Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3]([C:5]1[N:15]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[C:8]2[N:9]=[C:10]([S:13][CH3:14])[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4].[OH-].[Na+]>C1COCC1.O>[F:22][C:19]1[CH:20]=[CH:21][C:16]([N:15]2[C:8]3[N:9]=[C:10]([S:13][CH3:14])[N:11]=[CH:12][C:7]=3[CH:6]=[C:5]2[C:3]([OH:4])=[O:2])=[CH:17][CH:18]=1
Reactant: COC(=O)c1cc2cnc(SC)nc2n1-c1ccc(F)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CSc1ncc2cc(C(=O)O)n(-c3ccc(F)cc3)c2n1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 7-(4-fluorophenyl)-2-methylsulfanyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid methyl ester, 23, (3.1 g, 9.7 mmol) in THF (40 mL) is added a solution of NaOH (3.9 g, 97.0 mmol) in water (30 mL). The reaction is allowed to stir for 3 hours at room temperature before the mixture is diluted with H2O and extracted three times with EtOAc. The aqueous phase is acidified slowly to pH 1-2 with conc. HCl and then extracted three times with EtOAc. The combined organic phases are rinsed with brine, dried (MgSO4), filtered, and concentrated in vacuo to afford 2.5 g of the desired product which was used without further purification: 1H NMR (300 MHz, d6-DMSO) δ 9.06 (s, 1H), 7.44 (s, 1H), 7.52 (dd, J=8.2, 5.9 Hz, 2H), 7.38 (t, J=8.7 Hz, 1H), 2.44 (s, 3H); ESI+ MS: m/z (rel intensity) 304.0 (100, M++H).
Reaction SMILES: Br[CH2:2][C:3](Br)([C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:7]=1[F:13])[CH2:4]Br.[NH:15]1[CH:19]=[N:18][CH:17]=[N:16]1.C([O-])([O-])=O.[K+].[K+]>O>[F:13][C:7]1[CH:8]=[C:9]([F:12])[CH:10]=[CH:11][C:6]=1[CH:3]([CH2:4][N:15]1[CH:19]=[N:18][CH:17]=[N:16]1)[CH2:2][N:15]1[CH:19]=[N:18][CH:17]=[N:16]1
Reactant: c1nc[nH]n1
Reactant: Fc1ccc(C(Br)(CBr)CBr)c(F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: Fc1ccc(C(Cn2cncn2)Cn2cncn2)c(F)c1
Temperature: 25 °C
Yield: 23.9 %

Procedure:
To a mixture of 1,2,3-Tribromo-2-(2,4-difluorophenyl)propane (5 g, 12.7 mmol) and water (25 ml), 1,2,4-Triazole (3.5 g, 50.8 mmol) and K2CO3 (3.5 g, 25.5 mmol) were added. The mixture was heated to reflux for 15-18 hours with vigorous stirring. The reaction mixture was cooled to room temperature and the product was extracted with EtOAc (3×100 ml). The combined EtOAc phase was washed with water and dried (Na2SO4). Evaporation of the solvent in vacuo and purification of the residue on a silica gel column with EtOAc and EtOH:EtOAc (1:19) as the elements, furnished the title compound (0.88 g, 23%).
Reaction SMILES: [BH4-].[Na+].[CH2:3]([Si:5]([CH2:15][CH3:16])([CH2:13][CH3:14])[C:6]1[O:7][CH:8]=[C:9]([CH:11]=[O:12])[CH:10]=1)[CH3:4]>CO>[OH:12][CH2:11][C:9]1[CH:10]=[C:6]([Si:5]([CH2:13][CH3:14])([CH2:15][CH3:16])[CH2:3][CH3:4])[O:7][CH:8]=1
Reactant: CC[Si](CC)(CC)c1cc(C=O)co1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CC[Si](CC)(CC)c1cc(CO)co1
Reaction time: 1 h

Procedure:
Sodium borohydride (353 mg, 0.93 mmol) was added portionwise to a solution of 2-triethylsilyl-4-furaldehyde (1.64 g, 7.79 mmol) in methanol (10 ml) at 0°. After 1 hour, most of the methanol was evaporated and the residue dissolved in a minimum amount of dilute hydrochloric acid. Extraction (ethyl acetate), drying (magnesium sulfate) and evaporation gave an oil, which was purified by flash chromatography on silica using 20% ethyl ether/hexane. Fractions with Rf of about 0.07 (10% ethyl ether/hexane) gave after evaporation the title alcohol as a colorless oil.
Reaction SMILES: [F:1][C:2]([F:28])([F:27])[C:3]([C:10]1[CH:26]=[CH:25][CH:24]=[CH:23][C:11]=1[O:12][C:13]1[CH:14]=[N:15][C:16]2[C:21]([CH:22]=1)=[CH:20][CH:19]=[CH:18][CH:17]=2)([CH3:9])[O:4][Si](C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[F:28][C:2]([F:1])([F:27])[C:3]([C:10]1[CH:26]=[CH:25][CH:24]=[CH:23][C:11]=1[O:12][C:13]1[CH:14]=[N:15][C:16]2[C:21]([CH:22]=1)=[CH:20][CH:19]=[CH:18][CH:17]=2)([OH:4])[CH3:9]
Reactant: CC(O[Si](C)(C)C)(c1ccccc1Oc1cnc2ccccc2c1)C(F)(F)F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: CC(O)(c1ccccc1Oc1cnc2ccccc2c1)C(F)(F)F
Reaction time: 16 h
Yield: 78.7 %

Procedure:
After 0.17 g of 3-[2-(2,2,2-trifluoro-1-methyl-1-trimethylsilanyloxy-ethyl)-phenoxy]-quinoline was dissolved in 1.5 ml of tetrahydrofuran, 1 ml of tetrabutylammonium fluoride (1.0 M tetrahydrofuran solution) was added and the mixture was stirred for 16 hours. The reaction mixture was concentrated and then purified by silica gel column chromatography to obtain 0.11 g of 1,1,1-trifluoro-2-[2-(quinolin-3-yloxy)-phenyl]-propan-2-ol (Compound Number 29).
Reaction SMILES: [O-:1][C:2]#[N:3].[K+].[NH2:5][C:6]1[CH:11]=[CH:10][C:9](/[C:12](/[C:19]2[NH:24][C:23](=[O:25])[C:22]([Cl:26])=[CH:21][CH:20]=2)=[CH:13]\[CH:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)=[CH:8][CH:7]=1.C(=O)(O)[O-].[Na+].C(OCC)(=O)C>O.C(O)(=O)C>[Cl:26][C:22]1[C:23](=[O:25])[NH:24][C:19](/[C:12](/[C:9]2[CH:10]=[CH:11][C:6]([NH:5][C:2]([NH2:3])=[O:1])=[CH:7][CH:8]=2)=[CH:13]/[CH:14]2[CH2:15][CH2:16][CH2:17][CH2:18]2)=[CH:20][CH:21]=1
Reactant: Nc1ccc(/C(=C\C2CCCC2)c2ccc(Cl)c(=O)[nH]2)cc1
Reactant: N#C[O-]
Agent: O=C([O-])O
Agent: [K+]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Solvent: CCOC(C)=O
Product: NC(=O)Nc1ccc(/C(=C\C2CCCC2)c2ccc(Cl)c(=O)[nH]2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 21.3 %

Procedure:
A solution of potassium cyanate (41 mg) in water (2 mL) was added to a solution of 6-[(E)-1-(4-aminophenyl)-2-cyclopentylethenyl]-3-chloropyridin-2(1H)-one obtained in Example 1-105(1) (153 mg) in acetic acid (2 mL)-water (1 mL), and the mixture was stirred at room temperature for 30 minutes. Saturated aqueous sodium bicarbonate and ethyl acetate were sequentially added to the reaction solution. The organic layer was separated, washed with saturated aqueous sodium bicarbonate and brine and dried over sodium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform:methanol=9:1→8:2). This was powdered with ethyl acetate, and filtration operation gave the title compound as a light yellow powder (37 mg, 21%).
Reaction SMILES: N1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(Cl)(Cl)=O.[CH2:11]([Cl:13])Cl>>[CH2:11]([Cl:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:6][CH2:5][CH2:4][CH:3]=[CH2:2]
Reactant: ClCCl
Reactant: c1ccncc1
Solvent: O=S(Cl)Cl
Product: C=CCCCCCCCCCCl

Procedure:
A 1-liter, 3-neck flask equipped with a mechanical stirrer, reflux condenser, argon inlet and addition funnel was placed in an oil bath at 50° C. To the flask was added methylene chloride (400 milliliters), undecylenol (100 grams) and then pyridine (55.7 grams). Thionyl chloride (78.9 grams) in methylene chloride (100 milliliters) was added dropwise under reflux over 5 hours. The mixture was filtered, the solvent was removed from the filtrate using a rotary evaporator, and the resultant oil was refiltered and then distilled using a column packed with glass Raschig rings to yield two distillate portions. The fraction collected between 100° C. and 110° C. at 1 millimeter of mercury was retained and redistiiled using a Kugelrohr apparatus available from Aldrich. The yield of undecylenyl chloride was 40 grams of oil collected between 80° C. and 85° C. at 1 millimeter of mercury, which was identified using 13C NMR spectrometry.
Reaction SMILES: [CH:1]1([N:4]2[C:13]3[C:8](=[C:9]([CH3:16])[C:10]([F:15])=[C:11](Br)[CH:12]=3)[C:7](=[O:17])[C:6]([C:18]([OH:20])=[O:19])=[CH:5]2)[CH2:3][CH2:2]1.[O:21]=[C:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1>CN1CCCC1=O>[CH:1]1([N:4]2[C:13]3[C:8](=[C:9]([CH3:16])[C:10]([F:15])=[C:11]([N:25]4[CH2:26][CH2:27][C:22](=[O:21])[CH2:23][CH2:24]4)[CH:12]=3)[C:7](=[O:17])[C:6]([C:18]([OH:20])=[O:19])=[CH:5]2)[CH2:3][CH2:2]1
Reactant: Cc1c(F)c(Br)cc2c1c(=O)c(C(=O)O)cn2C1CC1
Reactant: O=C1CCNCC1
Solvent: CN1CCCC1=O
Product: Cc1c(F)c(N2CCC(=O)CC2)cc2c1c(=O)c(C(=O)O)cn2C1CC1
Temperature: 90 °C
Yield: 37.6 %

Procedure:
To a solution of 1-cyclopropyl-6-fluoro-7-bromo-5-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (0.58 g) in N-methyl-2-pyrrolidone (5 ml) is added 4-oxopiperidine (0.64 g) and the mixture is heated at 90° C. for 20 minutes. The solvent is distilled off under reduced pressure. To the resulting residue is added ethanol and the precipitated crystals are filtered to give 1-cyclopropyl-6-fluoro-7-(4-oxo-1-piperidinyl)-5-methyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (230 mg).
Reaction SMILES: [NH2-].[Na+].[CH:3]1[C:13]2[CH2:12][CH2:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=3[NH:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.[CH:18]([N:21]1[CH2:26][CH2:25][O:24][CH:23]([CH2:27]Cl)[CH2:22]1)([CH3:20])[CH3:19].O>C1C=CC=CC=1>[CH:18]([N:21]1[CH2:26][CH2:25][O:24][CH:23]([CH2:27][N:8]2[C:9]3[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=3[CH2:11][CH2:12][C:13]3[CH:3]=[CH:4][CH:5]=[CH:6][C:7]2=3)[CH2:22]1)([CH3:20])[CH3:19]
Reactant: c1ccc2c(c1)CCc1ccccc1N2
Reactant: CC(C)N1CCOC(CCl)C1
Agent: [NH2-]
Agent: [Na+]
Solvent: c1ccccc1
Solvent: O
Product: CC(C)N1CCOC(CN2c3ccccc3CCc3ccccc32)C1

Procedure:
To a suspension of sodium amide (0.5 g) in benzene was added a solution of 10,11-dihydro-5H-dibenz[b,f]azepine (1.0 g) in benzene at room temperature, and the resulting mixture was stirred under reflux for 1 hour. After cooling, a solution of 4-isopropyl-2-chloromethylmorpholine (1.0 g) in benzene was added to the reaction mixture at room temperature, and the resulting mixture was stirred at room temperature for 1 hour and refluxed for 20 hours with stirring. The reaction mixture was cooled and admixed with water. The benzene layer was separated, washed with water, dried over anhydrous magnesium sulfate and evaporated to afford 5-(4-isopropyl-2-morpholinylmethyl)-10,11-dihydro-5H-dibenz[b,f]azepine as an oily substance. M.P. 203.5° -- 204.5° C (oxalate).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH:14]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:15]([N:17]([CH2:20][CH3:21])[CH2:18][CH3:19])=[O:16])[CH2:10][CH2:9]2)=[C:4]([F:28])[CH:3]=1.[N:29]([C:32]1[C:33]([CH3:38])=[N:34][O:35][C:36]=1[CH3:37])=[C:30]=[O:31]>ClCCCl>[CH3:38][C:33]1[C:32]([NH:29][C:30](=[O:31])[NH:1][C:2]2[CH:7]=[CH:6][C:5]([N:8]3[CH2:13][CH2:12][N:11]([CH:14]([C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[C:15]([N:17]([CH2:18][CH3:19])[CH2:20][CH3:21])=[O:16])[CH2:10][CH2:9]3)=[C:4]([F:28])[CH:3]=2)=[C:36]([CH3:37])[O:35][N:34]=1
Reactant: Cc1noc(C)c1N=C=O
Reactant: CCN(CC)C(=O)C(c1ccccc1)N1CCN(c2ccc(N)cc2F)CC1
Solvent: ClCCCl
Product: CCN(CC)C(=O)C(c1ccccc1)N1CCN(c2ccc(NC(=O)Nc3c(C)noc3C)cc2F)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 63.8 %

Procedure:
A mixture of 2-[4-(4-amino-2-fluoro-phenyl)-piperazin-1-yl]-N,N-diethyl-2-phenyl-acetamide (0.30 mmol) and 4-isocyanato-3,5-dimethyl-isoxazole (1.0 mmol) in DCE (10 mL) was stirred at rt for 16 h. The solid that had formed was collected by filtration and dried under vacuum to give the title compound (100 mg, 64%). MS (ESI): mass calcd. for C28H35FN6O3, 522.28. m/z found, 523.4 [M+H]+. 1H NMR (CDCl3): 8.60-8.40 (br s, 1H), 7.60-7.25 (m, 6H), 6.78-6.71 (m, 1H), 6.68-6.57 (m, 1H), 4.21 (s, 1H), 3.60-3.40 (m, 2H), 3.39-3.15 (m, 2H), 2.95-2.45 (m, 8H), 2.24 (s, 3H), 2.13 (s, 3H), 1.11 (t, J=7.1, 3H), 1.05 (t, J=7.1, 3H).
Reaction SMILES: [NH2:1][C:2]1[C:3]([F:23])=[CH:4][C:5]([Br:22])=[C:6]([C:8]2[C:9](=[O:21])[N:10]([CH3:20])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([NH:18][CH3:19])[CH:12]=3)[CH:7]=1.[C:24]1([N:30]=[C:31]=[O:32])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C(Cl)Cl>[Br:22][C:5]1[C:6]([C:8]2[C:9](=[O:21])[N:10]([CH3:20])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([NH:18][CH3:19])[CH:12]=3)=[CH:7][C:2]([NH:1][C:31]([NH:30][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:32])=[C:3]([F:23])[CH:4]=1
Reactant: O=C=Nc1ccccc1
Reactant: CNc1cc2c(cn1)cc(-c1cc(N)c(F)cc1Br)c(=O)n2C
Solvent: ClCCl
Product: CNc1cc2c(cn1)cc(-c1cc(NC(=O)Nc3ccccc3)c(F)cc1Br)c(=O)n2C
Temperature: 25 °C
Reaction time: 12 h
Yield: 42.6 %

Procedure:
A solution of 3-(5-amino-2-bromo-4-fluoro-phenyl)-1-methyl-7-methylamino-1H-[1,6]naphthyridin-2-one (420 mg, 1.16 mmol) in DCM (25 mL) was treated with phenyl isocyanate (0.19 g, 1.62 mmol) and TEA (0.326 g, 3.23 mmol) and stirred at RT for 12 h. The mixture was concentrated under reduced pressure and washed with MTBE (1×). The crude product was purified by prep-HPLC separation (MeCN/H2O with 0.1% TFA) to give 1-(4-bromo-2-fluoro-5-(1-methyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)phenyl)-3-phenylurea (245 mg, 44% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.08 (s, 1H), 8.67 (s, 1H), 8.40 (s, 1H), 8.17 (d, J=8.8 Hz, 1H), 7.70 (s, 1H), 7.64 (d, J=10.8 Hz, 1H), 7.40 (d, J=7.6 Hz, 2H), 7.28-7.24 (t, J=7.6 Hz, 2H), 7.04-7.03 (m, 1H), 6.98-6.94 (t, J=8 Hz, 1H), 6.17 (s, 1H), 3.50 (s, 3H), 2.85 (d, J=4.8 Hz, 3H).
Reaction SMILES: C([Li])CCC.[C:6](#[N:8])[CH3:7].F[C:10]1[C:15]([I:16])=[CH:14][CH:13]=[CH:12][N:11]=1.CCOC(C)=O.CCCCCC>C1COCC1>[I:16][C:15]1[C:10]([CH2:7][C:6]#[N:8])=[N:11][CH:12]=[CH:13][CH:14]=1
Reactant: Fc1ncccc1I
Reactant: CC#N
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: C1CCOC1
Product: N#CCc1ncccc1I
Temperature: -78 °C
Reaction time: 0.75 h
Yield: 33.5 %

Procedure:
To a solution of n-butyllithium (11 mL, 27 mmol) in dry THF (150 mL) at −78° C., was added dry ACN (2 mL, 29 mmol). The resulting mixture was stirred at −78° C. for 45 minutes to generate a suspension of lithionitrile. 2-Fluoro-3-iodopyridine (5 g, 22 mmol) was added as a solution in 10 mL of THF, and the yellow mixture was allowed to warm slowly to room temperature. By the time that the temperature reached −19° C., the reaction had turned dark green. After 35 minutes (reaction temperature=−7° C.), TLC (0-30% EtOAc/hexane) showed a new lower spot and a trace of starting material. LCMS showed the desired mass ((M+H)+=245). The reaction was quenched with saturated NH4Cl and extracted with EtOAc. The combined organic layers were washed 3 times with saturated NH4Cl and brine, and then dried over MgSO4 and concentrated in vacuo to give a dark solid. The resulting product was purified by silica flash chromatography (0-50% EtOAc/hexane and then 10% MeOH/DCM) to give the title compound as a dark yellow solid (1.8 g, 33%). MS (m/z)=245 (M+H)+. Calculated for C7H5IN2 244.0.
Reaction SMILES: [F:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][CH2:7][CH2:8][C:9]2[CH:28]=[CH:27][C:12]([CH2:13][N:14]3[CH2:19][CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16][CH2:15]3)=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.Cl>CCO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH2:7][CH2:8][C:9]2[CH:28]=[CH:27][C:12]([CH2:13][N:14]3[CH2:15][CH2:16][NH:17][CH2:18][CH2:19]3)=[CH:11][CH:10]=2)=[CH:29][CH:30]=1
Reactant: CC(C)(C)OC(=O)N1CCN(Cc2ccc(CCOc3ccc(F)cc3)cc2)CC1
Agent: Cl
Solvent: CCO
Product: Fc1ccc(OCCc2ccc(CN3CCNCC3)cc2)cc1
Temperature: 40 °C
Reaction time: 3 h
Yield: 82.1 %

Procedure:
To an EtOH (25 mL) solution of tert-butyl 4-{4-[2-(4-fluorophenoxy)ethyl]-benzyl}piperazine-1-carboxylate (2.36 g) was added 6 M HCl (9.49 mL) at room temperature. After stirring at 40° C. for 3 hours, the solvent was removed under reduced pressure. The resulting precipitate was collected by filtration, and dissolved in water. The solution was alkalified with 5 M NaOH, and extracted with CH2Cl2. The organic layer was washed with saturated aqueous NaCl, dried over anhydrous MgSO4, and concentrated under reduced pressure to afford 1-{4-[2-(4-fluorophenoxy)ethyl]benzyl}piperazine as a colorless oil (1.47 g).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=O)[C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1)#[N:2].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:28])=CC=1>C1(C)C=CC=CC=1>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[S:28])[C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1)#[N:2]
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: Cc1ccc(C(=O)Nc2ccc(C#N)cc2)cc1
Solvent: Cc1ccccc1
Product: Cc1ccc(C(=S)Nc2ccc(C#N)cc2)cc1
Temperature: 25 °C
Yield: 135.4 %

Procedure:
The compound (1.26 g) obtained in Example 43-1 was dissolved in toluene (20 ml) and added with a Lawesson's reagent (1.29 g) and the whole was refluxed under heating for 2 hours. The reaction solution was cooled to room temperature and the precipitated solid was filtrated out. The resultant solid was subjected to recrystallization (methanol), thereby obtaining the subject compound (1.09 g) as a yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:22]=[C:23]([Cl:26])[C:24]=1[F:25])[C:5]([N:8]([CH2:18][C:19](=O)[CH3:20])[C:9](=[O:17])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([CH3:7])[CH3:6].[OH-].[K+]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:22]=[C:23]([Cl:26])[C:24]=1[F:25])[C:5]([N:8]1[CH2:18][C:19]([CH3:20])=[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:9]1=[O:17])([CH3:7])[CH3:6]
Reactant: CC(=O)CN(C(=O)Cc1ccccc1)C(C)(C)c1cc(Cl)c(F)c(Cl)c1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: CC1=C(c2ccccc2)C(=O)N(C(C)(C)c2cc(Cl)c(F)c(Cl)c2)C1
Yield: 66.1 %

Procedure:
4.0 g (0.01 mol) of N-(3,5-dichloro-4-fluoro-α,α-dimethylbenzyl)-N-(2-oxopropyl)phenylacetamide prepared in accordance with the method of Reference Example 8, was dissolved in 50 ml of ethyl alcohol, and 0.5 g (0.009 mol) of potassium hydroxide powder was added thereto. The mixture was refluxed under heating for 10 minutes. Then, the solvent was distilled off under reduced pressure, and water was added thereto and extracted with ethyl acetate. The ethyl acetate layer was dried over an hydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure, followed by purification by silica gal column chromatography (n-hexane/ethyl acetate) to obtain 2.5 g (yield: 67.5%) of the desired compound as colorless crystals
Reaction SMILES: Cl.[C:2]([C:5]1([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[CH2:10][CH2:9][CH2:8][NH:7][CH2:6]1)(=[O:4])[CH3:3].C(=O)(O)[O-].[Na+].[CH2:24](Cl)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>C(#N)C>[CH2:24]([N:7]1[CH2:8][CH2:9][CH2:10][C:5]([C:2](=[O:4])[CH3:3])([CH2:11][C:12]2[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=2)[CH2:6]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: CC(=O)C1(Cc2ccc(Cl)cc2)CCCNC1
Reactant: ClCc1ccccc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Product: CC(=O)C1(Cc2ccc(Cl)cc2)CCCN(Cc2ccccc2)C1
Temperature: 25 °C
Yield: 59.2 %

Procedure:
A suspension of 3-Acetyl-3-(4-Chlorobenzyl)-piperidine hydrochloride (0.7 g, 2.43 mmol) in acetonitrile (20 mL) was treated with solid sodium bicarbonate (200 mg, 4.8 mmol) and benzyl chloride (369 mg, 2.9 mol) and heated to reflux for 2 hours. The reaction was then cooled to room temperature, poured into saturated aqueous sodium bicarbonate (200 mL) and extracted with ethyl acetate (3×100 mL). The combined organic extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated at reduced pressure. The residue was chromatographed on silica gel eluting with 2% methanol/chloroform to give 492 mg of the title compound. 1H NMR CDCl3 δ 7.40-7.25 (m, 5H), 7.22 (d,=8.5 Hz, 2H), 6.90 (d,=8.5 Hz, 2H), 3.45 (m, 2H), 3.00 (m, 1H), 2.80-2.50 (m, 3H), 2.20-1.90 (m, 4H), 2.00 (s, 3H), 1.60-1.50 (m, 2H), 1.30-1.10 (m, 1H).
Reaction SMILES: [OH-].[Li+].[Br:3][C:4]1[CH:5]=[C:6]([CH:20]=[CH:21][CH:22]=1)[O:7][C@H:8]([C:10]1[CH:19]=[CH:18][C:13]([C:14]([O:16]C)=[O:15])=[CH:12][CH:11]=1)[CH3:9]>CO.O>[Br:3][C:4]1[CH:5]=[C:6]([CH:20]=[CH:21][CH:22]=1)[O:7][C@H:8]([C:10]1[CH:19]=[CH:18][C:13]([C:14]([OH:16])=[O:15])=[CH:12][CH:11]=1)[CH3:9]
Reactant: COC(=O)c1ccc([C@H](C)Oc2cccc(Br)c2)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: C[C@H](Oc1cccc(Br)c1)c1ccc(C(=O)O)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 98 %

Procedure:
Lithium hydroxide (2 g, 83.3 mmol) was added to a solution of (S)-methyl 4-(1-(3-bromophenoxy)ethyl)benzoate (1.8 g, 5.4 mmol) in methanol (100 mL) and water (10 mL). The reaction mixture was stirred at room temperature for 3 hours. After the reaction, the solvent was removed in vacuo. 3 mol/L hydrogen chloride (aq) was added to make pH 2-3, and the product was extracted with dichloromethane. The combined organic phase was washed with Sodium Chloride (aq) (20 mL×3), dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give (S)-4-(1-(3-bromophenoxy)ethyl)benzoic acid (1.7 g, 98%).
Reaction SMILES: C([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([O:15][CH3:16])=[O:14])[CH:11]=2)[C:6](=[C:17](OCC)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:5]1=[O:27])(=O)C.[CH2:28]([N:30]([CH2:33][C:34]1[CH:40]=[CH:39][C:37]([NH2:38])=[CH:36][CH:35]=1)[CH2:31][CH3:32])[CH3:29]>>[CH2:28]([N:30]([CH2:33][C:34]1[CH:35]=[CH:36][C:37]([NH:38]/[C:17](=[C:6]2\[C:5](=[O:27])[NH:4][C:12]3[C:7]\2=[CH:8][CH:9]=[C:10]([C:13]([O:15][CH3:16])=[O:14])[CH:11]=3)/[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:39][CH:40]=1)[CH2:31][CH3:32])[CH3:29]
Reactant: CCN(CC)Cc1ccc(N)cc1
Reactant: CCOC(=C1C(=O)N(C(C)=O)c2cc(C(=O)OC)ccc21)c1ccccc1
Product: CCN(CC)Cc1ccc(N/C(=C2\C(=O)Nc3cc(C(=O)OC)ccc32)c2ccccc2)cc1

Procedure:
Prepared from 1-acetyl-3-(1-ethoxy-1-phenylmethylene)-6-methoxycarbonyl-2-indolinone and 4-(diethylamino-methyl)-aniline Rf value: 0.4 (silica gel, methylene chloride/methanol=10:1) C28H29N3O3
Reaction SMILES: OCC([C@H]([C@@H]([C@@H](CO)O)O)O)=O.OCC1(O[C@H](CO)[C@@H](O)[C@@H]1O)OC.[S:26](=[O:30])(=O)([OH:28])[OH:27].CO[CH:33](OC)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>CO>[C:34]1([CH3:33])[CH:39]=[CH:38][C:37]([S:26]([OH:28])(=[O:30])=[O:27])=[CH:36][CH:35]=1
Reactant: COC(OC)c1ccccc1
Reactant: O=S(=O)(O)O
Agent: COC1(CO)O[C@H](CO)[C@@H](O)[C@@H]1O
Agent: O=C(CO)[C@@H](O)[C@H](O)[C@H](O)CO
Solvent: CO
Product: Cc1ccc(S(=O)(=O)O)cc1

Procedure:
In step one, fructose is converted to methyl fructofuranoside by reaction in methanol using sulfuric acid as the catalyst; this reaction yields an anomeric mixture of methyl α,β-fructofuranosides. In step two, the 1- and 3-hydroxyl groups of the product of step one are protected by conversion to a benzylidene derivative. For example, reaction of the described anomeric mixture of methyl α,β-fructofuransides with benzaldehyde dimethylacetal and a proton source such as p-toluenesulfonic acid, yields methyl 1,3-O-benzylidene-α-D-fructofuranoside. In step three, the 6-hydroxy group of the product of step two is protected by conversion to a trialkylsilyl ether. For example, reaction of 1,3-O-benzylidene-α-D-fructofuranoside with t-butyldimethylsilyl chloride and imidazole yields the t-butyldimethylsilyl ether derivative methyl 1,3-O-benzylidene-6-O-t-butyldimethylsilyl-α-D-fructofuranoside. In step four, the 4-hydroxy group of the product of step three is replaced with a hydrogen atom. For example, reaction of 1,3-O-benzylidene-6-O-t-butyldimethylsilyl-α-D-fructofuranoside with thiocarbonyldiimidazole affords an intermediate which is then reacted with tri-n-butyl tin hydride and azo(bis)isobutyronitrile (AIBN) to yield the deoxy derivative, methyl 1,3-O-benzylidene-6-O-t-butyl-dimethylsilyl-4-deoxy-α-D-fructofuranoside. In step five, the trialkylsilyl group is removed from the 6-O-trialkysilyl ether of the product of step four, and the resulting 6-hydroxy group is esterified. For example, reaction of methyl 1,3-O-benzylidene-6-O-t-butyl-dimethylsilyl-4-deoxy-α-D-fructofuranoside with tetrabutylammonium fluoride affords the 6-hydroxy derivative, methyl 1,3-O-benzylidene-4-deoxy-α-D-fructofuranoside which is then reacted with benzoyl chloride to give the O-ester derivative, methyl 6-O-benzoyl-1,3-O-benzylidene-4-deoxy-α-D-fructofuranoside. Compounds of Formula II, which serve as intermediates to compounds of Formula I (when A is H), are produced in step six in which the 1,3-O-benzylidene group is removed giving a derivative with 1,3-dihydroxy groups. For example, reaction of 6-O-benzoyl-1,3-O-benzylidene-4-deoxy-α-D-fructofuranoside in an acidic medium such as an alcohol containing p-toluenesulfonic acid yields the methyl 6-O-benzoyl-4-deoxy-α,β-D-fructofuranoside. The α anomer, methyl 6-O-benzoyl-4-deoxy-α-D-fructofuranoside, and β anomer, methyl 6-O-benzoyl-4-deoxy-β-D-fructofuranoside, of the anomeric mixture obtained in step six may then be separated from each other and isolated in anomerically pure form by chromatography.