Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([Cl:14])=[C:10](Cl)[CH:11]=2)[C:6](=[O:15])[C:5]([C:16]([OH:18])=[O:17])=[CH:4]1)[CH3:2].[CH3:19][N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1>O>[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([Cl:14])=[C:10]([N:23]3[CH2:24][CH2:25][N:20]([CH3:19])[CH2:21][CH2:22]3)[CH:11]=2)[C:6](=[O:15])[C:5]([C:16]([OH:18])=[O:17])=[CH:4]1)[CH3:2]
Reactant: CN1CCNCC1
Reactant: CCn1cc(C(=O)O)c(=O)c2cc(Cl)c(Cl)cc21
Solvent: O
Product: CCn1cc(C(=O)O)c(=O)c2cc(Cl)c(N3CCN(C)CC3)cc21
Yield: 30 %

Procedure:
A mixture of 1-ethyl-6,7-dichloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 2.86 g (0.01 mole), N-methylpiperazine 10 g (0.1 mole) and 15 ml water was heated in a sealed tube at 125°-130° C. (inner temperature) for 19 hours. After cooling, the reaction mixture was evaporated under vacuum and acidified with acetic acid. Insoluble matters were filtered off and the filtrate was neutralized with an aqueous solutiong of NaOH to pH 7, extracted with CHCl3, dried with anhydrous Na2SO4, and the solvent was distilled off. The residue was recrystallized from a mixed solvent of CHCl3 and benzene to give 1.05 g (30%) of 1-ethyl-6-chloro-7-(4-methyl-1-piperazinyl)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid. Colorless needles.
Reaction SMILES: [NH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[N:11]([O-])=[O:12].[Na+]>Cl.O>[N:11]([N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1)=[O:12]
Reactant: c1ccc2c(c1)CCCN2
Reactant: O=N[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Product: O=NN1CCCc2ccccc21
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 82.2 %

Procedure:
1,2,3,4-Tetrahydroquinoline (10 g, 75 mmol) was dissolved in 3N HCl (50 mL) at 0° C. The reaction mixture was stirred for 5 min. at 0° C., then a solution of sodium nitrite (6.22 g, 90 mmol) in water was added at 0° C., and the mixture stirred for 2 h at RT. After completion of reaction, water was added and the mixture extracted with EtOAc (2×200 mL). The combined organic layers were washed with water, dried over sodium sulfate and concentrated under vacuum to obtain 10 g of product.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([CH:12]=[CH:13][C:14]3[CH:15]=[C:16]([CH:20](Cl)[C:21]4[CH:22]=[C:23]([C:27]([CH3:30])([CH3:29])[OH:28])[CH:24]=[CH:25][CH:26]=4)[CH:17]=[CH:18][CH:19]=3)=[N:9]2)=[CH:4][CH:3]=1.[SH:32][CH2:33][CH:34]([CH3:40])[C:35]([O:37][CH2:38][CH3:39])=[O:36].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([CH:12]=[CH:13][C:14]3[CH:15]=[C:16]([CH:20]([S:32][CH2:33][CH:34]([CH3:40])[C:35]([O:37][CH2:38][CH3:39])=[O:36])[C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([OH:28])([CH3:30])[CH3:29])[CH:22]=4)[CH:17]=[CH:18][CH:19]=3)=[N:9]2)=[CH:4][CH:3]=1
Reactant: CCOC(=O)C(C)CS
Reactant: CC(C)(O)c1cccc(C(Cl)c2cccc(C=Cc3ccc4ccc(Cl)cc4n3)c2)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CCOC(=O)C(C)CSC(c1cccc(C=Cc2ccc3ccc(Cl)cc3n2)c1)c1cccc(C(C)(C)O)c1
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 52 %

Procedure:
To the crude chloride of Step 4 dissolved in 10 mL of DMF, ethyl 3-mercapto-2-methylpropanoate (Step 6; 350 μl, approx. 2.4 mmol) and Cs2CO3 (1.61 g, 4.9 mmol) were added and the mixture was stirred at r.t. for 3.5 h. 25% Aq NH4OAc was then added and the reaction mixture was extracted with EtOAc, dried over Na2SO4 and purified by flash chromatography on silica using EtOAc:toluene 7.5:92.5 and 10:90 to yield 347 mg of the title compound as an oil (52% yield for Steps 6 and 7).
Reaction SMILES: [Mg].II.[F:4][C:5]1[CH:12]=[CH:11][CH:10]=[CH:9][C:6]=1[CH2:7]Cl.CN(C)[C:15]([CH:17]1[CH2:19][CH2:18]1)=[O:16]>O1CCCC1.C(OCC)C>[F:4][C:5]1[CH:12]=[CH:11][CH:10]=[CH:9][C:6]=1[CH2:7][C:15]([CH:17]1[CH2:19][CH2:18]1)=[O:16]
Reactant: CN(C)C(=O)C1CC1
Reactant: Fc1ccccc1CCl
Agent: II
Agent: [Mg]
Solvent: CCOCC
Solvent: C1CCOC1
Product: O=C(Cc1ccccc1F)C1CC1

Procedure:
A 1000 ml round-bottomed flask is filled with magnesium (10.7 g, 0.44 mol). Iodine (0.2 g) is sublimated to the magnesium, then diethyl ether (240 ml) is added and under reflux, a solution of 2-fluorobenzyl chloride (47.8 ml, 0.4 mol) and diethyl ether (80 ml) is added to the reaction mixture. The mixture is refluxed for 2 hours and at this temperature a solution of cyclopropanecarboxylic acid dimethylamide (36.2 g, 0.32 mol), prepared according to example 1, and tetrahydrofuran (200 ml) are added. The reaction mixture is stirred for half an hour and under cooling aqueous hydrogen chloride (160 ml, 1:1) is added dropwise to the mixture. The organic layer is dried and the residue is fractionated in vacuo.
Reaction SMILES: C([O:3][C:4](=O)[CH2:5][C:6]1[CH:11]=[CH:10][N:9]=[CH:8][CH:7]=1)C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[N:9]1[CH:10]=[CH:11][C:6]([CH2:5][CH2:4][OH:3])=[CH:7][CH:8]=1
Reactant: CCOC(=O)Cc1ccncc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCCc1ccncc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 56.9 %

Procedure:
Fifteen grams (0.091 mol) of 4-pyridineacetic acid ethyl ester was dissolved in 180 ml of dry THF. The solution was transferred to a 1 l., 3-neck round bottom flask which had been flushed with nitrogen. To the mixture was added dropwise 55 ml of 1.0 M lithium aluminum hydride (0.055 mol) at approximately 0° C. The reaction mixture became yellow upon addition of the reducing agent. Following addition, the mixture was quenched with 2.1 ml of water at 0° C. followed by 2.1 ml of 15% by volume of sodium hydroxide and 6.3 ml of water. The mixture was allowed to stir at room temperature for approximately 4 hours and filtered through Celite. The filtrate was concentrated under vacuum to provide 6.38 g of 4-pyridineethanol. This material was used directly in the following reaction.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[CH:9][S:10][C:3]=12.C([Li])CCC.Cl[C:17]([O:19][CH3:20])=[O:18].CO>C1COCC1.ClCCl.CCCCCC.C(OCC)C>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:17]([O:19][CH3:20])=[O:18])[S:10][C:3]=12
Reactant: Clc1ccnc2ccsc12
Reactant: COC(=O)Cl
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: CCOCC
Solvent: CO
Product: COC(=O)c1cc2nccc(Cl)c2s1
Temperature: 25 °C

Procedure:
7-chlorothieno[3,2-b]pyridine (19.7 g, 0.116 mol) was taken up in THF (400 mL) and cooled to approximately −70 C. The n-butyllithium (1.6M, 80 mL, 0.128 mol) was added dropwise with stirring under an atmosphere of nitrogen. The solution was stirred at −70 C for 1 hour at which time neat methyl chloroformate was added via dropwise addition. The reaction mixture gradually warmed to room temperature and was stirred for over the weekend. The reaction mixture was treated with 25 mL of methanol and then concentrated to dryness leaving a maroon residue. The crude solid was taken up in dichloromethane and passed through a silica gel column eluting with 1:1 hexane/ethyl acetate. Fractions containing the product were combined and concentrated to give a red solid. Trituration with 9:1 hexane/diethyl ether afforded methyl 7-chlorothieno[3,2-b]pyridine-2-carboxylate as a pink solid after filtration. Yield: 14.5 g (55%); MS [M+H]+ 227.9; 1HNMR (CDCl3) δ: 8.7 (d, 1H), 8.3 (s, 1H), 7.4 (d, 1H) ppm.
Reaction SMILES: [F:1][C:2]([F:17])([S:13]([OH:16])(=[O:15])=[O:14])[C:3]([F:12])([F:11])[C:4]([F:10])([F:9])[C:5]([F:8])([F:7])[F:6].[OH-].[CH2:19]([N+:26]([CH3:29])([CH3:28])[CH3:27])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>>[CH2:19]([N+:26]([CH3:29])([CH3:28])[CH3:27])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[F:17][C:2]([F:1])([S:13]([O-:16])(=[O:15])=[O:14])[C:3]([F:11])([F:12])[C:4]([F:10])([F:9])[C:5]([F:8])([F:7])[F:6]
Reactant: O=S(=O)(O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Agent: C[N+](C)(C)Cc1ccccc1
Agent: [OH-]
Product: O=S(=O)([O-])C(F)(F)C(F)(F)C(F)(F)C(F)(F)F

Procedure:
Perfluorobutanesulfonic acid benzyltrimethylammonium salt is prepared by neutralising perfluorobutanesulfonic acid and benzyltrimethylammonium hydroxide in aqueous solution. Benzyltrimethylammonium hydroxide is obtainable from Aldrich.
Reaction SMILES: Br[C:2]1[C:6]([CH3:8])([CH3:7])[O:5]/[C:4](=[C:9]2/[C:10](=[O:19])[NH:11][C:12]3[C:17]/2=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=3)/[CH:3]=1.[CH:20]([C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1)=[O:21].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>C1COCC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[F:18][C:14]1[CH:13]=[C:12]2[C:17](/[C:9](=[C:4]3/[CH:3]=[C:2]([C:25]4[CH:26]=[CH:27][C:22]([CH:20]=[O:21])=[CH:23][CH:24]=4)[C:6]([CH3:8])([CH3:7])[O:5]/3)/[C:10](=[O:19])[NH:11]2)=[CH:16][CH:15]=1
Reactant: CC1(C)O/C(=C2/C(=O)Nc3cc(F)ccc32)C=C1Br
Reactant: O=Cc1ccc(B(O)O)cc1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC1(C)O/C(=C2/C(=O)Nc3cc(F)ccc32)C=C1c1ccc(C=O)cc1
Temperature: 65 °C
Yield: 51 %

Procedure:
To a mixture of (3E)-3-(4-bromo-5,5-dimethylfuran-2(5H)-ylidene)-6-fluoro-1,3-dihydro-2H-indol-2-one (2.0 g, 6.17 mmol), 4-formyl phenylboronic acid (1.85 g, 12.3 mmol), aqueous potassium carbonate (1 M, 31 mL, 31 mmol) in THF (120 mL) under a nitrogen atmosphere, was added palladium(0) tetrakis(triphenylphosphine) (356 mg, 0.3 mmol, 5 mol %). The mixture was heated at 65° C. overnight (20 h).The reaction was cooled to room temperature and ethyl acetate (500 mL) was added. The organic phase was washed with water (100 mL×2), dried over sodium sulfate, and evaporated. The residue was purified by silica gel column chromatography (5% CH3OH/CH2Cl2 elution). Trituration of the product obtained from the column chromatography with ethyl acetate/hexane (1/1), followed by isolation of the precipitate by filtration, provided 4-[(5E)-5-(6-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-2,2-dimethyl-2,5-dihydrofuran-3-yl]benzaldehyde as a red orange solid (1.1 g, yield 51%).
Reaction SMILES: [SH:1][CH2:2][C:3]([O:5][CH3:6])=[O:4].F[C:8]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:9]=1[CH:10]=O.C(OCC)(=O)C>CC#N.CCCCCC>[F:16][C:13]1[CH:14]=[CH:15][C:8]2[S:1][C:2]([C:3]([O:5][CH3:6])=[O:4])=[CH:10][C:9]=2[CH:12]=1
Reactant: COC(=O)CS
Reactant: O=Cc1cc(F)ccc1F
Solvent: CCOC(C)=O
Solvent: CC#N
Solvent: CCCCCC
Product: COC(=O)c1cc2cc(F)ccc2s1
Yield: 33.8 %

Procedure:
TEA (3.705 g, 36.619 mmol) was added to a solution of methyl 2-mercaptoacetate (3.293 g, 30.985 mmol) in CH3CN (12.5 mL). This was followed by the addition of 2,5-difluorobenzaldehyde (4 g, 28.169 mmol) in CH3CN (12.5 mL) and the resulting reaction mass was refluxed overnight under nitrogen atmosphere. The reaction was monitored by TLC (5% ethyl acetate in hexane). The reaction mass was concentrated under reduced pressure to obtain the crude product. Purification by column chromatography on silica gel (15% ethyl acetate in hexane) afforded 2 g of the product (33.89% yield).
Reaction SMILES: I[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.[CH2:12]([OH:15])[C:13]#[CH:14].C(N(CC)CC)C.O>C(#N)C.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>[CH3:9][O:8][C:6](=[O:7])[C:5]1[CH:10]=[CH:11][C:2]([C:14]#[C:13][CH2:12][OH:15])=[CH:3][CH:4]=1
Reactant: C#CCO
Reactant: COC(=O)c1ccc(I)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: O
Solvent: CCN(CC)CC
Solvent: CC#N
Product: COC(=O)c1ccc(C#CCO)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 87.5 %

Procedure:
To a solution of methyl 4-iodobenzoate (20 g, 76 mmol), propargyl alcohol (5.55 g, 99.0 mmol) and triethylamine (20 mL) in acetonitrile (200 mL) was added dichlorobis(triphenylphosphine)palladium(II) (1.55 g, 2.21 mmol), followed by Cul (454 mg, 2.38 mmol). The reaction mixture was stirred at room temperature for 24 h. Water was added and the aqueous solution was washed with EtOAc (3×). The organic solutions were combined, dried (MgSO4), filtered and concentrated. Purification by medium pressure chromatography (9:1 hexanes:EtOAc to 4:1 hexanes:EtOAc) provided 4-(3-hydroxy-prop-1-ynyl)-benzoic acid methyl ester (12.65 g).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:10](=[O:12])[NH:9][CH:8]=[N:7][C:6]=2[CH:5]=[C:4]([Cl:13])[N:3]=1.[H-].[Na+].[CH3:16]I.CO>CN(C=O)C>[Cl:1][C:2]1[C:11]2[C:10](=[O:12])[N:9]([CH3:16])[CH:8]=[N:7][C:6]=2[CH:5]=[C:4]([Cl:13])[N:3]=1
Reactant: CI
Reactant: O=c1[nH]cnc2cc(Cl)nc(Cl)c12
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CO
Product: Cn1cnc2cc(Cl)nc(Cl)c2c1=O
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
5,7-dichloropyrido[4,3-d]pyrimidin-4(3H)-one (1 g, 4.65 mmol) was dissolved in anhydrous DMF 15 mL, and NaH (60% mineral oil, 205 mg, 5.11 mmol) was slowly added into the reaction solution. The reaction was stirred at room temperature for 15 minutes, then CH3I (730 mg, 5.11 mmol) in DMF was added drop-wise into the solution. The reaction was heated to 50° C. for 1 hour and then cooled down to room temperature. Methanol was then added to quench the reaction and the solvent was removed under the vacuum. The crude product was purified by silica column chromatography using hexane/ethyl acetate 1:1 to obtain the final compound 5,7-dichloro-3-methylpyrido[4,3-d]pyrimidin-4(3H)-one. 1H NMR (DMSO-d6) δ 8.64 (s, 1H), 7.74 (s, 1H), 3.46 (s, 3H); ESI-MS m/z 230.1 (MH+).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH2:9])[C:5]([NH2:8])=[CH:6][CH:7]=1.CCN(C(C)C)C(C)C.O=[S:20](Cl)Cl>ClCCl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]2[C:4]([CH:3]=1)=[N:9][S:20][N:8]=2
Reactant: O=S(Cl)Cl
Reactant: Nc1ccc(Br)cc1N
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Brc1ccc2nsnc2c1
Temperature: 25 °C

Procedure:
To a solution of 4-bromobenzene-1,2-diamine (5.236 g, 28.0 mmol) and Hunig's base (19.5 mL, 112 mmol) in dichloromethane (160 mL) was added SOCl2 (4.08 mL, 56 mmol) dropwise at room temperature. The resulting reaction mixture was heated to reflux overnight. The reaction mixture was then allowed to cool to room temperature, and quenched with 10% HCl until pH=2. The resulting mixture was extracted with dichloromethane (200 mL×4), dried over Na2SO4 and concentrated. The crude compound was purified by flash column chromatography (silica gel, chloroform) to afford 5-bromobenzo[1,2,5]thiadiazole as a brown solid which was used directly in the next step. 1H NMR (CDCl3 500 MHz): δ: 8.21 (d, 1H, J=1.5 Hz), 7.87 (d, 1H, J=8.5 Hz), 7.69 (dd, 1H, J=8.5, 1.5 Hz).
Reaction SMILES: [C:1]([OH:24])(=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].O.[OH-].[Na+:27]>C(O)(C)(C)C>[C:1]([O-:24])(=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].[Na+:27]
Reactant: CCCCCCCCCCCCCCCCCCCCCC(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)(C)O
Solvent: O
Product: CCCCCCCCCCCCCCCCCCCCCC(=O)[O-]
Temperature: 75 °C
Reaction time: 1 h

Procedure:
88 kg of recrystallized behenic acid, 422 L of distilled water, 49.2 L of 5 mol/L sodium hydroxide, 120 L of t-butyl alcohol were admixed, and subjected to a reaction with stirring at 75° C. for one hour to give a solution of sodium behenate. Separately, 206.2 L of an aqueous solution of 40.4 kg of silver nitrate (pH 4.0) was provided, and kept at a temperature of 10° C. A reaction vessel charged with 635 L of distilled water and 30 L of t-butyl alcohol was kept at 30° C., and thereto were added the total amount of the solution of sodium behenate and the total amount of the aqueous silver nitrate solution with sufficient stirring at a constant flow rate over 93 minutes and 15 seconds, and 90 minutes, respectively.
Reaction SMILES: [C:1]([OH:24])(=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].C(O)(=O)CCCCCCCCCCCCCCCCC.[OH-].[Na+:46].[N+]([O-])(O)=O>O>[C:1]([O-:24])(=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].[Na+:46]
Reactant: CCCCCCCCCCCCCCCCCCCCCC(=O)O
Agent: CCCCCCCCCCCCCCCCCC(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O=[N+]([O-])O
Solvent: O
Product: CCCCCCCCCCCCCCCCCCCCCC(=O)[O-]
Temperature: 55 °C

Procedure:
Behenic acid of 32.4 g, 9.9 g of alginic acid and 5.6 g of stearic acid were dissolved in 945 ml of pure water at 90° C. Next, 98 ml of 1.5 mol/L sodium hydroxide solution was added thereto with high speed stirring. Then, 0.93 ml of concentrated nitric acid was added thereto, cooled to 55° C. and stirred for 30 min. to obtain the sodium behenate solution.
Reaction SMILES: [C:1]([OH:24])(=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].C1(C)C=CC=CC=1.[N+]([O-])([O-])=O.[Ag+:36]>O>[C:1]([O-:24])(=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].[Ag+:36]
Reactant: CCCCCCCCCCCCCCCCCCCCCC(=O)O
Agent: [Ag+]
Agent: O=[N+]([O-])[O-]
Solvent: Cc1ccccc1
Solvent: O
Product: CCCCCCCCCCCCCCCCCCCCCC(=O)[O-]
Reaction time: 0.5 h

Procedure:
To a solution of 54.4 g of behenic acid dissolved into 1200 ml of toluene were added 2400 ml of water, and the mixture liquid was homogenized by a high-speed homogenizer. To this solution, with stirring, were added dropwise spending about 30 minutes 400 ml of an aqueous ammoniacal silver nitrate solution containing 27.7 g of silver nitrate, with keeping the temperature of the reaction liquid at 60° C. The stirring was further continued for another 30 minutes. The resulting crystals were filtrated, washed with water, washed with methanol, and then dried under reduced pressure, whereby 65.0 g of silver behenate were obtained.
Reaction SMILES: [Na].[CH3:2][Sn:3](Cl)([CH3:5])[CH3:4].Cl[C:8]1[CH:13]=[C:12]([CH3:14])[N:11]=[C:10]([CH3:15])[CH:9]=1>COC(OC)C.COCOC.C(COC)OC.C(OCC)C>[CH3:14][C:12]1[CH:13]=[C:8]([Sn:3]([CH3:5])([CH3:4])[CH3:2])[CH:9]=[C:10]([CH3:15])[N:11]=1
Reactant: Cc1cc(Cl)cc(C)n1
Reactant: C[Sn](C)(C)Cl
Agent: COC(C)OC
Agent: [Na]
Solvent: CCOCC
Solvent: COCOC
Solvent: COCCOC
Product: Cc1cc([Sn](C)(C)C)cc(C)n1
Temperature: 0 °C
Reaction time: 2.5 h
Yield: 65.9 %

Procedure:
A mixture of 2,6-lutidine-N-oxide hydrochloride (48 g) and phosphorus oxychloride (110 ml) is heated 6.5 hours at reflux. After cooling the reaction mixture is carefully poured into crushed ice (1 kg). While the temperature is maintained below 15° C., concentrated ammonium hydroxide is added up to reach pH 8. The product that separates is extracted with ethyl ether (2×500 ml) which is dried and distilled off. The residue is dissolved in ethanol (400 ml) and boiled 3 hours with triethylamine (20 ml). After cooling, the solution is evaporated to dryness, treated with water (200 ml) and extracted with ethyl ether (4×150 ml). The combined extracts are dried and the solvent evaporated. The residue after distillation gives 4-chloro-2,6-dimethylpyridine (25 g), b.p. (15 mm)=67°-69° C. To a mixture of sodium (10 g, 30% dispersion in toluene) in anhydrous dimethyoxyethane (40 ml) cooled in an ice-bath and kept under argon, trimethyltin chloride (12.1 g) in dimethoxymethane (6 ml) is added over a one hour period while keeping the temperature at 0° C. The mixture is stirred 2.5 hours at 0° C.; then 4-chloro-2,6-dimethylpyridine (7 g) in dimethoxyethane is slowly dropped into. Stirring is continued for an additional hour then the reaction mixture is allowed to stand overnight at room temperature. The reaction mixture is diluted with ethyl ether (100 ml) and filtered. The solvent is evaporated, the residue dissolved in ethyl ether (100 ml) and filtered again. After evaporation of the solvent the residue is distilled giving 2,6-dimethyl-4-(trimethyl-stannyl)pyridine (8.8 g), b.p. (15 m)=130°-140° C.
Reaction SMILES: [CH3:1][C:2]1=[CH:3][CH2:4][CH2:5][C:6]([CH:8]=[CH:9][C@H:10]([CH:13]([CH3:15])[CH3:14])[CH2:11][CH2:12]1)=[CH2:7].C(C1C=CC=CC=1)(=O)C>CCCCCC>[CH3:14][CH:13]([C@H:10]1[C@@H:11]2[C@H:12]3[C:2](=[CH2:1])[CH2:3][CH2:4][C@H:5]3[C@:6]2([CH3:7])[CH2:8][CH2:9]1)[CH3:15]
Reactant: C=C1C=C[C@H](C(C)C)CCC(C)=CCC1
Agent: C=C1/C=C/[C@H](C(C)C)CC/C(C)=C/CC1
Solvent: CCCCCC
Solvent: CC(=O)c1ccccc1
Product: C=C1CC[C@@H]2[C@H]1[C@H]1[C@H](C(C)C)CC[C@]12C
Yield: 92.5 %

Procedure:
60 kg of leaves of Solidago gigantea Aiton var. leiophylla Fern. was steam-distilled and 120 g of essential oil was obtained. 100 g of the essential oil containing 40 g of germacrene D was dissolved in 20 l of n-hexane with addition of 50 g of acetophenone and was subjected to internal irradiation with the light of high pressure mercury lamp for 12 hours. After fractional distillation under reduced pressure, 37 g of β-bourbonene was obtained. (Conversion Ratio: 93%)
Reaction SMILES: [CH:1]([N:4]1[C:8]([C:9]2[N:10]=[C:11]3[C:17]4[CH:18]=[CH:19][C:20]([N:22]5[CH2:27][CH2:26][N:25]([CH2:28][C:29](O)=[O:30])[CH2:24][CH2:23]5)=[N:21][C:16]=4[O:15][CH2:14][CH2:13][N:12]3[CH:32]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].[CH3:33][N:34](C)C=O.C(N(CC)C(C)C)(C)C.CN>O1CCCC1>[CH:1]([N:4]1[C:8]([C:9]2[N:10]=[C:11]3[C:17]4[CH:18]=[CH:19][C:20]([N:22]5[CH2:23][CH2:24][N:25]([CH2:28][C:29]([NH:34][CH3:33])=[O:30])[CH2:26][CH2:27]5)=[N:21][C:16]=4[O:15][CH2:14][CH2:13][N:12]3[CH:32]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2]
Reactant: CN(C)C=O
Reactant: CC(C)n1ncnc1-c1cn2c(n1)-c1ccc(N3CCN(CC(=O)O)CC3)nc1OCC2
Agent: CN
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CNC(=O)CN1CCN(c2ccc3c(n2)OCCn2cc(-c4ncnn4C(C)C)nc2-3)CC1
Temperature: 25 °C

Procedure:
2-(4-(2-(1-Isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,2-f][1,4]oxazepin-9-yl)piperazin-1-yl)acetic acid (0.050 g, 0.00011 mol) was dissolved in N,N-Dimethylformamide (1.79 mL, 0.0231 mol) and treated sequentially with N,N-Diisopropylethylamine (0.119 mL, 0.000686 mol) 2.00 M of Methylamine in Tetrahydrofuran (0.228 mL) then N,N,N,N-Tetramethyl-O-(7-azabenzotriazol-1-yl)uronium Hexafluorophosphate (0.0521 g, 0.000137 mol). Stir at r.t. 2 h. Add sat. sodium bicarbonate, extract with ethyl acetate. Dry organics over sodium sulfate and concentrate to give 334, analyzed by rHPLC. MS: (ESI+)=452.2
Reaction SMILES: [N:1]1([C:6]2[CH:7]=[CH:8][C:9]([O:16][CH3:17])=[C:10]([CH:15]=2)[C:11](OC)=[O:12])[CH:5]=[CH:4][N:3]=[CH:2]1.O.[OH-].[Na+]>C1COCC1>[N:1]1([C:6]2[CH:7]=[CH:8][C:9]([O:16][CH3:17])=[C:10]([CH2:11][OH:12])[CH:15]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: COC(=O)c1cc(-n2ccnc2)ccc1OC
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: COc1ccc(-n2ccnc2)cc1CO
Temperature: 24 °C
Reaction time: 18 h

Procedure:
5-(1H-Imidazol-1-yl)-2-methoxybenzoic acid, methyl ester (2 g, 8.6 mmol) was cooled to 0° C. in anhydrous THF under N2 and LiAIH4 was added. The reaction mixture stirred for 18 h at 24° C., and water (0.7 ml) followed 15% sodium hydroxide solution (0.7 ml) and water (0.7 ml) was sequentially added dropwise. The resultant suspension was filtered and concentrated to give 1.3 g (74%); 1H NMR (300 MHz, DMSO-d6) δ3.81(3H, s), 4.52 (2H, d, J=4.3 Hz), 5.18 (1H, br, s), 7.04-7.06 (2H, m), 7.43 (1H, dd, J=8.7 Hz, 2.8 Hz), 7.52 (1H, d, J=2.8 Hz) 7.58 (1H, s), 8.07 (1H, s); MS(DCl)m/z: 205 (MH+).
Reaction SMILES: [C:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14](O)=[O:15])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].B#B.CO>C1COCC1>[C:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([CH2:14][OH:15])[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]
Reactant: CC(C)(C)OC(=O)N1CCOC(C(=O)O)C1
Agent: B#B
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCOC(CO)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 128.4 %

Procedure:
To a cooled (0° C.) solution of Boc-2-carboxymorpholine (1.01 g, 4.3 mmol) in anhydrous THF under argon (25 mL) was added 10.8 mL of a 1M solution of diborane in THF. After stirring at room temperature overnight, methanol was added (10 mL) and the reaction was heated to reflux for 30 min. The solvent was evaporated and the residue was dissolved in ethyl acetate, washed with brine. The combined organic layers were dried (MgSO4) and the solvent was evaporated to yield a colorless liquid (1.2 g) that was used in the next step without further purification.