Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[C:3]([NH:5][CH2:6][C:7]1[C:8]([F:19])=[CH:9][C:10]([Cl:18])=[C:11]([CH:17]=1)[C:12]([N:14]=[C:15]=[O:16])=O)=[O:4].[F:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29][NH:30]C(OC(C)(C)C)=O)=[CH:25][C:24]=1[C:38]([F:41])([F:40])[F:39].C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:18][C:10]1[C:11]([C:12]2[NH:14][C:15](=[O:16])[N:29]([C:26]3[CH:27]=[CH:28][C:23]([F:22])=[C:24]([C:38]([F:39])([F:40])[F:41])[CH:25]=3)[N:30]=2)=[CH:17][C:7]([CH2:6][NH:5][C:3](=[O:4])[C:2]([F:21])([F:20])[F:1])=[C:8]([F:19])[CH:9]=1
Reactant: O=C=NC(=O)c1cc(CNC(=O)C(F)(F)F)c(F)cc1Cl
Reactant: CC(C)(C)OC(=O)NNc1ccc(F)c(C(F)(F)F)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=C(NCc1cc(-c2nn(-c3ccc(F)c(C(F)(F)F)c3)c(=O)[nH]2)c(Cl)cc1F)C(F)(F)F
Yield: 32.4 %

Procedure:
The title compound was prepared according to the procedure described in Example-83 by using 5-((2,2,2-trifluoroacetamido)methyl)-2-chloro-4-fluorobenzoyl isocyanate (Intermediate-69, 0.400 g), tert-butyl 2-[4-fluoro-3-(trifluoromethyl)phenyl]hydrazinecarboxylate (Intermediate-80, 0.400 g), DCM (20 mL) and TFA (5.0 mL) to afford 0.200 g of the desired product.
Reaction SMILES: FC1C=CC(S(CCC)(=O)=O)=CC=1C#C[Si](C)(C)C.[C:20]([O:24][C:25](=[O:37])[CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=1[C:35]#[CH:36])([CH3:23])([CH3:22])[CH3:21].Br[C:39]1[CH:51]=[CH:50][C:42]([C:43]([N:45]([CH2:48][CH3:49])[CH2:46][CH3:47])=[O:44])=[C:41]([S:52]([CH:55]([CH3:57])[CH3:56])(=[O:54])=[O:53])[CH:40]=1>>[C:20]([O:24][C:25](=[O:37])[CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=1[C:35]#[C:36][C:39]1[CH:51]=[CH:50][C:42]([C:43]([N:45]([CH2:48][CH3:49])[CH2:46][CH3:47])=[O:44])=[C:41]([S:52]([CH:55]([CH3:57])[CH3:56])(=[O:53])=[O:54])[CH:40]=1)([CH3:23])([CH3:22])[CH3:21]
Reactant: CCN(CC)C(=O)c1ccc(Br)cc1S(=O)(=O)C(C)C
Reactant: C#Cc1cc(Cl)ccc1OCC(=O)OC(C)(C)C
Agent: CCCS(=O)(=O)c1ccc(F)c(C#C[Si](C)(C)C)c1
Product: CCN(CC)C(=O)c1ccc(C#Cc2cc(Cl)ccc2OCC(=O)OC(C)(C)C)cc1S(=O)(=O)C(C)C

Procedure:
Following the general method as outlined in Intermediate 107, starting from (4-chloro-2-ethynyl-phenoxy)-acetic acid tert-butyl ester (Intermediate 3) and 4-bromo-N,N-diethyl-2-(isopropylsulfonyl)benzamide (Intermediate 257), the title compound was obtained as a brown sticky solid after purification by flash column chromatography (silica), eluting with cyclohexane containing increasing amounts of EtOAc.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[CH2:8][CH:7]=[C:6]2[CH2:12][CH2:13][OH:14].[CH3:15][C:16]1[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1.Cl.C(OCC)C>N1C=CC=CC=1>[CH3:15][C:16]1[CH:21]=[CH:20][C:19]([S:22]([O:14][CH2:13][CH2:12][C:6]2[C:5]3[C:9](=[CH:10][CH:11]=[C:3]([O:2][CH3:1])[CH:4]=3)[CH2:8][CH:7]=2)(=[O:24])=[O:23])=[CH:18][CH:17]=1
Reactant: COc1ccc2c(c1)C(CCO)=CC2
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: Cl
Solvent: c1ccncc1
Solvent: CCOCC
Product: COc1ccc2c(c1)C(CCOS(=O)(=O)c1ccc(C)cc1)=CC2
Temperature: 25 °C
Yield: 84.1 %

Procedure:
1.27 g (0.0067 mol) of 5-methoxy-1H-indene-3-ethanol are dissolved in 11 ml of dry pyridine, the mixture is stirred, is cooled with an ice bath, 1.4 g (0.0073 mol) of 4-methylbenzenesulphonic acid chloride are added portionwise and stirring is maintained overnight while cold and then at room temperature for 4 h. The solution is poured onto a mixture of 16 ml of 10N hydrochloric acid and 48 g of ice, the mixture obtained is treated with diethyl ether, the organic phase is separated, is washed with water, in dried over magnesium sulphate and is filtered and the filtrate is evaporated under reduced pressure. 1.94 g of a colourless oily product are obtained, which product is used as is in the following stage.
Reaction SMILES: [CH3:1][C:2]1[C:12]([CH3:13])=[C:11]([C:14](=[O:19])[C:15](=[CH2:18])[CH2:16][CH3:17])[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][C:6]([OH:8])=[O:7]>S(=O)(=O)(O)O>[O:19]=[C:14]1[C:11]2[C:10](=[CH:9][C:3]([O:4][CH2:5][C:6]([OH:8])=[O:7])=[C:2]([CH3:1])[C:12]=2[CH3:13])[CH2:18][CH:15]1[CH2:16][CH3:17]
Reactant: C=C(CC)C(=O)c1ccc(OCC(=O)O)c(C)c1C
Agent: O=S(=O)(O)O
Product: CCC1Cc2cc(OCC(=O)O)c(C)c(C)c2C1=O

Procedure:
By following substantially the procedure described in Example 1, Step A, and using as the reactants [2,3-dimethyl-4-(2-methylenebutyryl)phenoxy]acetic acid (40 g.) and concentrated sulfuric acid (160 ml.), there is obtained 40 g. (100%) of (1-oxo-2-ethyl-6,7-dimethyl-5-indanyloxy)acetic acid which melts at 206° C. after recrystallization from acetonitrile (1.6 l.).
Reaction SMILES: [Br:1][C:2]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[C:6](Br)=[CH:5][C:3]=1[NH2:4].[CH2:13]([CH2:15][NH2:16])[OH:14]>C(O)C>[OH:14][CH2:13][CH2:15][NH:16][C:6]1[CH:5]=[C:3]([NH2:4])[C:2]([Br:1])=[CH:8][C:7]=1[N+:9]([O-:11])=[O:10]
Reactant: Nc1cc(Br)c([N+](=O)[O-])cc1Br
Reactant: NCCO
Solvent: CCO
Product: Nc1cc(NCCO)c([N+](=O)[O-])cc1Br

Procedure:
0.02 mole (5.92 g) of 2,5-dibromo-4-nitroaniline (compound B) is added to 15 ml of 96° ethanol to which 12 ml of ethanolamine have been added. The mixture is heated in refluxing alcohol for 6 h 30 min. After cooling and dilution of the reaction mixture with 100 ml of iced water, the expected product precipitates.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[N:7]=[C:8]([NH:17][C:18]([CH:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)=[O:19])[S:9][C:10]=1[C:11]1[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=1.Cl[C:27]1[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[CH:29][N:28]=1.C(=O)([O-])[O-].[K+].[K+].O>CN1C(=O)CCC1>[C:33]([C:30]1[CH:31]=[CH:32][C:27]([N:23]2[CH2:24][CH2:25][CH:20]([C:18]([NH:17][C:8]3[S:9][C:10]([C:11]4[CH:12]=[CH:13][N:14]=[CH:15][CH:16]=4)=[C:6]([C:2]4[O:1][CH:5]=[CH:4][CH:3]=4)[N:7]=3)=[O:19])[CH2:21][CH2:22]2)=[N:28][CH:29]=1)#[N:34]
Reactant: N#Cc1ccc(Cl)nc1
Reactant: O=C(Nc1nc(-c2ccco2)c(-c2ccncc2)s1)C1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN1CCCC1=O
Product: N#Cc1ccc(N2CCC(C(=O)Nc3nc(-c4ccco4)c(-c4ccncc4)s3)CC2)nc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 49.9 %

Procedure:
Compound 15 (177 mg, 0.50 mmol), 2-chloro-5-cyanopyridine (104 mg, 0.75 mmol) and potassium carbonate (207 mg, 1.50 mmol) were dissolved in NMP (4 mL), followed by stirring overnight under heating and reflux. The reaction mixture was allowed to cool down to room temperature, then poured into water, and the deposited precipitate was collected by filtration. The resulting precipitate was purified through silica gel column chromatography (chloroform:methanol=17:3) to afford the entitled Compound 16 (114 mg, 50%).
Reaction SMILES: [CH2:1]([C:3]1[N:8]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH:16]3[CH2:20][CH2:19][CH:18]([OH:21])[CH2:17]3)=[CH:11][CH:10]=2)[C:7](=[O:22])[C:6]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[C:36]3[NH:40][C:39](=[O:41])[O:38][N:37]=3)=[CH:26][CH:25]=2)=[C:5]([CH2:42][CH2:43][CH3:44])[N:4]=1)[CH3:2].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C1=CC=CC=2)=O>ClCCl.C(OCC)(=O)C>[CH2:1]([C:3]1[N:8]([C:9]2[CH:10]=[CH:11][C:12]([O:15][CH:16]3[CH2:20][CH2:19][C:18](=[O:21])[CH2:17]3)=[CH:13][CH:14]=2)[C:7](=[O:22])[C:6]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[C:36]3[NH:40][C:39](=[O:41])[O:38][N:37]=3)=[CH:26][CH:25]=2)=[C:5]([CH2:42][CH2:43][CH3:44])[N:4]=1)[CH3:2]
Reactant: CCCc1nc(CC)n(-c2ccc(OC3CCC(O)C3)cc2)c(=O)c1Cc1ccc(-c2ccccc2-c2noc(=O)[nH]2)cc1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CCCc1nc(CC)n(-c2ccc(OC3CCC(=O)C3)cc2)c(=O)c1Cc1ccc(-c2ccccc2-c2noc(=O)[nH]2)cc1
Reaction time: 1 h
Yield: 64.2 %

Procedure:
2-Ethyl-3-{4-[(3-hydroxycyclopentyl)oxy]phenyl}-5-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-6-propylpyrimidin-4(3H)-one (0.5 g) and 1,1,1-tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3(1H)-one (0.54 g) were dissolved in dichloromethane (10 mL) and the mixture was stirred for 1 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate solution 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 (0.32 g, 64%) as a colorless amorphous solid.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([CH2:10][C:11]([NH:13][C:14]2[C:19]([CH:20]([CH3:22])[CH3:21])=[CH:18][C:17]([OH:23])=[CH:16][C:15]=2[CH:24]([CH3:26])[CH3:25])=[O:12])[CH2:6][CH2:5]1.[CH:27](N(CC)C(C)C)(C)C.C[Si](C=[N+]=[N-])(C)C.[OH-].[Na+]>C(#N)C.CO>[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([CH2:10][C:11]([NH:13][C:14]2[C:19]([CH:20]([CH3:21])[CH3:22])=[CH:18][C:17]([O:23][CH3:27])=[CH:16][C:15]=2[CH:24]([CH3:26])[CH3:25])=[O:12])[CH2:6][CH2:5]1
Reactant: CCN(C(C)C)C(C)C
Reactant: CC(C)c1cc(O)cc(C(C)C)c1NC(=O)CN1CCN(CCO)CC1
Agent: C[Si](C)(C)C=[N+]=[N-]
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: CC#N
Product: COc1cc(C(C)C)c(NC(=O)CN2CCN(CCO)CC2)c(C(C)C)c1
Reaction time: 12 h
Yield: 82.8 %

Procedure:
Into a solution of the acetamide (640 mg, 1.76 mmol) in a mixed solvent (10 ml) of methanol and acetonitrile (1:4) were dropped N,N-diisopropylethylamine (0.43 ml, 2.46 mmol) and trimethylsilyl diazomethane (1.23 ml, 2.46 mmol) and the mixture was stirred for 12 hours. The residue obtained by evaporation of the solvent was made alkaline by adding 2N sodium hydroxide and then extracted with chloroform. The organic layer was washed with water and a saturated sodium chloride solution successively and dried over anhydrous sodium sulfate and the solvent was evaporated therefrom to provide 550 mg (yield 83%) of 2-[4-(2-hydroxyethyl)piperazin-1-yl]-N-(2,6-diisopropyl-4-methoxyphenyl)acetamide as colorless crystals.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]([CH:17]=1)[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9]1.[CH2:18]1[CH:26]2[N:21]([CH2:22][CH2:23][C:24](=O)[CH2:25]2)[CH2:20][CH2:19]1>[OH-].[K+].O>[CH2:18]1[CH:26]2[N:21]([CH2:22][CH:23]=[C:24]([C:4]3[CH:5]=[C:6]([CH:17]=[C:2]([OH:1])[CH:3]=3)[CH2:7][N:8]3[C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[CH:10]=[CH:9]3)[CH2:25]2)[CH2:20][CH2:19]1
Reactant: O=C1CCN2CCCC2C1
Reactant: Oc1cccc(Cn2ccc3ccccc32)c1
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: Oc1cc(Cn2ccc3ccccc32)cc(C2=CCN3CCCC3C2)c1

Procedure:
A mixture of 5-hydroxybenzyl-1H-indole (3.69 g, 16.5 mmol) and 7-octahydroindolizinone (2.98 g, 21.5 mmol) in methanolic potassium hydroxide (10% potassium hydroxide in methanol, 50 ml) was heated to reflux for 3.5 hours. The reaction was diluted with water and the precipitate was collected by filtration. The filter cake was triturated with hot diethyl ether and filtered. The filter cake was recrystallized from methanol and dried to give 1.45 g of tan flakes. (25.8%).
Reaction SMILES: CO[C:3]([C:5]1[C:6]([OH:33])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11](CC1C=CC=CC=1)[C:10](=[O:22])[C:9]([C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=1)=[CH:8]2)=[O:4].[NH2:34][CH2:35][CH2:36][C:37]([OH:39])=[O:38].C[O-].[Na+]>C([O-])(O)=O.[Na+]>[CH2:9]([N:14]1[CH:13]=[C:12]2[C:7](=[CH:8][CH:9]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:30])[F:31])=[CH:25][CH:24]=3)[C:10](=[O:22])[NH:11]2)[C:6]([OH:33])=[C:5]1[C:3]([NH:34][CH2:35][CH2:36][C:37]([OH:39])=[O:38])=[O:4])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: COC(=O)c1ncc2c(cc(-c3ccc(C(F)(F)F)cc3)c(=O)n2Cc2ccccc2)c1O
Reactant: NCCC(=O)O
Agent: C[O-]
Agent: O=C([O-])O
Agent: [Na+]
Product: O=C(O)CCNC(=O)C1=C(O)C2=CC(c3ccc(C(F)(F)F)cc3)C(=O)NC2=CN1Cc1ccccc1
Temperature: 25 °C
Yield: 88.5 %

Procedure:
A mixture of 1-benzyl-5-hydroxy-2-oxo-3-(4-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (30 mg, 0.066 mmol), β-alanine (589 mg, 6.6 mmol) and NaOMe solution (10.6 mL, 5.3 mmol, 0.5 M in MeOH) was refluxed for 16 h. After the mixture was cooled to r.t., the solvent was evaporated in vacuo. The residue was partitioned between EtOAc and water. 1 M HCl was added with vigorous stirring until pH was about 2. The aqueous layer was extracted with additional EtOAc, and the organic layers were combined, dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (5-50% EtOAc/hexanes+1% AcOH). The product isolated was dissolved in saturated NaHCO3 and washed several times with ether. The aqueous layer was acidified to pH about 2, and the resulting precipitate was isolated by filtration to give 15 mg of the title compound as a light yellow solid. MS: (+) m/z 512.34 (M+1).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]#[C:12][CH2:13]O.CS(Cl)(=O)=O.[NH:20]1[CH:24]=[CH:23][N:22]=[CH:21]1.[Na+].[I-]>C1COCC1.O.C(N(CC)CC)C>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]#[C:12][CH2:13][N:20]1[CH:24]=[CH:23][N:22]=[CH:21]1
Reactant: c1c[nH]cn1
Reactant: OCC#Cc1ccc2ccccc2c1
Agent: CS(=O)(=O)Cl
Agent: [I-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: O
Product: C(#Cc1ccc2ccccc2c1)Cn1ccnc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 30.9 %

Procedure:
To a cooled (0° C.) solution of 3-(2-naphthyl)-2-propyn-1-ol (2.67 g) in THF (100 ml) were added triethylamine (4.1 ml) and methanesulfonyl chloride (1.7 ml) successively. The mixture was stirred at room temperature for 1 hours. Imidazole (3.02 g) and NaI (0.5 g) were added to the mixture and resulting mixture was stirred at 60° C. for 3 hours. To the mixture was added water, and the mixture was concentrated. The residue was extracted with ethyl acetate. The extract was washed with water and brine, dried and concentrated. The residue was chromatographed on silica gel, eluting with ethyl acetate, followed by crystallization from cyclohexane to give the titled compound (1.05 g) as a colorless solid.
Reaction SMILES: Cl.[CH3:2][NH:3][OH:4].[S:5]1[CH:9]=[CH:8][C:7]2[CH:10]([N:14]=[C:15]=[O:16])[CH2:11][CH2:12][CH2:13][C:6]1=2>>[OH:4][N:3]([CH3:2])[C:15]([NH:14][CH:10]1[C:7]2[CH:8]=[CH:9][S:5][C:6]=2[CH2:13][CH2:12][CH2:11]1)=[O:16]
Reactant: O=C=NC1CCCc2sccc21
Reactant: CNO
Agent: Cl
Product: CN(O)C(=O)NC1CCCc2sccc21

Procedure:
In the manner described in Example 6, N-methylhydroxylamine hydrochloride and 4,5,6,7-tetrahydrobenzo[b]thien-4-yl isocyanate are allowed to react to afford 1-hydroxy-1-methyl-3-(4,5,6,7-tetrahydrobenzo[b]thien-4-yl)urea, which is recrystallized from acetone-hexane-ether to give crystals, with melting point 98° C. to 102° C.
Reaction SMILES: O[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([O:13][CH3:14])=[O:12])=[CH:5][CH:4]=1.S(Cl)([Cl:21])=O>N1C=CC=CC=1.C(Cl)Cl>[Cl:21][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([O:13][CH3:14])=[O:12])=[CH:5][CH:4]=1
Reactant: COC(=O)c1ccccc1-c1ccc(CO)cc1
Reactant: O=S(Cl)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: COC(=O)c1ccccc1-c1ccc(CCl)cc1
Reaction time: 16 h
Yield: 87.9 %

Procedure:
2.0 g (8.25 mmol) of methyl 2-(4'-hydroxymethylphenyl)benzoate was dissolved in 1.31 g of pyridine and methylene chloride (20 ml). 1.47 g (12.4 mmol) of thionyl chloride was dropwise added thereto at room temperature, followed by stirring as such for 16 hours and under reflux by heating for 5 hours. After the reaction liquid was cooled and concentrated, a saturated aqueous solution of sodium hydrogencarbonate was added thereto, followed by the extraction with methylene chloride. The organic phase was washed with water, dried and subjected to vacuum concentration. The residue was purified by silica gel column chromatography (a n-hexane/ethyl acetate system) to give 1.89 g of the title compound as an oil (yield 88%).
Reaction SMILES: [Si:1]([O:8][CH2:9][C@@H:10]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[C@H:11]([C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=1)/[CH:12]=C/C)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[BH4-].[Na+].C[OH:36].C(Cl)Cl>>[Si:1]([O:8][CH2:9][C@@H:10]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:29])[CH3:30])[C@H:11]([C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:23])([F:24])[F:22])=[CH:17][CH:16]=1)[CH2:12][OH:36])([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:3])[CH3:2]
Reactant: C/C=C/[C@@H](c1ccc(C(F)(F)F)cc1)[C@@H](CO[Si](C)(C)C(C)(C)C)NC(=O)OC(C)(C)C
Reactant: CO
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N[C@H](CO[Si](C)(C)C(C)(C)C)[C@@H](CO)c1ccc(C(F)(F)F)cc1
Temperature: -78 °C
Reaction time: 3 h
Yield: 97 %

Procedure:
Tert-butyl (2S,3S,E)-1-(tert-butyldimethylsilyloxy)-3-(4-(trifluoromethyl)phenyl)hex-4-en-2-ylcarbamate (2.0 g, 4.2 mmol) was dissolved in 40 mL of 1:1 MeOH/DCM, and the mixture was chilled to −78° C. Ozone was bubbled through the mixture until a blue color persisted. Nitrogen was then bubbled through the mixture for 15 minutes. NaBH4 (0.80 g, 21 mmol) was added, and the mixture was warmed to room temperature. After 3 hours, the mixture was quenched with aq NH4Cl. The mixture was extracted three times with 50 mL of DCM. The combined organic extracts were dried over MgSO4. Filtration and concentration under reduced pressure afforded tert-butyl (2S,3S)-1-(tert-butyldimethylsilyloxy)-4-hydroxy-3-(4-(trifluoromethyl)phenyl)butan-2-ylcarbamate (1.9 g, 97% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.56 (d, J=8.03 Hz, 2H) 7.32 (d, J=8.03 Hz, 2H) 4.51 (s, 1H) 4.22-4.16 (m, 1H) 3.90-3.66 (m, 3H) 3.47 (d, J=5.52 Hz, 2H) 3.15-3.20 (m, 1H) 1.45 (s, 9H) 0.84 (s, 9H) 0.01 (s, 3H)-0.01 (s, 3H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4](B(O)O)[C:5]([F:8])=[N:6][CH:7]=1.I[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C([O-])([O-])=O.[Na+].[Na+].C(OCC)(=O)C>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>[Br:1][C:2]1[CH:3]=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:5]([F:8])=[N:6][CH:7]=1
Reactant: Ic1ccccc1
Reactant: OB(O)c1cc(Br)cnc1F
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: CCOC(C)=O
Solvent: C1COCCO1
Product: Fc1ncc(Br)cc1-c1ccccc1
Temperature: 90 °C
Yield: 49.7 %

Procedure:
A solution of 5-bromo-2-fluoropyridin-3-ylboronic acid (620 mg, 2.82 mmol) and 1-iodobenzene (292 μL, 2.6 mmol) in 1,4-dioxane (50 μL) was degassed via nitrogen bubble for 15 mins. Then the mixture was added Pd(PPh3)4 (150 mg, 0.13 mmol) and aqueous Na2CO3 (24 μL, 5.7 mmol) and heated to 90° C. for 30 mins. The reaction was cooled to room temperature and poured into ethyl acetate (50 mL). The mixture was extracted with ethyl acetate, dried over Na2SO4, filtered and concentrated. The residue was purified via a flash column using 10% ethyl acetate in hexanes as an eluent. The product containing fractions were concentrated to give 5-bromo-2-fluoro-3-phenylpyridine (2.2) (326 mg, 49.8% yield).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.C(N(CC)C(C)C)(C)C.[O:20]=[C:21]1[CH2:26][NH:25][CH2:24][CH2:23][NH:22]1.O>CN(C=O)C>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([N:25]2[CH2:24][CH2:23][NH:22][C:21](=[O:20])[CH2:26]2)=[N:3][CH:4]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1ccc(Cl)nc1
Reactant: O=C1CNCCN1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: O
Product: O=C1CN(c2ccc([N+](=O)[O-])cn2)CCN1
Temperature: 85 °C
Yield: 67.9 %

Procedure:
To a solution of 2-chloro-5-nitropyridine (623 mg, 3.9 mmol) in DMF (6 mL) was added N,N-diisopropylethylamine (1.4 mL, 8.5 mmol) and 2-oxopiperazine (424 mg, 4.24 mmol). The reaction mixture was heated at 85° C. for 40 min by microwave. Then the reaction mixture was cooled to RT, and poured into water (150 mL). The precipitate was filtered, washed with water and dried under vacuum to yield 4-(5-nitropyridin-2-yl)piperazin-2-one as a solid (588 mg, 68% yield). MS (M+1): 223.3
Reaction SMILES: [C:1]([OH:4])(=O)[CH3:2].[NH2:5][CH2:6][CH2:7][NH:8][CH2:9][CH2:10]O.O>C1(C)C=CC=CC=1>[OH:4][CH2:1][CH2:2][N:8]1[CH2:7][CH2:6][N:5]=[C:9]1[CH3:10]
Reactant: NCCNCCO
Reactant: CC(=O)O
Solvent: O
Solvent: Cc1ccccc1
Product: CC1=NCCN1CCO

Procedure:
Sixty parts (1 mole) of acetic acid was added little by little to 104 parts (1 mole) of N-(beta-aminoethyl) ethanolamine and 16 parts of toluene. After generation of the heat of neutralization reaction ceased, the mixture was heated under reflux at 150° to 160° C. until 36 parts (2 moles) of water distilled. Finally, the solvent was removed under reduced pressure to give 128 parts of N-hydroxyethyl-2-methylimidazoline (amine value about 440). Then, 380 parts (1 mole) of bisphenol A diglycidyl ether having an epoxy equivalent of about 190, 85 parts (0.1mole) of polycaprolactone diol having a hydroxyl equivalent of about 425 and 1.28 parts of the N-hydroxyethyl-2-methylimidazoline obtained above were mixed under heat, and reacted at 140° C. until the epoxy value of the product decreased to 3.8 (mg equivalent/1 g of solids; the same unit applies hereinafter), and then 114 parts (0.5 mole) of bisphenol A was added, and the mixture was reacted at 130° C. until the epoxy value of the product decreased to 1.35. Then, the reaction mixture was diluted with 219 parts of ethylene glycol monobutyl ether and cooled. An 80% aqueous solution of a diethylene-triamine/ ethylene carbonate adduct (mole ratio 1:2) prepared in advance (139.5 parts; 0.4 mole) was added, and the misture was reacted at 90° C. until the amine value of the product decreased to 2 or below (mg of KOH/g of resin solids; the same unit applies hereinafter). The reaction mixture was further reacted with 38.4 parts (0.3 mole) of the above N-hydroxyethyl -2-methylimidazoline until there was no rise in viscosity. As a result, an epoxy resin derivative in accordance with this invention was obtained.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[CH:5]2[C:12](=[O:18])[C:13]1[S:17][CH:16]=[CH:15][CH:14]=1.[C:19](=[O:25])=[N:20]S(Cl)(=O)=O.C(#N)C.ClS(NC=O)(=O)=O>CS(C)=O>[Cl:1][C:2]1[N:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:19]([NH2:20])=[O:25])[C:6](=[O:11])[CH:5]2[C:12](=[O:18])[C:13]1[S:17][CH:16]=[CH:15][CH:14]=1
Reactant: O=C=NS(=O)(=O)Cl
Reactant: O=C1Nc2ccc(Cl)nc2C1C(=O)c1cccs1
Agent: O=CNS(=O)(=O)Cl
Solvent: CS(C)=O
Solvent: CC#N
Product: NC(=O)N1C(=O)C(C(=O)c2cccs2)c2nc(Cl)ccc21

Procedure:
The title compound was prepared from 5-chloro-3-(2-thenoyl)-4-azaoxindole (Example 1B), according to the procedure of Example 2C, using 5-chloro-3-(2-thenoyl)-4-azaoxindole (500 mg, 1.79 mmol), N-chlorosulfonyl isocyanate (0.18 mL, 2.15 mmol), and acetonitrile (15 mL). The crude N-chlorosulfonyl carboxamide was hydrolyzed by stirring in DMSO (1.5 mL) for 1 hour in a flask open to the air. The product was precipitated by addition of water and the precipitate was collected by filtration, and recrystallized from acetic acid. Yield: 36 mg (6%). MS m/e (relative percent) 323 (7), 321 (17), 280 (9), 278 (24), 196 (22), 194 (62), 170 (25), 168 (100). Exact mass calc'd for C13H8ClN3O3 S: 320.9975; found: 320.9977. IR (KBr disc) 1724, 1623, 1570, 1512, 1415 cm-1. M.p. 222°-224° C.