Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1C=CC(NC(C2C(=O)C(=NNC3C=CC(C4C=CC(NN=C5C(=O)C(C(NC6C=CC=CC=6)=O)=CC6C5=CC=CC=6)=C([Cl:55])C=4)=CC=3Cl)C3C(=CC=CC=3)C=2)=O)=CC=1.[CH3:59][N:60]([C:78]1[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=1)[N:61]=[CH:62][C:63]1[CH:64]=[CH:65][C:66]2[N:67]([CH2:76][CH3:77])[C:68]3[C:73]([C:74]=2[CH:75]=1)=[CH:72][CH:71]=[CH:70][CH:69]=3>>[CH3:59][N:60]([C:78]1[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=1)[N:61]=[CH:62][C:63]1[CH:64]=[CH:65][C:66]2[N:67]([CH2:76][CH2:77][Cl:55])[C:68]3[C:73]([C:74]=2[CH:75]=1)=[CH:72][CH:71]=[CH:70][CH:69]=3
Reactant: O=C(Nc1ccccc1)C1=Cc2ccccc2C(=NNc2ccc(-c3ccc(NN=C4C(=O)C(C(=O)Nc5ccccc5)=Cc5ccccc54)c(Cl)c3)cc2Cl)C1=O
Reactant: CCn1c2ccccc2c2cc(C=NN(C)c3ccccc3)ccc21
Product: CN(N=Cc1ccc2c(c1)c1ccccc1n2CCCl)c1ccccc1

Procedure:
In Example 7, instead of Chloro Diane Blue and 9-ethylcarbazole-3-carbaldehyde-1-methyl-1-phenylhydrazone represented by the formula (5), ##STR42## was employed as the charge carrier producing pigment, and 9-(β-chloroethyl)carbazole-3-carbaldehyde 1-methyl-1-phenylhydrazone represented by the formula (13) was employed as the charge transport material. ##STR43##
Reaction SMILES: Cl.[H][H].[N+:4]([C:7]12[CH2:16][CH:11]3[CH2:12][CH:13]([CH2:15][C:9]([OH:17])([CH2:10]3)[CH2:8]1)[CH2:14]2)([O-])=O>>[NH2:4][C:7]12[CH2:16][CH:11]3[CH2:12][CH:13]([CH2:15][C:9]([OH:17])([CH2:10]3)[CH2:8]1)[CH2:14]2
Reactant: O=[N+]([O-])C12CC3CC(CC(O)(C3)C1)C2
Reactant: [H][H]
Agent: Cl
Product: NC12CC3CC(C1)CC(O)(C3)C2
Yield: 95 %

Procedure:
An autocrave was charged with 10 ml of methanol were added 10 mmol of the 1-nitro-3-adamantanol obtained by the method of Preparation Example 4, 5% Pd-C (10 mol % as Pd, relative to a substrate) and 1 ml of hydrochloric acid, and the mixture was stirred in a hydrogen atmosphere at a temperature of 80° C. for 2 hours. And, as a result, the 1-nitro-3-adamantanol was converted into a 1-amino-3-adamantanol (yield:95%) with a conversion of 99%.
Reaction SMILES: [F:1][CH:2]([F:41])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:20][CH:19]4[O:21][CH:16]([CH2:17][CH2:18]4)[CH2:15]3)[N:11]=[C:10]([N:22]3[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][CH2:23]3)[N:9]=2)[C:6]2[CH:35]=[CH:36][CH:37]=[C:38]([O:39][CH3:40])[C:5]=2[N:4]=1.C(O)(C(F)(F)F)=O.N>C(Cl)Cl>[F:41][CH:2]([F:1])[C:3]1[N:7]([C:8]2[N:9]=[C:10]([N:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)[N:11]=[C:12]([N:14]3[CH2:20][CH:19]4[O:21][CH:16]([CH2:17][CH2:18]4)[CH2:15]3)[N:13]=2)[C:6]2[CH:35]=[CH:36][CH:37]=[C:38]([O:39][CH3:40])[C:5]=2[N:4]=1
Reactant: COc1cccc2c1nc(C(F)F)n2-c1nc(N2CCN(C(=O)OC(C)(C)C)CC2)nc(N2CC3CCC(C2)O3)n1
Agent: N
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1cccc2c1nc(C(F)F)n2-c1nc(N2CCNCC2)nc(N2CC3CCC(C2)O3)n1
Yield: 90.9 %

Procedure:
Reaction of tert-butyl 4-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1,3,5-triazin-2-yl]-1-piperazinecarboxylate (513 mg, 0.896 mmol) with an excess of TFA (2 mL) in CH2Cl2 (10 mL) at room temperature for 3 hrs, followed by treatment with aq. NH3 gave 385 mg (91% yield) of 3-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(1-piperazinyl)-1,3,5-triazin-2-yl]-8-oxa-3-azabicyclo[3.2.1]octane: mp 221-223° C.; 1H NMR (CDCl3) δ7.90 (dd, J=8.4, 0.6 Hz, 1H), 7.51 (t, JHF=53.6 Hz, 1H), 7.35 (t, J=8.2 Hz, 1H), 6.81 (d, J=7.7 Hz, 1H), 4.47 (d, J=9.6 Hz, 2H), 4.33 (t, J=12.1 Hz, 2H), 4.05 (s, 3H), 3.86 (br s, 4H), 3.28 (dd, J=32.5, 12.3 Hz, 2H), 2.95 (br s, 4H), 1.98 (dd, J=8.3, 4.5 Hz, 2H), 1.80 (m, 2H).
Reaction SMILES: [Br:1][C:2]1[C:11]2[S:12][C:13]([CH3:16])=[C:14]([CH3:15])[C:10]=2[C:9]([C:17]2[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[C:19]([Br:26])[C:18]=2OC)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[CH:7]2.[Sn](Cl)Cl.[C:32](OCC)(=[O:34])C>>[Br:26][C:19]1[C:20]([O:34][CH3:32])=[C:21]([NH2:23])[CH:22]=[C:17]([C:9]2[C:10]3[C:14]([CH3:15])=[C:13]([CH3:16])[S:12][C:11]=3[C:2]([Br:1])=[C:3]3[C:8]=2[CH:7]=[CH:6][CH:5]=[CH:4]3)[CH:18]=1
Reactant: COc1c(Br)cc([N+](=O)[O-])cc1-c1c2ccccc2c(Br)c2sc(C)c(C)c12
Reactant: CCOC(C)=O
Agent: Cl[Sn]Cl
Product: COc1c(N)cc(-c2c3ccccc3c(Br)c3sc(C)c(C)c23)cc1Br
Temperature: 70 °C
Reaction time: 0.5 h
Yield: 92 %

Procedure:
A stirred suspension of 9-bromo-4-(3-bromo-methoxy-5-nitro-phenyl)-2,3-dimethyl-naphtho[2,3-b]thiophene (0.372, 0.714 mmol), tin (II) dichloride (805 mg, 3.57 mmol) and ethyl acetate (4 mL)was heated to 70° C. where disolution occurred. After 30 min, the reaction mixture was cooled to room temperature, diluted with ethyl acetate and silica gel was added. The ethyl acetate was removed and the adsorbate was flash chromatographed (4:1 pet. ether: ethyl acetate) to provide the title compound as a white solid (0.324 g, 92%): mp 198-200° C.: NMR (DMSO-d6); 8.18 (d, J=8 Hz, 1H), 7.64 (ddd, J=8, 6, 1 Hz, 1H), 7.58 (d, J=8 Hz, 1H), 7.50 (ddd, J=8, 6, 1 Hz, 1H), 6.70 (d, J=2 Hz, 1H), 6.64 (d, J=2 Hz, 1H), 5.46 (s, 1H), 3.80 (s, 3H), 2.44 (d,J=1 Hz, 3H), 1.73 (d, J=1 Hz, 3H); MS (EI): 2 bromine isotope pattern 489 (50%, M+), 491 (100%, M+), 493 (60%, M+); Anal. Calc. for C21H17Br2NOS: C, 51.34; H, 3.49; N, 2.85. Found: C, 51.00; H, 3.43; N, 2.71.
Reaction SMILES: [C:1]1([C:7]#[CH:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Li])CCC.C(#N)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.CN(C)CCCCN(C)C.CCCCCCCCCCCCC>C1COCC1.[Zn+2].[Br-].[Br-]>[C:1]1([C:7]#[C:8][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C#Cc1ccccc1
Reactant: N#Cc1ccccc1
Agent: CCCCCCCCCCCCC
Agent: CN(C)CCCCN(C)C
Agent: [Br-]
Solvent: C1CCOC1
Product: C(#Cc1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 67 h
Yield: 72.5 %

Procedure:
A solution of phenylacetylene (0.439 ml; 0.409 g; 4.00 mmol) in THF (2 ml) was treated at 0° C. with n-butyllithium (1.6 ml; 4.0 mmol; 2.5 M in hexanes) and the resulting solution was allowed to warm to room temperature for 10 min. The solution was cooled to 0° C., then treated with a solution of ZnBr2 (0.901 g; 4.00 mmol) in THF (2 ml) and allowed to warm to room temperature for 30 min. Solvent was removed in vacuo, then THF (2 ml) was added. This solution was then added to a room temperature solution of benzonitrile (0.204 ml; 0.206 g; 2.00 mmol), dichlorobis(trimethylphosphine)nickel (0.0282 g; 5 mol %), N,N,N′,N′-tetramethyl-1,4-butanediamine (0.182 ml; 0.144 g; 1.00 mmol), and tridecane (0.244 ml; 0.184 g; 1.00 mmol) in THF (2 ml). The reaction mixture was then heated to 65° C. and stirred for 67 h; then a sample was withdrawn and quenched in a mixture of 1 M sodium citrate (aq) and MTBE. GC analysis of the organic phase of the hydrolyzed reaction sample showed the presence of 1.45 mmol (73% yield) of diphenylacetylene and 0.31 mmol of benzonitrile remaining in the reaction mixture.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([O-:7])[CH:2]=1.[K+].[NH2:9][C:10]1[CH:15]=[CH:14][C:13](I)=[CH:12][N:11]=1>CC(N(C)C)=O>[NH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:7][C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)=[CH:12][N:11]=1
Reactant: Nc1ccc(I)cn1
Reactant: [O-]c1cccnc1
Agent: [K+]
Solvent: CC(=O)N(C)C
Product: Nc1ccc(Oc2cccnc2)cn1

Procedure:
3.3 G. of potassium 3-pyridinolate, 5.47 g. of 2-amino 5-iodopyridine and 1.78 g. of cuprous oxide in 150 ml. of dimethylacetamide are heated at reflux under a nitrogen atmosphere for 24 hours. The solvent is removed in vacuo and the residue is extracted with chloroform. Chromatography of the methylene chloride soluble portion with silica gel and elution with ethyl acetate yields 2-amino-5-(3-pyridyloxy) pyridine.
Reaction SMILES: [Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[C:6](Cl)[N:5]2[N:15]=[C:16]([C:18]([O:20][CH3:21])=[O:19])[CH:17]=[C:4]2[N:3]=1.N>ClCCl.[Cl-].[Na+].O.[Zn]>[Cl:1][C:2]1[C:7]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[CH:6][N:5]2[N:15]=[C:16]([C:18]([O:20][CH3:21])=[O:19])[CH:17]=[C:4]2[N:3]=1
Reactant: COC(=O)c1cc2nc(Cl)c(-c3ccccc3)c(Cl)n2n1
Agent: N
Agent: [Cl-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: COC(=O)c1cc2nc(Cl)c(-c3ccccc3)cn2n1
Temperature: 60 °C
Reaction time: 3 h

Procedure:
2.00 g methyl 5,7-dichloro-6-phenylpyrazolo[1,5-a]pyrimidine-2-carboxylate are dissolved in 40 ml dichloromethane. 40 ml brine, 20 ml ammonia solution 25% w/w and 1.22 g zinc powder are added and the mixture is stirred at 60° C. for 3 h. The reaction mixture is filtrated over kieselgur and is washed with dichloromethane and water. The organic phase is separated and the water phase is extracted with dichloromethane. The combined dichloromethane phase is dried over Na2SO4 and evaporated. The crude product contains methyl 5,7-dichloro-6-phenylpyrazolo[1,5-a]pyrimidine-2-carboxylate. The crude product is dissolved again in 20 ml dichloromethane. 20 ml brine, 10 ml ammonia solution 25% w/w and 0.60 g zinc powder are added and the mixture is stirred at 60° C. for 45 min. The reaction mixture is filtrated over kieselgur and washed with dichloromethane and water. The organic phase is separated and the water phase is extracted with dichloromethane. The combined dichloromethane phase is dried over Na2SO4, the solvent is evaporated and the residue is purified by chromatography on silica gel (dichloromethane/ethyl acetate) to yield the desired compound.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[O:17][CH3:18])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:6].I[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([N+:26]([O-:28])=[O:27])[CH:21]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=C(C)C=C(C)C=1.O1CCCC1.C(OCC)(=O)C.[Cu]I>[N+:26]([C:22]1[CH:21]=[C:20]([NH:1][C:2]2[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=2[O:17][CH3:18])[C:5]([NH:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:6])[CH:25]=[CH:24][CH:23]=1)([O-:28])=[O:27]
Reactant: COc1ccc(C(=O)Nc2ccccc2)cc1N
Reactant: O=[N+]([O-])c1cccc(I)c1
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1cc(C)cc(C)c1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COc1ccc(C(=O)Nc2ccccc2)cc1Nc1cccc([N+](=O)[O-])c1
Reaction time: 48 h
Yield: 6.2 %

Procedure:
A mixture of 3-amino-4-methoxy-N-phenyl-benzamide (2.0 g, 8 mmol), 1-iodo-3-nitrobenzene (2.5 g, 10 mmol), potassium carbonate (2.8 g, 20 mmol), and copper(I) iodide (0.4 g, 2 mmol) in mesitylene (20 mL) was stirred under an inert atmosphere and heated to reflux. After 48 hours, the mixture was allowed to cool and was then diluted with tetrahydro-furan (100 mL) and filtered through Celite. The filtrate was stripped of solvent under reduced pressure to leave an oily residue which was dissolved in ethyl acetate (250 mL) and extracted successively with 2N hydrochloric acid (2×200 mL), water, 0.5 M aqueous potassium carbonate, water, and saturated aqueous sodium chloride, then dried over MgSO4. The solution was filtered and the filtrate stripped of solvent under reduced pressure. The resulting residue was subjected to chromatography on a column of silica gel in chloroform to afford the product (0.18 g); m.p. 220-221° C. after recrystallization from acetonitrile.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]#[C:10][C:11](Cl)=[O:12].[Cl:14][C:15]1[CH:28]=[C:27]([NH2:29])[CH:26]=[CH:25][C:16]=1[O:17][CH2:18][CH2:19][N:20]([CH2:23][CH3:24])[CH2:21][CH3:22]>C1(C)C=CC=CC=1>[Cl:14][C:15]1[CH:28]=[C:27]([NH:29][C:11](=[O:12])[C:10]#[C:9][C:3]2[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=2[Cl:1])[CH:26]=[CH:25][C:16]=1[O:17][CH2:18][CH2:19][N:20]([CH2:23][CH3:24])[CH2:21][CH3:22]
Reactant: O=C(Cl)C#Cc1ccc(Cl)cc1Cl
Reactant: CCN(CC)CCOc1ccc(N)cc1Cl
Solvent: Cc1ccccc1
Product: CCN(CC)CCOc1ccc(NC(=O)C#Cc2ccc(Cl)cc2Cl)cc1Cl
Temperature: 25 °C
Reaction time: 4 h

Procedure:
0.37 g (1.58 mmol) of (2,4-dichlorophenyl)propynoic acid chloride is dissolved in 15 mL of absolute toluene and while cooling with ice combined with 0.77 g (3.16 mmol) of [2-(2-chloro-4-aminophenoxy)ethyl]diethylamine, dissolved in 10 mL of absolute toluene, and stirred for 4 hours at ambient temperature. Then the reaction mixture is extracted with ethyl acetate and dilute aqueous ammonia solution. The organic phase is extracted with water and dried over sodium sulfate. The purification is carried out by column chromatography on silica gel (eluant: dichloromethane/methanol (9:1)). The product obtained is recrystallized from petroleum ether and dried in the vacuum drying chamber at 50° C. Yield: 0.21 g (30.2% of theory); melting point: 98° C.-100° C.; C21H21Cl3N2O2 (M=439.77); calc.: molecular ion peak (M+H)+: 439/441/443; found: molecular ion peak (M+H)+: 439/441/443; Rf value: 0.5 (silica gel, dichloromethane/methanol/ammonia (9:1:0.1)).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([CH:12]([OH:19])[CH2:13][N:14]1[CH:18]=[CH:17][N:16]=[CH:15]1)[CH:6]=[CH:5]2.[CH3:20]N(C)P(N(C)C)(N(C)C)=O.[H-].[Na+].IC>O>[CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([CH:12]([O:19][CH3:20])[CH2:13][N:14]1[CH:18]=[CH:17][N:16]=[CH:15]1)[CH:6]=[CH:5]2
Reactant: Cc1ccc2cc(C(O)Cn3ccnc3)ccc2c1
Reactant: CN(C)P(=O)(N(C)C)N(C)C
Agent: [H-]
Agent: [Na+]
Solvent: CI
Solvent: O
Product: COC(Cn1ccnc1)c1ccc2cc(C)ccc2c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 2.38 g. of 1-[2-(6-methyl-2-naphthyl)-2-hydroxyethyl]imidazole in 40 ml. of hexamethylphosphoramide under nitrogen is added 480 mg. of a 56% dispersion of sodium hydride in mineral oil. After stirring for 1 hour at room temperature, the temperature is adjusted to 50° C. and stirring is continued for 1 to 2 hours. The reaction mixture is then cooled to about 5° C. and 0.74 ml. of iodomethane is added dropwise. Thereafter, the solution is stirred at 5° to 10° C. for 1 hour, at room temperature for 4 hours and then heated at 50° C. for 2 hours. The reaction mixture is then poured into water and the resultant aqueous mixture extracted with ether and the ether extracts washed with water. The organic phase is dried over magnesium sulfate and evaporated. The resulting residue may be chromatographed on silica gel to effect purification of the free base. Elution of the gel with 5 to 10% methanol in dichloromethane yields 1-[2-(6-methyl-2-naphthyl)-2-(methoxy)ethyl]imidazole.
Reaction SMILES: [Cl-].[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]([C:12]2[N:13]=[C:14]([CH3:17])[NH:15][CH:16]=2)[NH3+:11])=[CH:6][CH:5]=1.[CH:18]1([C:21]2[CH:26]=[CH:25][C:24]([CH2:27][C:28](O)=[O:29])=[CH:23][CH:22]=2)[CH2:20][CH2:19]1.Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.C(N(CC)CC)C>O.C(Cl)Cl>[CH:18]1([C:21]2[CH:22]=[CH:23][C:24]([CH2:27][C:28]([NH:11][CH:10]([C:7]3[CH:6]=[CH:5][C:4]([O:3][CH3:2])=[CH:9][CH:8]=3)[C:12]3[N:13]=[C:14]([CH3:17])[NH:15][CH:16]=3)=[O:29])=[CH:25][CH:26]=2)[CH2:20][CH2:19]1
Reactant: O=C(O)Cc1ccc(C2CC2)cc1
Reactant: COc1ccc(C([NH3+])c2c[nH]c(C)n2)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2cccnc21
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: COc1ccc(C(NC(=O)Cc2ccc(C3CC3)cc2)c2c[nH]c(C)n2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 57.4 %

Procedure:
To a 50 ml round bottom flask equipped with a magnetic stir bar were added (4-methoxyphenyl)(2-methyl-1H-imidazol-4-yl)methanaminium chloride (0.350 g, 1.206 mmol), 4-cyclopropylphenylacetic acid (0.213 mg, 1.206 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.231 g, 1.206 mmol), 1-hydroxy-7-azabenzotriazole (0.164 mg, 1.206 mmol) and triethylamine (0.336 ml, 2.412 mmol) into 10.0 ml of CH2Cl2. The resulting solution was stirred at room temperature for 16 hours. The reaction mixture was diluted with water and the two layers were separated. The aqueous layer was extracted with CH2Cl2. The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuum. Purification by flash chromatography (SiO2, 0-10% methanol in CH2Cl2, gradient) gave the title compound as a white solid (0.260 g, 57%). 1H NMR (CDCl3, 400 MHz) δ 7.151 (m, 4H), 7.021 (d, J=8.24 Hz, 2H), 7.820 (d, J=8.60 Hz, 2H), 6.459 (s, 1H), 6.459 (br s, 1H), 5.989 (d, J=7.32 Hz, 1H), 3.778 (s, 3H), 3.552 (s, 2H), 2.355 (s, 3H), 1.870 (m, 1H), 0.950 (m, 2H), 0.669 (m, 2H). ES-MS [M+1]+: 376.3.
Reaction SMILES: [C:1]1([CH2:7][O:8][C@H:9]2[C@H:15]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C@@H:14]([CH2:24][O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[O:13][C@@H:10]2[CH:11]=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C=O.[C:35](=O)([O-])[O-:36].[K+].[K+].S(=O)(=O)(O)O>CO>[OH:12][CH2:11][C:10]1([O:13][C@H:14]([CH2:24][O:25][CH2:26][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C@@H:15]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C@@H:9]1[O:8][CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH2:35][OH:36]
Reactant: O=C[C@H]1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Reactant: O=C([O-])[O-]
Agent: C=O
Agent: O=S(=O)(O)O
Agent: [K+]
Solvent: CO
Product: OCC1(CO)O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1OCc1ccccc1

Procedure:
A 1.18 g portion of 2,5-anhydro-3,4,6-tris-O-(phenylmethyl)-D-mannose was dissolved in 8.5 ml of methanol, treated with 5.11 ml of 37% formalin and 480 mg of potassium carbonate and the mixture immersed in an 85° C. bath. After 4 hours the mixture was cooled, neutralized with 3.5 ml of 10% sulfuric acid and the volatiles removed. The residue was extracted with chloroform, giving 0.86 g of the desired compound after chromatography.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([CH3:9])[CH:8]=1)[NH2:5].[CH:10]([S:13](Cl)(=[O:15])=[O:14])([CH3:12])[CH3:11].N1C=CC=CC=1>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([NH:5][S:13]([CH:10]([CH3:12])[CH3:11])(=[O:15])=[O:14])[CH:6]=[C:7]([CH3:9])[CH:8]=1
Reactant: Cc1cc(N)cc(Br)c1
Reactant: CC(C)S(=O)(=O)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cc1cc(Br)cc(NS(=O)(=O)C(C)C)c1
Temperature: 25 °C
Reaction time: 25 h
Yield: 86.4 %

Procedure:
To a solution of 3-bromo-5-methylaniline (500 mg, 2.2 mmol) in DCM (5 mL), isopropylsulfonylchloride (0.3 mL, 2.7 mmol) was added, followed by the addition of pyridine (0.45 mL, 5.6 mmol). The reaction was stirred at room temperature for 25 hours at which time it was quenched with water and extracted with EtOAc. The organic layer was washed with brine, dried (MgSO4), and absorbed onto silica. Purification by flash chromatography (SiO2, 0-30% EtOAc in hexanes) afforded N-(3-bromo-5-methylphenyl)propane-2-sulfonamide (558 mg, 1.9 mmol, 85%) as a peach colored solid: 1H NMR (400 MHz, CDCl3) δ 1.41 (d, J=6.7 Hz, 6H) 2.31 (s, 3H) 3.33 (m, 1H) 6.84 (br s, 1H) 6.97 (s, 1H) 7.10 (s, 1H) 7.21 (s, 1H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[N:3]=1.C([Li])CCC.C(O[B:18]([O:23][CH:24]([CH3:26])[CH3:25])[O:19][CH:20]([CH3:22])[CH3:21])(C)C.OC(C(O)(C)C)(C)C>O1CCCC1>[F:8][C:4]1[N:3]=[C:2]([B:18]2[O:19][C:20]([CH3:21])([CH3:22])[C:24]([CH3:25])([CH3:26])[O:23]2)[CH:7]=[CH:6][CH:5]=1
Reactant: Fc1cccc(Br)n1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: CC(C)(O)C(C)(C)O
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC1(C)OB(c2cccc(F)n2)OC1(C)C
Temperature: 0 °C
Reaction time: 0.75 h
Yield: 67.1 %

Procedure:
A solution of 2-bromo-6-fluoropyridine (1.0 g) in tetrahydrofuran (10 ml) was cooled to −78° C. under argon atmosphere, and thereto was added a solution of n-butyl lithium (2.59 M hexane solution, 2.24 ml) in tetrahydrofuran (10 ml). The mixture was stirred at the same temperature for 45 minutes, and thereto was added dropwise a solution of triisopropoxyborane (1.28 g) in tetrahydrofuran (10 ml). The mixture was stirred at the same temperature for 2 hours, warmed, and further stirred at room temperature for one hour. Subsequently, a solution of pinacol (0.91 g) in tetrahydrofuran (10 ml) was added dropwise thereto, and stirred at room temperature for 20 minutes. Insoluble materials were filtered off. The filtrate was extracted with 2.5% sodium hydroxide, and the extract was cooled to 0° C., and was made weakly acidic with 2N aqueous hydrochloric acid solution. It was extracted with diethyl ether, washed with a small amount of brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was solidified with hexane to give 6-fluoro-2-pyridylboronic acid pinacol ester (850 mg) as a colorless solid. APCI-Mass m/Z 224 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]1[C:12]([CH2:15][CH3:16])=[N:13][N:14]=[C:7]1[C:6](O)=[N:5]2.P(Cl)(Cl)([Cl:20])=O.C(N(CCC)CCC)CC>>[Cl:20][C:6]1[C:7]2[N:8]([C:12]([CH2:15][CH3:16])=[N:13][N:14]=2)[C:9]2[C:4]([N:5]=1)=[CH:3][C:2]([Cl:1])=[CH:11][CH:10]=2
Reactant: O=P(Cl)(Cl)Cl
Reactant: CCc1nnc2c(O)nc3cc(Cl)ccc3n12
Agent: CCCN(CCC)CCC
Product: CCc1nnc2c(Cl)nc3cc(Cl)ccc3n12
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
In a flame-dried reaction flask under a dry nitrogen atmosphere, there were placed 5.1 g. (0.02 mole) of 7-chloro-1-ethyl-4-hydroxy-[1,2,4]triazolo[4,3-a]quinoxaline and 75 ml. of phosphorus oxychloride together with 5 ml. of tri-n-propylamine. The reaction mixture was then refluxed overnight for approximately 16 hours and finally cooled to room temperature prior to being slowly poured over ice/water. The resulting aqueous mixture was next stirred at room temperature for 15 minutes and filtered, and the solid product so obtained was subsequently washed with cold water and air-dried to constant weight to ultimately afford 4.2 g. (79%) of pure 4,7-dichloro-1-ethyl-[1,2,4]triazolo[4,3-a]quinoxaline, m.p. 217°-220° C. (decomp.). Mass Spectrum: m/e, 266 (P); m/e, 268 (P+2); m/e, 265 (P-1).
Reaction SMILES: [NH2:1][C:2]1[C:3]2[C:4]3[C:5](=[C:29]([CH3:32])[O:30][N:31]=3)[C:6](=[O:28])[N:7]([CH:12]3[CH2:17][CH2:16][CH2:15][CH:14]([CH2:18][NH:19][C:20](=[O:27])[C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH2:13]3)[C:8]=2[CH:9]=[CH:10][CH:11]=1.[CH3:33][C:34](O)=[O:35].CCN=C=NCCCN(C)C>CN(C=O)C.CN(C1C=CN=CC=1)C.CCOC(C)=O>[C:34]([NH:1][C:2]1[C:3]2[C:4]3[C:5](=[C:29]([CH3:32])[O:30][N:31]=3)[C:6](=[O:28])[N:7]([CH:12]3[CH2:17][CH2:16][CH2:15][CH:14]([CH2:18][NH:19][C:20](=[O:27])[C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH2:13]3)[C:8]=2[CH:9]=[CH:10][CH:11]=1)(=[O:35])[CH3:33]
Reactant: CC(=O)O
Reactant: Cc1onc2c1c(=O)n(C1CCCC(CNC(=O)c3ccccc3)C1)c1cccc(N)c21
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(=O)Nc1cccc2c1c1noc(C)c1c(=O)n2C1CCCC(CNC(=O)c2ccccc2)C1
Reaction time: 8 h
Yield: 81.1 %

Procedure:
To a solution of a compound from Example 667 (0.025 g, 0.06 mmol) and AcOH (0.02 mL, 0.36 mmol) in DMF (1 mL) under N2 was added EDCI (0.023 g, 0.12 mmol) and DMAP (0.002 g, 0.01 mmol). The solution was stirred overnight, diluted with EtOAc, washed (H2O then brine), dried (MgSO4), filtered, and concentrated. Flash chromatography (silica gel, acetone/CH2Cl2 gradient) gave the title compound (0.023 g, 82%). Mass Spectrum (ES+) (m/z) 473.3 [M+1]