Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([CH:12]=NN=P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=[O:11])=[CH:5][CH:4]=1.N([O-])=[O:35].[Na+].Cl>O1CCCC1.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:9][C:10]([CH:12]=[O:35])=[O:11])=[CH:7][CH:8]=1
Reactant: O=N[O-]
Reactant: COc1ccc(CC(=O)C=NN=P(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: Cl
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: COc1ccc(CC(=O)C=O)cc1
Reaction time: 0.5 h

Procedure:
A solution of 1.82 g of 1-(4-methoxyphenyl)-3-(triphenylphosphoranylidene-hydrazono)-acetone in 12 ml of tetrahydrofuran is mixed with 0.84 g of pulverized sodium nitrite and the mixture is diluted with 5 ml of water. The resulting suspension is cooled to 0°-5°, treated dropwise over the course of 7 minutes with 8.8 ml of 2N hydrochloric acid and then kept for a further 30 minutes at 0°-5°. The aqueous phase is twice washed with methylene chloride; the combined organic solutions are washed with a saturated aqueous sodium chloride solution, dried over sodium sulphate and evaporated under reduced pressure. The oily residue is chromatographed on 40 g of acid-washed silica gel. A small quantity of a by-product is eluted with benzene and, using 1200 ml of a 95:5-mixture of benzene and ethyl acetate, the 4-methoxybenzylglyoxal is obtained in the form of the hydrate, which is an oily product; infra-red absorption spectrum (in methylene chloride): characteristic bands at 2.96μ, 5.79-5.84μ, 6.23μ and 6.63μ. The anhydrous product melts at 139°-140° after recrystallisation from a mixture of chloroform and hexane; ultra-violet absorption spectrum:λmax 333 mμ (in ethanol or hydrochloric acid/ethanol) and λmax 367 mμ (in potassium hydroxide/ethanol); ethanol); infra-red absorption spectrum (in methylene chloride): characteristic bands at 3.00μ, 5.97μ, 6.09μ, 6.24μ, 6.61μ and 7.15μ.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:10]([F:13])([F:12])[F:11])[CH:5]=[C:6]([Cl:9])[C:7]=1F.[F:14][C:15]1[CH:23]=[C:22]2[C:18]([CH:19]=[CH:20][NH:21]2)=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:10]([F:13])([F:12])[F:11])[CH:5]=[C:6]([Cl:9])[C:7]=1[N:21]1[C:22]2[C:18](=[CH:17][CH:16]=[C:15]([F:14])[CH:23]=2)[CH:19]=[CH:20]1
Reactant: Fc1c(Cl)cc(C(F)(F)F)cc1Cl
Reactant: Fc1ccc2cc[nH]c2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Fc1ccc2ccn(-c3c(Cl)cc(C(F)(F)F)cc3Cl)c2c1
Temperature: 90 °C
Reaction time: 16 h

Procedure:
To a solution of 3,5-dichloro-4-fluorobenzotrifluoride (34.5 g) in dimethylformamide (250 ml) was added 6-fluoroindole (34.5 g) and potassium carbonate (20.4 g). The mixture was heated at 90° C. for 6 hours and then left to stir for 16 hours at room temperature. The reaction was diluted with water (1000 ml) and extracted with hexane (1000 ml). The organic fraction was separated and evaporated to dryness to give the title compound as a colourless liquid.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[N:12]=[N:11][C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)=[N:9]2)=[CH:4][CH:3]=1.[Br-].[N:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[Zn+].Cl.CCOCC>C1COCC1>[N:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[N:12]=[N:11][C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)=[N:9]2)=[CH:4][CH:3]=1
Reactant: Brc1ccc(-n2nnc(-c3ccccn3)n2)cc1
Reactant: [Zn+]c1ccccn1
Agent: Cl
Agent: [Br-]
Solvent: CCOCC
Solvent: C1CCOC1
Product: c1ccc(-c2ccc(-n3nnc(-c4ccccn4)n3)cc2)nc1
Temperature: 60 °C
Reaction time: 4 h

Procedure:
A solution of 2-[2-(4-bromophenyl)-2H-tetrazol-5-yl]pyridine (300 mg, 1 mmol), 2-pyridylzinc bromide (0.5M in THF, 2 mL) and tetrakis-(triphenylphosphine)palladium(0) (100 mg, 0.085 mmol) in anhydrous THF (10 mL) was degassed for 15 min and heated to 60° C. After 4 hours, a further equivalent of 2- pyridylzinc bromide (0.5M in THF, 2 mL) was added and the reaction mixture was heated at reflux overnight. The reaction mixture was then quenched with brine (25 mL), extracted with EtOAc (3×25 mL), dried over Na2SO4 and concentrated in vacuo. The crude residue was chromotographed on silica gel, eluting with EtOAc to afford a yellow solid. This was dissolved in anhydrous THF (10 mL) and HCl in ether (1.5 equiv) was added and the resulting precipitate was filtered to afford a yellow solid.
Reaction SMILES: [CH3:1][N:2]([CH3:13])[C:3]1[NH:4][C:5]2[CH:11]=[C:10]([NH2:12])[CH:9]=[CH:8][C:6]=2[N:7]=1.[C:14]([OH:25])(=O)[C:15]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][CH:16]=1>>[CH3:1][N:2]([CH3:13])[C:3]1[NH:7][C:6]2[CH:8]=[CH:9][C:10]([NH:12][C:19](=[O:21])[C:18]3[CH:17]=[CH:16][C:15]([C:14]([NH:12][C:10]4[CH:9]=[CH:8][C:6]5[NH:7][C:3]([N:2]([CH3:1])[CH3:13])=[N:4][C:5]=5[CH:11]=4)=[O:25])=[CH:23][CH:22]=3)=[CH:11][C:5]=2[N:4]=1
Reactant: CN(C)c1nc2ccc(N)cc2[nH]1
Reactant: O=C(O)c1ccc(C(=O)O)cc1
Product: CN(C)c1nc2cc(NC(=O)c3ccc(C(=O)Nc4ccc5[nH]c(N(C)C)nc5c4)cc3)ccc2[nH]1

Procedure:
Compound 435 was prepared according to the procedure similar to that described in Scheme V from 2-dimethylamino-5-aminobenzimidazole and terephthalic acid. [M+H]+ calcd for C26H26N8O2: 483.22; found: 483.02.
Reaction SMILES: [H-].[Na+].[I-].[CH3:4][S+](C)(C)=O.[F:9][C:10]1[C:18]2[C:14](=[CH:15][N:16]([CH3:19])[N:17]=2)[C:13](/[CH:20]=[CH:21]/[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:12][CH:11]=1.O>CS(C)=O>[F:9][C:10]1[C:18]2[C:14](=[CH:15][N:16]([CH3:19])[N:17]=2)[C:13]([CH:20]2[CH2:4][CH:21]2[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:12][CH:11]=1
Reactant: C[S+](C)(C)=O
Reactant: CCOC(=O)/C=C/c1ccc(F)c2nn(C)cc12
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: CCOC(=O)C1CC1c1ccc(F)c2nn(C)cc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 75.7 %

Procedure:
Under nitrogen atmosphere, to a suspension of sodium hydride (290 mg, 7.25 mmol) in dimethyl sulfoxide (45 mL) was added trimethylsulfoxonium iodide (1.73 g, 7.86 mmol) at 0° C., and the mixture was stirred at room temperature for 1 hr. To the reaction mixture was added a solution of ethyl (2E)-3-(7-fluoro-2-methyl-2H-indazol-4-yl)acrylate (1.50 g, 6.04 mmol) in dimethyl sulfoxide (15 mL) at 0° C., and the mixture was stirred at 70° C. for 27 hr. Water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=15/85-+50/50) to give the title compound (1.20 g, yield 76%).
Reaction SMILES: [C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:53]/[O:54][CH2:55][C:56]([O:58][CH:59]([C:66]2[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=2)[C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)=[O:57])/[C:27]([NH:29][CH:30]2[C:51](=[O:52])[N:32]3[C:33]([C:39]([O:41][CH2:42][C:43]4[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][CH:44]=4)=[O:40])=[C:34]([CH2:37]Cl)[CH2:35][S:36][C@H:31]23)=[O:28])[N:25]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([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.[SH:72][C:73]1[S:74][C:75]2[CH:76]=[N:77][CH:78]=[CH:79][C:80]=2[N:81]=1.SC1SC2C=CN=CC=2N=1>>[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:53]/[O:54][CH2:55][C:56]([O:58][CH:59]([C:66]2[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=2)[C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)=[O:57])/[C:27]([NH:29][CH:30]2[C:51](=[O:52])[N:32]3[C:33]([C:39]([O:41][CH2:42][C:43]4[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][CH:44]=4)=[O:40])=[C:34]([CH2:37][S:72][C:73]4[S:74][C:75]5[CH:76]=[N:77][CH:78]=[CH:79][C:80]=5[N:81]=4)[CH2:35][S:36][C@H:31]23)=[O:28])[N:25]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([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: Sc1nc2ccncc2s1
Reactant: COc1ccc(COC(=O)C2=C(CCl)CS[C@@H]3C(NC(=O)/C(=N\OCC(=O)OC(c4ccccc4)c4ccccc4)c4csc(NC(c5ccccc5)(c5ccccc5)c5ccccc5)n4)C(=O)N23)cc1
Agent: Sc1nc2cnccc2s1
Product: COc1ccc(COC(=O)C2=C(CSc3nc4ccncc4s3)CS[C@@H]3C(NC(=O)/C(=N\OCC(=O)OC(c4ccccc4)c4ccccc4)c4csc(NC(c5ccccc5)(c5ccccc5)c5ccccc5)n4)C(=O)N23)cc1
Yield: 75.2 %

Procedure:
Using 301 mg of p-methoxybenzyl 7-{(Z)-2-(2-tritylaminothiazol-4-yl)-2-diphenylmethoxycarbonylmethoxyiminoacetamido}-3-chloromethyl-3-cephem-4-carboxylate and 60 mg of 2-mercaptothiazolo[5,4-c]pyridine in place of p-methoxybenzyl 7-{(Z)-2-(2-tritylaminothiazol-4-yl)-2-methoxyiminoacetamido}-3-chloromethyl-3-cephem-4-carboxylate and 2-mercaptothiazolo[4,5-c]pyridine, respectively, the reaction and purification were carried out in the same manner as in Example 1(a) to obtain 256 mg of the title compound in a yield of 75%.
Reaction SMILES: [C:1]([CH2:3][C@H:4]1[O:9][C:8]([CH3:11])([CH3:10])[O:7][C@@H:6]([CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:5]1)#[N:2].N.[H][H]>CO.O>[NH2:2][CH2:1][CH2:3][C@H:4]1[O:9][C:8]([CH3:11])([CH3:10])[O:7][C@@H:6]([CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:5]1
Reactant: [H][H]
Reactant: CC(C)(C)OC(=O)C[C@H]1C[C@@H](CC#N)OC(C)(C)O1
Agent: N
Solvent: CO
Solvent: O
Product: CC(C)(C)OC(=O)C[C@H]1C[C@@H](CCN)OC(C)(C)O1
Reaction time: 16 h

Procedure:
A solution of (4R-cis)-1,1-dimethylethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate, 5.63 g (0.048 mol), in 100 mL of methanol saturated with gaseous ammonia is treated with 0.5 g of Raney nickel #30 and hydrogen gas in a shaker at 50 psi and 40° C. After 16 hours, thin layer chromatography indicates no starting nitrile present. The suspension is cooled, filtered through filter aid, and concentrated to an oil. This crude oil is purified by flash chromatography on silica gel with 30:20:1 (ethyl acetate:methanol:ammonium hydroxide) as eluent to give 4.93 g of (4R-cis)-1,1-dimethylethyl 6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxane-4-acetate (98.2 area %) as a clear oil with acceptable IR, NMR, C-NMR and MS spectra.
Reaction SMILES: [CH2:1]([NH:8][CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.CS(O[CH2:31][C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][C:39]=1[O:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[CH:35]=[O:36])(=O)=O>CN(C)C=O>[C:42]1([CH2:41][O:40][C:39]2[CH:38]=[CH:37][C:34]([CH:35]=[O:36])=[CH:33][C:32]=2[CH2:31][N:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1
Reactant: CS(=O)(=O)OCc1cc(C=O)ccc1OCc1ccccc1
Reactant: c1ccc(CCNCc2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=Cc1ccc(OCc2ccccc2)c(CN(CCc2ccccc2)Cc2ccccc2)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 87 %

Procedure:
To a solution of N-benzyl-N-(2-phenylethyl)amine (351 mg) and diisopropyl-ethylamine (145 mg) in dimethylformamide (1.5 ml) was added 3-[[(methylsulfonyl)oxy]methyl]-4-phenylmethoxybenzaldehyde (355 mg). After stirring at room temperature for 3 hours, the reaction mixture was partially concentrated under reduced pressure and the residue was purified by flash chromatography column using petroleum ether:diethyl ether (1:3) as eluant. The pure fractions were combined and evaporated under reduced pressure to give 4-phenylmethoxy-3-[[N-phenylmethyl-N-(2-phenylethyl)amino]methyl]benzaldehyde (420 mg) as a gum. 1H NMR (CDCl3) δ9.89 (s, 1H, CHO); 5.20 (s, 2H); 3.88 (s, 2H); 3.85 (s, 2H); 2.92 (m, 4H, CH2CH2).
Reaction SMILES: Cl[CH2:2][C:3]1[C:4]([CH3:15])=[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:7][CH:8]=1.[I-].[CH3:17][N+:18](C)(C)[CH2:19]C1C(C2C=CC=CC=2)=CC=CC=1>>[CH3:17][N:18]([CH2:2][C:3]1[C:4]([CH3:15])=[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:7][CH:8]=1)[CH3:19]
Reactant: C[N+](C)(C)Cc1ccccc1-c1ccccc1
Reactant: Cc1c(CCl)cccc1-c1ccccc1
Agent: [I-]
Product: Cc1c(CN(C)C)cccc1-c1ccccc1

Procedure:
An additional method for preparing the intermediate 3-chloromethyl-2-methyl[1,1'-biphenyl] involves a Sommelet-Hauser rearrangement of N,N,N-trimethyl[1,1'-biphenyl]-2-methanaminium iodide to give 3-dimethylaminomethyl-2-methyl-[1,1'-biphenyl], which is then converted into the 3-chloromethyl derivative by treatment with ethyl chloroformate. The N,N,N-trimethyl-[1,1'-biphenyl]-2-methanaminium iodide starting material may be prepared in four steps from 2-biphenylcarboxylic acid via the acid chloride, dimethyl carboxamide, and dimethylaminomethyl derivatives.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8](=[O:12])[CH2:7][CH2:6][CH2:5][C:4]=2[N:3]=1.[Br:13]Br.C(=O)([O-])[O-].[K+].[K+]>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[C:8](=[O:12])[CH:7]([Br:13])[CH2:6][CH2:5][C:4]=2[N:3]=1
Reactant: O=C1CCCc2nc(Cl)ccc21
Reactant: BrBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Product: O=C1c2ccc(Cl)nc2CCC1Br
Reaction time: 1 h

Procedure:
3-Aminocyclohex-2-enone (ex Aldrich) was reacted with methyl propiolate (ex Lancaster) to give 7,8-dihydro-2,5-quinoline-dione according to Speckamp et al J. Trav. Chem. Pays. bas., 91 157 (1972). The latter was converted to 2-chloro-7,8-dihydro-5-quinolinone by analogy with Example VI. The latter compound (2 g) was dissolved in chloroform (200 ml) and treated with bromine (0.53 ml) dropwise at room temperature. After 30 min solid potassium carbonate was added, the mixture was stirred for 1 hour, filtered and solvent removed to give 2-chloro-6-bromo-7,8-dihydro-5-quinolinone (2.86 g). This compound was heated at 110° C. with anhydrous lithium chloride (1.4 g) and dimethylformamide (45 ml) for 3 hours. The mixture was diluted with water, worked-up in conventional fashion and purified by column chromatography on silica (eluting with ether-hexane) to give 2-chloro-5-hydroxyquinoline (0.77 g).
Reaction SMILES: [OH:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:16]=[C:15]([C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:18]=3[C:28]([F:31])([F:30])[F:29])[O:14][N:13]=2)=[CH:8][CH:7]=1)[C:3](O)=[O:4].[NH2:32][CH2:33][CH2:34][NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39].CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[OH:1][CH:2]([C:6]1[CH:7]=[CH:8][C:9]([C:12]2[N:16]=[C:15]([C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[C:18]=3[C:28]([F:31])([F:29])[F:30])[O:14][N:13]=2)=[CH:10][CH:11]=1)[C:3]([NH:32][CH2:33][CH2:34][NH:35][C:36](=[O:42])[O:37][C:38]([CH3:40])([CH3:39])[CH3:41])=[O:4]
Reactant: CC(C)(C)OC(=O)NCCN
Reactant: O=C(O)C(O)c1ccc(-c2noc(-c3onc(-c4ccccc4)c3C(F)(F)F)n2)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: CC(C)(C)OC(=O)NCCNC(=O)C(O)c1ccc(-c2noc(-c3onc(-c4ccccc4)c3C(F)(F)F)n2)cc1
Reaction time: 1 h
Yield: 33.8 %

Procedure:
(R/S)-2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-V, 170 mg, 0.394 mmol), tert-butyl 2-aminoethylcarbamate (95 mg, 0.591 mmol), 4-methylmorpholine (159 mg, 1.577 mmol), and HATU (195 mg, 0.512 mmol) were dissolved in DMF (1 mL). The reaction mixture was stirred for 1 h and then was purified by prep HPLC (PHENOMENEX® Luna 5u 21×250 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 30 min, 25 mL/min, 220 nM, product retention=31.6 min) to provide (R/S)-tert-butyl 2-(2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamido)ethylcarbamate (80 mg, 0.133 mmol, 33.6% yield): LCMS=474.1 [M+H−C5H9O2]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.17 (2 H, d, J=8.35 Hz), 7.51-7.74 (7 H, m), 5.12 (1 H, s), 3.35 (2 H, br. s.), 3.17-3.22 (2 H, m), 1.43 (9 H, s); HPLC peak RT=9.8 min (Method A).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[C:13](I)[CH:12]=[CH:11][C:10]=1[N:16]1[S:20](=[O:22])(=[O:21])[N:19]([CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:18](=[O:29])[CH2:17]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:30]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])(=[O:33])[CH:31]=[CH2:32].C(N(CC)CC)C>C(#N)C>[C:35]([O:34][C:30](=[O:33])/[CH:31]=[CH:32]/[C:13]1[CH:12]=[CH:11][C:10]([N:16]2[CH2:17][C:18](=[O:29])[N:19]([CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[S:20]2(=[O:22])=[O:21])=[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:14]=1)([CH3:38])([CH3:37])[CH3:36]
Reactant: C[Si](C)(C)CCN1C(=O)CN(c2ccc(I)cc2OCc2ccccc2)S1(=O)=O
Reactant: C=CC(=O)OC(C)(C)C
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)/C=C/c1ccc(N2CC(=O)N(CC[Si](C)(C)C)S2(=O)=O)c(OCc2ccccc2)c1
Temperature: 100 °C

Procedure:
To a solution of 5-(2-benzyloxy-4-iodo-phenyl)-1,1-dioxo-2-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-3-one (544 mg, 1 mmol), t-butyl acrylate (154 mg, 1.2 mmol) and triethylamine (1.01 g, 10 mmol) in 5 mL of acetonitrile is added Pd (OAc)2 (10 mg). The mixture is heated at 100° C. for 18 h. After allowing to cool to RT the solvent is removed under reduced pressure and the residual oil purified by flash chromatography using methylene chloride to elute the title compound as an oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[O:9][N:10]=[C:11]3[CH:16]=[CH:15][C:14]([C:17]([C:25]4[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=4)([C:19]4[N:23]([CH3:24])[CH:22]=[N:21][CH:20]=4)[OH:18])=[CH:13][C:12]=23)[CH:5]=[CH:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+]>O.C1COCC1>[NH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([C:25]2[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=2)([OH:18])[C:19]2[N:23]([CH3:24])[CH:22]=[N:21][CH:20]=2)=[CH:13][C:12]=1[C:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=1)=[O:9]
Reactant: Cn1cncc1C(O)(c1ccc(Cl)cc1)c1ccc2noc(-c3cccc(Cl)c3)c2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: Cn1cncc1C(O)(c1ccc(Cl)cc1)c1ccc(N)c(C(=O)c2cccc(Cl)c2)c1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 49 %

Procedure:
TiCl3/15% in H2O (200 ml) was added at room temperature to a solution of intermediate (6-c) (38 g) in THF (300 ml). The mixture was stirred at room temperature for 90 minutes. The mixture was poured out on ice, basified with K2CO3, filtered over celite, washed with ethyl acetate and decanted. The organic layer was dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 97/3/0.1 and 95/5/0.1), yielding 18.7 g (49%) of (±)-[2-amino-5-[(4-chlorophenyl)hydroxy(1-methyl-1H-imidazol-5-yl)methyl]phenyl](3-chlorophenyl)methanone (intern. 6-d).
Reaction SMILES: [CH3:1][S:2][C:3]1[NH:4][CH:5]=[C:6]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:7]=1[N+:8]([O-:10])=[O:9].[OH:17]O>C(O)(=O)C>[CH3:1][S:2]([C:3]1[NH:4][CH:5]=[C:6]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:7]=1[N+:8]([O-:10])=[O:9])=[O:17]
Reactant: OO
Reactant: CSc1[nH]cc(-c2ccccc2)c1[N+](=O)[O-]
Solvent: CC(=O)O
Product: CS(=O)c1[nH]cc(-c2ccccc2)c1[N+](=O)[O-]
Reaction time: 5 h
Yield: 77.5 %

Procedure:
2-Methylthio-3-nitro-4-phenylpyrrole (3.00 g, 0.013 mol) was suspended in glacial acetic acid (200 ml), and 30% hydrogen peroxide (1,45 g, 0.013 mol) was added. The mixture was stirred at 80° for five hours, after which the mixture was evaporated to dryness and the solid residue was recrystallised from isopropanol to give 2-methylsulphinyl-3-nitro-4-phenyl pyrrole (2.52 g), m.p. 197° dec.
Reaction SMILES: [CH3:1][Si:2]([CH3:22])([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])Cl.[OH:23][Ge:24][OH:25].[CH:26]1[CH:27]=[CH:28][C:29]2[C:30](=[C:32]3[N:64]=[C:63]4[N:65]=[C:56]([C:57]5[CH:58]=[CH:59][CH:60]=[CH:61][C:62]=54)[N:55]=[C:53]4[NH:54][C:46]([C:47]5[CH:48]=[CH:49][CH:50]=[CH:51][C:52]=54)=[N:45][C:43]4=[N:44][C:36]([C:37]5[CH:38]=[CH:39][CH:40]=[CH:41][C:42]=54)=[N:35][C:34]=2[NH:33]3)[CH:31]=1>N1C=CC=CC=1>[CH3:1][Si:2]([CH3:22])([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[O:23][Ge:24][O:25][Si:2]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:63][CH2:62][CH2:61][CH2:60][CH2:59][CH2:58][CH2:57][CH3:56])([CH3:1])[CH3:22].[CH:27]1[CH:26]=[CH:31][C:30]2[C:29](=[C:34]3[N:35]=[C:36]4[N:44]=[C:43]([C:42]5[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=54)[N:45]=[C:46]4[NH:54][C:53]([C:52]5[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=54)=[N:55][C:56]4=[N:65][C:63]([C:62]5[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=54)=[N:64][C:32]=2[NH:33]3)[CH:28]=1
Reactant: O[Ge]O
Reactant: CCCCCCCCCCCCCCCCCC[Si](C)(C)Cl
Agent: c1ccc2c(c1)-c1nc-2nc2[nH]c(nc3nc(nc4[nH]c(n1)c1ccccc41)-c1ccccc1-3)c1ccccc21
Solvent: c1ccncc1
Product: CCCCCCCCCCCCCCCCCC[Si](C)(C)O[Ge]O[Si](C)(C)CCCCCCCCCCCCCCCCCC

Procedure:
[In analogy to a procedure by Wheeler et. al., J. Am. Chem. Soc. 106, 7404 (1984)] 3.3 g (9.5 mmol) of dimethyl-octadecyl-chlorosilane and 0.5 g (0.8 mmol) of dihydroxygermanium-phthalocyanine in 50 ml of pyridine are stirred for 2 hours at 50°. The solution is cooled and filtered using a suction filter. The solvent is removed in vacuo, and 250 ml of hexane are added to the residue. The resulting precipitate is filtered off with suction and washed first with hexane, then in portions with 200 ml of acetone/water (1:1). The residue is dried overnight under a high vacuum, then extracted with toluene in a Soxhlet, freed of solvent and dried, yielding bis(dimethyl-octadecyl-siloxy)germanium-phthalocyanine; NMR (pyridine-d5): δ=9.8-9.9 (m, 8H); 8.3-8.5 (m,8H): aromatic H's; 0.75-1.46 (various m's); 0.45(m); -0.03 (m); -0.88 (m); -1.91 (m); -2.48 (m, 4×CH3 : silyl side chains) ppm.
Reaction SMILES: [CH:1]1[C:2]2[C:17](=[O:18])[C:16]([C:19]([OH:21])=[O:20])=[CH:15][N:14]([CH:22]3[CH2:24][CH2:23]3)[C:3]=2[CH:4]=[C:5]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[C:6]=1[F:7].C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.[P:37](Cl)([O:42][CH2:43][CH3:44])([O:39][CH2:40][CH3:41])=[O:38]>C(Cl)Cl>[CH:22]1([N:14]2[C:3]3[C:2](=[CH:1][C:6]([F:7])=[C:5]([N:8]4[CH2:9][CH2:10][N:11]([P:37]([O:42][CH2:43][CH3:44])([O:39][CH2:40][CH3:41])=[O:38])[CH2:12][CH2:13]4)[CH:4]=3)[C:17](=[O:18])[C:16]([C:19]([OH:21])=[O:20])=[CH:15]2)[CH2:23][CH2:24]1
Reactant: O=C(O)c1cn(C2CC2)c2cc(N3CCNCC3)c(F)cc2c1=O
Reactant: CCOP(=O)(Cl)OCC
Agent: C/C(=N\[Si](C)(C)C)O[Si](C)(C)C
Solvent: ClCCl
Product: CCOP(=O)(OCC)N1CCN(c2cc3c(cc2F)c(=O)c(C(=O)O)cn3C2CC2)CC1
Reaction time: 0.17 h

Procedure:
A suspension of 2.816 g (8.5 mmol) of ciprofloxacin base in 100 ml of dry CH2Cl2 was stirred under argon as 3.46 g (17 mmol) of N,O-bis(trimethylsilyl)acetamide was added. After the solid had dissolved (2-3 hours), 1.47 g (8.5 mmol) of diethyl chlorophosphate was added. After 24 hours at approximately 23° the solution was evaporated, finally at 0.03 mm for 15 hours. Washing of the solid residue with water gave a white solid which was dried and then recrystallized from CH2Cl2 -toluene, boiling out the CH2Cl2 within 10 minutes to avoid thermal degradation. The product was 3.74 g (94%) of cream-colored solid, m.p. 192°-193° C.; NMR (CDCl3, 80 MHz) δ 1.36 (t, CH3), 3.30 (s, CH2N), 4.06 (5 peaks, OCH2); IR (KBr) 1028(P=O), 1630 (--COOH), 1724 cm-1 (C=O).