Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:16]=[C:17]([CH:29]=[CH:30][CH:31]=1)[CH2:18][S:19][C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][CH:28]=1)[C:23]([OH:25])=[O:24].S(=O)(=O)(O)O.[CH3:37]O>>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:16]=[C:17]([CH:29]=[CH:30][CH:31]=1)[CH2:18][S:19][C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][CH:28]=1)[C:23]([O:25][CH3:37])=[O:24]
Reactant: Cc1oc(-c2ccccc2)nc1COc1cccc(CSc2cccc(C(=O)O)c2)c1
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)c1cccc(SCc2cccc(OCc3nc(-c4ccccc4)oc3C)c2)c1
Yield: 67 %

Procedure:
A mixture of 3-[3-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]benzylthio]benzoic acid (3.20 g), conc. sulfuric acid (1 mL) and methanol (50 mL) was stirred with heating under reflux for 1 hr. The reaction mixture was concentrated, water was added to the residue and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to give methyl 3-[3-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]benzylthio]benzoate as an oil (2.20 g, yield 67%) from a fraction eluted with ethyl acetate-hexane (1:4, v/v).
Reaction SMILES: N1([C:6]([N:8]2[CH:12]=[CH:11][N:10]=[CH:9]2)=[O:7])C=CN=C1.[O:13]1[CH2:17][CH2:16][CH2:15][CH:14]1[CH2:18][CH2:19]C(O)=O>ClCCl>[N:8]1([C:6](=[O:7])[CH2:19][CH2:18][CH:14]2[CH2:15][CH2:16][CH2:17][O:13]2)[CH:12]=[CH:11][N:10]=[CH:9]1
Reactant: O=C(O)CCC1CCCO1
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: ClCCl
Product: O=C(CCC1CCCO1)n1ccnc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 100.1 %

Procedure:
Di-(1H-imidazol-1-yl)methanone (0.554 g, 3.42 mmol) was added in small portions to a stirred solution of 3-(tetrahydrofuran-2-yl)propanoic acid (0.469 g, 3.25 mmol) in dichloromethane (3 mL) at room temperature under argon. The reaction mixture is stirred at room temperature for 2 hours. The mixture was washed twice with water, dried over MgSO4 and concentrated resulting a quantitative yield of 1-(1H-imidazol-1-yl)-3-(tetrahydrofuran-2-yl)propan-1-one (632 mg, 100%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[NH:9][C:10]([CH3:16])=[C:11]([C:13]([OH:15])=O)[N:12]=1.CN(C(ON1[N:33]=[N:32][C:27]2C=[CH:29][CH:30]=[CH:31][C:26]1=2)=[N+](C)C)C.[B-](F)(F)(F)F.NN1CCCCC1.O>CN(C=O)C>[N:32]1([NH:33][C:13]([C:11]2[N:12]=[C:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])[NH:9][C:10]=2[CH3:16])=[O:15])[CH2:29][CH2:30][CH2:31][CH2:26][CH2:27]1
Reactant: Cc1[nH]c(-c2ccccc2Cl)nc1C(=O)O
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Agent: NN1CCCCC1
Solvent: CN(C)C=O
Solvent: O
Product: Cc1[nH]c(-c2ccccc2Cl)nc1C(=O)NN1CCCCC1
Reaction time: 0.02 h
Yield: 83.1 %

Procedure:
To 1 g of 2-(2-chloro-phenyl)-5-methyl-1H-imidazole-4-carboxylic acid in 10 ml of DMF was added 1.36 g of TBTU and 3.6 ml of Hünigs' base and the reaction mixture was stirred for 1 minute. Then 0.46 ml of 1-aminopiperidin was added and the reaction mixture was stirred for 1.5 hour at room temperature. After such time the reaction mixture was poured onto 200 ml of water and extracted with ethyl acetate (2×200 ml). The combined organic extracts were then washed with water (2×100 ml) and brine (50 ml), dried (MgSO4) and concentrated in vacuo to yield an oil which crystallized on standing. The residue was then triturated with heptane, the solid was filtered and dried to yield 1.12 g of the title compound, MS (ISP) 319.0 (M+H)+.
Reaction SMILES: [OH:1][CH:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[C:10]([CH:11]=[O:12])[C:5]=2[C:4](=[O:13])[O:3]1.[C:14](=O)([O-])[O-].[K+].[K+].IC>CN(C)C=O>[CH:2]([C:6]1[CH:7]=[CH:8][CH:9]=[C:10]([CH:11]=[O:12])[C:5]=1[C:4]([O:3][CH3:14])=[O:13])=[O:1]
Reactant: O=C([O-])[O-]
Reactant: O=Cc1cccc2c1C(=O)OC2O
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: COC(=O)c1c(C=O)cccc1C=O
Reaction time: 0.5 h
Yield: 83 %

Procedure:
To a solution of 1-hydroxy-3-oxo-1,3-dihydro-2-benzofuran-4-carbaldehyde (720 mg) in anhydrous dimethylformamide (4 ml) was added potassium carbonate (613 mg). It was stirred for 30 minutes to give a thick white suspension. Iodomethane (0.4 ml) was added and stirred for 3 days. More methyl iodide (0.4 ml) was added and stirring continued for 24 hours. Most of the dimethylformamide was evaporated in vacuo. The pale yellow residue was partitioned between ethyl acetate (25 ml) and water (25 ml) and the organic phase was washed with aqueous lithium chloride (50 ml) and saturated brine (25 ml), dried over sodium sulphate and evaporated to give a pale yellow solid (645 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[C:17]([I:19])[CH:16]=[C:15]([Cl:20])[C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([Cl:13])[C:8]=1[F:14])=O.S(Cl)([Cl:23])=O>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:18]=[C:17]([I:19])[CH:16]=[C:15]([Cl:20])[C:3]=1[C:4]([Cl:23])=[N:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([Cl:13])[C:8]=1[F:14]
Reactant: O=C(Nc1ccnc(Cl)c1F)c1c(Cl)cc(I)cc1Cl
Reactant: O=S(Cl)Cl
Solvent: Cc1ccccc1
Product: Fc1c(N=C(Cl)c2c(Cl)cc(I)cc2Cl)ccnc1Cl
Yield: 99 %

Procedure:
A solution of 2,6-dichloro-N-(2-chloro-3-fluoro-pyridin-4-yl)-4-iodobenzamide (2.83 g, 6.4 mmol) in thionyl chloride (23 mL) was heated to 90° C. for 56 hours then diluted with toluene and concentrated under reduced pressure to give the desired compound (2.94 g, 99% yield). 1H NMR (300 MHz, CDCl3): δ 8.22 (d, J=5.1 Hz, 1H), 7.84-7.76 (m, 2H), 6.95 (t, J=5.1 Hz, 1H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C:11]1[CH2:12][CH2:13][N:14]([CH3:17])[CH2:15][CH:16]=1>CO.[Pd].CCCCCC>[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:11]1[CH2:12][CH2:13][N:14]([CH3:17])[CH2:15][CH2:16]1
Reactant: CN1CC=C(c2c[nH]c3ccc(N)cc23)CC1
Agent: [Pd]
Solvent: CO
Solvent: CCCCCC
Product: CN1CCC(c2c[nH]c3ccc(N)cc23)CC1
Reaction time: 18 h

Procedure:
To a solution of 11.3 gm (50 mMol) 5-amino-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole in 250 mL methanol were added 3.0 gm 5% palladium on carbon. The mixture was hydrogenated at room temperature under an initial hydrogen pressure of 60 p.s.i. for 18 hours. The reaction mixture was filtered and the filtrate concentrated under reduced pressure to give a dark gum which was slurried in hexane to give the title compound as a brown solid.
Reaction SMILES: [CH3:1][Si:2]1([CH3:12])[O:7][Si:6]([CH3:9])([CH3:8])[O:5][Si:4]([CH3:11])([CH3:10])[O:3]1.[C:13]([O:18][Si:19](C)([CH3:21])[CH3:20])(=[O:17])[C:14]([CH3:16])=[CH2:15].[CH3:23]OC1C=CC(O)=CC=1.C(N(CC)CC)C>C1(C)C=CC=CC=1.[Cl-].[Zn+2].[Cl-]>[CH3:23][Si:2]([CH3:12])([CH3:1])[O:3][Si:4]([CH3:11])([CH3:10])[O:5][Si:6]([CH3:9])([CH3:8])[O:7][Si:19]([CH3:21])([CH3:20])[O:18][C:13](=[O:17])[C:14]([CH3:16])=[CH2:15]
Reactant: COc1ccc(O)cc1
Reactant: C[Si]1(C)O[Si](C)(C)O[Si](C)(C)O1
Reactant: C=C(C)C(=O)O[Si](C)(C)C
Agent: [Cl-]
Agent: [Zn+2]
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: C=C(C)C(=O)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C
Temperature: 25 °C
Reaction time: 11 h

Procedure:
50 g of hexamethylcyclotrisiloxane, 35.6 g of trimethylsilyl methacrylate, 2.5 g of zinc chloride and 0.4 g of 4-methoxy phenol were dissolved in 50 ml of toluene. After 11 h at 100° C., the mixture was allowed to cool until room temperature, 40 ml of triethylamine were then added and the salts were filtered. After evaporation of the solvent, distillation under reduced pressure (0.3 mbar, 80° C.) furnished pure nonamethyl-1-methacryloyloxy-tetrasiloxane.
Reaction SMILES: [CH2:1]([S:3][C:4]1[N:9]=[C:8]([NH:10][NH2:11])[CH:7]=[C:6]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:5]=1)[CH3:2].[C:18](OCC)(OCC)(OCC)[CH3:19]>>[CH2:1]([S:3][C:4]1[N:9]2[C:18]([CH3:19])=[N:11][N:10]=[C:8]2[CH:7]=[C:6]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:5]=1)[CH3:2]
Reactant: CCOC(C)(OCC)OCC
Reactant: CCSc1nc(NN)cc(-c2ccccc2)n1
Product: CCSc1nc(-c2ccccc2)cc2nnc(C)n12

Procedure:
Using the method of Example 19, 2-ethylthio-4-hydrazino-6-phenylpyrimidine was reacted with triethyl orthoacetate to provide 5-ethylthio-3-methyl-7-phenyl-1,2,4-triazolo[4,3-c]pyrimidine which was recrystallized from a 50/50 mixture of ethyl acetate/cyclohexanes to provide white crystals of 5-ethylthio-3-methyl-7-phenyl-1,2,4-triazolo[4,3-c]pyrimidine, m.p. 219.5°-220° C. Analysis: Calculated for C14H14N4S: %C, 62.2; %H, 5.2; %N, 20.7; Found: %C, 62.2; %H, 5.1; %N, 21.1.
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:5]=1[C:14]1[C:23]2[C:18](=[CH:19][C:20]([S:24]([N:27]([CH2:33][C:34]3[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][C:35]=3[O:42][CH3:43])[C:28]3[S:29][CH:30]=[CH:31][N:32]=3)(=[O:26])=[O:25])=[CH:21][CH:22]=2)[CH:17]=[CH:16][N:15]=1)[CH:2]=[CH2:3].C[N+]1([O-])CC[O:48]CC1.CC(O)(C)C.[OH2:57]>[Os](=O)(=O)(=O)=O>[OH:57][CH:2]([CH2:3][OH:48])[CH2:1][C:4]1[CH:9]=[C:8]([C:10]([F:11])([F:12])[F:13])[CH:7]=[CH:6][C:5]=1[C:14]1[C:23]2[C:18](=[CH:19][C:20]([S:24]([N:27]([CH2:33][C:34]3[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][C:35]=3[O:42][CH3:43])[C:28]3[S:29][CH:30]=[CH:31][N:32]=3)(=[O:25])=[O:26])=[CH:21][CH:22]=2)[CH:17]=[CH:16][N:15]=1
Reactant: C=CCc1cc(C(F)(F)F)ccc1-c1nccc2cc(S(=O)(=O)N(Cc3ccc(OC)cc3OC)c3nccs3)ccc12
Reactant: C[N+]1([O-])CCOCC1
Reactant: O
Agent: O=[Os](=O)(=O)=O
Solvent: CC(C)(C)O
Product: COc1ccc(CN(c2nccs2)S(=O)(=O)c2ccc3c(-c4ccc(C(F)(F)F)cc4CC(O)CO)nccc3c2)c(OC)c1
Reaction time: 2 h

Procedure:
A vial was charged with 1-(2-allyl-4-(trifluoromethyl)phenyl)-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (0.114 g, 0.182 mmol), NMO (0.043 g, 0.364 mmol), t-BuOH (0.607 ml), and water (0.304 ml). Osmium tetroxide (4% aq. soln.) (0.111 ml, 0.018 mmol) was added drop wise and the reaction was stirred for two hours. The reaction was quenched with saturated sodium thiosulfate solution and diluted with ethyl acetate. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via silica gel chromatography (12 g silica gel column, gradient elution 0 to 10% MeOH:DCM) to afford 1-(2-(2,3-dihydroxypropyl)-4-(trifluoromethyl)phenyl)-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide as a clear oil. m/z (ESI) 660.3 (M+H)+.
Reaction SMILES: Br[C:2]1[C:10]2[C:6](=[N:7][N:8]([C:11]3[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=3)[N:9]=2)[C:5](Br)=[CH:4][CH:3]=1.[S:18]1[C:22]([Sn](CCCC)(CCCC)CCCC)=[CH:21][CH:20]=[C:19]1[C:36]1[S:37][CH:38]=[CH:39][CH:40]=1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C)C=O>[S:37]1[C:38]([C:2]2[C:10]3[C:6](=[N:7][N:8]([C:11]4[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=4)[N:9]=3)[C:5]([C:22]3[S:18][C:19]([C:36]4[S:37][CH:38]=[CH:39][CH:40]=4)=[CH:20][CH:21]=3)=[CH:4][CH:3]=2)=[CH:39][CH:40]=[C:36]1[C:19]1[S:18][CH:22]=[CH:21][CH:20]=1
Reactant: Brc1ccc(Br)c2nn(-c3ccncc3)nc12
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccc(-c2cccs2)s1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Product: c1csc(-c2ccc(-c3ccc(-c4ccc(-c5cccs5)s4)c4nn(-c5ccncc5)nc34)s2)c1
Temperature: 90 °C
Reaction time: 2 h

Procedure:
A mixture of Intermediate A (704 mg, 2.0 mmol), 50% [2,2′-bithiophen]-5-yltributylstannane (2.50 g, 5.5 mmol), bis(triphenylphosphine)palladium(II) dichloride (200 mg, 0.28 mmol), and anhydrous dimethylformamide (20 mL) was stirred under argon and heated at 90° C. for 1 hour. TLC indicated no starting material left. Heating at 90° C. was continued for an additional 2 hours. The volatiles were removed under reduced pressure, and the crude product was purified by column chromatography using silica gel and dichloromethane/ethyl acetate (9:1) as an eluent. The obtained product was washed with ethyl acetate (50 mL) and dried in a vacuum oven to give 4,7-di([2,2′-bithiophen]-5-yl)-2-(pyridin-4-yl)-2H-benzo[d][1,2,3]triazole (Example 9) as red crystals, 150 mg (14%). 1H NMR (400 MHz, CDCl3): δ 8.88 (m, 2H, pyridine), 8.40 (m, 2H, pyridine), 8.09 (d, J=4.0 Hz, 2H, thiophene), 7.65 (s, 2H, benzotriazole), 7.31 (dd, J=3.7 and 1.1 Hz, 2H, thiophene), 7.29 (m, 2H, thiophene), 7.27 (m, 2H, thiophene), 7.08 (dd, J=5.2 and 3.7 Hz, 2H, thiophene). UV-vis spectrum (dichloromethane): λmax=478 nm. Fluorimetry (dichloromethane): λmax=584 nm.
Reaction SMILES: [Br:1][C:2]1[C:3]2[CH:12]=[CH:11][CH:10]=[CH:9][C:4]=2[O:5][C:6]=1C=O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH:24]([O:31][CH2:32][CH3:33])([O:28][CH2:29][CH3:30])OCC>C(=O)([O-])[O-].[Na+].[Na+]>[Br:1][C:2]1[C:3]2[CH:12]=[CH:11][CH:10]=[CH:9][C:4]=2[O:5][C:6]=1[CH:24]([O:28][CH2:29][CH3:30])[O:31][CH2:32][CH3:33]
Reactant: O=Cc1oc2ccccc2c1Br
Reactant: CCOC(OCC)OCC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: CCOC(OCC)c1oc2ccccc2c1Br
Reaction time: 8 h

Procedure:
To a solution of 2.6 g of 3-bromo-2-benzo[b]furancarboxaldehyde (see M. Cugnon de Sevricourt and M. Robba, Bull. Chim. Soc. Fr., 1977, 142) in 2.7 ml of triethyl orthoformate was added 33 mg of para-toluene sulfonic acid and the solution stirred at at roon temperature overnight. The solution was diluted with a 5% sodium carbonate solution and extracted with ether. The ether extracts were dried over sodium sulfate and evaporated to give 3-bromo-2-(diethoxymethyl)-benzo[b]furan as a liquid; 1H-NMR (200 MHz, CDCl3) d 5.76 (CHOEt).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([N:11]2[CH2:16][CH2:15][C@@H:14]([NH2:17])[C@H:13]([OH:18])[CH2:12]2)[C:9]=1[Cl:10])[C:5]#[N:6].C([O-])(=O)C.[K+].[Cl:24][CH2:25][C:26](Cl)=[O:27]>CC(C)=O.O>[NH2:1][C:2]1[C:9]([Cl:10])=[C:8]([N:11]2[CH2:16][CH2:15][C@@H:14]([NH:17][C:26](=[O:27])[CH2:25][Cl:24])[C@H:13]([OH:18])[CH2:12]2)[CH:7]=[C:4]([C:5]#[N:6])[CH:3]=1
Reactant: O=C(Cl)CCl
Reactant: N#Cc1cc(N)c(Cl)c(N2CC[C@@H](N)[C@H](O)C2)c1
Agent: CC(=O)[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Product: N#Cc1cc(N)c(Cl)c(N2CC[C@@H](NC(=O)CCl)[C@H](O)C2)c1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 47.4 %

Procedure:
(+/−)-3-amino-5-((3R,4R)-4-amino-3-hydroxypiperidin-1-yl)-4-chlorobenzonitrile (prepared from Example 171D) (1.0 g, 3.75 mmol) and potassium acetate (0.736 g, 7.50 mmol) were dissolved in acetone (20 ml)+water (6 mL). The solution was cooled to 0° C. under nitrogen. Chloroacetic chloride (0.373 ml, 4.69 mmol) was added dropwise and the mixture stirred at 0° C. for 10 minutes, then at room temperature for 60 minutes. The reaction mixture was partitioned between EtOAc and aq. NaHCO3 solutions. The organic layer was washed with brine and dried over MgSO4. MgSO4 was removed by filtration and volatiles evaporated in vacuum to afford (+/−)-N-((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-hydroxypiperidin-4-yl)-2-chloroacetamide (0.61 g); The material was used without further purification.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][C:13]=1[N+:14]([O-:16])=[O:15])[C:5](N(OC)C)=[O:6].[CH3:17][CH:18](C[AlH]CC(C)C)C>C1COCC1.Cl.CCOC(C)=O>[CH2:17]([C:3]1[C:2]([F:1])=[C:13]([N+:14]([O-:16])=[O:15])[CH:12]=[CH:11][C:4]=1[CH:5]=[O:6])[CH3:18]
Reactant: CON(C)C(=O)c1ccc([N+](=O)[O-])c(F)c1
Reactant: CC(C)C[AlH]CC(C)C
Agent: Cl
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCc1c(C=O)ccc([N+](=O)[O-])c1F
Reaction time: 1 h
Yield: 88 %

Procedure:
To a solution of THF (800 mL) cooled in an ice-salt/water bath was added 3-fluoro-N-methoxy-N-methyl-4-nitrobenzamide followed by addition of 1 M DIBAL in THF by addition funnel over 30 min. The solution was allowed to stir under N2 for 1 h. The reaction mixture was then carefully diluted with 1N HCl (500 mL) and EtOAc (500 mL), transferred to separatory funnel, and separated. The organic phase was washed with 1N HCl (3×250 mL), 1N NaOH (2×250 mL), and water (250 mL). All aqueous layers were back extracted with EtOAc (2×250 mL). The organic layers were combined, dried (MgSO4), filtered, and concentrated in vacuo to afford 67 g of the above compound (396 mmol, yield 88%). 1H-NMR (DMSO-d6) 10.06 (s, 1H), 8.36 to 8.32 (t, J=7.8 Hz, 1H), 8.06 to 8.03 (d, J=11.2 Hz, 1H), 7.95 to 7.93 (d, J=9.1 Hz, 1H).
Reaction SMILES: [Mg].Br[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH2:10][CH3:11].II.[CH3:14][O:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][C:20](=[O:25])[C:19]2=[O:26]>C(OCC)C.C1COCC1>[CH2:10]([O:9][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[C:19]1([OH:26])[C:18]2[C:22](=[CH:23][CH:24]=[C:16]([O:15][CH3:14])[CH:17]=2)[NH:21][C:20]1=[O:25])[CH3:11]
Reactant: CCOc1ccccc1Br
Reactant: COc1ccc2c(c1)C(=O)C(=O)N2
Agent: II
Agent: [Mg]
Solvent: C1CCOC1
Solvent: CCOCC
Product: CCOc1ccccc1C1(O)C(=O)Nc2ccc(OC)cc21
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
40 g (1.65 mol) of magnesium chips and 5% of the total amount of the 2-bromo-1-ethoxy benzene were added to 100 ml diethyl ether and after adding a few crystals iodine the mixture was carefully heated to initiate the reaction. To the refluxing mixture the remaining amount of 203 ml (1.65 mol) 2-bromo-1-ethoxy benzene, dissolved in 450 ml diethyl ether, was added slowly to maintain the reaction. Then 75 g (0.41 mol) of 5-methoxyisatine, suspended in 750 ml THF, were added to the cooled reaction mixture. After stirring the reaction mixture for 30 minutes at ambient temperature, the mixture was poured into an ice/aqueous NH4Cl mixture. The aqueous phase was extracted with ethyl acetate several times and the combined organic phase was washed with H2O, dried over magnesium sulfate and the solvent was removed in vacuo.
Reaction SMILES: C(O[C:6]([N:8]1[CH2:12][C:11](=[N:13][O:14][CH2:15][CH3:16])[CH2:10][C@H:9]1[C:17]([OH:19])=O)=[O:7])(C)(C)C.[N:20]([C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=1)=C=O.[CH2:31]([N:33]1[C:45]2[CH:44]=[CH:43][C:42]([NH2:46])=[CH:41][C:40]=2[C:39]2[C:34]1=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH3:32]>>[CH2:15]([O:14][N:13]=[C:11]1[CH2:12][N:8]([C:6]([NH:20][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=2)=[O:7])[C@H:9]([C:17]([NH:46][C:42]2[CH:43]=[CH:44][C:45]3[N:33]([CH2:31][CH3:32])[C:34]4[C:39]([C:40]=3[CH:41]=2)=[CH:38][CH:37]=[CH:36][CH:35]=4)=[O:19])[CH2:10]1)[CH3:16]
Reactant: COc1cccc(N=C=O)c1
Reactant: CCn1c2ccccc2c2cc(N)ccc21
Reactant: CCON=C1C[C@@H](C(=O)O)N(C(=O)OC(C)(C)C)C1
Product: CCON=C1C[C@@H](C(=O)Nc2ccc3c(c2)c2ccccc2n3CC)N(C(=O)Nc2cccc(OC)c2)C1

Procedure:
Following the general method as outlined in Example 22, starting from (2S,4EZ)-1-(tert-butoxycarbonyl)-4-(ethoxyimino)-2-pyrrolidinecarboxylic acid, 1-isocyanato-3-methoxybenzene, and 9-ethyl-9H-carbazol-3-amine the title compound was obtained in 60% purity by LC/MS. MS(ESI+): m/z=514.4.
Reaction SMILES: [CH3:1][N:2]1[C:6]2[CH:7]=[C:8](Br)[CH:9]=[CH:10][C:5]=2[NH:4][C:3]1=[O:12].[N+:13]([C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[CH:20][CH:21]=1)([O-:15])=[O:14]>>[CH3:1][N:2]1[C:6]2[CH:7]=[C:8]([C:20]3[CH:19]=[CH:18][CH:17]=[C:16]([N+:13]([O-:15])=[O:14])[CH:21]=3)[CH:9]=[CH:10][C:5]=2[NH:4][C:3]1=[O:12]
Reactant: Cn1c(=O)[nH]c2ccc(Br)cc21
Reactant: O=[N+]([O-])c1cccc(B(O)O)c1
Product: Cn1c(=O)[nH]c2ccc(-c3cccc([N+](=O)[O-])c3)cc21

Procedure:
Prepared from 1-methyl-6-bromo-1,3-dihydro-benzoimidazol-2-one and 3-nitro-phenyl boronic acid in the same fashion as that of Example 5. White solid: mp 264-265° C.; 1H-NMR (DMSO-d6) δ 11.0 (s, 1H), 8.47 (t, 1H, J=1.5 Hz), 8.19-8.15 (m, 2H), 7.75 (t, 1H, J=8.25 Hz), 7.58 (d, 1H, J=1.5 Hz), 7.43 (dd, 1H, J=8.25, 1.5 Hz), 7.1 (d, 1H, J=8.25 Hz), 3.37 (s, 3H); MS (ES) m/z 268([M−H]−, 50%); Anal. Calc. For C14H11N3O3: C, 62.45, H, 4.12, N, 15.61. Found: C, 61.48, H, 4.36 N, 14.75.
Reaction SMILES: C1(C([O:14][C:15]([CH:17]2[N:22]3[C:23](=[O:34])[C@@H:24]([C:25](=[O:33])[CH2:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[C@H:21]3[S:20][C:19]([NH2:35])=[C:18]2[CH2:36][C:37]2[O:41][C:40]([C:42]([O:44]C(C3C=CC=CC=3)C3C=CC=CC=3)=[O:43])=[CH:39][CH:38]=2)=[O:16])C2C=CC=CC=2)C=CC=CC=1.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>C1(C)C=CC=CC=1>[C:42]([C:40]1[O:41][C:37]([CH2:36][C:18]2[CH:17]([C:15]([OH:16])=[O:14])[N:22]3[C:23](=[O:34])[C@@H:24]([C:25](=[O:33])[CH2:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[C@H:21]3[S:20][C:19]=2[NH2:35])=[CH:38][CH:39]=1)([OH:44])=[O:43]
Reactant: NC1=C(Cc2ccc(C(=O)OC(c3ccccc3)c3ccccc3)o2)C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)[C@@H](C(=O)Cc3ccccc3)[C@H]2S1
Solvent: COc1ccccc1
Solvent: Cc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: NC1=C(Cc2ccc(C(=O)O)o2)C(C(=O)O)N2C(=O)[C@@H](C(=O)Cc3ccccc3)[C@H]2S1
Reaction time: 0.17 h

Procedure:
A mixture of 0.550 g of 3-(5-diphenylmethoxycarbonyl-furfuryl)-7β-phenylacetyl-amino-ceph-2-em-4ξ-carboxylic acid diphenylmethyl ester and 0.380 g of anisol is treated with 10 ml of trifluoroacetic acid and left to stand for 10 minutes at room temperature. The mixture is diluted with an equal volume of toluene and evaporated under reduced pressure. The residue is partitioned between ethyl acetate and a 10% aqueous dipotassium hydrogen phosphate solution (pH 7.8). The layers are separated, the aqueous phase is washed several times with ethyl acetate and the pH adjusted to 2.5 by addition of 20% aqueous phosphoric acid. After extraction with ethyl acetate, the resulting organic extracts are washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulphate and evaporated under reduced pressure. The residue is recrystallised from ethyl acetate and yields the 3-(5-carboxy-furfuryl)-7β-phenylacetyl-amino-ceph-2-em-4ξ-carboxylic acid, which melts at 194°-195°; [α]D20 = + 315° ± 1° (c = 1.010 in dioxan): thin-layer chromatogram (silica gel): Rf = 0.65 (system n-butanol/acetic acid/water 67:10:23) and Rf = 0.38 (system n-butanol/ethanol/water 40:10:50); infrared absorption spectrum (in mineral oil): characteristic bands at 2,99μ, 5,67μ, 5,76μ, 5,90μ, 6,04μ, 6,26μ, 6,51μ and 6,53μ (shoulder).
Reaction SMILES: [H-].[Na+].[NH:3]1[CH:7]=[N:6][CH:5]=[N:4]1.Br[CH:9]([CH3:23])[C:10]([C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=1[Cl:22])([OH:14])[C:11]#[C:12][CH3:13]>CS(C)=O.[Cl-].[Na+].O>[Cl:22][C:16]1[CH:17]=[C:18]([Cl:21])[CH:19]=[CH:20][C:15]=1[C:10]([OH:14])([CH:9]([N:3]1[CH:7]=[N:6][CH:5]=[N:4]1)[CH3:23])[C:11]#[C:12][CH3:13]
Reactant: c1nc[nH]n1
Reactant: CC#CC(O)(c1ccc(Cl)cc1Cl)C(C)Br
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CC#CC(O)(c1ccc(Cl)cc1Cl)C(C)n1cncn1
Temperature: 25 °C
Yield: 87.8 %

Procedure:
A suspension of sodium hydride (2.54 g) in dry dimethylsulphonyl (200 ml) was stirred at room temperature under argon and 1,2,4-triazol 21.9 g) was added in portions over 10 minutes, followed by further stirring for 10 minutes. A solution of 5-bromo-4-(2,4-dichlorophenyl)-4-hydroxy-hex-2-yne (17 g) in dry DMSO (50 ml) was added over 15 minutes. The resultant solution was heated at 100° C. for about 100 hours. Concentrated brine solution (200 ml) was added and the mixture extracted with ethyl acetate (3×150 ml). The extracts were combined, washed with water until neutral, dried over anhydrous magnesium sulphate and the solvent removed in vacuo to give 14.38 g of a brown solid. This solid was purified by flash chromatography, eluted with portions of ethyl acetate (50-100%) in hexane). Fractions containing the fastest running major triazole-active spot on thin-layer chromatography were combined to give 2.91 g (18%) of a white solid.