Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OP([CH2:9][C:10]1[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH:11]=1)(OCC)=O)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:30][C:31]1([CH3:49])[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([CH:41]([CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])[CH:42]=O)[CH:39]=2)[S:34][CH2:33][CH2:32]1>C1COCC1.CCCCCC>[CH3:49][C:31]1([CH3:30])[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([CH:41]([CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])/[CH:42]=[CH:9]/[C:10]3[CH:11]=[CH:12][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:18][CH:19]=3)[CH:39]=2)[S:34][CH2:33][CH2:32]1
Reactant: CCCCCC(C=O)c1ccc2c(c1)C(C)(C)CCS2
Reactant: CCOP(=O)(Cc1ccc(C(=O)OC)cc1)OCC
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCCCCC(/C=C/c1ccc(C(=O)OC)cc1)c1ccc2c(c1)C(C)(C)CCS2
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 39.3 %

Procedure:
0.51 g of methyl 4-(diethoxyphosphorylmethyl)-benzoate were dissolved in 7.5 ml THF and treated, at −20° C., with 1.8 ml of a 1M solution of lithium bis(trimethylsilyl)amide in hexane. After 15 min. at −20° C., a solution of 350 mg of (RS)-2-(4,4-dimethyl-thiochroman-6-yl)-heptanal in 7.5 ml THF was added. The reaction mixture was stirred at room temperature for 1.5 hour. The mixture quenched by the addition of 10 ml of water and the resulting mixture was partitioned in 25 ml ethyl acetate/15 ml sat. aq. sodium chloride solution. The phases were separated and the organic phase was dried over MgSO4. The solvent was removed in vacuo and the crude product was purified by flash chromatography (SiO2, 10% ethyl acetate/hexanes), giving 200 mg of the corresponding ester. 1H NMR (CDCl3): 7.94 (d, J=8.5 Hz, 2H), 7.38 (d, J=8.5 Hz, 2H), 7.19 (d, J=1.8 Hz, 1H), 7.03 (d, J=8.1 Hz, 1H), 6.91 (dd, J=8.1, 1.8 Hz, 1H), 6.45 (d, J=15.9 Hz, 1H), 6.38 (d, J=15.9 Hz, 1H), 3.90 (s, 3H), 3.30 (m, 1H), 3.05-3.00 (m, 2H), 2.00-1.90 (m, 2H), 1.85-1.75 (m, 2H), 1.33 (s, 6H), 1.40-1.30 (m, 6H), 0.86 (t, J=6.5 HZ, 3H).
Reaction SMILES: [O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][N:9]([CH2:12][CH2:13][CH2:14][N:15]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]4([CH2:25][CH2:24]4)[C:16]3=[O:26])[CH2:8][CH2:7]2)[N:5]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:4][N:3]1[CH2:33][C:34]1[CH:35]=[C:36]([CH:44]=[CH:45][CH:46]=1)[C:37]([O:39]C(C)(C)C)=[O:38].C(O)=O.C([O-])=O.[ClH:53]>O1CCOCC1>[ClH:53].[O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][N:9]([CH2:12][CH2:13][CH2:14][N:15]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]4([CH2:25][CH2:24]4)[C:16]3=[O:26])[CH2:8][CH2:7]2)[N:5]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH2:4][N:3]1[CH2:33][C:34]1[CH:35]=[C:36]([CH:44]=[CH:45][CH:46]=1)[C:37]([OH:39])=[O:38]
Reactant: CC(C)(C)OC(=O)c1cccc(CN2CN(c3ccccc3)C3(CCN(CCCN4C(=O)C5(CC5)c5ccccc54)CC3)C2=O)c1
Agent: Cl
Agent: O=C[O-]
Solvent: O=CO
Solvent: C1COCCO1
Product: O=C(O)c1cccc(CN2CN(c3ccccc3)C3(CCN(CCCN4C(=O)C5(CC5)c5ccccc54)CC3)C2=O)c1
Yield: 65 %

Procedure:
tert-Butyl 3-((4-oxo-8-(3-(2′-oxospiro[cyclopropane-1,3′-indoline]-1′-yl)propyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (0.27 g, 0.435 mmol) and formic acid (4 mL) were stirred at room temperature for 20 hours. The reaction was evaporated to dryness and the residue purified by PTLC (10% methanol/dichloromethane) to give product as an oil; 1H NMR (DMSO-d6); δ1.52 (m, 2H); 1.59 (m, 2H); 1.68 (d, J=13.6 Hz, 2H); 1.87 (m, 2H); 2.57-2.62 (m, 4H); 2.91 (m, 4H); 3.82 (t, J=6.4 Hz, 2H); 4.60 (s, 2H); 4.62 (s, 2H); 6.76 (t, J=7.2 Hz, 1H); 6.86 (d, J=8.4 Hz, 2H); 6.96-7.03 (m, 2H); 7.17-7.23 (m, 4H); 7.48-7.55 (m, 2H); 7.87-7.89 (m, 2H); 8.15 (s, 1H). The formate salt was dissolved in 4M hydrochloric acid in 1,4-dioxane (5 mL) and then evaporated under vacuum. The residue was dissolved in acetonitrile (5 mL) and water (5 mL) and lyophilized to give product as a white solid (0.17 g, 65%); HPLC rt 10.65 min; 1H NMR (DMSO-d6); δ1.54 (m, 2H); 1.62 (m, 2H); 1.90 (d, J=14.4 hz, 2H); 2.11 (m, 2H); 2.92-2.98 (m, 2H); 3.22 (m, 2H); 3.46-3.70 (m, 4H); 3.85 (t, J=7.2 hz, 2H); 4.64 (s, 2H); 4.65 (s, 2H); 6.79 (t, J=7.6 hz, 1H); 7.00-7.06 (m, 4H); 7.19-7.29 (m, 4H); 7.49-7.58 (m, 2H); 7.87-7.89 (m, 2H); 10.6 (br s, 1H); 13.1 (br s, 1H); MS for C34H36N4O4 m/z 565 (M+H)+.
Reaction SMILES: [CH2:1]=O.[OH:3][CH2:4][CH2:5][NH:6][CH2:7][CH2:8][O:9][CH2:10][CH:11]([OH:22])[CH2:12][CH2:13][CH2:14][CH:15]([CH2:19][CH2:20][CH3:21])[CH2:16][CH2:17][CH3:18]>C1(C)C=CC=CC=1.C(O)(C)C>[O:3]1[CH2:4][CH2:5][N:6]([CH2:7][CH2:8][O:9][CH2:10][CH:11]([OH:22])[CH2:12][CH2:13][CH2:14][CH:15]([CH2:19][CH2:20][CH3:21])[CH2:16][CH2:17][CH3:18])[CH2:1]1
Reactant: CCCC(CCC)CCCC(O)COCCNCCO
Reactant: C=O
Solvent: CC(C)O
Solvent: Cc1ccccc1
Product: CCCC(CCC)CCCC(O)COCCN1CCOC1
Temperature: 25 °C

Procedure:
To a 10 mL flask containing paraformaldehyde (52 mg, 1,73 mmol, 1 eq.) in toluene (1 mL), was added 1-[2-(2-hydroxy-ethylamino)-ethoxy]-6-propyl-nonan-2-ol (500 mg 1,73 mmol) diluted with isopropanol (1mL) before heating to reflux with a Dean-Stark trap for 17 h. The reaction was cooled to room temperature and, after evaporation, 520 mg of a mixture of products was obtained with the title compound as the major component (100% crude yield). 1H NMR (CDCl3, 400 MHz) d?(ppm); 4,33 (s, 2H); 3,78 (t, J=6,8 Hz, 2H); 3,83-3,74 (m, H); 3,70-3,57 (m, 2H); 3,55 (dd, J=2,7 Hz, J=10,0 Hz, H); 3,29 (dd, J=8,2 Hz, J=10,0 Hz, H); 3,02 (t, J=6,8 Hz, 2H); 2,81-2,74 (m, 2H); 1,50-1,12 (m, 15H); 0,87 (t, J=7,0 Hz, 6H′). 13C NMR (CDCl3, 129,9 MHz) d?(ppm): 87,0; 76,0; 70,5; 70,3; 63,3; 54,3; 52,7; 36,9; 36,0 (2C); 33,7; 33,5; 22,7; 19,8 (2C); 14,5 (2C)
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([O:12][CH3:13])=[O:11])#[CH:2].C(N(CC)CC)C.Cl[C:22]1[C:27]([C:28]([F:31])([F:30])[F:29])=[CH:26][N:25]=[C:24]([NH:32][C:33]2[CH:38]=[CH:37][C:36]([N:39]3[CH2:44][CH2:43][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:41][CH2:40]3)=[CH:35][CH:34]=2)[N:23]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.[Cu]I>[CH3:13][O:12][C:10](=[O:11])[CH2:9][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[C:1]#[C:2][C:26]1[C:27]([C:28]([F:30])([F:29])[F:31])=[CH:22][N:23]=[C:24]([NH:32][C:33]2[CH:34]=[CH:35][C:36]([N:39]3[CH2:40][CH2:41][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:43][CH2:44]3)=[CH:37][CH:38]=2)[N:25]=1
Reactant: C#Cc1ccccc1CC(=O)OC
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc(Nc3ncc(C(F)(F)F)c(Cl)n3)cc2)CC1
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COC(=O)Cc1ccccc1C#Cc1nc(Nc2ccc(N3CCN(C(=O)OC(C)(C)C)CC3)cc2)ncc1C(F)(F)F
Temperature: 120 °C
Yield: 89 %

Procedure:
To a nitrogen de-gassed solution of methyl 2-(2-ethynylphenyl)acetate (14: prepared according to the procedure of Peng, C. et al; Adv. Synth. Catal. 2008, 350, 2359-2364 or as detailed below) (0.114 g, 0.653 mmol) in dry DMF (6 mL) were added triethylamine (0.280 mL, 2.01 mmol) followed by tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate (I3) (0.230 g, 0.502 mmol), triphenylphosphine (0.020 g, 0.075 mmol), trans-dichlorobis(triphenylphosphine) palladium(II) (0.035 g, 0.050 mmol) and CuI (0.014 g, 0.075 mmol). The reaction mixture was heated under microwave irradiation at 120° C. for 20 minutes and then concentrated to dryness in vacuo and purified by silica gel chromatography (Biotage Isolera, 40 g Si cartridge, 0-80% EtOAc in cyclohexane) to give the title compound (I5) (0.267 g, 89% yield) as an orange glassy solid; 1H NMR (400 MHz, d6-DMSO) δ 10.27 (br s, 1H), 8.76 (s, 1H), 7.65-7.49 (m, 4H), 7.49-7.38 (m, 2H), 6.95 (d, J=9.1 Hz, 2H), 3.94 (s, 2H), 3.61 (s, 3H), 3.51-3.42 (m, 4H), 3.09-3.00 (m, 4H), 1.42 (s, 9H). LCMS Method C: rt 6.67 min; m/z 596.3 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:33][O:34][CH3:35])[C:8]([NH:10][CH:11]2[C:31](=[O:32])[N:13]3[C:14]([C:18]([O:20]CC4C=CC([N+]([O-])=O)=CC=4)=[O:19])=[CH:15][CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1.[OH-].[K+].Cl>C(O)C.O>[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:33][O:34][CH3:35])[C:8]([NH:10][CH:11]2[C:31](=[O:32])[N:13]3[C:14]([C:18]([OH:20])=[O:19])=[CH:15][CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1
Reactant: CON=C(C(=O)NC1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=CCS[C@H]12)c1csc(N)n1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CON=C(C(=O)NC1C(=O)N2C(C(=O)O)=CCS[C@H]12)c1csc(N)n1
Temperature: 5 °C
Reaction time: 0.25 h
Yield: 39.9 %

Procedure:
p-Nitrobenzyl 7-[2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylate (syn-isomer: 7.8 g.) was suspended in a mixture of ethanol (60 ml.) and water (60 ml.) 1 N Aqueous solution of potassium hydroxide (45 ml.) was added dropwise to the stirred suspension under ice-cooling over 10 minutes and stirred at 5° C. for 15 minutes. The resultant solution was adjusted to pH 7.0 with conc. hydrochloric acid, washed with ethyl acetate and the concentrated under reduced pressure to half of its initial volume. The concentrated solution was adjusted to pH 5.0 and subjected to column chromatography on macroporous, non-ionic adsorption resin "Diaion HP-20" (Trade mark; manufactured by Mitsubishi Chemical Industries Ltd.; 80 ml.), and eluted with 5% aqueous solution of isopropyl alcohol. The fractions containing the object compound were collected and adjusted to pH 3.2 with 10% hydrochloric acid. The precipitating crystals were collected by filtration, and dried to give 7-[2 -(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid (syn-isomer: 2.3 g.)
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6](=[O:22])[N:7]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:8]2=[O:13].N12CCCN=C1CCCCC2.ON1C2C=CC=CC=2N=N1.[CH3:44][N:45]1[C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[C:47]([CH2:54][C:55](O)=[O:56])=[CH:46]1.Cl.CN(C)CCCN=C=NCC>C(#N)C>[O:21]=[C:15]1[CH:14]([N:7]2[C:6](=[O:22])[C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH2:3][NH:2][C:55](=[O:56])[CH2:54][C:47]3[C:48]4[C:53](=[CH:52][CH:51]=[CH:50][CH:49]=4)[N:45]([CH3:44])[CH:46]=3)[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1
Reactant: NCc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O
Reactant: Cn1cc(CC(=O)O)c2ccccc21
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: C1CCC2=NCCCN2CC1
Solvent: CC#N
Product: Cn1cc(CC(=O)NCc2cccc3c2C(=O)N(C2CCC(=O)NC2=O)C3=O)c2ccccc21
Reaction time: 0.17 h
Yield: 79.3 %

Procedure:
To a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.2 mmol) in acetonitrile (60 mL), was added 1,8-diazabicyclo[5,4,0]undec-7-ene (0.8 g, 5.4 mmol). After stirring for 10 minutes, 1-hydroxybenzotriazole (0.4 g, 2.6 mmol) and 1-methyl-3-indoleacetic acid (0.5 g, 2.4 mmol) were added, followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.6 g, 3.2 mmol). The mixture was stirred at room temperature overnight and concentrated in vacuo. The residue was dissolved in CH2Cl2 (80 mL) and washed with water (3×40 mL) and brine (40 mL), and dried over MgSO4. Solvent was removed in vacuo, and the residue was purified by ISCO silica gel flash chromatography (Eluent: CH3OH: CH2Cl2 5:95) to afford N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-2-(1-methyl-1H-indol-3-yl)-acetamide (0.8 g, 83%) as a yellow solid: mp 231-233° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=3.53 min. (98%); 1H NMR (DMSO-d6) δ 2.02-2.07 (m, 1H), 2.54-2.63 (m, 2H), 2.83-2.91 (m, 1H), 3.62 (s, 2H), 3.73 (s, 3H), 4.70 (d, J=5.9 Hz, 2H), 5.10-5.16 (dd, J=5.2 and 12.7 Hz, 1H), 6.99-7.04 (dd, J=7.1 and 7.9 Hz, 1H), 7.12-7.17 (dd, J=7.1 and 7.9 Hz, 1H), 7.21 (s, 1H), 7.40 (d, J=8.2 Hz, 1H), 7.54-7.79 (m, 4H), 8.47 (t, J=5.9 Hz, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 21.95, 30.90, 32.23, 32.34, 37.86, 48.83, 107.82, 109.50, 118.39, 118.78, 121.07, 121.79, 127.06, 127.47, 128.27, 131.46, 133.19, 134.54, 136.53, 139.38, 166.91, 167.45, 169.77, 171.15, 172.71; Anal. Calcd. for C25H22N4O5: C, 65.49; H, 4.84; N, 12.22. Found: C, 65.11; H, 4.54; N, 12.05.
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:8]=[C:9]([CH3:19])[CH:10]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:12]=1)(=O)=O.[C-:22]#[N:23].[K+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:22]([C:7]1[CH:8]=[C:9]([CH3:19])[CH:10]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:12]=1)#[N:23]
Reactant: [C-]#N
Reactant: Cc1cc(OS(=O)(=O)C(F)(F)F)cc(-c2ccccc2)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [K+]
Solvent: C1COCCO1
Product: Cc1cc(C#N)cc(-c2ccccc2)c1
Yield: 20 %

Procedure:
A mixture of 3-trifluoromethanesulfonyloxy-5-phenyltoluene (35.6 g; 0.128 mol), tetrakis(triphenylphosphine)palladium (12 g; 0.01 mol) and KCN (15.11 g; 0.23 mol) in dioxan (300 ml) was heated at reflux under argon an atmosphere for 24 hours. After extraction with ether and evaporating, the residue was purified by flash chromatography eluting with petroleum ether/ethyl acetate (84/6) to give 3-cyano-5-phenyltoluene. Yield=20%.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:31][CH3:32])=[C:6]([CH:30]=1)[CH2:7][C@@H:8]1[CH2:14][N:13]([CH2:15][C:16]2[C:21]([O:22][CH3:23])=[CH:20][C:19]([O:24][CH3:25])=[CH:18][C:17]=2[O:26][CH3:27])[C:12](=O)[CH2:11][NH:10][C:9]1=[O:29].O1CCCC1.C1C=CC(OC2C=CC(P3(SP(C4C=CC(OC5C=CC=CC=5)=CC=4)(=S)S3)=[S:52])=CC=2)=CC=1>C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:31][CH3:32])=[C:6]([CH:30]=1)[CH2:7][C@@H:8]1[CH2:14][N:13]([CH2:15][C:16]2[C:21]([O:22][CH3:23])=[CH:20][C:19]([O:24][CH3:25])=[CH:18][C:17]=2[O:26][CH3:27])[C:12](=[S:52])[CH2:11][NH:10][C:9]1=[O:29]
Reactant: COc1cc(OC)c(CN2C[C@@H](Cc3cc(Cl)ccc3OC)C(=O)NCC2=O)c(OC)c1
Reactant: S=P1(c2ccc(Oc3ccccc3)cc2)SP(=S)(c2ccc(Oc3ccccc3)cc2)S1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COc1cc(OC)c(CN2C[C@@H](Cc3cc(Cl)ccc3OC)C(=O)NCC2=S)c(OC)c1
Reaction time: 3 h
Yield: 124.3 %

Procedure:
To the compound S140c described in WO 06-059801A, that is, (6R)-6-(5-chloro-2-methoxybenzyl)-1-(2,4,6-trimethoxybenzyl)-1,4-diazepane-2,5-dione (2.2 g) in a tetrahydrofuran (80 ml) solution, Belleau's reagent (1.5 g) was added under ice cooling, and the mixture was stirred at that temperature for 3 hours. The reaction solution was diluted with ethyl acetate, successively washed with saturated aqueous sodium hydrogencarbonate solution, water, and brine, dried over anhydrous sodium sulfate, then concentrated. The residue was purified by flash column chromatography (silica gel, hexane/ethyl acetate=35/65 to 1/99) to obtain the title compound (1.69 g).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[CH:12]=[N:13][C:14]([O:17][CH2:18][C:19]([OH:21])=O)=[N:15][CH:16]=2)=[O:10])=[CH:4][CH:3]=1.[NH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>CO.ClCCl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]([C:11]2[CH:16]=[N:15][C:14]([O:17][CH2:18][C:19](=[O:21])[NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[N:13][CH:12]=2)=[O:10])=[CH:6][CH:7]=1
Reactant: Nc1ccccc1
Reactant: O=C(O)COc1ncc(C(=O)Nc2ccc(F)cc2)cn1
Solvent: ClCCl
Solvent: CO
Product: O=C(COc1ncc(C(=O)Nc2ccc(F)cc2)cn1)Nc1ccccc1
Yield: 22 %

Procedure:
The titled compound was prepared from [5-(4-fluorophenylcarbamoyl)pyrimidin-2-yloxy]acetic acid using aniline (12 mg, 0.13 mmol) as the coupling partner. Chromatography (10% methanol/dichloromethane) through SiO2 yielded 14 mg (22%) of the titled compound. ESI-MS m/z 367 (MH+), 365 (M−H−).
Reaction SMILES: Br[CH2:2][C@H:3]([F:10])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].FC(F)(F)S(O[C:17]1[C:22]([F:23])=[CH:21][C:20]([CH:24]2[CH2:29][CH2:28][Si:27]([CH2:36][CH2:37][CH2:38][CH:39]=[CH2:40])(C3C=CC=CC=3)[CH2:26][CH2:25]2)=[CH:19][C:18]=1[F:41])(=O)=O>>[CH2:36]([Si@H:27]1[CH2:28][CH2:29][C@H:24]([C:20]2[CH:21]=[C:22]([F:23])[C:17]([CH2:2][C@H:3]([F:10])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9])=[C:18]([F:41])[CH:19]=2)[CH2:25][CH2:26]1)[CH2:37][CH2:38][CH:39]=[CH2:40]
Reactant: CCCCCC[C@@H](F)CBr
Reactant: C=CCCC[Si]1(c2ccccc2)CCC(c2cc(F)c(OS(=O)(=O)C(F)(F)F)c(F)c2)CC1
Product: C=CCCC[Si@H]1CC[C@H](c2cc(F)c(C[C@H](F)CCCCCC)c(F)c2)CC1

Procedure:
The general procedure of Example 18 was repeated-using (R)-1-bromo-2-fluorooctane and (2,6-difluoro-4-(4-(4-pentenyl)-4-phenyl-4-silacyclohexyl)phenyl) trifluoromethanesulfonate, thereby obtaining the intended compound.
Reaction SMILES: Cl[C:2]1[CH:15]=[CH:14][C:13]2[S:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5](=[O:16])[C:4]=2[CH:3]=1.[C:17]1([SH:23])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[OH-].[K+].CN(C)C=O>O>[C:17]1([S:23][C:2]2[CH:15]=[CH:14][C:13]3[S:12][C:11]4[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=4)[C:5](=[O:16])[C:4]=3[CH:3]=2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=c1c2ccccc2sc2ccc(Cl)cc12
Reactant: Sc1ccccc1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CN(C)C=O
Product: O=c1c2ccccc2sc2ccc(Sc3ccccc3)cc12
Temperature: 25 °C
Yield: 45 %

Procedure:
Uniformly mixed were 11.0 parts of 2-chlorothioxanthone, 4.9 parts of thiophenol, 2.5 parts of potassium hydroxide, 162 parts of N,N-dimethylformamide, and allowed to react at 130° C. for 9 hours. Subsequently, the reaction solution was cooled to room temperature (about 25° C.) and poured into 200 parts of distilled water, so that the product was precipitated. The product was filtered, and the residue was washed with water until the pH of the filtrate became neutral. Subsequently, the residue was dried under reduced pressure, so that a yellow powdery product was obtained. The product was purified by column chromatography (eluent: toluene/hexane=1/1 in volume ratio) to give 2-(phenylthio)thioxanthone in a yield of 45%. The product was identified by 1H-NMR {d6-dimethylsulfoxide, δ (ppm) 8.43 (1H, d), 8.25 (1H, s), 7.75-7.90 (3H, m), 7.66 (1H, d), 7.60 (1H, t), 7.42-7.46 (5H, m)}.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH2:7][NH:6][C:5](=[O:8])[CH:4]=1.C(O)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CS(O)(=O)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:1]([O:2][C:3]1[CH2:7][NH:6][C:5](=[O:8])[CH:4]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: OCc1ccccc1
Reactant: COC1=CC(=O)NC1
Agent: CS(=O)(=O)O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: O=C1C=C(OCc2ccccc2)CN1
Temperature: 80 °C
Reaction time: 24 h

Procedure:
5.7 g of 4-methoxy-3-pyrrolin-2-one and 10.8 g of benzyl alcohol were mixed with 0.4 g of methane sulfonic acid and stirred for 24 hours at 80° C. and 20 mbars. Then the reaction solution was mixed with 50 ml of ice water and 100 ml of methylene chloride and neutralized with 4 ml of saturated NaHCO3 solution. The aqueous phase was extracted twice more with 50 ml each of methylene chloride. After drying of the organic phase over Na2SO4 and distilling off of the solvent, the residue was mixed with 150 ml of ice water, heated to 100° C. and 100 ml of water-benzyl alcohol was azeotropically distilled off. The crystals precipitated during the cooling were recrystallized hot from 50 ml of toluene. 6.7 g of white, crystalline product with a melting point of 147° to 148° was obtained. For the product:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[N:10]([S:11]([C:14]3[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[CH:9]=[CH:8][C:5]2=[N:6][CH:7]=1.ClC1C=CC=C(C(OO)=[O:29])C=1>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[N:10]([S:11]([C:14]3[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[CH:9]=[CH:8][C:5]2=[N+:6]([O-:29])[CH:7]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Cc1ccc(S(=O)(=O)n2ccc3ncc(Br)cc32)cc1
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)n2ccc3c2cc(Br)c[n+]3[O-])cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 78.8 %

Procedure:
To a stirred solution of 6-bromo-1-tosyl-1H-pyrrolo[3,2-b]pyridine (6.87 g, 19.56 mmol) in DCM (100 mL) at 0° C. was added 3-chloroperbenzoic acid (77 wt %, 5.26 g, 23.47 mmol). The reaction mixture was stirred at RT until the starting material was completely consumed, as monitored by HPLC. After 8 h, the solution was washed with saturated aqueous NaHCO3 (2×). The organic phase was dried over MgSO4, concentrated in vacuo, and purified by silica gel chromatography (2% to 4% MeOH/DCM) to give the title compound as a white solid (5.66 g, 79%). 1H NMR (500 MHz, CDCl3) δ ppm 8.30 (s, 1H), 8.06 (s, 1H), 7.78 (d, 2H, J=8.0 Hz), 7.65 (d, 1H, J=3.5 Hz), 7.33 (d, 2H, J=8.0 Hz), 7.06 (d, 1H, J=3.5 Hz), 2.41 (s, 3H); ESI-MS m/z [M+H]+ calc'd for C14H11BrN2O3S, 367, 369; found 367, 369.
Reaction SMILES: Cl.C(N=C=NCCCN(C)C)C.[O:13]=[C:14]1[NH:22][C:17]2=[N:18][CH:19]=[CH:20][CH:21]=[C:16]2[C@@:15]21[CH2:33][C:25]1=[N:26][CH:27]=[C:28]([C:30](O)=[O:31])[CH:29]=[C:24]1[CH2:23]2.Cl.[NH2:35][C@H:36]1[CH2:41][C@@H:40]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=2[CH3:48])[C@@H:39]([CH3:49])[N:38]([CH2:50][C:51]([F:54])([F:53])[F:52])[C:37]1=[O:55].N1C2C(=NC=CC=2)N(O)N=1.C(N(CC)CC)C>CN(C=O)C>[CH3:49][C@H:39]1[N:38]([CH2:50][C:51]([F:53])([F:54])[F:52])[C:37](=[O:55])[C@@H:36]([NH:35][C:30]([C:28]2[CH:29]=[C:24]3[CH2:23][C@@:15]4([C:16]5[C:17](=[N:18][CH:19]=[CH:20][CH:21]=5)[NH:22][C:14]4=[O:13])[CH2:33][C:25]3=[N:26][CH:27]=2)=[O:31])[CH2:41][C@H:40]1[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=1[CH3:48]
Reactant: O=C(O)c1cnc2c(c1)C[C@@]1(C2)C(=O)Nc2ncccc21
Reactant: Cc1ccccc1[C@@H]1C[C@H](N)C(=O)N(CC(F)(F)F)[C@@H]1C
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2cccnc21
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1ccccc1[C@@H]1C[C@H](NC(=O)c2cnc3c(c2)C[C@@]2(C3)C(=O)Nc3ncccc32)C(=O)N(CC(F)(F)F)[C@@H]1C
Temperature: 23 °C
Reaction time: 18 h

Procedure:
N1-((Ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.10 g, 0.53 mmol) was added to a solution of (6S)-2′-oxo-1′,2′,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridine]-3-carboxylic acid (described in Intermediate 1) (111 mg, 0.39 mmol), (3S,5S,6R)-3-amino-6-methyl-5-(2-methylphenyl)-1-(2,2,2-trifluoroethyl)piperidin-2-one hydrochloride (described in Intermediate 6) (127 mg, 0.38 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (HOAt, 15 mg, 0.11 mmol), and triethylamine (0.16 mL, 0.91 mmol) in DMF (3 mL), and the resulting mixture was stirred at 23° C. for 18 h. The reaction mixture was then partitioned between saturated aqueous sodium bicarbonate solution (10 mL) and ethyl acetate (2×30 mL). The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel, eluting with 1% methanol→7% methanol/dichloromethane to afford the title compound. HRMS: m/z=564.2219 (M+1), calculated m/z=564.2234 for C30H28F3N5O3. 1H NMR (500 MHz, CDCl3) δ 8.91 (s, 1H), 8.56 (s, 1H), 8.17 (dd, 1H, J=5.0, 1.5 Hz), 8.05 (s, 1H), 7.30 (d, 1H, J=5.0 Hz), 7.20 (m, 3H), 7.12 (m, 2H), 6.89 (dd, 1H, J=7.5, 5.0 Hz), 5.00-4.94 (m, 1H), 4.55 (m, 1H), 3.93-3.90 (m, 1H), 3.81-3.76 (m, 2H), 3.68 (d, 1H, J=16.5 Hz), 3.31-3.23 (m, 2H), 3.17 (d, 1H, J=16.5 Hz), 2.75-2.67 (m, 2H), 2.41 (s, 3H), 1.11 (d, 3H, J=6.5 Hz).
Reaction SMILES: [BH4-].[Na+].[CH3:3][C:4]1[C:12]2[C:11]([CH:13]=[C:14]3[N:18]4[CH:19]=[CH:20][CH:21]=[CH:22][C:17]4=[N:16][C:15]3=[O:23])=[CH:10][S:9][C:8]=2[CH:7]=[CH:6][CH:5]=1>C(O)C.CO>[CH3:3][C:4]1[C:12]2[C:11]([CH2:13][CH:14]3[N:18]4[CH:19]=[CH:20][CH:21]=[CH:22][C:17]4=[N:16][C:15]3=[O:23])=[CH:10][S:9][C:8]=2[CH:7]=[CH:6][CH:5]=1
Reactant: Cc1cccc2scc(C=C3C(=O)N=C4C=CC=CN34)c12
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: CO
Product: Cc1cccc2scc(CC3C(=O)N=C4C=CC=CN43)c12
Temperature: -78 °C
Reaction time: 0.25 h

Procedure:
To a suspension of 121 mg (3.2 mmol) of sodium borohydride in 50 mL of ethanol is added a solution of 624 mg (2.1 mmol) of 3-(4-methyl-benzo[b]thiophen-3-ylmethylene)-imidazo[1,2-a]pyridin-2-one in 50 mL of methanol dropwise at −78° C. After stirring for 15 minutes at −78° C., the reaction mixture is quenched with saturated aqueous ammonium chloride solution at −78° C. The product is extracted with dichloromethane. The organic layer is dried over magnesium sulfate, filtered and concentrated in vacuo to give the desired compound.