Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]#[C:10][C:11]2[CH:36]=[CH:35][C:14]([C:15]([N:17]([CH3:34])[C@:18]([CH3:33])([C:23]([NH:25][O:26][CH:27]3[CH2:32][CH2:31][CH2:30][CH2:29][O:28]3)=[O:24])[C:19]([NH:21][CH3:22])=[O:20])=[O:16])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1)=O.[CH:37]1([NH2:40])[CH2:39][CH2:38]1>>[CH:37]1([NH:40][CH2:1][C:3]2[CH:4]=[CH:5][C:6]([C:9]#[C:10][C:11]3[CH:12]=[CH:13][C:14]([C:15]([N:17]([CH3:34])[C@:18]([CH3:33])([C:23]([NH:25][O:26][CH:27]4[CH2:32][CH2:31][CH2:30][CH2:29][O:28]4)=[O:24])[C:19]([NH:21][CH3:22])=[O:20])=[O:16])=[CH:35][CH:36]=3)=[CH:7][CH:8]=2)[CH2:39][CH2:38]1
Reactant: NC1CC1
Reactant: CNC(=O)[C@@](C)(C(=O)NOC1CCCCO1)N(C)C(=O)c1ccc(C#Cc2ccc(C=O)cc2)cc1
Product: CNC(=O)[C@@](C)(C(=O)NOC1CCCCO1)N(C)C(=O)c1ccc(C#Cc2ccc(CNC3CC3)cc2)cc1
Yield: 62 %

Procedure:
From (2S)-2-[{4-[(4-formylphenyl)ethynyl]benzoyl}(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (0.30 g) as obtained in Example 16-(1) and cyclopropylamine (0.19 mL), there was obtained (2S)-2-{[4-({4-[(cyclopropylamino)methyl]phenyl}ethynyl)benzoyl](methyl)amino}-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (white solid) (0.20 g, 62%) in the same manner as in Example 16-(2).
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](N(OC)C)=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:20]([Mg]Br)[CH2:21][CH:22]=[CH2:23]>C1COCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:15])[CH2:23][CH2:22][CH:21]=[CH2:20])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C=CCC[Mg]Br
Reactant: CON(C)C(=O)C1CCN(Cc2ccccc2)CC1
Solvent: C1CCOC1
Product: C=CCCC(=O)C1CCN(Cc2ccccc2)CC1
Reaction time: 4 h
Yield: 58.3 %

Procedure:
A solution of 1-benzyl-N-methoxy-N-methylpiperidine-4-carboxamide (8.88 g, 33.0 mmol) in THF (40 mL, 0.8 M) was cooled to 0° C. and treated with a 0.5 M solution of 3-butenylmagnesium bromide (51 mmol, 102 mL) in a dropwise manner. After stirring for 4 h the reaction was quenched with 1 N HCl (24 mL), neutralized with 5% aqueous sodium bicarbonate and diluted with ethyl acetate. The layers were separated and the aqueous phase was extracted with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride, dried over MgSO4, and concentrated in vacuo. The residue was chromatographed on silica (2-20% methanol in dichloromethane) to afford the desired product (4.95 g, 57%). Rf 0.22 (10% MeOH/CH2Cl2). 1H NMR (CDCl3, 300 MHz) δ 7.38-7.21 (m, 5H), 5.82-5.76 (m, 1H), 5.15-4.95 (m, 2H), 3.50 (s, 2H), 2.91 (d, J=11.2 Hz, 2H), 2.54 (t, J=7.3 Hz, 2H), 2.39-2.23 (m, 3H), 2.06-1.97 (m, 2H), 1.82-1.61 (m, 4H). ESI MS found for C17H23NO m/z [258.2 (M+1)].
Reaction SMILES: [CH2:1]([N:3]1[C:8](=[O:9])[CH2:7][O:6][C:5]2[N:10]=[C:11]([C:20]3[CH:25]=[CH:24][C:23]([C:26]4([NH:30]C(=O)OC(C)(C)C)[CH2:29][CH2:28][CH2:27]4)=[CH:22][CH:21]=3)[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:13][C:4]1=2)[CH3:2]>C(O)(C(F)(F)F)=O>[NH2:30][C:26]1([C:23]2[CH:22]=[CH:21][C:20]([C:11]3[C:12]([C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)=[CH:13][C:4]4[N:3]([CH2:1][CH3:2])[C:8](=[O:9])[CH2:7][O:6][C:5]=4[N:10]=3)=[CH:25][CH:24]=2)[CH2:27][CH2:28][CH2:29]1
Reactant: CCN1C(=O)COc2nc(-c3ccc(C4(NC(=O)OC(C)(C)C)CCC4)cc3)c(-c3ccccc3)cc21
Solvent: O=C(O)C(F)(F)F
Product: CCN1C(=O)COc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)cc21
Reaction time: 0.01 h
Yield: 107.3 %

Procedure:
tert-Butyl 1-(4-(1-ethyl-2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutylcarbamate (7 mg, 0.014 mmol) was dissolved in TFA (2 mL) and stirred for 30 seconds. The solution was immediately concentrated to dryness under reduced pressure. The residue was dissolved in diethyl ether (˜2 mL) and concentrated to dryness under reduced pressure three times. The residue was then slurried in diethyl ether (2 mL) and after settling the supernatant solvent removed by pipette. This was repeated three times. The remaining solvent was removed by freeze drying overnight to give the desired compound as an off-white solid (6 mg, 83% yield). 1H-NMR (500 MHz, MeOD) δ 7.57 (1H, s), 7.42 (2H, d), 7.38 (2H, d), 7.28-7.35 (3H, m), 7.20-7.28 (2H, m), 4.95 (2H, s), 4.10 (2H, q), 2.68-2.85 (2H, m), 2.50-2.65 (2H, m), 2.15-2.30 (1H, m), 1.90-2.05 (1H, m), 1.30 (3H, t). LCMS (Method A) RT=4.04 min, M+2H4=401.18.
Reaction SMILES: [F:1][C:2]1([F:21])[CH2:6][N:5](C(OC(C)(C)C)=O)[C@H:4]([CH2:14][C:15](=[O:20])[CH:16]=[C:17]([CH3:19])[CH3:18])[CH2:3]1>C(O)=O>[F:21][C:2]1([F:1])[CH2:6][NH:5][C@H:4]([CH2:14][C:15](=[O:20])[CH:16]=[C:17]([CH3:18])[CH3:19])[CH2:3]1
Reactant: CC(C)=CC(=O)C[C@@H]1CC(F)(F)CN1C(=O)OC(C)(C)C
Solvent: O=CO
Product: CC(C)=CC(=O)C[C@@H]1CC(F)(F)CN1

Procedure:
A HCO2H (20 ml) solution of (R)-tert-butyl 4,4-difluoro-2-(4-methyl-2-oxopent-3-enyl)pyrrolidine-1-carboxylate (1.10 g, 3.6 mmol) was stirred at room temperature for 6 hours until only trace amount of SM was detected by LC-MS. Solvent was removed in vacuo with bath temperature≦23° C. Compound 1-((R)-4,4-difluoropyrrolidin-2-yl)-4-methylpent-3-en-2-one was obtained as a light brown oil and was used directly in next reaction.
Reaction SMILES: [CH3:1]C([O-])(C)C.[K+].[I-].C[S+](C)(C)=O.[C:13]1([C:19]([C:21]2[N:26]=[C:25]3[S:27][C:28]([C:30]([O-:32])=[O:31])=[N:29][C:24]3=[CH:23][CH:22]=2)=[CH2:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[Na+]>CS(C)=O.Cl>[C:13]1([C:19]2([C:21]3[N:26]=[C:25]4[S:27][C:28]([C:30]([OH:32])=[O:31])=[N:29][C:24]4=[CH:23][CH:22]=3)[CH2:1][CH2:20]2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CC(C)(C)[O-]
Reactant: C=C(c1ccccc1)c1ccc2nc(C(=O)[O-])sc2n1
Agent: C[S+](C)(C)=O
Agent: Cl
Agent: [I-]
Solvent: CS(C)=O
Product: O=C(O)c1nc2ccc(C3(c4ccccc4)CC3)nc2s1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
Potassium 2-methylpropan-2-olate (0.66 g, 5.9 mmol) was dissolved in anhydrous DMSO (19.5 mL) under argon. Trimethylsulfoxonium iodide (1.3 g, 5.9 mmol) was added to the resulting solution in one portion. After 10 min, this dissolved, and the resulting clear solution was added via cannula (over ˜2 min) to a suspension of sodium 5-(1-phenylvinyl)thiazolo[5,4-b]pyridine-2-carboxylate (1.19 g, 3.9 mmol) in DMSO (5 mL) at 25° C. The resulting solution was stirred at 25° C. for 1 h. The reaction solution was then diluted with 1.0N HCl (8.0 mL) and partitioned between dichloromethane (400 mL) and water (400 mL). The organic layer was separated, and the aqueous layer was extracted with additional dichloromethane (200 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo to afford crude 5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-carboxylic acid as a yellow oil. MS (ESI) m/z: Calculated: 296.1; Observed: 297.0 (M++1).
Reaction SMILES: [C:1]([CH2:3][C:4]([O:6][CH3:7])=[O:5])#[N:2].[H-].[Na+].[C:10]([O:20][CH3:21])(=[O:19])[CH:11]=[CH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.Cl>C1(C)C=CC=CC=1.CO>[C:1]([CH:3]([CH:12]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:11][C:10]([O:20][CH3:21])=[O:19])[C:4]([O:6][CH3:7])=[O:5])#[N:2]
Reactant: COC(=O)CC#N
Reactant: COC(=O)C=Cc1ccccc1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CO
Product: COC(=O)CC(c1ccccc1)C(C#N)C(=O)OC
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a mixed solution of 5 g of methyl cyanoacetate, 20 mL of methanol, and 20 mL of toluene was added 1.61 g of sodium hydride (55% oil-dispersion) under ice-cooling. After stirring at room temperature for 30 minutes, to the reaction mixture was added 3.24 mL of methyl cinnamate, followed by stirring at 66° C. for 15 hours. The reaction mixture was cooled to room temperature, and 1 M hydrochloric acid was then added thereto to adjust the pH of the solution to about 7. After extraction with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 5.19 g of dimethyl 2-cyano-3-phenylpentanedioate.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:21][CH2:22][CH2:23][C@@H:24]3[CH2:29][CH2:28][CH2:27][CH2:26][NH:25]3)=[C:7]([C:13]3[CH:18]=[C:17]([CH3:19])[CH:16]=[C:15]([CH3:20])[CH:14]=3)[C:8](=[O:12])[NH:9]2)=[CH:4][C:3]=1[NH:30][C:31]([C:33]1[CH:38]=[CH:37][N:36]=[CH:35][N:34]=1)=[O:32].C=O.[C:41](O)(=O)C.C([BH3-])#N.[Na+]>CO.O1CCCC1>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:21][CH2:22][CH2:23][C@@H:24]3[CH2:29][CH2:28][CH2:27][CH2:26][N:25]3[CH3:41])=[C:7]([C:13]3[CH:18]=[C:17]([CH3:19])[CH:16]=[C:15]([CH3:20])[CH:14]=3)[C:8](=[O:12])[NH:9]2)=[CH:4][C:3]=1[NH:30][C:31]([C:33]1[CH:38]=[CH:37][N:36]=[CH:35][N:34]=1)=[O:32]
Reactant: CC(=O)O
Reactant: Cc1cc(C)cc(-c2c(OCC[C@@H]3CCCCN3)c3cc(NC(=O)c4ccncn4)c(Cl)cc3[nH]c2=O)c1
Agent: C=O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: Cc1cc(C)cc(-c2c(OCC[C@@H]3CCCCN3C)c3cc(NC(=O)c4ccncn4)c(Cl)cc3[nH]c2=O)c1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To a solution of pyrimidine-4-carboxylic acid (S)-[7-chloro-3-(3,5-dimethylphenyl)-2-oxo-4-(2-piperidin-2-yl-ethoxy)-1,2-dihydroquinolin-6-yl]-amide (prepared essentially as described in EXAMPLE 2, 9 mg in 0.40 mL methanol) was added 6 mg paraformaldehyde followed by 20 mg powdered 4A molecular sieves and 0.01 mL acetic acid and the mixture stirred at room temperature for 10 minutes. At this time, 5 mg sodium cyanoborohydride was added and the stirring continued. After 2 hours, 0.5 mL tetrahydrofuran was added to ensure homogeneity and after 60 hours the reaction was quenched by the addition of water. The reaction mixture was extracted with methylene chloride and the combined organics washed with brine and dried over sodium sulfate. Purification of the concentrate by flash chromatography on silica gel (methylene chloride:10% ammonium hydroxide in methanol, 95:5; then 92:8) gave the title compound (6.7 mg). MASS: 546 (M+H) ##STR167##
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[NH2:7][C:8]1[C:18]([Cl:19])=[CH:17][C:11]([C:12](OCC)=[O:13])=[C:10]([O:20][CH3:21])[CH:9]=1>O1CCCC1>[NH2:7][C:8]1[C:18]([Cl:19])=[CH:17][C:11]([CH2:12][OH:13])=[C:10]([O:20][CH3:21])[CH:9]=1
Reactant: CCOC(=O)c1cc(Cl)c(N)cc1OC
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1cc(N)c(Cl)cc1CO
Temperature: 0 °C

Procedure:
To a solution of lithium aluminium hydride (0.96 g, 0.025 mol) in tetrahydrofuran (100 mL) was added dropwise at room temperature a solution of ethyl 4-amino-5-chloro-2-methoxybenzoate (intermediate 37; 4.4 g, 0.019 mol) in tetrahydrofuran (25 mL). Then the mixture was refluxed for 2 hours. The excess of hydride was destroyed by successive addition of 1 ml of water, 1 ml of 4N NaOH solution and 2 ml of water, filtered through celite and washed with ethyl acetate. The organic solvent was reduced and hexane was added. The mixture was cooled at 0° C. during 1 hour and then the precipitate was filtrated and washed with hexane. The title compound was obtained as a pale yellow solid (80%) which was used in the next step without further purification.
Reaction SMILES: [NH2:1][C:2]1[C:10]([Br:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].Cl.CN.[CH3:15][N:16](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>CN(C=O)C.CCOC(C)=O>[NH2:1][C:2]1[C:10]([Br:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:16][CH3:15])=[O:5]
Reactant: Nc1c(Br)cccc1C(=O)O
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: CN
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CNC(=O)c1cccc(Br)c1N
Temperature: 25 °C
Reaction time: 1 h
Yield: 49.7 %

Procedure:
A yellow mixture of 2-amino-3-bromobenzoic acid (Oakwood Products, Inc., West Columbia, S.C., 2.07 g, 9.58 mmol), methanamine hydrochloride (0.712 g, 10.54 mmol), 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate (V) (4.37 g, 11.50 mmol), and Et3N (3.07 mL, 22.04 mmol) in DMF (19.16 mL) was stirred at RT for 1 h. The reaction mixture was diluted with EtOAc (200 mL), added to a separatory funnel, and washed with saturated aqueous NaHCO3 (2×100 mL); the organic layer was separated, dried over Na2SO4, and concentrated. The crude product in DCM was loaded onto the column and was purified via automated flash chromatography (silica gel) with 0-40% EtOAc in hexanes to give 2-amino-3-bromo-N-methylbenzamide (722a, 1.09 g, 4.76 mmol, 50% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 2.97 (d, J=4.89 Hz, 3H) 6.06 (br. s., 3H) 6.52 (t, J=7.92 Hz, 1H) 7.26 (dd, J=7.82, 1.17 Hz, 1H) 7.50 (dd, J=7.92, 1.27 Hz, 1H). MS (ESI, pos. ion) m/z: 228.9/230.9 (M+1).
Reaction SMILES: FC(F)(F)C(O)=O.[Si:8]([O:25][CH2:26][CH2:27][C:28]1([F:41])[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29]1)([C:21]([CH3:24])([CH3:23])[CH3:22])([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.N>ClCCl>[Si:8]([O:25][CH2:26][CH2:27][C:28]1([F:41])[CH2:29][CH2:30][NH:31][CH2:32][CH2:33]1)([C:21]([CH3:24])([CH3:22])[CH3:23])([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CC(C)(C)OC(=O)N1CCC(F)(CCO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)CC1
Agent: N
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(C)(C)[Si](OCCC1(F)CCNCC1)(c1ccccc1)c1ccccc1
Temperature: 0 °C
Reaction time: 5 h

Procedure:
2.80 ml (37.06 mmol) of trifluoroacetic acid are added slowly to a solution of 3 g (6.17 mmol) of tert-butyl 4-(2-{[tert-butyldiphenylsilyl]oxy}ethyl)-4-fluoro-1-piperidinecarboxylate, obtained in step 12.3, in 20 ml of dichloromethane. Stirring is continued at room temperature for 5 hours. The reaction mixture is poured into a mixture of ice-water and 28% aqueous ammonia. The phases are separated by settling, the aqueous phase is extracted twice with dichloromethane and the combined organic phases are washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated under reduced pressure.
Reaction SMILES: B.CSC.[OH:5][C@H:6]([C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1)[CH2:7][NH:8][C:9]([C@H:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([I:21])[CH:17]=2)[O:12]1)=O>O1CCCC1>[I:21][C:16]1[CH:17]=[C:18]2[C:13](=[CH:14][CH:15]=1)[O:12][C@@H:11]([CH2:9][NH:8][CH2:7][C@@H:6]([C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1)[OH:5])[CH2:20][CH2:19]2
Reactant: O=C(NC[C@H](O)c1cccnc1)[C@H]1CCc2cc(I)ccc2O1
Agent: B
Solvent: CSC
Solvent: C1CCOC1
Product: O[C@@H](CNC[C@H]1CCc2cc(I)ccc2O1)c1cccnc1
Temperature: 0 °C

Procedure:
Borane-dimethylsulfide complex (2.0 M in tetrahydrofuran, 46 mL, 92 mmol) was added dropwise (20 minutes) to a cooled (0° C.) and stirred solution of (2R)-N-[(2R)-2-hydroxy-2-(3-pyridinyl)ethyl]-6-iodo-3,4-dihydro-2H-chromene-2-carboxamide (Example 35, Method A, 7.75 g, 18.3 mmol) in tetrahydrofuran (300 mL). The solution was warmed to reflux for 1 hour and then cooled to room temperature. The reaction was quenched with addition of methanol (12 mL) and 2 M hydrochloric acid (95 mL), and then the resulting solution was heated at reflux for 1 hour. The reaction was cooled to room temperature and then the solution was adjusted to pH 9 using 1 M aqueous sodium hydroxide. The mixture was diluted with brine (500 mL) and the layers were separated. The aqueous layer was extracted with ethyl acetate (2×200 mL) and then the combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. Flash chromatography of the residue over silica gel using 30-50% ethyl acetate/hexane afforded product (6.32 g, 84%) as a waxy yellow solid: 1H NMR (acetone-d6, δ): 8.59 (d, J=1.9 Hz, 1 H), 8.44 (dd, J=5.0, 1.5 Hz, 1 H), 7.77 (ddd, J=8.0, 1.8, 1.8 Hz, 1 H), 7.25-7.39 (m, 3 H), 6.56 (d, J=8.4 Hz, 1 H), 4.80 (dd, J=8.4, 4.0 Hz, 1 H), 4.08-4.18 (m, 1 H), 2.67-3.00 (m, 10 H), 1.67-1.82 (m, 1 H); mass spectroscopy gave m/z=410.9 [M+H]+.
Reaction SMILES: CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[NH2:23][C:24]1[C:29]2=[C:30]([C:42]3[CH:47]=[CH:46][C:45]([NH:48][C:49]([NH:51][C:52]4[CH:57]=[C:56]([C:58]([F:61])([F:60])[F:59])[CH:55]=[CH:54][N:53]=4)=[O:50])=[CH:44][CH:43]=3)[C:31]([CH2:40][OH:41])=[C:32]([CH2:33][N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[N:28]2[N:27]=[CH:26][N:25]=1>CS(C)=O.CCOC(C)=O>[NH2:23][C:24]1[C:29]2=[C:30]([C:42]3[CH:43]=[CH:44][C:45]([NH:48][C:49]([NH:51][C:52]4[CH:57]=[C:56]([C:58]([F:60])([F:61])[F:59])[CH:55]=[CH:54][N:53]=4)=[O:50])=[CH:46][CH:47]=3)[C:31]([CH:40]=[O:41])=[C:32]([CH2:33][N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[N:28]2[N:27]=[CH:26][N:25]=1
Reactant: Nc1ncnn2c(CN3CCOCC3)c(CO)c(-c3ccc(NC(=O)Nc4cc(C(F)(F)F)ccn4)cc3)c12
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: Nc1ncnn2c(CN3CCOCC3)c(C=O)c(-c3ccc(NC(=O)Nc4cc(C(F)(F)F)ccn4)cc3)c12
Reaction time: 1 h
Yield: 74.8 %

Procedure:
Dess-Martin periodinane (703.6 mg, 1.66 mmol) was added to a stirring solution of Example 62 (600 mg, 1.11 mmol) dissolved in DMSO (3 mL). After 1 hour HPLC indicated that the reaction was complete. The reaction was diluted with EtOAc (200 mL) washed with aq. Sodium thiosulfate solution (2M) (2×), and saturated NaHCO3 solution (2×). The organic layer was dried (Na2SO4) and concentrated to give a brown powder which was triturated with 10% Et2O/Hexanes to afford 450 mg (0.83 mmol, 75.3%) of the title compound. 1H-NMR (DMSO-d6). δ 10.00 (s, 1H), 9.95 (s, 1H), 9.84 (s, 1H), 8.60 (d, J=5.4 Hz, 1H), 8.12 (s, 1H), 8.07 (s, 1H), 7.89 (d, J=8.7 Hz, 2H), 7.49 (d, J=8.4 Hz, 2H), 7.43 (d, J=5.1 Hz, 1H), 4.18 (s, 2H), 3.57-3.54 (m, 4H), 2.55-2.51 MS [M+H]+=541; LCMS RT=2.50 min.
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]23[CH2:23][CH:16]([C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][C:22]=42)[C:15]2[C:10]3=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:4][CH2:3]1.[Cl:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[CH2:31][C:32](O)=[O:33]>>[CH:21]1[C:22]2[C:9]3([CH2:8][N:5]4[CH2:6][CH2:7][CH:2]([NH:1][C:32](=[O:33])[CH2:31][C:26]5[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=5[Cl:24])[CH2:3][CH2:4]4)[CH2:23][CH:16]([C:15]4[C:10]3=[CH:11][CH:12]=[CH:13][CH:14]=4)[C:17]=2[CH:18]=[CH:19][CH:20]=1
Reactant: O=C(O)Cc1ccccc1Cl
Reactant: NC1CCN(CC23CC(c4ccccc42)c2ccccc23)CC1
Product: O=C(Cc1ccccc1Cl)NC1CCN(CC23CC(c4ccccc42)c2ccccc23)CC1

Procedure:
Using a procedure similar to that described in Example 6 except starting with 4-amino-1-[9,10-dihydro-9,10-methanoanthracen-9-ylmethyl]piperidine and 2-chlorophenylacetic acid, the title compound was obtained as a pink solid (71%), mp 212.0°-14.0° C.; MS(CI): 457 (M+H); NMR (300 MHz,DMSO-d6): 1.38(m, 2H), 1.70(m, 2H), 2.28(m, 2H), 2.46(s, 2H), 2.93(m, 2H), 3.30(m,submerged, 2H), 3.54(m, 3H), 4.31(s, 1H), 6.87-6.96(m, 4H), 7.17-7.41(m, 8H), 7.96(d, 1H, J=7.7 Hz).
Reaction SMILES: [H-].[Na+].[CH2:3]([O:5][C:6](=[O:14])[C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)[CH3:4].[Br:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]Br>CN(C=O)C>[CH2:3]([O:5][C:6](=[O:14])[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][Br:15])=[CH:9][CH:8]=1)[CH3:4]
Reactant: CCOC(=O)c1ccc(O)cc1
Reactant: BrCCCCCCCCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1ccc(OCCCCCCCCCCBr)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 63.7 %

Procedure:
Sodium hydride (1.55 g, 61 mmol) was suspended in DMF (150 mL) under an atmosphere of nitrogen. Ethyl-4-hydroxybenzoate (11) (5.06 g, 30 mmol) was added as a solution in DMF (30 mL) via syringe which was then washed with DMF (2×5 mL). The reaction mixture was then stirred at room temperature under an atmosphere of nitrogen for 2 hours. After this time, 1,10-dibromodecane (30.84 g, 103 mmol) was added as a solution in DMF (50 mL) via syringe which was then washed with DMF (2×5 mL). The reaction mixture was then stirred at room temperature under nitrogen for 19 hours. The reaction was quenched with water (200 mL) and the organic fragments extracted with diethyl ether (4×150 mL), dried over MgSO4, and excess solvent removed in vacuo to form a colorless oil. This was purified by flash column chromatography using CH2Cl2/hexane (1:1) to CH2Cl2/hexane (3:1) as eluting solvents to form a white crystalline solid. This was recrystallized from ethanol to form 4-(10-bromo-decyloxy)-benzoic acid ethyl ester (7.38 g, 19.1 mmol, 63%). Rf 0.65 (CH2Cl2), mp 41-42° C. FTIR, νmax/cm−1 1 3023, 2927, 2855, 1708, 1604, 1509, 1468, 1390, 1367, 1312, 1252, 1155, 1018, 851, 772. 1H NMR (CDCl3, 250 MHz), δ/ppm 7.96 and 6.87 (both 2 H, m, Ar—H); 4.32 (2 H, q, 3J=7.1 Hz, −CH2CH3); 3.97 (2 H, t, 3J=6.5 Hz, —OCH2—); 3.38 (2 H, t, 3J=6.9 Hz, —CH2Br); 1.80 (4 H, m, —OCH2CH2— and —CH2CH2Br); 1.42-1.27 (15 H, m, alkyl C—H). 13C{1H} NMR (CDCl3, 63 MHz), δ/ppm 166.2 (C=O); 152.6 and 122.4 (quat. Ar C); 131.3 and 113.8 (Ar C—H); 67.9 and 60.4 (—OCH2—); 33.9, 32.6, 29.2, 29.1, 29.0, 28.9, 28.5, 28.0, 25.8 (CH2); 14.2 (—CH3) λmax/nm (ε/dm3mol−1cm−1) 257 (24641). HRMS (FAB), M+/z C19H30BrO3 (MH+) requires 385.1378, found 385.1374.
Reaction SMILES: [C:1]([NH:4][C@@H:5]1[C@@H:11]([OH:12])[C@H:10]([F:13])[C@@H:9]([CH2:14][OH:15])[O:8][CH:6]1[OH:7])(=[O:3])[CH3:2].[C:16]([O-:21])(=[O:20])[C:17]([CH3:19])=[O:18].[Na+].[N-]=[N+]=[N-].[Na+].[OH-].[Na+].C(N[C@H]1[C@H]([C@@H]([C@@H](CO)O)O)OC(O)(C(=O)O)C[C@@H]1O)(=O)C>O>[C:1]([NH:4][C@H:5]1[C@H:11]([C@H:10]([F:13])[C@@H:9]([CH2:14][OH:15])[OH:8])[O:12][C:17]([OH:18])([C:16](=[O:21])[OH:20])[CH2:19][C@@H:6]1[OH:7])(=[O:3])[CH3:2]
Reactant: CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](F)[C@@H]1O
Reactant: CC(=O)C(=O)[O-]
Agent: CC(=O)N[C@H]1[C@H]([C@H](O)[C@H](O)CO)OC(O)(C(=O)O)C[C@@H]1O
Agent: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: O
Product: CC(=O)N[C@H]1[C@H]([C@H](F)[C@H](O)CO)OC(O)(C(=O)O)C[C@@H]1O
Temperature: 20 °C
Reaction time: 96 h
Yield: 19.2 %

Procedure:
The compound (16) (1.241 g), sodium pyruvate (1.200 g) and sodium azide (4.3 mg) were dissolved in distilled water (4.3 ml) and the pH of the resulting solution was adjusted to 10.59 by 2N sodium hydroxide. To this solution, 4.3 mg (112 U) of N-acetyl-neuraminic acid aldolase (NAL-300, manufactured by Toyobo Co., Ltd.) was added, followed by stirring mildly at 20° C. for 4 days. Thereafter, the reaction solution was desalted with an ion exchange resin (Dowex 50X8-200, H-type) and purified by an ion exchange chromatography (Dowex 1, HCOOH-type; aqueous 1.0M-HCOOH solution) to give 0.342 g of the candy-like titled compound (yield: 19.2%).
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1)=[CH2:2]>C(#N)C>[CH:2]#[C:1][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1
Reactant: C=Cc1ccc(O)cc1
Solvent: CC#N
Product: C#Cc1ccc(O)cc1

Procedure:
The same crude p-vinylphenol as used in Example 1 was subjected to azeotropic distillation with toluene without being subjected to vacuum flash distillation, to reduce the water content to 0.038%. A polymerization reaction was conducted in the same manner as in Example 1 except that 28.8 g of acetonitrile was added to 32.3 g of the above-obtained fraction. The reaction mixture was purified by the same reprecipitation as in Example 1, and the resulting precipitate was dried to obtain 6.5 g of a yellowish brown poly(p-vinylphenol). The polymer had a weight-average molecular weight (Mw) of 20,400, a number-average molecular weight (Mn) of 11,500, a light transmittance at a wavelength of 248 nm, of 68.0%, a light transmittance at a wavelength of 450 nm, of 83.2%, and a glass transition temperature of 177° C.