Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[C:14](=O)[CH2:13][CH2:12]2.[NH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][C:28]([O:30]C)=[O:29])=[CH:22][CH:21]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O.[OH-].[Li+].Cl>ClCCCl.O.CO>[CH3:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[CH:14]([NH:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][C:28]([OH:30])=[O:29])=[CH:22][CH:21]=1)[CH2:13][CH2:12]2
Reactant: COC(=O)CCc1ccc(N)cc1
Reactant: Cc1cccc(C)c1-c1ccc2c(c1)CCC2=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Li+]
Solvent: CC(=O)O
Solvent: O
Solvent: ClCCCl
Product: Cc1cccc(C)c1-c1ccc2c(c1)CCC2Nc1ccc(CCC(=O)O)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 36.8 %

Procedure:
5-(2,6-Dimethylphenyl)indan-1-one (690 mg, 2.92 mmol), methyl 3-(4-aminophenyl)propanoate (937 mg, 4.09 mmol) and acetic acid (526 mg, 8.76 mmol) were dissolved in 1,2-dichloroethane (20 mL), sodium triacetoxyborohydride (1.86 g, 8.76 mmol) was added by small portions at room temperature, and the mixture was stirred at room temperature for 16 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (5%-40% ethyl acetate/hexane). The obtained oil was dissolved in tetrahydrofuran (10 mL), methanol (6 mL), and water (6 mL), and lithium hydroxide monohydrate (133 mg, 3.18 mmol) was added. The mixture was stirred at room temperature for 3 hr. The reaction mixture was neutralized with 1 M hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (10%-60% ethyl acetate/hexane) to give the title compound (414 mg, yield 37%) as a colorless oil.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:14]=[CH:13][NH:12][N:11]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].Br[C:16]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+].OC1C=CC=C2C=1N=CC=C2>CN(C=O)C.O.[Cu]I>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:10]2[N:14]=[CH:13][N:12]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)[N:11]=2)=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: FC(F)(F)c1ccc(Br)cc1
Reactant: O=[N+]([O-])c1ccc(-c2nc[nH]n2)cc1
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: Oc1cccc2cccnc12
Solvent: CN(C)C=O
Solvent: O
Product: O=[N+]([O-])c1ccc(-c2ncn(-c3ccc(C(F)(F)F)cc3)n2)cc1
Temperature: 140 °C
Yield: 62.7 %

Procedure:
A mixture of 3-(4-nitrophenyl)-1H-1,2,4-triazole (20.0 g, 105 mmol), 1-bromo-4-(trifluoromethyl)benzene (28.0 g, 124 mmol), cesium carbonate (68.4 g, 210 mmol), copper(I) iodide (2.59 g, 13.6 mmol), and 8-hydroxyquinoline (1.80 g, 12.4 mmol) in N,N′-dimethylformamide/water (9:1, 142 mL) under nitrogen was heated to 140° C. for 18 hours. The reaction was cooled to room temperature (about 22° C.) and quenched with ammonium hydroxide (10 mL). The reaction mixture was extracted with ethyl acetate. The organic layer was separated and washed with water (3×100 mL) and brine (300 mL). The organic layer was separated and dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography (silica gel) using 0-65% ethyl acetate/petroleum ether as eluent provided the title compound as a white solid (22.0 g, 63%): 1H NMR (300 MHz, CDCl3) δ 8.72 (s, 1H), 8.42-8.34 (m, 4H), 7.94 (d, J=8.7 Hz, 2H), 7.84 (d, J=8.5 Hz, 2H); ESIMS m/z 335 ([M+H]+).
Reaction SMILES: O1C=CC=C1C(Cl)=O.[O:9]1[CH:13]=[CH:12][CH:11]=[C:10]1[C:14]([N:16]=[C:17]=[S:18])=[O:15].[CH3:19][O:20][C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][C:30]=1[O:31][CH3:32])[N:27]=[CH:26][CH:25]=[C:24]2[O:33][C:34]1[CH:40]=[CH:39][C:37]([NH2:38])=[CH:36][CH:35]=1.C1(C)C=CC=CC=1>C(O)C>[O:9]1[CH:13]=[CH:12][CH:11]=[C:10]1[C:14]([N:16]=[C:17]=[S:18])=[O:15].[CH3:19][O:20][C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][C:30]=1[O:31][CH3:32])[N:27]=[CH:26][CH:25]=[C:24]2[O:33][C:34]1[CH:35]=[CH:36][C:37]([NH:38][C:17]([NH:16][C:14]([C:10]2[O:9][CH:13]=[CH:12][CH:11]=2)=[O:15])=[S:18])=[CH:39][CH:40]=1
Reactant: COc1cc2nccc(Oc3ccc(N)cc3)c2cc1OC
Agent: O=C(Cl)c1ccco1
Agent: O=C(N=C=S)c1ccco1
Solvent: Cc1ccccc1
Solvent: CCO
Product: COc1cc2nccc(Oc3ccc(NC(=S)NC(=O)c4ccco4)cc3)c2cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 53 %

Procedure:
2-Furancarbonyl isothiocyanate was prepared using commercially available 2-furancarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 2-Furancarbonyl isothiocyanate was dissolved in ethanol (1 ml) to prepare a solution. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]aniline (50 mg), toluene (5 ml), and ethanol (1 ml) were added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (40 mg, yield 53%).
Reaction SMILES: C([Li])CCC.Br[C:7]1[CH:8]=[CH:9][C:10]([O:13][CH3:14])=[N:11][CH:12]=1.[N+:15]([C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH:20]=[O:21])([O-:17])=[O:16].[K+].[Br-]>O1CCCC1.CCCCCC>[N+:15]([C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH:20]([C:7]1[CH:12]=[N:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1)[OH:21])([O-:17])=[O:16]
Reactant: COc1ccc(Br)cn1
Reactant: O=Cc1ccccc1[N+](=O)[O-]
Agent: [Br-]
Agent: [K+]
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: COc1ccc(C(O)c2ccccc2[N+](=O)[O-])cn1
Temperature: -85 °C

Procedure:
n-Butyllithium (6.7 ml of a 1.6M hexane solution) was added dropwise to a stirred, cooled (-100° C.) solution of 5-bromo-2-methoxypyridine (2.0 g, Eur. J. Med. Chem. 1977, 12, 531) in anhydrous tetrahydrofuran (60 ml), under a nitrogen atmosphere. After 20 minutes a solution of 2-nitrobenzaldehyde (1.61 g) in anhydrous tetrahydrofuran (30 ml)was added dropwise and the reaction mixture was stirred whilst maintaining the temperature between -90° and -100° C. for 2 hours. The reaction mixture was warmed to -85° C. then quenched with saturated aqueous ammonium chloride solution then allowed to warm to room temperature. The organic layer was separated and the aqueous extracted with ethyl acetate (3×100 ml). The combined organics were dried (magnesium sulphate) then evaporated to give a gum which was purified by column chromatography on silica using ethyl acetate/petroleum ether (60-80) (1:4) to afford an oil which solidified to give a low melting solid on standing (1.42 g). Rf =0.30 in 33% ethyl acetate/petroleum ether (60-80) on silica plates; 1H NMR (360 MHz, CDCl3) δ 2.60 (1H, broad s), 3.91 (3H, s), 6.43 (1H, s), 6.70 (1H, d, J=9 Hz), 7.48 (1H, dd, J=1 and 8 Hz), 7.53 (1H, dd, J=3 and 9 Hz), 7.67 (1H, dd, J=1 and 8 Hz), 7.83 (1H, d, J=8 Hz), 7.96 (1H, dd, J=1 and 8 Hz), 8.11 (1H, d, J=3 Hz); MS, m/z 261 for (M+H)+ ; IR (KBr) 3300 cm-1 (v. broad).
Reaction SMILES: FC(F)(F)C(O)=O.[CH3:8][O:9][C:10](=[O:26])[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([O:20]C(C)(C)C)=[O:19])=[C:13]([CH3:25])[CH:12]=1>ClCCl>[CH3:8][O:9][C:10](=[O:26])[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([OH:20])=[O:19])=[C:13]([CH3:25])[CH:12]=1
Reactant: COC(=O)c1ccc(CC(=O)OC(C)(C)C)c(C)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)c1ccc(CC(=O)O)c(C)c1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 81 %

Procedure:
Trifluoroacetic acid (15 ml) was added to a solution of 4-tert-butoxycarbonylmethyl-3-methyl-benzoic acid methyl ester from Example E32.1 (2.84 g, 10.7 mmol) in dichloromethane (15 ml). The mixture was stirred for 90 min at room temperature, concentrated in vacuo and azeotroped with toluene. The residue was recrystallised from EtOAc and hexane to yield the title compound (1.81 g, 81%).
Reaction SMILES: [CH2:1]([C:12]1[N:16]=[C:15]([C:17]2[CH:24]=[CH:23][C:20]([CH:21]=O)=[CH:19][CH:18]=2)[O:14][N:13]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].[CH3:25][O:26][C:27]1[CH:34]=[CH:33][CH:32]=[CH:31][C:28]=1[CH2:29][NH2:30]>>[CH3:25][O:26][C:27]1[CH:34]=[CH:33][CH:32]=[CH:31][C:28]=1[CH2:29][NH:30][CH2:21][C:20]1[CH:23]=[CH:24][C:17]([C:15]2[O:14][N:13]=[C:12]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[N:16]=2)=[CH:18][CH:19]=1
Reactant: COc1ccccc1CN
Reactant: CCCCCCCCCCCc1noc(-c2ccc(C=O)cc2)n1
Product: CCCCCCCCCCCc1noc(-c2ccc(CNCc3ccccc3OC)cc2)n1

Procedure:
The same procedure as employed in the preparation of Example 357 (step a) but using 4-(3-undecyl-1,2,4-oxadiazol-5-yl)benzaldehyde and 2-methoxybenzylamine gave the title compound as an oil. M+(LC/MS(ESI)): 450.5. HPLC (Condition A), Rt: 4.70 min (HPLC purity: 92.7%).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[CH:9][C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)=[CH:4][C:3]=1[O:20][CH3:21].[C:22]([O:27][CH2:28][CH:29]1[O:31][CH2:30]1)(=[O:26])[C:23]([CH3:25])=[CH2:24].O>CN(C)C(=O)C.[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH3:21][O:20][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)[CH:6]=[CH:7][C:2]=1[O:1][CH2:30][CH:29]([OH:31])[CH2:28][O:27][C:22](=[O:26])[C:23]([CH3:25])=[CH2:24]
Reactant: COc1cc(C=Cc2ccc3ccccc3n2)ccc1O
Reactant: C=C(C)C(=O)OCC1CO1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Solvent: O
Solvent: CC(=O)N(C)C
Product: C=C(C)C(=O)OCC(O)COc1ccc(C=Cc2ccc3ccccc3n2)cc1OC
Yield: 50 %

Procedure:
In 5 cm3 of N,N-dimethylacetamide, 2.77 g of the produced quinoline derivative was dissolved and 1.42 g of glycidyl methacrylate and 0.10 g of tetrabutylammonium chloride were added thereto. The resultant mixture was reacted by maintaining it at 90° to 100° C. for 5 hours. The reaction product was mixed with water. The oily substance separated consequently was extracted via ethyl acetate, washed thoroughly with water, and dried. The dry product was distilled to expel the solvent and then separated and purified by silica gel chromatography, to afford 2-{2-[3-methoxy-4-(2-hydroxy-3-methacryloyloxypropyloxy)-phenyl]-ethenyl}-quinoline in a yield of 50%. When this product was recrystallized via ethyl acetatehexane, there was obtained a pure product having a melting point of 119° C. It was identified by elementary analysis and infrared absorption spectrometry.
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH:8]=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH3:12][C:13]1[CH:18]=[CH:17][N:16]=[CH:15][N:14]=1.C(OC(=O)C)(=O)C>O>[N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[CH:12][C:13]2[CH:18]=[CH:17][N:16]=[CH:15][N:14]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: Cc1ccncn1
Reactant: O=Cc1ccc([N+](=O)[O-])cc1
Solvent: O
Solvent: CC(=O)OC(C)=O
Product: O=[N+]([O-])c1ccc(C=Cc2ccncn2)cc1
Temperature: 120 °C
Yield: 77 %

Procedure:
The starting compound is prepared as follows. p-Nitrobenzaldehyde (24.2 g), 4-methyl-pyrimidine (15.5 g) and acetic anhydride (16.7 g) are mixed at room temperature, and the mixture is heated at 120° C. for 5 hours. After cooling, the mixture is poured into water (500 ml), and the aqueous mixture is extracted several times with chloroform. The combined chloroform extracts are dried over magnesium sulfate and concentrated until crystals separated. Addition of ether gives 4-[2-(p-nitrophenyl) ethenyl]pyrimidine (28 g), m.p. 213°-215° C.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[C:10]([CH2:17][C:18]([OH:20])=O)=[CH:11][C:12]([O:15][CH3:16])=[N:13][CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[C:9]2=[CH:14][N:13]=[C:12]([O:15][CH3:16])[CH:11]=[C:10]2[CH2:17][C:18]1=[O:20])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COc1cc(CC(=O)O)c(NC(=O)OC(C)(C)C)cn1
Agent: On1nnc2cccnc21
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCCl
Solvent: ClCCl
Product: COc1cc2c(cn1)N(C(=O)OC(C)(C)C)C(=O)C2
Temperature: 25 °C
Reaction time: 2 h
Yield: 101.5 %

Procedure:
(5-tert-Butoxycarbonylamino-2-methoxy-pyridin-4-yl)-acetic acid (10 g, 35.4 mmol) was dissovled in DCM (142 mL) and EDC (7.5 g, 39 mmol), HOAt (5.4 g, 39 mmol) and DIPEA (15 mL, 85.7 mmol) were sequentially added, under N2. The reaction was stirred for 2 h at ambient temperature then quenched by addition of saturated aqueous NaHCO3 and extracted with DCM (×3). The combined organic extracts were washed with water and brine then dried over MgSO4 and concentrated in vacuo. The product was purified by column chromatography to yield the title compound (9.5 g) as a pale brown solid. 1H NMR (DMSO-c/6): 8.38 (1H, s), 6.83 (1H, s), 3.84 (3H, s), 3.77 (2H, s), 1.57 (9H, s). MS: [M+H]+=265.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:11]([CH3:32])([CH3:31])[CH2:12][C:13]([CH2:19][C:20]2[NH:28][C:27]3[C:22](=[N:23][C:24]([CH2:29][OH:30])=[CH:25][CH:26]=3)[CH:21]=2)([OH:18])[C:14]([F:17])([F:16])[F:15])[C:5]2[O:9][CH2:8][CH2:7][C:6]=2[CH:10]=1>CC(C)=O.[O-2].[Mn+4].[O-2]>[Cl:1][C:2]1[CH:3]=[C:4]([C:11]([CH3:32])([CH3:31])[CH2:12][C:13]([OH:18])([C:14]([F:17])([F:16])[F:15])[CH2:19][C:20]2[NH:28][C:27]3[C:22](=[N:23][C:24]([CH:29]=[O:30])=[CH:25][CH:26]=3)[CH:21]=2)[C:5]2[O:9][CH2:8][CH2:7][C:6]=2[CH:10]=1
Reactant: CC(C)(CC(O)(Cc1cc2nc(CO)ccc2[nH]1)C(F)(F)F)c1cc(Cl)cc2c1OCC2
Agent: [Mn+4]
Agent: [O-2]
Solvent: CC(C)=O
Product: CC(C)(CC(O)(Cc1cc2nc(C=O)ccc2[nH]1)C(F)(F)F)c1cc(Cl)cc2c1OCC2
Temperature: 25 °C
Reaction time: 1 h
Yield: 71.2 %

Procedure:
To a solution of alcohol of Example 93 (0.882 g, 1.88 mmol) in 25 mL of acetone was added manganese (IV) oxide (3.99 g, 9.41 mmol). The black suspension was stirred at room temperature for 1 hour. The solution was filtered through diatomaceous earth and the acetone was evaporated in vacuo to give the title compound (0.625 g, 74.0% yield) as a yellow foam.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:5]2[C:10]([CH3:11])=[N:9][N:8]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)=[CH:15][CH:14]=3)[C:6]=2[N:7]=1.[C:31]1(/[CH:37]=[CH:38]/B(O)O)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.O.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[CH3:11][C:10]1[C:5]2[C:4]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[CH:3][C:2](/[CH:38]=[CH:37]/[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[N:7][C:6]=2[N:8]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:15][CH:14]=2)[N:9]=1
Reactant: CCOC(=O)c1cc(Cl)nc2c1c(C)nn2Cc1ccc(Oc2ccccc2)cc1
Reactant: OB(O)/C=C/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: C1COCCO1
Solvent: O
Product: CCOC(=O)c1cc(/C=C/c2ccccc2)nc2c1c(C)nn2Cc1ccc(Oc2ccccc2)cc1
Temperature: 90 °C
Reaction time: 8 h
Yield: 90 %

Procedure:
(see, e.g., Greig, I. R., et al., J Med Chem 2006, 49, 7487-92; Li, X., et al., J Med Chem 2003, 46, 5663-73). To a mixture of 50 (205 mg, 0.49 mmol), Pd(PPh3)4 (27 mg, 0.02 mmol) and (E)-2-phenylvinylboronic acid (112 mg, 0.74 mmol) in 1,4-dioxane: H2O (3 mL/2 mL) was added Na2CO3 (153 mg, 1.45 mmol), followed by stirring at 90° C. overnight. To the reaction mixture was added H2O (10 mL) and the aqueous layer was extracted with EtOAc (10 mL×2). The combined organic layer was washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. Crude was subjected to flash column chromatography on silica gel to provide the title compound (216 mg, 90%) as a light yellow oil which solidified upon standing. 1H NMR (500 MHz, CDCl3) δ 7.80 (d, J=16.1 Hz, 1H), 7.74 (s, 1H), 7.63 (d, J=7.6 Hz, 2H), 7.41 (t, J=7.6 Hz, 2H), 7.39-7.33 (m, 3H), 7.30 (t, J=7.7 Hz, 3H), 7.07 (t, J=7.4 Hz, 1H), 6.98 (d, J=8.6 Hz, 2H), 6.95 (d, J=8.3 Hz, 2H), 5.69 (s, 2H), 4.51 (q, J=7.1 Hz, 2H), 2.71 (s, 3H), 1.49 (t, J=7.0 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 165.76, 157.04, 156.79, 154.93, 152.39, 141.19, 136.28, 134.74, 133.60, 132.13, 129.69, 129.50, 128.81, 127.69, 127.33, 123.28, 118.94, 118.82, 116.48, 110.28, 61.93, 49.80, 16.30, 14.30.
Reaction SMILES: C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[N+:34]([C:37]1[CH:42]=[CH:41][C:40]([OH:43])=[CH:39][CH:38]=1)([O-:36])=[O:35].O[CH2:45][CH2:46][N:47]1[CH2:51][CH2:50][CH2:49][CH2:48]1>C1COCC1>[N+:34]([C:37]1[CH:42]=[CH:41][C:40]([O:43][CH2:45][CH2:46][N:47]2[CH2:51][CH2:50][CH2:49][CH2:48]2)=[CH:39][CH:38]=1)([O-:36])=[O:35]
Reactant: OCCN1CCCC1
Reactant: O=[N+]([O-])c1ccc(O)cc1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: O=[N+]([O-])c1ccc(OCCN2CCCC2)cc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 53.3 %

Procedure:
To a mixture of PPh3 (866 mg, 3.3 mmol) in THF (6 mL) is added DIAD (0.65 mL, 3.3 mmol) at 0° C. The suspension was stirred for 10 minutes, then heated to room temperature. To the mixture, 4-nitrophenol (460 mg, 3.3 mmol) and 1-(2-hydroxyethyl)-pyrrolidine (0.26 mL, 2.2 mmol) is added, and the mixture is stirred at room temperature for 16 hours, then concentrated. The residue is taken up in EtOAc, washed with 1N NaOH aqueous solution and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product is purified by column chromatography (SiO2, MeOH:CH2Cl2=1:99 to 10:90) to give 277 mg of 1-[2-(4-Nitro-phenoxy)-ethyl]-pyrrolidine as a white solid.
Reaction SMILES: [CH:1]1([C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH2:3][CH2:2]1.[N+:10]([O-])(O)=O.[OH-].[Na+].[N+](C1CC1C1C=CC=CC=1)([O-])=O.[N+](C1C=CC(C2CC2)=CC=1)([O-])=O>C(OC(=O)C)(=O)C.C(O)C.O=[Pt]=O>[CH:1]1([C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[NH2:10])[CH2:3][CH2:2]1
Reactant: O=[N+]([O-])O
Reactant: c1ccc(C2CC2)cc1
Agent: O=[Pt]=O
Agent: O=[N+]([O-])C1CC1c1ccccc1
Agent: O=[N+]([O-])c1ccc(C2CC2)cc1
Solvent: CC(=O)OC(C)=O
Solvent: CCO
Product: Nc1ccccc1C1CC1
Reaction time: 1 h

Procedure:
A solution of 5 g (42 mmol) of cyclopropylbenzene in 20 ml of acetic anhydride is cooled to 15° C. While keeping the temperature below 20° C., 3.7 ml of 68% nitric acid are added slowly. The reaction mixture is stirred for one hour at that temperature, hydrolysed, rendered alkaline with 2N sodium hydroxide solution and extracted twice with 100 ml of ether. The organic phase is then dried and concentrated to yield a mixture of 2-nitrocyclo-propylbenzene and 4-nitrocyclopropylbenzene. The mixture is dissolved in 15 ml of ethanol and hydrogenated at normal temperature and pressure in the presence of 50 mg of PtO2. The residue obtained after filtering off the catalyst and evaporating off the solvent is purified by chromatography on silica gel to yield the title product.
Reaction SMILES: [NH2:1][CH2:2][CH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][O:4]1.[N+:9]([C:12]1[C:17]([CH:18]=O)=[CH:16][C:15]([O:20][CH3:21])=[C:14]([O:22][CH3:23])[CH:13]=1)([O-:11])=[O:10]>C(O)C>[N+:9]([C:12]1[C:17]([CH:18]=[C:8]2[CH2:7][CH2:6][CH2:5][O:4][CH:3]2[CH2:2][NH2:1])=[CH:16][C:15]([O:20][CH3:21])=[C:14]([O:22][CH3:23])[CH:13]=1)([O-:11])=[O:10]
Reactant: COc1cc(C=O)c([N+](=O)[O-])cc1OC
Reactant: NCC1CCCCO1
Solvent: CCO
Product: COc1cc(C=C2CCCOC2CN)c([N+](=O)[O-])cc1OC

Procedure:
A solution of 2-aminomethyltetrahydropyran (51 g, 0.44 mole) and ethanol (50 ml) was slowly added to a heated suspension of 6-nitroveratraldehyde (84 g, 0.4 mole) and ethanol (600 ml). The resulting solution was refluxed for 1.5 hrs and cooled overnight. The solution was concentrated to dryness and the oil was dissolved in chloroform and washed with water. The chloroform extract was concentrated leaving a dark oil which crystallized upon standing. The solid was suspended in hexane and filtered (117 g, 95%), m.p. 89°-96°.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[Na+].O1CCOCC1.[C:20]([NH:28][C:29]1[CH:38]=[C:37](Br)[CH:36]=[CH:35][C:30]=1[C:31]([O:33][CH3:34])=[O:32])(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C(O)(=O)C>[NH:1]([C:37]1[CH:36]=[CH:35][C:30]([C:31]([O:33][CH3:34])=[O:32])=[C:29]([NH:28][C:20](=[O:27])[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:38]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(=O)c1ccc(Br)cc1NC(=O)c1ccccc1
Reactant: Nc1ccccc1
Agent: [Fe+2]
Agent: CC(C)(C)[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: CC(=O)O
Product: COC(=O)c1ccc(Nc2ccccc2)cc1NC(=O)c1ccccc1
Temperature: 25 °C

Procedure:
0.16 mL of aniline, 0.12 g of 1,1′-bis(diphenylphosphino)ferrocene, 0.057 g of (1,1′-bis(diphenylphosphino)ferrocene)palladium(II) dichloride methylene chloride complex and 0.17 g of sodium tert-butoxide were added to 6 mL of dioxane solution containing 0.58 g of methyl 2-(benzamido)-4-bromobenzoate, and the resulting mixture was heated to reflux under nitrogen atmosphere for 4 hours. After the reaction mixture was cooled to room temperature, 1 mL of acetic acid was added and the solvent was evaporated under reduced pressure. The obtained residue was purified with silica gel column chromatography [eluent; hexane:ethyl acetate=5:1] to obtain 0.43 g of methyl 4-(anilino)-2-(benzamido)benzoate as colorless oil.
Reaction SMILES: COC[N:4]1[C:8](=[O:9])[N:7](COC)[CH:6]2[N:13](COC)[C:14]([N:16](COC)[CH:5]12)=[O:15].C1CCC(NS(O)(=O)=O)CC1.CC(O)CN(CC(O)C)CCN(CC(O)C)CC(O)C.CC(C1CCC(O)CC1)(C1CCC(O)CC1)C>>[CH:6]12[NH:13][C:14](=[O:15])[NH:16][CH:5]1[NH:4][C:8]([NH:7]2)=[O:9]
Reactant: COCN1C(=O)N(COC)C2C1N(COC)C(=O)N2COC
Agent: CC(C)(C1CCC(O)CC1)C1CCC(O)CC1
Agent: CC(O)CN(CCN(CC(C)O)CC(C)O)CC(C)O
Agent: O=S(=O)(O)NC1CCCCC1
Product: O=C1NC2NC(=O)NC2N1
Temperature: 120 °C

Procedure:
Into a reaction vessel equipped as in Example A was charged 1064 grams tetramethoxymethyl glycoluril (TMMGU) and 532 grams hydrogenated bisphenol-A which was melted and heated to 120° C. 14 grams of Polycat 200 catayst was added slowly over a 30-minute period at 110°-120° C. to control foaming. The batch temperature was then raised slowly to 160° C. and foaming controlled with 2 grams additions of Quadrol. Total Quadrol added is 10.4 grams. Upon reaching a tack temperature of 80°-85° C., the batch was discharged into a tray. The product, a methoxy-methyl-functional copolymer of TMMGU and HBPA, has a tack temperature of 84° C., a viscosity at 50% non-volatile content in meta-pyrol of K and a methoxy equivalent weight of 212. A small amount of self-condensation had also occurred in this reaction in addition to the primary methoxyhydroxyl reaction.
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[C:3]1[C:14]([CH2:15][CH2:16][NH2:17])=[C:6]2[C:7]3[CH2:13][CH2:12][O:11][C:8]=3[CH:9]=[CH:10][N:5]2[N:4]=1.C(N(CC)CC)C.[C:27](Cl)(=[O:29])[CH3:28]>O1CCCC1.C(=O)([O-])O.[Na+]>[F:19][C:2]([F:1])([F:18])[C:3]1[C:14]([CH2:15][CH2:16][NH:17][C:27](=[O:29])[CH3:28])=[C:6]2[C:7]3[CH2:13][CH2:12][O:11][C:8]=3[CH:9]=[CH:10][N:5]2[N:4]=1
Reactant: CC(=O)Cl
Reactant: NCCc1c(C(F)(F)F)nn2ccc3c(c12)CCO3
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(=O)NCCc1c(C(F)(F)F)nn2ccc3c(c12)CCO3
Temperature: 25 °C
Reaction time: 1 h
Yield: 75.9 %

Procedure:
To a solution of 2-[2-(trifluoromethyl)-8,9-dihydrofuro[3,2-c]pyrazolo[1,5-a]pyridin-1-yl]ethanamine (70 mg, 0.26 mmol) and triethylamine (72 μL, 0.52 mmol) in tetrahydrofuran (3 mL) was added acetyl chloride (22 μL, 0.31 mmol) under ice-cooling, and the mixture was stirred at room temperature for 1 hr. The reaction solution was diluted with saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=70/30→100/0) and recrystallization (ethyl acetate/hexane) to give the title compound (61.8 mg, yield 76%).