Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CS([C:5]1[N:6]=[N:7][C:8]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:10]=1)(=O)=O.[OH-:24].[K+].Cl>O.C1COCC1>[C:11]1([C:9]2[C:8]([C:17]3[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=3)=[N:7][NH:6][C:5](=[O:24])[N:10]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: Cc1ccc(-c2nnc(S(C)(=O)=O)nc2-c2ccccc2)cc1
Reactant: [OH-]
Agent: Cl
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: Cc1ccc(-c2n[nH]c(=O)nc2-c2ccccc2)cc1
Yield: 92.1 %

Procedure:
To a solution of 3-(methylsulfonyl)-5-phenyl-6-p-tolyl-1,2,4-triazine (98.9 mg, 0.304 mmol) in a 1:1 mixture of H2O/THF (6.0 mL) was added potassium hydroxide (109.1 mg, 1.945 mmol). The mixture was heated at reflux for 1 h. The reaction mixture was cooled to room temperature and neutralized with 1 M HCl, then extracted with CH2Cl2. The combined organic phases were washed with H2O and brine, dried over MgSO4, and concentrated to give the title compound as a yellow solid (73.7 mg). LCMS m/z=264.1 [M+H]+.
Reaction SMILES: Cl[C:2]1[CH:27]=[CH:26][C:5]([C:6]([NH:8]C2C=CC(Cl)=C(NC(=O)C3C=CC=C(Cl)C=3)C=2)=[O:7])=[CH:4][N:3]=1.[CH2:28]([N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)[CH3:29]>>[CH2:28]([N:30]1[CH2:35][CH2:34][N:33]([C:2]2[CH:27]=[CH:26][C:5]([C:6]([NH2:8])=[O:7])=[CH:4][N:3]=2)[CH2:32][CH2:31]1)[CH3:29]
Reactant: O=C(Nc1ccc(Cl)c(NC(=O)c2cccc(Cl)c2)c1)c1ccc(Cl)nc1
Reactant: CCN1CCNCC1
Product: CCN1CCN(c2ccc(C(N)=O)cn2)CC1

Procedure:
6-chloro-N-(4-chloro-3-(3-chlorobenzamido)phenyl)nicotinamide (0.16 mmol) was used in general procedure 3 with 1-ethylpiperazin (0.83 mmol). The product was purified by RP-HPLC to give N-(4-chloro-3-(3-chlorobenzamido)phenyl))-6-(4-ethylpiperazin-1-yl)nicotinamide. MS (Q1) 498.1 (M)+
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[C:10]([O:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][N:17]=1)[CH:9]=2)=[O:5])[CH3:2].[C:23](OC(=O)C)(=[O:25])[CH3:24].O>N1C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[C:10]([O:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:23](=[O:25])[CH3:24])=[CH:18][N:17]=1)[CH:9]=2)=[O:5])[CH3:2]
Reactant: CC(=O)OC(C)=O
Reactant: CCOC(=O)c1cc2ccc(Oc3ccc(N)cn3)cc2[nH]1
Solvent: c1ccncc1
Solvent: O
Product: CCOC(=O)c1cc2ccc(Oc3ccc(NC(C)=O)cn3)cc2[nH]1
Reaction time: 2 h
Yield: 29.1 %

Procedure:
To a solution of 6-(5-aminopyridin-2-yloxy)-1H-indole-2-carboxylic acid ethyl ester (2.6 g, 8.6 mmol) in pyridine (13 mL) was added acetic anhydride (2.2 g, 21 mmol) under ice cooling and the mixture was stirred for 2 hours. Water (30 mL) was added to the reaction mixture and extracted with AcOEt, the organic layer was washed with 2 M HCl, saturated aqueous NaHCO3 and brine, dried over anhydrous sodium sulfate and evaporated. The residue was crystallized with 2-propyl alcohol and filtrated to give 0.85 g of the title compound. The filtrate was evaporated and the residue was purified by silica gel column chromatography (n-hexane:AcOEt=1:3) to give 1.26 g (total of 2.11 g) of the title compound as pale yellow crystals.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=[O:10].[Cl:12][C:13]1[CH:14]=[C:15]([CH:17]=[C:18]([Cl:21])[C:19]=1[Cl:20])[NH2:16]>>[Cl:12][C:13]1[CH:14]=[C:15]([NH:16][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[CH2:8][C:9]([OH:11])=[O:10])[CH:17]=[C:18]([Cl:21])[C:19]=1[Cl:20]
Reactant: O=C(O)Cc1ccccc1Br
Reactant: Nc1cc(Cl)c(Cl)c(Cl)c1
Product: O=C(O)Cc1ccccc1Nc1cc(Cl)c(Cl)c(Cl)c1

Procedure:
In the manner described in example 3, 2-bromophenylacetic acid is condensed with 3,4,5-trichloroaniline to yield 2-[(3,4,5-trichlorophenyl)amino]phenylacetic acid.
Reaction SMILES: [Br:1][C:2]1[C:6]([N+:7]([O-:9])=[O:8])=[C:5](Br)[N:4]([CH3:11])[N:3]=1.[C:12]([NH2:16])([CH3:15])([CH3:14])[CH3:13].O>C(O)C>[Br:1][C:2]1[C:6]([N+:7]([O-:9])=[O:8])=[C:5]([NH:16][C:12]([CH3:15])([CH3:14])[CH3:13])[N:4]([CH3:11])[N:3]=1
Reactant: Cn1nc(Br)c([N+](=O)[O-])c1Br
Reactant: CC(C)(C)N
Solvent: CCO
Solvent: O
Product: Cn1nc(Br)c([N+](=O)[O-])c1NC(C)(C)C
Yield: 78 %

Procedure:
1.5 g (5.26 mmoles) of 3,5-dibromo-1-methyl-4-nitropyrazole are heated in a solution of 20 ml tert-butylamine in 30 ml ethanol for 20 hours at boiling temperature. After cooling, the reaction mixture is poured on 150 ml water, the separated product is filtered and washed with 100 ml water. After vacuum drying, 1.14 g (78 percent of theory) of 3-bromo-5-tert-butylamino-1-methyl-4-nitropyrazole are obtained in the form of pale yellow flakes with a melting point of 75° to 77° C.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=1.CCCCCC.[Li]CCCC.[C:19]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1COCC1>[C:27]1([C:19]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)([C:2]2[CH:3]=[N:4][CH:5]=[N:6][CH:7]=2)[OH:26])[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: Brc1cncnc1
Reactant: O=C(c1ccccc1)c1ccccc1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: OC(c1ccccc1)(c1ccccc1)c1cncnc1
Temperature: -100 °C
Reaction time: 0.5 h
Yield: 48.4 %

Procedure:
A solution of 5-bromopyrimidine (10 g, 0.063 mol) in a mixture of dry THF (150 mL) and hexane (50 mL) was cooled to −100° C. To this cooled solution was added n-BuLi (4 g, 21 mL, 0.062 mol) over a period of 30 min and stirred for another 30 min. A solution of benzophenone (11.5 g, 0.063 mol) in dry THF (50 mL) was added to this at the same temperature over a period of 30 min. The reaction mixture was warmed slowly to RT and allowed to stir another 1 h at RT. The reaction was quenched with cold water (200 mL), ethyl acetate was added and the organic layer was separated. The organic layer was dried, concentrated and the crude product was purified by column chromatography on silica gel (up-to 25% ethyl acetate in pet ether) to give the product (8 g). TLC: Pet. ether/EtOAc, 1:1, Rf=0.3.
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.[NH:8]1[C:16]2[C:11](=[C:12]([CH2:17][N:18]3[CH2:23][CH2:22][CH:21]([C:24]4[CH:25]=[C:26]([NH:30][C:31](=[O:35])[CH:32]([CH3:34])[CH3:33])[CH:27]=[CH:28][CH:29]=4)[CH2:20][CH2:19]3)[CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9]1>>[CH3:34][CH:32]([CH3:33])[C:31]([NH:30][C:26]1[CH:27]=[CH:28][CH:29]=[C:24]([CH:21]2[CH2:22][CH2:23][N:18]([CH2:17][C:12]3[CH:13]=[CH:14][CH:15]=[C:16]4[C:11]=3[CH:10]=[CH:9][N:8]4[C:2]3[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=3)[CH2:19][CH2:20]2)[CH:25]=1)=[O:35]
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(Cc3cccc4[nH]ccc34)CC2)c1
Reactant: Ic1ccncc1
Product: CC(C)C(=O)Nc1cccc(C2CCN(Cc3cccc4c3ccn4-c3ccncc3)CC2)c1

Procedure:
Prepared by Procedure C and Scheme Q1, with CuBr in place of Cu, using 4-iodopyridine and N-{3-[1-(1H-indol-4-ylmethyl)-4-piperidinyl]phenyl}-2-methylpropanamide: ESMS m/e: 453.2 (M+H)+.
Reaction SMILES: [OH:1][CH:2]1[CH2:5][N:4]([C:6]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([N:17]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[C:19]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[CH:18]3)(=[O:16])=[O:15])=[CH:10][CH:9]=2)=[O:7])[CH2:3]1.C(N(CC)CC)C.[CH3:39][N:40]([CH3:44])[C:41](Cl)=[O:42]>CN(C)C1C=CN=CC=1.ClCCl>[C:26]1([C:19]2[C:20]3[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:17]([S:14]([C:11]3[CH:10]=[CH:9][C:8]([C:6]([N:4]4[CH2:5][CH:2]([O:1][C:41](=[O:42])[N:40]([CH3:44])[CH3:39])[CH2:3]4)=[O:7])=[CH:13][CH:12]=3)(=[O:16])=[O:15])[CH:18]=2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: O=C(c1ccc(S(=O)(=O)n2cc(-c3ccccc3)c3ccccc32)cc1)N1CC(O)C1
Reactant: CN(C)C(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CN(C)C(=O)OC1CN(C(=O)c2ccc(S(=O)(=O)n3cc(-c4ccccc4)c4ccccc43)cc2)C1
Reaction time: 15 h
Yield: 74 %

Procedure:
Combine (3-Hydroxy-azetidin-1-yl)-[4-(3-phenyl-indole-1-sulfonyl)-phenyl]-methanone (95 mg, 0.219 mmol), triethylamine (0.200 mL, 1.43 mmol, excess) and 4-dimethylaminopyridine (5 mg, 0.04 mmol) in dichloromethane (1.0 mL) and treat with N,N-dimethylcarbamoyl chloride (0.050 mL) at room temperature. Stir for 15 h, load directly onto pre-packed silica gel column and purify by flash column chromatography (EtOAc/Hexanes) to yield 82 mg of Dimethyl-carbamic acid 1-[4-(3-phenyl-indole-1-sulfonyl)-benzoyl]-azetidin-3-yl ester as a white foam (74%). LRMS: MH+ 503.97.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:17]=[C:18]([Cl:20])[CH:19]=1)[O:5][C:6]1[C:7]([N+:14]([O-])=O)=[C:8]([CH:10]=[CH:11][C:12]=1[Cl:13])[NH2:9].O.O.[Sn](Cl)Cl.N#N>CO>[Br:1][C:2]1[CH:3]=[C:4]([CH:17]=[C:18]([Cl:20])[CH:19]=1)[O:5][C:6]1[C:12]([Cl:13])=[CH:11][CH:10]=[C:8]([NH2:9])[C:7]=1[NH2:14]
Reactant: Nc1ccc(Cl)c(Oc2cc(Cl)cc(Br)c2)c1[N+](=O)[O-]
Agent: Cl[Sn]Cl
Agent: N#N
Solvent: O
Solvent: CO
Product: Nc1ccc(Cl)c(Oc2cc(Cl)cc(Br)c2)c1N
Temperature: 75 °C
Reaction time: 10 h

Procedure:
3-(3-bromo-5-chlorophenoxy)-4-chloro-2-nitroaniline (5.7 g, 15 mmol) and tin(II) chloride dihydrate (17 g, 75 mmol) were suspended in MeOH (100 mL) and heated to 75° C. under a reflux condenser and N2. After 10 hours, the reaction was allowed to cool to room temperature. The reaction was concentrated under reduced pressure, diluted with ethyl acetate (150 mL) and 10% aqueous sodium carbonate (250 mL) was added with vigorous stirring until the pH was 10. The mixture was filtered through celite. The resulting biphasic filtrate was separated and the aqueous extracted again with ethyl acetate (150 mL). The combined organic fractions were dried (MgSO4), filtered and the solvent was evaporated under reduced pressure to yield the title product. LRMS (M+1)=348.7.
Reaction SMILES: CS(O[CH2:6][C:7]1[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18](=[O:26])[C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)=[C:10]([CH3:27])[O:9][N:8]=1)(=O)=O.CN(C=O)C.[N-:33]=[N+:34]=[N-:35].[Na+]>O>[N:33]([CH2:6][C:7]1[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)=[O:26])=[C:10]([CH3:27])[O:9][N:8]=1)=[N+:34]=[N-:35]
Reactant: [N-]=[N+]=[N-]
Reactant: Cc1onc(COS(C)(=O)=O)c1-c1ccccc1C(=O)c1ccc(Cl)cc1
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1onc(CN=[N+]=[N-])c1-c1ccccc1C(=O)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a round bottomed flask was added (4-chlorophenyl)(2-(3-(hydroxymethyl)-5-methylisoxazol-4-yl)phenyl)methanone (47.2 mg, 0.144 mmol), DCM, and Et3N (40.1 μl, 0.288 mmol). The solution was cooled to 0° C. before addition of Ms-Cl (13.47 μl, 0.173 mmol). The reaction was stirred at 0° C. for 30 min before addition of water. The layers were separated and the aqueous was extracted with DCM. The combined organics were dried over Na2SO4, filtered, and concentrated to afford crude (4-(2-(4-chlorobenzoyl)phenyl)-5-methylisoxazol-3-yl)methyl methanesulfonate. To a round bottomed flask was added (4-(2-(4-chlorobenzoyl)phenyl)-5-methylisoxazol-3-yl)methyl methanesulfonate (58.4 mg, 0.144 mmol), DMF, and sodium azide (28.1 mg, 0.432 mmol). The reaction was stirred at room temperature for 2 h before diluting with water and extracting the aqueous with EtOAc. The combined organics were washed with brine, dried over Na2SO4, filtered, and concentrated to afford crude (2-(3-(azidomethyl)-5-methylisoxazol-4-yl)phenyl) (4-chlorophenyl)methanone. To a round bottomed flask was added (2-(3-(azidomethyl)-5-methylisoxazol-4-yl)phenyl)(4-chlorophenyl)methanone (50.8 mg, 0.144 mmol), toluene (3 mL), and trimethylphosphine solution (216 μl, 1M in toluene, 0.216 mmol). The reaction was stirred at room temperature over 2 days before purifying via Biotage (EtOAc/hex) to afford 6-(4-chlorophenyl)-1-methyl-4H-benzo[c]isoxazolo[4,3-e]azepine. LC/MS m/z 309 [M+H]+; 1H NMR (400 MHz, Acetone) δ 7.70-7.76 (m, 1H), 7.63-7.70 (m, 1H), 7.32-7.49 (m, 6H), 5.10 (br. s, 1H), 4.10 (br. s, 1H), 2.68 (s, 3H).
Reaction SMILES: I[C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:4][CH:3]=1.[CH2:15]([OH:19])[CH2:16][C:17]#[CH:18]>C(N(CC)CC)C.ClCCl.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[OH:19][CH2:15][CH2:16][C:17]#[C:18][C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:4][CH:3]=1
Reactant: C#CCCO
Reactant: CC(C)(C)OC(=O)c1ccc(I)cc1
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)c1ccc(C#CCCO)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 145.8 %

Procedure:
A mixture of 1,1-dimethylethyl 4-iodobenzoate (1.1 g, 3.62 mmol, e.g. which can be preparable e.g. according to E. C. Taylor, J. Org. Chem., 1995, 60(24), 7947), 3-butyn-1-ol (0.36 ml, 4.70 mmol, 1.3 equivalents), bis(triphenylphosphine)palladium(II)dichloride [(PPh3)2PdCl2] (0.13 g, 018 mmol, 5 mol %) and copper(I)iodide (0.014 g, 0.07 mmol, 2 mol %) in triethylamine (5 ml) was stirred at room temperature for 18 hours. The mixture was diluted with dichloromethane (50 ml) and washed with water (50 ml). The organic phase was collected by passing through a hydrophobic frit and evaporated to give a dark brown oil (1.3 g). This was purified by flash chromatography on silica gel (100 g silica cartridge, FlashMaster II), eluting with a gradient of 0 to 100% ethyl acetate in cyclohexane over 20 minutes. Fractions containing product (obtained from 4:1 cyclohexane:ethyl acetate eluant) were pooled and evaporated to dryness to give the title compound as a brown gummy oil (0.9 g). 1H NMR (400 MHz, chloroform-d) δ (delta) ppm 1.60 (9H, s), 1.85 (1H, t, J=6.27 Hz), 2.73 (2H, t, J=6.27 Hz), 3.85 (2H, q, J=6.27 Hz), 7.45 (2H, d, J=8.53 Hz), 7.92 (2H, d, J=8.53 Hz).
Reaction SMILES: [C:1]1([C:7]2[N:12]=[C:11]([C:13]([OH:15])=O)[CH:10]=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(Cl)([Cl:18])=O>C1(C)C=CC=CC=1>[C:1]1([C:7]2[N:12]=[C:11]([C:13]([Cl:18])=[O:15])[CH:10]=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=S(Cl)Cl
Reactant: O=C(O)c1cccc(-c2ccccc2)n1
Solvent: Cc1ccccc1
Product: O=C(Cl)c1cccc(-c2ccccc2)n1
Temperature: 40 °C
Reaction time: 13 h

Procedure:
A 2-L three neck round bottomed flask equipped with an overhead stirrer, thermocouple, heating mantle with digital temperature controller, condenser and nitrogen inlet/outlet was charged with 100.0 g (0.502 mol) of 6-phenyl-2-pyridinecarboxylic acid and 1500 mL of toluene (Kf<0.02 wt %) then warmed to 40° C. Thionyl chloride (110 mL; 1.51 mol, 3 eq) was then added to the thin slurry via addition funnel over 20 minutes. The thin slurry was heated to 75° C. and stirred overnight (typically 10-16 hr), until it became a clear solution. Reaction was assayed via HPLC for conversion as the methyl ester derivative. After cooling the reaction mixture to room temperature the solvent and excess thionyl chloride were removed in vacuo as follows: Reaction mixture was stripped under full vacuum at 40° C. (bath temperature) to approximately ⅓ its original volume (˜500 ml) and then (1000 ml) of fresh toluene was added. Concentration was continued, again stripping to ⅓ original volume (˜500 ml) followed by re-dilution with 1000 ml of fresh toluene. The total amount of toluene removed was ˜2000 mL.
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:12]([CH2:31][O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[O:11][C@H:10]1[O:40][C@H:41]1[C@H:50]([OH:51])[C@@H:49]([CH2:52][OH:53])[O:48][C@H:43]([O:44][CH2:45][CH:46]=[CH2:47])[C@@H:42]1[O:54][CH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:62][O:63][C:64]1[CH:69]=[CH:68][C:67](O)=[CH:66][CH:65]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O.C1(C)C=CC=CC=1>C(Cl)Cl>[CH2:1]([O:8][C@@H:9]1[C@@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@H:13]([O:23][CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C@@H:12]([CH2:31][O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[O:11][C@H:10]1[O:40][C@H:41]1[C@H:50]([OH:51])[C@@H:49]([CH2:52][O:53][C:67]2[CH:68]=[CH:69][C:64]([O:63][CH3:62])=[CH:65][CH:66]=2)[O:48][C@H:43]([O:44][CH2:45][CH:46]=[CH2:47])[C@@H:42]1[O:54][CH2:55][C:56]1[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C=CCO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O[C@@H]2O[C@H](COCc3ccccc3)[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@H]2OCc2ccccc2)[C@H]1OCc1ccccc1
Reactant: COc1ccc(O)cc1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: C=CCO[C@H]1O[C@H](COc2ccc(OC)cc2)[C@@H](O)[C@H](O[C@@H]2O[C@H](COCc3ccccc3)[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@H]2OCc2ccccc2)[C@H]1OCc1ccccc1
Temperature: 0 °C
Reaction time: 0.67 h
Yield: 68.7 %

Procedure:
Allyl 3-O-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-2-O-benzyl-α-D-glucopyranoside 14 (10.1 g, 12.1 mmol), 4-methoxyphenol (3.76 g, 30.3 mmol), and triphenylphosphine (4,77 g, 18.2 mmol) were combined in a flask, cooled to 0° C. before adding anhydrous CH2Cl2 (100 mL). This solution was stirred for 40 minutes and then a solution of diethylazodicarboxylate (DEAD) in toluene (40% by weight, 8.84 mL, 19.4 mmol) was added. The reaction mixture was stirred at 0° C. for 45 minutes, and then allowed to warm to room temperature overnight. The reaction mixture was diluted with CH2Cl2, washed with 1N NaOH (200 mL, 100 mL), 1 N HCl (200 mL), saturated NaHCO3 (200 mL), and brine, dried over Na2SO4, filtered and concentrated. The residue was purified on a silica gel column eluted using an ethyl acetate:heptane step gradient (1:10→1:5→1:3) to give allyl 3-O-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-2-O-benzyl-6-O-(4-methoxyphenyl)-α-D-glucopyranoside 14 (7.81 g, 69%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH2:7][CH2:8][C:9]2=[O:12])=[CH:5][CH:4]=1.[N+:13]([O-])([O-:15])=[O:14].[K+]>S(=O)(=O)(O)O>[CH3:1][O:2][C:3]1[C:11]([N+:13]([O-:15])=[O:14])=[C:10]2[C:6]([CH2:7][CH2:8][C:9]2=[O:12])=[CH:5][CH:4]=1
Reactant: O=[N+]([O-])[O-]
Reactant: COc1ccc2c(c1)C(=O)CC2
Agent: O=S(=O)(O)O
Agent: [K+]
Product: COc1ccc2c(c1[N+](=O)[O-])C(=O)CC2
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 56.6 %

Procedure:
To a solution of 6-methoxy-1-indanone (30.0 g, 185 mmol.) in conc. sulfuric acid (130 mL) was added a solution of potassium nitrate (24.3 g, 0.24 mol.) in conc. sulfuric acid (100 mL), while maintaining the inner temperature below 0° C. The mixture was stirred for 20 minutes at the same temperature, which was then poured into ice-water, followed by extraction with ethyl acetate. The extract solution was washed with water and an aqueous solution of sodium hydrogencarbonate, which was then dried over anhydrous magnesium sulfate, followed by distilling off the solvent under reduced pressure. The residue was recrystallized from ethyl acetate/hexane to afford the title compound (yield 21.7 g, 58%).
Reaction SMILES: C([NH:9][C:10]1[N:18]=[CH:17][N:16]=[C:15]2[C:11]=1[N:12]=[CH:13][N:14]2[C@@H:19]1[O:24][C@H:23]([C:25]([OH:27])=[O:26])[C@@H:22]([NH:28][C:29](=[O:36])[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C@H:20]1[OH:21])(=O)C1C=CC=CC=1.C(N)CCC>>[NH2:9][C:10]1[N:18]=[CH:17][N:16]=[C:15]2[C:11]=1[N:12]=[CH:13][N:14]2[C@@H:19]1[O:24][C@H:23]([C:25]([OH:27])=[O:26])[C@@H:22]([NH:28][C:29](=[O:36])[C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C@H:20]1[OH:21]
Reactant: O=C(Nc1ncnc2c1ncn2[C@@H]1O[C@H](C(=O)O)[C@@H](NC(=O)c2ccccc2)[C@H]1O)c1ccccc1
Solvent: CCCCN
Product: Nc1ncnc2c1ncn2[C@@H]1O[C@H](C(=O)O)[C@@H](NC(=O)c2ccccc2)[C@H]1O
Yield: 47.7 %

Procedure:
1-(6-Amino-9H-purin-9-yl)-3-benzoylamino-1,3-dideoxy-β-D-ribofuranuronic acid (75 mg) was prepared by reacting 1-(6-benzoylamino-9H-purin-9-yl)-3-benzoylamino-1,3-dideoxy-β-D-ribofuranuronic acid (200 mg) prepared in Example 19 with n-butylamine (2.5 ml) according to a similar manner to that of Example 23, mp. 237°-239° C. (dec.).
Reaction SMILES: [CH:1]1[C:11]2[CH2:10][NH:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[NH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.C(N(CC)C(C)C)(C)C.[CH:25]1([C:31]2[CH:39]=[CH:38][C:34]([C:35](Cl)=[O:36])=[CH:33][CH:32]=2)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1>ClCCl>[CH:25]1([C:31]2[CH:32]=[CH:33][C:34]([C:35]([N:9]3[CH2:10][C:11]4[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=4[NH:6][C:7]4[CH:15]=[CH:14][CH:13]=[CH:12][C:8]3=4)=[O:36])=[CH:38][CH:39]=2)[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]1
Reactant: c1ccc2c(c1)CNc1ccccc1N2
Reactant: O=C(Cl)c1ccc(C2CCCCC2)cc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=C(c1ccc(C2CCCCC2)cc1)N1Cc2ccccc2Nc2ccccc21
Reaction time: 8 h

Procedure:
5,11-Dihydro-10H-dibenzo[b,e][1,4]diazepine (1.96 g) in dichloromethane (50 mL) containing N,N-diisopropylethyl amine (1.3 g) was reacted with the crude 4-cyclohexylbenzoyl chloride prepared as described above (2.22 g). The reaction mixture was kept at room temperature overnight, then washed with water and saturated aqueous sodium bicarbonate. The solution was dried over anhydrous sodium sulfate and filtered through a short column of Magnesol® which was eluted with several additional volumes of dichloromethane. The total effluent was refluxed with the gradual addition of hexane until crystallization was noted. Cooling and filtration afforded the title compound as colorless crystals (1.28 g), m.p. 175–176° C.
Reaction SMILES: C([O:8][C:9]1[CH:10]=[C:11]([CH:25]=[CH:26][C:27]=1[N:28]1[CH2:32][C:31](=[O:33])[NH:30][S:29]1(=[O:35])=[O:34])[O:12][CH:13]1[C:19](=[O:20])[NH:18][C:17]2[CH:21]=[CH:22][CH:23]=[CH:24][C:16]=2[CH2:15][CH2:14]1)C1C=CC=CC=1>CCO.CC(O)=O.[Pd]>[OH:8][C:9]1[CH:10]=[C:11]([CH:25]=[CH:26][C:27]=1[N:28]1[CH2:32][C:31](=[O:33])[NH:30][S:29]1(=[O:34])=[O:35])[O:12][CH:13]1[C:19](=[O:20])[NH:18][C:17]2[CH:21]=[CH:22][CH:23]=[CH:24][C:16]=2[CH2:15][CH2:14]1
Reactant: O=C1CN(c2ccc(OC3CCc4ccccc4NC3=O)cc2OCc2ccccc2)S(=O)(=O)N1
Agent: [Pd]
Solvent: CCO
Solvent: CC(=O)O
Product: O=C1CN(c2ccc(OC3CCc4ccccc4NC3=O)cc2O)S(=O)(=O)N1

Procedure:
A solution of 3-[3-benzyloxy-4-(1,1,4-trioxo-1,2,5-thiadiazolidin-2-yl)-phenoxy]-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (244 mg) in 30 mL of EtOH/HOAc (2:1) is hydrogenated at 1 atm over Pd/C (100 mg) for 4 h. The catalyst is filtered and the filtrate evaporated. The residual solid is triturated with ether to give the title compound: (M−1)−=402.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[O:9][C:10]2[CH:18]=[CH:17][CH:16]=[CH:15][C:11]=2[C:12](=O)[N:13]=1.[NH:19]([C:21]1[CH:29]=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=1)[NH2:20]>CO>[CH:16]1[CH:17]=[CH:18][C:10]([OH:9])=[C:11]([C:12]2[N:13]=[C:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[OH:1])[N:19]([C:21]3[CH:29]=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=3)[N:20]=2)[CH:15]=1
Reactant: NNc1ccc(C(=O)O)cc1
Reactant: O=c1nc(-c2ccccc2O)oc2ccccc12
Solvent: CO
Product: O=C(O)c1ccc(-n2nc(-c3ccccc3O)nc2-c2ccccc2O)cc1
Temperature: 27.5 °C
Reaction time: 0.17 h
Yield: 79 %

Procedure:
A mixture of methanol (450.0 ml), 2-(2-hydroxyphenyl)-benz[1,3]oxazin-4-one (30.0 gm) were stir for 10 min at 25-30° C. To the above contents 4-hydrazino benzoic acid (20.03 gm) was added. The contents were heated to reflux temperature 65-70° C. The contents were maintained for 4 hours at 65-70° C. The reaction mass was cooled Slowly to 0-5° C. and maintained it for 1 hour at 0-5° C. The reaction mass was filtered and washed with methanol (30.0 ml). Compound was taken into methylene chloride and stir for 10 min 25-30° C. The contents were heated to reflux temperature (40-45° C.) and maintained the contents for 1 hr at reflux temperature. Cool the contents to 25-30° C. and stirred for 1 hr at 25-30° C. The reaction mass was filtered and washed with methylene chloride (30.0 ml). Dried the compound at 60-65° C. Yield: 79.0%.