Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Na].C[Si](C)(C)N[Si](C)(C)C.[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][C:19]([OH:21])=O)=[CH:14][CH:13]=1.[Cl:22][C:23]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:24]=1C(OC)=O.Cl>C1COCC1>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([CH2:18][C:19]([C:30]2[CH:29]=[CH:24][C:23]([Cl:22])=[CH:32][C:31]=2[Cl:33])=[O:21])=[CH:16][CH:17]=1
Reactant: O=C(O)Cc1ccc(Cl)cc1
Reactant: COC(=O)c1ccc(Cl)cc1Cl
Agent: C[Si](C)(C)N[Si](C)(C)C
Agent: Cl
Agent: [Na]
Solvent: C1CCOC1
Product: O=C(Cc1ccc(Cl)cc1)c1ccc(Cl)cc1Cl
Temperature: -60 °C
Reaction time: 0.67 h
Yield: 62.2 %

Procedure:
420 ml of a 2M solution of the sodium salt of hexamethyldisilazane in THF are cooled to −60° C., under a nitrogen atmosphere, 350 ml of THF are added, and then, dropwise, a solution of 57.6 g of 4-chlorophenylacetic acid in 70 ml of THF and the mixture is kept stirred for 1 hour at −60° C. 66 g of methyl 2,4-dichlorobenzoate are then added, dropwise and at −60° C., the mixture is kept stirred for 40 minutes at −60° C. and then the temperature is allowed to rise to 0° C. The reaction mixture is poured over an ice/1 liter of 2N HCl mixture, extracted with ether, the organic phase is washed with a saturated NaHCO3 solution, with water, the organic phase is dried over Na2SO4, the solvent is concentrated under vacuum to a volume of 150 ml, 200 ml of pentane are added and the crystallized product formed is drained. 60 g of the expected compound are obtained.
Reaction SMILES: [NH2:1][C:2]1[C:3]([F:23])=[CH:4][C:5]([Cl:22])=[C:6]([CH:21]=1)[O:7][C:8]1[CH:20]=[CH:19][CH:18]=[CH:17][C:9]=1[O:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13].Cl[C:25]([O:27][CH2:28][CH3:29])=[O:26].O1CCCC1.Cl>N1C=CC=CC=1>[Cl:22][C:5]1[CH:4]=[C:3]([F:23])[C:2]([NH:1][C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:21][C:6]=1[O:7][C:8]1[CH:20]=[CH:19][CH:18]=[CH:17][C:9]=1[O:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13]
Reactant: CCOC(=O)Cl
Reactant: CCOC(=O)COc1ccccc1Oc1cc(N)c(F)cc1Cl
Agent: Cl
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: CCOC(=O)COc1ccccc1Oc1cc(NC(=O)OCC)c(F)cc1Cl
Temperature: 25 °C

Procedure:
Into a mixture of ethyl [2-(5-amino-2-chloro-4-fluorophenoxy)phenoxy]acetate [Intermediate compound A3-23], ethyl chloroformate and tetrahydrofuran is added dropwise pyridine, and the mixture is stirred at room temperature. Dilute hydrochloric acid is added to the reaction solution, and this is extracted with ethyl acetate. The organic layer is washed with saturated saline, dried over anhydrous magnesium sulfate, and concentrated to obtain ethyl [2-(2-chloro-4-fluoro-5-ethoxycarbonylaminophenoxy)phenoxy]acetate [Intermediate compound A8-23].
Reaction SMILES: [CH3:1][N:2]([S:10]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH:21]=[C:22]=[CH:23][CH3:24])=[CH:15][CH:14]=1)(=[O:12])=[O:11])[C@H:3]([C:7](O)=[O:8])[CH:4]([CH3:6])[CH3:5].[OH:25][N:26]1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.CN1CCOCC1.NO>CN(C)C=O>[OH:25][NH:26][C:7](=[O:8])[CH:3]([N:2]([CH3:1])[S:10]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH:21]=[C:22]=[CH:23][CH3:24])=[CH:15][CH:14]=1)(=[O:12])=[O:11])[CH:4]([CH3:6])[CH3:5]
Reactant: On1nnc2ccccc21
Reactant: CC=C=CCOc1ccc(S(=O)(=O)N(C)[C@H](C(=O)O)C(C)C)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: NO
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: CC=C=CCOc1ccc(S(=O)(=O)N(C)C(C(=O)NO)C(C)C)cc1
Yield: 62.6 %

Procedure:
The procedure of Example 13 was followed using the product from Example 21 (185 mg, 0.52 mmol), 1-hydroxybenzotriazol (84 mg, 0.62 mmol), 1-[3-(dimethylamino)-propyl]-3-ethylcarbodimide hydrochloride (140 mg, 0.73 mmol), N-methylmorpholine (0.86 mmol, 0.78 mmol), and hydroxylamine (0.159 ml, 2.6 mmol) in dimethylformamide (5 ml) to give 120 mg (63%) of the product.
Reaction SMILES: C=O.C(N[CH2:6][CH3:7])C.[CH2:8]1[CH2:12]O[CH2:10][CH2:9]1>>[CH:10]#[C:9][CH2:8][C:12]#[C:12][CH2:8][CH2:9][CH2:10][CH2:6][CH3:7]
Reactant: C1CCOC1
Reactant: CCNCC
Agent: C=O
Product: C#CCC#CCCCCC

Procedure:
19.5 G (0.65 mole) of paraformaldehyde, 54.8 g (0.75 mole) of diethylamine, 2.6 g of hydrated copper (II) acetate and 65 ml of THF were charged into a 1 l reactor. The mixture was maintained at reflux for 30 min and, still at reflux, the solution of deca-1,4-diyne obtained as described above was added thereto. The reaction mixture was kept at reflux for 11/2 h until the deca-1,4-diyne had completely disappeared. The mixture was then extracted at 0° with a 15% solution of HCl (3×70 ml) and the acidic layers were extracted with two fractions of 50 ml each of petroleum ether 80:100°, then 150 ml of a 30% NaOH solution were added thereto at 0°. The basic phase thus obtained was extracted with three fractions of 150 ml each of ethyl acetate and the organic extracts treated with a saturated aqueous solution of NaCl, dried over Na2SO4, filtered and evaporated to give 105 g of N,N-diethyl-undeca-2,5-diynyl-amine.
Reaction SMILES: [F:1][C:2]1[C:12]([N:13]2[C:18](=[O:19])[CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[NH:15][C:14]2=[O:24])=[CH:11][C:5]2[NH:6][C:7](=[O:10])[CH2:8][O:9][C:4]=2[CH:3]=1.[C:25](=O)([O-])[O-].[K+].[K+].CI>CN(C)C=O>[F:1][C:2]1[C:12]([N:13]2[C:18](=[O:19])[CH:17]=[C:16]([C:20]([F:21])([F:22])[F:23])[N:15]([CH3:25])[C:14]2=[O:24])=[CH:11][C:5]2[NH:6][C:7](=[O:10])[CH2:8][O:9][C:4]=2[CH:3]=1
Reactant: O=C([O-])[O-]
Reactant: O=C1COc2cc(F)c(-n3c(=O)cc(C(F)(F)F)[nH]c3=O)cc2N1
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: Cn1c(C(F)(F)F)cc(=O)n(-c2cc3c(cc2F)OCC(=O)N3)c1=O
Reaction time: 4 h
Yield: 119.9 %

Procedure:
0.85 g of 3-(7-fluoro-3-oxo-2H-1,4-benzoxazin-6-yl)-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione was dissolved in 8.5 ml of N,N-dimethylformamide. Then 0.17 g of anhydrous potassium carbonate and 0.15 ml of methyl iodide were added and the mixed solution was stirred for 4 hours. After the reaction was completed, N,N-dimethylformamide was distilled off and the residue was extracted with ethyl acetate by adding water. The extract was washed with a saturated sodium chloride aqueous solution and dried over anhydrous sodium sulfate, and then ethyl acetate was distilled off to obtain a crude product. This product was purified by column chromatography using chloroform as developing solvent to yield 0.53 g of the objective compound as pale yellow crystals.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12](=[O:14])[CH3:13])=[C:5]2[NH:15][C@H:16]1[CH2:21][CH2:20][C@H:19]([CH2:22][N:23]([CH3:25])[CH3:24])[CH2:18][CH2:17]1.[OH:26][C:27]1[N:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C1(N)C(F)=C(F)C(F)=C(N)C=1F.[ClH:48].Cl>>[ClH:1].[ClH:48].[CH3:24][N:23]([CH2:22][C@H:19]1[CH2:20][CH2:21][C@H:16]([NH:15][C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([C:30]4[CH:31]=[N:32][C:27]([OH:26])=[CH:28][CH:29]=4)[N:3]=3)[N:8]=[CH:7][C:6]=2[C:12](=[O:14])[CH3:13])[CH2:17][CH2:18]1)[CH3:25]
Reactant: OB(O)c1ccc(O)nc1
Reactant: CC(=O)c1cnc2ccc(Cl)nc2c1N[C@H]1CC[C@H](CN(C)C)CC1
Agent: Cl
Agent: Nc1c(F)c(N)c(F)c(F)c1F
Product: CC(=O)c1cnc2ccc(-c3ccc(O)nc3)nc2c1N[C@H]1CC[C@H](CN(C)C)CC1

Procedure:
Following general procedure II, 1-(6-Chloro-4-{trans-4-[(dimethylamino)methyl]cyclohexylamino}-1,5-naphthyridin-3-yl)ethanone (74 g, 0.21 mmol) was reacted with (6-hydroxypyridin-3-yl)boronic acid (43 g, 0.31 mmol) followed by formation of the dihydrochloride salt to afford the desired product (49 g, 48%) as a yellow solid: 1H NMR (500 MHz, CD3OD) δ 9.14 (s, 1H), 8.41-8.29 (m, 4H), 6.76 (d, J=9.5 Hz, 1H), 5.58-5.50 (m, 1H), 3.13 (d, J=6.7 Hz, 2H), 2.94 (s, 6H), 2.75 (s, 3H), 2.49-2.40 (m, 2H), 2.08-2.00 (m, 3H), 1.73-1.61 (m, 2H), 1.39-1.27 (m, 2H); ESI MS m/z 420 [M+H]+; HPLC>99% (AUC), tR=8.43 min.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]([CH2:30][CH2:31][C:32]([O:34][CH3:35])=[O:33])[C:8]([C:10]1[CH:29]=[CH:28][C:13]2[N:14]([CH3:27])[C:15]([CH2:17][NH:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]#[N:26])=[CH:21][CH:20]=3)=[N:16][C:12]=2[CH:11]=1)=[O:9].[ClH:36].CO.C(=O)([O-])[O-].[NH4+:43].[NH4+]>ClCCl.CO>[ClH:36].[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]([CH2:30][CH2:31][C:32]([O:34][CH3:35])=[O:33])[C:8]([C:10]1[CH:29]=[CH:28][C:13]2[N:14]([CH3:27])[C:15]([CH2:17][NH:18][C:19]3[CH:24]=[CH:23][C:22]([C:25](=[NH:43])[NH2:26])=[CH:21][CH:20]=3)=[N:16][C:12]=2[CH:11]=1)=[O:9]
Reactant: COC(=O)CCN(C(=O)c1ccc2c(c1)nc(CNc1ccc(C#N)cc1)n2C)c1ccccn1
Reactant: [NH4+]
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CO
Solvent: ClCCl
Product: COC(=O)CCN(C(=O)c1ccc2c(c1)nc(CNc1ccc(C(=N)N)cc1)n2C)c1ccccn1
Yield: 78 %

Procedure:
Prepared analogously to Example 25d from 1-methyl-2-[N-(4-cyanophenyl)-aminomethyl]-benzimidazol-5-yl-carboxylic acid-N-(2-pyridyl)-N-(2-methoxycarbonylethyl)-amide and methanolic hydrochloric acid, methanol and ammonium carbonate. Yield: 78% of theory, C26H27N7O3 (485.6) Rf value: 0.31 (silica gel; dichloromethane/methanol=5:1) ##EQU43##
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1F.[CH3:12][S:13]([O-:15])=[O:14].[Na+]>CS(C)=O>[F:1][C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[S:13]([CH3:12])(=[O:15])=[O:14]
Reactant: O=[N+]([O-])c1ccc(F)c(F)c1
Reactant: CS(=O)[O-]
Agent: [Na+]
Solvent: CS(C)=O
Product: CS(=O)(=O)c1ccc([N+](=O)[O-])cc1F
Temperature: 130 °C
Yield: 74 %

Procedure:
A mixture of 3,4-difluoronitrobenzene (10 g, 62.9 mmol) and sodium methanesulfinate (8.3 g, 69.1 mmol) in DMSO (60 mL) was heated at 130° C. for 8 hours. After cooling down to room temperature, the mixture was poured into ice-water. The whole was extracted with ethyl acetate (200 mL×2), the combined organic layer washed with water (80 mL), brine (80 mL), dried over MgSO4, and concentrated in vacuo. The residue was crystallized from hexane and triturated withhexane to give the subtitle compound (10.2 g, 74% yield).
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([OH:12])=O)=O.[CH3:13][NH:14][NH2:15]>CCO>[CH3:13][N:14]1[C:10](=[O:12])[CH2:9][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[CH:1]=[N:15]1
Reactant: CNN
Reactant: O=Cc1ccccc1CC(=O)O
Solvent: CCO
Product: CN1N=Cc2ccccc2CC1=O
Yield: 50 %

Procedure:
To a solution of ortho-formylphenylacetic acid (10 g, 61 mmol) (Bleasdale, et al., J. Chem. Soc. Perkin Trans., 1991, 1683) in 60 mL of EtOH was added N-methylhydrazine (4.2 g, 91 mmol) and refluxed for 1 h. The reaction mixture cooled, solvent removed and transferred the crude reaction mixture to a vacuum sublimation apparatus. The imine was heated at 140° C. under high vacuum for 1 h and collected the cyclized product by extracting with hot 20% ethyl acetate in hexane (Nagarajan, et al., J. Med. Chem., 1972, 15 (10), 1091). The product was crystallized from 20% ethyl acetate in hexane. 4,5-dihydro-3-methyl-3H-2,3-benzodiazepin-4-one was obtained in 50% yield.
Reaction SMILES: [NH2:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:5]=[C:4]([OH:14])[C:3]=1[C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:28]([O:31][CH2:32][CH2:33]Br)(=[O:30])[CH3:29]>CN(C)C=O>[C:28]([O:31][CH2:32][CH2:33][O:14][C:4]1[C:3]([C:15]2[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=2)=[C:2]([NH2:1])[N:6]([CH2:7][C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:5]=1)(=[O:30])[CH3:29]
Reactant: Cc1ccc(-c2c(O)nn(Cc3ccccc3)c2N)cc1
Reactant: CC(=O)OCCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CC(=O)OCCOc1nn(Cc2ccccc2)c(N)c1-c1ccc(C)cc1
Reaction time: 8 h

Procedure:
To a stirring suspension of 5-amino-1-benzyl-4-(4-methylphenyl)-1H-pyrazol-3-ol (Preparation 42) (2.4 g) and cesium carbonate (8.4 g) in dimethylformamide (30 ml) under nitrogen at room temperature was added 2-bromoethyl acetate (1.44 g) and the reaction mixture stirred overnight. The reaction was quenched with 2M hydrochloric acid (100 ml) and extracted into ethyl acetate (2×100 ml). The two combined organic extracts were further washed with water (2×100 ml), then dried (MgSO4) and the solvent removed under reduced pressure to give the crude material. This was purified using the Biotage™ Flash 40 system (90 g Silica) with a gradient elution of hexane (75% to 30%) and ethyl acetate (25% to 70%) to yield the title product as a brown oil.(1.75 g, ca. 60%)
Reaction SMILES: [CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[C:13]([NH:15][NH2:16])=[O:14].[F:17][C:18]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:19]=1[C:20](O)=O>>[F:17][C:18]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:19]=1[C:20]1[O:14][C:13]([C:3]2[C:4]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)=[N:5][O:6][C:2]=2[CH3:1])=[N:15][N:16]=1
Reactant: O=C(O)c1cc(F)ccc1F
Reactant: Cc1onc(-c2ccccc2)c1C(=O)NN
Product: Cc1onc(-c2ccccc2)c1-c1nnc(-c2cc(F)ccc2F)o1
Yield: 68 %

Procedure:
As described for example 2, 5-methyl-3-phenyl-isoxazole-4-carboxylic acid hydrazide (200 mg, 0.92 mmol) was converted using 2,5-difluorobenzoic acid instead of o-toluic acid to the title compound (SiO2, heptane:ethyl acetate:dichloromethane=70:10:20 to 40:40:20, 211 mg, 68%) which was obtained as a white solid. MS: m/e=340.2 [M+H]+.
Reaction SMILES: [CH2:1]([C:3]1[C:4](=[O:19])[NH:5][C:6](=[O:18])[NH:7][C:8]=1[O:9][C:10]1[CH:15]=[C:14]([CH3:16])[CH:13]=[C:12]([CH3:17])[CH:11]=1)[CH3:2].C1(C)C=CC(S(O[CH2:30][CH:31]2[CH2:34][CH2:33][CH2:32]2)(=O)=O)=CC=1>>[CH:31]1([CH2:30][N:7]2[C:8]([O:9][C:10]3[CH:11]=[C:12]([CH3:17])[CH:13]=[C:14]([CH3:16])[CH:15]=3)=[C:3]([CH2:1][CH3:2])[C:4](=[O:19])[NH:5][C:6]2=[O:18])[CH2:34][CH2:33][CH2:32]1
Reactant: Cc1ccc(S(=O)(=O)OCC2CCC2)cc1
Reactant: CCc1c(Oc2cc(C)cc(C)c2)[nH]c(=O)[nH]c1=O
Product: CCc1c(Oc2cc(C)cc(C)c2)n(CC2CCC2)c(=O)[nH]c1=O
Yield: 58.5 %

Procedure:
5-Ethyl-6-(3,5-dimethylphenoxy)-2,4-pyrimidinedione and (cyclobutyl)methyl para-toluenesulfonate were reacted by the same way with the example 1 to obtain the titled compound (192 mg, yield: 58.5%).
Reaction SMILES: [F:1][CH2:2][C:3]1([CH2:19][F:20])[CH:8]=[C:7]([C:9]([OH:11])=[O:10])[C:6]2[CH:12]=[C:13]([N+:16]([O-:18])=[O:17])[CH:14]=[CH:15][C:5]=2[O:4]1.S(=O)(=O)(O)O.[CH2:26](O)[CH3:27]>>[F:20][CH2:19][C:3]1([CH2:2][F:1])[CH:8]=[C:7]([C:9]([O:11][CH2:26][CH3:27])=[O:10])[C:6]2[CH:12]=[C:13]([N+:16]([O-:18])=[O:17])[CH:14]=[CH:15][C:5]=2[O:4]1
Reactant: O=C(O)C1=CC(CF)(CF)Oc2ccc([N+](=O)[O-])cc21
Reactant: CCO
Agent: O=S(=O)(O)O
Product: CCOC(=O)C1=CC(CF)(CF)Oc2ccc([N+](=O)[O-])cc21
Temperature: 0 °C

Procedure:
A mixture of 41.7 of 2,2-bisfluoromethyl-6-nitro-2H-1-benzopyran-4-carboxylic acid, 20 ml of sulfuric acid and 300 ml of ethyl alcohol was heated under refluxing for 6 hours. The reaction mixture was poured into ice-water, and the precipitated crystals were separated by filtration to obtain 42.7 g of ethyl 2,2-bisfluoromethyl-6-nitro-2H-1-benzopyran-4-carboxylate having a melting point of 96°-98° C.
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([NH2:24])[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:27])[F:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[Cl:37]>>[CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([N:24]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[Cl:37])[CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[Cl:37])[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:26])[F:27])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Nc1cccc(-c2c(Cc3ccccc3)cnc3c(C(F)(F)F)cccc23)c1
Reactant: Clc1ccccc1CBr
Product: FC(F)(F)c1cccc2c(-c3cccc(N(Cc4ccccc4Cl)Cc4ccccc4Cl)c3)c(Cc3ccccc3)cnc12

Procedure:
This compound was prepared according to the procedure of example 41, substituting 3-(3-benzyl-8-trifluoromethyl-quinolin-4-yl)-phenylamine and 1-bromomethyl-2-chloro-benzene MS (ESI) m/z 627.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7]([C:9]1[C:17]([Cl:18])=[C:16]([Cl:19])[C:15]([Cl:20])=[C:14]([Cl:21])[C:10]=1[C:11]([OH:13])=[O:12])=O.[CH3:22][N:23]([CH3:33])[C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([N:30]([CH3:32])[CH3:31])[CH:25]=1>C(OC(=O)C)(=O)C>[CH3:31][N:30]([CH3:32])[C:26]1[CH:25]=[C:24]([N:23]([CH3:33])[CH3:22])[CH:29]=[CH:28][C:27]=1[C:7]1([C:3]2[N:2]([CH3:1])[CH:6]=[CH:5][CH:4]=2)[C:9]2[C:10](=[C:14]([Cl:21])[C:15]([Cl:20])=[C:16]([Cl:19])[C:17]=2[Cl:18])[C:11](=[O:13])[O:12]1
Reactant: Cn1cccc1C(=O)c1c(Cl)c(Cl)c(Cl)c(Cl)c1C(=O)O
Reactant: CN(C)c1cccc(N(C)C)c1
Solvent: CC(=O)OC(C)=O
Product: CN(C)c1ccc(C2(c3cccn3C)OC(=O)c3c(Cl)c(Cl)c(Cl)c(Cl)c32)c(N(C)C)c1

Procedure:
Employing the procedure of part B of Example 17 hereinabove, 3.70 g (0.01 mole) of 2-[(1-methyl-2-pyrrolyl)carbonyl]-3,4,5,6-tetrachlorobenzoic acid, prepared as described in part A above, and 2.0 g (0.012 mole) of N,N,N',N'-tetramethyl-m-phenylenediamine were interacted in the presence of 10 ml of acetic anhydride to obtain 3-[2,4-bis(dimethylamino)phenyl]-3-(1-methyl-2-pyrrolyl)-4,5,6,7-tetrachlorophthalide (Formula IV: R0 =R1 =R2 =R3 =Cl; R=R7 =CH3 ; R4 =N(CH3)2).
Reaction SMILES: [CH2:1]1[O:11][C:4]2([CH2:9][CH2:8][C:7](=[O:10])[CH2:6][CH2:5]2)[O:3][CH2:2]1.C([N-]C(C)C)(C)C.[Li+].[Br:20][C:21]1[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=1[CH2:23]Br>C1COCC1>[Br:20][C:21]1[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=1[CH2:23][CH:8]1[C:7](=[O:10])[CH2:6][CH2:5][C:4]2([O:3][CH2:2][CH2:1][O:11]2)[CH2:9]1
Reactant: O=C1CCC2(CC1)OCCO2
Reactant: BrCc1ccccc1Br
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: O=C1CCC2(CC1Cc1ccccc1Br)OCCO2
Temperature: -78 °C
Reaction time: 1 h

Procedure:
A solution of 1,4-cyclohexanedione mono-ethylene acetal (20 g, 28 mmol) in THF (360 ml) is added dropwise under nitrogen to a solution, cooled to −78° C., of 1M lithium diisopropylamide in THF (150 mmol, 150 ml), and the mixture is then allowed to return to room temperature. After stirring for 1 hour, the mixture is cooled to −78° C. and 35.2 g (141 mmol) of 2-bromobenzyl bromide are added dropwise. After stirring for 30 minutes at −78° C., the temperature of the mixture is returned to 0° C. The mixture is stirred for 3 hours at 0° C. and then hydrolysed and extracted with ether. The organic phase is washed with a saturated NaCl solution, dried over MgSO4 and concentrated in vacuo. The title compound is purified by flash chromatography over a column.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4](=[O:39])[C:5]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH:18]2[O:38][CH:19]2[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]2[C:32](=[O:33])[C:31]([O:34][CH3:35])=[CH:30][C:29](=[O:36])[C:28]=2[OH:37])=[C:6]([OH:10])[C:7](=[O:9])[CH:8]=1.Cl(O)(=O)(=O)=[O:41].C(OCC)C>O1CCCC1>[CH3:35][O:34][C:31]1[C:32](=[O:33])[C:27]([CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH:19]([OH:41])[CH:18]([OH:38])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][C:5]2[C:4](=[O:39])[C:3]([O:2][CH3:1])=[CH:8][C:7](=[O:9])[C:6]=2[OH:10])=[C:28]([OH:37])[C:29](=[O:36])[CH:30]=1
Reactant: [O-][Cl+3]([O-])([O-])O
Reactant: COC1=CC(=O)C(O)=C(CCCCCCCC2OC2CCCCCCCC2=C(O)C(=O)C=C(OC)C2=O)C1=O
Solvent: C1CCOC1
Solvent: CCOCC
Product: COC1=CC(=O)C(O)=C(CCCCCCCC(O)C(O)CCCCCCCC2=C(O)C(=O)C=C(OC)C2=O)C1=O
Temperature: 25 °C
Reaction time: 4 h

Procedure:
37 Milligrams of 1,16-bis(5-methoxy-2-hydroxy-1,4-benzoquinon-3-yl)-8,9-epoxyhexadecane was dissolved in 2 ml of tetrahydrofuran, to this solution was added 0.5 ml of 5% perchloric acid aqueous solution and the mixture was stirred at room temperature for 4 hours. Then, 30 ml of diethyl ether was added to the reaction mixture, and the organic layer was washed with a saturated sodium chloride aqueous solution in several times, and dried over anhydrous sodium sulfate. This extract was purified by means of a preparative thin layer chromatography [adsorbent: "Silica gel 60 F254 " manufactured by E. Merck A. G., developing solvent: chloroform-methanol (85:15 mixture by volume/volume)], then recrystallized from ethyl acetate-n-hexane to obtain 12 mg of 1,16-bis(5-methoxy-2-hydroxy-1,4-benzoquinon-3-yl)-8,9-dihydroxyhexadecane. Yellow powdery crystals.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([S:9][CH:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)[N:4]=1.C([O:17][C:18](=[O:29])[CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[C:23]([F:28])[CH:22]=1)C>>[CH:10]1([S:9][C:5]2[N:4]=[C:3]([CH2:2][O:27][C:24]3[CH:25]=[CH:26][C:21]([CH2:20][CH2:19][C:18]([OH:29])=[O:17])=[CH:22][C:23]=3[F:28])[CH:8]=[CH:7][CH:6]=2)[CH2:14][CH2:13][CH2:12][CH2:11]1
Reactant: CCOC(=O)CCc1ccc(O)c(F)c1
Reactant: ClCc1cccc(SC2CCCC2)n1
Product: O=C(O)CCc1ccc(OCc2cccc(SC3CCCC3)n2)c(F)c1
Yield: 85.6 %

Procedure:
2-Chloromethyl-6-cyclopentylsulfanyl-pyridine (0.032 g, 0.14 mmol) obtained in Step C of Preparation Example 27 and 3-(3-fluoro-4-hydroxy-phenyl)-propionic acid ethyl ester (0.030 g, 0.14 mmol) obtained in Step C of Preparation Example 6 were used to react sequentially in the same manner as in Steps A and B of Example 1 to obtain the title compound (0.045 g, 84%).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.[CH2:12]([OH:15])[C:13]#[CH:14]>C(NCC)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[F:9][C:8]([F:11])([F:10])[C:5]1[CH:6]=[CH:7][C:2]([C:14]#[C:13][CH2:12][OH:15])=[CH:3][CH:4]=1
Reactant: C#CCO
Reactant: FC(F)(F)c1ccc(Br)cc1
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCNCC
Product: OCC#Cc1ccc(C(F)(F)F)cc1
Temperature: 50 °C
Reaction time: 0.58 h
Yield: 50.2 %

Procedure:
In 50 ml of diethylamine were dissolved 5.0 g (22 mmol) of 4-bromo-α,α,α-trifluorotoluene and 1.25 g (22 mmol) of propargyl alcohol, and 80 mg (0.11 mmol) of bis(triphenylphosphine)palladium (II) chloride and 40 mg (0.22 mmol) of copper (I) iodide were added to the solution, followed by stirring of the resulting mixture at 50° C. for 35 minutes. To the mixture were added 40 mg (0.06 mmol) of bis(triphenylphosphine)palladium (II) chloride, and the resulting mixture was stirred for a further 35 minutes. After the mixture was dried, the crude product obtained by evaporation of the solvent was subjected to column chromatography using 50 g of silica gel and eluted with a mixed solvent of ethyl acetate-hexane (3:17) to obtain 2.21 g (yield: 50%) of the title compound as an oil.
Reaction SMILES: Cl[SiH:2]1[N:6]([C:7]([CH3:14])([CH3:13])[CH2:8][C:9]([CH3:12])([CH3:11])[CH3:10])[CH:5]=[CH:4][N:3]1[C:15]([CH3:22])([CH3:21])[CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18].[NH3:23]>CCCCCC>[NH2:23][SiH:2]1[N:6]([C:7]([CH3:14])([CH3:13])[CH2:8][C:9]([CH3:12])([CH3:11])[CH3:10])[CH:5]=[CH:4][N:3]1[C:15]([CH3:22])([CH3:21])[CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18]
Reactant: CC(C)(C)CC(C)(C)N1C=CN(C(C)(C)CC(C)(C)C)[SiH]1Cl
Reactant: N
Solvent: CCCCCC
Product: CC(C)(C)CC(C)(C)N1C=CN(C(C)(C)CC(C)(C)C)[SiH]1N
Temperature: 25 °C
Reaction time: 41 h
Yield: 88 %

Procedure:
In an argon atmosphere, 5.42 g (15.7 mmol) of Si(tOctNCHCHNtOct)(H)Cl was dissolved in 20 mL of hexane. The resulting solution was deaerated by Freeze-Pump-Thaw cycling and after creating an ammonia atmosphere in the reaction vessel by connecting thereto a balloon having an internal volume of 5 L and being filled with ammonia, the solution was stirred at room temperature for 41 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: 115° C./1.2×102 Pa) to obtain 2-amino-1,3-bis(1,1,3,3-tetramethylbutyl)-1,3-diaza-2-silacyclopent-4-ene (Si(tOctNCHCHNtOct)(H)NH2) as a pale yellow liquid (yielded amount: 4.52 g, yield: 88%). The thus-obtained Si(tOctNCHCHNtOct)(H)NH2 was measured for the 1H and 13C NMR spectra, as a result, these spectra agreed with spectra of that obtained in Example-24.