Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[CH2:5]2.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C1COCC1.O=[C:28]1[C:36]2[C:31](=[CH:32][C:33]([CH2:37][CH2:38][C:39]([OH:41])=[O:40])=[CH:34][CH:35]=2)[CH2:30][O:29]1.S(=O)(=O)(O)O>C1COCC1.O>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[C:28]1[C:36]2[C:31](=[CH:32][C:33]([CH2:37][CH2:38][C:39]([OH:41])=[O:40])=[CH:34][CH:35]=2)[CH2:30][O:29]1
Reactant: O=C1Cc2cc(F)ccc2N1
Reactant: O=C(O)CCc1ccc2c(c1)COC2=O
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: O=S(=O)(O)O
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)CCc1ccc2c(c1)COC2=C1C(=O)Nc2ccc(F)cc21
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 58.9 %

Procedure:
To a stirred solution of 5-fluorooxindole (218 mg, 1.44 mmol) in anhydrous THF (10 ml) under nitrogen was added 1.0M LiHMDS/THF solution (2.9 ml, 2.9 mmol). After the mixture was stirred at room temperature for 10 minutes, 3-(1-Oxo-1,3-dihydro-isobenzofuran-5-yl)-propionic acid (100 mg, 0.48 mmol) was added. After the mixture was stirred at room temperature for 2 hours, 1 M sulfuric acid solution (10 ml) was added. The mixture was heated at 60° C. for 2 hours, and then poured into 150 ml of water. The resulting solid was filtered, rinsed with water, dried in vacuo to give the title compound as a yellow solid (96 mg, 59%).
Reaction SMILES: [CH:1]1([CH2:6][C@H:7]([CH2:38][N:39]([CH:48]=[O:49])[O:40]CC2C=CC=CC=2)[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][N:21]=[C:20]([CH2:24][N:25]([CH3:27])[CH3:26])[N:19]=3)=[O:16])[CH2:13][CH2:12][N:11]2C(OCC2C=CC=CC=2)=O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1>[OH-].[OH-].[Pd+2].CO>[CH:1]1([CH2:6][C@H:7]([CH2:38][N:39]([CH:48]=[O:49])[OH:40])[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][N:21]=[C:20]([CH2:24][N:25]([CH3:26])[CH3:27])[N:19]=3)=[O:16])[CH2:13][CH2:12][NH:11]2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: CN(C)Cc1nccc(NC(=O)[C@@H]2CCN(C(=O)OCc3ccccc3)N2C(=O)[C@H](CC2CCCC2)CN(C=O)OCc2ccccc2)n1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: CN(C)Cc1nccc(NC(=O)[C@@H]2CCNN2C(=O)[C@H](CC2CCCC2)CN(O)C=O)n1
Reaction time: 2 h
Yield: 58.1 %

Procedure:
A mixture of phenylmethyl (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-3-[({2-[(dimethylamino)methyl]-4-pyrimidinyl}amino)carbonyl]-1-pyrazolidine carboxylate (104 mg, 0.155 mmol) and Pearlman's catalyst (21.74 mg, 0.031 mmol) in methanol (8.6 ml) was degassed and placed under 1 atm of H2 at ambient temperature. After 2 hrs, the reaction mixture was filtered and concentrated to give a residue which was purified by RP-HPLC to give (3S)-2-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-{2-[(dimethyl amino)methyl]-4-pyrimidinyl}-3-pyrazolidine carboxamide (41 mg, 0.090 mmol, 58% yield). MS (ES+) m/z 448.2 (MH+).
Reaction SMILES: [N+:1]([C:4]1[C:9](O)=[C:8]([NH2:11])[CH:7]=[C:6](C)[CH:5]=1)([O-:3])=[O:2].C1(N2C(=[O:24])C=C(CS(O)(=O)=O)N2)C=CC=CC=1>[Cr].O>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([OH:24])=[C:8]([NH2:11])[CH:9]=1)([O-:3])=[O:2]
Reactant: Cc1cc(N)c(O)c([N+](=O)[O-])c1
Reactant: O=c1cc(CS(=O)(=O)O)[nH]n1-c1ccccc1
Agent: [Cr]
Solvent: O
Product: Nc1cc([N+](=O)[O-])ccc1O

Procedure:
45.4 Parts of the 1:1 chromium complex (obtained by the known process and containing 1 atom of chromium for each molecule of monoazo dyestuff) of the azo dyestuff from diazotised 6-nitro-4-methyl-2-amino-1-hydroxybenzene and 1-phenyl-3-sulphomethyl-5-pyrazolone are stirred in 1000 parts of hot water together with 33.9 parts of the monoazo dyestuff obtained by the known process from diazotised 4-nitro-2-amino-1-hydroxybenzene. The suspension is adjusted to pH 7 to 8 by addition of 20 parts vy volume of concentrated sodium hydroxide solution and subsequently stirred at 90°-95° C. until both starting dyestuffs can no longer be detected. The unitary chromium mixed complex present in clear solution is precipitated by the addition of sodium chloride, isolated by filtration, washed with sodium chloride solution, and then dried in vacuo. After it has been ground, the dyestuff is in the form of a dark red, readily water-soluble powder from a bath containing ammonium sulphate dyes wool or polyamide fibres in full scarlet shades with good fastness properties. It has the following constitution: ##STR15##
Reaction SMILES: [C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH:27]([F:29])[F:28])[CH:24]=4)[NH:19][N:18]=3)[N:15]=2)[N:10]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[CH2:39][CH2:40][CH2:41][N:42]1[CH2:46][CH2:45][C:44]([F:48])([F:47])[CH2:43]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH:27]([F:28])[F:29])[CH:24]=4)[N:19]([CH2:39][CH2:40][CH2:41][N:42]4[CH2:46][CH2:45][C:44]([F:48])([F:47])[CH2:43]4)[N:18]=3)[N:15]=2)[N:10]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: FC1(F)CCN(CCCCl)C1
Reactant: CC(C)(C)NC(=O)c1cn(COCC[Si](C)(C)C)c2ncc(-c3n[nH]c4ccc(OC(F)F)cc34)nc12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CC(C)(C)NC(=O)c1cn(COCC[Si](C)(C)C)c2ncc(-c3nn(CCCN4CCC(F)(F)C4)c4ccc(OC(F)F)cc34)nc12
Yield: 71.4 %

Procedure:
N-tert-Butyl-2-(5-(difluoromethoxy)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (100 mg, 188 μmol), 1-(3-chloropropyl)-3,3-difluoropyrrolidine (34.6 mg, 188 μmol) and cesium carbonate (184 mg, 565 μmol) in dimethylformamide (2 mL) were heated in a microwave at 100° C. for 30 min. The mixture was cooled and partitioned between ethyl acetate and water. The organic phase was washed with water 3 times then dried and concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes) gave N-tert-butyl-2-(5-(difluoromethoxy)-1-(3-(3,3-difluoropyrrolidin-1-yl)propyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (91 mg, 72%). MS (M+H)+=678.
Reaction SMILES: [Br-].[C:2]([O:6][C:7](=[O:10])[CH2:8][Zn+])([CH3:5])([CH3:4])[CH3:3].Br[C:12]1[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][C:13]=1[C:14](/[N:16]=[C:17]1/[N:18]([CH2:27][C@H:28]2[CH2:32][CH2:31][CH2:30][O:29]2)[N:19]([CH3:26])[C:20]([C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:21]/1)=[O:15].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>CCOCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:22]([C:20]1[N:19]([CH3:26])[N:18]([CH2:27][C@H:28]2[CH2:32][CH2:31][CH2:30][O:29]2)/[C:17](=[N:16]/[C:14]([C:13]2[CH:33]=[C:34]([C:37]([F:38])([F:39])[F:40])[CH:35]=[CH:36][C:12]=2[CH2:8][C:7]([O:6][C:2]([CH3:5])([CH3:4])[CH3:3])=[O:10])=[O:15])/[CH:21]=1)([CH3:25])([CH3:23])[CH3:24]
Reactant: Cn1c(C(C)(C)C)c/c(=N\C(=O)c2cc(C(F)(F)F)ccc2Br)n1C[C@H]1CCCO1
Reactant: CC(C)(C)OC(=O)C[Zn+]
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: COc1cccc(OC)c1-c1ccccc1P(C1CCCCC1)C1CCCCC1
Solvent: CCOCC
Product: Cn1c(C(C)(C)C)c/c(=N\C(=O)c2cc(C(F)(F)F)ccc2CC(=O)OC(C)(C)C)n1C[C@H]1CCCO1
Temperature: 50 °C
Reaction time: 8 h
Yield: 68.2 %

Procedure:
A solution of (2-tert-butoxy-2-oxoethyl)zinc(II) bromide (2.13 mL, 1.07 mmol) in ether (3 mL) was added to a mixture of Example 88 (260 mg, 0.532 mmol), palladium acetate (12.0 mg, 0.053 mmol), and dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (82 mg, 0.20 mmol). The mixture was stirred at 50° C. overnight then quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate (3×10 mL). The organic extracts were combined, washed with water, dried (MgSO4), filtered, and concentrated. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 15-100% solvent A in hexanes, solvent A=10:1:0.5 ethyl acetate:methanol:triethyl amine) to afford the title compound (0.19 g, 0.363 mmol, 68.2% yield). 1H NMR (300 MHz, CDCl3) δ ppm 1.41 (s, 9H) 1.42 (s, 9H) 1.72-1.88 (m, 3H) 2.00-2.10 (m, 1H) 3.62 (q, J=7.27 Hz, 1H) 3.68-3.82 (m, 2H) 3.87 (s, 3H) 4.19 (d, J=7.93 Hz, 2H) 4.23-4.32 (m, 1 H) 4.53-4.61 (m, 1H) 7.01 (s, 1H) 7.30 (d, J=8.33 Hz, 1H) 7.51 (dd, J=8.13, 1.39 Hz, 1H) 8.38 (s, 1H); MS (DCI/NH3) m/z 524 (M+H)+.
Reaction SMILES: [NH:1]1[C:7](=O)[CH2:6]C[CH2:4][C:3]2[CH:9]=[CH:10][CH:11]=[CH:12][C:2]1=2.[CH2:13]([NH2:16])[CH:14]=[CH2:15].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.ClCCl>[CH2:13]([NH:16][CH2:4][C:3]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:2]=1[NH:1][CH:7]=[CH:6]2)[CH:14]=[CH2:15]
Reactant: C=CCN
Reactant: O=C1CCCc2ccccc2N1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Solvent: ClCCCl
Product: C=CCNCc1cccc2cc[nH]c12
Temperature: 22 °C
Reaction time: 5 h
Yield: 81.9 %

Procedure:
To a solution of indole-7-carboxaldehyde 1 (4.00 g, 27.6 mmol) in 1,2-dichloroethane (120 mL) at 20-24° C. was added allylamine (2.50 mL, 33.1 mmol), acetic acid (3.4 mL), and sodium triacetoxyborohydride (5.85 g, 27.6 mmol). The resulting mixture was stirred at 20-24° C. for 5 hours. An additional 1.5 g (7.1 mmol) of sodium triacetoxyborohydride was added and the resulting mixture was stirred overnight. The mixture was diluted with dichloromethane (300 mL), washed carefully with aqueous sodium bicarbonate (100 mL), and the layers were separated. The organic layer was washed with water (100 mL), saturated aqueous sodium chloride (100 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with 10-30% ethyl acetate in hexanes. Fractions containing product were combined and concentrated under reduced pressure to provide 4.21 g (82%) of the desired compound as a light yellow oil.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:7]=[C:8]2[O:12][CH2:11][O:10][C:9]=12)[CH:5]=[O:6].[CH3:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C:2]1[CH:3]=[C:4]([CH:7]=[C:8]2[O:12][CH2:11][O:10][C:9]=12)[CH:5]=[O:6]
Reactant: COc1ccccc1B(O)O
Reactant: O=Cc1cc(Br)c2c(c1)OCO2
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: COCCOC
Solvent: CCOC(C)=O
Product: COc1ccccc1-c1cc(C=O)cc2c1OCO2
Temperature: 25 °C
Yield: 32.4 %

Procedure:
A mixture of 3-bromo-4,5-methylenedioxybenzaldehyde (2.51 g, 10.97 mmol), 2-methoxyphenylboronic acid (2.00 g, 13.16 mmol) and potassium carbonate (3.41 g, 24.68 mmol) in 1,2-dimethoxyethane (70 mL) and water (3.5 mL) was degassed with argon for 30 minutes. Tetrakis(triphenylphosphine)palladium(0) (0.63 g, 0.548 mmol) was added and the mixture heated at reflux under argon overnight. The solution was cooled to room temperature, diluted with ethyl acetate (100 mL) and washed successively with water (50 mL) and brine (50 mL), dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was purified on silica gel (eluent: hexane:ether, 9:1) to give 0.910 g of 3-(2-methoxyphenyl)-4,5-methylenedioxybenzaldehyde (32%) as a white solid. 1H NMR (300 MHz; CDCl3): δ 3.84 (s, 3H); 6.07 (s, 2H); 7.00–7.10 (m, 2H); 7.31 (brs, 1H); 7.30–7.45 (m, 2H); 7.53 (brs, 1H); 9.83 (s, 1H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]([O:10][CH3:11])=[O:9])[S:5][C:6]=1[CH3:7].[S:12]1[CH:16]=[CH:15][CH:14]=[C:13]1[S:17](Cl)(=[O:19])=[O:18]>N1C=CC=CC=1>[CH3:7][C:6]1[S:5][C:4]([C:8]([O:10][CH3:11])=[O:9])=[CH:3][C:2]=1[NH:1][S:17]([C:13]1[S:12][CH:16]=[CH:15][CH:14]=1)(=[O:19])=[O:18]
Reactant: COC(=O)c1cc(N)c(C)s1
Reactant: O=S(=O)(Cl)c1cccs1
Solvent: c1ccncc1
Product: COC(=O)c1cc(NS(=O)(=O)c2cccs2)c(C)s1
Temperature: 25 °C
Reaction time: 2 h
Yield: 96.3 %

Procedure:
To a mixture of methyl 4-amino-5-methylthiophene-2-carboxylate (20 g) and pyridine (100 mL) was added 2-thiophen-sulfonyl chloride (23.5 g) at 0° C., and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated, water was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography to give methyl 5-methyl-4-[(2-thienylsulfonyl)amino]thiophene-2-carboxylate (35.7 g, yield 96%) as pale-yellow crystals from a fraction eluted with ethyl acetate-hexane (1:3, volume ratio).
Reaction SMILES: Br[CH2:2][C:3]1[O:7][N:6]=[C:5]([NH:8][C:9](=[O:12])[O:10][CH3:11])[CH:4]=1.ClCC1N(C)N=C(C)N=1.[CH:22]1([C:27]2([CH2:35][CH2:36][C:37]3[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=3)[O:32][C:31](=[O:33])[CH2:30][C:29](=[O:34])[CH2:28]2)[CH2:26][CH2:25][CH2:24][CH2:23]1>>[CH:22]1([C:27]2([CH2:35][CH2:36][C:37]3[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=3)[O:32][C:31](=[O:33])[C:30]([CH2:2][C:3]3[O:7][N:6]=[C:5]([NH:8][C:9](=[O:12])[O:10][CH3:11])[CH:4]=3)=[C:29]([OH:34])[CH2:28]2)[CH2:26][CH2:25][CH2:24][CH2:23]1
Reactant: COc1ccc(CCC2(C3CCCC3)CC(=O)CC(=O)O2)cc1
Reactant: COC(=O)Nc1cc(CBr)on1
Agent: Cc1nc(CCl)n(C)n1
Product: COC(=O)Nc1cc(CC2=C(O)CC(CCc3ccc(OC)cc3)(C3CCCC3)OC2=O)on1
Yield: 13 %

Procedure:
The title compound was prepared as described in Example B(53), using methyl 5-(bromomethyl)isoxazol-3-ylcarbamate (prepared as described: Sircar, J. C.; Capiris, T. U.S. Pat. No. 4,489,077, Dec. 18, 1984) in place of 5-(chloromethyl)-1,3-dimethyl-1H-1,2,4-triazole, and using 6-cyclopentyl-6-[2-(4-methoxyphenyl)ethyl]dihydro-2H-pyran-2,4(3H)-dione in place of 6-[2-(3-chloro-4-methoxyphenyl)ethyl]-6-cyclopentyldihydro-2H-pyran-2,4(3H)-dione. Yield: 13%. 1H NMR (300 MHz, DMSO-d6) δ 1.15-1.65 (m, 8H), 1.80 (m, 2H), 2.25 (m, 1H), 2.39-2.51 (m, 3H, overlap with DMSO-d5), 2.68 (d, J=17.4 Hz, 1H), 3.51 (s, 2H), 3.56 (s, 3H), 3.61 (s, 3H), 6.24 (s, 1H), 6.72 (d, J=8.4 Hz, 2H), 6.95 (d, J=8.4 Hz, 2H), 10.47 (s, 1H), 11.15 (br s, 1H). LC-MS (APCI) calcd for C25H30N2O7: 470.21; found (M+H+) 471.1 m/z.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8]O)=[N:6][CH:7]=1.S(Cl)([Cl:12])=O>C(Cl)Cl>[Cl:12][CH2:8][C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][N:6]=1
Reactant: OCc1ccc(F)cn1
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: Fc1ccc(CCl)nc1
Reaction time: 0.5 h
Yield: 70.4 %

Procedure:
To a solution of (5-fluoro-pyridin-2-yl)-methanol (945 mg, 7.43 mmol) described in Manufacturing Example 41-1-1 in methylene chloride (70 mL) was added dropwise thionyl chloride (813 μL, 11.1 mmol) at room temperature, which was stirred for 30 minutes. This reaction solution was partitioned by addition of water, sodium hydrogencarbonate and methylene chloride. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under a reduced pressure. The residue was purified by NH silica gel column chromatography (hexane: diethyl ether=1:1) to obtain the title compound (761.1 mg, 70%).
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([O-:5])=[O:4].[NH+]1C=CC=CC=1.[F:14][C:15]([F:19])([F:18])[CH2:16]O.FC(F)(F)C(Cl)=O>>[F:1][C:2]([F:7])([F:6])[C:3]([O:5][CH2:16][C:15]([F:19])([F:18])[F:14])=[O:4]
Reactant: OCC(F)(F)F
Reactant: O=C([O-])C(F)(F)F
Agent: O=C(Cl)C(F)(F)F
Agent: c1cc[nH+]cc1
Product: O=C(OCC(F)(F)F)C(F)(F)F
Yield: 566.8 %

Procedure:
30 g (0.16 mole) of pyridinium trifluoroacetate in 355 g (3.55 mole) of 2,2,2-trifluoroethanol were introduced as an initial charge into a laboratory circulating reactor apparatus (one-liter four-necked flask fitted with KPG stirrer, a Prominent pump, and a 30 cm column packed with Raschig rings), and the initial charge was circulated at an internal temperature of 54° C. 134 g (1.01 mole) of trifluoroacetyl chloride were subsequently metered into the flask via an immersed inlet tube over a period of 100 minutes. After the trifluoroacetyl chloride addition was complete, the mixture was allowed to react for a further 10 minutes. Subsequent fractional distillation of the reaction mixture via a Vigreux column (temperature at the distillation head: from 54° to 56° C.) yielded 177.8 g of trifluoroethyl trifluoroacetate, corresponding to 89.8% of the theoretical yield. The trifluoroethanol/pyridinium salt mixture remaining in the reservoir flask can be used again for esterification with equal effectiveness.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=1)[C:6](O)=[O:7])#[N:2].CN(C=O)C.C(Cl)(=O)C([Cl:24])=O.CO.ClCCl>ClCCl>[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=1)[C:6]([Cl:24])=[O:7])#[N:2]
Reactant: O=C(Cl)C(=O)Cl
Reactant: N#Cc1cc(C(=O)O)cc(C(F)(F)F)c1
Solvent: CO
Solvent: ClCCl
Solvent: CN(C)C=O
Product: N#Cc1cc(C(=O)Cl)cc(C(F)(F)F)c1
Temperature: 0 °C
Reaction time: 1.5 h

Procedure:
In a 3-neck 100 mL round-bottomed flask, 3-cyano-5-(trifluoromethyl)benzoic acid (2.5 g, 1 eq.) was dissolved in dichloromethane (25 mL, 10 Vol) and cool to 0° C. added DMF (0.2 mL, cat.). Then added oxalyl chloride drop wise in 0.5 hr. The reaction mixture was stirred at 0° C. for 1-2 hr. Reaction completion was monitored on TLC using MeOH:dichloromethane (1:9) mobile phase. Reaction mixture was concentrated under reduced pressure to afford 3.0 g of crude 3-cyano-5-(trifluoromethyl)benzoyl chloride, which was immediately used for next step.
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]#[C:5][C:6]1[CH:15]=[CH:14][C:9]([C:10]([O:12][CH3:13])=[O:11])=[CH:8][CH:7]=1.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]=[C:24]=[O:25])=[CH:19][CH:18]=1.C(N(CC)CC)C>C1COCC1.C(OCC)(=O)C>[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([NH:23][C:24](=[O:25])[NH:2][CH2:3][C:4]#[C:5][C:6]2[CH:15]=[CH:14][C:9]([C:10]([O:12][CH3:13])=[O:11])=[CH:8][CH:7]=2)=[CH:19][CH:18]=1
Reactant: O=C=Nc1ccc(Cl)cc1
Reactant: COC(=O)c1ccc(C#CCN)cc1
Agent: Cl
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: COC(=O)c1ccc(C#CCNC(=O)Nc2ccc(Cl)cc2)cc1
Reaction time: 0.5 h

Procedure:
To a solution of methyl 4-(3-aminoprop-1-ynyl)benzoate hydrochloride (see Example 1, Steps 1-3 above; 150 mg, 0.66 mmol) in THF (5 ml) was added 4-chlorophenyl isocyanate (102 mg, 0.66 mmol) and triethylamine (278 μL, 2.0 mmol). The reaction mixture was stirred for 30 min, diluted with ethyl acetate (50 ml), and sequentially washed with water (25 ml), 0.5M aqueous HCl (25 ml), saturated sodium bicarbonate (25 ml), and finally with brine (25 ml). The organic phase was dried over sodium sulfate and concentrated in vacuo to provide methyl 4-[3-(3-(4-chlorophenyl)-ureido)prop-1-ynyl]-benzoate as a white solid.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[CH2:11][OH:12].[CH3:13][S:14](Cl)(=[O:16])=[O:15].C(N(CC)CC)C>C(Cl)Cl>[CH3:13][S:14]([O:12][CH2:11][C:3]1[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[Br:1])(=[O:16])=[O:15]
Reactant: O=[N+]([O-])c1ccc(Br)c(CO)c1
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCc1cc([N+](=O)[O-])ccc1Br
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of the (2-bromo-5-nitrophenyl)methanol from Step A (0.33 g, 1.42 mmol) in methylene chloride (20 ml) at 0° C., methanesulfonyl chloride (0.13 ml, 1.70 mmol) and triethylamine (0.3 ml, 2.1 mmol) were added. The solution was stirred at 0° C. for 1 h. The reaction was diluted with methylene chloride (30 ml). The solution was washed with water, brine, and dried over sodium sulfate. The title compound was obtained by flash column chromatography using 10:90 EtOAc/hexane as the eluant. 1H NMR (CDCl3, 500 MHz) δ 8.40 (d, J=2.5 Hz, 1H), 8.17 (dd, J=8.5, 3.0 Hz, 1H), 7.82 (d, J=8.5 Hz, 1H), 5.40 (s, 2H), 3.20 (s, 3H).
Reaction SMILES: F[C:2]1(C(C2C=CC=CC=2)=O)[CH:16]=[CH:15][C:5]([C:6](C2C=CC(F)=CC=2)=[O:7])=[CH:4][CH2:3]1.[Cl:25][C:26]1[CH:40]=[CH:39][C:29]([C:30]([C:32]2[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=2)=[O:31])=[CH:28][C:27]=1C(C1C=CC=CC=1)=O.FC1C=CC(C(C2C=CC(F)=CC=2)=O)=CC=1C(C1C=CC=CC=1)=O.[N+](C1C=C(C=CC=1F)C(C1C=CC(F)=C([N+]([O-])=O)C=1)=O)([O-])=O.[N+](C1C=C(C=CC=1Cl)C(C1C=CC(Cl)=C([N+]([O-])=O)C=1)=O)([O-])=O>>[Cl:25][C:26]1([C:6]([C:5]2[CH:15]=[CH:16][CH:2]=[CH:3][CH:4]=2)=[O:7])[CH:40]=[CH:39][C:29]([C:30]([C:32]2[CH:33]=[CH:34][C:35]([Cl:38])=[CH:36][CH:37]=2)=[O:31])=[CH:28][CH2:27]1
Reactant: O=C(C1=CCC(F)(C(=O)c2ccccc2)C=C1)c1ccc(F)cc1
Reactant: O=C(c1ccc(Cl)cc1)c1ccc(Cl)c(C(=O)c2ccccc2)c1
Agent: O=C(c1ccc(Cl)c([N+](=O)[O-])c1)c1ccc(Cl)c([N+](=O)[O-])c1
Agent: O=C(c1ccc(F)c([N+](=O)[O-])c1)c1ccc(F)c([N+](=O)[O-])c1
Agent: O=C(c1ccc(F)cc1)c1ccc(F)c(C(=O)c2ccccc2)c1
Product: O=C(C1=CCC(Cl)(C(=O)c2ccccc2)C=C1)c1ccc(Cl)cc1

Procedure:
##STR16## 4,4'-difluoroterephthalophenone: ##STR17## 4,4'-dichloro-isophthalophenone: ##STR18## 4,4'-difluoro-isophthalophenone: ##STR19## 4,4'-bis-(p-chlorobenzoyl)-diphenyl ether: ##STR20## 4,4'-bis-(p-fluorobenzoyl)-diphenyl ether: ##STR21## 3,3'-dinitro-4,4'-dichlorobenzophenone 3,3'-dinitro-4,4'-difluorobenzophenone
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]([OH:12])=[O:11])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1>C(#N)C>[CH:5]1[C:6]([C:10]([OH:12])=[O:11])=[CH:7][CH:8]=[C:9]2[C:4]=1[C:3]1[C:2]([NH:1]2)=[C:2]2[NH:1][C:9]3[CH:8]=[CH:7][C:6]([C:10]([OH:12])=[O:11])=[CH:5][C:4]=3[C:3]2=[C:2]2[NH:1][C:9]3[CH:8]=[CH:7][C:6]([C:10]([OH:12])=[O:11])=[CH:5][C:4]=3[C:3]=12
Reactant: O=C(O)c1ccc2[nH]ccc2c1
Solvent: CC#N
Product: O=C(O)c1ccc2[nH]c3c4[nH]c5ccc(C(=O)O)cc5c4c4c5cc(C(=O)O)ccc5[nH]c4c3c2c1
Reaction time: 0.25 h
Yield: 89.9 %

Procedure:
15 ml of acetonitrile was poured into a 200 ml three-neck flask, and 1.61 g of indole-5-carboxylic acid was dissolved therein. On the other hand, preparation of an oxidant solution was performed by dissolving 47.4 g of cupric tetrafluoroborate n-hydrate (Cu content: 20%) in 100 ml of acetonitrile and agitating the mixture for 15 minutes. pH of the reaction solution was less than 1. Then the prepared oxidant solution was dripped over 60 minutes into the indole-5-carboxylic acid solution, and the resultant mixture solution was agitated for 5 hours at the temperature of 30° C. Color of the reaction solution changed from yellow to blue-green with slight heat generation. After the end of the reaction, the reaction liquid was suction-filtered with a perforated funnel, and the filtrate was washed with acetonitrile and then methanol, and was dried to obtain 1.43 g of 6,11-dihydro-5H-diindolo [2,3-a:2′,3′-c] carbazole-2,9,14-tricarboxylic acid (indole-5-calboxylic acid trimer) with a blue-green color (yield: 89%). The resultant trimer was pressure-molded with a tablet molding machine and the mold was cut into a piece with the diameter of 10 mm and thickness of 1 mm. A conductivity thereof was measured by the four terminal method, and found to be 0.40 S/cm. The result of elemental analysis was: <C9.00H4.95N0.98O1.98Cl0.13>3.