Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[F:9][B-](F)(F)F.F[N+]1C(C(Cl)(Cl)Cl)=CC=CC=1Cl>ClC(Cl)CCl>[F:9][C:6]1[CH:7]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]=1[OH:8]
Reactant: Oc1ccc(Br)cc1
Reactant: F[B-](F)(F)F
Agent: F[n+]1c(Cl)cccc1C(Cl)(Cl)Cl
Solvent: ClCC(Cl)Cl
Product: Oc1ccc(Br)cc1F
Temperature: 45 °C

Procedure:
A mixture of 0.86 g of 4-bromophenol, 1.67 g of N-fluoro-2-chloro-6-(trichloromethyl)pyridinium fluoroborate, and 40 ml of 1,1,2-trichloroethane was placed in a 100 ml 3-necked round bottomed flask equipped with a magnetic stirring bar, a thermometer, and a reflux condenser. The mixture was heated to 45° C. and allowed to react at that temperature for 23 hours under nitrogen. The mixture was then allowed to cool. Analysis by standardized gas-liquid chromatography using a mass spectrometer detector indicated that the title product was present in 74 percent conversion. The product identity was confirmed by its known 19F and 1H NMR spectra.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[NH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[C:9]1([N:8]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:5]2[CH:6]=[CH:7][C:2]([NH:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:3][CH:4]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: Brc1ccc(N(c2ccccc2)c2ccccc2)cc1
Reactant: Nc1ccccc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)[O-]
Solvent: Cc1ccccc1
Product: c1ccc(Nc2ccc(N(c3ccccc3)c3ccccc3)cc2)cc1
Yield: 88.4 %

Procedure:
In a two-neck round bottom flask, (4-bromo-phenyl)-diphenyl-amine (12 g, 0.037 mol), aniline (16.26 ml, 0.178 mol), BINAP (0.4 g, 3% mol), Pd(OAc)2 (7.4 g, 4% mol), and NaOtBu (17.2 g, 0.178 mol) are dissolved in toluene (300 mL), and then are maintained for 18 hours by reflux. On completion of the reaction, the flask having the resultant solution is cooled, and then toluene, a solvent of the reaction, is removed from the resultant solution. After that, the resultant solution having no toluene reacts on methylene-chloride and water, and then methylene-chloride is removed therefrom, and is performed by silica gel column chromatography with a solvent of methylene-chloride and hexane at a ratio of 2 to 1. After that, the solvent is removed from the resultant solution of completing silica gel column chromatography, and is recrystallized and filtered with methylene-chloride and petroleum ether, thereby obtaining a white solid, N,N,N′-triphenyl-benzene-1,4-diamine (11.0 g, 88%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:14]=[CH:13][C:6]2[CH:7]=[C:8]([C:10](O)=[O:11])[O:9][C:5]=2[CH:4]=1.C(Cl)(=O)C([Cl:18])=O>O1CCCC1.CN(C)C=O>[CH3:1][O:2][C:3]1[CH:14]=[CH:13][C:6]2[CH:7]=[C:8]([C:10]([Cl:18])=[O:11])[O:9][C:5]=2[CH:4]=1
Reactant: O=C(Cl)C(=O)Cl
Reactant: COc1ccc2cc(C(=O)O)oc2c1
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: COc1ccc2cc(C(=O)Cl)oc2c1
Reaction time: 0.08 h

Procedure:
To a stirred solution of 6.0 g (0.031 mole) of 6-methoxy-2-benzofurancarboxylic acid (A. McGookin, A. Robertson, and W. B. Whalley, J. Chem. Soc. 787 (1940)) in 100 ml of tetrahydrofuran (under a nitrogen atmosphere) was added in one portion, 3.3 ml (4.8 g; 0.038 mole) of oxalyl chloride. The mixture was stirred for 5 minutes, then treated with 3 drops of N,N-dimethylformamide. After stirring at room temperature for 2 hours, the solvent was evaporated to leave a residue of crude 6-methoxy-2-benzofurancarbonyl chloride, mp 96°-99° (a mp of 101° is given by A. McGookin, etc., cited above). The residue was re-dissolved in 100 ml of dichloromethane, and the solution was filtered. The filtrate was added dropwise over 20 minutes to an ice-cooled solution of 3.6 g (0.037 mole) of N,0-dimethylhydroxylamine hydrochloride and 9.4 ml (7.7 g; 0.077 mole) of 1-methylpiperidine in 100 ml of dichloromethane. After stirring for 2 hours, the mixture was added to 400 ml of ice-cold 5% aqueous hydrochloric acid. The layers were separated, and the aqueous layer was extracted with fresh dichloromethane (3×100 ml). The combined organic layers were washed with water (1×200 ml), 3% aqueous sodium bicarbonate (2×200 ml), and water again. The extracts were dried (anhydrous magnesium sulfate) and evaporated. Trituration of the residue with ether yielded 5.4 g (74% yield) of the analytically pure amide product, mp 73°-77°.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[CH:10][C:5]([O:6][CH:7](O)[CH3:8])=[CH:4][CH:3]=1.[H-].[Na+].S(OC)([O:17][CH3:18])(=O)=O>C1COCC1>[CH3:18][O:17][CH2:8][CH2:7][O:6][C:5]1[CH:10]=[CH:11][C:2]([Br:1])=[CH:3][CH:4]=1
Reactant: CC(O)Oc1ccc(Br)cc1
Reactant: COS(=O)(=O)OC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COCCOc1ccc(Br)cc1
Temperature: 0 °C
Yield: 103.5 %

Procedure:
To an ice-cooled solution of 4-bromophenoxyethanol (5 g, 23.0 mmol) in THF (30 ml) was added a suspension of sodium hydride (1.10 g, 46.1 mmol) in THF (30 ml), with stirring. After 20 minutes dimethyl sulfate (4.37 ml, 46.1 mmol) was added dropwise. The reaction mixture was stirred for 4 hours at room temperature then quenched slowly with saturated aq. ammonium chloride (50 ml). The mixture was extracted with ethyl acetate (100 ml) and the organic extract was washed successively with 1M hydrochloric acid (50 ml) and brine (50 ml), dried over anhydrous magnesium sulfate and filtered. The solvent was removed under reduced pressure to leave 4-(2-methoxy-ethoxy)-bromobenzene (5.5 g, ca. quant.) as a pale brown oil. 1H-NMR; δ (CDCl3), 7.36 (2H, d, J=9.1 Hz), 6.80 (2H, d, J=9.1 Hz), 4.09 (2H, t, J=4.7 Hz), 3.74 (2H, t, J=4.7 Hz) and 3.45 (3H, s).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:15])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][CH:7]=1)[CH3:2].[H-].[Na+].I[CH3:19]>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:15])[CH:5]([C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][CH:7]=1)[CH3:19])[CH3:2]
Reactant: CCOC(=O)Cc1ccc([N+](=O)[O-])cc1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)C(C)c1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 14 h

Procedure:
To a stirred solution of (4-Nitro-phenyl)-acetic acid ethyl ester (3.88 g) in DMF (15 mL) was slowly added sodium hydride (0.78 g) and iodomethane (1.21 mL) at 0□. After stirred for 14 h at room temperature, this reaction mixture was quenched with water. This mixture was extracted with diethyl ether, and combined organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The resulting residue was chromatographed on silica gel (n-Hex:EtOAc=10:1 to 4:1) to afford the product as pale yellow oil. (89.1%)
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:14][NH2:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:17]1[CH:22]=[C:21]([C:23]#[N:24])[CH:20]=[CH:19][N:18]=1>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:14][NH:15][C:17]1[CH:22]=[C:21]([C:23]#[N:24])[CH:20]=[CH:19][N:18]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCCC[C@H]1CN
Reactant: N#Cc1ccnc(Cl)c1
Product: CC(C)(C)OC(=O)N1CCCC[C@H]1CNc1cc(C#N)ccn1
Yield: 14.3 %

Procedure:
The title compound (0.24 g) was prepared from (S)-2-aminomethyl-piperidine-1-carboxylic acid tert-butyl ester (1.14 g) and 2-chloro-4-cyanopyridine (0.74 g) according to the method of D28.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([N+:9]([O-])=O)=[CH:4][N:3]=1>Cl>[NH2:9][C:5]1[CH:6]=[C:7]([Cl:8])[C:2]([Cl:1])=[N:3][CH:4]=1
Reactant: O=[N+]([O-])c1cnc(Cl)c(Cl)c1
Agent: Cl
Product: Nc1cnc(Cl)c(Cl)c1
Temperature: 5 °C
Reaction time: 2 h
Yield: 51.4 %

Procedure:
2,3-Dichloro-5-nitropyridine (50.0 g, 0.26 mol) was dissolved in 500 ml conc. HCl, and the solution cooled to 5° C. Stannous chloride dihydrate (160 g) was added over 30 minutes. The reaction was stirred for 2 hours at 5° C. and then heated on a stram bath for 90 minutes. The mixture was cooled and extracted with ethyl acetate. The organic fractions were washed with 10 percent sodium hydroxide, then dried over anhydrous magnesium sulfate, and the solvent evaporated in vacuo to give 21.8 g (50 percent) of the amine, m.p. 110°-113° C.
Reaction SMILES: [CH3:1][Mg]Br.[CH3:4][C:5]([C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([Cl:13])[CH:8]=1)=[O:6]>CCOCC>[Cl:13][C:9]1[CH:8]=[C:7]([C:5]([OH:6])([CH3:1])[CH3:4])[CH:12]=[CH:11][CH:10]=1
Reactant: CC(=O)c1cccc(Cl)c1
Reactant: C[Mg]Br
Solvent: CCOCC
Product: CC(C)(O)c1cccc(Cl)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 93.6 %

Procedure:
Methylmagnesium bromide (3.6 mL, 10.67 mmol, Aldrich, 3 M solution in ether) was added to a cooled (−10° C.) solution of 3-chloroacetophenone (1.5 g, 9.7 mmol) in anhydrous ether slowly over 30 min. After complete addition, the reaction mixture was slowly warmed to room temperature, stirred for 18 hours. Again cooled (−5° C.), than quenched with sat. ammonium chloride solution over 30 min. The reaction mixture was extracted with ether, dried, filtered and concentrated to afford 1.55 g of 2-(3-chlorophenyl)propan-2-ol.
Reaction SMILES: [H-].[Na+].[CH3:3][N:4]([CH2:6][CH2:7][OH:8])[CH3:5].Cl.Cl[C:11]1[CH:16]=[CH:15][C:14]([S:17]([CH2:20][CH2:21][NH:22][CH:23]([CH3:25])[CH3:24])(=[O:19])=[O:18])=[CH:13][CH:12]=1.[C:26]([OH:33])(=[O:32])/[CH:27]=[CH:28]\[C:29]([OH:31])=[O:30]>CCCCCC.CS(C)=O>[C:26]([OH:33])(=[O:32])/[CH:27]=[CH:28]\[C:29]([OH:31])=[O:30].[CH3:3][N:4]([CH3:5])[CH2:6][CH2:7][O:8][C:11]1[CH:16]=[CH:15][C:14]([S:17]([CH2:20][CH2:21][NH:22][CH:23]([CH3:25])[CH3:24])(=[O:18])=[O:19])=[CH:13][CH:12]=1
Reactant: CN(C)CCO
Reactant: CC(C)NCCS(=O)(=O)c1ccc(Cl)cc1
Agent: Cl
Agent: O=C(O)/C=C\C(=O)O
Agent: [H-]
Solvent: CS(C)=O
Solvent: CCCCCC
Product: CC(C)NCCS(=O)(=O)c1ccc(OCCN(C)C)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 102.2 %

Procedure:
A mixture of 0.124 mole of sodium hydride (4.96 g of a 60% dispersion in oil; washed with hexane) and 13 g (0.146 mole) of 2-(N,N-dimethylamino)ethanol in 400 ml of dimethyl sulfoxide was stirred at room temperature and under an atmosophere of nitrogen for approximately 0.5 hr. To this solution was added 15.4 g (0.0519 mole) of N-[2-[(4-chlorophenyl)sulfonyl]ethyl]-1-methylethanamine hydrochloride [1:1] (from Preparation 23), and the mixture was stirred at 80°-100° C. for approximately 2 hr. The solvent was removed in vacuo, and the residue was partitioned between methylene chloride and dilute sodium hydroxide. The methylene chloride solution was dried over magnesium sulfate, and the solvent was removed in vacuo to give a liquid. This was treated with approximately 0.1 mole of maleic acid, and the resulting salt was recrystallized from methanol-diethyl ether to give 22.83 g (80.6%) of the product as a white crystalline solid, mp 177.5°-178.5° C.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([O:11][B:12](OC(C)C)[O:13]C(C)C)(C)C.[Li]CCCC.[C:26]1([N:32]([CH2:36][CH2:37][OH:38])[CH2:33][CH2:34][OH:35])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C1COCC1>[N:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[B:12]([OH:13])[OH:11].[C:26]1([N:32]([CH2:36][CH2:37][OH:38])[CH2:33][CH2:34][OH:35])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: Brc1ccccn1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: OCCN(CCO)c1ccccc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: OB(O)c1ccccn1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
Under nitrogen, a stirred solution of 2-bromopyridine (843 g, 5.33 mol) and triisopropylborate (1.20 kg, 6.40 mol) in THF (6.74 l) was cooled to −75° C. A 1.6M solution of n-BuLi in hexanes (4.00 l, 6.40 mol) was added at such a rate that the temperature did not exceed −67° C. After completion of the addition, the reaction was allowed to warm to room temperature and stirred at this temperature for 16 hours. After this time, a solution of N-phenyldiethanolamine (966 g, 5.33 mol) in THF (966 ml) was added and the resulting mixture heated at reflux for 4 hours. The solvent was distilled and replaced with isopropanol until the head temperature was 76° C. (distilling 11.3 l and adding in 8.4 l of isopropanol during the process). The mixture was cooled to room temperature and stirred at this temperature for 12 hours. The mixture was filtered, the solid washed with isopropanol (1.7 l) and dried in vacuo overnight at 40° C. to give 1605 g of the subtitle compound. Analysis by 1H NMR showed a ratio of pyridine: N-phenyldiethanolamine (or lithium alkoxide): isopropyl of 1:1.25:1.55.
Reaction SMILES: [Cl:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[F:12][C:13]([F:19])([CH:16]([F:18])[F:17])[CH2:14][OH:15]>>[Cl:1][C:2]1[C:3]([O:15][CH2:14][C:13]([F:19])([F:12])[CH:16]([F:18])[F:17])=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8]
Reactant: OCC(F)(F)C(F)F
Reactant: O=C(O)c1cnc(Cl)c(Cl)c1
Product: O=C(O)c1cnc(OCC(F)(F)C(F)F)c(Cl)c1
Yield: 97 %

Procedure:
The title compound is prepared in 97% yield (7.29 g, a pale brown solid) from 5,6-dichloronicotinic acid (5.00 g, 26.0 mmol) and 2,2,3,3-tetrafluoropropan-1-ol (5.16 g, 39.1 mmol) in a similar manner to Step-1 of Amine-1.
Reaction SMILES: N1(CC2N3C=C(C)C=CC3=NC=2C2C=CC(C)=CC=2)C=CN=C1.Cl.Cl[CH2:26][C:27]1[N:31]2[CH:32]=[C:33]([CH3:36])[CH:34]=[CH:35][C:30]2=[N:29][C:28]=1[C:37]1[CH:42]=[CH:41][C:40]([CH3:43])=[CH:39][CH:38]=1.[NH:44]1[C:48]([C:49]([O:51][CH3:52])=[O:50])=[N:47][CH:46]=[N:45]1>>[CH3:52][O:51][C:49]([C:48]1[N:47]=[CH:46][N:45]([CH2:26][C:27]2[N:31]3[CH:32]=[C:33]([CH3:36])[CH:34]=[CH:35][C:30]3=[N:29][C:28]=2[C:37]2[CH:42]=[CH:41][C:40]([CH3:43])=[CH:39][CH:38]=2)[N:44]=1)=[O:50]
Reactant: Cc1ccc(-c2nc3ccc(C)cn3c2CCl)cc1
Reactant: COC(=O)c1ncn[nH]1
Agent: Cc1ccc(-c2nc3ccc(C)cn3c2Cn2ccnc2)cc1
Agent: Cl
Product: COC(=O)c1ncn(Cc2c(-c3ccc(C)cc3)nc3ccc(C)cn23)n1

Procedure:
The title compound was prepared according to Method A and the experimentals described for compound 1 from 3-(chloromethyl)-6-methyl-2-p-tolylimidazo[1,2-a]pyridine hydrochloride and methyl 1H-1,2,4-triazole-5-carboxylate. The two isomers were separated by silica gel chromatography eluted with 20% acetone to flash out the less polar spot and 50% acetone to flash out the second spot (more polar spot). Compound 10: m/e+ 362 for C20H20N5O2 [M+H]+; 1H-NMR (400 MHz, CDCl3) δ 7.95 (s, 2H), 7.65 (d, J=8.0 Hz, 2H), 7.56 (d, J=9.1 Hz, 1H), 7.23 (d, J=8.0 Hz, 2H), 7.10 (dd, J=1.4, 9.1 Hz, 1H), 6.15 (s, 2H), 3.98 (s, 3H), 2.38 (s, 3H), 2.31 (s, 3H) ppm; Compound 11: m/e+ 362 for C20H20N5O2 [M+H]+; 1H-NMR (400 MHz, CDCl3) δ 7.91 (s, 1H), 7.74 (s, 1H), 7.58 (d, J=9.5 Hz, 1H), 7.54 (d, J=7.7 Hz, 2H), 7.24 (d, J=7.7 Hz, 2H), 7.14 (d, J=9.5 Hz, 1H), 5.81 (s, 2H), 3.98 (s, 3H), 2.37 (s, 3H), 2.29 (s, 3H) ppm.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@:8]2([O:17][C@H:16]([CH2:18][OH:19])[C@@H:14]([OH:15])[C@H:12]([OH:13])[C@H:10]2[OH:11])[OH:9])=[CH:4][C:3]=1[CH2:20][C:21]1[CH:26]=[CH:25][C:24](OS(C(F)(F)F)(=O)=O)=[CH:23][CH:22]=1.[C:35]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=1)#[CH:36]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@:8]2([O:17][C@H:16]([CH2:18][OH:19])[C@@H:14]([OH:15])[C@H:12]([OH:13])[C@H:10]2[OH:11])[OH:9])=[CH:4][C:3]=1[CH2:20][C:21]1[CH:22]=[CH:23][C:24]([C:36]#[C:35][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=2)=[CH:25][CH:26]=1
Reactant: C#Cc1ccccn1
Reactant: O=S(=O)(Oc1ccc(Cc2cc([C@@]3(O)O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)ccc2Cl)cc1)C(F)(F)F
Product: OC[C@H]1O[C@](O)(c2ccc(Cl)c(Cc3ccc(C#Cc4ccccn4)cc3)c2)[C@H](O)[C@@H](O)[C@@H]1O

Procedure:
The compound was obtained starting from 1-chloro-4-(β-D-glucopyranos-1-yl)-2-(4-trifluoromethylsulfonyloxy-benzyl)-benzene and 2-ethynyl-pyridine.
Reaction SMILES: [OH-].[Na+].FC(F)(F)C(O)=O.[Br:10][C:11]1[N:19](S(C2C=CC=CC=2)(=O)=O)[C:18]2[C:13](=[N:14][C:15]([Cl:29])=[CH:16][CH:17]=2)[CH:12]=1.C([O-])([O-])=O.[K+].[K+].[CH2:36](Br)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>C1COCC1.CO.CN(C=O)C.O>[CH2:36]([N:19]1[C:18]2[C:13](=[N:14][C:15]([Cl:29])=[CH:16][CH:17]=2)[CH:12]=[C:11]1[Br:10])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1
Reactant: O=S(=O)(c1ccccc1)n1c(Br)cc2nc(Cl)ccc21
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: Clc1ccc2c(cc(Br)n2Cc2ccccc2)n1
Reaction time: 1 h

Procedure:
1.0 M NaOH in water (5 mL, 5 mmol) was added to a solution of 2-bromo-5-chloro-1-(phenylsulfonyl)-1H-pyrrolo[3,2-b]pyridine trifluoroacetate (0.268 g, 0.552 mmol, from Step 1) in THF (5 mL) and methanol (5 mL) and the reaction was stirred for 1 hour. Water was added and THF and MeOH were removed in vacuo. The product was extracted with EtOAc. The extracts were dried over sodium sulfate, filtered and concentrated. A solution of this residue in DMF (3 mL) was treated with K2CO3 (0.23 g, 1.6 mmol) and benzyl bromide (0.0656 mL, 0.552 mmol, Aldrich). After stirring overnight, the reaction was partitioned between water and ethyl acetate and extracted a total of three times. The combined extracts were dried over sodium sulfate, filtered and concentrated. The product was purified by flash chromatography, eluting with a gradient from 0-30% EtOAc in hexanes to afford product as a white crystalline solid. Yield: (177 mg, 99%).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:9]=[CH:10][CH:11]=1)[NH2:8])(=[O:3])[CH3:2].[CH2:12](Br)[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].C(=O)([O-])[O-].[Na+].[Na+]>>[C:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:9]=[CH:10][CH:11]=1)[NH:8][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])(=[O:3])[CH3:2]
Reactant: CCCCCCCCBr
Reactant: CC(=O)Nc1cccc(N)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: CCCCCCCCNc1cccc(NC(C)=O)c1

Procedure:
3-Acetylaminoaniline (15 parts) was reacted with n-octyl bromide (19.3 parts) at 100° C. for 4 hours in the presence of anhydrous sodium carbonate (5.3 parts) to obtain 3-acetylamino-N-n-octylaniline. Thereafter, reaction was further continued at 120° to 130° C. for 4 hours with addition of n-amyl bromide (15.1 parts) and anhydrous sodium carbonate (5.3 parts) to obtain 3-acetylamino-N-n-octyl-N-n-pentylaniline (coupling component). In the same manner as in Example 1, 2-cyano-4-nitro-6-chloroaniline was diazotized and coupled with the above coupling component to obtain 43.8 parts of a dye (8).
Reaction SMILES: [CH:1]([O:14][CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:21][C:22]1[CH:27]=[C:26]([CH:28]=O)[CH:25]=[CH:24][N:23]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.ClCCl>[CH:1]([O:14][CH:15]1[CH2:20][CH2:19][N:18]([CH2:28][C:26]2[CH:25]=[CH:24][N:23]=[C:22]([Br:21])[CH:27]=2)[CH2:17][CH2:16]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: c1ccc(C(OC2CCNCC2)c2ccccc2)cc1
Reactant: O=Cc1ccnc(Br)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: Brc1cc(CN2CCC(OC(c3ccccc3)c3ccccc3)CC2)ccn1
Reaction time: 0.83 h
Yield: 69.4 %

Procedure:
A mixture of 904 mg of 4-benzhydryloxypiperidine synthesized in Production Example 1, 6.4 mL of dichloromethane, and 629 mg of 2-bromo-4-pyridinecarbaldehyde was stirred for 50 minutes. Sodium triacetoxyborohydride (1.075 g) was added thereto little by little, and the resulting mixture was stirred for 14 hours. The resulting mixture was diluted with ethyl acetate, and the diluted mixture was thrown into sodium bicarbonate water. The organic layer was collected by separation and washed with a saturated saline solution. The washed organic layer was dried over magnesium sulfate, and the solvent was distilled off. The resulting product was subjected to a silica gel column chromatography (hexane/ethyl acetate (volume ratio)=2:1 to 1:1) to give the title compound (1.027 g).
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)=[CH:10][C:9]=1[NH:19][C:20]([C:22]1[S:26][C:25]2[CH:27]=[C:28]([CH:31]([C:33](=[O:35])[NH2:34])[F:32])[CH:29]=[CH:30][C:24]=2[CH:23]=1)=[O:21])(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)=[CH:10][C:9]=1[NH:19][C:20]([C:22]1[S:26][C:25]2[CH:27]=[C:28]([CH:31]([C:33](=[O:35])[NH2:34])[F:32])[CH:29]=[CH:30][C:24]=2[CH:23]=1)=[O:21]
Reactant: CC(C)(C)OC(=O)Nc1ccc(-c2cccs2)cc1NC(=O)c1cc2ccc(C(F)C(N)=O)cc2s1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: NC(=O)C(F)c1ccc2cc(C(=O)Nc3cc(-c4cccs4)ccc3N)sc2c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of (2-{[6-(carbamoyl-fluoro-methyl)-benzo[b]thiophene-2-carbonyl]-amino}-4-thiophen-2-yl-phenyl)-carbamic acid tert-butyl ester (163 mg, 0.31 mmol)) in methylene chloride (2 mL) was added trifluoroacetic acid (1 mL) and the solution was stirred at ambient temperature for 16 hours. The reaction was evaporated to dryness. The residue was washed with sat. NaHCO3 and MeOH, and the solid was filtered. 1H NMR (DMSO-d6) δ 10.03 (br s, 1H), 8.33 (s, 1H), 8.11 (s, 1H), 8.02 (d, J=8.2 Hz, 1H), 7.93 (s, 1H), 7.62 (br d, J=2.4 Hz, 1H), 7.51 (d, J=8.2 Hz, 1H), 7.45 (d, J=1.8 Hz, 1H), 7.33 (dd, J=5.0, 1.8 Hz, 1H), 7.29 (dd, J=8.2, 1.8 Hz, 1H), 7.23 (dd, J=3.5, 1.8 Hz, 1H), 7.02 (dd, J=5.2, 3.5 Hz, 1H), 6.79 (d, J=8.2 Hz, 1H), 5.93 (d, J=45.7 Hz, 1H), 5.24 (s, 2H). cal'd 427 (MH+), exp 427 (MH+).
Reaction SMILES: Br[C:2]1[N:6]([CH:7]([CH3:9])[CH3:8])[C:5]2[CH:10]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=3[F:28])[N:11]([C:14]3[N:15]([CH3:20])[N:16]=[C:17]([CH3:19])[CH:18]=3)[C:12](=[O:13])[C:4]=2[CH:3]=1.[CH3:29][O:30][C:31]1[C:36](B2OC(C)(C)C(C)(C)O2)=[CH:35][N:34]=[C:33]([N:46]([CH3:48])[CH3:47])[N:32]=1.BrC1N(C(C)C)C2C(C3C=CC(Cl)=CC=3)N(C3C=C(Cl)C=CC=3C)C(=O)C=2C=1.COC1C(B2OC(C)(C)C(C)(C)O2)=CN=C(N)N=1>>[Cl:27][C:24]1[CH:25]=[CH:26][C:21]([CH:10]2[C:5]3[N:6]([CH:7]([CH3:9])[CH3:8])[C:2]([C:36]4[C:31]([O:30][CH3:29])=[N:32][C:33]([N:46]([CH3:47])[CH3:48])=[N:34][CH:35]=4)=[CH:3][C:4]=3[C:12](=[O:13])[N:11]2[C:14]2[N:15]([CH3:20])[N:16]=[C:17]([CH3:19])[CH:18]=2)=[C:22]([F:28])[CH:23]=1
Reactant: Cc1cc(N2C(=O)c3cc(Br)n(C(C)C)c3C2c2ccc(Cl)cc2F)n(C)n1
Reactant: COc1nc(N(C)C)ncc1B1OC(C)(C)C(C)(C)O1
Agent: COc1nc(N)ncc1B1OC(C)(C)C(C)(C)O1
Agent: Cc1ccc(Cl)cc1N1C(=O)c2cc(Br)n(C(C)C)c2C1c1ccc(Cl)cc1
Product: COc1nc(N(C)C)ncc1-c1cc2c(n1C(C)C)C(c1ccc(Cl)cc1F)N(c1cc(C)nn1C)C2=O

Procedure:
The title compound was prepared in analogy to the procedure described for Example 25 but 2-bromo-6-(4-chloro-2-fluoro-phenyl)-5-(2,5-dimethyl-2H-pyrazol-3-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one (Intermediate BI) and 4-methoxy-N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (Intermediate W) were used instead of 2-bromo-5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one and 4-methoxy-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine respectively. ESI-MS: tR=1.19 min, [M+H]+ 538/540 (LC-MS 1).
Reaction SMILES: Br[C:2]1[CH:9]=[C:8]([CH3:10])[C:7]([N+:11]([O-:13])=[O:12])=[CH:6][C:3]=1[C:4]#[N:5].[CH3:14][S-:15].[Na+]>CN(C=O)C>[CH3:10][C:8]1[C:7]([N+:11]([O-:13])=[O:12])=[CH:6][C:3]([C:4]#[N:5])=[C:2]([S:15][CH3:14])[CH:9]=1
Reactant: C[S-]
Reactant: Cc1cc(Br)c(C#N)cc1[N+](=O)[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CSc1cc(C)c([N+](=O)[O-])cc1C#N
Temperature: 60 °C

Procedure:
To a solution of 2-bromo-4-methyl-5-nitrobenzonitrile (3 g, 12.45 mmol) in DMF (124 mL), sodium thiomethoxide (1.31 g, 18.67 mmol) was added and the reaction heated to 60° C. for 1 h. The reaction was then cooled to room temperature, quenched with a sat. aq. solution of NaHCO3 and extracted with EtOAc. The organic extract was dried over MgSO4, filtered and concentrated. The resulting residue was purified using FCC eluting with heptanes:EtOAc 1:1 to give the title compound. MS (ESI−) m/z 207.3 (M−H).