Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4](=[O:5])[C:2]1=[O:3].S(OOS([O-])(=O)=O)([O-])(=O)=[O:13].[K+].[K+].S(=O)(=O)(O)O>O>[O:5]=[C:4]1[C:2](=[O:3])[NH:1][C:11]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[O:13]1
Reactant: O=S(=O)([O-])OOS(=O)(=O)[O-]
Reactant: O=C1Nc2ccccc2C1=O
Agent: O=S(=O)(O)O
Agent: [K+]
Solvent: O
Product: O=c1[nH]c2ccccc2oc1=O
Reaction time: 24 h

Procedure:
14.7 parts of isatin are introduced into a suspension of 29 parts of potassium peroxydisulfate in 280 parts of 30% strength sulfuric acid at room temperature. The reaction mixture is then stirred for 24 hours without cooling, after which it is poured into water. The product is filtered off and dried, giving 11 parts of 2,3-dioxo-1,4-benzoxazine, of melting point 279°-283° C. (with decomposition).
Reaction SMILES: Br[C:2]1[C:7]([NH2:8])=[CH:6][C:5]([Br:9])=[CH:4][N:3]=1.[CH3:10][O:11][C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.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>[Br:9][C:5]1[CH:6]=[C:7]([NH2:8])[C:2]([C:15]2[CH:16]=[CH:17][C:12]([O:11][CH3:10])=[CH:13][CH:14]=2)=[N:3][CH:4]=1
Reactant: COc1ccc(B(O)O)cc1
Reactant: Nc1cc(Br)cnc1Br
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: COc1ccc(-c2ncc(Br)cc2N)cc1
Temperature: 90 °C
Reaction time: 19 h

Procedure:
A stirred mixture of 2,5-dibromopyridin-3-amine (860 mg, 3.41 mmol), 4-methoxyphenylboronic acid (519 mg, 3.41 mmol), trans-dichlorobis(triphenylphosphine)palladium (II) (120.5 mg, 0.17 mmol), and 2.0M sodium carbonate (5.1 mL, 10.2 mmol) in 1,4-dioxane (15 mL) was heated to 90° C. After 19 h, the reaction was cooled to rt then diluted with water. After extraction with EtOAc, the organic extraction was dried over anhydrous sodium sulfate. After filtration and concentration, the residue was purified on silica gel (0-20% EtOAc in hexanes) to afford a white solid as 5-bromo-2-(4-methoxyphenyl)pyridin-3-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.15 (1H, d, J=2.0 Hz), 7.65 (2H, m), 7.20 (1H, d, J=2.0 Hz), 7.06 (2H, m), 4.11 (5H, m).
Reaction SMILES: [CH3:1][C:2]1[C:6]([C:7]2[C:8](=[O:14])[NH:9][C:10](=[O:13])[NH:11][CH:12]=2)=[CH:5][S:4][N:3]=1.C(N(CC)CC)C.[CH:22]([CH:24]=[CH2:25])=[O:23]>CN(C)C=O>[CH3:1][C:2]1[C:6]([C:7]2[C:8](=[O:14])[NH:9][C:10](=[O:13])[N:11]([CH2:25][CH2:24][CH:22]=[O:23])[CH:12]=2)=[CH:5][S:4][N:3]=1
Reactant: Cc1nscc1-c1c[nH]c(=O)[nH]c1=O
Reactant: C=CC=O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1nscc1-c1cn(CCC=O)c(=O)[nH]c1=O
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
5-(3-methyl-4-isothiazolyl)-2,4(1H,3H)-pyrimidinedione (Pre 47, 0.126 mmol) was dissolved in N,N-Dimethylformamide (DMF) (1 ml). TRIETHYLAMINE (0.021 ml, 0.151 mmol) was added and the mixture was stirred at room temperature for 5 minutes. Acrolein (8.42 μl, 0.126 mmol) was added and the mixture was stirred at room temperature monitoring the reaction progression by LCMS. After 7 hrs Acrolein (3 μl) was added and the mixture was stirred at rt overnight.
Reaction SMILES: [CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([CH:16]=[O:17])=[N:13][C:12]=1[CH3:18])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S([CH2:29][N+:30]#[C-:31])(C1C=CC(C)=CC=1)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>CO>[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([C:16]2[O:17][CH:31]=[N:30][CH:29]=2)=[N:13][C:12]=1[CH3:18])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: [C-]#[N+]CS(=O)(=O)c1ccc(C)cc1
Reactant: Cc1nc(C=O)sc1C(=O)NCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: Cc1nc(-c2cnco2)sc1C(=O)NCc1ccccc1
Reaction time: 50 h
Yield: 63 %

Procedure:
To a solution of N-benzyl-2-formyl-4-methylthiazole-5-carboxamide (1.09 g, 4.17 mmol) in methanol (60 mL) was added tosylmethyl isocyanide (1.15 g, 5.88 mmol) and potassium carbonate (1.47 g, 10.69 mmol). The reaction mixture was stirred for 50 hours and concentrated in vacuo. The residue was diluted with chloroform and washed with water and brine. The organic solution was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography to afford the title compound in 63% yield (1.00 g): 1H NMR (300 MHz, CDCl3) δ 7.95 (s, 1H), 7.70 (s, 1H), 7.42-7.26 (m, 5H), 6.06 (t, J=5.6 Hz, 1H), 4.61 (d, J=5.6 Hz, 2H), 2.72 (s, 3H); MS (ES+) m/z 300.1 (M+1).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([OH:12])[CH:10]=2)[C:5]([CH3:13])=[N:4][N:3]=1.[CH2:14](Br)[C:15]#[CH:16].C([O-])([O-])=O.[K+].[K+].CC(C)=O>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH2:16][C:15]#[CH:14])[CH:10]=2)[C:5]([CH3:13])=[N:4][N:3]=1
Reactant: C#CCBr
Reactant: Cc1nnc(Cl)c2cc(O)ccc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CC(C)=O
Product: C#CCOc1ccc2c(C)nnc(Cl)c2c1
Temperature: 68 °C
Reaction time: 23 h
Yield: 55.4 %

Procedure:
The mixture of 4-chloro-6-hydroxy-1-methylphthalazine (5) (195 mg, 1.00 mmol), 80% propargyl bromide (1.30 mmol) in toluene (145 μL), K2CO3 (187 mg, 1.35 mmol), and acetone (8 mL) is stirred at 68° C. under argon for 23 h, then cooled to room temperature, and concentrated. The residue is diluted with H2O (50 mL) and extracted with ethyl acetate (70 mL and 60 mL). The extract is washed (brine) and dried. After solvent removal at reduced pressure, the residue is purified on silica gel (33% to 50% ethyl acetate/hexane) to give 129 mg (55%) of 6 as a light-yellow solid, mp 169-171° C. IR 3077, 1401, 1217 cm−1; 1H NMR (CDCl3) δ 2.66 (t, J=2.4 Hz, 1H, C≡CH), 2.97 (s, 3H, CH3), 4.96 (d, J=2.4 Hz, 2H, CH2C≡CH), 7.62 (dd, J=9.3, 2.7 Hz, 1H, 7-PhthH), 7.69 (d, J=2.7 Hz, 1H, 5-PhthH), 8.05 ppm (d, J=9.3 Hz, 1H, 8-PhthH).
Reaction SMILES: [CH2:1]([N:8]1[CH2:18][CH2:17][C:11]2[N:12]=[CH:13][N:14]=[C:15](Cl)[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:19][C:20]([F:29])([F:28])[C:21]1[N:26]=[CH:25][C:24]([NH2:27])=[CH:23][CH:22]=1.I.O>O1CCOCC1>[CH2:1]([N:8]1[CH2:18][CH2:17][C:11]2[N:12]=[CH:13][N:14]=[C:15]([NH:27][C:24]3[CH:25]=[N:26][C:21]([C:20]([F:29])([F:19])[F:28])=[CH:22][CH:23]=3)[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Clc1ncnc2c1CN(Cc1ccccc1)CC2
Reactant: Nc1ccc(C(F)(F)F)nc1
Agent: I
Solvent: O
Solvent: C1COCCO1
Product: FC(F)(F)c1ccc(Nc2ncnc3c2CN(Cc2ccccc2)CC3)cn1
Temperature: 130 °C
Yield: 95 %

Procedure:
6-Benzyl-4-chloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (0.5 g, 1.93 mmol) was dissolved in anhydrous dioxane (3 mL) and 6-trifluoromethylpyridin-3-ylamine was added (469 mg, 2.9 mmol), followed by HI/H2O (0.3 mL, 47%). The mixture was heated at 130° C. for 600 s in a Personal Chemistry microwave. The solvents were removed under vacuum and the residue was dissolved in ethyl acetate and washed with sat. NaHCO3 and brine. The organic layer was dried over Na2SO4, filtered and evaporated to give the product as an orange solid (700 mg, 95% crude). The crude product was used for the subsequent step.
Reaction SMILES: [CH:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-])=O)=[CH:7][C:6]=1[C:14]([F:17])([F:16])[F:15])([CH3:3])[CH3:2].C(O)(=O)C>[Fe].CO>[CH:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([NH2:11])=[CH:7][C:6]=1[C:14]([F:15])([F:16])[F:17])([CH3:3])[CH3:2]
Reactant: CC(C)Oc1ccc([N+](=O)[O-])cc1C(F)(F)F
Agent: [Fe]
Solvent: CC(=O)O
Solvent: CO
Product: CC(C)Oc1ccc(N)cc1C(F)(F)F

Procedure:
137.5 g of iron filings were added in portions to a refluxing mixture of 113.3 g of 2A, 1200 ml of 5% aqueous acetic acid and 50 ml of methanol. The resulting mixture was refluxed for one hour and filtered while hot. Work-up by either extraction of the cooled filtrate gave 4-isopropoxy-3-(trifluoromethyl)aniline (2B), as an amber oil.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([OH:9])=[C:4]([CH3:10])[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:17](Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN(C=O)C.O>[Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([O:9][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:4]([CH3:10])[CH:3]=1
Reactant: Cc1cc(Br)cc(C)c1O
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1cc(Br)cc(C)c1OCc1ccccc1
Reaction time: 6 h
Yield: 98.5 %

Procedure:
Dissolve 4-bromo-2,6-dimethyl-phenol (20.1 g, 100 mmol) in DMF (250 mL) under nitrogen. Add cesium carbonate (48.9 g, 150 mmol) and benzyl bromide (13.1 mL, 110 mmol) and heat at 70° C. stirring mechanically for 6 h. Dilute with water (400 mL) and extract with 3/1 diethyl ether/hexanes (2×400 mL). Wash combined organics with brine (300 mL) and then dry (MgSO4), filter and concentrate in vacuo to give 28.67 g (99%) of the title compound as an oil which solidified on standing. 1H NMR(CDCl3): δ7.51-7.37 (m, 5H), 7.22 (s, 2H), 4.82 (s, 2H), 2.31 (s, 6H).
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4](Cl)[N:3]=1.[CH3:12][O:13][C:14]1[CH:21]=[CH:20][C:17]([NH:18][CH3:19])=[CH:16][CH:15]=1>>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([N:18]([C:17]2[CH:20]=[CH:21][C:14]([O:13][CH3:12])=[CH:15][CH:16]=2)[CH3:19])[N:3]=1
Reactant: CNc1ccc(OC)cc1
Reactant: Clc1nc(Cl)c2nc[nH]c2n1
Product: COc1ccc(N(C)c2nc(Cl)nc3[nH]cnc23)cc1

Procedure:
The title compound was prepared from 2,6-dichloro-9H-purine (50 mg, 0.265) and 4-methoxy-N-methylaniline (40 mg, 0.291 mmol) by a procedure similar to example 1b and was isolated as off white powder (10 mg, 20%). 1H NMR (CDCl3): 7.81 (s, 1H), 7.37 (d, J=8.4 Hz, 2H), 7.04 (d, J=8.4 Hz, 2H), 3.93 (s, 3H), 3.77 (s, 3H).
Reaction SMILES: C(Cl)(=O)C([Cl:4])=O.[F:7][C:8]1[C:9]([NH:34][C@@H:35]([C:41]([CH3:44])([CH3:43])[CH3:42])[CH2:36][S:37](O)(=[O:39])=[O:38])=[CH:10][C:11]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([F:23])[CH:21]=3)[N:16]([S:24]([C:27]3[CH:33]=[CH:32][C:30]([CH3:31])=[CH:29][CH:28]=3)(=[O:26])=[O:25])[CH:15]=2)=[N:12][CH:13]=1.CN(C=O)C>ClCCl>[F:7][C:8]1[C:9]([NH:34][C@@H:35]([C:41]([CH3:44])([CH3:43])[CH3:42])[CH2:36][S:37]([Cl:4])(=[O:39])=[O:38])=[CH:10][C:11]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[C:20]([F:23])[CH:21]=3)[N:16]([S:24]([C:27]3[CH:33]=[CH:32][C:30]([CH3:31])=[CH:29][CH:28]=3)(=[O:26])=[O:25])[CH:15]=2)=[N:12][CH:13]=1
Reactant: O=C(Cl)C(=O)Cl
Reactant: Cc1ccc(S(=O)(=O)n2cc(-c3cc(N[C@H](CS(=O)(=O)O)C(C)(C)C)c(F)cn3)c3cc(F)cnc32)cc1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)n2cc(-c3cc(N[C@H](CS(=O)(=O)Cl)C(C)(C)C)c(F)cn3)c3cc(F)cnc32)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Oxalyl chloride (3.5 mL, 38.7 mmol) was added to a solution of (S)-2-(5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3yl)pyridin-4-ylamino)-3,3-dimethylbutane-1-sulfonic acid, 57a, (7.3 g, 12.9 mmol) in dichloromethane (130 mL), followed by the slow, dropwise addition of DMF (2 mL). The yellow colored solution was stirred at room temperature for 1 hour. The solvent was removed under reduced pressure to afford 8.4 g of the desired product as a foamy yellow solid: LC/MS (60-90% ACN/water 5 min with 0.9% FA) m/z 585.72 (M+H) RT=2.30 minutes.
Reaction SMILES: [CH2:1]([NH2:3])[CH3:2].Cl[SiH:5]1[N:9]([C:10]([CH3:17])([CH3:16])[CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:8]=[CH:7][N:6]1[C:18]([CH3:25])([CH3:24])[CH2:19][C:20]([CH3:23])([CH3:22])[CH3:21]>CCCCCC>[CH3:24][C:18]([N:6]1[CH:7]=[CH:8][N:9]([C:10]([CH3:17])([CH3:16])[CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])[SiH:5]1[NH:3][CH2:1][CH3:2])([CH3:25])[CH2:19][C:20]([CH3:23])([CH3:22])[CH3:21]
Reactant: CC(C)(C)CC(C)(C)N1C=CN(C(C)(C)CC(C)(C)C)[SiH]1Cl
Reactant: CCN
Solvent: CCCCCC
Product: CCN[SiH]1N(C(C)(C)CC(C)(C)C)C=CN1C(C)(C)CC(C)(C)C
Temperature: 25 °C
Reaction time: 12 h
Yield: 97 %

Procedure:
In an argon atmosphere, 6.80 g (151 mmol) of ethylamine was dissolved in 20 mL of hexane, and a solution obtained by dissolving 5.26 g (15.2 mmol) of Si(tOctNCHCHNtOct)(H)Cl in 10 mL of hexane was added thereto at −20° C. After stirring at room temperature for 12 hours, insoluble matters produced were separated by filtration, and the solvent was removed by distillation from the filtrate under atmospheric pressure. The obtained residue was distilled under reduced pressure (distillation temperature: 128° C./1.4×102 Pa) to obtain 1,3-bis(1,1,3,3-tetramethylbutyl)-2-ethylamino-1,3-diaza-2-silacyclopent-4-ene (Si(tOctNCHCHNtOct)(H)NHEt) as a pale yellow liquid (yielded amount: 5.22 g, yield: 97%).
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][C:6]([Br:9])=[CH:5][C:4]=1[C:10]([CH3:14])([CH3:13])[CH:11]=[O:12].Cl.N1C=CC=CC=1.Cl>CCOCC>[Br:9][C:6]1[CH:7]=[CH:8][C:3]2[O:2][CH:11]([OH:12])[C:10]([CH3:14])([CH3:13])[C:4]=2[CH:5]=1
Reactant: COc1ccc(Br)cc1C(C)(C)C=O
Agent: Cl
Solvent: c1ccncc1
Solvent: CCOCC
Product: CC1(C)c2cc(Br)ccc2OC1O
Temperature: 0 °C
Reaction time: 0.83 h

Procedure:
2-(2-Methoxy-5-bromophenyl)-2-methyl-1-propanal (30 g, 0.115 mole) was added to molten pyridine hydrochloride (60 g) and the mixture heated with stirring at 190°-200° C. for 50 minutes. Addition to ice-water containing a little hydrochloric acid and isolated through ether gave, after recrystallisation from petroleum ether (b.p. 80°-100° C.) 11.7 g (42%) title product m.p. 114°-5° C.
Reaction SMILES: [C:1]1([CH3:16])[CH:6]=[CH:5][C:4]([S:7]([NH:10][C@H:11]([C:13](O)=[O:14])[CH3:12])(=[O:9])=[O:8])=[CH:3][CH:2]=1.C(Cl)(=O)C([Cl:20])=O>CN(C)C=O.ClCCl>[S:7]([NH:10][C@H:11]([C:13]([Cl:20])=[O:14])[CH3:12])([C:4]1[CH:5]=[CH:6][C:1]([CH3:16])=[CH:2][CH:3]=1)(=[O:9])=[O:8]
Reactant: O=C(Cl)C(=O)Cl
Reactant: Cc1ccc(S(=O)(=O)N[C@@H](C)C(=O)O)cc1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)N[C@@H](C)C(=O)Cl)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
30.0 g of N-(p-toluenesulfonyl)-alanine and 6 to 7 drops of DMF (dimethylformamide) were dissolved in 100 ml of dichloromethane and 5 ml of oxalyl chloride was added dropwise. After stirring for 3 hours at room temperature the reaction mixture was evaporated down to an oily residue which was dissolved in 100 ml of dichloromethane. The dichloromethane was again evaporated and the resulting residue dissolved in 50 ml of dichloromethane followed by the addition of 100 ml hexane. After standing in the refrigerator overnight the crystals, so formed, were filtered and dried.
Reaction SMILES: [CH3:1][NH:2][C:3](=[O:6])[CH:4]=[CH2:5].C(N(CC)CC)C.[CH3:14][Si:15](Cl)([CH3:17])[CH3:16]>C(#N)C>[CH3:1][N:2]([Si:15]([CH3:17])([CH3:16])[CH3:14])[C:3](=[O:6])[CH:4]=[CH2:5]
Reactant: C=CC(=O)NC
Reactant: C[Si](C)(C)Cl
Solvent: CC#N
Solvent: CCN(CC)CC
Product: C=CC(=O)N(C)[Si](C)(C)C
Temperature: 25 °C
Reaction time: 6 h
Yield: 45 %

Procedure:
N-methylacrylamide (50.9 g, 0.6 mole) and triethylamine (67 g, 0.67 mole) were added to 300 mL of acetonitrile in a 500 mL round-bottomed flask. The reaction vessel was fitted with a reflux condenser topped with a rubber stopper that contained two needles, one connected to a source of nitrogen gas and other to an oil bubbler. A solution of trimethylsilyl chloride (72.4 g, 0.67 mole) in a 50 mL acetonitrile was added dropwise to this mixture. A white precipitate formed almost immediately. The amount of precipitate continued to increase throughout the addition and the color of the solution changed from colorless to orange. After the addition was completed, the resulting slurry was allowed to stir at room temperature for six hours. The mixture was filtered using vacuum filtration in a dry bag filled with nitrogen. The white precipitate was collected as a filter cake. NMR-T60 analysis indicated the filter cake was the triethylammonium chloride, the expected by-product. The orange colored filtrate concentrated in vacuo gave a dark red material. The crude mixture was subjected to vacuum fractional distillation. The first fraction distilled at 22°-35° C. at 0.3 mm Hg. NMR analysis showed it was mostly acetonitrile and a small amount of product. The second fraction distilled at 35°-45° C. at 0.3 mm Hg and appeared to be the desired pure product on NMR analysis. The third fraction distilled at 70°-80° C. at 0.3 mm Hg. NMR analysis showed it was N-methyl acrylamide. The pot contained uncharacterized polymerized material as a black viscous material. The reaction gave about 45% yield.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1O)[C:5]#[N:6].CC(C)[O-:13].[Ti+4:15].CC(C)[O-:18].CC(C)[O-].CC(C)[O-]>C1(C)C=CC=CC=1>[C:5]([C:4]1[CH:7]=[CH:8][CH:9]=[C:2]([O-:1])[C:3]=1[O-:13])#[N:6].[Ti+4:15].[C:5]([C:4]1[CH:7]=[CH:8][CH:9]=[C:2]([O-:1])[C:3]=1[O-:18])#[N:6]
Reactant: N#Cc1ccc(O)c(O)c1
Reactant: CC(C)[O-]
Agent: [Ti+4]
Solvent: Cc1ccccc1
Product: N#Cc1cccc([O-])c1[O-]
Temperature: 100 °C

Procedure:
A solution of 3,4-dihydroxybenzonitrile (5.00 g, 37.0 mmol) and toluene (45 ml) was dehydrated by distilling 5 mL of the solution. Thereafter, 5.25 g (18.5 mmol) of titanium(IV) isopropoxide (TTIP) was added to the solution while stirring. The mixed solution was refluxed for 1 hour, and then, while the distillation temperature was 100° C. or higher, distilled until the amount of the solution became half. After the distillation, solid content of the product was isolated by suction filtering using a membrane suction filter. The residual solid content was heated to 100° C. under vacuum using a vacuum dryer so that remaining volatile components were completely removed. The solid content (3,4-dihydroxybenzonitrile-titanium complex) was brown in color. The yield amount was 5.80 g (18.5 mmol), and the yield percentage was 100%. 3.14 g of 3,4-dihydroxybenzonitrile-titanium complex was dissolved into 100 mL of ethanol to produce a coating liquid.
Reaction SMILES: [C:1]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH:12]1[C:16](=[O:17])[C:15](=[O:18])[CH2:14][C:13]1=[O:19])([O:3][CH2:4][CH3:5])=[O:2].[N+](=[CH2:22])=[N-]>CCOCC>[C:1]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]1[C:13](=[O:19])[CH2:14][C:15](=[O:18])[C:16]=1[O:17][CH3:22])([O:3][CH2:4][CH3:5])=[O:2]
Reactant: CCOC(=O)CCCCCCC1C(=O)CC(=O)C1=O
Reactant: C=[N+]=[N-]
Solvent: CCOCC
Product: CCOC(=O)CCCCCCC1=C(OC)C(=O)CC1=O

Procedure:
Five grams (5 g) of 2-(6'-carboethoxyhexyl)-cyclopentan-1,3,4-trione was reacted with diazomethane in ether according to conventional procedures to give 3.8 g of 2-(6'-carbethoxyhexyl)-3-methoxy-4-oxo-2-cyclopenten-1-one, b.p. 165°-170°C/0.4-0.6 mmHg.
Reaction SMILES: [O:1]=[C:2]([C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]=[CH:18][CH:17]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][NH:8][CH2:7][C@@H:6]1[CH2:11][C:12]([O:14][CH3:15])=[O:13].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Cl[CH2:37][CH2:38][S:39][C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([F:46])[CH:41]=1>C(#N)C.O>[F:46][C:42]1[CH:41]=[C:40]([S:39][CH2:38][CH2:37][N:8]2[CH2:9][CH2:10][C@@H:5]([CH2:4][CH2:3][C:2](=[O:1])[C:16]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH3:27])[CH:24]=4)[N:19]=[CH:18][CH:17]=3)[C@@H:6]([CH2:11][C:12]([O:14][CH3:15])=[O:13])[CH2:7]2)[CH:45]=[CH:44][CH:43]=1
Reactant: COC(=O)C[C@H]1CNCC[C@H]1CCC(=O)c1ccnc2ccc(OC)cc12
Reactant: Fc1cccc(SCCCl)c1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Product: COC(=O)C[C@H]1CN(CCSc2cccc(F)c2)CC[C@H]1CCC(=O)c1ccnc2ccc(OC)cc12
Temperature: 20 °C
Yield: 103.1 %

Procedure:
2.26 g of methyl(3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-acetate, dissolved beforehand in 50 cm3 of acetonitrile, were added dropwise, with stirring and at a temperature in the region of 20° C., followed by 6.91 g of potassium carbonate and 2 g of potassium iodide, to a solution of 4 g of 1-[(2-chloroethyl)thio]-3-fluorobenzene in 50 cm3 of acetonitrile. The mixture was heated for 18 hours at a temperature in the region of 70° C. After a further addition of 0.3 g of potassium iodide and additional heating at a temperature in the region of 70° C. for 4 hours, the reaction mass was cooled to approximately 20° C., 200 cm3 of water were added and extraction was carried out with 2 times 150 cm3 of ethyl acetate. The combined extracts were washed with 300 cm3 of water, dried over magnesium sulfate, filtered, and evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45 μ; diameter 5.2 cm; silica volume 950 cm3), elution was carried out with a dichloromethane/methanol (99/1 by volume) mixture, and approximately 6-cm3 fractions were collected. Fractions 24 to 36 were combined and concentrated under the above conditions. 3.3 g of methyl (3R,4R)-1-[2-(3-fluorophenylthio)ethyl]-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-acetate were obtained in the form of an oil with a yellow color.
Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])[OH:4].[OH2:13]>>[CH2:11]([OH:12])[C@H:9]1[O:10][C@H:2]([O:1][C@H:7]2[C@H:5]([OH:6])[C@@H:3]([OH:4])[C@H:2]([OH:1])[O:13][C@@H:9]2[CH2:11][OH:12])[C@H:3]([OH:4])[C@@H:5]([OH:6])[C@@H:7]1[OH:8]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Reactant: O
Product: OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O
Temperature: 130 °C

Procedure:
A suspension containing 2 parts by weight of corn starch and 7 parts by weight of water was added with a commercially-available liquefying α-amylase derived from a microorganism, and heated to 90°-100° C. to effect gelatinization and liquefaction. Thereafter, the mixture was heated at 130° C. to cease the enzymatic reaction, followed by recoverying a liquefied solution with a dextrose equivalent (DE) of about 2. The resultant solution was first cooled to 55° C., then added with 150 units per g starch of isoamylase (EC 3.2.1.68) derived from a microorganism of the species Pseudomonas amyloderamosa commercialized by Hayashibara Biochemical Laboratories Inc., Okayama, Japan, and 40 units per g dextrin of β-amylase (EC 3.2.1.2) commercialized by Nagase Biochemicals Ltd., Kyoto, Japan. The resultant mixture was kept at pH 5.0 and subjected to an enzymatic reaction for 24 hours to obtain a maltose-rich saccharide solution which was then heated to inactivate the remaining enzyme. Thus, a maltose-rich saccharide solution was obtained.