Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[C:7]([CH2:8][CH2:9][OH:10])=[C:6]([OH:11])[N:5]=[C:4]([S:12][CH2:13][C:14]2[CH:23]=[CH:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=2)[N:3]=1.[Si:24](Cl)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25].C(Cl)Cl>N1C=CC=CC=1>[NH2:1][C:2]1[C:7]([CH2:8][CH2:9][O:10][Si:24]([CH3:26])([CH3:25])[C:27]([CH3:30])([CH3:29])[CH3:28])=[C:6]([OH:11])[N:5]=[C:4]([S:12][CH2:13][C:14]2[CH:23]=[CH:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=2)[N:3]=1
Reactant: Nc1nc(SCc2ccc3ccccc3c2)nc(O)c1CCO
Reactant: CC(C)(C)[Si](C)(C)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)OCCc1c(N)nc(SCc2ccc3ccccc3c2)nc1O
Temperature: 0 °C
Reaction time: 2 h

Procedure:
2-(4-amino-6-hydroxy-2-[2-naphthylmethyl]thio-5-pyrimidinyl)-ethanol (Cpd #279; 106 mg, 0.32 mmol) is dissolved in pyridine (0.64 ml) and the solution is cooled to 0° C. then treated with t-butyl dimethylsilyl chloride (0.058 g, 0.39 mmol). The solution is stirred at 0° C. for 2 hours and two new spots developed in the mixture. The reaction mixture is poured into methylene chloride and washed 3× with 1 M HCl, 10% HCl, 3× H2O, 2× 6% NaHCO3, dried with MgSO4, then concentrated in vacuo. The crude product is then purified by chromatography (SiO2 1:1 hexane/ethyl acetate): 60 mg (0.18 mmol, 57%), mp 156-158° C.
Reaction SMILES: [C:1]([CH2:3][CH2:4][N:5]([CH2:7][CH2:8][CH2:9][C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[NH:12][CH:11]=1)[CH3:6])#[N:2].N>[Ni].O1CCOCC1>[NH:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]([CH2:9][CH2:8][CH2:7][N:5]([CH3:6])[CH2:4][CH2:3][CH2:1][NH2:2])=[CH:11]1
Reactant: CN(CCC#N)CCCc1c[nH]c2ccccc12
Agent: [Ni]
Agent: N
Solvent: C1COCCO1
Product: CN(CCCN)CCCc1c[nH]c2ccccc12

Procedure:
36.2 g N-(2-cyanoethyl)-N-methyl-3-(3-indolyl)propyl amine are hydrogenated at normal pressure and at room temperature with 20 g Raney-nickel catalyst in 400 ml dioxan and 400 ml of a 10% ammonia solution. N-[3-(3-indolyl)propyl]-N-methyl-1,3-diaminopropane is obtained after working up. M.pt of the neutral fumarate: 180°-181° (with decomposition) after crystallization from ethanol.
Reaction SMILES: [NH2:1][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3]1.C(N(CC)CC)C.[CH2:18]([S:22](Cl)(=[O:24])=[O:23])[CH2:19][CH2:20][CH3:21]>C(Cl)Cl>[CH2:18]([S:22]([NH:1][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3]1)(=[O:24])=[O:23])[CH2:19][CH2:20][CH3:21]
Reactant: NC1Cc2ccccc2C1
Reactant: CCCCS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCS(=O)(=O)NC1Cc2ccccc2C1
Reaction time: 1 h
Yield: 90.9 %

Procedure:
To 87.44 g of 2-aminoindane dissolved in 800 ml of methylene chloride was added 66.43 g of triethylamine, and 102.8 g of n-butylsulfonyl chloride was added dropwise thereto under ice cooling. The mixture was stirred at the same temperature for 1 hour. The reaction mixture was washed with diluted hydrochloric acid and dried, and then the solvent was removed. The resulting crystals were recrystallized from isopropyl ether to obtain 151.12 g of 2-n-butylsulfonylaminoindane.
Reaction SMILES: Br[C:2]1[N:6]([CH3:7])[C:5]([CH3:8])=[N:4][CH:3]=1.C([Li])CCC.CON(C)[C:17]([C:19]1[N:23]([CH3:24])[N:22]=[N:21][CH:20]=1)=[O:18].[Cl-].[NH4+]>O1CCCC1>[CH3:7][N:6]1[C:2]([C:17]([C:19]2[N:23]([CH3:24])[N:22]=[N:21][CH:20]=2)=[O:18])=[CH:3][N:4]=[C:5]1[CH3:8]
Reactant: Cc1ncc(Br)n1C
Reactant: CON(C)C(=O)c1cnnn1C
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Product: Cc1ncc(C(=O)c2cnnn2C)n1C
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A solution of 5-bromo-1,2-dimethyl-1H-imidazole (1.5 g, 7.54 mmol) in tetrahydrofuran (25 mL) was cooled to −66° C. Maintaining a temperature of <−50° C., n-butyllithium (3.2 mL, 2.5 M in hexanes, 8.3 mmol) was added over 5 minutes. The reaction mixture was stirred for 15 minutes and then a solution of N-methoxy-N,1-dimethyl-1H-1,2,3-triazole-5-carboxamide (1.3 g, 7.54 mmol, Intermediate 77: step a) in tetrahydrofuran (3 mL) was added over 3 minutes. The mixture was allowed to warm to room temperature while stirring over 30 minutes. Half-saturated aqueous ammonium chloride solution (40 mL) was added and the layers were mixed and separated. The aqueous layer was extracted twice with tetrahydrofuran (50 mL) and then with dichloromethane (50 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated to dryness. The material was triturated with isopropyl alcohol (29 mL), filtered, and rinsed twice with hexanes (25 mL) providing the title compound as a white solid.
Reaction SMILES: [Cl:1][C:2]1[C:10]([Cl:11])=[C:9]2[C:5]([CH2:6][CH:7]([CH:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[C:8]2=[O:12])=[CH:4][C:3]=1[O:18][CH3:19].N#N.CC(C)([O-])C.[K+].[CH2:28](I)[CH2:29][CH2:30][CH3:31]>C1C=CC=CC=1.C(O)(C)(C)C.O>[CH2:28]([C:7]1([CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)[CH2:6][C:5]2[C:9](=[C:10]([Cl:11])[C:2]([Cl:1])=[C:3]([O:18][CH3:19])[CH:4]=2)[C:8]1=[O:12])[CH2:29][CH2:30][CH3:31]
Reactant: CCCCI
Reactant: COc1cc2c(c(Cl)c1Cl)C(=O)C(C1CCCC1)C2
Agent: CC(C)(C)[O-]
Agent: N#N
Agent: [K+]
Solvent: CC(C)(C)O
Solvent: c1ccccc1
Solvent: O
Product: CCCCC1(C2CCCC2)Cc2cc(OC)c(Cl)c(Cl)c2C1=O

Procedure:
A solution of 6,7-dichloro-2-cyclopentyl-2,3-dihydro-5-methoxy-1H-inden-1-one (7.2 g) in benzene (70 ml) was heated at reflux in a N2 atmosphere and treated over a 5 minute period with a solution of potassium t-butoxide (4.2 g) in t-butanol (70 ml). The solution was refluxed for 3/4 hour, treated with butyl iodide (11 ml), refluxed for an additional 3/4 hour, cooled, treated with water (50 ml) and the organic solvents were distilled at reduced pressure. The aqueous slurry was extracted with ether washed with water, dried over MgSO4 and evaporated at reduced pressure. Treatment of the residue with hexane (100 ml) gave 6.9 g of 2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-5-methoxy-1H-inden-1-one, m.p. 122°-123° C.
Reaction SMILES: [OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]2[C@H:8]3[C@H:17]([CH2:18][CH2:19][C@:3]12[CH3:4])[C@@H:16]1[C@H:11]([CH2:12][C:13](=[O:20])[CH2:14][CH2:15]1)[CH2:10][CH2:9]3.N1C=CN=C1.[C:26]([Si:30](Cl)([CH3:32])[CH3:31])([CH3:29])([CH3:28])[CH3:27].CCCCCC.CCOC(C)=O>CN(C=O)C.O>[Si:30]([O:1][C@H:2]1[CH2:7][CH2:6][C@H:5]2[C@H:8]3[C@H:17]([CH2:18][CH2:19][C@:3]12[CH3:4])[C@@H:16]1[C@H:11]([CH2:12][C:13](=[O:20])[CH2:14][CH2:15]1)[CH2:10][CH2:9]3)([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:32])[CH3:31]
Reactant: C[C@]12CC[C@H]3[C@@H](CC[C@H]4CC(=O)CC[C@@H]43)[C@@H]1CC[C@@H]2O
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CCCCCC
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)O[C@H]1CC[C@H]2[C@@H]3CC[C@H]4CC(=O)CC[C@@H]4[C@H]3CC[C@]12C
Temperature: 0 °C
Yield: 99.1 %

Procedure:
10 g of 17β-hydroxy-5α-estran-3-one was dissolved in 150 ml of DMF. 3.7 g of imidazole were then added and the mixture was cooled to 0° C. 6.5 g of t-butyl dimethyl silyl chloride were added and the mixture was stirred and gradually warmed to room temperature followed by stirring for two days. TLC (hexane/EtOAc (9:1)) revealed that the reaction was complete. The reaction mixture was diluted with water and then extracted with 500 ml of hexane/EtOAc (9:1) (2×). The combined organic layers were washed with brine, dried over MgSO4, filtered, and evaporated under reduced pressure to produce crude product (14.6 g). The entire crude yield was flash chromatographed with the Aldrich flash chromatography system. The 600 ml column was filled with 7 inches of 230-400 mesh silica gel, eluting with hexane/EtOAc (10: 1). Once the sample was loaded, 30 ml fractions were taken. Fraction numbers 4-13, yielded 14 g of the title compound, m.p. 103°-104° C.
Reaction SMILES: [C:1]([C:5]1[N:10]=[C:9]([NH:11][CH2:12][C:13]2[O:14][CH:15]=[CH:16][N:17]=2)[C:8]([C:18]([N:20]([CH2:38][CH:39]([CH3:41])[CH3:40])[C@@H:21]2[CH2:26][N:25]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:24][C@H:23]([C:34]([O:36]C)=[O:35])[CH2:22]2)=[O:19])=[CH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>CO>[C:30]([O:29][C:27]([N:25]1[CH2:26][C@@H:21]([N:20]([C:18]([C:8]2[C:9]([NH:11][CH2:12][C:13]3[O:14][CH:15]=[CH:16][N:17]=3)=[N:10][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[N:6][CH:7]=2)=[O:19])[CH2:38][CH:39]([CH3:41])[CH3:40])[CH2:22][C@@H:23]([C:34]([OH:36])=[O:35])[CH2:24]1)=[O:28])([CH3:32])([CH3:33])[CH3:31]
Reactant: COC(=O)[C@@H]1C[C@H](N(CC(C)C)C(=O)c2cnc(C(C)(C)C)nc2NCc2ncco2)CN(C(=O)OC(C)(C)C)C1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CC(C)CN(C(=O)c1cnc(C(C)(C)C)nc1NCc1ncco1)[C@H]1C[C@@H](C(=O)O)CN(C(=O)OC(C)(C)C)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 98.6 %

Procedure:
1-tert-Butyl 3-methyl (3R,5S)-5-[({2-tert-butyl-4-[(1,3-oxazol-2-ylmethyl)amino]pyrimidin-5-yl}carbonyl) (2-methylpropyl)amino]piperidine-1,3-dicarboxylate (0.26 g) was dissolved in methanol (3 ml), 2 M aqueous sodium hydroxide solution (1.0 ml) was added and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, the residue was diluted with saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the object compound (0.25 g).
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([NH:44][S:45]([CH3:48])(=[O:47])=[O:46])[C:8]([O:42][CH3:43])=[C:9]([NH:11][C:12]([C:14]2[S:18][C:17]3[C:19]([NH:23][C:24](=[O:41])[C:25]4[CH:30]=[CH:29][C:28]([NH:31]CC5C=CC(OC)=CC=5)=[N:27][CH:26]=4)=[CH:20][CH:21]=[CH:22][C:16]=3[CH:15]=2)=[O:13])[CH:10]=1)([CH3:4])([CH3:3])[CH3:2]>FC(F)(F)C(O)=O>[NH2:31][C:28]1[CH:29]=[CH:30][C:25]([C:24]([NH:23][C:19]2[C:17]3[S:18][C:14]([C:12](=[O:13])[NH:11][C:9]4[CH:10]=[C:5]([C:1]([CH3:3])([CH3:4])[CH3:2])[CH:6]=[C:7]([NH:44][S:45]([CH3:48])(=[O:47])=[O:46])[C:8]=4[O:42][CH3:43])=[CH:15][C:16]=3[CH:22]=[CH:21][CH:20]=2)=[O:41])=[CH:26][N:27]=1
Reactant: COc1ccc(CNc2ccc(C(=O)Nc3cccc4cc(C(=O)Nc5cc(C(C)(C)C)cc(NS(C)(=O)=O)c5OC)sc34)cn2)cc1
Solvent: O=C(O)C(F)(F)F
Product: COc1c(NC(=O)c2cc3cccc(NC(=O)c4ccc(N)nc4)c3s2)cc(C(C)(C)C)cc1NS(C)(=O)=O
Temperature: 75 °C
Yield: 84.8 %

Procedure:
To N-[2-(5-tert-Butyl-3-methanesulfonylamino-2-methoxy-phenylcarbamoyl)-benzo[b]thiophen-7-yl]-6-(4-methoxy-benzylamino)-nicotinamide (Example 1) (20 mg) in a sealed tube was added 90 μL of trifluoroacetic acid. The clear solution was purged with Ar and then heated to 75° C. in a sealed tube 12 h. The reaction was cooled to room temperature and diluted with toluene to remove excess trifluoroacetic acid in vacuo. The resulting trifluoroacetic acid salt of the desired product was dissolved in EtOAc and washed with saturated NaHCO3 solution and brine. The organics were dried over MgSO4, filtered and concentrated to give a foam which was further purified by flash chromatography on silica gel (7%-10% MeOH/CH2Cl2) to provide the title compound as a white solid (14 mg, 85% yield), m.p. 234-235° C.
Reaction SMILES: Cl[C:2]1[CH:9]=[CH:8][C:7]([N+:10]([O-])=O)=[CH:6][C:3]=1[C:4]#[N:5].[CH3:13][N:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1>>[NH2:10][C:7]1[CH:8]=[CH:9][C:2]([N:17]2[CH2:18][CH2:19][N:14]([CH3:13])[CH2:15][CH2:16]2)=[C:3]([CH:6]=1)[C:4]#[N:5]
Reactant: CN1CCNCC1
Reactant: N#Cc1cc([N+](=O)[O-])ccc1Cl
Product: CN1CCN(c2ccc(N)cc2C#N)CC1
Yield: 62.5 %

Procedure:
By the reaction and treatment in the same manner as in Starting Material Synthetic Example 4 using 2-chloro-5-nitrobenzonitrile (15 g) and methylpiperazine (9.8 g), the title compound (11.1 g) was obtained. melting point: 45-46° C.
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.N(C(C)(C)C#N)=N[C:11](C)(C)[C:12]#N.[CH3:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]>O>[CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH:22]([C:23]1[CH:28]=[CH:27][C:26]([CH:11]=[CH2:12])=[CH:25][CH:24]=1)=[CH2:21]
Reactant: CCCCCCCC
Reactant: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: O
Solvent: C=Cc1ccccc1
Product: C=Cc1ccc(C=C)cc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
1 g of the amphiphilic macromolecule reversible addition-fragmentation chain transfer agent and 80 g of deionized water were formulated into an aqueous solution as an aqueous phase, which was added and uniformly mixed with an oil phase consisting of 6 g of styrene, 12 g of p-vinyl benzene, 0.1 g of azobisisobutyronitrile and 9 g of n-octane, and prepared by an ultrasonic crasher into a miniemulsion under the effect of a high shear field. The miniemulsion was transferred to a reactor and subjected to the reaction at a temperature of 80° C. which stopped after 4 hours, and then cooled to the room temperature and discharged to yield polymeric nanocapsules with highly crosslinked shells which were formed by the polymerization of styrene and p-divinyl benzene, wherein the polymeric nanocapsules have an average diameter of 90 nm.
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[NH2:10][OH:11].Cl.[OH-].[Na+].CCOC(C)=O.CCCCCC>CCO>[F:1][C:2]1[CH:9]=[CH:8][C:5]([C:6](=[N:10][OH:11])[NH2:7])=[CH:4][CH:3]=1
Reactant: N#Cc1ccc(F)cc1
Reactant: NO
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: NC(=NO)c1ccc(F)cc1
Yield: 62.9 %

Procedure:
To a stirred solution of 4-fluorobenzonitrile (10 g, 82.5 mmol) in EtOH (71 mL) was added NH2OH.HCl (6.42 g, 92.1 mmol), followed by NaOH pellets (3.69 g, 92.1 mmol). The resulting reaction mixture was then heated at reflux for 3 h. The reaction progress was monitored by TLC using solvent system EtOAc:Hexane (1:1). After completion of reaction the solvent was evaporated under reduced pressure and the minimum amount of water (ca. 30 mL) was added to the residue. The mixture was extracted with dichloromethane (3×300 mL), dried over Na2SO4, and concentrated under vacuum. The crude compound obtained was recrystallized from hot toluene to obtain 8.0 g (63%) of 4-fluoro-N′-hydroxybenzimidamide as a colorless solid. 1H NMR (400 MHz, DMSO-d6): δ 9.6 (s, 1H), 7.07-7.67 (m, 2H), 7.18 (t, 2H, J=8.8 Hz), 5.80 (br s, 2H); LC-MS m/z calculated for [M+H]+ 155.05. found 155.1.
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]3[C:34]4[C:29](=[CH:30][C:31]([O:37][CH3:38])=[C:32]([O:35][CH3:36])[CH:33]=4)[N:28]=[CH:27][CH:26]=3)=[CH:20][CH:19]=2)=[O:16])[CH2:10][CH2:9]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O>ClCCCl>[CH3:36][O:35][C:32]1[CH:33]=[C:34]2[C:29](=[CH:30][C:31]=1[O:37][CH3:38])[N:28]=[CH:27][CH:26]=[C:25]2[O:24][C:21]1[CH:22]=[CH:23][C:18]([NH:17][C:15]([NH:14][CH:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]2)=[O:16])=[CH:19][CH:20]=1
Reactant: COc1cc2nccc(Oc3ccc(NC(=O)NC4CCN(Cc5ccccc5)CC4)cc3)c2cc1OC
Agent: CC(Cl)OC(=O)Cl
Solvent: ClCCCl
Product: COc1cc2nccc(Oc3ccc(NC(=O)NC4CCNCC4)cc3)c2cc1OC
Yield: 168.7 %

Procedure:
N-(1-Benzyl-4-piperidyl)-N′-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}urea (100 mg) was dissolved in 1,2-dichloroethane (25 ml) to prepare a solution. 1-Chloroethyl chloroformate (0.10 ml) was then added to the solution, and the mixture was heated under reflux overnight. The solvent was removed by distillation under the reduced pressure. Methanol (20 ml) was added to the residue, followed by heating under reflux for 2 hr. The solvent was removed by distillation under the reduced pressure to give 139 mg of N-{4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N′-(4-piperidyl)urea (1).
Reaction SMILES: Br[CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([C:13]([O:15]C)=[O:14])=[CH:5][CH:4]=1.C(=O)([O-])[O-].[K+].[K+].[NH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=1>CN(C=O)C>[N:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[NH:23][CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([C:13]([OH:15])=[O:14])=[CH:5][CH:4]=1
Reactant: COC(=O)c1ccc(CBr)c2ccccc12
Reactant: Nc1ccccn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C(O)c1ccc(CNc2ccccn2)c2ccccc12
Temperature: 25 °C
Reaction time: 15 h
Yield: 9.5 %

Procedure:
The compound obtained in Example 17-2 (1.6728 g) was dissolved in DMF (33 ml). After the addition of potassium carbonate (1.66 g) and 2-aminopyridine (0.68 g), the mixture was stirred for 15 hours at room temperature. After the reaction, the solvent was removed by distillation and the residue was dissolved in chloroform. The organic layer was washed with 1 mol/l aqueous solution of hydrochloric acid and saturated brine, and dried over anhydrous sodium sulfate. Then, the solvent was removed by distillation. The residue was dissolved in DMF (44 ml). Triethylamine. (1.58 ml) and di-t-butyldicarbonate (2.60 ml) were added and the mixture was stirred for 6 hours at room temperature. After the reaction, the solvent was removed by distillation. The residue was dissolved in ethyl acetate. The solution was washed with 0.5 mol/l aqueous solution of hydrochloric acid and saturated brine, and dried over anhydrous sodium sulfate. The solvent was removed by distillation. The residue was dissolved in methanol (6 ml), and 1 mol/l aqueous solution of sodium hydroxide (6 ml) was added. After the reaction for one day, the reaction solution was concentrated. The residue was dissolved again in methanol and neutralized with ion-exchange resin CG50. The resin was removed by filtration. The filtrate was concentrated. The residue was purified by silica gel column chromatography (15 g, chloroform/methanol=5/1) to obtain the title compound (159 mg) as a colorless viscous liquid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][C:9](=O)[CH2:10]2)=[CH:5][CH:4]=1.[N+](C1C=CC=CC=1S([N:26]([CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=1)[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([CH2:34][NH2:35])=[CH:30][CH:29]=1)(=O)=O)([O-])=O.[BH3-]C#N.[Na+]>CO.C(OC)(OC)OC.C(O)(=O)C>[N:38]1[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=1[CH2:36][NH:26][CH2:27][C:28]1[CH:29]=[CH:30][C:31]([CH2:34][NH:35][CH:9]2[CH2:8][CH2:7][C:6]3[C:11](=[CH:12][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[CH2:10]2)=[CH:32][CH:33]=1
Reactant: COc1ccc2c(c1)CC(=O)CC2
Reactant: NCc1ccc(CN(Cc2ccccn2)S(=O)(=O)c2ccccc2[N+](=O)[O-])cc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Solvent: COC(OC)OC
Product: COc1ccc2c(c1)CC(NCc1ccc(CNCc3ccccn3)cc1)CC2
Yield: 76.3 %

Procedure:
Using General Procedure G: 7-methoxy-2-tetralone (60 mg, 0.34 mmol), N-(2-nitrobenzenesulfonyl)-N-(2-pyridinylmethyl)-1,4-benzenedimethanamine (100 mg, 0.24 mmol) and NaBH3CN (59 mg, 0.94 mmol) in MeOH (3 mL), trimethyl orthoformate (1.7 mL) and acetic acid (3 drops) were reacted for 3.5 hours. Following work-up, the crude material was purified by chromatography on silica gel (CH2Cl2/MeOH/NH4OH 98:1:1) to give the desired product (71 mg, 52%) as a yellow foam.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH:6]=[C:5]([C:8]2[CH:9]=[C:10]([NH2:18])[CH:11]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:13]=2)[CH2:4][CH2:3]1>CCO>[CH3:1][N:2]1[CH2:3][CH2:4][CH:5]([C:8]2[CH:9]=[C:10]([NH2:18])[CH:11]=[C:12]([C:14]([F:15])([F:16])[F:17])[CH:13]=2)[CH2:6][CH2:7]1
Reactant: CN1CC=C(c2cc(N)cc(C(F)(F)F)c2)CC1
Solvent: CCO
Product: CN1CCC(c2cc(N)cc(C(F)(F)F)c2)CC1

Procedure:
Into a 100 mL round bottom flask was placed 3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-5-(trifluoromethyl)benzenamine (2.05 g, 8 mmol) and EtOH (40 mL). Flask sparged with argon, then 10% Palladium on carbon (100 mg) is added. Argon removed and replaced with hydrogen via balloon, stirs overnight at RT. Work up: Filtered reaction mixture through Celite® under inert atmosphere. Removed solvents under reduced pressure. Purified via silica column using 0 to 100% 90/10/1 (DCM/MeOHINH4OH) gradient in DCM. Affords a pale yellow oil. LC-MS (+) shows mass 259 (M+H), as expected for C13H17F3N2, mw 258.28.
Reaction SMILES: [CH3-].[CH3:2][C:3]1[C:8]([CH3:9])=[CH:7][C:6]2[N:10]([C@H:13]3[O:17][C@H:16]([CH2:18][OH:19])[C@@H:15]([O:20][P:21]([O:24][CH:25]([CH2:27][NH:28][C:29]([CH2:31][CH2:32][C@@:33]4([CH3:90])[C:49]5=[N:50][C@@H:35]([C@:36]6([CH3:85])[N-:74][C:39](=[C:40]([CH3:73])[C:41]7[C@:62]([CH2:64][C:65]([NH2:67])=[O:66])([CH3:63])[C@H:61]([CH2:68][CH2:69][C:70]([NH2:72])=[O:71])[C:43](=[CH:44][C:45]8[C:53]([CH3:55])([CH3:54])[C@H:52]([CH2:56][CH2:57][C:58]([NH2:60])=[O:59])[C:47](=[C:48]5[CH3:51])[N:46]=8)[N:42]=7)[C@@H:38]([CH2:75][CH2:76][C:77]([NH2:79])=[O:78])[C@@:37]6([CH2:81][C:82]([NH2:84])=[O:83])[CH3:80])[C@@H:34]4[CH2:86][C:87]([NH2:89])=[O:88])=[O:30])[CH3:26])([O-:23])=[O:22])[C@H:14]3[OH:91])[CH:11]=[N:12][C:5]=2[CH:4]=1.[Co+3:92].[As:93].C[Si]([Br:98])(C)C>[O-2].[Ti+4].[O-2].CO>[CH3-:2].[CH3:2][C:3]1[C:8]([CH3:9])=[CH:7][C:6]2[N:10]([C@H:13]3[O:17][C@H:16]([CH2:18][OH:19])[C@@H:15]([O:20][P:21]([O:24][CH:25]([CH2:27][NH:28][C:29]([CH2:31][CH2:32][C@@:33]4([CH3:90])[C:49]5=[N:50][C@@H:35]([C@:36]6([CH3:85])[N-:74][C:39](=[C:40]([CH3:73])[C:41]7[C@:62]([CH2:64][C:65]([NH2:67])=[O:66])([CH3:63])[C@H:61]([CH2:68][CH2:69][C:70]([NH2:72])=[O:71])[C:43](=[CH:44][C:45]8[C:53]([CH3:55])([CH3:54])[C@H:52]([CH2:56][CH2:57][C:58]([NH2:60])=[O:59])[C:47](=[C:48]5[CH3:51])[N:46]=8)[N:42]=7)[C@@H:38]([CH2:75][CH2:76][C:77]([NH2:79])=[O:78])[C@@:37]6([CH2:81][C:82]([NH2:84])=[O:83])[CH3:80])[C@@H:34]4[CH2:86][C:87]([NH2:89])=[O:88])=[O:30])[CH3:26])([O-:23])=[O:22])[C@H:14]3[OH:91])[CH:11]=[N:12][C:5]=2[CH:4]=1.[Co+3:92].[As:93].[Br-:98]
Reactant: C[Si](C)(C)Br
Agent: [Co+3]
Agent: [Ti+4]
Agent: C/C1=C2/N=C(/C=C3\N=C(/C(C)=C4\[N-][C@@](C)([C@@H]5N=C1[C@](C)(CCC(=O)NCC(C)OP(=O)([O-])O[C@H]1[C@@H](O)[C@@H](n6cnc7cc(C)c(C)cc76)O[C@@H]1CO)[C@H]5CC(N)=O)[C@@](C)(CC(N)=O)[C@@H]4CCC(N)=O)[C@@](C)(CC(N)=O)[C@@H]3CCC(N)=O)C(C)(C)[C@@H]2CCC(N)=O
Solvent: CO
Product: [Br-]
Reaction time: 2 h

Procedure:
In a quartz cell, a methanol solution of methylcobalamin, arsenic (inorganic trivalent arsenic) and trimethylsulfoxoniuim bromide (TMSBr) was prepared. The total volume of the solution was 0.5 mL, the concentration of methylcobalamin was 148 μmol/L, the concentration of arsenic was 6.5 mmol/L, and the concentration of TMSBr was 532 mmol/L. Further, 50 mg of titanium oxide was mixed thereto. The quartz cell was irradiated with an ultraviolet ray for 24 hours using a high-pressure mercury lamp (365 nm of central wavelength, 5 mW/cm2). A qualitative analysis was performed on a yielded product every 2 hours using a HPLC-ICP-MS, and the number of catalyst cycle was determined. The result is shown in FIG. 1.
Reaction SMILES: [Cl-].C[N+:3]1C(=O)N(C)[CH:6]=[CH:7][CH:8]=1.[C:11]([C:14]1[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=1)(=O)[CH3:12].C(O)(=O)C.C([O-])(=O)C.[NH4+].[OH-].[Na+]>C(#N)C.C(N(CC)CC)C>[N:3]1[CH:8]=[CH:7][CH:6]=[CH:12][C:11]=1[C:14]1[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=1
Reactant: Cn1ccc[n+](C)c1=O
Reactant: CC(=O)c1ccncc1
Agent: CC(=O)[O-]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CC#N
Solvent: CCN(CC)CC
Solvent: CC(=O)O
Product: c1ccc(-c2ccncc2)nc1
Temperature: 25 °C
Yield: 79.5 %

Procedure:
14.0 g (87 mmol) of 1,3-dimethyl-2,3-dihydro-2-oxopyrimidinium chloride obtained in Example 1 was dissolved in 25 ml of acetonitrile and mixed with 10 g (83 mmol) of 4-acetylpyridine, and 12.6 g (125 mmol) of triethylamine was added dropwise thereto at 45° C. or less. After 30 minutes of the reaction at 45° C., acetonitrile and triethylamine were evaporated under a reduced pressure, and 25 ml (416 mmol) of acetic acid and 39 g (454 mmol) of ammonium acetate were added to the residual liquid to carry out the reaction at 120° C. for 8 hours. After completion of the reaction, this was cooled to room temperature, neutralized with 217 g of 25% sodium hydroxide aqueous solution and then extracted three times with 200 ml of toluene. The organic layer was concentrated and then purified by distillation under a reduced pressure to obtain 10.3 g (yield 80%) of the title compound (purity 99.9%, melting point 56-57° C.).