Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O)C#C.[CH2:5]([OH:19])[C:6]#[C:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].COCCO[AlH2-]OCCOC.[Na+]>CCOCC>[CH2:5]([OH:19])/[CH:6]=[CH:7]/[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCCCCCC#CCO
Agent: C#CCO
Agent: COCCO[AlH2-]OCCOC
Agent: [Na+]
Solvent: CCOCC
Product: CCCCCCCCCCC/C=C/CO

Procedure:
trans-2-Tetradecen-1-ol was prepared by reduction of the propargyl alcohol by the method described by Jones and Denmark (Org. Syn., 1985, 64, 182-8) using 8.0 g (38 mmole) of 2-tetradecyn-1-ol in 30 ml of ether and 16 ml (55 mmole) of Red-Al in 40 ml of ether. Kugelrohr distillation afforded 7.67 g of clear oil. 1H NMR δ 5.66 (m, 2), 4.08 (d, 2, J=5 Hz) 2.03 (dd, 2, J=6, 13 Hz), 1.60 (br, 1), 1.4-1.2 (m, 18), 0.88 (t, 3, J=7 Hz).
Reaction SMILES: [Br:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([CH:9]2[CH2:13][CH2:12][CH:11](O)[CH2:10]2)=[C:4]([F:15])[CH:3]=1.[C:16]1(=[O:26])[NH:20][C:19](=[O:21])[C:18]2=[CH:22][CH:23]=[CH:24][CH:25]=[C:17]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[Br:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([CH:9]2[CH2:13][CH2:12][CH:11]([N:20]3[C:16](=[O:26])[C:17]4[C:18](=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:19]3=[O:21])[CH2:10]2)=[C:4]([F:15])[CH:3]=1
Reactant: OC1CCC(c2cc(F)c(Br)cc2F)C1
Reactant: O=C1NC(=O)c2ccccc21
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: O=C1c2ccccc2C(=O)N1C1CCC(c2cc(F)c(Br)cc2F)C1
Temperature: 25 °C
Reaction time: 18 h
Yield: 76.8 %

Procedure:
To a solution of 13.9 g (50 mmol) of 3-(4-bromo-2,5-difluorophenyl)cyclopentanol, 7.4 g (50 mmol) of phthalimide and 13.1 g (50 mmol) of triphenylphosphine in 50 ml of dry tetrahydrofuran was added dropwise at room temperature a solution of 8.7 g (50 mmol) of diethyl azodicarboxylate in 20 ml of dry tetrahydrofuran. The reaction was stirred at room temperature for 18 hours and the solvent was removed in vacuo. The residue was triturated with ether and the solid removed by filtration. The filtrate was evaporated in vacuo and the residue was chromatographed on silica gel (E. Merck -230-400 Mesh) eluting with chloroform-ethyl acetate (4:1) to give 15.6 g of the title compound; mp 47°-48°.
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10](=[O:15])[CH2:9]2)=[O:4].[I-].[K+].C(N(CC)CC)C.[CH2:25]([CH:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C(#N)C>[CH2:25]([CH:32]1[CH2:37][CH2:36][N:35]([CH2:2][C:3]([NH:5][C:6]2[CH:7]=[C:8]3[C:12](=[CH:13][CH:14]=2)[NH:11][C:10](=[O:15])[CH2:9]3)=[O:4])[CH2:34][CH2:33]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: c1ccc(CC2CCNCC2)cc1
Reactant: O=C(CCl)Nc1ccc2c(c1)CC(=O)N2
Agent: [I-]
Agent: [K+]
Solvent: CC#N
Solvent: CCN(CC)CC
Product: O=C(CN1CCC(Cc2ccccc2)CC1)Nc1ccc2c(c1)CC(=O)N2
Yield: 64.2 %

Procedure:
A mixture of 0.9 g (4 mmol) of 2-chloro-N-(2-oxo-2,3-dihydro-1H-indol-5-yl)-acetamide, 0.7 g (4 mmol) of potassium iodide, 0.6 ml (4 mmol) of triethylamine, 0.53 ml (3 mmol) of 4-benzyl-piperidine and 50 ml of acetonitrile is refluxed for 20 hours. The reaction mixture is concentrated and 30 ml of water and 30 ml of chloroform are added to the residue. The organic layer is separated and the water phase is extracted three times with 10 ml of chloroform. The combined organic layers are dried over sodium sulfate, concentrated and the residue is treated with diethylether and the precipitated crystals are filtered off to yield 0.7 g (64%) of the title compound. Melting Point: 176-180° C. (diethylether)
Reaction SMILES: [NH:1]=[C:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[CH3:8].[OH-].[Na+].O.[C:12]1([N:18]=[C:19]=[O:20])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C1C=CC=CC=1>[C:12]1([NH:18][C:19]([N:1]=[C:2]2[CH2:7][CH2:6][CH2:5][CH2:4][N:3]2[CH3:8])=[O:20])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CN1CCCCC1=N
Reactant: O=C=Nc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: c1ccccc1
Product: CN1CCCCC1=NC(=O)Nc1ccccc1
Temperature: 25 °C

Procedure:
The hydrochloride salt of 2-imino-1-methylpiperidine (7.43 g.; 0.05 mole) is converted to free base by adding 5 mls. of 50% NaOH to an aqueous slurry (using a minimal amount of water) of the salt and then extracting with benzene. After drying over K2CO3 the benzene solution is stirred at room temperature and 5.96 g. (0.05 mole) of phenylisocyanate, dissolved in anhydrous benzene, is added dropwise. Cloudiness occurs and eventually solid precipitates from the solution. The reaction mixture is stirred at room temperature overnight (about 17 hours). The solid is collected, m.p. = 145°-158° C. The filtrate is taken to dryness in vacuo to give further solid material. Repeated recrystallizations of the combined solids from methanol yields the pure product, 1-phenyl-3-(1-methyl-2-piperidylidene)urea, m.p. = 160°-161° C.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:17]([NH:19][C@H:20]([C:25]([OH:27])=O)[CH2:21][CH2:22][CH2:23][CH3:24])=[O:18])[CH2:13][CH:14]([CH3:16])[CH3:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:28]N1CCOCC1.ClC(OCC)=O.[N+](=C)=[N-]>C1COCC1.C(OCC)C>[C:25]([CH:20]([NH:19][C:17](=[O:18])[C@H:12]([CH2:13][CH:14]([CH3:15])[CH3:16])[NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])[CH2:21][CH2:22][CH2:23][CH3:24])(=[O:27])[CH3:28]
Reactant: CCCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)OCc1ccccc1)C(=O)O
Reactant: CN1CCOCC1
Agent: C=[N+]=[N-]
Agent: CCOC(=O)Cl
Solvent: CCOCC
Solvent: C1CCOC1
Product: CCCCC(NC(=O)[C@H](CC(C)C)NC(=O)OCc1ccccc1)C(C)=O
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
In 150 g of anhydrous THF were dissolved 5.4 g of N-benzyloxycarbonyl-L-leucyl-L-norleucine prepared in the same manner as in Example 1-(b) and 3.4 ml of N-methylmorpholine, and 1.6 g of ethyl chloroformate was added thereto under ice-cooling, followed by stirring at 0° C. for 30 minutes. The reaction mixture was added to an excess diazomethane solution in diethyl ether, and the solution was allowed to stand at 0° C. for 1 hour. The solvent was removed by distillation under reduced pressure, and the residue was purified by medium-pressure column chromatography on silica gel to obtain 4.0 g of the titled compound as a colorless crystal.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[C:13]([O:16][CH3:17])[CH:14]=2)[C:9](=O)[CH2:8][CH:7]1[CH3:27])=[O:5])[CH3:2].Cl.[NH2:29][OH:30].C([O-])(=O)C.[Na+].O>C(O)C>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[C:13]([O:16][CH3:17])[CH:14]=2)[C:9](=[N:29][OH:30])[CH2:8][CH:7]1[CH3:27])=[O:5])[CH3:2]
Reactant: CCOC(=O)N1c2cc(OC)c(OCc3ccccc3)cc2C(=O)CC1C
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CCOC(=O)N1c2cc(OC)c(OCc3ccccc3)cc2C(=NO)CC1C
Reaction time: 2 h
Yield: 98.9 %

Procedure:
To a stirred solution of 6-benzyloxy-7-methoxy-2-methyl-4-oxo-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester (1.99 g, 5.39 mmol) in 95% ethanol (20 mL) was added hydroxylamine hydrochloride (1.1 g, 16 mmol) and sodium acetate (1.1 g, 14 mmol), and the mixture was heated at reflux. After 2 h, water (50 mL) was added, and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic phases were washed with brine (30 mL), dried over sodium sulfate, filtered and concentrated in vacuo to give 2.05 g of the title compound (99%).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:31])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]2[C:7]=1[C:8](=[O:30])[C:9]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][C:20]=1[Cl:29])=[C:10]([CH3:17])[NH:11]2.CN(C)C=O.C(=O)([O-])[O-].[K+].[K+].Cl[C:44](OC(=O)C)([F:46])[F:45]>O>[CH3:1][O:2][C:3](=[O:31])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]2[C:7]=1[C:8]([O:30][CH:44]([F:46])[F:45])=[C:9]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:26])=[O:27])=[CH:21][C:20]=1[Cl:29])[C:10]([CH3:17])=[N:11]2
Reactant: CC(=O)OC(F)(F)Cl
Reactant: COC(=O)COc1ccc(Cl)c2[nH]c(C)c(Cc3ccc(S(C)(=O)=O)cc3Cl)c(=O)c12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)COc1ccc(Cl)c2nc(C)c(Cc3ccc(S(C)(=O)=O)cc3Cl)c(OC(F)F)c12
Temperature: 70 °C
Reaction time: 16 h

Procedure:
A mixture of [8-chloro-3-(2-chloro-4-methanesulfonylbenzyl)-2-methyl-4-oxo-1,4-dihydroquinolin-5-yloxy]acetic acid methyl ester (0.34 g), N,N-dimethylformamide (15 mL), potassium carbonate (0.58 g) and acetic acid chlorodifluoromethyl ester (0.4 mL) was stirred at 70° C. for 16 hours. The mixture was diluted with water, extracted with ethyl acetate and the combined extracts were dried over sodium sulfate and then the solvent removed under reduced pressure. Purification of the residue by column chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (7:3 by volume) gave title compound, 0.37 g.
Reaction SMILES: C(N(S(F)(F)[F:7])CC)C.[CH3:10][O:11][C:12]([C:14]1([CH:17](O)[CH2:18][CH2:19][CH2:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:16][O:15]1)=[O:13]>C(Cl)Cl>[CH3:10][O:11][C:12]([C:14]1([CH:17]([F:7])[CH2:18][CH2:19][CH2:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:16][O:15]1)=[O:13]
Reactant: COC(=O)C1(C(O)CCCCc2ccccc2)CO1
Reactant: CCN(CC)S(F)(F)F
Solvent: ClCCl
Product: COC(=O)C1(C(F)CCCCc2ccccc2)CO1
Temperature: -78 °C
Reaction time: 1.5 h
Yield: 58.8 %

Procedure:
To a solution of 2.44 g (15 mmol; 2.0 ml) of diethylaminosulfur trifluoride in 50 ml of methylene chloride cooled to -78° C. under a nitrogen atmosphere is added dropwise a solution of 2.00 g (7.6 mmol) of 2-[1-hydroxy-5-phenylpentyl]-2-oxiranecarboxylic acid methyl ester (isomer A) in 50 ml of methylene chloride over 30 minutes. The mixture is stirred at -78° C. for 90 minutes and then is allowed to come to room temperature. The mixture is stirred at room temperature for 1.5 hours, is quenched with a saturated aqueous solution of sodium bicarbonate and is extracted with ethyl ether. The combined ethereal extracts are dried over magnesium sulfate, filtered and rotoevaporated. The resulting oil is purified chromatographically (silica gel; hexane:ethyl acetate (9:1)) to give 1.19 g of the title compound (Rf 0.54 in hexane:ethyl ether (3:2)): IR (neat) γ 1750 cm-1 ; NMR (CDCl3) δ 1.40-1.96 (6H, m), 2.64 (2H, t, J=8 Hz), 3.07 (1H, dd, J=4, 6 Hz), 3.15 (1H, d, J=6 Hz), 3.15 (1H, d, J=6 Hz), 3.79 (3H, s), 5.14 (1H, ddd, JHF =48 Hz, J=10, 3 Hz), 7.21 (2H, d, J=8 Hz) and 7.31 (2H, d, J=8 Hz).
Reaction SMILES: [H-].[Na+].CS(C)=O.[Br-].[C:8]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([OH:10])=[O:9].[C:35]([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)(=O)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>O1CCCC1>[C:36]1([C:35]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[CH:15][CH2:14][CH2:13][CH2:12][CH2:11][C:8]([OH:10])=[O:9])[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1
Reactant: O=C(O)CCCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=C(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CS(C)=O
Product: O=C(O)CCCCC=C(c1ccccc1)c1ccccc1
Yield: 70.6 %

Procedure:
The reaction was carried out as in Example 87 using the following reagents: sodium hydride (56% dispersion in oil; 8.6 g); dimethylsulfoxide (100 mL), (5-carboxypentyl)triphenylphosphonium bromide (37.64 g); benzophenone (18 g) and tetrahydrofuran (100 mL). The acid, isolated in the normal manner, was crystallized from hexane to give 16.3 g of 7,7-diphenyl-6-heptenoic acid, mp 71.5°-72.5° C. A portion was recrystallized from hexane to give the analytical sample, mp 72.5°-73.5° C. Anal. Calculated for C19H20O2 : C, 81.40; H, 7.19. Found: C, 81.61; H, 7.40.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:9](=O)[CH2:10][NH:11][C:12](=[O:23])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]([F:22])([F:21])[F:20])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.Cl.[NH2:26][OH:27]>C(O)C>[Cl:1][C:2]1[C:3]([C:9](=[N:26][OH:27])[CH2:10][NH:11][C:12](=[O:23])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]([F:22])([F:21])[F:20])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: O=C(NCC(=O)c1ncc(Cl)cc1Cl)c1ccccc1C(F)(F)F
Reactant: NO
Agent: Cl
Solvent: CCO
Product: O=C(NCC(=NO)c1ncc(Cl)cc1Cl)c1ccccc1C(F)(F)F
Temperature: 25 °C
Reaction time: 96 h
Yield: 96.2 %

Procedure:
To 2.8 g of N-[2-(3,5-dichloropyridin-2-yl)-2-oxoethyl]-2-(trifluoromethyl)benzamide in 19 ml of ethanol, 1.0 g of hydroxylamine hydrochloride was added, and the mixture was stirred at room temperature for 96 hours. After completion of the reaction, the solvent was evaporated under reduced pressure, the resulting residue was mixed with 50 ml of water and extracted with ethyl acetate (50 ml×2), the resulting organic layers were combined, dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from 5:95 to 50:50) as the eluent to obtain 2.8 g of the desired product as white crystals.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([CH:10]=1)[C:7]([NH2:9])=[O:8].Br[CH2:13][CH2:14][CH3:15].[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH2:13][CH2:14][CH3:15])=[C:6]([CH:10]=1)[C:7]([NH2:9])=[O:8]
Reactant: CCCBr
Reactant: NC(=O)c1cc(Cl)ccc1O
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCOc1ccc(Cl)cc1C(N)=O

Procedure:
A stirred mixture of 5-chloro-2-hydroxybenzamide (20 g), 1-bromopropane (13.4 ml), potassium iodide (2.49 g) and anhydrous potassium carbonate (24.15 g) in acetone (250 ml) was heated under reflux for 20 hours. The cooled reaction mixture was filtered and the filter cake was washed with acetone. The filtrate and washings were combined and evaporated under reduced pressure to yield a residue which was washed with water, dilute aqueous sodium hydroxide, water and with diethyl ether to yield a crude product (19.85 g). This was recrystallised from acetonitrile, partitioned between chloroform and dilute aqueous sodium hydroxide, and was recrystallised from ethanol to yield 5-chloro-2-propoxybenzamide (16.78 g).
Reaction SMILES: FC(F)(F)C(O)=O.FC(F)(F)S(O)(=O)=O.COC1C=C(OC)C=CC=1C[N:21]1[CH2:27][CH2:26][C:25]([F:29])([F:28])[CH2:24][C@@H:23]([N:30]([CH2:40][C:41]2[CH:42]=[N:43][C:44]([O:47][CH3:48])=[CH:45][CH:46]=2)[S:31]([CH2:34][CH2:35][C:36]([F:39])([F:38])[F:37])(=[O:33])=[O:32])[C:22]1=[O:49]>ClCCl>[F:29][C:25]1([F:28])[CH2:26][CH2:27][NH:21][C:22](=[O:49])[C@H:23]([N:30]([CH2:40][C:41]2[CH:42]=[N:43][C:44]([O:47][CH3:48])=[CH:45][CH:46]=2)[S:31]([CH2:34][CH2:35][C:36]([F:38])([F:39])[F:37])(=[O:33])=[O:32])[CH2:24]1
Reactant: COc1ccc(CN2CCC(F)(F)C[C@@H](N(Cc3ccc(OC)nc3)S(=O)(=O)CCC(F)(F)F)C2=O)c(OC)c1
Agent: O=S(=O)(O)C(F)(F)F
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(CN([C@@H]2CC(F)(F)CCNC2=O)S(=O)(=O)CCC(F)(F)F)cn1

Procedure:
A mixture containing trifluoroacetic acid/trifluoromethanesulfonic acid (5:2 v/v, 0.76 ml) was added to 3,3,3-trifluoro-propane-1-sulfonic acid [(R)-1-(2,4-dimethoxy-benzyl)-5,5-difluoro-2-oxo-azepan-3-yl]-(6-methoxy-pyridin-3-ylmethyl)-amide (0.2 g, 0.24 mmol) in dichloromethane (10 ml). After 2 h the reaction mixture was concentrated under reduced pressure and the residue taken up in ethyl acetate and washed with water, saturated aqueous sodium bicarbonate and brine, dried (Na2SO4), filtered, concentrated under reduced pressure and purified over silica gel (heptane-ethyl acetate, 9:1-0:1): white solid 72 mg (69%);
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:11]([F:14])([F:13])[F:12])[C:7](O)=[N:8][CH:9]=1)([O-:3])=[O:2].P(Cl)(Cl)(Cl)(Cl)[Cl:16].P(Cl)(Cl)(Cl)=O>>[Cl:16][C:7]1[C:6]([C:11]([F:14])([F:13])[F:12])=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][N:8]=1
Reactant: O=[N+]([O-])c1cnc(O)c(C(F)(F)F)c1
Reactant: ClP(Cl)(Cl)(Cl)Cl
Solvent: O=P(Cl)(Cl)Cl
Product: O=[N+]([O-])c1cnc(Cl)c(C(F)(F)F)c1

Procedure:
A mixture of EXAMPLE 288A (1.69 g), phosphorus pentachloride (2.03 g), and phosphoryl trichloride (0.97 mL) was heated at 90° C. for 3 hours. After cooling, the reaction mixture was poured into ice, and extracted with ethyl acetate three times. The extract was washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with 10% ethyl acetate in hexanes to provide the title compound.
Reaction SMILES: C(O[CH2:5][C:6]1[CH2:7][S:8][C@@H:9]2[CH:16]([NH:17][C:18](=[O:29])[C:19]([C:23]3[N:24]=[C:25]([NH2:28])[S:26][CH:27]=3)=[N:20][O:21][CH3:22])[C:15](=[O:30])[N:10]2[C:11]=1[C:12]([OH:14])=[O:13])(=O)C.[C:31]([O-:34])(=[S:33])[CH3:32].[K+].P(O)(O)([O-])=O.[Na+].O>C(O)=O>[C:31]([S:33][CH2:5][C:6]1[CH2:7][S:8][C@@H:9]2[CH:16]([NH:17][C:18](=[O:29])[C:19]([C:23]3[N:24]=[C:25]([NH2:28])[S:26][CH:27]=3)=[N:20][O:21][CH3:22])[C:15](=[O:30])[N:10]2[C:11]=1[C:12]([OH:14])=[O:13])(=[O:34])[CH3:32]
Reactant: CC([O-])=S
Reactant: CON=C(C(=O)NC1C(=O)N2C(C(=O)O)=C(COC(C)=O)CS[C@H]12)c1csc(N)n1
Agent: O=P([O-])(O)O
Agent: [K+]
Agent: [Na+]
Solvent: O=CO
Solvent: O
Product: CON=C(C(=O)NC1C(=O)N2C(C(=O)O)=C(CSC(C)=O)CS[C@H]12)c1csc(N)n1
Reaction time: 0.08 h

Procedure:
A solution of the syn isomer of 4.55 g of 3-acetoxymethyl-7-[{2-(2-amino-4-thiazolyl)-2-methoxyiminoacetyl}amino]-ceph-3-eme-4-carboxylic acid, 1.7 g of potassium thioacetate. 2 g of deshydrated monosodium phosphate 1.05 g sodium acid carbonate and 20 ml of distilled water was heated at 70° C. for 90 minutes and the mixture was acidified with 2 ml of formic acid and was extracted 4 times with 60 ml of methyl acetate (insolubles vacuum filtered). The organic solution was washed with water and evaporated to dryness. The residue was dissolved in 20 ml of acetone containing 10% of water and 0.5 g of activated carbon were added thereto. The mixture was stirred for 5 minutes and was vacuum filtered and the filter was washed with acetone containing 10% of water. The filter eas evaporated to dryness and the residue was treated with absolute ethanol and was vacuum filtered. The product was washed with alcohol and then with ether to obtain 1.9 g of the pure syn isomer of 3-acetylthiomethyl-7-[{2-(2-amino-4-thiazolyl)-2-methoxyiminoacetyl}amino]-ceph-3-eme-4-carboxylic acid which was identical to the product of Example 6.
Reaction SMILES: [OH:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([C:8]2[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=3[O:10][C:9]=2[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:7])=[CH:4][CH:3]=1.[CH3:25][N:26]([CH3:31])[CH2:27][CH2:28][CH2:29]Cl>>[CH3:25][N:26]([CH3:31])[CH2:27][CH2:28][CH2:29][O:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([C:8]2[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=3[O:10][C:9]=2[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)=[O:7])=[CH:23][CH:24]=1
Reactant: O=C(c1ccc(O)cc1)c1c(-c2ccccc2)oc2ccccc12
Reactant: CN(C)CCCCl
Product: CN(C)CCCOc1ccc(C(=O)c2c(-c3ccccc3)oc3ccccc23)cc1

Procedure:
When 3-(4-hydroxybenzoyl)-2-phenylbenzofuran is reacted with 3-dimethylaminopropyl chloride by the procedure described in Example 1, 3-[4-(3-dimethylaminopropoxy)benzoyl]-2-phenylbenzofuran is obtained.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:10]=2)[CH:7]=1.C(N(CC)CC)C.[CH3:23][S:24](Cl)(=[O:26])=[O:25]>C1COCC1>[CH3:23][S:24]([N:1]([C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:10]=2)[CH:7]=1)[S:24]([CH3:23])(=[O:26])=[O:25])(=[O:26])=[O:25]
Reactant: CCOC(=O)c1cn2cc(N)ccc2n1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CCOC(=O)c1cn2cc(N(S(C)(=O)=O)S(C)(=O)=O)ccc2n1
Temperature: 0 °C
Yield: 42.3 %

Procedure:
Ethyl 6-aminoimidazo[1,2-a]pyridine-2-carboxylate (0.975 mmol, 0.2 g) was dissolved in THF (10 ml). Triethylamine (9.75 mmol, 0.986 g) was added and the mixture was cooled to 0° C. Methanesulfonyl chloride (9.75 mmol, 1.116 g) was slowly added and the mixture was allowed to cool to RT. The stirring continued at RT until the reaction was finished. The solvent was evaporated, DCM was added and washed with NaHCO3 solution and water. The organic phase was dried, filtered and evaporated. The crude product was purified with flash chromatography. 0.149 g of the title compound was obtained. 1H-NMR (400 MHz, DMSO-d6): δ 1.33 (t, 3H), 3.61 (s, 6H), 4.34 (q, 2H), 7.50 (dd, 1H), 7.69-7.74 (m, 1H), 8.54-8.56 (m, 1H), 9.00-9.02 (m, 1H).
Reaction SMILES: [CH:1]1([C:4]2[CH:5]=[C:6]([CH3:25])[C:7]([N:10]3[CH2:15][CH2:14][N:13]([C:16]([C:18]4[CH:23]=[CH:22][C:21](I)=[CH:20][CH:19]=4)=[O:17])[CH2:12][CH2:11]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.[CH3:26][C@@H:27]1[O:31][C:30](=[O:32])[NH:29][CH2:28]1>>[CH:1]1([C:4]2[CH:5]=[C:6]([CH3:25])[C:7]([N:10]3[CH2:15][CH2:14][N:13]([C:16]([C:18]4[CH:23]=[CH:22][C:21]([N:29]5[CH2:28][C@H:27]([CH3:26])[O:31][C:30]5=[O:32])=[CH:20][CH:19]=4)=[O:17])[CH2:12][CH2:11]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1
Reactant: Cc1cc(C2CC2)cnc1N1CCN(C(=O)c2ccc(I)cc2)CC1
Reactant: C[C@H]1CNC(=O)O1
Product: Cc1cc(C2CC2)cnc1N1CCN(C(=O)c2ccc(N3C[C@H](C)OC3=O)cc2)CC1
Yield: 81.9 %

Procedure:
By reaction and treatment in the same manner as in Example 149 and using [4-(5-cyclopropyl-3-methylpyridin-2-yl)piperazin-1-yl](4-iodophenyl)methanone (447 mg) described in Preparation Example 97 and (S)-5-methyloxazolidin-2-one (121 mg) described in Preparation Example 42, the title compound (344 mg) was obtained.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:11][C:10]([O:13][C:14]2[C:15]([F:32])=[CH:16][C:17]3[O:22][CH2:21][C:20](=S)[N:19]([CH:24]([C:26](OCC)=[O:27])[CH3:25])[C:18]=3[CH:31]=2)([CH3:12])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[NH2:34][NH2:35]>CCO>[C:1]([O:5][C:6]([N:8]1[CH2:9][C:10]([O:13][C:14]2[CH:31]=[C:18]3[C:17](=[CH:16][C:15]=2[F:32])[O:22][CH2:21][C:20]2[N:19]3[CH:24]([CH3:25])[C:26](=[O:27])[NH:34][N:35]=2)([CH3:12])[CH2:11]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)C(C)N1C(=S)COc2cc(F)c(OC3(C)CN(C(=O)OC(C)(C)C)C3)cc21
Reactant: NN
Solvent: O
Solvent: CCO
Product: CC1C(=O)NN=C2COc3cc(F)c(OC4(C)CN(C(=O)OC(C)(C)C)C4)cc3N21
Temperature: 25 °C
Yield: 45.9 %

Procedure:
To a solution of 3-[4-(1-ethoxycarbonyl-ethyl)-7-fluoro-3-thioxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yloxy]-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (0.080 g, 0.171 mmol) in EtOH (5 mL) was added hydrazine hydrate (0.085 g, 1.707 mmol) and the mixture was heated to reflux for 2 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was purified by preparative TLC (eluting with 30% EtOAc in petroleum ether) to give 3-(7-fluoro-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yloxy)-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (0.033 g, 46%) as a white solid. LC/MS (Table 1, Method 2) Rt=1.144 min.; MS m/z: 421 [M+H]+.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:13][CH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)[CH2:3][N:4]([CH3:12])[C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].[C:20]([N:22]=[C:23](SC)[S:24][CH3:25])#[N:21]>CC#N.CCN(CC)CC>[C:20]([N:22]=[C:23]([NH:1][C@@H:2]([CH2:13][CH:14]1[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]1)[CH2:3][N:4]([CH3:12])[C:5](=[O:11])[O:6][C:7]([CH3:9])([CH3:10])[CH3:8])[S:24][CH3:25])#[N:21]
Reactant: CN(C[C@@H](N)CC1CCCCC1)C(=O)OC(C)(C)C
Reactant: CSC(=NC#N)SC
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CSC(=NC#N)N[C@@H](CC1CCCCC1)CN(C)C(=O)OC(C)(C)C
Yield: 30.5 %

Procedure:
To a solution of (S)-tert-butyl 2-amino-3-cyclohexylpropyl(methyl)carbamate (1.08 g, 4 mmol) in CH3CN (15 mL) and Et3N (3 mL) was added dimethyl cyanocarbonimidodithioate (642 mg, 4.4 mmol). The mixture was heated to reflux for 4 h. The reaction mixture was concentrated to give the residue, which was purified by column to give (S)-tert-butyl 2-((cyanoimino)(methylthio)methylamino)-3-cyclohexylpropyl(methyl)carbamate (450 mg, 31%).