Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([P:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.BrC(Br)(Br)Br.CC[O:27]CC>C1(C)C=CC=C(C)C=1>[C:14]1([P:7](=[O:27])([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: CCOCC
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Agent: BrC(Br)(Br)Br
Solvent: Cc1cccc(C)c1
Product: O=P(c1ccccc1)(c1ccccc1)c1ccccc1

Procedure:
2.15 gms. of triphenylphosphine and 2.85 gms. of tetrabromomethane were added to a solution of 1.65 gms. of 19-hydroxy cholesterylacetate [prepared according to the method of J. Am. Chem. Soc. 86(1964), 1528] in 70 mls. of dry ether and 10 mls. of dry m-xylene. A white precipitate of triphenylphosphine oxide was formed. Then the mixture was refluxed for 20 hours, the progress of the reaction being examined with the aid of thin-layer chromatography (toluene/ethyl acetate 3:1; silica gel H). After completion of the reaction 100 mls. of n-hexane and 0.5 mls. of methanol were added and approx. 15 minutes later the mixture was filtered and the filtrate evaporated. The residue was taken up in 10 mls. of ether and thereafter 15 mls. of n-hexane were added. Then this hexane/ether mixture was brought on to a column filled with 40 gms. of deactivated Al2O3 and subsequently was eluated with an ether/n-hexane mixture (2:3). The composition of the column fractions was examined with the aid of thin-layer chromatography. The fractions, in which 19-bromocholesterylacetate was present, (Rf = 0.7) were collected and evaporated at a film evaporator. Upon crystallization of the residue from ether/methanol, 1.45 gms. of the product were obtained, having a melting point of 91°-92° C. The structure was confirmed by means of NMR- and mass-spectrometry.
Reaction SMILES: C[O:2][C:3]([C:5]1[N:6]=[CH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2)=O.CC(C[AlH]CC(C)C)C>O1CCCC1>[CH:7]1[C:8]2[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:14]=[C:5]([CH:3]=[O:2])[N:6]=1
Reactant: COC(=O)c1cc2ccccc2cn1
Agent: CC(C)C[AlH]CC(C)C
Solvent: C1CCOC1
Product: O=Cc1cc2ccccc2cn1
Temperature: 0 °C
Reaction time: 2 h
Yield: 54.8 %

Procedure:
To a cooled solution 0° C. of isoquinoline-3-carboxylic acid methyl ester (1.0 g, 5.34 mmol) in anhydrous tetrahydrofuran (100 ml), is added a solution of DIBAL-H (11.8 ml, 11.8 mmol). The reaction mixture is stirred at 0° C. for 2 hours and then quenched with saturated aqueous sodium potassium tartrate and stirred for 2 hours. The layers are separated and the aqueous layer is extracted with ethyl acetate. The combined organic extracts are washed with 1N HCl, 2N NaOH, and dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude reaction mixture is purified on silica gel eluting with 20% ethyl acetate/hexanes to give isoquinoline-3-carboxaldehyde (0.46 g, 54%). 1H NMR (CDCl3): δ=10.24 (1H, brs), 9.32 (1H, brs), 8.35 (1H, brs), 8.02 (2H, brd), 7.77 (2H, brs).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:17](N(OC)C)=[O:18])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Al+3].[Li+].[H-].[H-].[H-].C1COCC1.S([O-])(O)(=O)=O.[K+]>CC1CCCO1.O>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH:17]=[O:18])([CH3:4])([CH3:2])[CH3:3]
Reactant: CON(C)C(=O)[C@H](Cc1ccccc1)NC(=O)OC(C)(C)C
Agent: O=S(=O)([O-])O
Agent: [Al+3]
Agent: [H-]
Solvent: O
Solvent: CC1CCCO1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N[C@H](C=O)Cc1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
1090 mg (3.5 mmol) Nα-(tert-butoxycarbonyl)-N-methoxy-N-methyl-L-phenylalanine-amide was dissolved in 20 mL 2-methyltetrahydrofuran and cooled to 0° C. Then 4.2 mL (4.2 mmol) of a 1M lithium aluminum hydride solution was added slowly to THF, and the reaction mixture was stirred for 30 min at 0° C. Next 5% aqueous potassium hydrogen sulfate solution was added cautiously. The batch was then diluted with water and extracted with MTBE. The organic phase was dried over magnesium sulfate and concentrated in vacuo, yielding 820 mg (94% of the theoretical) of the title compound.
Reaction SMILES: F[C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1)[C:5]#[N:6].[CH3:14][C:15]1[NH:16][CH:17]=[CH:18][N:19]=1>>[CH3:14][C:15]1[N:16]([C:2]2[CH:3]=[C:4]([CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=2)[C:5]#[N:6])[CH:17]=[CH:18][N:19]=1
Reactant: Cc1ncc[nH]1
Reactant: N#Cc1cc(F)cc(C(F)(F)F)c1
Product: Cc1nccn1-c1cc(C#N)cc(C(F)(F)F)c1

Procedure:
The title compound is prepared using an analogous method as described in Example 1.1, utilising 3-fluoro-5-(trifluoromethyl)-benzonitrile (Lancaster Synthesis GmbH) and 2-methyl-imidazole (Fluka, Buchs, Switzerland), with a reaction temperature of 145° C. for 24 hours.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH2:8][CH2:9][CH2:10]2)=[CH:6][C:5]=1[NH:13]C(=O)C)([O-:3])=[O:2].[CH]Cl>CCO.O>[N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH2:8][CH2:9][CH2:10]2)=[CH:6][C:5]=1[NH2:13])([O-:3])=[O:2]
Reactant: CC(=O)Nc1cc2c(cc1[N+](=O)[O-])CCC2
Agent: [CH]Cl
Solvent: O
Solvent: CCO
Product: Nc1cc2c(cc1[N+](=O)[O-])CCC2
Reaction time: 16 h
Yield: 73 %

Procedure:
A suspension of the mixture of acetamides 17 and 18 in EtOH (400 mL) and cHCl (180 mL) was stirred at 80° C. for 6 h. The resulting solution was cooled and diluted with water (400 mL) and allowed to stand for 16 h. The precipitate was filtered, washed with water, and air-dried to give amine 2 (27.52 g, 73%, from 16) as an orange powder: mp 129-131° C. [lit. (Schroeder, E.; et al., European J. Med. Chem. 1982, 17, 35) mp (EtOH) 128.5-129.5° C.]; 1H NMR δ 7.93 (s, 1H, H-7), 6.55 (s, 1H, H-4), 5.99 (br s, 2H, NH2), 2.79-2.88 (m, 4H, H-1, H-3), 2.02-2.10 (m, 2H, H-2); 13C NMR δ 154.3, 144.2, 134.0, 131.3, 120.8, 113.5, 33.0, 31.4, 25.7.
Reaction SMILES: [CH2:1]([O:3][C:4]1[C:5]([F:17])=[C:6]([C:15]#[N:16])[C:7](=[CH:10][C:11]=1[O:12][CH2:13][CH3:14])[C:8]#[N:9])[CH3:2].[S:18](=[O:22])(=[O:21])([OH:20])[OH:19].C(N(CC)CC)C>[OH-].[Pd+2].[OH-].[C].COCCOC>[S:18]([OH:22])([OH:21])(=[O:20])=[O:19].[CH2:13]([O:12][C:11]1[CH:10]=[C:7]2[C:6](=[C:5]([F:17])[C:4]=1[O:3][CH2:1][CH3:2])[C:15]([NH2:16])=[N:9][CH2:8]2)[CH3:14]
Reactant: CCOc1cc(C#N)c(C#N)c(F)c1OCC
Agent: [Pd+2]
Agent: O=S(=O)(O)O
Agent: [OH-]
Solvent: CCN(CC)CC
Solvent: COCCOC
Product: CCOc1cc2c(c(F)c1OCC)C(N)=NC2
Temperature: -23 °C
Reaction time: 29 h
Yield: 0 %

Procedure:
A mixture of 4,5-diethoxy-3-fluorophthalonitrile (2.34 g, 10 mol) prepared in Preparation Example 1, sulfuric acid (0.56 mL, 10 mol), 20% palladium hydroxide-carbon (0.59 g, 50% hydrate) (20% palladium-carbon powder, palladium hydroxide type (hydrate), N.E. Chemical Corporation) and 1,2-dimethoxyethane (23 mL) was stirred at −23° C. under hydrogen atmosphere (atmospheric pressure) for 29 hours. After insoluble matter in the reaction mixture was filtered off, the residue was washed with methanol (23 mL), and the combined filtrate was divided into five equal portions. To one of them, triethylamine (0.14 mL, 1 mol) was added, and the mixture was stirred at 60° C. for three hours and concentrated at 40° C. under reduced pressure. Methanol (2.3 mL) and 1,2-dimethoxyethane (6.9 mL) were added to the residue, then sulfuric acid (0.11 mL, 2 mol) was added on ice, and the mixture was stirred. Precipitated crystals were filtered, washed with a 5% methanol-1,2-dimethoxyethane solution, and dried at room temperature under reduced pressure to give 0.45 g of the title compound (yield: 72%) as grayish white crystals.
Reaction SMILES: FC(F)(F)C(O)=O.[NH2:8][CH2:9][C:10]1[C:23]([O:24][CH3:25])=[CH:22][CH:21]=[C:20]2[C:11]=1[O:12][C:13]1[C:14]([CH2:30][C:31]([O:33][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)=[O:32])=[C:15]([O:28][CH3:29])[CH:16]=[CH:17][C:18]=1[C:19]2([CH3:27])[CH3:26].[CH2:41]([O:48][C:49]([NH:51][C@H:52]([C:54](O)=[O:55])[CH3:53])=[O:50])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(=O)(O)[O-].[Na+]>C(#N)C>[CH2:41]([O:48][C:49]([NH:51][C@H:52]([C:54]([NH:8][CH2:9][C:10]1[C:23]([O:24][CH3:25])=[CH:22][CH:21]=[C:20]2[C:11]=1[O:12][C:13]1[C:14]([CH2:30][C:31]([O:33][CH2:34][C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)=[O:32])=[C:15]([O:28][CH3:29])[CH:16]=[CH:17][C:18]=1[C:19]2([CH3:27])[CH3:26])=[O:55])[CH3:53])=[O:50])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1
Reactant: COc1ccc2c(c1CN)Oc1c(ccc(OC)c1CC(=O)OCc1ccccc1)C2(C)C
Reactant: C[C@H](NC(=O)OCc1ccccc1)C(=O)O
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: O=C([O-])O
Solvent: CC#N
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc2c(c1CNC(=O)[C@H](C)NC(=O)OCc1ccccc1)Oc1c(ccc(OC)c1CC(=O)OCc1ccccc1)C2(C)C
Temperature: 25 °C
Reaction time: 36 h
Yield: 81.1 %

Procedure:
A solution of 0.35 g of benzyl 5-aminomethyl-3,6-dimethoxy-9,9-dimethylxanthene-4-acetate trifluoroacetate in 70 ml of acetonitrile was cooled to 0° and treated with 0.15 g of N-benzyloxycarbonyl-L-alanine. A total of 0.36 g of O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate and 0.17 g of sodium bicarbonate were added in several portions. The reaction mixture was stirred for a total of 36 hours and thereby warmed to room temperature, whereupon it was diluted with ice-water and extracted with methylene chloride. The organic phase was washed with water, dried over magnesium sulphate and concentrated. The residue was chromatographed several times over silica gel in chloroform/methanol, whereby 0.33 g of benzyl 5-[(N-benzyloxycarbonyl-L-alanyl)aminomethyl]-3,6-dimethoxy-9,9-dimethylxanthene-4-acetate was obtained as a colourless foam; IR 1728, 1673, 1605, 1494 cm-1.
Reaction SMILES: [NH3:1].[CH2:2]([O:4][C:5]([C@H:7]1[CH2:12][CH2:11][C@@H:10]([N:13]2[C:17]3[N:18]=[CH:19][N:20]=[C:21](Cl)[C:16]=3[C:15]([I:23])=[CH:14]2)[CH2:9][CH2:8]1)=[O:6])[CH3:3]>>[CH2:2]([O:4][C:5]([C@H:7]1[CH2:12][CH2:11][C@@H:10]([N:13]2[C:17]3[N:18]=[CH:19][N:20]=[C:21]([NH2:1])[C:16]=3[C:15]([I:23])=[CH:14]2)[CH2:9][CH2:8]1)=[O:6])[CH3:3]
Reactant: N
Reactant: CCOC(=O)[C@H]1CC[C@@H](n2cc(I)c3c(Cl)ncnc32)CC1
Product: CCOC(=O)[C@H]1CC[C@@H](n2cc(I)c3c(N)ncnc32)CC1
Temperature: -78 °C

Procedure:
Gaseous ammonia was bubbled into an'PrOH (1 mL) solution of cis-4-(4-chloro-5-iodo-pyrrolo[2,3-d]pyrimidin-7-yl)-cyclohexanecarboxylic acid ethyl ester (30 mg, 70% pure by HPLC peak area, 0.048 mmol) in a glass pressure tube, cooled to −78° C. in a dry ice/acetone bath, for 15 min. The tube was equipped with a Teflon washer, sealed and heated to 110° C. for 7 h. After that time, the excess NH3 and the solvent were evaporated. The residue was used for the next reaction without purification. A portion of above crude material were purified by HPLC to give the title compound as pale yellow oil. 1H NMR (CDCl3, 400 MHz): δ=1.31 (t, 3H, J=7.6 Hz), 1.63-1.98 (m, 6 H), 2.29-2.35 (m, 2 H), 2.73 (m, 1 H), 4.22 (q, 2 H, J=7.6 Hz), 4.64-4.71 (m, 1 H), 5.58 (brs, 2 H), 7.11 (s, 1 H), 8.26 (s, 1 H). MS (ES+): 415.0 [MH+]. tR=2.7 min (polar—5 min).
Reaction SMILES: [Br:1][C:2]1[C:6]2[CH:7]=[N:8][C:9]([C:11]([O:13]C)=[O:12])=[CH:10][C:5]=2[N:4]([C:15]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:3]=1.[OH-].[K+].Cl>CO>[Br:1][C:2]1[C:6]2[CH:7]=[N:8][C:9]([C:11]([OH:13])=[O:12])=[CH:10][C:5]=2[N:4]([C:15]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:3]=1
Reactant: COC(=O)c1cc2c(cn1)c(Br)nn2C(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)c1cc2c(cn1)c(Br)nn2C(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 50 °C

Procedure:
To a suspension of methyl 3-bromo-1-trityl-1H-pyrazolo[4,3-c]pyridine-6-carboxylate (6.0 g, 12.04 mmol) in MeOH (60 mL) was added KOH (1 N, 42.1 mL, 42.1 mmol). The reaction mixture was heated to 50° C. for 1 h. After cooling down to room temperature, 1 N HCl was added until the pH of the reaction mixture reached 4. The solid was collected by filtration and washed with H2O to afford 3-bromo-1-trityl-1H-pyrazolo[4,3-c]pyridine-6-carboxylic acid. MS ESI calc'd. for C26H19BrN3O2 [M+H]+ 484. found 484.
Reaction SMILES: [CH2:1]([NH:9][NH2:10])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.O=[C:12]([CH2:18][C:19](=O)[CH3:20])[C:13]([O:15][CH2:16][CH3:17])=[O:14]>>[CH3:20][C:19]1[N:9]([CH2:1][CH2:2][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)[N:10]=[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:18]=1
Reactant: CCOC(=O)C(=O)CC(C)=O
Reactant: NNCCc1ccccc1
Product: CCOC(=O)c1cc(C)n(CCc2ccccc2)n1

Procedure:
The title compound was prepared from phenethyl hydrazine (3.92 g, 0.029M) (obtained by the method of J. H. Biel U.S. Pat. No. 3,000,903) and ethyl 2,4-dioxovalerate (4.55 g, 0.029M) as described in Example 1, Preparation 1 as a yellow oil (3.84 g, 52%); νmax(CH2Cl2) 1720 cm−1; δH(CDCl3) 1.40 (3H, t, J7 Hz), 1.90 (3H, s), 3.14 (2H, t, J7 Hz), 4.30 (2H, t, J7 Hz), 4.41 (2H, q, J7 Hz), 6.48 (1H, s), 6.97-7.09 (2H, m), and 7.20-7.37 (3H, m); E.I. m/e 258.
Reaction SMILES: [Cl:1][C:2]1[C:11]([N+:12]([O-])=O)=[C:10]([NH:15][CH2:16][CH2:17][NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1>[Pt].C(#N)C>[NH2:12][C:11]1[C:2]([Cl:1])=[N:3][C:4]2[C:9]([C:10]=1[NH:15][CH2:16][CH2:17][NH:18][C:19](=[O:25])[O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[CH:8][CH:7]=[CH:6][CH:5]=2
Reactant: CC(C)(C)OC(=O)NCCNc1c([N+](=O)[O-])c(Cl)nc2ccccc12
Agent: [Pt]
Solvent: CC#N
Product: CC(C)(C)OC(=O)NCCNc1c(N)c(Cl)nc2ccccc12
Yield: 104.6 %

Procedure:
Platinum on carbon (1.5 g of 5%) was added to a solution of tert-butyl 2-[(2-chloro-3-nitroquinolin-4-yl)amino]ethylcarbamate (13.99 g, 38.19 mmol) in acetonitrile (100 mL) in a Parr vessel. The mixture was placed under hydrogen pressure (30 psi, 2.1×105 Pa) for three hours and then filtered through a layer of CELITE filter agent. The filtrate was concentrated under reduced pressure and further dried overnight on a vacuum pump to provide 13.46 g of tert-butyl 2-[(3-amino-2-chloroquinolin-4-yl)amino]ethylcarbamate as a light brown solid.
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[O:3][C:4]1[CH:11]=[CH:10][C:7]([CH2:8]Br)=[CH:6][CH:5]=1.[C-:14]#[N:15].[Na+].O>CN(C=O)C>[F:1][C:2]([F:13])([F:12])[O:3][C:4]1[CH:11]=[CH:10][C:7]([CH2:8][C:14]#[N:15])=[CH:6][CH:5]=1
Reactant: FC(F)(F)Oc1ccc(CBr)cc1
Reactant: [C-]#N
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: N#CCc1ccc(OC(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution containing 2.085 g (8.18 mmol) of 4-trifluoromethoxybenzyl bromide in 10 mL dry DMF was added 441 mg (8.99 mmol) of sodium cyanide. The reaction was stirred for 1 h at room temperature, poured into water and extracted with of ethyl acetate (2×40 mL). The combined organic extracts were dried (MgSO4) and evaporated. The crude product was used in the next reaction without further purification.
Reaction SMILES: S(O)(O)(=O)=O.[CH2:6]([N:8]([CH2:17][CH2:18]NS(C)(=O)=O)[C:9]1[CH:14]=[CH:13][C:12]([NH2:15])=[C:11]([CH3:16])[CH:10]=1)[CH3:7].C(=O)([O-])[O-].[Na+].[Na+].C1COCC1.S(OOS([O-])(=O)=O)([O-])(=O)=O.[NH4+].[NH4+]>O>[CH3:7][CH2:6][N:8]([C:9]1[CH:14]=[CH:13][C:12]([NH2:15])=[C:11]([CH3:16])[CH:10]=1)[CH2:17][CH3:18]
Reactant: CCN(CCNS(C)(=O)=O)c1ccc(N)c(C)c1
Agent: O=C([O-])[O-]
Agent: O=S(=O)(O)O
Agent: O=S(=O)([O-])OOS(=O)(=O)[O-]
Solvent: O
Solvent: C1CCOC1
Product: CCN(CC)c1ccc(N)c(C)c1
Temperature: 25 °C

Procedure:
To a mixture of 0.73 g of the following coupler for comparison (C-2) (Compound (2) described in U.S. Pat. No. 5,455,149), 0.80 g of N-ethyl-N-(β-methanesulfonamidoethyl)-3-methyl-4-aminoaniline sulfate, 3.75 g of sodium carbonate, 60 ml of THF and 50 ml of water, a solution of 1.45 g of ammonium persulfate dissolved in 10 ml of water was gradually added with stirring at room temperature. After stirring the reaction mixture at 60° C. for 10 minutes, the THF layer was separated and purified by silica gel column chromatography, to obtain a dye for comparison (CD-2) which was a yellow azomethine dye for comparison as shown below.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.[CH:6]1([C:11](Cl)=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7]1>ClC1C=CC=CC=1Cl>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:11]([CH:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1)=[O:12]
Reactant: O=C(Cl)C1CCCC1
Reactant: c1ccsc1
Solvent: Clc1ccccc1Cl
Product: O=C(c1cccs1)C1CCCC1
Reaction time: 1.5 h

Procedure:
Graphite (6.0 g) was added to a mixture of thiophene (2.46 g, 29.2 mmol) and cyclopentanecarboxylic acid chloride (29.2 mmol assumed--the crude mixture from Example 1) in 50 mL of o-dichlorobenzene. The mixture was heated and kept at 80° C. for 1.5 hours. It is understood that lower temperatures can be used for longer times, or higher temperatures for shorter times while achieving good yields of cyclopentyl 2-thienyl ketone. After cooling down to room temperature, graphite was removed by filtration and washed with a small portion of the o-dichlorobenzene solvent. The product mixture was subjected to mild heating to remove the residual amount of HCl. The crude cyclopentyl 2-thienyl ketone of 84% purity (GC, area % analysis) was transferred, without purification, to the bromination step of Example 3.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[C:17]([F:25])[CH:16]=1.[Cl-].C(C1C=CC=C(C(C)C)C=1[N+]1C=CN(C2C(C(C)C)=CC=CC=2C(C)C)C=1)(C)C.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:23])([F:24])[F:22])=[C:17]([F:25])[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: Fc1cc(Br)ccc1C(F)(F)F
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Agent: CC(C)(C)[O-]
Agent: CC(C)c1cccc(C(C)C)c1-n1cc[n+](-c2c(C(C)C)cccc2C(C)C)c1
Agent: [Cl-]
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1CCN(c2ccc(C(F)(F)F)c(F)c2)CC1
Temperature: 100 °C
Reaction time: 5 h
Yield: 85.9 %

Procedure:
Tert-butyl-1-piperazine-carboxylate (740 mg, 3.05 mmol) and 4-bromo-2-fluoro-1-trifluoromethyl-benzene (530 mg. 2.85 mmol) were dissolved in anhydrous toluene (6 mL, degassed). In a separate, septum-equipped vial were placed tri(dibenzylideneacetone)dipalladium(0) (152 mg, 0.17 mmol), 1,3-bis(2,6-di-i-propylphenyl)imidazolium chloride (283 mg, 0.67 mmol) and sodium t-butoxide (400 mg, 4.2 mmol). This “catalytic” vial was equipped with a magnetic stirbar and flushed with dry nitrogen. The reactant solution was next transferred to the “catalytic” vial and the mixture was stirred at 100° C. for 5 hours. After this period the mixture was combined with 20 mL of hexane/EtOAc (2:1) and was passed through a pad of Celite. The resulting filtrate was concentrated and purified using silica gel chromatography (0-20% EtOAc/Hexane) to yield 853 mg (86%) of 4-(3-Fluoro-4-trifluoromethyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester as a yellow residue. 1H NMR (400 MHz. CDCl3) 7.44-7.40 (m, 1H), 6.65-6.58 (m, 2H), 3.59-3.56 (m, 4H), 3.27-3.25 (m, 4H), 1.49 (s, 9H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[C:17]([F:25])[CH:16]=1.[Cl-].C(C1C=CC=C(CCC)C=1[N+]1C=CN(C2C(CCC)=CC=CC=2CCC)C=1)CC.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:23])([F:24])[F:22])=[C:17]([F:25])[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: Fc1cc(Br)ccc1C(F)(F)F
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Agent: CC(C)(C)[O-]
Agent: CCCc1cccc(CCC)c1-n1cc[n+](-c2c(CCC)cccc2CCC)c1
Agent: [Cl-]
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1CCN(c2ccc(C(F)(F)F)c(F)c2)CC1
Temperature: 100 °C
Reaction time: 5 h
Yield: 85.9 %

Procedure:
Tert-butyl-1-piperazine-carboxylate (740 mg, 3.05 mmol) and 4-bromo-2-fluoro-1-trifluoromethyl-benzene (530 mg. 2.85 mmol) were dissolved in anhydrous toluene (6 mL, degassed). In a separate, septum-equipped vial were placed tri(dibenzylideneacetone)dipalladium (0) (152 mg, 0.17 mmol), 1,3-bis(2,6-di-1-propylphenyl)imidazolium chloride (283 mg, 0.67 mmol) and sodium t-butoxide (400 mg, 4.2 mmol). This “catalytic” vial was equipped with a magnetic stirbar and flushed with dry nitrogen. The reactant solution was next transferred to the “catalytic” vial and the mixture was stirred at 100° C. for 5 hours. After this period the mixture was combined with 20 mL of hexane/EtOAc (2:1) and was passed through a pad of Celite. The resulting filtrate was concentrated and purified using silica gel chromatography (0-20% EtOAc/Hexane) to yield 853 mg (86%) of 4-(3-Fluoro-4-trifluoromethyl-phenyl)-piperazine-1-carboxylic acid tert-butyl ester as a yellow residue. 1H NMR (400 MHz, CDCl3) δ 7.44-7.40 (m, 1H), 6.65-6.58 (m, 2H), 3.59-3.56 (m, 4H), 3.27-3.25 (m, 4H), 1.49 (s, 9H).
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: O
Solvent: CN(C)C=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.