Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N([O-])=O.[Na+].N[C:6]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[Cl:19])[C:11](=[O:12])[CH:10]=[CH:9][CH2:8][CH2:7]1.[OH-:20].[Na+]>O.Cl>[Cl:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[C:6]1([OH:20])[C:11](=[O:12])[CH:10]=[CH:9][CH2:8][CH2:7]1
Reactant: [OH-]
Reactant: NC1(c2ccccc2Cl)CCC=CC1=O
Agent: Cl
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Product: O=C1C=CCCC1(O)c1ccccc1Cl
Temperature: 25 °C
Yield: 28 %

Procedure:
Sodium nitrite (16 mg, 0.23 mmol) in water (0.5 ml) was added to a stirred solution of 6-amino-6-(2-chlorophenyl)-2-cyclohexen-1-one (50 mg, 0.23 mmol) in 1/3N HCl (1.5 ml) at 0° C. After 1 h the reaction was neutralized with sodium hydroxide and allowed to warm to room temperature for 30 minutes. The reaction was partitioned between saturated bicarbonate and ethyl acetate, the organic phase was washed with brine, dried (Na2SO4), and the solvent removed by evaporation. Purification was achieved by preparative thin layer chromatography on silica gel eluting with 3:2 ethyl acetate/hexane. Isolation of the UV active band at Rf 0.7 gave 6-(2-Chlorophenyl)-6-hydroxy-2-cyclohexen-1-one (14.2 mg, 28%).
Reaction SMILES: C[O:2][C:3]([CH:5]1[CH2:10][CH:9]([C:11]([O:13]C)=[O:12])[CH2:8][N:7]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:6]1)=[O:4].C([O-])([O-])=O.[K+].[K+]>CO.O>[C:18]([O:17][C:15]([N:7]1[CH2:6][CH:5]([C:3]([OH:4])=[O:2])[CH2:10][CH:9]([C:11]([OH:13])=[O:12])[CH2:8]1)=[O:16])([CH3:21])([CH3:19])[CH3:20]
Reactant: COC(=O)C1CC(C(=O)OC)CN(C(=O)OC(C)(C)C)C1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CO
Product: CC(C)(C)OC(=O)N1CC(C(=O)O)CC(C(=O)O)C1

Procedure:
To a solution of piperidine-1,3,5-tricarboxylic acid 1-tert-butyl ester 3,5-dimethyl ester (6.8 g, 22.5 mmol) in MeOH/water (4:1, 120 mL) is added K2CO3 (9.4 g, 68 mmol).
Reaction SMILES: [CH2:1]([N:3]1[C:8]2[CH:9]=[C:10]([CH3:13])[CH:11]=[N:12][C:7]=2[S:6](=[O:15])(=[O:14])[NH:5][CH2:4]1)[CH3:2].[OH-].[Na+].[C:18]1(C)C=CC(S(OC)(=O)=O)=CC=1>C(#N)C>[CH3:18][N:5]1[CH2:4][N:3]([CH2:1][CH3:2])[C:8]2[CH:9]=[C:10]([CH3:13])[CH:11]=[N:12][C:7]=2[S:6]1(=[O:14])=[O:15]
Reactant: COS(=O)(=O)c1ccc(C)cc1
Reactant: CCN1CNS(=O)(=O)c2ncc(C)cc21
Agent: [Na+]
Agent: [OH-]
Solvent: CC#N
Product: CCN1CN(C)S(=O)(=O)c2ncc(C)cc21

Procedure:
A solution of 0.2 g of 4-ethyl-6-methyl-2,3- dihydro-4H-pyrido[3,2-e][1,2,4]thiadiazine 1,1-dioxide (Example 79) in 10 cm3 of acetonitrile is treated with 2 equivalents of NaOH and then brought to reflux for 15 minutes with stirring. The mixture is treated with 0.18 g of methyl p-toluenesulfonate and stirred for 2 hours at ambient temperature. The solvent is then removed under reduced pressure and the residue is taken up in 5 cm3 of water. The precipitate is collected on a filter, washed with water and dried. It is purified by chromatography on a silica column (1/1 chloroform/diethyl ether).
Reaction SMILES: [C:1]([NH:11][C:12]([CH3:17])([CH3:16])[C:13]([OH:15])=[O:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].CN(C1C=CC=CN=1)C.[CH3:27][C:28]1([CH3:36])[CH2:32][CH2:31][C:30]([CH3:34])([CH3:33])[CH:29]1O>ClCCCl.C(Cl)Cl>[CH3:27][C:28]1([CH3:36])[CH2:32][CH2:31][C:30]([CH3:34])([CH3:33])[CH:29]1[O:14][C:13](=[O:15])[C:12]([NH:11][C:1]([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2])([CH3:17])[CH3:16]
Reactant: CC1(C)CCC(C)(C)C1O
Reactant: CC(C)(NC(=O)OCc1ccccc1)C(=O)O
Agent: CN(C)c1ccccn1
Solvent: ClCCCl
Solvent: ClCCl
Product: CC(C)(NC(=O)OCc1ccccc1)C(=O)OC1C(C)(C)CCC1(C)C
Reaction time: 96 h

Procedure:
To a stirred solution of 2 g (0.008 mol) of N-Cbz-2-aminoisobutyric acid in dry Cl(CH2)2Cl containing 1.9 g dicyclohexylcarbodiimide and 0.1 g dimethylaminopyridine (DMAP), all at 0° C., is added, via an addition funnel, 1.3 g of 2,2,5,5-tetramethylcyclopentanol dissolved in CH2Cl2. After stirring for 4 days, the mixture is filtered, and the filtrate is washed with 5% HCl (1×50 ml), saturated NaHCO3 (1×50 ml), and water (1×50 ml). The organic layer is separated, dried over MgSO4 and evaporated to yield N-Cbz-2-aminoisobutyric acid 2,2,5,5-tetramethylcyclopentyl ester.
Reaction SMILES: Br[C:2]1[C:3]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)=[N:4][N:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=12.[F:18][C:19]1[CH:24]=[C:23](B(O)O)[CH:22]=[CH:21][N:20]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C:3]2[C:2]([C:23]3[CH:22]=[CH:21][N:20]=[C:19]([F:18])[CH:24]=3)=[C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][N:5]3[N:4]=2)=[CH:12][CH:13]=1
Reactant: Fc1ccc(-c2nn3ccccc3c2Br)cc1
Reactant: OB(O)c1ccnc(F)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Fc1ccc(-c2nn3ccccc3c2-c2ccnc(F)c2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 27.3 %

Procedure:
A solution of 3-bromo-2-(4-fluorophenyl)-pyrazolo[1,5-a]pyridine (Example le. 1.30 g, 4.5 mmol), 2-fluoro-4-pyridinylboronic acid (Example 46a. 694 mg, 4.9 mmol) and dichlorobis(triphenylphosphine)palladium (316 mg, 0.45 mmol) in DMF (100 mL) was placed in a pre-heated oil bath at 110° C. To the reaction was added, in a dropwise manner, 2M aqueous sodium carbonate (4.5 mL, 9.0 mmol). The reaction was allowed to stir for 2 h and then cooled to room temperature and filtered through a pad of Celite. The Celite pad was washed with ethyl acetate and the filtrate was concentrated to dryness at 50° C. under vacuum. The residue was partitioned between ethyl acetate and water. The layers were separated and the organic phase was dried (MgSO4). The drying agent was removed by filtration and the filtrate was concentrated and purified by silica gel chromatography to yield the title compound (378 mg, 1.23 mmol, 27%). 1H NMR (CDCl3) δ 8.57 (d, 1H, J=6.9 Hz), 8.22(d, 1H, J=5.4 Hz), 7.7(d, 1H, J=9.0 Hz), 7.75(m, 2H), 7.33(m, 1H), 7.14(m, 3H), 6.95(m, 2H). MS (ES+ve) 308 (100, M+).
Reaction SMILES: [C:1]([O:5][C:6](=[O:43])[CH:7]([NH:23][C:24](=[O:42])[CH:25]([NH:30]C(C(N1CCCCCC1)=O)=O)[CH2:26][CH:27]([CH3:29])[CH3:28])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15]CC2C=CC=CC=2)=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].O1[CH2:48][CH2:47][CH2:46][CH2:45]1>[Pd]>[C:1]([O:5][C:6](=[O:43])[CH:7]([NH:23][C:24](=[O:42])[CH:25]([NH:30][C:24]([N:23]1[CH2:45][CH2:46][CH2:47][CH2:48][CH2:6][CH2:7]1)=[O:42])[CH2:26][CH:27]([CH3:28])[CH3:29])[CH2:8][C:9]1[CH:10]=[CH:11][C:12]([OH:15])=[CH:13][CH:14]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: C1CCOC1
Reactant: CC(C)CC(NC(=O)C(=O)N1CCCCCC1)C(=O)NC(Cc1ccc(OCc2ccccc2)cc1)C(=O)OC(C)(C)C
Agent: [Pd]
Product: CC(C)CC(NC(=O)N1CCCCCC1)C(=O)NC(Cc1ccc(O)cc1)C(=O)OC(C)(C)C
Yield: 95 %

Procedure:
A solution of the product from Example 1 (0.20 g, 0.35 mmol) in 16 mL of tetrahydrofuran was hydrogenated at 52 psi over 20% Pd/C for 48 hours. The reaction mixture was filtered through Celite using methanol and concentrated. The resulting foam was purified by chromatography (silica gel, 1:1 heptane/ethyl acetate). The product was isolated as a foam and dried under vacuum to give the title compound (0.16 g, 95%).
Reaction SMILES: F[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[O:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:11]=2[N:12]=1.[CH2:21]([SH:24])[CH2:22][CH3:23].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[CH2:21]([S:24][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:8]1[O:9][C:10]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:11]=2[N:12]=1)[CH2:22][CH3:23]
Reactant: Fc1cnccc1-c1nc2cc(C(F)(F)F)ccc2o1
Reactant: CCCS
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCSc1cnccc1-c1nc2cc(C(F)(F)F)ccc2o1
Temperature: 50 °C
Yield: 89.4 %

Procedure:
A mixture of 0.28 g of 2-(3-fluoropyridin-4-yl)-5-(trifluoromethyl)benzoxazole, 0.15 g of 1-propanethiol, 0.40 g of potassium carbonate and 2 ml of DMF was stirred while heating at 50° C. for one hour. The reaction mixture was cooled to room temperature, and then water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 0.30 g of 2-(3-propylthiopyridin-4-yl)-5-(trifluoromethyl)benzoxazole (hereinafter, referred to as “active compound 42”).
Reaction SMILES: [I:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[S:12][C:13](S(C)=O)=[N:14][N:15]=3)[CH:9]=2)[N:4]([S:19]([C:22]2[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=2)(=[O:21])=[O:20])[CH:3]=1.[CH3:29][O:30][C:31]1[CH:38]=[CH:37][C:34]([CH2:35][NH2:36])=[CH:33][CH:32]=1>O1CCOCC1>[I:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[S:12][C:13]([NH:36][CH2:35][C:34]4[CH:37]=[CH:38][C:31]([O:30][CH3:29])=[CH:32][CH:33]=4)=[N:14][N:15]=3)[CH:9]=2)[N:4]([S:19]([C:22]2[CH:23]=[CH:24][C:25]([CH3:26])=[CH:27][CH:28]=2)(=[O:21])=[O:20])[CH:3]=1
Reactant: Cc1ccc(S(=O)(=O)n2cc(I)c3cc(-c4nnc(S(C)=O)s4)ccc32)cc1
Reactant: COc1ccc(CN)cc1
Solvent: C1COCCO1
Product: COc1ccc(CNc2nnc(-c3ccc4c(c3)c(I)cn4S(=O)(=O)c3ccc(C)cc3)s2)cc1
Temperature: 100 °C
Yield: 52.4 %

Procedure:
To a mixture of 2-(3-iodo-1-tosyl-1H-indol-5-yl)-5-(methylsulfinyl)-1,3,4-thiadiazole (423 mg, 0.757 mmol) in dioxane (3.0 mL) was added 4-methoxybenzylamine (0.294 mL, 2.268 mmol) at RT. The reaction was heated at 100° C. for 24 h. The solvent was removed and the residue was sonicated in MeOH and filtered. The filtrate was concentrated and the residue was purified with flash chromatography (eluting with 0-50% EtOAc in DCM) to give 5-(3-iodo-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-thiadiazol-2-amine (245 mg, 0.397 mmol, 47%). MS (ESI, pos. ion) m/z: 617 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 8.40 (t, J=5.67 Hz, 1H), 8.16 (s, 1H), 8.03 (d, J=8.61 Hz, 1H), 7.94 (d, J=8.41 Hz, 2H), 7.79 (dd, J=8.71, 1.66 Hz, 1H), 7.62 (d, J=1.56 Hz, 1H), 7.42 (d, J=8.41 Hz, 2H), 7.32 (d, J=8.61 Hz, 2H), 6.92 (d, J=8.61 Hz, 2H), 4.46 (d, J=5.67 Hz, 2H), 3.73 (s, 3H), 2.33 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[CH2:11][CH2:12][C:13](=[O:16])[NH:14][N:15]=2)[CH:5]=[C:6]([Cl:9])[C:7]=1[OH:8].C(=O)([O-])[O-].[K+].[K+].[CH2:23](Br)[CH:24]=[CH2:25]>CC(C)=O>[CH2:25]([O:8][C:7]1[C:6]([Cl:9])=[CH:5][C:4]([C:10]2[CH2:11][CH2:12][C:13](=[O:16])[NH:14][N:15]=2)=[CH:3][C:2]=1[Cl:1])[CH:24]=[CH2:23]
Reactant: C=CCBr
Reactant: O=C1CCC(c2cc(Cl)c(O)c(Cl)c2)=NN1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: C=CCOc1c(Cl)cc(C2=NNC(=O)CC2)cc1Cl
Yield: 93 %

Procedure:
In 50 ml. of acetone was mixed 5 g. of 6-(3,5-dichloro-4-hydroxyphenyl)-4,5-dihydro-3(2H)-pyridazinone obtained in Example 5 and 3.3 g. of anhydrous potassium carbonate and to the resulting mixture was added dropwise 2.4 g. of allyl bromide at room temperature while stirring. After completion of the addition, the mixture was heated under reflux for 4 hours. After cooling, the reaction mixture was filtered, the filtrate was concentrated under reduced pressure and the residue was recrystallized from ethanol to give 5.3 g. of the desired product of m.p. 137° C. (Yield 93%).
Reaction SMILES: [CH2:1]([NH:3][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:5]=1[CH3:11])[CH3:2].C([O:14][CH:15]=[C:16]([C:22](OCC)=O)[C:17]([O:19]CC)=[O:18])C>O>[CH2:1]([N:3]1[C:4]2[C:9](=[CH:8][CH:7]=[C:6]([F:10])[C:5]=2[CH3:11])[C:15](=[O:14])[C:16]([C:17]([OH:19])=[O:18])=[CH:22]1)[CH3:2]
Reactant: CCNc1cccc(F)c1C
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Solvent: O
Product: CCn1cc(C(=O)O)c(=O)c2ccc(F)c(C)c21
Temperature: 110 °C
Yield: 68.3 %

Procedure:
Nine grams of N-ethyl-2-methyl-3-fluoroaniline is allowed to react with 15 g of diethyl ethoxymethylenemalonate under heating at 110° C. for 30 minutes. Then, polyphosphoric acid (obtained from 50 g each of phosphoric acid and phosphorus pentaoxide) is added to be subjected to the reaction at 140° C. for 40 minutes. After the reaction is completed, the mixture is poured into 600 g of water and ice to obtain crystals. The crystals are recovered by filtration, and a 10% sodium hydroxide solution is added to the filtrate and the mixture is refluxed for 1 hour. After refluxing, the reaction mixture is treated with activated carbon and adjusted to pH 2 with concentrated hydrochloric acid, whereby there separate out light yellow crystals. Recrystallization from dimethylformamide yields 10 g of 1-ethyl-7-fluoro-8-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid as the white, needle-like crystals. mp. 245°-246° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([CH2:18][CH2:19][C:20]3[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=3)[S:17][C:13]=2[N:12]2[C:27]([CH3:30])=[N:28][N:29]=[C:11]2[CH2:10][N:9]=1.[OH-].[K+].[CH:33](I)([CH3:35])[CH3:34]>COCCO>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([CH2:18][CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH:33]([CH3:35])[CH3:34])=[CH:22][CH:21]=3)[S:17][C:13]=2[N:12]2[C:27]([CH3:30])=[N:28][N:29]=[C:11]2[CH2:10][N:9]=1
Reactant: CC(C)I
Reactant: Cc1nnc2n1-c1sc(CCc3ccc(O)cc3)cc1C(c1ccccc1Cl)=NC2
Agent: [K+]
Agent: [OH-]
Solvent: COCCO
Product: Cc1nnc2n1-c1sc(CCc3ccc(OC(C)C)cc3)cc1C(c1ccccc1Cl)=NC2
Temperature: 90 °C
Reaction time: 4 h
Yield: 54.7 %

Procedure:
A mixture of 0.5 g of thienotriazolodiazepine compound obtained in Example 5, 0.2 g of potassium hydroxide and 0.62 g of isopropyl iodide in 20 ml of 2-methoxyethanol is stirred at 90° C. for 4 hours, and then the resulting mixture is concentrated to dryness. The residue is dissolved in 50 ml of chloroform, washed with water and dried over anhydrous magnesium sulfate. After separating by filtration, the filtrate is concentrated under reduced pressure and the residue is crystallized from isopropyl ether-ethyl acetate to give 0.3 g of 4-(2-chlorophenyl)-2-[2-(4-isopropoxyphenyl)ethyl]-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine as colorless crystals, melting at 121°-124° C.
Reaction SMILES: [OH:1][N:2]=[C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]3([C:32]4[C:23](=[CH:24][C:25]5[O:30][CH2:29][CH2:28][O:27][C:26]=5[CH:31]=4)[O:22][CH2:21]3)[C:13]2=[O:33])[CH:6]=1)[NH2:4].ON=[C:36]([C:38]1C=CC=C(CN2C3C(=CC=CC=3)C3(COC4C=C5C(=CC3=4)CCO5)C2=O)C=1)N>>[CH3:36][C:38]1[O:1][N:2]=[C:3]([C:5]2[CH:6]=[C:7]([CH:8]=[CH:9][CH:10]=2)[CH2:11][N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]3([C:32]4[C:23](=[CH:24][C:25]5[O:30][CH2:29][CH2:28][O:27][C:26]=5[CH:31]=4)[O:22][CH2:21]3)[C:13]2=[O:33])[N:4]=1
Reactant: NC(=NO)c1cccc(CN2C(=O)C3(COc4cc5c(cc43)CCO5)c3ccccc32)c1
Reactant: NC(=NO)c1cccc(CN2C(=O)C3(COc4cc5c(cc43)OCCO5)c3ccccc32)c1
Product: Cc1nc(-c2cccc(CN3C(=O)C4(COc5cc6c(cc54)OCCO6)c4ccccc43)c2)no1

Procedure:
Following the procedure as described in EXAMPLE 11.27 and making non-critical variations using N′-hydroxy-3-[(2′-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-1′(2′H)-yl)methyl]benzenecarboximidamide to replace N′-hydroxy-3-[(2′-oxo-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-1′(2′H)-yl)methyl]benzenecarboximidamide, 1′-[3-(5-methyl-1,2,4-oxadiazol-3-yl)benzyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one was obtained (65%) as a colorless solid: mp 90-95° C. (ethyl acetate/diethyl ether); 1H NMR (300 MHz, CDCl3) δ 7.89-7.87 (m, 2H), 7.58-7.53 (m, 2H), 7.25-7.15 (m, 2H), 7.03-6.95 (m, 2H), 6.50 (s, 1H), 6.20 (s, 1H), 5.15-4.64 (m, 4H), 4.16-4.07 (m, 4H), 2.62 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 178.1, 177.3, 167.8, 155.2, 144.7, 142.4, 138.4, 137.9, 132.2, 130.8, 130.2, 129.3, 127.2, 126.3, 125.5, 124.2, 123.7, 121.5, 111.6, 109.9, 99.3, 80.0, 64.7, 64.0, 57.8, 43.1, 12.4; MS (ES+) m/z 467.8 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([CH:10]=[CH:11][C:12](=O)[CH3:13])=[C:5]([CH3:15])[C:4]=1[CH3:16].Br[CH2:18]/[CH:19]=[CH:20]/[C:21]([O:23][CH3:24])=[O:22]>>[CH3:24][O:23][C:21](=[O:22])[CH:20]=[CH:19][CH:18]=[C:12]([CH3:13])[CH:11]=[CH:10][C:6]1[C:7]([CH3:9])=[CH:8][C:3]([O:2][CH3:1])=[C:4]([CH3:16])[C:5]=1[CH3:15]
Reactant: COC(=O)/C=C/CBr
Reactant: COc1cc(C)c(C=CC(C)=O)c(C)c1C
Product: COC(=O)C=CC=C(C)C=Cc1c(C)cc(OC)c(C)c1C

Procedure:
In a manner similar to Example 5, reaction of 4-(4-methoxy-2,3,6-trimethylphenyl)-3-buten-2-one with methyl 4-bromocrotonate afforded the desired compound. Crystallization from ether-petroleum ether gave yellow crystals, m.p. 104°-109° C. MS(EI): 300(m+), 285(m+ --CH3), 241(m+ --CO2CH3).
Reaction SMILES: N(C(C)(C)C#N)=N[C:3](C)(C)C#N.[CH3:13][C:14]([C:16]([O:18][CH2:19][CH2:20][CH2:21][Si:22](OC)([O:25][CH3:26])[O:23][CH3:24])=[O:17])=[CH2:15]>C1(C)C=CC=CC=1>[C:16]([O:18][CH2:19][CH2:20][CH2:21][Si:22]([CH3:3])([O:25][CH3:26])[O:23][CH3:24])(=[O:17])[C:14]([CH3:13])=[CH2:15]
Reactant: C=C(C)C(=O)OCCC[Si](OC)(OC)OC
Reactant: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: Cc1ccccc1
Product: C=C(C)C(=O)OCCC[Si](C)(OC)OC

Procedure:
Next, the 51.99 mg of silk fibroin fiber having a vinyl group (hereinafter referred to as a vinyl introduction SF), 10 ml of anhydrous toluene, 132.19 mg of azobisisobutyronitrile as an initiator, and 1.0 g of methacryloxypropylmethyldimethoxysilane (Product No KBM-503 produced by Shin-Etsu Chemical Co.Ltd: hereinafter referred to as KBM) were contained in a polymer glass tube, and then were subjected to several sets of deairing/nitrogen gas filling. Then, the materials were sealed to react with each other at 60° C. for a predetermined period. The resultant is a silk fibroin fiber (hereinafter referred to as KBM-g-SF) in which a high molecular chain containing an alkoxysilyl group in its end is bonded to a polymer-based material through graft polymerization. Table 1 shows the introduction ratio (%) of alkoxysilyl group in this case at each given reaction time. Note that, the introduction ratio was found according to the following Formula (1), in which ag expresses the weight of the vinyl introduced SF and bg expresses the weight of the KBM-g-SF. Introduction ratio (%)=((b−a)/a)×100  (1)
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12](Br)=[N:13][N:14]=[C:10]3[CH2:9][N:8]=[C:7](C3C=CC=CC=3)[C:6]=2[CH:22]=1.[NH:23]1[CH2:28][CH2:27][S:26][CH2:25][CH2:24]1.C(Cl)Cl>O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([N:23]4[CH2:28][CH:27]([C:2]5[CH:3]=[CH:4][CH:5]=[CH:6][CH:22]=5)[S:26][CH2:25][CH2:24]4)=[N:13][N:14]=[C:10]3[CH2:9][N:8]=[CH:7][C:6]=2[CH:22]=1
Reactant: C1CSCCN1
Reactant: Clc1ccc2c(c1)C(c1ccccc1)=NCc1nnc(Br)n1-2
Solvent: O
Solvent: ClCCl
Product: Clc1ccc2c(c1)C=NCc1nnc(N3CCSC(c4ccccc4)C3)n1-2
Temperature: 120 °C

Procedure:
A mixture of 2.0 gm (5.35 mmol) of 8-chloro-1-bromo-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine and 2.0 ml of thiomorpholine was heated under nitrogen in an oil bath at 120° C. for 18 hr and then allowed to cool. The reaction mixture was treated with methylene chloride and water. The organic layer was separated, washed with dilute brine and concentrated in vacuo. The residue was recrystallized from methanol to yield 1.40 gm (72.7%) with m.p. 241°-243° C. and 0.46 gm (23.9%) with m.p. 239°-241° C. of the title product. Analysis of the title product for carbon, hydrogen, nitrogen, chlorine and sulphur revealed 60.47% C, 4.58% H, 18.03% N, 9.14% Cl, and 8.09% S. Calculated values for such an analysis for the title product are: 60.67% C, 4.58% H, 17.69% N, 8.98% Cl, and 8.10% S.
Reaction SMILES: [NH2:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]([OH:11])=[CH:4][C:3]=1[Cl:12].CCN(C(C)C)C(C)C.[O:22]1[CH2:27][CH2:26][CH:25]([C:28](Cl)=[O:29])[CH2:24][CH2:23]1>C(Cl)Cl>[Cl:12][C:3]1[CH:4]=[C:5]([OH:11])[CH:6]=[C:7]([N+:8]([O-:10])=[O:9])[C:2]=1[NH:1][C:28]([CH:25]1[CH2:26][CH2:27][O:22][CH2:23][CH2:24]1)=[O:29]
Reactant: O=C(Cl)C1CCOCC1
Reactant: Nc1c(Cl)cc(O)cc1[N+](=O)[O-]
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=C(Nc1c(Cl)cc(O)cc1[N+](=O)[O-])C1CCOCC1
Reaction time: 2 h

Procedure:
0.40 g (2.12 mmol) 4-amino-3-chloro-5-nitrophenol were placed in 5 mL DCM. 0.44 mL (2.54 mmol) DIPEA and 0.26 mL (2.54 mmol) tetrahydro-2H-pyran-4-carbonyl chloride were added and at RT the mixture was stirred for 2 h. A further 0.26 mL (2.54 mmol) tetrahydro-2H-pyran-4-carbonyl chloride were added and the mixture was stirred overnight at RT. The reaction mixture was diluted with DCM and washed with water. The organic phase was evaporated down i.vac.
Reaction SMILES: [Br:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[S:8](Cl)([C:11]1[CH:17]=[CH:16][C:14]([CH3:15])=[CH:13][CH:12]=1)(=[O:10])=[O:9]>N1C=CC=CC=1.ClCCl.Cl>[Br:1][CH:2]1[CH2:7][CH2:6][N:5]([S:8]([C:11]2[CH:17]=[CH:16][C:14]([CH3:15])=[CH:13][CH:12]=2)(=[O:10])=[O:9])[CH2:4][CH2:3]1
Reactant: BrC1CCNCC1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)N2CCC(Br)CC2)cc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
4-Bromopiperidine (5.75 g, 23.5 mmol) was dissolved in pyridine (50 mL) and treated with tosyl chloride (5.8 g, 30.5 mmol). The reaction mixture was stirred for 12 h at r.t. and then diluted with dichloromethane (150 mL) and HCl (1 M aqueous solution, 50 mL). The organic layer was washed with brine (80 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (40% EtOAc/hexane) to give 4-bromo-1-tosylpiperidine as a white solid: 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J=8.2 Hz, 2H), 7.34 (d, J=8.2 Hz, 2H), 4.27-4.24 (m, 1H), 3.20-3.17 (m, 2H), 3.13-3.11 (m, 2H), 2.46 (s, 3H), 2.23-2.17 (m, 2H), 2.08-2.05 (m, 2H); MS (ESI) 318.0 (M+H)+.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[CH:8]([CH2:12][C:13]13[CH2:22][CH:17]4[CH2:18][CH:19]([CH2:21][CH:15]([CH2:16]4)[CH2:14]1)[CH2:20]3)[CH2:7]2.[C:23]([C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1)([CH3:26])([CH3:25])[CH3:24].C(=O)([O-])[O-].[Na+].[Na+].C(O)CO>O>[C:23]([C:27]1[CH:32]=[CH:31][C:30]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:10]=2[C:9](=[O:11])[CH:8]([CH2:12][C:13]24[CH2:14][CH:15]5[CH2:21][CH:19]([CH2:18][CH:17]([CH2:16]5)[CH2:22]2)[CH2:20]4)[CH2:7]3)=[CH:29][CH:28]=1)([CH3:26])([CH3:25])[CH3:24]
Reactant: CC(C)(C)c1ccc(B(O)O)cc1
Reactant: O=C1c2c(Cl)cccc2CC1CC12CC3CC(CC(C3)C1)C2
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: OCCO
Product: CC(C)(C)c1ccc(-c2cccc3c2C(=O)C(CC24CC5CC(CC(C5)C2)C4)C3)cc1
Temperature: 125 °C

Procedure:
71.8 g (228 mmole) 7-Chloro-2-(1-adamantylmethyl)-indan-1-one, 49 g (1.2 eq.) 4-tert-butyl-benzene boronic acid, 53 g sodium carbonate, 750 ml ethylene glycol and 150 ml water were placed in a 2 l-roundbottom flask equipped with a mechanical stirrer and a reflux condenser. The mixture was degassed three times by slight evacuation and recharging with argon. A premixed catalyst solution consisting of 103 mg (0.2 mole %) palladium acetate, 3 ml NaTPPTS (2.6 M in water, 0.8 mole %) and 2 ml of water was added and the mixture was refluxed at 125° C. until complete conversion (approx. 6 h). 300 ml of water were added and the mixture was extracted three times with 150 ml of toluene each. The combined organic layers were washed twice with 100 ml water and once with 100 ml of a saturated sodium chloride solution. Drying over magnesium sulphate and evaporation of the solvent in vacuo yielded 94.1 g (quant.) of the desired product as a yellow sticky oil. 1H-NMR (400 MHz, CDCl3): δ=7.52 (t, 1H, aromatic), 7.41, 7.36 (2×d, 4H, aromatic), 7.21 (m, 2H, aromatic), 3.37 (m, 1H, COCH), 2.77-2.68 (m, 2H, benzylic), 1.42-1.18 (m, 26H, aliphatic & C(CH3)3) ppm.