Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.N([O-])=O.[Na+].C(OCC)(=O)C.C(OCC)C.[H+].[B-](F)(F)(F)[F:29]>>[F:29][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2
Reactant: F[B-](F)(F)F
Reactant: Nc1cccc2ncccc12
Agent: O=N[O-]
Agent: [H+]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CCOCC
Product: Fc1cccc2ncccc12
Reaction time: 1 h
Yield: 24.5 %

Procedure:
To a suspension of 5-aminoquinoline (10.0 g, 0.069 mol) in 48% HBF4 (40 mL) at 0° C. was added portionwise sodium nitrite. This was stirred for 1 hour and then poured into 1:1 ethyl acetate/diethyl ether (50 mL). The resulting suspension was filtered and the solid dried. This solid was added portionwise to refluxing xylene (80 mL) and stirred for 2 hours then allowed to cool. The xylene was decanted off and the residue was dissolved in 1N aqueous hydrochloric acid (100 mL). After neutralization with sodium carbonate, the mixture was extracted with ethyl acetate (3×80 mL). The extracts were dried over sodium sulfate, filtered and the volatiles were removed in vacuo. The residue was purified by silica gel column chromatography, eluting with 2% ethyl acetate in petroleum ether to afford 5-fluoroquinoline as a colorless oil (2.5 g, 24.5%).
Reaction SMILES: [CH3:1][O:2][C:3]1[N:4]=[N+:5]([O-])[C:6]2[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:7]=2[N:8]=1.[H][H]>[Ni].C(O)C>[CH3:1][O:2][C:3]1[N:4]=[N:5][C:6]2[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:7]=2[N:8]=1
Reactant: [H][H]
Reactant: COc1nc2ccc(Cl)cc2[n+]([O-])n1
Agent: [Ni]
Solvent: CCO
Product: COc1nnc2cc(Cl)ccc2n1

Procedure:
21.2 g (0.1 mole) of 3-methoxy-7-chloro-benzo-1,2,4-triazine 1-oxide and 5 g of Raney nickel in 150 ml of ethanol were initially introduced into a stirred VA autoclave. A pressure of 15 atmospheres of hydrogen was applied at 30° C. The mixture was stirred at 30° to 50° C for 5 hours and during this time further hydrogen was fed in under pressure until the pressure remained constant. The autoclave was let down, the catalyst was filtered off and the filtrate was evaporated in vacuo. The residue was recrystallized from wash benzine. 15.2 g. that is to say 78% of theory, of 3-methoxy-7-chlorobenzo-1,2,4-triazine with a melting point of 122° C were obtained.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]2[C:11]([C:16]#N)=[N:12][CH:13]=[CH:14][CH:15]=2)=[CH:4][CH:3]=1.[OH-:18].[Na+]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]2[CH2:8][CH2:9][C:10]3[CH:15]=[CH:14][CH2:13][NH:12][C:11]=3[C:16](=[O:18])[C:4]=2[CH:3]=1
Reactant: [OH-]
Reactant: N#Cc1ncccc1CCc1ccc(F)cc1
Agent: [Na+]
Product: O=C1C2=C(C=CCN2)CCc2ccc(F)cc21
Yield: 64 %

Procedure:
The product of Step B hereof (31.5 g, 139 mmol) is cyclized in polyphosphoric acid (1.24 kg) at 200° C. for 51/2 hours. The hot reaction is poured into ice and then basified with 50% NaOH solution. The product is extracted three times with CHCl3 and then washed with brine. The organic phase is dried (Na2SO4), filtered, and solvent is removed to give the desired product (20.4 g) in 64% yield, m.p. 78°-81° C. after recrystallization from diisopropyl ether.
Reaction SMILES: Br[CH2:2][C:3](=O)[CH:4]([CH3:6])[CH3:5].[CH3:8][CH2:9][O:10][C:11]([C:13]([NH2:15])=[S:14])=[O:12]>>[CH2:9]([O:10][C:11]([C:13]1[S:14][CH:2]=[C:3]([CH:4]([CH3:6])[CH3:5])[N:15]=1)=[O:12])[CH3:8]
Reactant: CC(C)C(=O)CBr
Reactant: CCOC(=O)C(N)=S
Product: CCOC(=O)c1nc(C(C)C)cs1
Temperature: 25 °C
Yield: 50.2 %

Procedure:
A neat solution of 5.58 g (34 mmol) of 1-Bromo-3-methyl-butan-2-one and 4.50 g (34 mmol) of ethyl thioxamate (Aldrich) was heated at 70° C. over 18 h and then cooled to room temperature. The mixture was partitioned between sat. aqueous NaHCO3 and EtOAc, the EtOAc layer dried (MgSO4), concentrated and chromatographed over SiO2 (eluted with 2% to 40% EtOAc/hexanes) to afford 3.4 g (48% overall) of 4-isopropylthiazole-2-carboxylic acid ethyl ester as an oil: 1H NMR (500 MHz, CDCl3) δ ppm 1.32 (d, J=7 Hz, 6H), 1.42 (t, J=7.2 Hz, 3H), 3.23 (m, 1H), 4.46 (q, J=7.2 Hz, 2H), 7.18 (s, 1H).
Reaction SMILES: [CH3:1][Si:2]([CH3:15])([CH3:14])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[CH:11]=[C:10]([CH2:12][OH:13])[N:9]=[CH:8]1.C(N(CC)CC)C.[Si:23](Cl)([C:36]([CH3:39])([CH3:38])[CH3:37])([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>ClCCl.CN(C1C=CN=CC=1)C>[Si:23]([O:13][CH2:12][C:10]1[N:9]=[CH:8][N:7]([CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:15])([CH3:14])[CH3:1])[CH:11]=1)([C:36]([CH3:39])([CH3:38])[CH3:37])([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: C[Si](C)(C)CCOCn1cnc(CO)c1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)[Si](OCc1cn(COCC[Si](C)(C)C)cn1)(c1ccccc1)c1ccccc1

Procedure:
1-(2-Trimethylsilylethoxymethyl)-1H-imidazole-4-methanol (100 g, WO 01/02145) was dissolved in dichloromethane (1 L), and triethylamine (hereinafter sometimes referred to as TEA) (122 mL), 4-(N,N-dimethylamino)pyridine (hereinafter sometimes referred to as DMAP) (5.35 g) and tert-butyldiphenylsilyl chloride (hereinafter sometimes referred to as TBDPSCl) (149 mL) were added under stirring. After stirring for a day, the reaction mixture was washed with water and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by flash chromatography (ethyl acetate/hexane=25%→50%) using a silica gel column (trade name: Ultrapack E, manufactured by Yamazen Corporation) to give the title compound (146 g).
Reaction SMILES: Cl[CH:2]([C:15](=O)[CH3:16])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([Cl:10])=[C:6]([C:11]([F:14])([F:13])[F:12])[CH:5]=1.[CH3:18][O:19][C:20]1[CH:21]=[C:22]([NH:32][C:33]([NH2:35])=[S:34])[CH:23]=[CH:24][C:25]=1[N:26]1[CH:30]=[C:29]([CH3:31])[N:28]=[CH:27]1>C(O)C>[Cl:10][C:7]1[CH:8]=[CH:9][C:4]([CH2:3][C:2]2[S:34][C:33]([NH:32][C:22]3[CH:23]=[CH:24][C:25]([N:26]4[CH:30]=[C:29]([CH3:31])[N:28]=[CH:27]4)=[C:20]([O:19][CH3:18])[CH:21]=3)=[N:35][C:15]=2[CH3:16])=[CH:5][C:6]=1[C:11]([F:14])([F:13])[F:12]
Reactant: CC(=O)C(Cl)Cc1ccc(Cl)c(C(F)(F)F)c1
Reactant: COc1cc(NC(N)=S)ccc1-n1cnc(C)c1
Solvent: CCO
Product: COc1cc(Nc2nc(C)c(Cc3ccc(Cl)c(C(F)(F)F)c3)s2)ccc1-n1cnc(C)c1

Procedure:
The title compound was prepared in analogy to example 1 step e) from crude 2-chloro-1-(4-chloro-3-trifluoromethyl-phenyl)-butan-3-one and 53 mg (0.2 mmol) [3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-thiourea in ethanol (1 ml). The crude product was purified on silica gel with methylene chloride/methanol 9/1 yielding 87 mg (88%) of the title compound as a brown solid. MS ISP (m/e): 493.2/495.2 (100/35) (M+H)+. 1H NMR (CDCl3, 300 MHz): δ (ppm)=7.63 (s, 1H), 7.51 (s, 1H), 7.43 (d, 1H), 7.30 (d, 1H), 7.23 (s, 1H), 7.15 (d, 1H), 6.90 (d, 1H), 6.85 (s, 1H), 4.00 (s, 2H), 3.82 (s, 3H), 2.31 (s, 6H).
Reaction SMILES: [NH2:1][C:2]1[NH:6][N:5]=[N:4][CH:3]=1.C([BH3-])#N.[Na+].[CH:11]1([O:16][C:17]2[CH:18]=[C:19]([CH:22]=[CH:23][C:24]=2[O:25][CH3:26])[CH:20]=O)[CH2:15][CH2:14][CH2:13][CH2:12]1>CO.Cl>[CH:11]1([O:16][C:17]2[CH:18]=[C:19]([CH:22]=[CH:23][C:24]=2[O:25][CH3:26])[CH2:20][NH:1][C:2]2[NH:6][N:5]=[N:4][CH:3]=2)[CH2:12][CH2:13][CH2:14][CH2:15]1
Reactant: Nc1cnn[nH]1
Reactant: COc1ccc(C=O)cc1OC1CCCC1
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: COc1ccc(CNc2cnn[nH]2)cc1OC1CCCC1
Temperature: 25 °C
Reaction time: 64 h
Yield: 27.9 %

Procedure:
To a stirred solution of 5-amino-1,2,3-triazole (3.0 g, 0.036 mol) in 100 ml of methanol and 15 ml of 1N HCl was added sodium cyanoborohydride (1.89 g, 0.030 mol) and 3-cyclopentyloxy-4-methoxybenzaldehyde (6.6 g, 0.30 mol). The reaction mixture was stirred at room temperature for 64 hours and then acidified to pH 2 with concentrated HCl. The solution was evaporated at reduced pressure and the residue was treated with water (100 ml) and extracted twice with 100 ml portions of ethyl acetate. The ethyl acetate extracts were combined and extracted twice with 50 ml portions of 3N HCl and then discarded. The aqueous extracts were combined with the original aqueous layer and basified to pH 12 with potassium hydroxide pellets. The alkaline solution was extracted twice with 100 ml portions of ethyl acetate. The ethyl acetate extracts were combined and evaporated to give a solid which was crystallized from ethyl acetate to give 2.9 g (34%) of the title compound mp 113-114° C. collected in two crops.
Reaction SMILES: [F:1][C:2]1[C:7]([C:8]([O:10][CH2:11][CH2:12][O:13][CH3:14])=[O:9])=[C:6]([S:15]([N:18]=[C:19]=[O:20])(=[O:17])=[O:16])[CH:5]=[CH:4][CH:3]=1.[NH2:21][C:22]1[N:27]=[C:26]([O:28][CH3:29])[N:25]=[C:24]([O:30][CH3:31])[N:23]=1>C(Cl)Cl.CN(C=O)C>[F:1][C:2]1[C:7]([C:8]([O:10][CH2:11][CH2:12][O:13][CH3:14])=[O:9])=[C:6]([S:15]([NH:18][C:19]([NH:21][C:22]2[N:27]=[C:26]([O:28][CH3:29])[N:25]=[C:24]([O:30][CH3:31])[N:23]=2)=[O:20])(=[O:16])=[O:17])[CH:5]=[CH:4][CH:3]=1
Reactant: COCCOC(=O)c1c(F)cccc1S(=O)(=O)N=C=O
Reactant: COc1nc(N)nc(OC)n1
Solvent: ClCCl
Solvent: CN(C)C=O
Product: COCCOC(=O)c1c(F)cccc1S(=O)(=O)NC(=O)Nc1nc(OC)nc(OC)n1
Temperature: 25 °C
Reaction time: 14 h

Procedure:
7.1 g of β-methoxyethyl 6-fluoro-2-isocyanatosulfonylbenzoate in 20 ml of methylene chloride were added over 10 minutes at 25° C. to a stirred mixture of 4 g of 2-amino-4,6-dimethoxy-1,3,5-triazine in 40 ml of DMF under nitrogen; the temperature rose to 32° C. After the mixture had been stirred for 14 hours at 25° C., the solvent was removed under reduced pressure and the residue was stirred with ether and twice with 3N HCL. It was then taken up in acetone, insoluble mater was separated off and the filtrate was concentrated to dryness. 7 g of the compound shown in the title, of melting point 179° C.-182° C. were obtained.
Reaction SMILES: [H-].[Na+].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]([O:14][CH3:15])=[O:13])=[CH:4]1.[CH2:16](I)[CH3:17].O>CN(C=O)C>[CH2:16]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]([O:14][CH3:15])=[O:13])=[CH:4]1)[CH3:17]
Reactant: CCI
Reactant: COC(=O)c1c[nH]c2ccccc12
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCn1cc(C(=O)OC)c2ccccc21
Temperature: 0 °C

Procedure:
In DMF (8.0 ml) was suspended sodium hydride (60% in oil, 273.9 mg, 6.846 mmol). To the resulting suspension was added methyl indole-3-carboxylate (399.8 mg, 2.282 mmol) under stirring at 0° C. The reaction mixture was stirred for 40 minutes at the same temperature. To the mixture was added ethyl iodide (0.27 ml, 3.423 mmol) at 0° C., followed by stirring at the same temperature for further 2 hours. Water was added to the reaction mixture to terminate the reaction. The reaction mixture was extracted with ethyl acetate. The extract was washed successively with 1N HCl and saturated brine, dried over anhydrous sodium sulfate and distilled under reduced pressure to remove the solvent, whereby methyl 1-ethylindole-3-carboxylate was obtained. The resulting compound was provided for the subsequent reaction without further purification.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[C:8]([C:9]([O:11][CH3:12])=[O:10])[C:7]([OH:14])=[CH:6][CH:5]=1)([O-:3])=[O:2].N1C=CN=C1.[C:20]([Si:24](Cl)([CH3:26])[CH3:25])([CH3:23])([CH3:22])[CH3:21].O>CN(C=O)C>[CH3:12][O:11][C:9](=[O:10])[C:8]1[CH:13]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=[CH:6][C:7]=1[O:14][Si:24]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:26])[CH3:25]
Reactant: COC(=O)c1cc([N+](=O)[O-])ccc1O
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)c1cc([N+](=O)[O-])ccc1O[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 16 h
Yield: 31 %

Procedure:
A solution of methyl 5-nitrosalicylate (10.0 g, 50.7 mmol) and imidazole (3.8 g, 55.8 mol) in DMF (50 mL) at 0° C. was treated with t-butylchloro-dimethyl-silane and stirred 16 h at room temperature. The reaction mixture was poured into water (100 mL) and extracted with ether (3×50 mL). The combined extracts were washed with water (4×100 mL) and brine (50 mL), dried over magnesium sulfate, and concentrated. The crude residue was purified by flash chromatography (silica gel, 4×15 cm, eluted with 95/5 hexanes/EtOAc) to yield 2-(tert-butyl-dimethyl-silanyloxy)-5-nitro-benzoic acid methyl ester as a white solid (4.9 g, 31%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]2[CH:16]=[N:15][NH:14][C:13](=[O:17])[CH2:12]2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].CS(C)=O.BrN1C(=O)CCC1=O>O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[CH:16]=[N:15][NH:14][C:13](=[O:17])[CH:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: COc1ccc(C2C=NNC(=O)C2)cc1OC
Agent: O=C1CCC(=O)N1Br
Solvent: O
Solvent: CS(C)=O
Product: COc1ccc(-c2cn[nH]c(=O)c2)cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 64.8 %

Procedure:
5-(3,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-one (288 mg) was suspended in a mixed solvent of dimethyl sulfoxide (3 ml) and water (0.1 ml), to which N-bromosuccinimide (438 mg) was added under cooling on ice. After the addition was complete, the reaction temperature was raised to room temperature and stirred for 2 hours. The reaction mixture was poured into an ice-cold water and the deposit was filtered. The residue was purified with flash chromatography (SiO2: eluted with ethyl acetate) to obtain the title compound (185 mg, yield 64.7%).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:14]=1[NH:13][C:12]1[CH2:11][CH2:10][CH2:9][C:8](=[O:15])[C:7]2=1.CCCCC.[H-].[Na+].[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CN(C=O)C.C(Br)C1C=CC=CC=1>[CH2:23]([N:13]1[C:12]2[CH2:11][CH2:10][CH2:9][C:8](=[O:15])[C:7]=2[C:6]2[C:14]1=[C:2]([CH3:1])[CH:3]=[CH:4][CH:5]=2)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: BrCc1ccccc1
Reactant: Cc1cccc2c3c([nH]c12)CCCC3=O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCCCC
Product: Cc1cccc2c3c(n(Cc4ccccc4)c12)CCCC3=O
Reaction time: 0.5 h
Yield: 72.5 %

Procedure:
8-Methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one (0.1967 g, 0.99 mmol) is added to a slurry of pentane-washed NaH (0.0485 g, 0.0012 mol) in DMF (2 mL) and after stirring for 30 min, benzyl bromide (0.14 mL, 0.0012 mol) is added. After 3 h starting material still remained, so additional benzyl bromide (0.015 mL, 0.013 mmol) is added and the mixture is stirred overnight at room temperature. The mixture is then partitioned between aq. sodium bicarbonate and ethyl acetate and the organic layer is dried over sodium sulfate and concentrated to dryness. The resulting solids are recrystallized from ethyl acetate/hexane/dichloromethane to give 0.2076 g (73%) of the title compound; mp 165-166° C.; MS (ESI+) for C20H19NO m/z 290.2 (M+H)+; IR (drift) 2940, 1637, 1599, 1538, 1494, 1462, 1447, 1416, 1357, 1322, 1121, 787, 752, 727, 697 cm−1; 1H NMR (CDCl3) δ2.21, 2.51, 2.59, 2.82, 5.58, 6.89, 6.95, 7.16, 7.29, 8.23. Anal. Calcd for C20H19NO: C, 83.01; H, 6.62; N, 4.84. Found: C, 82.53; H, 6.62; N, 4.86.
Reaction SMILES: Cl[CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([CH3:24])=[C:20]([OH:25])[CH:19]=3)=[C:10]([C:15]#[N:16])[CH:11]=[N:12]2)=[CH:7][C:6]=1[O:26][CH3:27].[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1.[I-].[Na+]>COCCOC>[OH:25][C:20]1[CH:19]=[C:18]([NH:17][C:9]2[C:8]3[C:13](=[CH:14][C:5]([O:4][CH2:3][CH2:2][N:28]4[CH2:33][CH2:32][O:31][CH2:30][CH2:29]4)=[C:6]([O:26][CH3:27])[CH:7]=3)[N:12]=[CH:11][C:10]=2[C:15]#[N:16])[CH:23]=[CH:22][C:21]=1[CH3:24]
Reactant: C1COCCN1
Reactant: COc1cc2c(Nc3ccc(C)c(O)c3)c(C#N)cnc2cc1OCCCl
Agent: [I-]
Agent: [Na+]
Solvent: COCCOC
Product: COc1cc2c(Nc3ccc(C)c(O)c3)c(C#N)cnc2cc1OCCN1CCOCC1

Procedure:
A mixture of 1 g (2.38 mmol) of 7-(2-chloro-ethoxy)-4-(3-hydroxy-4-methyl-phenylamino)-6-methoxy-quinoline-3-carbonitrile, 3.4 g (39 mmol) of morpholine, and 0.08 g of sodium iodide in 22 ml ethylene glycol dimethyl ether refluxed for 34 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and the residue was chromatographed on silica gel eluting with ethyl acetate-methanol-triethylamine 70:30:2.5 giving 1.05 of the title compound as a light orange solid: mass spectrum (electrospray, m/e) M+H 435.0; (M+2H)+2 218.0.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][CH:29]=1)[O:5][CH2:6][CH:7]1[O:11][C:10](=[O:12])[N:9]([C:13]([CH3:26])([CH3:25])[CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][CH:17]=2)[CH2:8]1.C(OCC)(=O)C.[BH4-].[Na+]>C(O)(C)(C)C>[NH2:22][C:19]1[CH:20]=[CH:21][C:16]([O:15][CH2:14][C:13]([N:9]2[CH2:8][CH:7]([CH2:6][O:5][C:4]3[CH:27]=[CH:28][CH:29]=[C:2]([Cl:1])[CH:3]=3)[O:11][C:10]2=[O:12])([CH3:25])[CH3:26])=[CH:17][CH:18]=1
Reactant: CC(C)(COc1ccc([N+](=O)[O-])cc1)N1CC(COc2cccc(Cl)c2)OC1=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(C)(C)O
Solvent: CCOC(C)=O
Product: CC(C)(COc1ccc(N)cc1)N1CC(COc2cccc(Cl)c2)OC1=O
Reaction time: 6 h
Yield: 90.2 %

Procedure:
6.32 g of stannous chloride dihydrate were added to a solution of 2.34 g of 5-(3-chlorophenoxymethyl)-3-[2-(4-nitrophenoxy)-1,1-dimethylethyl]oxazolidin-2-one (prepared as described in Preparation 108) in 70 ml of a 9:1 by volume mixture of ethyl acetate and t-butanol. 0.11 g of sodium borohydride was then added to the mixture over an oil bath at 66° C. The mixture was stirred at the same temperature for 6 hours. At the end of this time, the solvent was removed from the reaction mixture by evaporation under reduced pressure, and the residue was neutralized by adding an aqueous sodium hydrogencarbonate solution. The insolubles which had precipitated were removed by filtration, and the filtrate was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The ethyl acetate was removed from the extract by evaporation under reduced pressure, to give 1.96 g of the title compound having an Rf value of 0.34 (on silica gel thin layer chromatography, using a 4:1 by volume mixture of ethyl acetate and hexane as the developing solvent).
Reaction SMILES: [C:1]1([N:7]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[C:28]4[C:24](=[N:25][NH:26][N:27]=4)[C:23]([C:29]4[CH:34]=[CH:33][C:32]([N:35]([C:42]5[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=5)[C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)=[CH:31][CH:30]=4)=[CH:22][CH:21]=3)=[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.Cl[C:49]1[C:58]2[C:53](=[CH:54][CH:55]=[CH:56][CH:57]=2)[N:52]=[C:51]([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[CH:50]=1.[H-].[Na+].C(=O)=O>ClC1C=CC=CC=1.CN(C)C=O>[C:8]1([N:7]([C:14]2[CH:15]=[CH:16][C:17]([C:20]3[C:28]4[C:24](=[N:25][N:26]([C:49]5[C:58]6[C:53](=[CH:54][CH:55]=[CH:56][CH:57]=6)[N:52]=[C:51]([C:59]6[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=6)[CH:50]=5)[N:27]=4)[C:23]([C:29]4[CH:34]=[CH:33][C:32]([N:35]([C:36]5[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=5)[C:42]5[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=5)=[CH:31][CH:30]=4)=[CH:22][CH:21]=3)=[CH:18][CH:19]=2)[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: Clc1cc(-c2ccccc2)nc2ccccc12
Reactant: c1ccc(N(c2ccccc2)c2ccc(-c3ccc(-c4ccc(N(c5ccccc5)c5ccccc5)cc4)c4n[nH]nc34)cc2)cc1
Agent: O=C=O
Agent: [H-]
Agent: [Na+]
Solvent: Clc1ccccc1
Solvent: CN(C)C=O
Product: c1ccc(-c2cc(-n3nc4c(-c5ccc(N(c6ccccc6)c6ccccc6)cc5)ccc(-c5ccc(N(c6ccccc6)c6ccccc6)cc5)c4n3)c3ccccc3n2)cc1
Temperature: 50 °C

Procedure:
A mixture of Intermediate D (605 mg, 1.0 mmol), 4-chloro-2-phenylquinoline (481 mg, 2.0 mmol), 60% NaH (80 mg, 2.0 mmol), and dimethylformamide (15 mL) was stirred under argon and heated at 50° C. for 3 hours. After cooling, the mixture was diluted with chlorobenzene (50 mL) and treated with a piece of dry ice to reduce the pH. The volatiles were removed under reduced pressure, and the residue was chromatographed using silica gel and hexane/dichloromethane (2:1) as an eluent to give 4,7-bis(4-(N,N-diphenylamino)phenyl)-2-(2-phenylquinolin-4-yl)-2H-benzo[d][1,2,3]triazole (Example 17) as orange-pink crystals, 640 mg (79%). 1H NMR (400 MHz, CDCl3): δ 8.70 (m, 3H, 2-phenylquinazolin-4-yl), 8.22 (d, J=8.4 Hz, 1H, 2-phenylquinazolin-4-yl), 8.12 (d, J=8.8 Hz, 4H, p-phenylene), 7.97 (ddd, J=8.4, 6.9 and 1.4 Hz, 1H, 2-phenylquinazolin-4-yl), 7.76 (s, 2H, benzotriazole), 7.68 (ddd, J=8.5, 7.0 and 1.1 Hz, 1H, 2-phenylquinazolin-4-yl), 7.53 (m, 3H, 2-phenylquinazolin-4-yl), 7.25-7.30 (m, 8H, Ph), 7.21 (d, J=8.4 Hz, 4H, p-phenylene), 7.16-7.19 (m, 8H, Ph), 7.05 (tt, J=7.3 and 1.1 Hz, 4H, Ph), 2.86 (s, 3H, quinaldine). UV-vis spectrum (dichloromethane): λmax=452 nm. Fluorimetry (dichloromethane): λmax=654 nm.
Reaction SMILES: [OH:1][CH2:2][C:3]1[N:8]=[C:7]([NH:9][C:10]([NH2:12])=[S:11])[CH:6]=[CH:5][CH:4]=1.Br[CH:14]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH:15](OC)OC.Cl.C([O-])([O-])=O.[Na+].[Na+]>CCO.O>[C:20]1([C:14]2[S:11][C:10]([NH:9][C:7]3[CH:6]=[CH:5][CH:4]=[C:3]([CH2:2][OH:1])[N:8]=3)=[N:12][CH:15]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: NC(=S)Nc1cccc(CO)n1
Reactant: COC(OC)C(Br)c1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: OCc1cccc(Nc2ncc(-c3ccccc3)s2)n1
Reaction time: 7 h

Procedure:
(6-Hydroxymethyl-pyridin-2-yl)-thiourea (6-3) 1.05 g (5.73 mmol) and (1-bromo-2,2-dimethoxy-ethyl)-benzene (2.11 g, 8.60 mmol) were stirred in 18 mL EtOH. Concentrated HCl (aq), 6 mL, was added and the mixture was heated to reflux. After 7 h, additional (1-bromo-2,2-dimethoxy-ethyl)-benzene (1.05 g, 4.30 mmol) and conc HCl (aq), 3 mL were added. The reaction was then heated at reflux for an additional 14.5 h. The reaction was poured into 120 mL water and the pH was adjusted to 7 with Na2CO3 (s). A precipitate formed which was filtered and washed with water. The solid was triurated with 50 mL ether, filtered and washed with ether to provide the titled compound as a white solid. 1H NMR(CD3OD): δ7.72 (t, 1H, J=7.7 Hz), 7.58 (s overlapping with d, 3H), 7.38 (t, 2H, 7.5 Hz), 7.25 (t, 1H, J=7.3 Hz), 7.07 (d, 1H, J=7.5 Hz), 6.90 (d, 1H, J=8.3 Hz), 4.76 (s, 2H). Mp: 196-198° C. M+1: 284.0.
Reaction SMILES: [CH2:1]([C:3]1[CH:16]=[CH:15][C:6]([O:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10](F)[N:9]=2)=[C:5]([O:17][CH3:18])[CH:4]=1)[CH3:2].[CH2:19]([NH2:23])[CH2:20][CH2:21][CH3:22]>>[CH2:19]([NH:23][C:10]1[CH:11]=[CH:12][CH:13]=[C:8]([O:7][C:6]2[CH:15]=[CH:16][C:3]([CH2:1][CH3:2])=[CH:4][C:5]=2[O:17][CH3:18])[N:9]=1)[CH2:20][CH2:21][CH3:22]
Reactant: CCc1ccc(Oc2cccc(F)n2)c(OC)c1
Reactant: CCCCN
Product: CCCCNc1cccc(Oc2ccc(CC)cc2OC)n1
Temperature: 80 °C

Procedure:
To 2-(4-ethyl-2-methoxyphenoxy)-6-fluoropyridine (94 mg; 0.32 mmol), under argon, was added butylamine (0.5 mL). The reaction was heated to 80° C. for 18 hours. The mixture was concentrated in vacuo. After quenching with saturated NaHCO3 (10 mL), extractions with dichloromethane (3*5 mL), the organic phase was dried over NaSO4, and concentrated in vacuo to give the title compound as a light brown oil used without further purification (87 mg; 0.29 mmol; 89%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[N+:25]([O-])=O)[CH2:13][C:14]([O:16][CH3:17])=[O:15])(=[O:11])=[O:10])=[CH:5][CH:4]=1.[H][H]>C(O)C.C(OCC)(=O)C.[Pd]>[NH2:25][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[CH2:18][N:12]([S:9]([C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)(=[O:11])=[O:10])[CH2:13][C:14]([O:16][CH3:17])=[O:15]
Reactant: COC(=O)CN(Cc1ccccc1[N+](=O)[O-])S(=O)(=O)c1ccc(OC)cc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCO
Product: COC(=O)CN(Cc1ccccc1N)S(=O)(=O)c1ccc(OC)cc1
Yield: 103.1 %

Procedure:
To a solution of 4.2 g of methyl 2-[(4-methoxybenzenesulfonyl)-(2-nitrobenzyl)amino]acetate in 200 ml of ethanol-ethyl acetate (1:1) was added 0.42 g of 10% Pd on carbon (wet--50% H2O) and the mixture shaken in a Parr hydrogenator under 35 pounds per square inch of hydrogen for 4.5 hours at room temperature. The mixture was filtered through diatomaceous earth and the filtrate concentrated to dryness under vacuum to give 4.0 g of crystals. m.p. 100°-102° C.