Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[N:6]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([O:13][CH:14]([CH3:16])[CH3:15])=[C:9]([C:17]([F:20])([F:19])[F:18])[CH:8]=2)[S:4][N:3]=1.[CH2:21]([C:23]1[C:28](/[CH:29]=[CH:30]/[O:31][CH3:32])=[CH:27][CH:26]=[CH:25][C:24]=1B1OC(C)(C)C(C)(C)O1)[CH3:22].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:21]([C:23]1[C:28](/[CH:29]=[CH:30]/[O:31][CH3:32])=[CH:27][CH:26]=[CH:25][C:24]=1[C:2]1[N:6]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([O:13][CH:14]([CH3:16])[CH3:15])=[C:9]([C:17]([F:20])([F:19])[F:18])[CH:8]=2)[S:4][N:3]=1)[CH3:22]
Reactant: CCc1c(/C=C/OC)cccc1B1OC(C)(C)C(C)(C)O1
Reactant: CC(C)Oc1ccc(-c2nc(Br)ns2)cc1C(F)(F)F
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCc1c(/C=C/OC)cccc1-c1nsc(-c2ccc(OC(C)C)c(C(F)(F)F)c2)n1
Temperature: 120 °C
Yield: 97.5 %

Procedure:
To a solution of 3-bromo-5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,2,4-thiadiazole (D45) (487 mg), 2-{2-ethyl-3-[(E)-2-(methyloxy)ethenyl]phenyl}-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (573 mg) and tripotassium phosphate (845 mg) in N,N-dimethylformamide (DMF) (4 mL) and water (0.800 mL) stirred under nitrogen at room temp was added Pd(Ph3P)4 (153 mg). The reaction mixture was sealed and heated under microwave at 120° C. for 10 min. After cooling the reaction, the mixture was concentrated and purified by column chromatography to give 3-{2-ethyl-3-[(E)-2-(methyloxy)ethenyl]phenyl}-5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,2,4-thiadiazole (D49) (580 mg) as a colorless oil. MS (ES): C23H23F3N2O2S requires 448. found 449.1 (M+H+).
Reaction SMILES: Br[C:2]1[C:3]2[C:10]([F:11])=[CH:9][CH:8]=[CH:7][C:4]=2[S:5][CH:6]=1.C([Li])CCC.CON(C)[C:20](=[O:23])[CH2:21][CH3:22]>O1CCCC1.CCOCC>[F:11][C:10]1[C:3]2[CH:2]=[C:6]([C:20](=[O:23])[CH2:21][CH3:22])[S:5][C:4]=2[CH:7]=[CH:8][CH:9]=1
Reactant: Fc1cccc2scc(Br)c12
Reactant: CCC(=O)N(C)OC
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCOCC
Product: CCC(=O)c1cc2c(F)cccc2s1
Temperature: -70 °C
Reaction time: 0.5 h
Yield: 23.2 %

Procedure:
A solution of 3-bromo-4-fluorobenzo[b]thiophene (3.0 g) in tetrahydrofuran (10 ml) was added dropwise under nitrogen at −60-−70° C. over 10 minutes to a stirred solution of n-butyllithium (2.5M solution in hexanes; 6.75 ml) in ether (30 ml), then the mixture was stirred at −70° C. for 30 minutes. A solution of N-methoxy-N-methylpropionamide (1.31 g) in tetrahydrofuran (10 ml) was added dropwise at −70° C. over 10 minutes, then the mixture was stirred at −70° C. for 5 hours and allowed to stand at ambient temperature for 12 hours. The mixture was quenched by the addition of saturated aqueous ammonium chloride solution (40 ml), then the organic layer was separated, washed with saturated aqueous sodium chloride solution (40 ml), dried (MgSO4) and the solvents were removed in vacuo. The residue was purified by flash chromatography over silica using a 10:1 mixture of petroleum ether (b.p. 60-80° C.) and ethyl acetate as eluant. Appropriate fractions were combined and the solvents removed in vacuo to give 1-(4-fluorobenzo[b]thiophen-2-yl)propan-1-one (0.54 g) as a colourless solid which was used without further purification.
Reaction SMILES: [H-].C([Al+]CC(C)C)C(C)C.[C:11]([C:13]1([CH2:36][CH2:37][CH3:38])[CH2:18][CH2:17][CH:16]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][C:28]([CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])=[CH:27][CH:26]=3)=[CH:21][CH:20]=2)[CH2:15][CH2:14]1)#N.C[OH:40]>CCCCCC>[CH:11]([C:13]1([CH2:36][CH2:37][CH3:38])[CH2:18][CH2:17][CH:16]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][C:28]([CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])=[CH:27][CH:26]=3)=[CH:21][CH:20]=2)[CH2:15][CH2:14]1)=[O:40]
Reactant: CO
Reactant: CCCCCc1ccc(-c2ccc(C3CCC(C#N)(CCC)CC3)cc2)cc1
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: CCCCCC
Product: CCCCCc1ccc(-c2ccc(C3CCC(C=O)(CCC)CC3)cc2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
55 ml of a 1M solution of diisobutyl-aluminium hydride (DIBAH) in n-hexane are added to a solution of 8.6 g (0.05 mole) of 4-(4-cyano-4-propyl-cyclohexyl)-4'-n-pentylbiphenyl (Example 1) in 100 ml of hexane at 0°, under a nitrogen atmosphere and with exclusion of moisture. The mixture is stirred at room temperature for one hour and 5 ml of methanol are then carefully added. The reaction mixture is poured into 200 ml of ice-cold 10% H2SO4 and stirred for 30 minutes. The organic phase is then separated off and the aqueous phase is extracted twice more with hexane. The combined organic phases are neutralised with NaHCO3 solution and then dried. Purification by chromatography gives 4-(4-formyl-4-propylcyclohexyl)-4'-pentylbiphenyl.
Reaction SMILES: [Cl:1][C:2]1[S:6][C:5]([C:7]([OH:9])=O)=[CH:4][CH:3]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:37][CH2:38][C:39]1[N:40]=[CH:41][N:42]([C:44]2[CH:53]=[CH:52][C:51]([N:54]3[CH:59]=[CH:58][CH:57]=[CH:56][C:55]3=[O:60])=[CH:50][C:45]=2[C:46]([O:48][CH3:49])=[O:47])[CH:43]=1>CN(C=O)C>[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:37][CH2:38][C:39]2[N:40]=[CH:41][N:42]([C:44]3[CH:53]=[CH:52][C:51]([N:54]4[CH:59]=[CH:58][CH:57]=[CH:56][C:55]4=[O:60])=[CH:50][C:45]=3[C:46]([O:48][CH3:49])=[O:47])[CH:43]=2)=[O:9])=[CH:4][CH:3]=1
Reactant: O=C(O)c1ccc(Cl)s1
Reactant: COC(=O)c1cc(-n2ccccc2=O)ccc1-n1cnc(CN)c1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Product: COC(=O)c1cc(-n2ccccc2=O)ccc1-n1cnc(CNC(=O)c2ccc(Cl)s2)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 5-chlorothiophene-2-carboxylic acid 1-5 (40 mg, 0.25 mmol) and TEA (0.068 mL, 0.49 mmol) in DMF (2 mL), BOP (142 mg, 0.32 mmol) was added. After 5 min of mixing, the solution was added to the sample methyl 2-(4-(aminomethyl)-1H-imidazol-1-yl)-5-(2-oxopyridin-1(2H)-yl)benzoate prepared above. The mixture was then stirred at room temperature for 1 h before it was purified by HPLC to give the title compound (4 mg). MS 469.0 and 471.0 (M+H, Cl pattern).
Reaction SMILES: [F:1][C:2]1[C:3]([I:11])=[C:4]2[NH:10][N:9]=[CH:8][C:5]2=[N:6][CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].Cl[CH2:19][C:20]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:21]>CN(C=O)C>[F:1][C:2]1[CH:7]=[N:6][C:5]2=[CH:8][N:9]([CH2:19][C:20]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:21])[N:10]=[C:4]2[C:3]=1[I:11]
Reactant: Fc1cnc2cn[nH]c2c1I
Reactant: CC(C)(C)OC(=O)NC(=O)CCl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)NC(=O)Cn1cc2ncc(F)c(I)c2n1
Temperature: 110 °C

Procedure:
To a solution of 6-fluoro-7-iodo-1H-pyrazolo[4,3-b]pyridine (150 mg, 0.570 mmol) in DMF (4 mL) was added Cs2CO3 (279 mg, 0.855 mmol) and tert-butyl 2-chloroacetylcarbamate (121 mg, 0.627 mmol). The mixture was heated at 110° C. for 2 hours. The mixture was then cooled and the reaction was concentrated under vacuum to give a residue. The residue was partitioned between saturated sodium bicarbonate solution and EtOAc (25 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (25 mL). The combined organic layers were, dried over Na2SO4 and evaporated to give tert-butyl 2-(6-fluoro-7-iodo-2H-pyrazolo[4,3-b]pyridin-2-yl)acetylcarbamate. MS [M+H] found 421.2.
Reaction SMILES: C[O:2][C:3](=[O:17])[C:4]1[CH:9]=[C:8]([C:10](=[O:12])[CH3:11])[CH:7]=[CH:6][C:5]=1[O:13][CH:14]([CH3:16])[CH3:15].[OH-].[Na+]>C1COCC1>[C:10]([C:8]1[CH:7]=[CH:6][C:5]([O:13][CH:14]([CH3:16])[CH3:15])=[C:4]([CH:9]=1)[C:3]([OH:17])=[O:2])(=[O:12])[CH3:11]
Reactant: COC(=O)c1cc(C(C)=O)ccc1OC(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CC(=O)c1ccc(OC(C)C)c(C(=O)O)c1
Temperature: 80 °C

Procedure:
To 25.8 mmol 5-acetyl-2-isopropoxy-benzoic acid methyl ester in 100 ml THF was added 400 mmol 2 M aq NaOH, and the mixture was heated at 80° C. for 2 h. The mixture was then cooled to RT and extracted twice with ether. The aqueous phase was acidified with 15% aq hydrochloric acid and extracted 3 times with ethyl acetate. The combined organic phases were dried with Na2SO4. Evaporation in vacuo followed by trituration in ether afforded the title compound. MS (m/e): 221.2 ([M−H]−, 100%)
Reaction SMILES: [C:1]([O:4][CH:5](SC)[C:6](=[O:26])[C@@H:7]([NH:15][C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=[O:3])[CH3:2].[BH4-].[Na+].Cl>CCO.O>[C:1]([O:4][CH2:5][CH:6]([OH:26])[C@@H:7]([NH:15][C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=[O:3])[CH3:2]
Reactant: CSC(OC(C)=O)C(=O)[C@H](Cc1ccccc1)NC(=O)OCc1ccccc1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CC(=O)OCC(O)[C@H](Cc1ccccc1)NC(=O)OCc1ccccc1
Temperature: -20 °C
Reaction time: 2 h

Procedure:
To a suitable reactor was added crude 3b in EtOH (100 mL) solution at 20-30° C. under N2. The mixture was cooled to −25 to −15° C., and NaBH4 (0.77 g) in H2O (7.7 mL) was added at below −8° C. The reaction mixture was warmed to −10 to −5° C. and stirred for 2 hr. The reaction was deemed completed as determined by TLC. 1N HCl aqueous solution (20 mL) was added at below 10° C. The mixture was extracted with EtOAc (100 mL×2). The separated organic portions were combined and concentrated under at 40-50° C. reduced pressure to afford crude 4b. The diastereomeric ratio of crude 4b was determined to be 97/3 by HPLC analysis.
Reaction SMILES: [F:1][CH2:2][C@@H:3]1[C@@H:7]([C:8]2[CH:13]=[CH:12][C:11](I)=[CH:10][CH:9]=2)[O:6][C:5]([CH3:16])([CH3:15])[N:4]1[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].[C:24]([Si:26]([CH3:29])([CH3:28])[CH3:27])#[CH:25].N1CCCCC1>[Cu]I.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.C1(C)C=CC=CC=1>[F:1][CH2:2][C@@H:3]1[C@@H:7]([C:8]2[CH:13]=[CH:12][C:11]([C:25]#[C:24][Si:26]([CH3:29])([CH3:28])[CH3:27])=[CH:10][CH:9]=2)[O:6][C:5]([CH3:16])([CH3:15])[N:4]1[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]
Reactant: C#C[Si](C)(C)C
Reactant: CC(C)(C)OC(=O)N1[C@H](CF)[C@@H](c2ccc(I)cc2)OC1(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: Cc1ccccc1
Solvent: C1CCNCC1
Product: CC(C)(C)OC(=O)N1[C@H](CF)[C@@H](c2ccc(C#C[Si](C)(C)C)cc2)OC1(C)C
Temperature: 35 °C
Yield: 88.4 %

Procedure:
To a toluene (40 ml) solution of (4S,5R)-tert-butyl 4-(fluoromethyl) -5-(4-iodophenyl)-2,2-dimethyloxazolidine-3-carboxylate (2.0 g, 4.6 mmols) is added ethynyltrimethylsilane (451 mg, 4.6 mmols), copper (I)iodide (88 mg, 0.46 mmols, 0.1 equivs), Bis(triphenylphosphine)palladium(II) dichloride (165 mg, 0.23 mmols, 0.05 equivs) and piperidine (782 mg, 9.2 mmols, 2 equivs). The mixture is heated in an atmosphere of nitrogen at 35° C. for six hours. The mixture is filtered through a pad of Celite. The pad of Celite is washed with ethylacetate (2×15 ml). The combined organic filtrates were concentrated using rotary evaporation at reduced pressure to give a crude viscous oil. The oil is purified by flash column chromatography (grading from 100% hexanes to 15% EtOAc) to give the title compound (1.65 g): m/z (Cl) 306 ([M+H]+−Boc).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][N:3]=1.[C:11](=O)(O)[O-].[Na+]>CO>[CH3:11][O:9][C:8]([C:6]1[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[CH:7]=1)=[O:10]
Reactant: O=C([O-])O
Reactant: O=C(O)c1ccnc(Cl)c1
Agent: [Na+]
Solvent: CO
Product: COC(=O)c1ccnc(Cl)c1
Reaction time: 0.67 h

Procedure:
2-Chloropyridine-4-carboxylic acid (15.5 g, 98 mmol) was suspended in methanol (175 ml) and anhydrous hydrogen chloride gas was slowly bubbled through the reaction mixture while cooling in a methanol/water (20/80) dry ice bath. Bubbling was continued for 40 min. during which time the suspension cleared to a partial solution. Ice bath was removed and the reaction mixture was heated to reflux under anhydrous conditions for 30 min. to give a clear yellow solution. The solution was cooled in an ice bath and saturated sodium bicarbonate was slowly added with stirring till the pH was neutral. The, organics were removed in vacuo and the product was extracted into ethyl acetate. The ethyl acetate layer was dried over sodium sulfate, filtered, and concentrated in vacuo to yield 2-chloropyridine-4-carboxylic acid methyl ester as a brown liquid.
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.Br[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O.Cl>[CH2:21]([O:8][C:5]1[CH:6]=[CH:7][C:2]([I:1])=[CH:3][CH:4]=1)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH3:10]
Reactant: CCCCCCCCCCCCBr
Reactant: Oc1ccc(I)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCCCCCCCCCCOc1ccc(I)cc1

Procedure:
4-Iodophenol (3.03 g, 1.38×10−2 mol), 1-bromododecane (6.65 ml, 2.77×10−2 mol) and K2CO3 (3.81 g, 2.76×10−2 mol) were dissolved in 50 ml of dry DMF and refluxed for 3.5 h under N2. After cooling, the solution was diluted with water, 2M HCl, and extracted with CH2Cl2. The combined organic layers were washed with saturated aq. NaHCO3, water, and dried over Na2SO4. The product was chromatographed on silica gel with 3:1 hexane:CHCl3 as the eluent. Yield=5.274 g (98% based on 3.03 g of 4-iodophenol). 1H NMR (250 MHz, CDCl3): δ 7.53 (d, 2H, J=8.8 Hz, Ph), 6.67 (d, 2H, J=9.0 Hz, Ph), 3.90 (t, 2H, J=6.5 Hz, —OCH2—), 1.76 (quint, 2H, J=6.6 Hz, —OCH2CH2—), 1.13-1.48 (m, 18H, —CH2—), 0.88 (t, 3H, J=6.4 Hz, —CH3). CI MS m/z: 388.125 (M+) (calcd 388.126).
Reaction SMILES: C([O:3][C:4](=[O:24])[CH2:5][O:6][C:7]1[CH:22]=[CH:21][C:10]2[C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[Cl:20])=[N:12][O:13][C:9]=2[C:8]=1[Cl:23])C.O.Cl>C(O)C.[OH-].[Na+]>[Cl:23][C:8]1[C:9]2[O:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[Cl:20])[C:10]=2[CH:21]=[CH:22][C:7]=1[O:6][CH2:5][C:4]([OH:24])=[O:3]
Reactant: CCOC(=O)COc1ccc2c(-c3ccccc3Cl)noc2c1Cl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=C(O)COc1ccc2c(-c3ccccc3Cl)noc2c1Cl
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of 5.86 g of the ester in 200 ml of hot ethanol, 6 ml of 50% NaOH is added. A precipitate forms and the suspension is refluxed for one hour. Two hundred milliliters of water are added to the mixture and enough concentrated HCl to make the mixture acidic. The mixture is and enough concentrated HCl to make the mixture acidic. The mixture is stirred 18 hours at room temperature. A solid product precipitates out and is filtered and recrystallized from toluene giving {[7-chloro-3-(2-chlorophenyl)-1,2-benzisoxazol-6-yl]oxy}acetic acid, mp 165°-168° C.
Reaction SMILES: [CH2:1]([O:3][C:4]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH2:14][CH2:15][CH2:16][C:17]([O:19]CC)=O)=[CH:9][CH:8]=1)=[O:5])[CH3:2].[H-].[Na+].O>O1CCCC1>[CH2:1]([O:3][C:4](=[O:5])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH2:14][CH2:15][CH2:16][C:17]2=[O:19])=[CH:9][CH:8]=1)[CH3:2]
Reactant: CCOC(=O)CCCNc1ccc(CC(=O)OCC)cc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CCOC(=O)Cc1ccc(N2CCCC2=O)cc1
Yield: 58.5 %

Procedure:
A mixture in tetrahydrofuran (50 ml) of ethyl 4-[4-(ethoxycarbonylmethyl)phenyl]aminobutanoate (2.4 g. 8.3 mmols) and sodium hydride (oily) (0.5 g, 12 mmols) was stirred, while heated under reflux, for 18 hours. The reaction mixture was poured into water, and extracted with ethyl acetate. The extract was washed with brine, and then dried with anhydrous magnesium sulfate. This was concentrated under reduced pressure, and the residue was purified through silica gel column chromatography to give a solid of ethyl[4-(2-oxopyrrolidin-1-yl)phenyl]acetate (1.2 g, 59%).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[N:8]([CH3:25])[C:9](=[O:24])[C:10]1[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([C:20]([F:23])([F:22])[F:21])[CH:11]=1.[F:26][C:27]1[CH:28]=[CH:29][C:30]([O:36][CH3:37])=[C:31](B(O)O)[CH:32]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:26][C:27]1[CH:32]=[CH:31][C:30]([O:36][CH3:37])=[C:29]([C:2]2[CH:7]=[CH:6][N:5]=[CH:4][C:3]=2[N:8]([CH3:25])[C:9](=[O:24])[C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([C:20]([F:23])([F:22])[F:21])[CH:11]=2)[CH:28]=1
Reactant: COc1ccc(F)cc1B(O)O
Reactant: CN(C(=O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1cnccc1Br
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1ccc(F)cc1-c1ccncc1N(C)C(=O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Temperature: 100 °C

Procedure:
To a solution of N-(4-bromo-pyridin-3-yl)-N-methyl-3,5-bis-trifluoromethyl-benzamide (100 mg, 0.23 mmol, example 25, intermediate a) and 5-fluoro-2-methoxybenzeneboronic acid (CAS RN 179897-94-0) (59.7 mg, 0.35 mmol) in dry DMF (3 mL) was added potassium carbonate (129.4 mg, 0.94 mmol) at 25° C. in a sealed tube and the reaction mixture was purged with argon for 10 min. Then Pd(PPh3)4 (27.05 mg, 0.023 mmol) was added and again purged with argon for 15 min. The reaction mixture was heated at 100° C. for 16 hours. The reaction mass was cooled to 25° C., filtered through a bed of celite and washed with EtOAc. The solvent was evaporated and the residue was dissolved in EtOAc and washed with water. The organic layer was washed with brine, dried over Na2SO4 and evaporated. The resulting crude product was purified by preparative HPLC. Off-white solid (55 mg, 50%). MS (ESI): m/z=473.2 [M+H]+.
Reaction SMILES: C(O)(=O)C.[ClH:5].Cl.[C:7]([NH:11][CH2:12][C:13]([C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22](=[O:31])[C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)=[C:17]([OH:32])[CH:16]=1)=[O:14])([CH3:10])([CH3:9])[CH3:8]>CN(C)C=O>[ClH:5].[OH:32][C:17]1[CH:16]=[C:15]([CH:20]=[CH:19][C:18]=1[O:21][C:22](=[O:31])[C:23]1[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=1)[CH:13]([OH:14])[CH2:12][NH:11][C:7]([CH3:10])([CH3:9])[CH3:8]
Reactant: COc1ccc(C(=O)Oc2ccc(C(=O)CNC(C)(C)C)cc2O)cc1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CC(=O)O
Product: COc1ccc(C(=O)Oc2ccc(C(O)CNC(C)(C)C)cc2O)cc1

Procedure:
Using a procedure similar to that described above in Example 58A, 26 g. of 3,4-dihydroxyphenyl tert-butylaminomethyl ketone hydrochloride was reacted with 16 g. of sodium methoxide in 300 ml. of N,N-dimethylformamide under an atmosphere of nitrogen and then 17 g. of p-anisoyl chloride was added to produce 3-hydroxy-4-(p-anisoyloxy)phenyl tert-butylaminomethyl ketone hydrochloride. This salt was converted to the free base which was treated with acetic acid to yield 35 g. of the acetate salt, m.p. 170°-175° C. (dec.)(uncorr.). By treating the salt in N,N-dimethylformamide with concentrated hydrochloric acid there was obtained 28 g. of the hydrochloride salt, m.p >235° C. (dec.)(uncorr.). When this hydrochloride is catalytically hydrogenated, using a procedure similar to that described above in Example 30B, there is obtained 3-hydroxy-4-(p-anisoyloxy)-alpha-(tert-butylaminomethyl)benzyl alcohol hydrochloride.
Reaction SMILES: [CH2:1]([C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[C:5]([O:23]COC)=[C:6]([O:21][CH3:22])[CH:7]=[C:8]2/[CH:13]=[C:14](\[CH3:20])/[C:15]([O:17]CC)=[O:16])[CH3:2]>CC(C)=O>[CH2:1]([C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[C:5]([OH:23])=[C:6]([O:21][CH3:22])[CH:7]=[C:8]2/[CH:13]=[C:14](/[CH3:20])\[C:15]([OH:17])=[O:16])[CH3:2]
Reactant: CCOC(=O)/C(C)=C/c1cc(OC)c(OCOC)c2c(CC)cccc12
Solvent: CC(C)=O
Product: CCc1cccc2c(/C=C(/C)C(=O)O)cc(OC)c(O)c12
Yield: 53 %

Procedure:
15.6 g of ethyl (E)-3-(5-ethyl-3-methoxy-4-methoxymethoxy-1-naphthyl)-2-methylpropenoate was dissolved in 300 ml of acetone and irradiated for 2 hours with light from a high pressure mercury lamp through a Pyrex filter. The solvent was evaporated and the resultant residue was purified by silica gel column chromatography (3% ethyl acetate/hexane) to obtain 6.6 g of the titled compound as a yellow oil. At the same time, 9.0 g of a mixture of E and Z isomers was obtained.
Reaction SMILES: [NH2:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[O:4][CH2:5][CH2:6][CH2:7][C:8]([O:10]CC)=[O:9].[CH3:17][CH:18]([CH3:37])[CH2:19][CH2:20][CH2:21][N:22]1[C:30]2[C:25](=[CH:26][C:27](/[C:31](/[CH3:36])=[CH:32]/[C:33](O)=[O:34])=[CH:28][CH:29]=2)[CH:24]=[CH:23]1>>[CH3:17][CH:18]([CH3:37])[CH2:19][CH2:20][CH2:21][N:22]1[C:30]2[C:25](=[CH:26][C:27](/[C:31](/[CH3:36])=[CH:32]/[C:33]([NH:1][C:2]3[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=3[O:4][CH2:5][CH2:6][CH2:7][C:8]([OH:10])=[O:9])=[O:34])=[CH:28][CH:29]=2)[CH:24]=[CH:23]1
Reactant: CCOC(=O)CCCOc1ccccc1N
Reactant: C/C(=C\C(=O)O)c1ccc2c(ccn2CCCC(C)C)c1
Product: C/C(=C\C(=O)Nc1ccccc1OCCCC(=O)O)c1ccc2c(ccn2CCCC(C)C)c1

Procedure:
0.41 g of compound 11 was obtained in a similar manner to those described in the Examples 1 and 2 using 2.33 g of ethyl 4-(2-aminophenoxy)butyrate and 1.49 g of 3-[1-(4-methylpentyl)indol-5-yl]isocrotonic acid obtained according to the procedures described in the Reference Examples 1-4.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH2:4][S:5][C@@H:6]2[CH:26]([NH:27][C:28](=[O:37])[CH2:29][O:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:25](=[O:38])[N:7]2[C:8]=1[C:9]([O:11][CH:12]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10].[F:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=1O>>[F:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=1[O:1][CH2:2][C:3]1[CH2:4][S:5][C@@H:6]2[CH:26]([NH:27][C:28](=[O:37])[CH2:29][O:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:25](=[O:38])[N:7]2[C:8]=1[C:9]([O:11][CH:12]([C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:10]
Reactant: O=C(COc1ccccc1)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(CO)CS[C@H]12
Reactant: Oc1ccccc1F
Product: O=C(COc1ccccc1)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(COc3ccccc3F)CS[C@H]12

Procedure:
The procedure described in Example 1(a) was repeated, but using 2.00 g of diphenylmethyl 3-hydroxymethyl-7-phenoxyacetamido-3-cephem-4-carboxylate and o-fluorophenol, to afford 510 mg of the title compound as a powder.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH2:7][C:6]([CH:12]=[O:13])=[CH:5]2.I[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:15]([O:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH2:7][C:6]([CH:12]=[O:13])=[CH:5]2)[CH2:16][CH2:17][CH2:18][CH3:19]
Reactant: CCCCCI
Reactant: O=CC1=Cc2cc(O)ccc2OC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCCCOc1ccc2c(c1)C=C(C=O)CO2
Reaction time: 1 h

Procedure:
2 g (11.4 mmol) of the hydroxyaldehyde obtained in Step A and also 2.7 g (13.6 mmol) of iodopentane are added to a suspension of 1.9 g (13.6 mmol) of potassium carbonate in 50 ml of anhydrous acetone; the medium is then heated at reflux. After one hour, 1.2 g of potassium carbonate are added to the solution, and that operation is then re-started after one hour. At the end of 12 hours of heating at reflux, the solution is allowed to cool, the salts are filtered off over Celite and the solvent is then evaporated in vacuo. Chromatography on a silica column (eluant:petroleum ether/ethyl acetate 90/10) yields the title aldehyde in the form of a yellow syrup.