Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[N:10]=2)[N:5]=[CH:4][C:3]=1[C:14]([O:16][CH2:17][CH3:18])=[O:15].[CH3:19][O:20][C:21]1[CH:27]=[CH:26][C:24]([NH2:25])=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1>[CH3:13][O:12][C:9]1[N:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][C:3]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:2]2[NH:25][C:24]1[CH:26]=[CH:27][C:21]([O:20][CH3:19])=[CH:22][CH:23]=1
Reactant: COc1ccc(N)cc1
Reactant: CCOC(=O)c1cnc2ccc(OC)nc2c1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CCOC(=O)c1cnc2ccc(OC)nc2c1Nc1ccc(OC)cc1
Temperature: 25 °C
Reaction time: 7 h

Procedure:
A mixture of ethyl 4-chloro-6-methoxy-1,5-naphthyridine-3-carboxylate (1.68 g), 4-methoxyaniline (0.78 g), dry THF (50 ml) and anhydrous potassium carbonate (1.74 g) was stirred at ambient temperature for 7 hours. Further amounts of 4-methoxyaniline (0.4 g) and anhydrous potassium carbonate (0.9 g) were added and the mixture stirred at ambient temperature for 32 hours. The mixture was evaporated to dryness and the residue diluted with water (100 ml). The mixture was extracted into dichloromethane to give an oil which solidified. The solid was purified by column chromatography on silica using ethyl acetate as the mobile phase to give ethyl 6-methoxy-4-(4-methoxyanilino)-1,5-naphthyridine-3-carboxylate, m.p. 115°-117° C.
Reaction SMILES: [N+:1]([C:4]1[C:17]2[C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:19])[C:8]=2[CH:7]=[CH:6][CH:5]=1)([O-])=O.[CH:20]1(N)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1>ClC1C=CC=CC=1Cl>[CH:20]1([NH:1][C:4]2[C:17]3[C:16](=[O:18])[C:15]4[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=4)[C:9](=[O:19])[C:8]=3[CH:7]=[CH:6][CH:5]=2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1
Reactant: O=C1c2ccccc2C(=O)c2c1cccc2[N+](=O)[O-]
Reactant: NC1CCCCC1
Solvent: Clc1ccccc1Cl
Product: O=C1c2ccccc2C(=O)c2c(NC3CCCCC3)cccc21

Procedure:
1-Nitroanthraquinone is refluxed with an excess of cyclohexylamine in o-dichlorobenzene to yield 1-cyclohexylamino anthraquinone which is further brominated in aqueous pyridine to yield the corresponding 1-cyclohexylamino-4-bromoanthraquinone. This compound is further condensed with p-amino acetanilide to yield 1-cyclohexylamino-4-(p-acetaminoanilino)anthraquinone as a bright green pleochroic dye having an optical order parameter 0.7.
Reaction SMILES: [CH3:1][O-:2].[Na+].[Cl:4][C:5]1[N:14]=[C:13](Cl)[C:12]2[C:7](=[CH:8][C:9]([O:18][CH3:19])=[C:10]([O:16][CH3:17])[CH:11]=2)[N:6]=1>CO>[Cl:4][C:5]1[N:14]=[C:13]([O:2][CH3:1])[C:12]2[C:7](=[CH:8][C:9]([O:18][CH3:19])=[C:10]([O:16][CH3:17])[CH:11]=2)[N:6]=1
Reactant: C[O-]
Reactant: COc1cc2nc(Cl)nc(Cl)c2cc1OC
Agent: [Na+]
Solvent: CO
Product: COc1cc2nc(Cl)nc(OC)c2cc1OC
Temperature: 25 °C
Reaction time: 12 h
Yield: 100.1 %

Procedure:
Sodium methoxide (0.12 g, 2.2 mmole) was added to a solution of 2,4-dichloro-6,7-dimethoxyquinazoline (0.52 g, 2 mmol) in methanol (20 mL) at 25° C. The mixture was stirred at 25° C. for 12 h and was concentrated in vacuo to give a white solid residue. Purification of the residue by flash column chromatography (gradient elution 30 to 60% EtOAc/hexanes) provided the title compound (0.51 g, quantitative yield): TLC (Rf =0.50; CH2Cl2); 1H NMR (CDCl3) δ 7.33 (s, 1H), 7.21 (s, 1H), 4.20 (s, 3H), 4.01 (s, 6H); 13C NMR (CDCl3) δ 166.9, 156.1, 154.3, 149.8, 149.5, 109.0, 106.2, 101.4, 56.4, 56.3, 55.0; HRMS (FAB) m/z 255.0531 (M+H)+ (C11H11N2O3Cl requires 255.0536); Anal. (C11H11N2O3Cl·1/2H2O·1/4CH3OH) C, H, N.
Reaction SMILES: [CH3:1][C@H:2]1[NH:7][C:6](=[O:8])[C@@H:5]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:4][C@H:3]1[C:17]1[C:22]([F:23])=[CH:21][CH:20]=[C:19]([F:24])[C:18]=1[F:25].C(O[Li])(C)(C)C.FC(F)(F)S(O[CH2:38][C:39]([F:42])([F:41])[F:40])(=O)=O.CN1C(=O)N(C)CCC1>C1COCC1>[CH3:1][C@H:2]1[N:7]([CH2:38][C:39]([F:42])([F:41])[F:40])[C:6](=[O:8])[CH:5]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:14])([CH3:15])[CH3:13])[CH2:4][C@H:3]1[C:17]1[C:22]([F:23])=[CH:21][CH:20]=[C:19]([F:24])[C:18]=1[F:25]
Reactant: O=S(=O)(OCC(F)(F)F)C(F)(F)F
Reactant: C[C@H]1NC(=O)[C@@H](NC(=O)OC(C)(C)C)C[C@H]1c1c(F)ccc(F)c1F
Agent: [Li]OC(C)(C)C
Solvent: CN1CCCN(C)C1=O
Solvent: C1CCOC1
Product: C[C@@H]1[C@H](c2c(F)ccc(F)c2F)CC(NC(=O)OC(C)(C)C)C(=O)N1CC(F)(F)F
Temperature: 0 °C
Reaction time: 3 h

Procedure:
To a solution of 21 (10 g, 87% purity, 24.3 mmol) in THF (70 ml) was added tert-BuOLi (2.5 g, 31.2 mmol) at 5° C. in one portion. The solution was cooled to between 0 and 5° C. and trifluoroethyl trifluoromethanesulfonate (10.0 g, 43 mmol) was added in one portion. DMPU (7 mL) was added slowly over 15 min while maintaining the reaction temperature below 5° C. After the mixture was stirred at 0° C. for 3 h, additional tert-BuOLi (0.9 g, 11.2 mmol) was added. The mixture was aged for an additional 90 min. The mixture was quenched with 0.2 N HCl (70 ml), followed by addition of heptane (80 ml). The organic layer was separated and aqueous layer extracted with heptane (30 ml). The combined organic layers were washed with 15% aqueous citric acid (50 mL) and 5% aqueous NaHCO3 (50 mL). The solution was concentrated under vacuum at 40° C. and the resulting oil was dissolved in iPAc (30 mL). The solution was used directly in the next step without further purification. The HPLC analysis indicated that the solution contained 22 (9.8 g, 92% as cis and trans mixture in a ratio of 6.5 to 1) along with 4% of starting material 21 and 8% of a N,N′-alkylated compound. Analytically pure 22 (cis isomer) was isolated by chromatography on silica gel with ethyl acetate and heptane as an eluant. 1H NMR (CDCl3, 500 MHz): δ 7.15 (m, 1H), 6.85 (m, 1H), 5.45 (broad, s, 1H), 4.90 (m, H), 4.20 (m, 1H), 3.92 (m, 2H), 3.28 (m, 1H), 2.70 (m, 2H), 1.48 (s, 9H), 1.20 (d, J=5.9 Hz, 3H); 13C NMR (CDCl3, 100 MHz): δ 170.2, 156.9 (ddd, J=245, 6.3, 2.7 Hz), 156.0, 149.6 (ddd, J=251, 14.8, 8.8 Hz), 147.6 (ddd, J=246, 13.9, 3.6 Hz), 124.5 (q, J=281 Hz), 117.6 (dd, J=19.2, 3.7 Hz), 116.4 (dd, J=19.1, 10.4 Hz), 111.4 (ddd, J=25.8, 6.4, 4.1 Hz), 56.6, 52.8, 45.3 (q, J=34.2 Hz), 35.2, 28.7, 28.3 (br t, J=4 Hz), 14.6; HRMS: m/z calcd for C19H22F6N2O3 (M+H): 441.1607. found 441.1617.
Reaction SMILES: C(O[CH2:9][C@@H:10]([CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[C:11]([OH:13])=[O:12])C1C=CC=CC=1.CC[OH:21]>[Pd]>[OH:21][CH:16]([CH2:17][CH3:18])[CH2:15][CH2:14][C@@H:10]([CH3:9])[C:11]([OH:13])=[O:12]
Reactant: CCCCC[C@H](COCc1ccccc1)C(=O)O
Reactant: CCO
Agent: [Pd]
Product: CCC(O)CC[C@@H](C)C(=O)O
Reaction time: 8 h

Procedure:
To a solution of (R)-3-benzyloxy-2-pentyl-propionic acid (1.54 g, 6.16 mmol) in EtOH (100 mL) was added 10% Pd/C (310 mg). The reaction mixture was subjected to hydrogenation overnight at room temperature. After the reaction was completed, the reaction mixture was filtered through a pad of Celite, and washed with EtOH (50 mL×3). Removal of the solvent provided the title compound. No further purification was required. 1H NMR (400 MHz, CHCl3) δ 6.30 (br s, 1H), 3.81 (d, J=5.4 Hz, 2H), 2.64 (m, 1H), 1.69 (m, 1H), 1.56 (m, 1H), 1.41-1.27 (m, 6H), 0.91 (t, J=7.7 Hz, 3H). MH+161.
Reaction SMILES: [Na].[O-]CC.[Na+].[C:6]([O:14]CC)(=O)[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9].[NH2:17][C:18]1[N:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:21]=[CH:20][C:19]=1[C:29]#[N:30]>C(O)C>[CH2:11]([O:10][C:8]([C:7]1[C:6](=[O:14])[NH:17][C:18]2[N:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:21]=[CH:20][C:19]=2[C:29]=1[NH2:30])=[O:9])[CH3:12]
Reactant: N#Cc1cnn(-c2ccccc2)c1N
Reactant: CCOC(=O)CC(=O)OCC
Agent: CC[O-]
Agent: [Na+]
Agent: [Na]
Solvent: CCO
Product: CCOC(=O)c1c(N)c2cnn(-c3ccccc3)c2[nH]c1=O
Yield: 40.2 %

Procedure:
Sodium pellets (0.86 g, 37.4 mmol) were added carefully to dry ethanol (40 ml) in a round-bottomed flask with a condenser in place and under nitrogen. The resulting solution of sodium ethoxide was allowed to cool to room temperature before addition of diethyl malonate (4.74 ml, 31.2 mmol). 5-Amino-1-phenylpyrazole-4-carbonitrile (2.30 g, 12.5 mmol) was added portionwise and the mixture heated at reflux for 4 h. The mixture was cooled and the ethanol removed in vacuo. Water (25 ml) was added to the residue and the solid was filtered off, washing with water. 4-Amino-6,7-dihydro-6-oxo-1-phenyl-1H-pyrazolo [3,4-b]pyridine-5-carboxylic acid ethyl ester (1.5 g, 40%) was obtained as a white solid. δH (400 MHz; DMSO) 1.35 (3H, t, J=7), 4.40 (2H, q, J=7), 7.30-7.34 (1H, m), 7.49-7.54 (2H, m), 8.04 (2H, br s), 8.09 (2H, br d, J=8), 8.44 (1H, s), 12.20 (1H, br s).
Reaction SMILES: I[CH:2]([CH2:4][CH2:5][CH2:6][CH3:7])[CH3:3].[NH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[OH:15]>>[CH3:3][CH:2]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[OH:15])[CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: CCCCC(C)I
Reactant: Nc1ccccc1O
Product: CCCCC(C)Nc1ccccc1O
Reaction time: 5.33 h

Procedure:
The same procedure as in Example 4 was repeated except for using 2-iodohexane in place of 2-iodobutane, to conduct the reaction. As a result, it was confirmed that the rate of conversion of o-aminophenol was 93%, the selectivity to the N-monoalkylated compound was 41% and the oxygen absorption initiation time as an index of determining an oxidation-inhibiting property thereof was 320 min.
Reaction SMILES: [CH:1]1([C:5]2[C:13](I)=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[C:7]([CH3:15])[CH:6]=2)[CH2:4][CH2:3][CH2:2]1.[Li]CCCC.[C:21](=O)([O:24]C)[O:22][CH3:23]>C1COCC1>[CH:1]1([C:5]2[C:13]([C:21]([O:22][CH3:23])=[O:24])=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[C:7]([CH3:15])[CH:6]=2)[CH2:4][CH2:3][CH2:2]1
Reactant: Cc1cc(C2CCC2)c(I)cc1C(=O)O
Reactant: COC(=O)OC
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: COC(=O)c1cc(C(=O)O)c(C)cc1C1CCC1
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 55.2 %

Procedure:
To a solution of 4-cyclobutyl-5-iodo-2-methylbenzoic acid (compound 230.1, 3.00 g, 9.49 mmol, 1.00 equiv) in THF (40 mL) under nitrogen at −78° C. was added dropwise n-BuLi (9.5 mL, 2.50 equiv, 2.5 M in THF). After 10 minutes, a solution of dimethyl carbonate (2.56 g, 28.4 mmol, 3.00 equiv) in THF (10 mL) was added dropwise at −78° C. The resulting solution was stirred for 1 h at −78° C., then carefully quenched by slow addition of 50 mL of water. The pH was adjusted to ˜4 with hydrogen chloride (aq., 1 M). The resulting mixture was extracted with 2×80 mL of ethyl acetate, the combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (1:10-1:2) as eluent to furnish 1.30 g (55%) of 4-cyclobutyl-5-(methoxycarbonyl)-2-methylbenzoic acid as a white solid.
Reaction SMILES: O(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O.[CH2:16]([O:23][N:24]1[C:30](=[O:31])[N:29]2[CH2:32][C@H:25]1[CH2:26][CH2:27][C@H:28]2[C:33]([NH:35][NH:36][C:37](=O)[CH2:38][CH2:39][CH2:40][NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:34])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:16]([O:23][N:24]1[C:30](=[O:31])[N:29]2[CH2:32][C@H:25]1[CH2:26][CH2:27][C@H:28]2[C:33]1[O:34][C:37]([CH2:38][CH2:39][CH2:40][NH:41][C:42](=[O:48])[O:43][C:44]([CH3:46])([CH3:47])[CH3:45])=[N:36][N:35]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: CC(C)(C)OC(=O)NCCCC(=O)NNC(=O)[C@@H]1CC[C@@H]2CN1C(=O)N2OCc1ccccc1
Agent: O=C([O-])O
Agent: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NCCCc1nnc([C@@H]2CC[C@@H]3CN2C(=O)N3OCc2ccccc2)o1
Temperature: 0 °C
Reaction time: 3 h
Yield: 54 %

Procedure:
Tf2O (8.0 mL, 0.0474 mol) was added dropwise to a −78° C. solution of tert-butyl 4-(2-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)hydrazinyl)-4-oxobutylcarbamate (7.5 g, 0.0158 mol) and Py (10.2 mL, 0.126 mol) in dry DCM (120 mL). The reaction mixture was allowed to warm to 0° C. then the reaction mixture was stirred at 0° C. for 3 hrs. Sat. NaHCO3 was added at 0° C. very slowly. The organic layer was separated and the water layer was exacted with DCM (3×). The combined organic layer was washed with water, saturated sodium chloride, dried over Na2SO4, and concentrated. The residue was purified by silica gel column (gradient elution 0˜25% EtOAc/petroleum ether) to afford tert-butyl 3-(5-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octan-2-yl)-1,3,4-oxadiazol-2-yl)propylcarbamate (3.9 g, 54%) as a yellow solid. ESI-MS (EI+, m/z): 458 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 7.45-7.37 (m, 5H), 5.08 (d, J=14.5 Hz, 1H), 4.93 (d, J=14.5 Hz, 1H), 4.70-4.66 (m, 1H), 3.37 (br s, 1H), 3.23-3.21 (m, 2H), 2.94-2.88 (m, 3H), 2.79 (d, J=14.5 Hz, 1H), 2.30-2.28 (m, 2H), 2.11-1.97 (m, 4H), 1.45 (s, 9H).
Reaction SMILES: S(Cl)(Cl)=O.[F:5][C:6]1[CH:19]=[C:18]2[C:9]([S:10](=[O:25])(=[O:24])[C:11]3[CH:12]=[C:13]([C:21]([NH2:23])=O)[CH:14]=[CH:15][C:16]=3[C:17]2=[O:20])=[CH:8][CH:7]=1>CN(C=O)C>[C:21]([C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[C:17](=[O:20])[C:18]1[CH:19]=[C:6]([F:5])[CH:7]=[CH:8][C:9]=1[S:10]2(=[O:25])=[O:24])#[N:23]
Reactant: NC(=O)c1ccc2c(c1)S(=O)(=O)c1ccc(F)cc1C2=O
Solvent: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: N#Cc1ccc2c(c1)S(=O)(=O)c1ccc(F)cc1C2=O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Thionyl chloride (75 g) was cooled to 5° C. and DMF (150 ml) was added dropwise and the temperature was maintained below 10° C. The amide prepared in (a) supra, 19.1 g, (0.05 mol) was added and the mixture was allowed to warm to room temperature and was stirred for 2 hr. The mixture was poured onto 1 L of ice and was filtered. The solid was washed with H2O, 2×300 ml and dried. The nitrile was dissolved in hot acetic acid (800 ml), treated with charcoal and filtered through a celite bed. The solution was cooled, and the crystals were collected by filtration and dried in vacuo to give 14.48 g of 6-cyano-2-fluorothioxanthene-9-one 10,10-dioxide, m.p.=260°-262°0 C.; TLC on silica gel (butanol:acetic acid:H2O/5:4:1), Rf =0.82.
Reaction SMILES: FC(F)(F)C(O)=O.[CH3:8][O:9][C:10](=[O:35])[C@@H:11]([NH:14][C:15]([C:17]1[S:18][C:19]([C:24](=[O:34])[NH:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([OH:33])[CH:28]=2)=[CH:20][C:21]=1[CH2:22][CH3:23])=[O:16])[CH2:12][NH2:13].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.[S:77]1[CH:81]=[CH:80][CH:79]=[C:78]1[C:82](O)=[O:83]>CN(C=O)C.CCOC(C)=O>[CH3:8][O:9][C:10](=[O:35])[C@@H:11]([NH:14][C:15]([C:17]1[S:18][C:19]([C:24](=[O:34])[NH:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([OH:33])[CH:28]=2)=[CH:20][C:21]=1[CH2:22][CH3:23])=[O:16])[CH2:12][NH:13][C:82]([C:78]1[S:77][CH:81]=[CH:80][CH:79]=1)=[O:83]
Reactant: O=C(O)c1cccs1
Reactant: CCc1cc(C(=O)NCc2cccc(O)c2)sc1C(=O)N[C@@H](CN)C(=O)OC
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCc1cc(C(=O)NCc2cccc(O)c2)sc1C(=O)N[C@@H](CNC(=O)c1cccs1)C(=O)OC
Temperature: 25 °C
Reaction time: 15 h
Yield: 31.5 %

Procedure:
To a solution of (S)-3-Amino-2-{[3-ethyl-5-(3-hydroxy-benzylcarbamoyl)-thiophene-2-carbonyl]-amino}-propionic acid methyl ester trifluoro-acetic acid salt (0.46 mmol) in anhydrous DMF (10 mL) was added triethylamine (0.19 mL, 1.38 mmol), HBTU (0.26 g, 0.69 mmol), HOBT (0.074 g, 0.55 mmol), and 2-Thiophenecarboxylic acid (0.071 g, 0.55 mmol). The mixture was stirred at room temperature 15 h, treated with EtOAc (30 mL), washed with brine, dried over sodium sulfate, filtered and evaporated. The solid residue was purified by column (30-60% EtOAc in hexane) to give 0.0747 g (31%) white foam product. MS m/e 516.0 (M+H+).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH2:12][C:13]([OH:15])=[O:14])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[Cl:16][C:17]1[CH:18]=[C:19]([S:24]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=2)(=[O:26])=[O:25])[CH:20]=[CH:21][C:22]=1F>>[Cl:16][C:17]1[CH:18]=[C:19]([S:24]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=2)(=[O:25])=[O:26])[CH:20]=[CH:21][C:22]=1[O:1][C:2]1[CH:3]=[C:4]([CH2:12][C:13]([OH:15])=[O:14])[CH:5]=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:7]=1
Reactant: O=S(=O)(Cc1ccccn1)c1ccc(F)c(Cl)c1
Reactant: O=C(O)Cc1cc(O)cc(C(F)(F)F)c1
Product: O=C(O)Cc1cc(Oc2ccc(S(=O)(=O)Cc3ccccn3)cc2Cl)cc(C(F)(F)F)c1

Procedure:
The title compound was prepared as described in example 2 step (iii) but instead using the product from example 25 step (iv) and the product from step (ii).
Reaction SMILES: C([Si](C)(C)[O:6][CH:7]1[CH2:11][CH2:10][N:9]([S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[NH:21][C:22]2[C:27]([Cl:28])=[CH:26][N:25]=[C:24](Cl)[N:23]=2)(=[O:14])=[O:13])[CH2:8]1)(C)(C)C.[NH2:32][C:33]1[CH:34]=[CH:35][C:36]2[CH2:42][CH2:41][CH2:40][C:39](=[O:43])[NH:38][C:37]=2[CH:44]=1>>[Cl:28][C:27]1[C:22]([NH:21][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[S:12]([N:9]2[CH2:10][CH2:11][CH:7]([OH:6])[CH2:8]2)(=[O:13])=[O:14])=[N:23][C:24]([NH:32][C:33]2[CH:34]=[CH:35][C:36]3[CH2:42][CH2:41][CH2:40][C:39](=[O:43])[NH:38][C:37]=3[CH:44]=2)=[N:25][CH:26]=1
Reactant: Nc1ccc2c(c1)NC(=O)CCC2
Reactant: CC(C)(C)[Si](C)(C)OC1CCN(S(=O)(=O)c2ccccc2Nc2nc(Cl)ncc2Cl)C1
Product: O=C1CCCc2ccc(Nc3ncc(Cl)c(Nc4ccccc4S(=O)(=O)N4CCC(O)C4)n3)cc2N1

Procedure:
The title compound was prepared by combining {2-[3-(tert-butyl-dimethyl-silanyloxy)-pyrrolidine-1-sulfonyl]-phenyl}-(2,5-dichloro-pyrimidin-4-yl)-amine (Example N?, 100.4 mg, 0.199 mmol) and 8-amino-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (38.4 mg, 0.218 mmol) in an analogous manner described in Example 1492 and was obtained as a white powder (57 mg, 54%) that had the following properties: m.p: 155-160° C.; LC/MS (m/e): 529 (M+H); 1H-NMR (DMSO-d6, 400 MHz): δ 9.56 (s, 1H), 9.44 (m, 2H), 8.65 (m, 1H), 8.29 (s, 1H), 7.85 (d, J=7.9, 1H), 7.66 (m, 1H), 7.40-7.20 (series of m, 3H), 7.10 (d, J=8.2, 1H), 4.99 (d, J=2.8, 1H), 4.18 (m, 1H), 3.26 (m, 3H), 3.05 (d, J=10.1, 1H), 2.63 (m, 2H), 2.16 (m, 2H), 2.08 (m, 2H), 1.82 (m, 1H), 1.67 (m, 1H).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:22])[C:5]([N:19]=[N+]=[N-])=[CH:6][C:7]1[O:8][C:9]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=[CH:10][CH:11]=1)[CH3:2]>CC1C=CC(C)=CC=1>[CH2:1]([O:3][C:4]([C:5]1[NH:19][C:11]2[CH:10]=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=3)[O:8][C:7]=2[CH:6]=1)=[O:22])[CH3:2]
Reactant: CCOC(=O)C(=Cc1ccc(-c2ccc(Cl)cc2)o1)N=[N+]=[N-]
Solvent: Cc1ccc(C)cc1
Product: CCOC(=O)c1cc2oc(-c3ccc(Cl)cc3)cc2[nH]1
Temperature: 140 °C
Yield: 78.4 %

Procedure:
The obtained 2-Azido-3-[5-(4-chloro-phenyl)-furan-2-yl]-acrylic acid ethyl ester (21 mg, 0.066 mmol) was dissolved in p-xylene and the mixture was heated to 140° C. for half an hour. The solvent was thereafter evaporated to give 15 mg (78% yield) of 2-(4-chloro-phenyl)-4H-furo[3,2-b]pyrrole-5-carboxylic acid ethyl ester as a red solid.
Reaction SMILES: O1[CH:6]=[CH:5][C:4](=[O:7])[CH:3]=[CH:2]1.[C:8]([O:12][C:13](=[O:16])[NH:14][NH2:15])([CH3:11])([CH3:10])[CH3:9]>C(O)C>[C:8]([O:12][C:13]([NH:14][N:15]1[CH:6]=[CH:5][C:4](=[O:7])[CH:3]=[CH:2]1)=[O:16])([CH3:11])([CH3:10])[CH3:9]
Reactant: O=c1ccocc1
Reactant: CC(C)(C)OC(=O)NN
Solvent: CCO
Product: CC(C)(C)OC(=O)Nn1ccc(=O)cc1
Yield: 55.2 %

Procedure:
4-Pyranone (1 g, 10.4 mmol) and t-butylcarbazate (1.32 g, 10 mmol) were heated at reflux in ethanol for 48 h. The solvent was gradually allowed to distil from the mixture and the residue was chromatographed on silica gel 60, eluting with ethanol, dichloromethane (1:19) to give the title compound (1.16 g, 50%); υmax (KBr) 1723, 1630, and 1550cm-1 ; δH 1.54 (9H, s), 6.47 (2H, d), and 7.60 (2H, d); M+ 210.
Reaction SMILES: S(Cl)(Cl)=O.[OH:5][C:6]1[CH:14]=[CH:13][C:9]([C:10]([OH:12])=[O:11])=[CH:8][N:7]=1.[CH3:15]O>>[OH:5][C:6]1[CH:14]=[CH:13][C:9]([C:10]([O:12][CH3:15])=[O:11])=[CH:8][N:7]=1
Reactant: O=C(O)c1ccc(O)nc1
Reactant: CO
Solvent: O=S(Cl)Cl
Product: COC(=O)c1ccc(O)nc1

Procedure:
To methanol (100 ml) in an ice bath was added thionyl chloride (16 ml) followed by addition of 6-hydroxynicotinic acid (10 g).
Reaction SMILES: [C:1]1([S:7]([CH2:9][C:10]([OH:12])=O)=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(N=C=NC2CCCCC2)CCCCC1.[NH2:28][CH:29]1[C:47](=[O:48])[N:31]2[C:32]([C:44]([OH:46])=[O:45])=[C:33]([CH2:36][S:37][C:38]3[S:42][C:41]([CH3:43])=[N:40][N:39]=3)[CH2:34][S:35][C@H:30]12>C(Cl)Cl.C(N(CC)CC)C.C(O)C>[C:1]1([S:7]([CH2:9][C:10]([NH:28][CH:29]2[C:47](=[O:48])[N:31]3[C:32]([C:44]([OH:46])=[O:45])=[C:33]([CH2:36][S:37][C:38]4[S:42][C:41]([CH3:43])=[N:40][N:39]=4)[CH2:34][S:35][C@H:30]23)=[O:12])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C(O)CS(=O)c1ccccc1
Reactant: Cc1nnc(SCC2=C(C(=O)O)N3C(=O)C(N)[C@H]3SC2)s1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CCN(CC)CC
Solvent: CCO
Solvent: ClCCl
Product: Cc1nnc(SCC2=C(C(=O)O)N3C(=O)C(NC(=O)CS(=O)c4ccccc4)[C@H]3SC2)s1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 16.6 %

Procedure:
To 8 ml of methylene chloride were added 0.37 g of phenylsulfinylacetic acid of the R form ([α]D20 :+183°, C=1.00, ethanol) and 0.41 g of dicyclohexylcarbodiimide, and the mixture was agitated at room temperature for 1.5 hours. Then, a solution consisting of 0.69 g of 7-amino-3-(2-methyl-1,3,4-thiadiazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid, 0.28 ml of triethylamine and 8 ml of methylene chloride was added to the above mixture, and the resulting mixture was agitated at room temperature overnight. The reaction mixture was filtered, and the filtrate was post-treated in the same manner as described in Example 19 to obtain 0.17 g of 7-(phenylsulfinylacetamido)-3-(2-methyl-1,3,4-thiadiazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid of the R form, the IR and NMR spectra of which were found to be in agreement with those of the intended product.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:18])[C:5](=[CH2:17])[CH2:6][CH2:7][CH2:8][CH2:9][O:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)[CH3:2].ClC1C=CC=C(C(OO)=[O:27])C=1>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:5]1([CH2:6][CH2:7][CH2:8][CH2:9][O:10][CH:11]2[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]2)[CH2:17][O:27]1)=[O:18])[CH3:2]
Reactant: C=C(CCCCOC1CCCCC1)C(=O)OCC
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CCOC(=O)C1(CCCCOC2CCCCC2)CO1

Procedure:
2.4 g of the title compound, in the form of a colourless oil, which is purified by chromatography on silica gel (migrating agent: 90:10 petroleum ether/ethyl acetate), are obtained by the procedure described in Example 1a) from 4.9 g of 6-cyclohexyloxy-2-methylenehexanoic acid ethyl ester and 7 g of m-chloroperbenzoic acid in 50 ml of methylene chloride.
Reaction SMILES: [Al+3].[Cl-].[Cl-].[Cl-].[CH3:5][C:6]([N:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)([CH3:22])[C:7]([C:9]1[CH:14]=[CH:13][C:12]([S:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:11][CH:10]=1)=[O:8].[Br:29][C:30]([CH3:35])([CH3:34])[C:31](Br)=[O:32]>ClCCl>[Br:29][C:30]([CH3:35])([CH3:34])[C:31]([C:19]1[CH:20]=[CH:21][C:16]([S:15][C:12]2[CH:13]=[CH:14][C:9]([C:7](=[O:8])[C:6]([CH3:5])([N:23]3[CH2:24][CH2:25][O:26][CH2:27][CH2:28]3)[CH3:22])=[CH:10][CH:11]=2)=[CH:17][CH:18]=1)=[O:32]
Reactant: CC(C)(Br)C(=O)Br
Reactant: CC(C)(C(=O)c1ccc(Sc2ccccc2)cc1)N1CCOCC1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CC(C)(Br)C(=O)c1ccc(Sc2ccc(C(=O)C(C)(C)N3CCOCC3)cc2)cc1
Reaction time: 2.5 h
Yield: 100 %

Procedure:
4.30 (32.20 mol) of AlCl3 were added in portion under stirring to a solution of 2.5 g (7.32 mmol) of 2-methyl-2-morpholin yl-1-(4-phenylsulphanyl-phenyl)-propan-1-one and 1.81 g (7.69 mmol) of α-bromoisobutyrylbromide (97.5% w/w) in 50 ml of dichloromethane, between 0 e 5° C. At the end of the addition the temperature was brought to 25° C. then, after 2.5 h, the reaction was quenched in 200 ml of iced water. The organic phase was separated and washed with water and 5% NaOH then dried with sodium sulphate, filtered and evaporated obtaining 3.59 g of product as a reddish oil.