Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([NH:10][C:11]([C:13]2[NH:14][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:16][CH:17]=2)=[O:12])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:31][C:32]1[CH:36]=[C:35]([C:37]2[S:38][C:39]([Cl:42])=[CH:40][CH:41]=2)[O:34][N:33]=1>CN(C=O)C>[CH:1]([N:4]1[CH2:5][CH2:6][CH:7]([NH:10][C:11]([C:13]2[N:14]([CH2:31][C:32]3[CH:36]=[C:35]([C:37]4[S:38][C:39]([Cl:42])=[CH:40][CH:41]=4)[O:34][N:33]=3)[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:16][CH:17]=2)=[O:12])[CH2:8][CH2:9]1)([CH3:3])[CH3:2]
Reactant: CC(C)N1CCC(NC(=O)c2ccc(-c3ccccc3)[nH]2)CC1
Reactant: Clc1ccc(-c2cc(CBr)no2)s1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CC(C)N1CCC(NC(=O)c2ccc(-c3ccccc3)n2Cc2cc(-c3ccc(Cl)s3)on2)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 18.4 %

Procedure:
To a solution of 5-phenyl-1H-pyrrole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide (50 mg) in DMF (2 mL) was added Cs2CO3 (105 mg). The mixture was stirred for 30 min at RT. 3-Bromomethyl-5-(5-chloro-thiophen-2-yl)-isoxazole (45 mg) was added and stirring was continued for 3 h at RT. The mixture was filtered and directly subjected to preparative HPLC(CH3CN/H2O gradient+0.05% TFA) to give 1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-phenyl-1H-pyrrole-2-carboxylic acid (1-isopropyl-piperidin-4-yl)-amide (15 mg) as its trifluoroacetate salt. MS (ESI+): m/e=509 [M+H]+, chloro pattern.
Reaction SMILES: [N:1]1([CH2:7][C:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C([Li])CCC.[Cl:23][CH2:24][N:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1.O>CCOCC>[ClH:23].[ClH:23].[N:1]1([CH2:7][C:8]2[C:17]([CH2:24][N:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: c1ccc2cc(CN3CCCCC3)ccc2c1
Reactant: ClCN1CCCCC1
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: O
Product: Cl
Product: c1ccc2cc(CN3CCCCC3)c(CN3CCCCC3)cc2c1

Procedure:
To a stirred solution of 2-piperidinomethylnaphthalene (5.6 g) in dry ether (200 ml) was added, under nitrogen, a 1.5M ethereal solution of butyl lithium (18.3 ml) and the mixture was kept at room temperature for 24 hours. N-(Chloromethyl)piperidine (7.34 g) was added, the mixture was heated under reflux for 1 hour, and poured into water (1 l). The precipitated material was extracted into ether, the extract was washed with water, dried over anhydrous magnesium sulphate and evaporated to dryness. The residue was purified by chromatography on silica and an ethereal solution of the product was treated with ethereal hydrogen chloride. 1,2-Bis(piperidinomethyl)naphthalene dihydrochloride crystallised from propan-2-ol as prisms, m.p. 240°.
Reaction SMILES: Cl[CH2:2][C:3]([N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[NH:9][C:8](=[O:16])[C:7]2[N:17]([CH3:21])[CH:18]=[C:19]([CH3:20])[C:6]1=2)=[O:4].C(N(CC)CC)C.[CH2:29]([N:31]([CH2:34][CH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][NH:36]1)[CH2:32][CH3:33])[CH3:30]>CN(C)C=O>[CH2:29]([N:31]([CH2:34][CH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][N:36]1[CH2:2][C:3]([N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[NH:9][C:8](=[O:16])[C:7]2[N:17]([CH3:21])[CH:18]=[C:19]([CH3:20])[C:6]1=2)=[O:4])[CH2:32][CH3:33])[CH3:30]
Reactant: CCN(CC)CC1CCCCN1
Reactant: Cc1cn(C)c2c1N(C(=O)CCl)c1ccccc1NC2=O
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCN(CC)CC1CCCCN1CC(=O)N1c2ccccc2NC(=O)c2c1c(C)cn2C

Procedure:
A mixture of 4-(chloroacetyl)-1,3-dimethyl-1,4,9,10-tetrahydropyrrolo[3,2-b][1,5]-benzodiazepin-10-one (2.0 g, 0.0066 mol), dimethylformamide (30 ml), triethylamine (1 ml, 0.0071 mol) and 2-[(diethylamino)methyl]piperidine (1.7 g, 0.01 mol) is heated to 30°-40° C. for two hours with stirring. The solvent is distilled off under water jet vacuum, the residue taken up in water (10 ml), made alkline with potassium carbonate and extracted exhaustively with dichloromethane. The combined methylene chloride extracts are dried over sodium sulfate and concentrated. The crude product thus obtained is purified by chromatography on silica gel using dichloromethane/methanol (9:1 v/v). After recrystallization from ethyl acetate/methanol (95:5) the desired compound (1.4 g) is obtained in the form of colorless crystals, Mp. 176°-178° C.
Reaction SMILES: [Br:1][C:2]1[C:3](Cl)=[C:4]([N+:9]([O-:11])=[O:10])[C:5]([NH2:8])=[N:6][CH:7]=1.[C:13]1([NH:19][C:20](=[O:28])[CH2:21][N:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(N(C(C)C)CC)(C)C>C(O)(C)C>[NH2:8][C:5]1[C:4]([N+:9]([O-:11])=[O:10])=[C:3]([N:25]2[CH2:26][CH2:27][N:22]([CH2:21][C:20]([NH:19][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[O:28])[CH2:23][CH2:24]2)[C:2]([Br:1])=[CH:7][N:6]=1
Reactant: Nc1ncc(Br)c(Cl)c1[N+](=O)[O-]
Reactant: O=C(CN1CCNCC1)Nc1ccccc1
Solvent: CC(C)O
Solvent: CCN(C(C)C)C(C)C
Product: Nc1ncc(Br)c(N2CCN(CC(=O)Nc3ccccc3)CC2)c1[N+](=O)[O-]
Temperature: 45 °C

Procedure:
To a mixture of 5-bromo-4-chloro-3-nitro-pyridin-2-ylamine (0.126 g, 0.50 mmol) and isopropanol (10 ml) was added N-phenyl-2-piperazin-1-yl-acetamide×2HCl salt (0.160 g, 0.55 mmol) followed by diisopropylethylamine (0.32 ml, 1.76 mmol). The reaction mixture was heated at 45° C. for 18 h, then allowed to cool to room temperature and the solvents were removed in vacuo. The residue was absorbed on silica gel and the free running powder was placed on a 10 g isolute silica column which was eluted with 30% ethyl acetate in dichloromethane. The title compound was obtained as a pale yellow solid (0.134 g, 62%); 1H-NMR (500 MHz, DMSO-d6) 2.67 (br s, 4H, piperazine N(CH2)2), 3.12 (br s, 4H, piperazine N(CH2)2), 3.19 (s, 2H, NCH2CO), 7.06 (m, 3H, 2-NH2, p-ArH), 7.31 (t, J=7.44 Hz, 2H, m-ArH), 7.62 (d, J=8.29 Hz, 2H, o-ArH), 8.16 (s, 1H, 6-H), 9.76 (s, 1H, CONH);
Reaction SMILES: [CH3:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[C:5](=[O:16])[NH:4][N:3]=1.Br[CH2:18][CH2:19][CH2:20][Cl:21].C(Cl)(Cl)Cl.CO>CN(C)C=O>[CH3:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[C:5](=[O:16])[N:4]([CH2:18][CH2:19][CH2:20][Cl:21])[N:3]=1
Reactant: COc1cc2c(C)n[nH]c(=O)c2cc1OC
Reactant: ClCCCBr
Solvent: ClC(Cl)Cl
Solvent: CO
Solvent: CN(C)C=O
Product: COc1cc2c(C)nn(CCCCl)c(=O)c2cc1OC

Procedure:
1-[4-Methyl-6,7-dimethoxy-1(2H)-phthalazinone-2-yl]-3-chloropropane was prepared analogous to Example 1 (a) by reaction of 4-methyl-6,7-dimethoxy-1(2H)-phthalazinone with 1-bromo-3-chloro-propane in dimethylformamide. Rf -value (chloroform/methanol = 9/1) : 0.9.
Reaction SMILES: C([BH3-])#N.[Na+].[CH:5]1([C:8]2[NH:9][C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH2:7][CH2:6]1.O.[OH-].[Na+]>C(O)(=O)C.C(OCC)(=O)C>[CH:5]1([CH:8]2[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[NH:9]2)[CH2:7][CH2:6]1
Reactant: c1ccc2[nH]c(C3CC3)cc2c1
Agent: [BH3-]C#N
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Solvent: O
Product: c1ccc2c(c1)CC(C1CC1)N2
Temperature: 15 °C
Reaction time: 2 h
Yield: 94.8 %

Procedure:
1.0 g of sodium cyanoborohydride is gradually added to a solution of 1.25 g of 2-cyclopropylindole in 80 ml of acetic acid under argon cooled to a temperature of about 15° C. The reaction mixture is stirred at a temperature of about 15° C. for 2 hours, and is then treated with 100 ml of water. It is then cooled to a temperature of about 5° C. and alkalinized by gradual addition of 140 ml of a 30% sodium hydroxide solution. The reaction mixture is diluted with 200 ml of ethyl acetate and is then stirred at ambient temperature for 15 hours. After settling out, the organic phase is separated and the aqueous phase is extracted with 3×200 ml of ethyl acetate. The organic phases are combined, dried over anhydrous magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. The residue is taken up in a mixture of 60 ml of ethyl acetate, 40 ml of water and 10 ml of concentrated sodium hydroxide, and then the mixture is stirred at ambient temperature for 10 minutes. After settling out, the organic phase is separated and the aqueous phase is extracted with 2×50 ml of ethyl acetate. The organic phases are combined, dried over anhydrous magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. 1.2 g of (±)-2-cyclopropylindoline are thus obtained in the form of a brown oil which is used as it is.
Reaction SMILES: [Mg].[F:2][CH:3](Br)[C:4]1C=CC=C[CH:5]=1.[F:11][C:12]([F:33])([F:32])[CH2:13][N:14]1[C:19](=[O:20])[C:18](Cl)=[C:17]([C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][CH:23]=2)[CH:16]=[N:15]1.N1N[C:36](=O)[CH:37]=[CH:38][CH:39]=1>C1COCC1.CCOCC>[F:11][C:12]([F:33])([F:32])[CH2:13][N:14]1[C:19](=[O:20])[C:18]([CH2:36][C:37]2[CH:5]=[CH:4][C:3]([F:2])=[CH:39][CH:38]=2)=[C:17]([C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][CH:23]=2)[CH:16]=[N:15]1
Reactant: CS(=O)(=O)c1ccc(-c2cnn(CC(F)(F)F)c(=O)c2Cl)cc1
Reactant: FC(Br)c1ccccc1
Reactant: O=c1cccn[nH]1
Agent: [Mg]
Solvent: C1CCOC1
Solvent: CCOCC
Product: CS(=O)(=O)c1ccc(-c2cnn(CC(F)(F)F)c(=O)c2Cc2ccc(F)cc2)cc1
Temperature: 40 °C
Yield: 28 %

Procedure:
Magnesium turnings (500 mg) were placed in a dry 250 mL round bottom flask. Anhydrous ether (20 mL) was added under N2 at room temperature then fluorobenzyl bromide (3 mL) was added and stirred. The reaction was heated at 40° C. for 2 hours. All magnesium was consumed resulting in a pale brownish-yellow solution. The 2-(2,2,2-trifluoroethyl)-4-chloro-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone prepared in Example 193E was dissolved in dry THF (25 mL) and transferred to the Grignard solution. The mixture was heated for 3 hours. TLC (2:1 hexanes/ethyl acetate) indicated that the pyridazinone starting material was consumed.) The reaction was cooled to room temperature then quenched with a saturated NH4Cl solution. The product was extracted with ethyl acetate (250 mL); and the organic layer was washed with saturated NH4Cl, and brine. The ethyl acetate solution was dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure. The product was isolated as an orange residue. Purification using a silica gel column (20:80 ethyl acetate/pentanes) provided the title compound as a pale yellow powder (yield: 140 mg, 28%). 1H NMR (300 MHz, CDCl3) δ 3.13 (s, 3H), 4.85 (m, 2H), 6.93 (m, 4H), 7.49 (d, J=9 Hz, 2H) 7.72 (s, 1H), 8.08 (d, J=9 Hz, 2H). MS (DCI/NH3) m/z 441 (M+H)+. Anal. calc. for C20H16F4N2O3S.0.5H2O: C, 53.45; H, 3.81; N, 6.23. Found C, 53.45; H, 3.81; N, 6.23.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)[N:3]=1.[I:22][C:23]1[N:24]=[CH:25][NH:26][C:27]=1[CH3:28]>>[I:22][C:23]1[N:24]=[CH:25][N:26]([C:2]2[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([C:12]3[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=3)[N:3]=2)[C:27]=1[CH3:28]
Reactant: Cc1[nH]cnc1I
Reactant: FC(F)(F)c1ccc(-c2cc(C(F)(F)F)nc(Cl)n2)cc1
Product: Cc1c(I)ncn1-c1nc(-c2ccc(C(F)(F)F)cc2)cc(C(F)(F)F)n1

Procedure:
The title compound was prepared from 2-chloro-4-trifluoromethyl-6-(4-trifluoromethyl-phenyl)-pyrimidine (example A.2) (0.33 g, 1.0 mmol) and commercially available 4-iodo-5-methyl-imidazole (0.25 g, 1.2 mmol) according to the general procedure IVa. Obtained as an off-white solid (0.43 g, 85%). MS (ISP) 498.8 [(M+H)+]; mp 202° C.
Reaction SMILES: Cl.[NH2:2][C:3]1[C:4]2[CH:16]=[C:15]([CH3:17])[S:14][C:5]=2[NH:6][C:7]2[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=2[N:9]=1.CS(C)=O.[C:22]1([CH3:28])C=CC=CC=1.O>CN1CCNCC1>[CH3:17][C:15]1[S:14][C:5]2[NH:6][C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=3[N:9]=[C:3]([N:2]3[CH2:28][CH2:22][N:6]([CH3:7])[CH2:5][CH2:4]3)[C:4]=2[CH:16]=1
Reactant: Cc1cc2c(s1)Nc1ccccc1N=C2N
Reactant: Cc1ccccc1
Agent: CN1CCNCC1
Agent: Cl
Solvent: O
Solvent: CS(C)=O
Product: Cc1cc2c(s1)Nc1ccccc1N=C2N1CCN(C)CC1
Temperature: 50 °C
Reaction time: 2 h

Procedure:
4-Amino-2-methyl-10H-thieno[2,3-b][1,5]benzodiazepine, hydrochloride (100 g) was refluxed in a mixture of N-methylpiperazine (349 mL), dimethylsulphoxide (465 mL) and toluene (465 mL) under a nitrogen atmosphere for 20 hours. The mixture was cooled to 50° C., and water (465 mL) was added at 50-55° C. in 20 min. Then the reaction mass was cooled to 5° C. and stirred for 2 h. The product was filtered and washed with water (100 mL, 20° C.). Dried the product at 60-70° C. under reduced pressure to give crude 2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine or Olanzapine.
Reaction SMILES: [C:1]1([CH3:10])[CH:6]=[CH:5][CH:4]=[C:3]([C:7]([NH2:9])=[O:8])[CH:2]=1.[CH3:11][C:12]([CH:15]=O)([CH3:14])[CH3:13].[NH:17]1[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[N:19]=[N:18]1.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[N:17]1([CH:15]([NH:9][C:7](=[O:8])[C:3]2[CH:4]=[CH:5][CH:6]=[C:1]([CH3:10])[CH:2]=2)[C:12]([CH3:13])([CH3:14])[CH3:11])[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[N:19]=[N:18]1
Reactant: Cc1cccc(C(N)=O)c1
Reactant: c1ccc2[nH]nnc2c1
Reactant: CC(C)(C)C=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Product: Cc1cccc(C(=O)NC(n2nnc3ccccc32)C(C)(C)C)c1

Procedure:
meta-Toluamide, pivaldehyde, benzotriazole and p-toluenesulfonic acid were processed as described in Example 53A to provide the desired product.
Reaction SMILES: [Cl:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:22])[C:12]3[CH:20]=[C:19](I)[CH:18]=[N:17][C:13]=3[N:14]([CH3:16])[N:15]=2)=[O:9])=[CH:4][CH:3]=1.C(NCC)C.[CH2:30]([OH:33])[C:31]#[CH:32]>CCOC(C)=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.[Cu]I>[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:22])[C:12]3[CH:20]=[C:19]([C:32]#[C:31][CH2:30][OH:33])[CH:18]=[N:17][C:13]=3[N:14]([CH3:16])[N:15]=2)=[O:9])=[CH:4][CH:3]=1
Reactant: Cn1nc(C(=O)NCc2ccc(Cl)cc2)c(=O)c2cc(I)cnc21
Reactant: C#CCO
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCOC(C)=O
Solvent: CCNCC
Product: Cn1nc(C(=O)NCc2ccc(Cl)cc2)c(=O)c2cc(C#CCO)cnc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 71 %

Procedure:
Under an argon atmosphere, a mixture of N-(4-chlorobenzyl)-6-iodo-1-methyl-4-oxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxamide (Preparation 23, 0.053 g), dichlorobis(triphenylphosphine)palladium (II) (4.1 mg), copper(I) iodide (18.3 mg), and diethylamine (1.5 mL) is treated with a solution of propargyl alcohol (11 μL). The reaction mixture is stirred at room temperature overnight. The mixture is diluted with EtOAc and then filtered through a Celite-packed, sintered-glass funnel. The cake is washed with CHCl3 until the washings are colorless. The organic filtrate is washed with aqueous saturated ammonium chloride and water, dried (Na2SO4) and concentrated in vacuo. The crude solid is triturated with ether, filtered and washed with ether to give 0.032 g (71%) of the title compound as a light brown solid. Physical characteristics: mp 201-206° C.; 1H NMR (400 MHz, DMSO-d6) δ4.21, 4.39, 4.54, 5.51, 7.40, 8.52, 9.0, 9.7; IR (drift) 3368, 1660, 1612, 1597, 1551, 1479, 1410, 1397, 1377, 1353, 1256, 1036, 812, 674, 650 cm−1; MS (EI) m/z 382 (M+, 6); HRMS (FAB) m/z 383.0917 (C19H15ClN4O3+H).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([S:15]([NH:18][CH:19]([C:25]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[O:26][SiH2:27][C:28]([CH3:31])([CH3:30])[CH3:29])[C:20]([OH:24])([CH3:23])[CH:21]=[CH2:22])(=[O:17])=[O:16])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:50](Br)[CH:51]=[CH2:52]>CN(C)C=O.C(OCC)(=O)C>[CH2:52]([N:18]([CH:19]([C:25]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1)[O:26][SiH2:27][C:28]([CH3:31])([CH3:30])[CH3:29])[C:20]([OH:24])([CH3:23])[CH:21]=[CH2:22])[S:15]([C:12]1[CH:11]=[CH:10][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:14][CH:13]=1)(=[O:17])=[O:16])[CH:51]=[CH2:50]
Reactant: C=CC(C)(O)C(NS(=O)(=O)c1ccc(OCc2ccccc2)cc1)C(O[SiH2]C(C)(C)C)(c1ccccc1)c1ccccc1
Reactant: C=CCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: C=CCN(C(C(C)(O)C=C)C(O[SiH2]C(C)(C)C)(c1ccccc1)c1ccccc1)S(=O)(=O)c1ccc(OCc2ccccc2)cc1
Reaction time: 24 h
Yield: 102.6 %

Procedure:
To a solution of 4-benzyloxy-N-[1-(tert-butyl-diphenyl-silanyloxymethyl)-2-hydroxy-2-methyl-but-3-enyl]-benzenesulfonamide (compound of formula VI, 1.6 g, 2.6 mmol) in 5 ml of dimethylformamide was added cesium carbonate (1.7 g, 5.2 mmol) and allyl bromide (0.63 g, 5.2 mmol). After stirring at a temperature of about 20 to about 25° C. for about 24 hours, an additional 0.4 g of cesium carbonate and 0.2 ml of allyl bromide was added, and the mixture was stirred at a temperature of about 20° C. to about 25° C. for about 24 hours. The mixture was diluted with ethyl acetate, washed 4 times with water, dried over sodium sulfate, filtered and concentrated in vacuo to afford 1.75 g of N-allyl-4-benzyloxy-N-[1-(tert-butyl-diphenyl-silanyloxymethyl)-2-hydroxy-2-methyl-but-3-enyl]-benzenesulfonamide (compound of formula VII) as a colorless syrup.
Reaction SMILES: C[O:2][Si:3][O:4]C.[CH:6]1[CH:7]=[CH:8][C:9]2[C:10](=[C:12]3[N:44]=[C:43]4[N:45]=[C:36]([C:37]5[CH:38]=[CH:39][CH:40]=[CH:41][C:42]=54)[N:35]=[C:33]4[NH:34][C:26]([C:27]5[CH:28]=[CH:29][CH:30]=[CH:31][C:32]=54)=[N:25][C:23]4=[N:24][C:16]([C:17]5[CH:18]=[CH:19][CH:20]=[CH:21][C:22]=54)=[N:15][C:14]=2[NH:13]3)[CH:11]=1.O>CN(C)C=O>[OH:2][Si:3][OH:4].[CH:7]1[CH:6]=[CH:11][C:10]2[C:9](=[C:14]3[N:15]=[C:16]4[N:24]=[C:23]([C:22]5[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=54)[N:25]=[C:26]4[NH:34][C:33]([C:32]5[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=54)=[N:35][C:36]4=[N:45][C:43]([C:42]5[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=54)=[N:44][C:12]=2[NH:13]3)[CH:8]=1
Reactant: CO[Si]OC
Agent: c1ccc2c(c1)-c1nc-2nc2[nH]c(nc3nc(nc4[nH]c(n1)c1ccccc41)-c1ccccc1-3)c1ccccc21
Solvent: CN(C)C=O
Solvent: O
Product: O[Si]O
Temperature: 25 °C

Procedure:
10 g of dimethoxysilicon phthalocyanine synthesized in Synthesis Example 2 was added to 10 g of water and 90 g of N,N-dimethylformamide (90% DMF aqueous solution) and reacted at 120° C. for 3 hours. The reaction product was thermally filtrated and washed with DMF and acetone in the order named. After the product was stirred in 50 ml of acetone at room temperature, crystals were separated by filtration and dried to obtain 8.4 g of dihydroxysilicon phthalocyanine. As the result of carrying out structural analysis by mass spectrum (negative measurement) and IR spectrum (KBr method), the same spectra as those of Example 22 were obtained. Therefore, it was confirmed that the product was dihydroxysilicon phthalocyanine.
Reaction SMILES: CN(C)C=O.[CH3:6][O:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][C:17]=1[OH:18])[N:14]=[CH:13][CH:12]=[C:11]2[O:19][C:20]1[C:21]([CH3:30])=[N:22][C:23]2[C:28]([CH:29]=1)=[CH:27][CH:26]=[CH:25][CH:24]=2.C(=O)([O-])[O-].[K+].[K+].[CH2:37]([CH:39]1[O:41][CH2:40]1)Br>O>[CH3:6][O:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][C:17]=1[O:18][CH2:37][CH:39]1[CH2:40][O:41]1)[N:14]=[CH:13][CH:12]=[C:11]2[O:19][C:20]1[C:21]([CH3:30])=[N:22][C:23]2[C:28]([CH:29]=1)=[CH:27][CH:26]=[CH:25][CH:24]=2
Reactant: COc1cc2c(Oc3cc4ccccc4nc3C)ccnc2cc1O
Reactant: BrCC1CO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1cc2c(Oc3cc4ccccc4nc3C)ccnc2cc1OCC1CO1
Temperature: 80 °C
Reaction time: 8 h
Yield: 53.1 %

Procedure:
N,N-Dimethylformamide (3 ml) was added to 6-methoxy-4-(2-methyl-quinolin-3-yloxy)-quinolin-7-ol (compound 352) (100 mg), potassium carbonate (125 mg), and epibromohydrin (124 mg), and the mixture was stirred at 80° C. overnight. The reaction solution was cooled to room temperature, water was added to the reaction solution, and the mixture was extracted with chloroform. The chloroform layer was washed with water and was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using chloroform-methanol to give the title compound (62 mg, yield 53%).
Reaction SMILES: [Li][CH2:2]CCC.[CH3:6][CH2:7][C:8]([C:10]1[CH:15]=[CH:14][C:13]([Br:16])=[CH:12][CH:11]=1)=O>CCOCC.[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:16][C:13]1[CH:14]=[CH:15][C:10]([C:8](=[CH2:2])[CH2:7][CH3:6])=[CH:11][CH:12]=1
Reactant: [Li]CCCC
Reactant: CCC(=O)c1ccc(Br)cc1
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Solvent: CCOCC
Product: C=C(CC)c1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 32.9 %

Procedure:
To a solution of n-BuLi (2.79 ml, 1.6M solution in hexane, 4.46 mmol) in ether was added solid methyltriphenylphosphonium bromide (1.59 g, 4.46 mmol) in three portions. The mixture was stirred at rt for 4 h, and then a solution of 4-bromopropio-phenone (1.00 g, 4.69 mmol) in ether was added and the mixture was gently refluxed overnight. The mixture was filtered and the filtrate was washed with water and brine, dried (MgSO4), filtered and concentrated in vacuo to give a residue which was purified by flash column chromatography to give 1-bromo-4-(1-methylenepropyl)-benzene (310 mg, 31%) as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ 7.45 (d, J=9.0 Hz, 2H), 7.28 (d, J=9.0 Hz, 2H), 5.26 (m, 1H), 5.07 (m, 1H), 2.48 (q, J=7.5 Hz, 2H), 1.09 (t, J=7.5 Hz, 3H).
Reaction SMILES: CO[C:3]([C:5]1[S:9][C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)=[N:7][C:6]=1[CH:20]([CH3:22])[CH3:21])=[O:4].Cl.[CH3:24][O:25][NH2:26].[CH:27]([Mg]Cl)(C)C.[Cl-].[NH4+]>C(OCC)C.O1CCCC1>[CH3:24][O:25][N:26]([CH3:27])[C:3]([C:5]1[S:9][C:8]([C:10]2[CH:11]=[CH:12][C:13]([C:16]([F:17])([F:19])[F:18])=[CH:14][CH:15]=2)=[N:7][C:6]=1[CH:20]([CH3:22])[CH3:21])=[O:4]
Reactant: CC(C)[Mg]Cl
Reactant: COC(=O)c1sc(-c2ccc(C(F)(F)F)cc2)nc1C(C)C
Reactant: CON
Agent: Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: CON(C)C(=O)c1sc(-c2ccc(C(F)(F)F)cc2)nc1C(C)C
Temperature: -30 °C
Yield: 21.8 %

Procedure:
4-Isopropyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid methyl ester (14 g, 40.1 mmol) is dissolved into anhydrous tetrahydrofuran (THF) (200 mL) and then cooled to −30° C. while stirring under nitrogen. N-methyl, N-methoxy amine hydrochloride (0.881 g, 9.04 mmol) is then added to the solution in one portion. Isopropyl magnesium chloride (8.73 mL, 2M soln. in THF, 17.46 mmol) is slowly added to the cooled suspension over 1 h. TLC will show complete consumtion of starting material, then 30% solution of ammonium chloride is added with stirring. The reaction is diluted with diethyl ether and extracted. The organic layer is collected and washed with cold water (2×) and brine. The solution is then dried over anhydrous sodium sulfate, filtered, and concentrated. The 4-Isopropyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid methoxy-methyl-amide (0.705 g, 1.97 mmol) is obtained in pure form after flash column chromatography.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=O)([O-:3])=[O:2].[CH:12]([O:15][C:16](=[O:23])[CH:17]=[C:18]([NH2:22])[O:19][CH2:20][CH3:21])([CH3:14])[CH3:13]>C(O)C>[CH:12]([O:15][C:16]([C:17]1[CH:7]([C:6]2[CH:9]=[CH:10][CH:11]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[CH:17]([C:16]([O:15][CH:12]([CH3:13])[CH3:14])=[O:23])[C:18]([O:19][CH2:20][CH3:21])=[N:22][C:18]=1[NH2:22])=[O:23])([CH3:14])[CH3:13]
Reactant: CCOC(N)=CC(=O)OC(C)C
Reactant: O=Cc1cccc([N+](=O)[O-])c1
Solvent: CCO
Product: CCOC1=NC(N)=C(C(=O)OC(C)C)C(c2cccc([N+](=O)[O-])c2)C1C(=O)OC(C)C

Procedure:
Heating a solution of 6.1 g of 3-nitrobenzaldehyde and 13.9 g of 3-amino-3-ethoxyacrylic acid isopropyl ester in 100 ml of ethanol for 8 hours yields 2-amino-6-ethoxy-4-(3-nitrophenyl)-4,5-dihydropyridine-3,5-dicarboxylic acid diisopropyl ester of melting point 130°C (ether/petroleum ether).