Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: F[C:2]1[CH:7]=[C:6]([C:8]2[C:9]([O:16][CH3:17])=[N:10][C:11]([CH3:15])=[CH:12][C:13]=2[CH3:14])[CH:5]=[CH:4][C:3]=1[C:18]1[N:22]([CH:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[N:21]=[CH:20][C:19]=1[C:29]([NH2:31])=[O:30].O>CN1C(=O)CCC1>[CH3:17][O:16][C:9]1[C:8]([C:6]2[CH:7]=[CH:2][C:3]3[C:18]4[N:22]([CH:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[N:21]=[CH:20][C:19]=4[C:29](=[O:30])[NH:31][C:4]=3[CH:5]=2)=[C:13]([CH3:14])[CH:12]=[C:11]([CH3:15])[N:10]=1
Reactant: COc1nc(C)cc(C)c1-c1ccc(-c2c(C(N)=O)cnn2C2CCOCC2)c(F)c1
Solvent: CN1CCCC1=O
Solvent: O
Product: COc1nc(C)cc(C)c1-c1ccc2c(c1)[nH]c(=O)c1cnn(C3CCOCC3)c12
Temperature: 90 °C
Reaction time: 0.5 h
Yield: 60.2 %

Procedure:
KTB (655 mg) was added to a solution of 5-[2-fluoro-4-(2-methoxy-4,6-dimethylpyridin-3-yl)phenyl]-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxamide (1.52 g) in NMP (15 mL), and the mixture was stirred at 90° C. for 30 minutes. KTB (40 mg) was added to the reaction mixture, and the mixture was stirred at 90° C. for 30 minutes. Further, KTB (40 mg) was added to the reaction mixture, and the mixture was stirred at 90° C. for 30 minutes. The reaction mixture was cooled to room temperature. Water (3 mL) was added to the reaction mixture. The solid was precipitated. After stirring for one hour directly, the precipitated solid was collected by filtration. The residue was washed with water (1 mL). The resulting solid was suspended in 1-propanol/water (9/1) (2 mL) and dissolved by heating under reflux. The solution was cooled to room temperature over one hour. The precipitated solid was collected by filtration. The resulting solid was dried under reduced pressure at 50° C. to give the title compound (872 mg). The instrumental data were identical to those of the title compound synthesized in Example 4.
Reaction SMILES: [CH2:1]([OH:3])[CH3:2].[H-].[Na+].Cl[C:7]1[CH:8]=[CH:9][C:10]2[CH2:11][N:12]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13][CH2:14][O:15][C:16]=2[N:17]=1.O>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:3][C:7]1[CH:8]=[CH:9][C:10]2[CH2:11][N:12]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13][CH2:14][O:15][C:16]=2[N:17]=1)[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCOc2nc(Cl)ccc2C1
Reactant: CCO
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: [H-]
Solvent: Cc1ccccc1
Solvent: O
Product: CCOc1ccc2c(n1)OCCN(C(=O)OC(C)(C)C)C2
Temperature: 70 °C
Reaction time: 0.25 h
Yield: 30 %

Procedure:
To a solution of ethanol (0.10 mL) in toluene (4 mL) was added sodium hydride (0.14 g), and the resulting mixture was stirred at 70° C. for 15 min under a nitrogen atmosphere. A mixture of tert-butyl 8-chloro-2,3-dihydropyrido[3,2-f][1,4]oxazepine-4(5H)-carboxylate (0.50 g), BINAP (0.033 g), Pd2(dba)3 (0.024 g) and toluene (4 mL) was added, and the resulting mixture was stirred at 100° C. for 2 hr under an argon atmosphere. The reaction solution was poured into water, and the resulting product was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (solvent gradient; 0→40% ethyl acetate/hexane) to give tert-butyl 8-ethoxy-2,3-dihydropyrido[3,2-f][1,4]oxazepine-4(5H)-carboxylate (0.16 g, 30%) as a colorless oil.
Reaction SMILES: [CH:1](/[CH:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][CH2:5]1)=[CH:2]\[CH3:3]>CO>[CH2:1]([CH:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][CH2:5]1)[CH2:2][CH3:3]
Reactant: C/C=C/C1CCc2ccccc21
Solvent: CO
Product: CCCC1CCc2ccccc21

Procedure:
A MeOH (6 mL) solution of the trans-propenylindane acid from 144b (11.8 mg, 0.18 mmol) was hydrogenated under 50 psi H2 for 1 h to give propylindane acid. MS Found: (M+Na)+=317.
Reaction SMILES: [CH:1](NC(C)C)(C)C.[Li]CCCC.[CH3:13][C:14]1([C:26]([O-:28])=[O:27])[CH2:18][CH2:17][CH2:16][N:15]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].C([N-]C(C)C)(C)C.[Li+].CI>C1COCC1>[CH3:13][C:14]1([C:26]([O:28][CH3:1])=[O:27])[CH2:18][CH2:17][CH2:16][N:15]1[C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20]
Reactant: CC(C)(C)OC(=O)N1CCCC1(C)C(=O)[O-]
Reactant: CC(C)NC(C)C
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CI
Product: COC(=O)C1(C)CCCN1C(=O)OC(C)(C)C
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 63.2 %

Procedure:
To a solution of diisopropylamine (1.59 g, 15.7 mmol) in THF (10 mL) was added n-BuLi (7.54 mL, 2.5 M in n-hexane) dropwise at 0° C. Then the solution was stirred at the same temperature for 30 min. 1-tert-butyl 2-methylpyrrolidine-1,2-dicarboxylate (3.0 g, 13.0 mmol) was dissolved in 50 mL THF and cooled to −78° C. To the solution was added prepared lithium diisopropylamide (15.7 mmol) dropwise. After the reaction mixture was kept at −78° C. for 3 h, MeI (1.6 mL, 25.7 mmol) was added. The mixture was allowed to warm to 0° C. and stirred for 2 h. Then the reaction mixture was quenched with water (30 mL) and extracted with EtOAc (3×50 mL). The combined organic layers were dried over Na2SO4 and concentrated under vacuum to give 2 g of the crude product. MS (ESI): 244 (MH+).
Reaction SMILES: [Cl:1][C:2]1[C:3](C(OCC)=O)=[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][N:5]2[CH:10]=1.C(=O)([O-])O.[Na+]>O.S(=O)(=O)(O)O>[Cl:1][C:2]1[CH:3]=[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][N:5]2[CH:10]=1
Reactant: CCOC(=O)c1c(Cl)cn2ccccc12
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Product: Clc1cc2ccccn2c1

Procedure:
To a suspension of 0.20 g of ethyl 2-chloropyrolo [1,2-a]pyridin-1-carboxylate in 10 ml of water, 1.5 ml of sulfuric acid is added and refluxed for 3 hours. After cooling, the mixture is neutralized with an aqueous saturated sodium hydrogen carbonate solution and extracted with ethyl acetate. The extract is dried on anhydrous sodium sulfate and distilled to remove ethyl acetate. The residue is purified by silica gel chromatography (eluent: ethyl acetate-hexane) to give crystals of the title compound
Reaction SMILES: Cl.Cl.[NH2:3][CH2:4][C:5]1[NH:13][C:12]2[C:11]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=4)=[C:17]([Cl:30])[CH:16]=3)=[N:10][CH:9]=[N:8][C:7]=2[CH:6]=1.Cl.[CH3:32][N:33]([CH3:40])[CH2:34]/[CH:35]=[CH:36]/[C:37](O)=[O:38].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1>CN(C)C=O.O.C(N(CC)CC)C>[Cl:30][C:17]1[CH:16]=[C:15]([NH:14][C:11]2[C:12]3[NH:13][C:5]([CH2:4][NH:3][C:37](=[O:38])/[CH:36]=[CH:35]/[CH2:34][N:33]([CH3:40])[CH3:32])=[CH:6][C:7]=3[N:8]=[CH:9][N:10]=2)[CH:20]=[CH:19][C:18]=1[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=1
Reactant: NCc1cc2ncnc(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)c2[nH]1
Reactant: CN(C)C/C=C/C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: O
Solvent: CN(C)C=O
Product: CN(C)C/C=C/C(=O)NCc1cc2ncnc(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)c2[nH]1
Yield: 64.3 %

Procedure:
A solution of 6-(aminomethyl)-N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidin-4-amine dihydrochloride (150 mg), (2E)-4-(dimethylamino)but-2-enoic acid hydrochloride (105 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (244 mg), 1-hydroxybenzotriazole monohydrate (196 mg) and triethylamine (0.30 mL) in N,N-dimethylformamide (5 mL) was stirred at room temperature for 2 days. Water was added to the reaction system and the mixture was extracted with ethyl acetate. The organic layer washed with saturated brine, dried over magnesium sulfate and concentrated under reduced pressure, and the residue was separated and purified by column chromatography (basic silica gel, eluent, methanol:ethyl acetate=1:9→1:4) to give the title compound (104.2 mg) as pale-brown powder crystals.
Reaction SMILES: [H][H].[CH3:3][CH:4]([CH3:25])[CH2:5][O:6][C:7](=[O:24])[NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH2:16][CH2:17][S:18](=[O:22])(=[O:21])[CH2:19][CH:20]=2)=[C:11]([F:23])[CH:10]=1>>[CH3:3][CH:4]([CH3:25])[CH2:5][O:6][C:7](=[O:24])[NH:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]2[CH2:20][CH2:19][S:18](=[O:22])(=[O:21])[CH2:17][CH2:16]2)=[C:11]([F:23])[CH:10]=1
Reactant: [H][H]
Reactant: CC(C)COC(=O)Nc1ccc(C2=CCS(=O)(=O)CC2)c(F)c1
Product: CC(C)COC(=O)Nc1ccc(C2CCS(=O)(=O)CC2)c(F)c1

Procedure:
Following the general procedure of EXAMPLE 4 (and using knowledge known to those skilled in the art regarding reduction of unsaturated cyclic double bonds with hydrogen) and making non-critical variations but starting with 2-methylpropyl[4-(3,6-dihydro-1,1-ioxido-2H-thiopyran-4-yl)-3-fluorophenyl]carbamate (XV, EXAMPLE 12), the title compound is obtained, TLC Rf=0.73 (methanol/methylene chloride, 5/95); mp=181-182°;NMR (CDCl3) δ 7.36, 7.13, 7.01, 6.87, 3.95, 3.33-3.05, 2.42-2.33, 2.18, 2.01-1.94 and 0.96; CMR (CDCl3) δ 159.5, 153.5, 138.4, 127.3, 124.3, 114.2, 106.2, 71.5, 51.5, 34.4, 30.1, 27.9 and 18.9; MS (CI, NH3) m/z (relative intensity) 361 (100), 343 (30), 344 (10), 251(10), 243 (7) and 151(22).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH:9]([C:14]2[CH:15]=[C:16]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=3)[CH:17]=[CH:18][CH:19]=2)[CH2:10][CH2:11][CH2:12][CH3:13])[CH:5]=[CH:4][C:3]=1[O:30][CH2:31][C:32]([O:34]CC)=[O:33].O.[OH-].[Na+].Cl>C1COCC1>[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH:9]([C:14]2[CH:15]=[C:16]([C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:27])([F:28])[F:29])=[CH:22][CH:21]=3)[CH:17]=[CH:18][CH:19]=2)[CH2:10][CH2:11][CH2:12][CH3:13])[CH:5]=[CH:4][C:3]=1[O:30][CH2:31][C:32]([OH:34])=[O:33]
Reactant: CCCCC(Oc1ccc(OCC(=O)OCC)c(C)c1)c1cccc(-c2ccc(C(F)(F)F)cc2)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CCCCC(Oc1ccc(OCC(=O)O)c(C)c1)c1cccc(-c2ccc(C(F)(F)F)cc2)c1
Temperature: 25 °C
Yield: 98.3 %

Procedure:
Ethyl {[2-methyl-4-({1-[4′-(trifluoromethyl)-3-biphenylyl]pentyl}oxy)phenyl]oxy}acetate (138 mg, 0.28 mmol) was dissolved in THF (1.5 mL), water (0.5 mL) and aqueous NaOH (2M, 0.52 mL, 1.04 mmol) and the mixture stirred at 70° C. for 2 hours, cooled to rt and acidified to pH4 with aqueous hydrochloric acid (2M). The mixture was then partitioned between EtOAc and water, the layers separated and the organic layer washed with brine, dried (Na2SO4) and concentrated to give the title compound as a colourless gum (130 mg).
Reaction SMILES: [CH:1]([C:4]([C:22]1[CH:27]=[C:26]([O:28][CH3:29])[C:25]([O:30][CH3:31])=[C:24]([O:32][CH3:33])[CH:23]=1)([CH2:7][CH2:8][NH:9][CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[O:20][CH3:21])[C:5]#[N:6])([CH3:3])[CH3:2].C=O.[CH:36](O)=O.C(=O)([O-])[O-].[K+].[K+]>O>[CH:1]([C:4]([C:22]1[CH:27]=[C:26]([O:28][CH3:29])[C:25]([O:30][CH3:31])=[C:24]([O:32][CH3:33])[CH:23]=1)([CH2:7][CH2:8][N:9]([CH2:10][CH2:11][CH2:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[O:20][CH3:21])[CH3:36])[C:5]#[N:6])([CH3:3])[CH3:2]
Reactant: COc1ccccc1OCCCNCCC(C#N)(c1cc(OC)c(OC)c(OC)c1)C(C)C
Reactant: O=CO
Agent: C=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: COc1ccccc1OCCCN(C)CCC(C#N)(c1cc(OC)c(OC)c(OC)c1)C(C)C

Procedure:
A mixture of 0.39 g of alpha-isopropyl-alpha-[2-[N-[3-(2-methoxyphenoxy)propyl]amino]ethyl]-3,4,5-trimethoxyphenylacetonitrile, 1 ml of 37% formalin, and 1 ml of 90% formic acid was refluxed for 1 hour. After cooling, to the mixture were added water and potassium carbonate to make it alkaline. The solution was extracted with chloroform. The extract was washed with water, dried, and evaporated to give 0.23 g of desired compound as a yellow oil.
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@H:14]2[CH2:15][O:16][C@H:12]([O:13]2)[C@H:11]([CH3:17])[C@H:10]1O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].C(=S)=S.CI.C([SnH](CCCC)CCCC)CCC>C1COCC1.C1(C)C=CC=CC=1.CCOCC>[CH2:1]([O:8][C@@H:9]1[C@H:14]2[CH2:15][O:16][C@H:12]([O:13]2)[C@H:11]([CH3:17])[CH2:10]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C[C@H]1[C@@H]2OC[C@@H](O2)[C@@H](OCc2ccccc2)[C@@H]1O
Agent: CCCC[SnH](CCCC)CCCC
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CI
Solvent: S=C=S
Product: C[C@@H]1C[C@H](OCc2ccccc2)[C@H]2CO[C@@H]1O2
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of 1,6-anhydro-4-O-benzyl-2-deoxy-2-C-methyl-β-D-glucopyranose (Tetrahedron Lett. 22 (1981) 4315-4318) (0.280 g) in dry THF (10 ml) was stirred while sodium hydride (1.2 eq) was added slowly. When effervescence had ceased, a large excess (>10 eq) of carbon disulphide was added and the solution was stirred at room temperature for 0.5 h. Methyl iodide (5 eq) was then added and the solution was stirred a further 0.5 h at room temperature. Ether (50 ml) was added and the mixture was washed with water. The aqueous washings were back extracted with ether and the combined ether extracts were washed with saturated aqueous sodium chloride and then dried (MgSO4) and concentrated to a light yellow syrup. This was dissolved in toluene (25 ml) and heated under reflux in a nitrogen atmosphere while tributyltin hydride (1.05 eq) in toluene (2 ml) was added slowly over 3 h. The solution was then heated under reflux for a further 16 h before being concentrated again to dryness.
Reaction SMILES: O=[C:2]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:3][CH2:4][NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9].Cl.[F:20][C:21]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:22]=1[C:23](=[S:26])[NH:24][NH2:25].C(N(CC)CC)C>CCO>[F:20][C:21]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:22]=1[C:23]1[S:26][C:2]([CH2:3][CH2:4][NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9])([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[NH:25][N:24]=1
Reactant: NNC(=S)c1cc(F)ccc1F
Reactant: CC(C)(C)OC(=O)NCCC(=O)c1ccccc1
Agent: Cl
Solvent: CCO
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)NCCC1(c2ccccc2)NN=C(c2cc(F)ccc2F)S1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a cooled (0° C.) solution of tert-butyl 3-oxo-3-phenylpropylcarbamate (0.68 g, 2.73 mmol) and 2,5-difluorobenzothiohydrazide hydrochloride (0.613 g, 2.73 mmol) in EtOH (27 mL) was added triethylamine (0.57 mL, 4.09 mmol). After stirring at room temperature for 8 hours, the mixture was heated to 65° C. for 16 hours. The mixture was concentrated under reduced pressure and the residue was dissolved in ethyl acetate (100 mL). The solution was washed with water and brine (40 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was chromatographed (30% ethyl acetate in hexanes) to provide the crude product as a brown syrup which was used directly in the next step.
Reaction SMILES: Cl[Si](Cl)(C)C.[CH2:6]([O:8][C:9](=[O:23])[CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([S:18](Cl)(=O)=O)=[CH:14][C:13]=1[CH3:22])[CH3:7].CN1CCN(C)C1=O.O>ClC(Cl)C.ClCCCl.[Zn]>[CH2:6]([O:8][C:9](=[O:23])[CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([SH:18])=[CH:14][C:13]=1[CH3:22])[CH3:7]
Reactant: CCOC(=O)COc1ccc(S(=O)(=O)Cl)cc1C
Agent: C[Si](C)(Cl)Cl
Agent: [Zn]
Solvent: ClCCCl
Solvent: O
Solvent: CN1CCN(C)C1=O
Product: CCOC(=O)COc1ccc(S)cc1C
Temperature: 52 °C

Procedure:
This compound can also be made by the following procedure: To a stirred suspension of Zn powder (10 μm, 78.16 g, 1.2 mol) and dichlorodimethyl silane (154.30 g, 145.02 mL, 1.2 mol) in 500 mL of dichloroethane is added a solution of (4-chlorosulfonyl-2-methyl-phenoxy)-acetic acid ethyl ester (100 g, 0.34 mol) and 1,3-dimethylimidazolidin-2-one (116.98 g, 112.05 mL, 1.02 mol) in 1 L of DCE. Addition is at a rate so as to maintain the internal temperature at ˜52° C., cooling with chilled water as necessary. After addition is complete, the mixture is heated at 75° C. for 1 hour. It is then cooled to room temperature, filtered and concentrated iv. Add MTBE, washed twice with saturated LiCl solution concentrate iv again. Take up the residue in CH3CN, ish with hexane (4×) and concentrate iv to yield a biphasic mixture. Let stand in a separatory funnel and separate layers, keeping the bottom layer for product. Filtration through a plug of silica gel (1 Kg, 25% EtOAc/hexane) and subsequent concentration yielded 61 g (79%) of a clear, colorless oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:32]=[CH:33][C:34]=1[O:35][CH3:36])[CH2:6][CH:7]1[C:13]2[CH:14]=[C:15]([O:20][CH3:21])[C:16]([O:18][CH3:19])=[CH:17][C:12]=2[CH2:11][CH2:10][CH2:9][N:8]1[CH:22]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:23](O)=[O:24].[F:37][C:38]([F:42])([F:41])[CH2:39][NH2:40]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:32]=[CH:33][C:34]=1[O:35][CH3:36])[CH2:6][CH:7]1[C:13]2[CH:14]=[C:15]([O:20][CH3:21])[C:16]([O:18][CH3:19])=[CH:17][C:12]=2[CH2:11][CH2:10][CH2:9][N:8]1[CH:22]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:23]([NH:40][CH2:39][C:38]([F:42])([F:41])[F:37])=[O:24]
Reactant: NCC(F)(F)F
Reactant: COc1ccc(CC2c3cc(OC)c(OC)cc3CCCN2C(C(=O)O)c2ccccc2)cc1OC
Product: COc1ccc(CC2c3cc(OC)c(OC)cc3CCCN2C(C(=O)NCC(F)(F)F)c2ccccc2)cc1OC

Procedure:
prepared by reaction of [1-(3,4-dimethoxy-benzyl)-7,8-dimethoxy-1,3,4,5-tetrahydro-benzo[c]azepin-2-yl]-phenyl-acetic acid with 2,2,2-trifluoroethylamine.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)([O-:3])=O.C([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[N+:18]([O-])=O)C>>[N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)(=[N:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:12]=1)[O-:3]
Reactant: CCc1ccccc1[N+](=O)[O-]
Reactant: O=[N+]([O-])c1ccccc1
Product: [O-][N+](=Nc1ccccc1)c1ccccc1

Procedure:
The reduction reaction was carried out in the same manner as set forth in Example 6 except for using a mixture of 1.0 mmol of nitrobenzene and 1.0 mmol of o-ethyl nitrobenzene instead of using nitrobenzene alone, and using 16.5 mg (the amount required for swelling of the reactant, i.e., the mixture, in 100%) of Polymer supported reagent-2, and thereby an azoxybenzene derivative of a symmetrical structure and an azoxybenzene derivative of an asymmetrical structure were obtained as a main product, respectively. Besides, a small amount of an azobenzene derivative of a symmetrical structure was also synthesized.
Reaction SMILES: [OH:1][C:2]1[C:6]([CH:7]([CH3:9])[CH3:8])=[C:5]([C:10]2[S:11][CH:12]=[CH:13][CH:14]=2)[O:4][N:3]=1.[C:15]([O:19][C:20]([NH:22][CH2:23][CH2:24]O)=[O:21])([CH3:18])([CH3:17])[CH3:16]>>[C:15]([O:19][C:20]([NH:22][CH2:23][CH2:24][O:1][C:2]1[C:6]([CH:7]([CH3:9])[CH3:8])=[C:5]([C:10]2[S:11][CH:12]=[CH:13][CH:14]=2)[O:4][N:3]=1)=[O:21])([CH3:18])([CH3:17])[CH3:16]
Reactant: CC(C)c1c(O)noc1-c1cccs1
Reactant: CC(C)(C)OC(=O)NCCO
Product: CC(C)c1c(OCCNC(=O)OC(C)(C)C)noc1-c1cccs1
Yield: 85.5 %

Procedure:
3-Hydroxy-4-isopropyl-5-(2-thienyl)isoxazole (209 mg) and 2-(N-tert-butoxycarbonylamino)ethanol (193 mg) were subjected to reaction and post-treatment in a similar manner to that described in Example 1(a) to obtain the title compound (301 mg, 86%) as colorless crystals.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]1[CH2:12][CH2:11][N:10]([CH2:13][C:14](OCC)=[O:15])[CH2:9][CH2:8]1.CC(C[AlH]CC(C)C)C>C1(C)C=CC=CC=1>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]1[CH2:8][CH2:9][N:10]([CH2:13][CH:14]=[O:15])[CH2:11][CH2:12]1
Reactant: CCOC(=O)CN1CCC(c2ccccn2)CC1
Agent: CC(C)C[AlH]CC(C)C
Solvent: Cc1ccccc1
Product: O=CCN1CCC(c2ccccn2)CC1
Temperature: -78 °C
Reaction time: 3 h
Yield: 81.1 %

Procedure:
To a stirred solution of ethyl 2-(4-(pyridin-2-yl)piperidin-1-yl)acetate (600 mg, 2.416 mmol) in toluene (20 mL) was added DIBAL-H (3.62 mL, 3.62 mmol, 1M in toluene) at −78° C. and stirred for 3 h at −78° C. The reaction mixture was quenched with methanol (0.5 mL) and then brine (10 mL) was added. The reaction mixture was filtered through celite and the filtrate was dried over sodium sulphate and concentrated under reduced pressure to afford 2-(4-(pyridin-2-yl)piperidin-1-yl)acetaldehyde (400 mg, 77% yield) as pale yellow solid. LCMS (ES) m/e 205.16 (M+H)+.
Reaction SMILES: Cl[C:2]1[C:3]2[C:10]([I:11])=[CH:9][N:8]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=3)[C:4]=2[N:5]=[CH:6][N:7]=1.[NH3:21].O>O1CCOCC1>[I:11][C:10]1[C:3]2[C:2]([NH2:21])=[N:7][CH:6]=[N:5][C:4]=2[N:8]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[CH:9]=1
Reactant: N
Reactant: O=[N+]([O-])c1cccc(-n2cc(I)c3c(Cl)ncnc32)c1
Solvent: C1COCCO1
Solvent: O
Product: Nc1ncnc2c1c(I)cn2-c1cccc([N+](=O)[O-])c1
Yield: 97 %

Procedure:
A solution of 4-chloro-5-iodo-7-(3-nitrophenyl)-7H-pyrrolo[2,3-d]pyrimidine (500 mg, 1.25 mmol), NH3.H2O (3 mL) and dioxane (6 mL) in a sealed tube was heated to 120° C. in a microwave reactor for 40 min. The yellow precipitate was collected by filtration to provide 5-iodo-7-(3-nitrophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (69) (460 mg, 97%). LC-MS (ESI): m/z (M+1) 382.
Reaction SMILES: [F:1][CH:2]1[CH:7]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:6][CH2:5][NH:4][CH2:3]1.[C:14]([O:18][C:19]([N:21]([CH2:23][CH:24]=O)[CH3:22])=[O:20])([CH3:17])([CH3:16])[CH3:15].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(O)(=O)C>C1COCC1>[F:1][CH:2]1[CH:7]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:6][CH2:5][N:4]([CH2:24][CH2:23][N:21]([C:19]([O:18][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:20])[CH3:22])[CH2:3]1
Reactant: CCOC(=O)CC1CCNCC1F
Reactant: CN(CC=O)C(=O)OC(C)(C)C
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: CCOC(=O)CC1CCN(CCN(C)C(=O)OC(C)(C)C)CC1F
Reaction time: 24 h
Yield: 55.8 %

Procedure:
To a solution of ethyl 3-fluoro-4-piperidinylacetate (230 mg, 1.22 mmol) and 2-(N-tert-butoxy carbonyl-N-methylamino)acetaldehyde (211 mg, 1.22 mmol) in THF (5 mL) was added NaBH(OAc)3 (386 mg, 1.82 mmol) and acetic acid (70.0 mL, 1.22 mmol) at room temperature After being sired for 24 hr, the reaction mixture was quenched by the addition of sat. NaHCO3 solution and extracted with EtOAc. The extracts were washed with brine, dried over Na2CO3, and concentrated to dryness. Chromatography of the residue with CHCl3—MeOH (6:1, v/v) as eluent gave ethyl 3-fluoro-1-[2-(N-tert-butoxycarbonyl-N-methylamino)ethyl]-4-piperidinylacetate (236 mg, 56%) as a reddish oil. 1H-NMR (CDCl3) δ1.25 (t, J=7.1 Hz, 3H), 1.45 (s, 9H), 1.53 1.79 (m, 2H), 1.90-2.09 (m, 2H), 2.15 (dd, J=16.4, 7.1 Hz, 1H), 2.45-2.58 (m, 2H), 2.87 (s, 3H), 2.90-2.99 (m, 2H), 3.20 (m, 1H), 3.24-3.45 (m, 2H), 4.14 (q, J=7.1 Hz, 2H), 4.61, 4.73 (each broad s, 1H); ESI-MS m/z 347.
Reaction SMILES: [C:1]([CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:4])[CH2:2][CH3:3].[H-].[Na+].Br[CH2:14][C:15]([C:17]1[CH:22]=[CH:21][C:20](C)=[CH:19][N:18]=1)=[O:16].[Cl-].[NH4+]>C1COCC1>[CH2:9]([O:8][C:6](=[O:7])[CH:5]([CH2:14][C:15](=[O:16])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1)[C:1](=[O:4])[CH2:2][CH3:3])[CH3:10]
Reactant: CCOC(=O)CC(=O)CC
Reactant: Cc1ccc(C(=O)CBr)nc1
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CCOC(=O)C(CC(=O)c1ccccn1)C(=O)CC
Reaction time: 0.5 h
Yield: 79.9 %

Procedure:
Ethyl propionylacetate 18 (5 g, 34.7 mmol) was added slowly to a stirred suspension of sodium hydride (60% dispersion in mineral oil, 1.665 g, 41.65 mmol, 1.2 equiv) in THF (50 ml) at 0° C. and the mixture was stirred for 30 min. Compound 19b (8.092 g, 38.17 mmol, 1.1 equiv) in THF (5 ml) was added dropwise and the reaction mixture was stirred at room temperature for 16 h. Saturated aqueous ammonium chloride (30 ml) was added and the mixture was subsequently extracted with diethyl ether (3×30 ml). The combined organic layers were washed with brine and dried over anhydrous sodium sulfate. The solvent was removed in vacuo to give a dark yellow oil that was purified by flash column chromatography (10% EtOAc/hexanes) to give the diketoester 20b (7.3 g, 76%) as a yellow oil: TLC Rf=0.33 (silica gel, 20% EtOAc/hexane); 1H NMR (400 MHz, CDCl3) δ 8.50 (broad s, 1H), 7.89 (d, J=8.0 Hz, 1H), 7.66 (dd, J=1.6 Hz, 8.0 Hz, 1H), 4.20 (q, J=7.2 Hz, 2H), 4.15 (dd, J=6.0 Hz, 8.0 Hz, 1H), 3.92 (dd, J=8.4 Hz, 18.8 Hz, 1H), 3.74 (dd, J=6.0 Hz, 18.8 Hz, 1H), 2.85-2.66 (m, 2H), 2.41 (s, 3H), 1.27 (t, J=7.2 Hz, 3H), 1.10 (t, J=7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 205.5, 198.9, 169.6, 150.7, 149.8, 138.1, 137.3, 121.7, 61.8, 53.5, 37.1, 36.2, 18.9, 14.2, 7.9; HRMS calcd for C15H19NO4+Na+ 300.1212; found 300.1200 [M+Na+].