0.73 mmol), lithium chloride (41 mg, 0.97 mmol), and toluene (15 mL). The mixture was purged three times with nitrogen, and heated to 120° C. for 4 hours. LC showed formation of the desired product, which was purified by silica gel chromatography (Hexane-EtOAc). The resulting oil yellow oil was then dissolved in methanol (10 mL). The solution was cooled to −78° C. To this solution was bubbled ozone through until it turned light blue. Excess ozone was removed by bubbling nitrogen through the solution, which was followed by addition of dimethyl sulfide (0.21 mL, 2.9 mmol). The reaction was allowed to warm to RT slowly. LC showed formation of the desired product. The reaction was diluted with EtOAc (50 mL), washed with brine, dried over sodium sulfate, adsorbed onto silica gel, and purified by flash chromatography as a mixture of (7-chloro-1-oxo-1,3-dihydro-2-benzofuran-5-yl)acetaldehyde and (6-chloro-3-oxo-1,3-dihydro-2-benzofuran-4-yl)acetaldehyde. LC/MS: (IE, m/z) (M+1)+=211.1.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[CH:4][C:3]=1[N:11]1[CH:15]=[C:14]([CH3:16])[N:13]=[C:12]1[CH3:17]>[Pd].CO>[CH3:17][C:12]1[N:11]([C:3]2[CH:4]=[CH:5][C:6]([NH2:8])=[CH:7][C:2]=2[F:1])[CH:15]=[C:14]([CH3:16])[N:13]=1
Reactant: Cc1cn(-c2ccc([N+](=O)[O-])cc2F)c(C)n1
Agent: [Pd]
Solvent: CO
Product: Cc1cn(-c2ccc(N)cc2F)c(C)n1
Temperature: 25 °C
Reaction time: 18 h
Yield: 104.4 %

Procedure:
Step T (2): 10% Palladium on carbon (2.99 g, 2.81 mmol) was added under an atmosphere of nitrogen to a chilled (ice-water bath) solution of 1-(2-fluoro-4-nitrophenyl)-2,4-dimethyl-1H-imidazole (6.6 g, 28.1 mmol) dissolved in methanol (150 mL). The flask was repeatedly evacuated and flushed with hydrogen gas (double balloon). The resulting mixture was allowed to warm to rt and left to stir for 18 h under the hydrogen atmosphere. The vessel was subsequently purged with nitrogen gas. The crude reaction mixture was filtered through a short plug of diatomaceous earth (Celite®). The reaction vessel and Celite® were rinsed with fresh methanol. The combined filtrates were concentrated in vacuo. The residue was dried under high vacuum to afford 4-(2,4-dimethyl-1H-imidazol-1-yl)-3-fluoroaniline (6.02 g, quanitative yield) as a blackish/grey solid. LC-MS (M+H)+ 206.2. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.00 (t, J=8.5 Hz, 1 H), 6.60 (s, 1 H), 6.43-6.53 (m, 2 H), 3.98 (br. s., 2 H), 2.16-2.28 (m, 6 H).
Reaction SMILES: [Si]([O:8][CH2:9][CH2:10][C:11]1[NH:12][C:13]2[C:18]([CH:19]=1)=[CH:17][C:16]([CH2:20][C:21]([O-:23])=[O:22])=[CH:15][CH:14]=2)(C(C)(C)C)(C)C.[F-].[CH2:25]([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[OH:8][CH2:9][CH2:10][C:11]1[NH:12][C:13]2[C:18]([CH:19]=1)=[CH:17][C:16]([CH2:20][C:21]([O:23][CH3:25])=[O:22])=[CH:15][CH:14]=2
Reactant: CCCC[N+](CCCC)(CCCC)CCCC
Reactant: CC(C)(C)[Si](C)(C)OCCc1cc2cc(CC(=O)[O-])ccc2[nH]1
Agent: [F-]
Solvent: C1CCOC1
Product: COC(=O)Cc1ccc2[nH]c(CCO)cc2c1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of methyl 2-(2-(t-butyldimethylsilyl-oxyethyl)-indole-5-acetate (400 mg; 1.15 mmol) in ca. 4 ml of THF was added a 1 M tetrabutylammonium fluoride in THF (1.2 mL; 1.05 eq) at 0° C. After 15 minutes, the reaction was allowed to warm to room temperature and stirred for an additional 3 hours. It was concentrated, diluted with water and extracted with ethyl acetate. The organic layer was washed with water, dried (Na2SO4), concentrated and chromatographed (silica gel, hexane:ethyl acetate 4:1) to yield 241 mg of the title compound as a colorless oil.