Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]2[C:7]3[CH:14]=[CH:13][N:12]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:8]=3[N:9]=[CH:10][N:11]=2)[CH:3]=[N:2]1.[C:23](#[N:30])[CH:24]=[CH:25][CH2:26][CH2:27][CH2:28][CH3:29].N12CCCN=C1CCCCC2>C(#N)C>[CH3:20][Si:19]([CH3:22])([CH3:21])[CH2:18][CH2:17][O:16][CH2:15][N:12]1[C:8]2[N:9]=[CH:10][N:11]=[C:6]([C:4]3[CH:5]=[N:1][N:2]([CH:25]([CH2:26][CH2:27][CH2:28][CH3:29])[CH2:24][C:23]#[N:30])[CH:3]=3)[C:7]=2[CH:14]=[CH:13]1
Reactant: CCCCC=CC#N
Reactant: C[Si](C)(C)CCOCn1ccc2c(-c3cn[nH]c3)ncnc21
Solvent: CC#N
Solvent: C1CCC2=NCCCN2CC1
Product: CCCCC(CC#N)n1cc(-c2ncnc3c2ccn3COCC[Si](C)(C)C)cn1
Temperature: 25 °C
Yield: 85.5 %

Procedure:
To a solution of 4-(1H-pyrazol-4-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (6.1 g, 19 mmol) in acetonitrile (58 mL) was added crude hept-2-enenitrile (2.6 g, 23 mmol), followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (3.49 mL, 23.4 mmol). The resulting mixture was stirred at room temperature over the weekend and then evaporated to dryness. The residue was purified on silica gel, eluting with 0 to 50% of ethyl acetate in hexane, to give the desired product (6.90 g, 84%). LCMS calculated for C22H33N6OSi(M+H)+: m/z=425.2. Found: 425.4. The racemic mixture was applied on an OD-H column (3×25 cm, 5 μM), eluting with 15% ethanol and 85% hexane mixture at a flow rate of 28 mL/min to give the two desired enantiomers. First peak retention time of 9.46 min; second peak (3.45 g) retention time of 12.35 min.
Reaction SMILES: I([O-])(=O)(=O)=O.[Na+].[O:7]1[C:11]2[CH:12]=[CH:13][C:14]([CH:16]3[CH2:20][CH:19]([OH:21])[CH:18]([OH:22])[CH2:17]3)=[CH:15][C:10]=2[O:9][CH2:8]1>C1COCC1.O>[O:7]1[C:11]2[CH:12]=[CH:13][C:14]([CH:16]([CH2:20][CH:19]=[O:21])[CH2:17][CH:18]=[O:22])=[CH:15][C:10]=2[O:9][CH2:8]1
Reactant: OC1CC(c2ccc3c(c2)OCO3)CC1O
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: O
Solvent: C1CCOC1
Product: O=CCC(CC=O)c1ccc2c(c1)OCO2
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of sodium periodate (1.91 mmol, 0.41 g) in THF (3 mL) and H2O (2 mL) at 0° C. was added diol 99 (1.91 mmol, 0.42 g). The reaction mixture was stirred at room temperature for 3 h. The reaction mixture was filtered, and the resulting dialdehyde 100 was used as is, as an aqueous solution.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][C:19]=1[F:20])[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9](=[O:16])[NH:8][N:7]=1.[C:21]([CH2:24][C:25]1([C:30](O)=[O:31])[CH2:29][CH2:28][CH2:27][CH2:26]1)(O)=[O:22]>>[F:20][C:19]1[CH:18]=[CH:17][C:4]([CH2:5][C:6]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:16])[NH:8][N:7]=2)=[CH:3][C:2]=1[N:1]1[C:21](=[O:22])[CH2:24][C:25]2([CH2:29][CH2:28][CH2:27][CH2:26]2)[C:30]1=[O:31]
Reactant: Nc1cc(Cc2n[nH]c(=O)c3ccccc23)ccc1F
Reactant: O=C(O)CC1(C(=O)O)CCCC1
Product: O=C1CC2(CCCC2)C(=O)N1c1cc(Cc2n[nH]c(=O)c3ccccc23)ccc1F
Temperature: 200 °C

Procedure:
A stirred mixture of 4-(3-amino-4-fluorobenzyl)-2H-phthalazin-1-one (0.1 g, 0.37 mmol; prepared in a manner similar to that described in Example 23) and 1-(carboxymethyl)cyclopentane-1-carboxylic acid (0.064 g, 0.37 mmol) was heated at 200° C. in a sealed tube until the starting materials had been consumed (the reaction was followed by tlc using a 1:1 mixture of ethyl acetate and hexane as eluant). The warm mixture was poured into an ice/water mixture (10 ml) and the resulting solid was collected by filtration. The crude product was recrystallised from ethyl acetate/hexane (the hot solution required filtration to remove traces of undissolved solids) to give 2-[2-fluoro-5-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)phenyl]-2-azaspiro[4.4]nonane-1,3-dione (0.03 g) as an off-white solid, m.pt. 215–220° C.; 250 MHz 1H-nmr (d6-DMSO) δ (ppm): 1.7–2.2 (m, 8H) (4× cyclopentyl CH2), 2.9 (s, 2H) (—COCH2—), 4.35 (s, 2H) (ArCH2—), 7.3–7.45 (m, 2H) (2×ArH), 7.5–7.6 (m, 1H) (ArH), 7.8–8.1 (m, 3H) (3×ArH), 8.3 (d, 1H) (ArH), 12.7 (s, 1H) (CONH); m/z (M+H)+. 406, 91.4% purity.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]2[C:7](=[O:16])[C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=3[CH:10]=[CH:11][C:2]=12.ClC1C=CC=C(C(OO)=[O:25])C=1>C(Cl)(Cl)Cl>[N+:1]1([O-:25])[CH:6]=[CH:5][CH:4]=[C:3]2[C:7](=[O:16])[C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=3[CH:10]=[CH:11][C:2]=12
Reactant: O=c1c2ccccc2ccc2ncccc12
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClC(Cl)Cl
Product: O=c1c2ccccc2ccc2c1ccc[n+]2[O-]
Temperature: 25 °C
Reaction time: 8 h
Yield: 99.9 %

Procedure:
To a solution of 2.07 grams (0.01 mole) of benzo[4,5]cyclohepta[1,2-b]pyridin-5-one in 25 milliliters of chloroform was added dropwise, a solution of 2.0 grams (0.01 mole) of m-chloroperbenzoic acid in 30 milliliters of chloroform and the resulting solution stirred for 7 hours at room temperature. At this time an additional 0.5 gram of m-chloroperbenzoic acid was added and the mixture stirred overnight at room temperature. The resulting reaction mixture was washed successively with two 100 milliliter portions of 10 percent aqueous sodium hydroxide and two 100 milliliter portions of water and then dried over magnesium sulfate. The dried solution was filtered to remove the drying agent and the chloroform was vaporized to obtain 2.23 grams of a benzo[4,5]cyclohepta[1,2-b]pyridin-5-one N-oxide intermediate.
Reaction SMILES: [OH:1][C:2]1[C:3]([C:12]([NH:14][CH2:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18](C(OC(C)(C)C)=O)[CH:17]=2)=[O:13])=[N:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.FC(F)(F)C(O)=O>C(Cl)Cl>[OH:1][C:2]1[C:3]([C:12]([NH:14][CH2:15][C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][CH:17]=2)=[O:13])=[N:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2
Reactant: CC(C)(C)OC(=O)n1cc(CNC(=O)c2ncc3cccnc3c2O)c2ccccc21
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(NCc1c[nH]c2ccccc12)c1ncc2cccnc2c1O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of tert-butyl 3-({[(8-hydroxy-1,6-naphthyridin-7-yl)carbonyl]amino}methyl)-1H-indole-1-carboxylate from Example 10 (12.0 mg, 0.0029 mmol) in CH2Cl2 (1 ml) was treated with trifluroacetic acid (TFA) (1 ml) and resulting mixture was stirred at room temperature for 1 hr and then the solvent was evaporated in vacuo. The resulting material was dissolved in DMSO (1 ml) and aged for 24 hrs at room temperature. This solution was purified by preparative HPLC. (Gilson semi preparative HPLC system and a YMC Combiprep Pro Column (50×20 mm I.D., C18, S-5 um, 120A) eluting with 5-95% acetonitrile/water (0.1% TFA) at 15 min/min) to afford the title compound after lyophilization.
Reaction SMILES: [CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:10]1[C:11]2[CH:24]=[C:23]([Cl:25])[S:22][C:12]=2[N:13]=[C:14]([C:16]2[CH:21]=[N:20][CH:19]=[CH:18][N:17]=2)[N:15]=1>>[N:17]1[CH:18]=[CH:19][N:20]=[CH:21][C:16]=1[C:14]1[N:15]=[C:10]([NH:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:11]2[CH:24]=[C:23]([Cl:25])[S:22][C:12]=2[N:13]=1
Reactant: Clc1cc2c(Cl)nc(-c3cnccn3)nc2s1
Reactant: NCc1ccccc1
Product: Clc1cc2c(NCc3ccccc3)nc(-c3cnccn3)nc2s1

Procedure:
With the procedure of Example 1, the reaction of benzylamine with 4-chloro-2-(pyrazin-2-yl)-6-chloro-thieno-[2,3-d]-pyrimidine yields 2-(pyrazin-2-yl)-4-benzylamino-6-chloro-thieno-[2,3-d]-pyrimidine.
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH:12]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)C#N)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.Br>>[Cl:1][C:2]1[C:3]([CH2:12][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)=[N:4][CH:5]=[C:6]([C:8]([F:10])([F:11])[F:9])[CH:7]=1
Reactant: N#CC(c1ccc(Cl)cc1)c1ncc(C(F)(F)F)cc1Cl
Agent: Br
Product: FC(F)(F)c1cnc(Cc2ccc(Cl)cc2)c(Cl)c1
Temperature: 23 °C
Reaction time: 68 h

Procedure:
4.3 g of 3-chloro-2-[1-(4-chlorophenyl)-1-cyanomethyl]-5-trifluoromethylpyridine (prepared by the method of Example 1) were heated under reflux in 50 ml of 47% strength aqueous hydrogen bromide solution for 3 hours and then stirred for another 68 hours at 23° C. The reaction mixture was subsequently poured into 500 ml of ice water. The mixture was stirred for a further 30 minutes and the solid that had formed was separated off, washed with water and then dried. Yield: 3.0 g (75%) of colorless crystals; mp.: 54-56° C.).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][NH:13][C:14](=[O:22])[C:15]1[CH:20]=[CH:19][C:18](I)=[CH:17][CH:16]=1.[C:23]1([CH3:32])[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.O.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>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][NH:13][C:14]([C:15]1[CH:20]=[CH:19][C:18]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[CH3:32])=[CH:17][CH:16]=1)=[O:22]
Reactant: Cc1ccccc1B(O)O
Reactant: O=C(NCCc1c[nH]c2ccc(Cl)cc12)c1ccc(I)cc1
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: [Na+]
Solvent: O
Solvent: COCCOC
Product: Cc1ccccc1-c1ccc(C(=O)NCCc2c[nH]c3ccc(Cl)cc23)cc1
Yield: 68.7 %

Procedure:
N-(2-(5-chloro-1H-indol-3-yl)ethyl)-2′-methylbiphenyl-4-carboxamide was prepared according to method B with N-(2-(5-chloro-1H-indol-3-yl)ethyl)-4-iodobenzamide (0.075 g; 0.176 mmol), o-tolylboronic acid (0.025 g; 0.176 mmol), tetrakis(triphenylphosphine)palladium (0.010 g; 0.009 mmol), sodium carbonate (0.037 g; 0.353 mmol), in dimethoxyethane (3 mL) and water (1 mL), irradiated in a microwave oven at 130° C. for 15 minutes. Flash chromatography on silica gel (eluent 2 to 10% ethyl acetate in dichloromethane) furnished 0.047 g (68%) of N-(2-(5-chloro-1H-indol-3-yl)ethyl)-2′-methylbiphenyl-4-carboxamide as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[C:4](=[O:14])[CH:5]([Cl:13])[C:6]1[CH:11]=[CH:10][C:9](F)=[CH:8][CH:7]=1.[F:16]C1C=CC=CC=1C=O.FC1C=CC(C=O)=CC=1>>[CH3:1][O:2][C:3](=[O:15])[C:4](=[O:14])[CH:5]([Cl:13])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[F:16]
Reactant: COC(=O)C(=O)C(Cl)c1ccc(F)cc1
Reactant: O=Cc1ccccc1F
Agent: O=Cc1ccc(F)cc1
Product: COC(=O)C(=O)C(Cl)c1ccccc1F

Procedure:
This compound was synthesised as 3-chloro-3-(4-fluoro-phenyl)-2-oxo-propionic acid methyl ester but using 2-fluorobenzaldehyde instead 4-fluorobenzaldehyde.
Reaction SMILES: [C:1]1([CH:7]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:8][CH:9]2[C:14](=O)[CH:13]3[CH2:16][CH2:17][N:10]2[CH2:11][CH2:12]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[K+].NN.C(O)COCCO>O.CCCCC>[C:18]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:8][CH:9]2[CH2:14][CH:13]3[CH2:16][CH2:17][N:10]2[CH2:11][CH2:12]3)[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: O=C1C2CCN(CC2)C1CC(c1ccccc1)c1ccccc1
Agent: NN
Agent: [K+]
Agent: [OH-]
Solvent: CCCCC
Solvent: OCCOCCO
Solvent: O
Product: c1ccc(C(CC2CC3CCN2CC3)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 2.75 h

Procedure:
9.3 Parts of 2-(2,2-diphenylethyl-1-azabicyclo[2.2.2]octan-3-one, 1.3 parts of potassium hydroxide, 3.6 parts by volume of an 85% solution of hydrazine in water and 59 parts diethylene glycol are refluxed together, with stirring, under nitrogen for 2.75 hours. Stirring and heating are then discontinued and the reaction mixture is allowed to stand overnight. The mixture is then heated to distill under nitrogen until a head temperature of 235° C. is reached. After cooling to room temperature, the mixture is partitioned between 900 parts by volume of 5% sodium chloride solution and two 600 parts by volume portions of ethyl ether. The ethereal extracts are combined, washed with water, dried over anhydrous sodium sulfate and stripped in vacuo to give an residual oil which solidifies upon standing. This solid is dissolved in 300 parts by volume of hot n-pentane. The solution is then concentrated on the steam bath to 45 parts by volume and cooled to room temperature to give a solid precipitate which is filtered off, washed with n-pentane and dried in vacuo to give a white solid 2-(2,2-diphenylethyl)-1-azabicyclo[2.2.2]octane, melting at about 87.5°-89° C. This compound is represented by the following structural formula ##STR4##
Reaction SMILES: Cl.[CH2:2]([C:5]1[S:6][CH:7]=[C:8]([CH2:10]Cl)[N:9]=1)[CH2:3][CH3:4].[C:12]1([N:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C>[CH2:2]([C:5]1[S:6][CH:7]=[C:8]([CH2:10][N:21]2[CH2:22][CH2:23][N:18]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH2:19][CH2:20]2)[N:9]=1)[CH2:3][CH3:4]
Reactant: CCCc1nc(CCl)cs1
Reactant: c1ccc(N2CCNCC2)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Product: CCCc1nc(CN2CCN(c3ccccc3)CC2)cs1

Procedure:
A mixture of 2-n-propyl-4-chloromethylthiazole hydrochloride (3.18g; 0.015 mole), 1-phenylpiperazine (2.43g; 0.015 mole) and sodium carbonate (anhydrous, 10g) in absolute ethanol (60ml) was stirred and boiled under reflux for 6 hours. The suspension was filtered and the filtrate evaporated to a yellow oil. This was dissolved in boiling benzene and treated with decolourising charcoal. After filtration, the benzene was removed giving a yellow oil which crystallised 4.27g. This solid was recrystallised from petroleum ether (b.p. 60°-80° C.) at 0° C. to give a white crystalline solid (m.p. 38°-39° C.)
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]2[S:13][CH:14]=[C:15]([CH3:17])[CH:16]=2)=[N:4][N:3]=1>CN1CCCC1=O>[C:6]1([C@H:5]([NH:4][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]([C:12]3[S:13][CH:14]=[C:15]([CH3:17])[CH:16]=3)=[N:4][N:3]=2)[CH3:12])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: Cc1csc(-c2nnc(Cl)c3ccccc23)c1
Solvent: CN1CCCC1=O
Product: Cc1csc(-c2nnc(N[C@H](C)c3ccccc3)c3ccccc23)c1
Temperature: 140 °C
Reaction time: 8 h
Yield: 18.9 %

Procedure:
200 mg of 1-chloro-4-(4-methyl-2-thienyl)phthalazine and 100 mg of D-α-phenylethylamine were dissolved in 2 ml of N-methylpyrrolidone, and the solution was stirred at 140° C. for 8 hours. After the solution was subjected to after-treatment, it was purified by column chromatography, thereby obtaining 25 mg of (R)-1-(α-phenylethylamino)-4-(4-methyl-2-thienyl)phthalazine.
Reaction SMILES: CC(=O)CC(=O)C.O.[OH-].[Ba+2:10].[OH-].C(O)CCC.[C:17]([OH:21])(=[O:20])[CH2:18][CH3:19]>CCCCO.CCCCO.CCCCO.CCCCO.[Ti]>[C:17]([O-:21])(=[O:20])[CH2:18][CH3:19].[Ba+2:10].[C:17]([O-:21])(=[O:20])[CH2:18][CH3:19]
Reactant: CCC(=O)O
Agent: [Ti]
Agent: [Ba+2]
Agent: [OH-]
Solvent: CCCCO
Solvent: O
Solvent: CC(=O)CC(C)=O
Product: CCC(=O)[O-]
Reaction time: 12 h

Procedure:
2,4 pentanedione (Acac) is degassed by a freeze/pump/thaw method on a Schlenk line over a bed of grade 4A molecular sieves and back filled with argon gas. In a nitrogen-filled drybox, 34.041 g of titanium(IV) n-butoxide (Acros; 0.100 moles) are placed into a 100 ml bottle, and 20.020 g of 2,4 pentanedione (0.200 moles; Aldrich) is then added dropwise and left to stir for 12 hours. In a fumehood, 31.750 g of barium hydroxide hydrate (0.101 moles; Aldrich) is added to a 500 ml volumetric flask. 200 ml of a 50:50 solution of 1-butanol/propanoic acid would then be added and stirred to form barium propanoate. The titanium solution [bis(acetylacetonato)/bis(butoxo)titanium] is then removed from the drybox and added to the volumetric flask containing the barium hydroxide solution. The round bottom flask is rinsed several times with 50:50 1-butanol:propanoic acid solution into the volumetric flask. A 50:50 1-butanol:propanoic acid solution is then added to the 500 ml flask up to the mark, and a stir bar is then added. The solution is stirred for an additional 12 hours.
Reaction SMILES: [CH:1]([C:3]1[C:11]([O:12][CH3:13])=[CH:10][C:9]([CH3:14])=[C:8]2[C:4]=1[CH:5]=[CH:6][N:7]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=O.[C:22](Br)(Br)([Br:24])[Br:23].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C(Cl)Cl>[Br:23][C:22]([Br:24])=[CH:1][C:3]1[C:11]([O:12][CH3:13])=[CH:10][C:9]([CH3:14])=[C:8]2[C:4]=1[CH:5]=[CH:6][N:7]2[C:15]([O:17][C:18]([CH3:21])([CH3:19])[CH3:20])=[O:16]
Reactant: BrC(Br)(Br)Br
Reactant: COc1cc(C)c2c(ccn2C(=O)OC(C)(C)C)c1C=O
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COc1cc(C)c2c(ccn2C(=O)OC(C)(C)C)c1C=C(Br)Br
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
To a solution of tert-butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate (902 mg, 3.12 mmol) in CH2Cl2 (30 mL), CBr4 (1.55 g, 4.68 mmol) was added at 0° C. followed by PPh3 (2.45 g, 9.35 mmol). The mixture was stirred at room temperature for 1.5 hours. The reaction mixture was concentrated and directly purified via FCC eluting with Heptane/DCM 100:0 to 0:100 to provide the title compound. MS (ESI+) m/z 446.0, 448.0, 444.0, 446.9 (M+H).
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+].[Br:14][CH2:15][CH2:16][CH2:17]Br>CC(C)=O>[Br:14][CH2:15][CH2:16][CH2:17][O:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Oc1ccccc1
Reactant: BrCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: BrCCCOc1ccccc1
Yield: 89.9 %

Procedure:
Phenol (1.0 g, 10.6 mmol) was dissolved in acetone (20 mL). Anhydrous potassium carbonate (7.34 g, 53.1 mmol) and 1,3-dibromopropane (8.58 g, 42.5 mmol) was added to the solution. The reaction mixture was refluxed in an oil bath for 12 h. After the reaction, the potassium carbonate was removed by suction filtration and solvent was removed under reduced pressure to give the crude product which was then purified by column chromatography using ethyl acetate:hexane (3:7) to give product 26 (2.05 g, 90%). 1H NMR (400 MHz, CDCl3) δ 2.24 (m, 2H), 3.54 (t, J=6.4 Hz, 2H), 4.03 (t, J=5.8 Hz, 2H), 6.86 (m, 3H), 7.21 (m, 2H).
Reaction SMILES: [F:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]([F:18])=[C:4](F)[C:3]=1F.[CH2:21]([C:23]1[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30][CH3:31])[C:24]=1[NH2:25])[CH3:22]>>[CH2:21]([C:23]1[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30][CH3:31])[C:24]=1[NH:25][C:4]1[C:3]([NH:25][C:24]2[C:26]([CH2:30][CH3:31])=[CH:27][CH:28]=[CH:29][C:23]=2[CH2:21][CH3:22])=[C:2]([F:1])[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]=1[F:18])[CH3:22]
Reactant: O=C1c2ccccc2C(=O)c2c(F)c(F)c(F)c(F)c21
Reactant: CCc1cccc(CC)c1N
Product: CCc1cccc(CC)c1Nc1c(F)c2c(c(F)c1Nc1c(CC)cccc1CC)C(=O)c1ccccc1C2=O
Reaction time: 8 h
Yield: 74.6 %

Procedure:
2 g of 1,2,3,4-Tetrafluoroanthraquinone and 25 g of 2,6-diethylaniline were charged in a 50 cc, four necked flask and the reaction was carried out at 160° C. for about 8 hours. After completion of reaction, 2,6-diethylaniline was distilled out from the reaction solution and then a column purification using a column with a silica gel was effected to give rise to 2.87 g of 2,3-bis(2,6-diethylanilino)-1,4-difluoroanthraquinone (Dye 23') (yield 74.6 mol %). The physical properties of Dye 23' and analytical values defining the compound are tabulated in table 24.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]2[C:17]3[C:12](=[CH:13][C:14]([NH:21][C:22](=[O:26])[O:23][CH2:24][CH3:25])=[C:15]([N+:18]([O-])=O)[CH:16]=3)[CH2:11][CH2:10]2)=[CH:4][CH:3]=1>CO.[Ni]>[NH2:18][C:15]1[CH:16]=[C:17]2[C:12]([CH2:11][CH2:10][CH:9]2[NH:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)=[CH:13][C:14]=1[NH:21][C:22](=[O:26])[O:23][CH2:24][CH3:25]
Reactant: CCOC(=O)Nc1cc2c(cc1[N+](=O)[O-])C(Nc1ccc(F)cc1)CC2
Agent: [Ni]
Solvent: CO
Product: CCOC(=O)Nc1cc2c(cc1N)C(Nc1ccc(F)cc1)CC2
Reaction time: 4 h

Procedure:
To a solution of ethyl 1-(4-fluorophenylamino)-6-nitro-2,3-dihydro-1H-inden-5-ylcarbamate (250 mg) in 20 ml of methanol was added a catalytic amount of Raney Ni, and the resulting mixture was hydrogenated under ambient temperature and pressure for 4 hours. The reaction mixture was filtered through celite and washed with methanol. The filtrate was evaporated to dryness in vacuo and the residue was purified by column (hexane/EtOAc, 3:1) to give a white solid product. MS: 330 (M+1).
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:36][CH2:37][CH2:38][O:39][C:40]1[N:41]=[C:42]2[C:47](=[CH:48][CH:49]=1)[N:46]=[C:45]([CH2:50][CH3:51])[CH:44]=[C:43]2[O:52][CH2:53][C:54]1[CH:59]=[CH:58][C:57]([C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=2[C:66]2[N:67]=[N:68][N:69]([C:71]([C:84]3[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=3)([C:78]3[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=3)[C:72]3[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=3)[N:70]=2)=[CH:56][CH:55]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>O1CCCC1.C(OCC)(=O)C>[CH2:50]([C:45]1[CH:44]=[C:43]([O:52][CH2:53][C:54]2[CH:55]=[CH:56][C:57]([C:60]3[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=3[C:66]3[N:67]=[N:68][N:69]([C:71]([C:84]4[CH:85]=[CH:86][CH:87]=[CH:88][CH:89]=4)([C:78]4[CH:79]=[CH:80][CH:81]=[CH:82][CH:83]=4)[C:72]4[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=4)[N:70]=3)=[CH:58][CH:59]=2)[C:42]2[C:47](=[CH:48][CH:49]=[C:40]([O:39][CH2:38][CH2:37][OH:36])[N:41]=2)[N:46]=1)[CH3:51]
Reactant: CCc1cc(OCc2ccc(-c3ccccc3-c3nnn(C(c4ccccc4)(c4ccccc4)c4ccccc4)n3)cc2)c2nc(OCCO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)ccc2n1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCc1cc(OCc2ccc(-c3ccccc3-c3nnn(C(c4ccccc4)(c4ccccc4)c4ccccc4)n3)cc2)c2nc(OCCO)ccc2n1
Reaction time: 1 h
Yield: 89.9 %

Procedure:
A 1M solution of tetrabutylammonium fluoride in tetrahydrofuran (THF) (67.8 ml) was added to a solution of compound E (32.1 g) in dry THF (400 ml), and the solution was left to stand for 1 hour. The solution was then diluted with ethyl acetate (400 ml), washed with water (400 ml) and dried (MgSO4). Volatile material was removed by evaporation, and the residue triturated with ether to give 2-ethyl-6-(2-hydroxyethoxy)-4-[(2'-(2-triphenylmethyl-2H-tetrazol-5-yl)biphenyl-4-yl)methoxy]-1,5-naphthyridine (A) (21.6 g), as a white solid, m.p. 170°-173° C.; NMR (d6 -DMSO): 1.3(t,3H), 2.85(q,2H), 3.75(q,2H), 4.45(t,2H), 4.85(t,1H), 5.35(s,2H), 6.8-6.9(m,7H), 7.1-7.7 (complex m,17H), 7.8(dd,1H), 8.15(d,1H).
Reaction SMILES: ClC1C=CC=CC=1C(Cl)=O.Cl[C:12]1[CH:17]=[CH:16][C:15]([C:18]#[N:19])=[CH:14][N:13]=1.[Cl:20][C:21]1[CH:26]=[C:25](Cl)[CH:24]=[CH:23][C:22]=1[C:28]1[C:33]([C:34]2[NH:35][CH:36]=[CH:37][N:38]=2)=[CH:32][N:31]=[C:30]([NH:39][CH2:40][CH2:41][NH:42]C2C=CC([N+]([O-])=O)=CN=2)[N:29]=1>>[Cl:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:28]1[C:33]([C:34]2[NH:38][CH:37]=[CH:36][N:35]=2)=[CH:32][N:31]=[C:30]([NH:39][CH2:40][CH2:41][NH:42][C:12]2[N:13]=[CH:14][C:15]([C:18]#[N:19])=[CH:16][CH:17]=2)[N:29]=1
Reactant: N#Cc1ccc(Cl)nc1
Reactant: O=[N+]([O-])c1ccc(NCCNc2ncc(-c3ncc[nH]3)c(-c3ccc(Cl)cc3Cl)n2)nc1
Agent: O=C(Cl)c1ccccc1Cl
Product: N#Cc1ccc(NCCNc2ncc(-c3ncc[nH]3)c(-c3ccccc3Cl)n2)nc1

Procedure:
6-[(2-{[4-(2-chlorophenyl)-5-imidazol-2-ylpyrimidin-2-yl]amino}ethyl)amino]-pyridine-3-carbonitrile was prepared from 2-chlorobenzoyl chloride and 2-chloro-5-(cyano)pyridine using the general method for [4-(2,4-dichlorophenyl)-5-imidazol-2-ylpyrimidin-2-yl]{2-[(5-nitro(2-pyridyl))amino]ethyl}amine.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N+:9]([O-])=O)[CH:5]=[CH:6][C:7]=1[Cl:8].C(O[CH2:16][CH2:17][CH2:18]C)(=O)C>[Pt]>[CH:17]([NH:9][C:4]1[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=1)([CH3:18])[CH3:16]
Reactant: O=[N+]([O-])c1ccc(Cl)c(Cl)c1
Reactant: CCCCOC(C)=O
Agent: [Pt]
Product: CC(C)Nc1ccc(Cl)c(Cl)c1
Yield: 84.5 %

Procedure:
480.0 g (2.5 mol) of 3,4-dichloronitrobenzene were reacted in 2500 ml of butyl acetate under the reaction conditions described in Example 1 with 10 g of sulfited platinum catalyst F1OP. After the solvent had been distilled off in vacuo, the residue was fractionated to give 431.0 g of N-isopropyl-3,4-dichloroaniline at a purity of 98.9% (GC) in the boiling range 143° to 148° C. (13.33 to 16 bar), which corresponds to a yield of 84.5% of theory.