Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[C:7](=[O:8])[CH:6]=[CH:5][N:4]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[N:3]=1.[C:19]1([C:25]2[S:26][CH:27]=[CH:28][C:29]=2B(O)O)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[C:19]1([C:25]2[S:26][CH:27]=[CH:28][C:29]=2[C:2]2[C:7](=[O:8])[CH:6]=[CH:5][N:4]([C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=3)[N:3]=2)[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: O=c1ccn(-c2cccc(C(F)(F)F)c2)nc1Br
Reactant: OB(O)c1ccsc1-c1ccccc1
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: COCCOC
Solvent: O
Product: O=c1ccn(-c2cccc(C(F)(F)F)c2)nc1-c1ccsc1-c1ccccc1
Temperature: 80 °C
Yield: 22.6 %

Procedure:
A mixture of 3-bromo-1-[3-(trifluoromethyl)phenyl]pyridazin-4(1H)-one (137 mg, 0.428 mmol), (2-phenylthiophen-3-yl)boronic acid (87.4 mg, 0.428 mmol), Na2CO3 (136 mg, 1.28 mmol) and Pd(PPh3)4 (24.7 mg, 0.021 mmol) in DME (1.6 mL) and water (0.49 mL) was heated to 80° C. for 18 h under Ar atmosphere. The mixture was diluted with water, extracted with AcOEt, washed with NaHCO3 aqueous solution, dried over Na2SO4, filtered, concentrated in vacuo, purified by column chromatography on basic silica gel (hexane/AcOEt=80/20 to 0/100) and recrystallized with AcOEt/heptane to yield the title compound (38.6 mg, 23% yield) as a white solid: mp 167-168° C. 1H NMR (DMSO-d6, 300 MHz): δ ppm 6.62 (1H, d, J=8.0 Hz), 7.30-7.41 (5H, m), 7.47 (1H, brs), 7.51 (1H, d, J=5.2 Hz), 7.55-7.72 (4H, m), 8.91 (1H, d, J=8.0 Hz). Anal. Calcd for C21H13F3N2OS: C, 63.31; H, 3.29; N, 7.03. Found: C, 63.08; H, 3.37; N, 7.01.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].CC([O-])(C)C.[K+].Cl[C:19]1[C:28]2[C:23](=[CH:24][C:25]([O:31][CH3:32])=[C:26]([O:29][CH3:30])[CH:27]=2)[N:22]=[CH:21][N:20]=1.C([O-])([O-])=O.[K+].[K+]>CS(C)=O.CCOC(C)=O>[CH3:30][O:29][C:26]1[CH:27]=[C:28]2[C:23](=[CH:24][C:25]=1[O:31][CH3:32])[N:22]=[CH:21][N:20]=[C:19]2[O:8][C:5]1[CH:6]=[CH:7][C:2]([NH2:1])=[C:3]([N+:9]([O-:11])=[O:10])[CH:4]=1
Reactant: Nc1ccc(O)cc1[N+](=O)[O-]
Reactant: COc1cc2ncnc(Cl)c2cc1OC
Agent: CC(C)(C)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: COc1cc2ncnc(Oc3ccc(N)c([N+](=O)[O-])c3)c2cc1OC
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 4-amino-3-nitrophenol (0.8 g, 5.34 mmol, 1.2 eq) in DMSO (3.8 mL, 5×) was treated with KOt-Bu (0.6 g, 5.34 mmol, 1.2 eq), and the mixture was stirred at RT for 2 h. The contents were treated with 4-chloro-6,7-dimethoxyquinazoline (1.0 g, 4.45 mmol, 1.0 eq) and K2CO3 (0.33 g, 2.4 mmol, 0.53 eq) then heated at 110° C. for 16 h. The mixture was cooled to RT, diluted with EtOAc and washed with NaHCO3 (sat). To remove the emulsion, the mixture was filtered through Celite, then the organic layer was washed with brine, 1N NaOH, then brine again. The organic portion was dried with Na2SO4, filtered and evaporated to give the title compound as a brown solid. MS(MH+)=343.1; Calc'd 342.31 for C16H14N4O5.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:20]2[C:21]([C:26]#[N:27])=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][C:9]1[C:14](=[O:15])[NH:13][C:12]([CH3:16])=[N:11][C:10]=1[CH2:17][CH2:18][CH3:19].Br[CH2:29][C:30](=[O:35])[C:31]([CH3:34])([CH3:33])[CH3:32].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>C(OCC)(=O)C>[CH3:32][C:31]([CH3:34])([CH3:33])[C:30](=[O:35])[CH2:29][N:13]1[C:14](=[O:15])[C:9]([CH2:8][C:7]2[CH:6]=[CH:5][C:4]([C:20]3[C:21]([C:26]#[N:27])=[CH:22][CH:23]=[CH:24][CH:25]=3)=[CH:3][C:2]=2[F:1])=[C:10]([CH2:17][CH2:18][CH3:19])[N:11]=[C:12]1[CH3:16]
Reactant: CC(C)(C)C(=O)CBr
Reactant: CCCc1nc(C)[nH]c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCCc1nc(C)n(CC(=O)C(C)(C)C)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1F
Temperature: 25 °C
Reaction time: 4 h
Yield: 25.8 %

Procedure:
A mixture of 3′-fluoro-4′-[(2-methyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (2.04 g), 1-bromo-3,3-dimethylbutan-2-one (1.53 g), potassium carbonate (1.59 g) and N,N-dimethylformamide (30 mL) was stirred at room temperature for 4 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.67 g, 26%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:22]=[CH:21][C:18]([CH2:19]Br)=[C:17]([C:23]([F:26])([F:25])[F:24])[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C-:27]#[N:28].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:22]=[CH:21][C:18]([CH2:19][C:27]#[N:28])=[C:17]([C:23]([F:26])([F:25])[F:24])[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: [C-]#N
Reactant: CC(C)(C)OC(=O)N1CCC(Oc2ccc(CBr)c(C(F)(F)F)c2)CC1
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCC(Oc2ccc(CC#N)c(C(F)(F)F)c2)CC1
Temperature: 25 °C
Reaction time: 14 h

Procedure:
To a stirred solution of 4-(N-tert-butyloxy-carbonyl-4-piperidinyloxy)-2-trifluoromethylbenzyl bromide (0.37 g, 0.87 mmol) from Step 4 above in DMF (4 mL) was added NaCN (0.064 g, 1.3 mmol). The mixture was stirred at ambient temperature for 14 h. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (2×25 mL). The organic phase was dried (MgSO4), filtered, and the solvent was removed under reduced pressure to give 4-(N-tert-butyloxycarbonyl-4-piperidinyloxy)-2-trifluoromethylphenylacetonitrile was a pale yellow gum (HPLC retention time=11.4 min (method A)).
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]2[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[N:8][O:9][C:10]=2[CH3:11])[N:3]=[CH:2]1.[CH3:18][S:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1>>[CH3:11][C:10]1[O:9][N:8]=[C:7]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:6]=1[C:4]1[N:3]=[CH:2][N:1]([C:23]2[CH:24]=[CH:25][C:20]([S:19][CH3:18])=[CH:21][CH:22]=2)[CH:5]=1
Reactant: Cc1onc(-c2ccccc2)c1-c1c[nH]cn1
Reactant: CSc1ccc(B(O)O)cc1
Product: CSc1ccc(-n2cnc(-c3c(-c4ccccc4)noc3C)c2)cc1
Yield: 45 %

Procedure:
As described for Example 3, 4-(1H-imidazol-4-yl)-5-methyl-3-phenyl-isoxazole (112.6 mg, 0.5 mmol) was converted, using 4-methylthiophenylboronic acid instead of 4-fluorophenylboronic acid, to the title compound (78 mg, 45%) which was obtained as a white solid. MS (ESI): m/e=348.0 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.[Cl:15][C:16]([Cl:21])([Cl:20])[C:17](Cl)=[O:18].C(N(C(C)C)CC)(C)C>ClCCl>[Cl:15][C:16]([Cl:21])([Cl:20])[C:17]([N:12]1[CH2:13][CH2:14][N:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[CH2:10][CH2:11]1)=[O:18]
Reactant: O=C(Cl)C(Cl)(Cl)Cl
Reactant: COc1ccccc1N1CCNCC1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccccc1N1CCN(C(=O)C(Cl)(Cl)Cl)CC1
Reaction time: 18 h
Yield: 91 %

Procedure:
A solution of 1-(2-methoxyphenyl) piperazine (7.0 g) in dichloromethane (30 ml) was added over 0.25 h to a stirred solution of trichloroacetyl chloride (4.06 ml) in dichloromethane (40 ml) at room temperature under argon. Diisopropylethylamine (5.95 ml) was then added and the whole was stirred for 18 h. The reaction mixture was washed with water (2×100 ml), dried (Na2SO4) and concentrated to give the title compound (D3) as an oil (11.2 g, 91%). MH+337/339.
Reaction SMILES: [NH2:1][CH2:2][CH:3]([OH:5])[CH3:4].C1(C)C=CC=CC=1.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][CH2:21]Cl)=[CH:16][CH:15]=1>O>[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][NH:1][CH2:2][CH:3]([OH:5])[CH3:4])=[CH:16][CH:15]=1
Reactant: ClCCc1ccc(Cl)cc1
Reactant: CC(O)CN
Solvent: Cc1ccccc1
Solvent: O
Product: CC(O)CNCCc1ccc(Cl)cc1
Temperature: 85 °C
Reaction time: 2 h

Procedure:
In a separate 250-mL round-bottom flask equipped with a magnetic stir bar, a thermocouple, a condenser, and a nitrogen bubbler vented to a caustic scrubber, was charged 1-aminopropan-2-ol (60.1 g, 800 mmol), which was then heated to 85° C. To this was slowly added the toluene solution of 1-chloro-4-(2-chloroethyl)benzene from Step A while maintaining the reaction temperature at <99° C. On completion of the addition, stirring was continued at 90 to 95° C. for 2 h. Toluene (50 mL) and water (25 mL) were added and the mixture was stirred at 70 to 75° C. for 15 minutes before the phases were separated at room temperature. The upper aqueous phase was extracted with toluene (2×25 mL) at 70 to 75° C. Then, the combined organic phases were washed with water (2×25 mL) at 70 to 75° C., and concentrated by distillation under reduced pressure at 60° C. (bath). The residue was diluted with toluene to a total volume of 112.5 mL and the yellow solution was stirred under nitrogen overnight at 50° C. (bath). Karl Fischer titration showed 0.091% water.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][O:11][C:12]1[CH:16]=[C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:14][N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:23](I)[CH2:24][CH3:25]>>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][O:11][C:12]1[C:16]([CH2:23][CH2:24][CH3:25])=[C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:14][N:13]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCCI
Reactant: CC(C)(C)OC(=O)NCCOc1cc(-c2ccccc2)on1
Product: CCCc1c(OCCNC(=O)OC(C)(C)C)noc1-c1ccccc1
Yield: 65 %

Procedure:
3-(2-(N-tert-Butoxycarbonylamino)ethoxy)-5-phenylisoxazole (0.3 g) and propyl iodide (0.29 ml) were subjected to reaction and post-treatment in a similar manner to that described in Example 14(a) to obtain the title compound (0.22 g, 65%) as a colorless oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[N:11]1[C:19](=O)[C:18]2[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=2[NH:12]1.[Cl:21]C(OC(Cl)(Cl)Cl)=O>C1(C)C=CC=CC=1.ClCCCl>[Cl:21][C:19]1[N:11]([C:3]2[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=2[F:1])[N:12]=[C:13]2[C:18]=1[CH2:17][CH2:16][CH2:15][CH2:14]2
Reactant: O=C(Cl)OC(Cl)(Cl)Cl
Reactant: O=c1c2c([nH]n1-c1cc([N+](=O)[O-])ccc1F)CCCC2
Solvent: Cc1ccccc1
Solvent: ClCCCl
Product: O=[N+]([O-])c1ccc(F)c(-n2nc3c(c2Cl)CCCC3)c1

Procedure:
To a solution of 2-(2-fluoro-5-nitrophenyl)1,2,4,5,6,7-hexahydro-3H-indazol-3-one (66.87 g) in toluene (125 ml) and 1,2-dichloroethane (175 ml), there was added trichloromethyl chloroformate (71.57 g), and the resultant mixture was allowed to react in an autoclave at a temperature of 120° to 130° C. under a pressure of 25 kg/cm2, for 3 hours. After cooling, the solvent was removed by distillation. The residue was purified by silica gel column chromatography using a mixture of ethyl acetate and n-hexane (1 : 6) as an eluent to give 3-chloro-2-(2-fluoro-5-nitrophenyl)-4,5,6,7-tetrahydro-2H-indazole. m.p., 109.1° C.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.C([Li])CCC.[Li].[C:12]1(=[O:22])[O:17][C:15](=[O:16])[C:14]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:13]12.Cl>O1CCCC1>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:12]([C:13]1[CH:21]=[CH:20][CH:19]=[CH:18][C:14]=1[C:15]([OH:17])=[O:16])=[O:22]
Reactant: c1ccoc1
Reactant: O=C1OC(=O)c2ccccc21
Agent: Cl
Agent: [Li]
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: O=C(O)c1ccccc1C(=O)c1ccco1
Reaction time: 1 h
Yield: 18.5 %

Procedure:
3.4 g of furan was dissolved in 30 ml of tetrahydrofuran, and the solution was added dropwise to 34 ml of normal butyllithium (1.6M, hexane solution) at -40° C. After stirring the resultant solution at 0° C. for 4 hours, the lithium reagent was added dropwise to a solution of 7.4 g of phthalic anhydride in 100 ml of tetrahydrofuran at -70° C. After stirring the solution at the same temperature for 1 hour, the reaction solution was poured into 0.5-N hydrochloric acid, and extracted with chloroform. By purification by column chromatography (eluent: chloroform, methanol), 2.0 g of o-(2-furoyl) benzoic acid was obtained.
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH:7]=[CH2:8].[CH2:9]([O:11][SiH:12]([O:16][CH2:17][CH3:18])[O:13][CH2:14][CH3:15])[CH3:10].C([Si](C=C)(C)O[Si](C)(C)C)=C>C1(C)C=CC=CC=1>[CH2:8]([Si:12]([O:16][CH2:17][CH3:18])([O:13][CH2:14][CH3:15])[O:11][CH2:9][CH3:10])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH3:1]
Reactant: C=CCCCCCC
Reactant: CCO[SiH](OCC)OCC
Agent: C=C[Si](C)(C=C)O[Si](C)(C)C
Solvent: Cc1ccccc1
Product: CCCCCCCC[Si](OCC)(OCC)OCC
Temperature: 50 °C
Yield: 1.5 %

Procedure:
224 mg Of octene-1, 328 mg of triethoxysilane, and 56 mg of toluene were placed in a glass reaction tube. Next, 0.001 ml of a toluene solution of a 0-valent platinum complex of divinyltetramethyldisiloxane (platinum content: 0.4 wt %) was added to this mixture. The reaction tube was sealed with Teflon tape and heated for 30 minutes in an oil bath at 50° C. When the contents were analyzed by GC-MS following cooling, the conversion rate of octene-1 was 2.5% and n-octyltriethoxysilane was produced at a yield of 1.5%.
Reaction SMILES: [C:1]([OH:5])(=[O:4])[CH:2]=[O:3].[CH3:6][C@H:7]1[CH2:12][C@@H:11](O)[C@H:10]([CH:14]([CH3:16])[CH3:15])[CH2:9][CH2:8]1.S(=O)(=O)(O)O>C1CCCCC1.O>[C:1]([O:5][CH:9]1[CH:10]([CH:14]([CH3:16])[CH3:15])[CH2:11][CH2:12][CH:7]([CH3:6])[CH2:8]1)(=[O:4])[CH:2]=[O:3]
Reactant: CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O
Reactant: O=CC(=O)O
Agent: O=S(=O)(O)O
Solvent: C1CCCCC1
Solvent: O
Product: CC1CCC(C(C)C)C(OC(=O)C=O)C1
Temperature: 25 °C
Reaction time: 6 h

Procedure:
A mixture of aqueous glyoxalic acid (200 g; 50% w/v), L-menthol (632.4 g) and concentrated sulfuric acid (3.5 g) in cyclohexane (600 mL) was refluxed at 80° C. to 85° C. for 3 to 4 hours. Water (115 mL) was removed by azeotropic distillation using a Dean Stark trap. The resulting solution was allowed to cool to room temperature and diluted with de-ionized water (500 mL). The organic layer was separated and diluted with de-ionized water (800 mL). The pH of the resultant mixture was adjusted to 5 using aqueous sodium carbonate (10%; 15 ml). The organic layer was separated and washed twice with aqueous sodium bisulfite (2×70 g in 2×800 mL of de-ionized water). The pH of the organic layer was again adjusted to 5 using aqueous sodium carbonate (10%; 20 ml) and aqueous solution of formaldehyde (130 mL) was added to it in one hour at room temperature. The pH of the resultant mixture was again adjusted to 7.5 using aqueous sodium carbonate (10%; 15 ml) and stirred for about 6 hours at room temperature. The suspension obtained was filtered and washed with de-ionized water (2×200 mL) at room temperature. The wet mass obtained was suspended in de-ionized water (1000 mL) and stirred for 2 hours at 40° C. to 45° C. The resultant mixture was cooled to 20° C. to 25° C. and stirred at the same temperature for one hour. The suspension was filtered and washed with de-ionized water (200 mL) at room temperature to give menthyl glyoxalate as wet mass.
Reaction SMILES: [CH3:1][C:2]1[S:3][C:4]2[CH:13]=[CH:12][C:11]([Br:14])=[CH:10][C:5]=2[C:6]([CH3:9])([CH3:8])[CH:7]=1.CC1C2C=C(Br)C=CC=2SC(C)=C1C.[H][H]>C(OCC)(=O)C.[Pd]=S>[CH3:1][CH:2]1[CH2:7][C:6]([CH3:9])([CH3:8])[C:5]2[C:4](=[CH:13][CH:12]=[C:11]([Br:14])[CH:10]=2)[S:3]1
Reactant: [H][H]
Reactant: CC1=CC(C)(C)c2cc(Br)ccc2S1
Agent: S=[Pd]
Agent: CC1=C(C)C(C)c2cc(Br)ccc2S1
Solvent: CCOC(C)=O
Product: CC1CC(C)(C)c2cc(Br)ccc2S1

Procedure:
A solution of 500 mg (1.9 mmol) of 2,4,4-trimethyl-6-bromo-(4H)-1-benzothiopyran (Compound 50) in 5 ml of ethyl acetate was treated with 500 mg of 10% palladium sulfide on carbon and then shaken under an atmosphere (30 psi) of hydrogen in a Parr apparatus for 24 hours. The mixture was filtered through celite and the solvent was removed in-vacuo. The residue was purified by flash chromatography (silica; hexanes) to give the title compound as a colorless oil. PMR (CDCl3): & 1.21 (3H, s), 1.33 (3H, d, J=6.6Hz), 1.36 (3H, s), 1.64-1.89 (2H, m), 3.37-3.50 (1H, m), 7.10 (1H, dd, J=8.4 Hz, 2.1Hz), 7.19 (1H, d, 8.4 Hz), 7.20 (1H, d, 2.1 Hz)
Reaction SMILES: Cl[CH2:2][C:3]([O:5][CH3:6])=[O:4].[CH2:7]([C:9]1[CH:24]=[CH:23][C:12]([C:13]([C:15]2[CH:20]=[CH:19][C:18]([CH2:21][CH3:22])=[CH:17][CH:16]=2)=[O:14])=[CH:11][CH:10]=1)[CH3:8].C([O-])C.[Na+].O>C1COCC1>[CH2:21]([C:18]1[CH:19]=[CH:20][C:15]([C:13]2([C:12]3[CH:11]=[CH:10][C:9]([CH2:7][CH3:8])=[CH:24][CH:23]=3)[O:14][CH:2]2[C:3]([O:5][CH3:6])=[O:4])=[CH:16][CH:17]=1)[CH3:22]
Reactant: CCc1ccc(C(=O)c2ccc(CC)cc2)cc1
Reactant: COC(=O)CCl
Agent: CC[O-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CCc1ccc(C2(c3ccc(CC)cc3)OC2C(=O)OC)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 59.1 %

Procedure:
A solution of 15 ml (168 mmol) of methyl chloroacetate and 20 g (84 mmol) of 4,4′-diethylbenzophenone in 20 ml of THF was added dropwise to a suspension of 9.1 g (168 mmol) of sodium ethanolate in 80 ml of THF at −10° C. The mixture was warmed to room temperature and stirred for 2 hours. The mixture was added to water and extracted with ether. The organic phase was washed with sodium bicarbonate solution and citric acid solution and dried over magnesium sulfate, and the solvent was distilled off. 15.4 g of a crude oil were isolated and were immediately employed further.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[S:15](Cl)(=[O:17])=[O:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.[C:25]([O:29][C:30](=[O:40])[CH2:31][CH:32]([NH2:39])[C:33]([N:35]([O:37][CH3:38])[CH3:36])=[O:34])([CH3:28])([CH3:27])[CH3:26]>ClCCl>[C:25]([O:29][C:30](=[O:40])[CH2:31][C@H:32]([NH:39][S:15]([C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)(=[O:17])=[O:16])[C:33]([N:35]([O:37][CH3:38])[CH3:36])=[O:34])([CH3:26])([CH3:28])[CH3:27]
Reactant: O=S(=O)(Cl)c1ccccc1OCc1ccccc1
Reactant: CON(C)C(=O)C(N)CC(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: c1ccncc1
Product: CON(C)C(=O)[C@H](CC(=O)OC(C)(C)C)NS(=O)(=O)c1ccccc1OCc1ccccc1
Reaction time: 16 h
Yield: 92 %

Procedure:
To 2-benzyloxy-benzenesulfonyl chloride (3.11 g, 11 mmol) in dichloromethane (50 mL) and pyridine (2.6 mL, 3 equiv) was added 3-amino-N-methoxy-N-methyl-succinamic acid tert-butyl ester (1 equiv). The reaction stirred for 16 h and was washed with 10% sulfuric acid, water, and then brine. To give (S)-3-(2-benzyloxy-benzenesulfonylamino)-N-methoxy-N-methyl-succinamic acid tert-butyl ester as a yellow oil (4.82 g, 92%) that was sufficiently pure for further use. 1H NMR (CDCl3) 7.88(d,1H), 7.57(d,2H), 7.40(m,3H), 7.17(d,1H), 7.03(m,2H), 5.92(d,1H), 5.25(s,2H), 4.73(bs,1H), 3.57(s,3H), 2.86(s,3H), 2.63-2.39(AB quartet, 2H), 1.40(s,9H).
Reaction SMILES: [BH4-].[Na+].[CH3:3][NH:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11]O)=[CH:7][C:6]=1[N+:13]([O-:15])=[O:14].O=S(Cl)[Cl:18]>>[CH3:3][NH:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][Cl:18])=[CH:7][C:6]=1[N+:13]([O-:15])=[O:14]
Reactant: O=S(Cl)Cl
Reactant: CNc1ccc(CO)cc1[N+](=O)[O-]
Agent: [BH4-]
Agent: [Na+]
Product: CNc1ccc(CCl)cc1[N+](=O)[O-]

Procedure:
4-Chloro-3-nitro-benzaldehyde is reacted with methylamine to yield 4-(methylamino)-3-nitrobenzaldehyde (8) which is then reduced by NaBH4 to N-methyl-4-hydroxymethyl-2-nitroaniline (9). Reaction of SOCl2 with 8 will give N-methyl-4-chloromethyl-2-nitroaniline (10). Structures of 8, 9 and 10 may be characterized by 1H NMR and elemental analysis. 10 is used as an electrophile to react with sodium CD alkoxide (11) to yield 2-O-(4-methylamino-3-nitro) benzyl-β-CD (12). The addition of 10 to 11 is a novel method for mono-functionalizing the 2-position of CD's (Rong, P., and D'Souza, V. T., Tetrahedron Lett., 31:4275 (1990)). 12 is hydrogenated by agents such as H2 /Pd, H2 /Pt, H2 /Ni, Sn/HCl, Fe/HCl and Zn/HCl, and then condensed with alloxan monohydrate to yield 2-flavo-CD (13). Compounds 11 and 12 can be characterized by 1H and 13C NRM. 2-Flavo-α-CD, β-CD and γ-CD may be synthesized by the same method. ##STR12##
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][NH:8][C:9]([C@H:11]([C@@H:21]([CH2:30][CH:31]([CH3:33])[CH3:32])[C:22]([NH:24][NH:25][CH2:26][CH:27]([CH3:29])[CH3:28])=[O:23])[CH2:12]/[CH:13]=[CH:14]/[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:10].[C:34](O)(=[O:40])[CH2:35][CH2:36][C:37]([CH3:39])=[O:38].Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][NH:8][C:9]([C@H:11]([C@@H:21]([CH2:30][CH:31]([CH3:33])[CH3:32])[C:22]([NH:24][N:25]([C:34](=[O:40])[CH2:35][CH2:36][C:37](=[O:38])[CH3:39])[CH2:26][CH:27]([CH3:28])[CH3:29])=[O:23])[CH2:12]/[CH:13]=[CH:14]/[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:10]
Reactant: CC(=O)CCC(=O)O
Reactant: CC(C)CNNC(=O)[C@H](CC(C)C)[C@H](C/C=C/c1ccccc1)C(=O)NOC1CCCCO1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CN(C)C=O
Product: CC(=O)CCC(=O)N(CC(C)C)NC(=O)[C@H](CC(C)C)[C@H](C/C=C/c1ccccc1)C(=O)NOC1CCCCO1
Temperature: 25 °C
Reaction time: 8 h
Yield: 102.3 %

Procedure:
A solution of 0.459 g of (E)-2(R)-[1(S)-[(tetrahydro-2(RS)-pyranyloxy)carbamoyl]-4-phenyl-3-butenyl]-2′-isobutyl-4-methylvalerohydrazide in 5 ml of dimethylformamide was treated with 0.232 g of levulinic acid and 0.384 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride. The mixture was stirred overnight at room temperature and evaporated. The residue in ethyl acetate was washed with 5% aqueous citric acid solution, 5% aqueous sodium hydrogen carbonate solution, saturated sodium chloride solution, and then dried over anhydrous magnesium sulphate and evaporated to give 0.570 g of (E)-2(R)-[1(S)-[(tetrahydro-2(RS)-pyranyloxy)carbamoyl]-4-phenyl-3-butenyl]-2′-(4-oxovaleryl)-2′-isobutyl-4-methylvalerohydrazide in the form of a white foam.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8](I)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:12].[O:13]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[CH:15]=[C:14]1B(O)O.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:14]2[O:13][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[CH:15]=2)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:12]
Reactant: OB(O)c1cc2ccccc2o1
Reactant: O=C1NCc2c(Cl)ccc(I)c21
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CCN(CC)CC
Solvent: CC#N
Product: O=C1NCc2c(Cl)ccc(-c3cc4ccccc4o3)c21
Yield: 18.5 %

Procedure:
In a similar manner to Step 2 of Example 1, 4-chloro-7-iodoisoindolinone (80.0 mg, 0.273 mmol) was dissolved in acetonitrile (4.0 mL), and the solution was treated with 2-benzofuraneboronic acid (133 mg, 0.819 mmol), palladium acetate (7.4 mg, 0.033 mmol), tri(o-tolyl)phosphine (20 mg, 0.066 mmol) and triethylamine (0.381 mL, 2.73 mmol), followed by purification by preparative thin-layer chromatography (chloroform/acetonitrile=15/1) to obtain Compound 170 (14.3 mg, yield 18%).
Reaction SMILES: [NH:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4](=O)[C:2]1=[O:3].Cl.[CH3:13][O:14][NH2:15].O.O.O.C([O-])(=O)C.[Na+]>CO.O>[CH3:13][O:14][N:15]=[C:4]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[NH:1][C:2]1=[O:3]
Reactant: CON
Reactant: O=C1Nc2ccccc2C1=O
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CON=C1C(=O)Nc2ccccc21
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 91.1 %

Procedure:
In 3.8 l of methanol was dissolved 176 g of isatin while heating, and a solution of 100 g of O-methylhydroxylamine hydrochloride and 136 g of sodium acetate trihydrate in 400 ml of water was added thereto. The resulting mixture was stirred at room temperature for 10 minutes, followed by concentration. Water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogencarbonate, dried over anhydrous sodium sulfate, and concentrated to give 192 g (91%) of 3-methoxyiminoindolin-2-one. The resulting crude product was used in the subsequent reaction without being purified.