Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([S:7][C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1.C(=O)([O-])[O-].[K+].[K+].Cl>C1(C)C=CC=CC=1.CN(C=O)C>[C:1]1([S:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)=[CH:10][CH:9]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Oc1ccc(Sc2ccccc2)cc1
Reactant: BrC1CCCC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Product: c1ccc(Sc2ccc(OC3CCCC3)cc2)cc1
Reaction time: 16 h
Yield: 100 %

Procedure:
A solution was prepared by combining 11.3 g of 4-hydroxyphenyl phenyl sulfide which had been synthesized according to the well-known formulation, 8.2 g of bromocyclopentane, 7.6 g of potassium carbonate, and 40 g of DMF. The solution was aged at 80° C. for 16 hours. The aged solution was cooled to room temperature, to which 100 g of 5 wt % dilute hydrochloric acid was added to quench the reaction. To the solution, 150 g of toluene was added for extraction. The organic layer was separated and washed with water. It was combined with 5 wt % sodium hydroxide aqueous solution. The organic layer was separated and washed with water again. On subsequent concentration in vacuum, 13.8 g of the target compound, 4-cyclopentyloxyphenyl phenyl sulfide was obtained as oily matter. Yield 100%.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH2:8])[CH:3]=1.C(N(C(C)C)CC)(C)C.[N:18]1([CH2:24][CH2:25][CH2:26][N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1>C(O)CCC>[N:27]1([CH2:26][CH2:25][CH2:24][N:18]2[CH2:19][CH2:20][N:21]([C:2]3[N:7]=[CH:6][N:5]=[C:4]([NH2:8])[CH:3]=3)[CH2:22][CH2:23]2)[CH2:28][CH2:29][O:30][CH2:31][CH2:32]1
Reactant: Nc1cc(Cl)ncn1
Reactant: C(CN1CCNCC1)CN1CCOCC1
Solvent: CCCCO
Solvent: CCN(C(C)C)C(C)C
Product: Nc1cc(N2CCN(CCCN3CCOCC3)CC2)ncn1
Temperature: 125 °C
Reaction time: 18 h

Procedure:
6-Chloropyrimidin-4-amine 7-2 (0.368 g, 2.84 mmol) and diisopropylethylamine (0.367 g, 2.84 mmol) were suspended in n-butanol. 4-(3-piperazin-1-ylpropyl)morpholine 10-1 (0.61 g, 2.84 mmol) was then added. The reaction was stirred at 125° C. for 18 hours. Upon cooling the resulting solid was filtered off, washed with ethyl ether and dried to afford 10-2. 1NMR (DMSO): 7.94 ppm (s, 1H); 6.18 ppm (s, 2H); 5.58 ppm (s, 1H); 3.56 ppm (t, 4H); 3.39 ppm (t, 4H); 2.38 ppm (t, 4H); 2.31 ppm (m, 8H); 1.60 ppm (p, 2H).
Reaction SMILES: [C:1]1([O:7][C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N1C=CC=CC=1.[C:17]1([CH2:23][CH2:24][CH2:25][NH2:26])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C(Cl)Cl>[C:1]1([O:7][C:8](=[O:9])[NH:26][CH2:25][CH2:24][CH2:23][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NCCCc1ccccc1
Reactant: O=C(Cl)Oc1ccccc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=C(NCCCc1ccccc1)Oc1ccccc1
Reaction time: 24 h

Procedure:
Chloroformic acid phenyl ester (3.29 g, 21.0 mmol.) and pyridine (1.74 g, 22.0 mmol.) were added to a solution of 3-phenylpropylamine (2.7 g, 20.0 mmol.) in abs. DCM (50 ml), and stirring was carried out for 24 h at RT. For working up, the mixture was washed in succession with water (2×20 ml), 1M HCl (2×20 ml) and 1N NaOH (2×20 ml) and then the organic phase was dried, filtered and concentrated. (3-Phenylpropyl)carbamic acid phenyl ester was obtained in a yield of 4.11 g by recrystallisation from EE/hexane (1:1) (white solid, m.p. 55–56° C.).
Reaction SMILES: [F:1][C:2]1[CH:11]=[CH:10][C:9]2[N:12]=[C:13]([C@@H:14]([NH2:16])[CH3:15])[N:7]3[C:8]=2[C:3]=1[CH2:4][CH2:5][CH2:6]3.Cl[C:18]1[N:26]=[CH:25][N:24]=[C:23]2[C:19]=1[N:20]=[CH:21][N:22]2C1CCCCO1.CCN(C(C)C)C(C)C>C(O)CCC>[F:1][C:2]1[CH:11]=[CH:10][C:9]2[N:12]=[C:13]([C@@H:14]([NH:16][C:18]3[N:26]=[CH:25][N:24]=[C:23]4[C:19]=3[N:20]=[CH:21][NH:22]4)[CH3:15])[N:7]3[C:8]=2[C:3]=1[CH2:4][CH2:5][CH2:6]3
Reactant: Clc1ncnc2c1ncn2C1CCCCO1
Reactant: C[C@H](N)c1nc2ccc(F)c3c2n1CCC3
Solvent: CCCCO
Solvent: CCN(C(C)C)C(C)C
Product: C[C@H](Nc1ncnc2[nH]cnc12)c1nc2ccc(F)c3c2n1CCC3
Temperature: 90 °C
Reaction time: 16 h
Yield: 58.2 %

Procedure:
A mixture of (5)-1-(7-fluoro-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2-yl)ethylamine (48.5 mg, 0.221 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (52.9 mg, 0.221 mmol), and DIPEA (0.113 mL, 0.663 mmol) in n-butanol (1 mL) was stirred in a sealed vial at 90° C. for 16 h. After cooling to RT, volatiles were removed under reduced pressure. The residue was dissolved in MeOH (3 mL) and the resulting solution was cooled in an ice bath. HCl in isopropanol (1.25 M, 2 mL) was added and the mixture stirred at 0° C. for 1 h and then concentrated under reduced pressure. The residue was dissolved in MeOH and loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 0.5 M NH3 in MeOH, further purification by column chromatography (Si—PCC, gradient 2-14% 2M NH3/MeOH in DCM) afforded 398 as a white solid (43.4 mg, 58%). LCMS (Method J): RT 4.80 min [M+H]+ 338.2. 1H NMR ((CD3)2SO, 400 MHz): 12.81 (1H, bs), 8.23 (1H, s), 8.15 (1H, s), 7.96 (1H, d, J=7.8 Hz), 7.37 (1H, dd, J=8.8, 4.2 Hz), 6.92 (1H, dd, J=10.5, 8.8 Hz), 5.80 (1H, bs), 4.29-4.16 (2H, m), 2.87 (2H, t, J=6.1 Hz), 2.16-2.05 (2H, m), 1.68 (3H, d, J=6.8 Hz)
Reaction SMILES: [C:1]1([CH3:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl-].[Al+3].[Cl-].[Cl-].[CH2:12]([SiH:15]([Cl:17])[Cl:16])[CH:13]=[CH2:14].[Cl-].[Na+]>>[CH3:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:13]([CH3:14])[CH2:12][SiH:15]([Cl:17])[Cl:16]
Reactant: C=CC[SiH](Cl)Cl
Reactant: Cc1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Agent: [Na+]
Product: Cc1ccccc1C(C)C[SiH](Cl)Cl
Temperature: 50 °C
Yield: 71 %

Procedure:
In the same apparatus and procedures as EXAMPLE 1, 19.3 g (210 mmol) of toluene and 0.9 g (7.0 mmol) of aluminum chloride were placed and reacted with 10.0 g (70 mmol) of allyldichlorosilane under the dry nitrogen atmosphere for 30 min. After stirring the solution for another an hour, 2.0 g (30 mmol) of sodium chloride was added to reaction mixture, warmed up to 50° C. and stirred for two hours to deactivate the catalyst. Vacuum distillation of the reaction products gave 11.7 g (bp, 73°-76° C./0.5 mmHg) of of 3-(methylphenyl)-1,1-dichloro-1-silabutane in 71% yield.
Reaction SMILES: [C:1]([NH:8][C@H:9]([C:25]([OH:27])=O)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CC[N:30](C(C)C)C(C)C.C(OC(Cl)=O)C(C)C.N.C(O)(C)C>C1COCC1>[C:21]([O:20][C:18](=[O:19])[O:17][C:14]1[CH:15]=[CH:16][C:11]([CH2:10][C@H:9]([NH:8][C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[C:25](=[O:27])[NH2:30])=[CH:12][CH:13]=1)([CH3:24])([CH3:23])[CH3:22]
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccc(OC(=O)OC(C)(C)C)cc1)C(=O)O
Reactant: CCN(C(C)C)C(C)C
Agent: CC(C)COC(=O)Cl
Agent: N
Solvent: CC(C)O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N[C@@H](Cc1ccc(OC(=O)OC(C)(C)C)cc1)C(N)=O
Yield: 62.2 %

Procedure:
N,O-Bis-Boc-(S)-tyrosine from example 64 (5.00 g, 13.11 mmol) was dissolved in THF (20 mL), the solution stirred under an argon atmosphere and cooled in an ice bath. DIEA (5.70 mL, 32.7 mmol) was added followed by isobutylchloroformate (2.55 mL, 19.6 mmol). After 45 min a solution of 2M ammonia in isopropanol (39.3 mL, 78.6 mmol) was added and the mixture stirred at room temperature for 18 h. The solvent was evaporated, the residue taken in EtOAC (100 mL), washed with 5% aqueous citric acid (2×50 mL), 5% aqueous sodium bicarbonate (2×50 mL) and brine. After drying (MgSO4) and evaporation of the solvent, the residue was dissolved in chloroform (15 mL), stirred vigorously and Et2O (150 mL) was added. The suspension was stirred for 20 min. then the solid filtered and air dried to yield 3.10 g (62%) of the title compound.
Reaction SMILES: Cl[C:2]1[C:7]([CH3:8])=[CH:6][N:5]=[C:4]([CH2:9][OH:10])[C:3]=1[CH3:11].[CH3:12][O-:13].[Na+]>CN(C)C=O.CO>[OH:10][CH2:9][C:4]1[C:3]([CH3:11])=[C:2]([O:13][CH3:12])[C:7]([CH3:8])=[CH:6][N:5]=1
Reactant: Cc1cnc(CO)c(C)c1Cl
Reactant: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: CN(C)C=O
Product: COc1c(C)cnc(CO)c1C
Yield: 55 %

Procedure:
In a round bottom flask equipped with a stirrer, a condenser and a nitrogen bubbler, 4-Chloro-2-hydroxymethyl-3,5-Lutidine (1 eq.) was dissolved in Dimethylformamide (3-9 volumes) and Methanol (1.5-4.5 volumes). Sodium methoxide (4 eq.) was added and the temperature was raised to (95-100ℑ C.). At the end of the reaction the solvent was distilled under vacuum. Water (2 volumes) was added to the residue and the product was extracted with dichloromethane (2×4 volumes). The combined organic extracts were dried over sodium sulfate, filtered and evaporated. The crude product, 2-hydroxymethyl-4-Methoxy-3,5-lutidine, was obtained in 55% yield.
Reaction SMILES: [OH-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([N+:10](=[N:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)[O-])[CH:7]=[CH:8][CH:9]=1>[Ni].CO.O>[Cl:3][C:4]1[CH:5]=[C:6]([NH:10][NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)[CH:7]=[CH:8][CH:9]=1
Reactant: [O-][N+](=Nc1cccc(Cl)c1)c1cccc(Cl)c1
Agent: [Ni]
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: Clc1cccc(NNc2cccc(Cl)c2)c1
Temperature: 10 °C
Yield: 89 %

Procedure:
1.2 g of sodium hydroxide and 0.25 g of Raney nickel are added to a suspension of 53.4 g of 3,3'-dichloroazoxybenzene in 60 ml of methanol and 15 ml of water and the hydrogenation reaction is carried out under a hydrogen pressure of 10 bars. After 90 minutes the mixture is cooled to 10° C. and the product is isolated by filtration. 3,3'-Dichlorohydrazobenzene is obtained in a yield of 89% of theory.
Reaction SMILES: [CH:1]([C:3]1[C:4]([F:12])=[C:5]([C:8]([F:11])=[CH:9][CH:10]=1)[C:6]#[N:7])=[CH2:2].C1C=C(Cl)C=C(C(OO)=[O:21])C=1>C(Cl)Cl>[F:12][C:4]1[C:3]([CH:1]2[CH2:2][O:21]2)=[CH:10][CH:9]=[C:8]([F:11])[C:5]=1[C:6]#[N:7]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: C=Cc1ccc(F)c(C#N)c1F
Solvent: ClCCl
Product: N#Cc1c(F)ccc(C2CO2)c1F
Temperature: 25 °C
Reaction time: 48 h

Procedure:
3-Ethenyl-2,6-difluorobenzonitrile (1.70 g, 10.3 mmol) was added to DCM (10 mL) at 0° C. Then mCPBA (5.33 g, 30.9 mmol) was added and the mixture was stirred at RT for 48 h. The reaction mixture was washed with saturated aqueous Na2S2O3, then with 1N NaOH, and brine. The organic layer was separated and dried over Na2SO4, filtered, and evaporated to dryness. The crude product was purified by MPLC chromatography through a 120 g Redi-sep column, eluting with a 0-100% EtOAc/hexane solvent system. 2,6-Difluoro-3-(oxiran-2-yl)benzonitrile was isolated.
Reaction SMILES: CNC([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH2:8]2)=O.[O:15]=[C:16]1CC2[C:18](=CC(C(O)=O)=CC=2)[NH:17]1>>[CH3:18][NH:17][C:16]([C:13]1[CH:12]=[C:11]2[C:7]([CH2:8][C:9](=[O:14])[NH:10]2)=[CH:6][CH:5]=1)=[O:15]
Reactant: O=C1Cc2ccc(C(=O)O)cc2N1
Reactant: CNC(=O)c1ccc2c(c1)CC(=O)N2
Product: CNC(=O)c1ccc2c(c1)NC(=O)C2
Yield: 19 %

Procedure:
The compound was synthesized according to the method described for N-methyl-2-oxoindoline-5-carboxamide except substituting 2-oxoindoline-6-carboxylic acid (89 mg, 0.500 mmol), to obtain the title compound (18 mg, 19%). 1H NMR (400 MHz, CD3OD) δ 7.52 (d, J=7.6 Hz, 1H), 7.15 (d, J=8.0 Hz, 1H), 6.40 (d, J=7.6 Hz, 1H), 3.33 (s, 2H), 2.87 (s, 31-1); MS ESI 191.0 [M+H]+, calcd for [C10H10N2O2+H]+ 191.08.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([O:17][CH3:18])=[C:13]([OH:16])[CH:14]=2)[C:9](=O)[CH2:8][CH:7]1[CH3:20])=[O:5])[CH3:2].Cl.[NH2:22][OH:23].C([O-])(=O)C.[Na+].O>C(O)C>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([O:17][CH3:18])=[C:13]([OH:16])[CH:14]=2)[C:9](=[N:22][OH:23])[CH2:8][CH:7]1[CH3:20])=[O:5])[CH3:2]
Reactant: NO
Reactant: CCOC(=O)N1c2cc(O)c(OC)cc2C(=O)CC1C
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CCOC(=O)N1c2cc(O)c(OC)cc2C(=NO)CC1C
Reaction time: 8 h
Yield: 88.3 %

Procedure:
7-Hydroxy-6-methoxy-2-methyl-4-oxo-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester (5.10 g, 18.3 mmol) was dissolved in ethanol (100 mL), and hydroxylamine hydrochloride (3.81 g, 54.8 mmol) was added, followed by sodium acetate (3.74 g, 45.7 mmol). The mixture was heated at reflux for 2 h and then left to stand at room temperature overnight. Water (100 mL) was added, and the volatiles were removed in vacuo to give a yellow slurry. This slurry was filtered and washed with water to give the title compound as a fine powder (4.755 g, 89%).
Reaction SMILES: [CH3:1][C:2]1[C:10]2[N:9]=[C:8]3[C:11]4[C:16]([CH2:17][C:7]3([CH3:18])[C:6]=2[C:5]([CH3:19])=[C:4]([O:20][CH3:21])[C:3]=1[CH3:22])=[CH:15][CH:14]=[CH:13][CH:12]=4.[CH3:23][Li].[NH4+].[Cl-]>C1COCC1.CCOCC>[CH3:23][C@@:8]12[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH2:17][C@:7]1([CH3:18])[C:6]1[C:5]([CH3:19])=[C:4]([O:20][CH3:21])[C:3]([CH3:22])=[C:2]([CH3:1])[C:10]=1[NH:9]2
Reactant: [Li]C
Reactant: COc1c(C)c(C)c2c(c1C)C1(C)Cc3ccccc3C1=N2
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: COc1c(C)c(C)c2c(c1C)[C@@]1(C)Cc3ccccc3[C@@]1(C)N2
Temperature: -78 °C
Reaction time: 1 h

Procedure:
To a cold (-80° C.) solution of 1.1 g (0.0038 mol) of 9b,10-dihydro-6,7,9,9b-tetramethyl-8-methoxyindeno[1,2-b]indole in 20 ml of dry THF was added 4 ml of 1.6M methyl lithium in ether under argon. The mixture was stirred at -78° C. for 1 hour and then at -20° C. for 1 hour. After attaining 0° C. aqueous NH4Cl and ether was added. The phases were separated, and the organic phase was washed once with water, dried (MgSO4) and evaporated. The resulting crude product was purified by chromatography on silica using ethyl acetate/isooctane (2/10) as eluant. This gave 0.3 g (25%) of the expected product. 1H NMR (CDCl3): 1.41 (3H,s), 1.43 (3H,s), 1.96 (3H,s), 2.07 (3H,s), 2.35 (3H,s), 3.0 (1H,d), 3.55 (3H,s), 3.65 (1H,d), 7.1 (3H,m), 7.25 (1H,m).
Reaction SMILES: [H-].[Na+].[C:3]1([C:9]2[C:10]([C:14]([O:16][CH3:17])=[O:15])=[CH:11][NH:12][CH:13]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:18]([O:25][C:26]1[CH:27]=[C:28]2[C:33](=[CH:34][CH:35]=1)[CH:32]=[C:31]([CH2:36]Cl)[CH:30]=[CH:29]2)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.CN(C)C=O>O>[CH2:18]([O:25][C:26]1[CH:27]=[C:28]2[C:33](=[CH:34][CH:35]=1)[CH:32]=[C:31]([CH2:36][N:12]1[CH:13]=[C:9]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:10]([C:14]([O:16][CH3:17])=[O:15])=[CH:11]1)[CH:30]=[CH:29]2)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: ClCc1ccc2cc(OCc3ccccc3)ccc2c1
Reactant: COC(=O)c1c[nH]cc1-c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1cn(Cc2ccc3cc(OCc4ccccc4)ccc3c2)cc1-c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 79.6 %

Procedure:
Sodium hydride (60%, oily, 0.36 g) was added to a mixture of methyl 4-phenylpyrrole-3-carboxylate (1.81 g), 6-benzyloxy-2-chloromethylnaphthalene (2.54 g) and N,N-dimethylformamide (35 ml), and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into water, which was extracted with ethyl acetate. The ethyl acetate layer was washed with water, then with saturated aqueous sodium chloride solution, dried (MgSO4), then concentrated. The residue was subjected to silica gel column chromatograpy, and methyl 1-(6-benzyloxy-2-naphthylmethyl)-4-phenylpyrrole-3-carboxylate (3.20 g, yield: 80%) was obtained as colorless crystals from the fraction eluted with tetrahydrofuran-hexane (1:2, volume ratio). This was recrystallized from ethyl acetate-hexane. Melting point: 109–110° C.
Reaction SMILES: [CH3:1][C:2]1[C:10]([B:11]2[O:15][C:14]([CH3:17])([CH3:16])[C:13]([CH3:19])([CH3:18])[O:12]2)=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].S(Cl)([Cl:22])=O>CN(C=O)C.C(Cl)(Cl)Cl>[CH3:1][C:2]1[C:10]([B:11]2[O:15][C:14]([CH3:17])([CH3:16])[C:13]([CH3:19])([CH3:18])[O:12]2)=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([Cl:22])=[O:5]
Reactant: O=S(Cl)Cl
Reactant: Cc1c(B2OC(C)(C)C(C)(C)O2)cccc1C(=O)O
Solvent: ClC(Cl)Cl
Solvent: CN(C)C=O
Product: Cc1c(B2OC(C)(C)C(C)(C)O2)cccc1C(=O)Cl
Reaction time: 3 h
Yield: 70.5 %

Procedure:
2-Methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid (1.2 g, 46.0 mmol) was placed into 40 ml scintillation vial equipped with a small stir bar. 10.0 ml of anhydrous chloroform was added following by 1.8 ml of thionyl chloride and 2 drops of anhydrous DMF. After 3 hours, the solvent and excess thionyl chloride were evaporated under vacuum. The brown residue was treated with 40 ml of hexane, filtered, and concentrated to give 985 mg (Yield=70.5%) of the product as a greenish oil. 1H NMR (CDCl3, 400 MHz) δ 8.15 (d, 1H), 7.95 (d, 1H), 7.3 (t, 1H), 2.75 (s, 3H), 1.4 (s, 12H). The reaction was run several times and the yield was ranging from 60 to 99%.
Reaction SMILES: [C:1]1([CH:7]=[CH:8][CH:9]=[CH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:17][SiH:18]([Cl:20])[Cl:19]>[Cl-].C([P+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[Cl:17][Si:18]([Cl:20])([Cl:19])[CH:10]([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[CH:9]=[CH:8][CH:7]([Si:18]([Cl:20])([Cl:19])[Cl:17])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C(C=Cc1ccccc1)=Cc1ccccc1
Reactant: Cl[SiH](Cl)Cl
Agent: CCCC[P+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Solvent: Cc1ccccc1
Product: Cl[Si](Cl)(Cl)C(C=CC(c1ccccc1)[Si](Cl)(Cl)Cl)c1ccccc1
Temperature: 180 °C
Yield: 26 %

Procedure:
As in Example 1, 1,4-diphenyl-1,3-butadiene (2.00 g, 9.70 mmol), trichlorosilane (5.25 g, 38.76 mmol), tetrabutylphosphonium chloride (0.29 g, 0.98 mmol) and 5 mL of toluene (solvent) were added in a 25 mL stainless steel tube under nitrogen atmosphere. After sealing the cylinder with a cap, the reactor was maintained at 180° C. for 8 hours. After removing the solvent and unreacted trichlorosilane and tetrachlorosilane through simple distillation, this reaction mixture was distilled under reduced pressure to separate the catalyst and the product. The product was recrystallized from 10 mL of n-hexane for 4 days to yield 1.51 g (yield: 51%) of 2,5-diphenyl-1,1-dichlorosilacyclo-3-pentene and 1.20 g (yield: 26%) of 1,4-bis(trichlorosilyl)-1,4-diphenyl-2-butene.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[N:4][N:5]([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:6](=[O:8])[CH:7]=1.[CH3:15][Si](C)(C)N[Si](C)(C)C.[Li].CI>O1CCCC1>[CH3:1][C:2]1[CH:3]=[N:4][N:5]([CH:9]([CH3:15])[C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:6](=[O:8])[CH:7]=1
Reactant: C[Si](C)(C)N[Si](C)(C)C
Reactant: CCOC(=O)Cn1ncc(C)cc1=O
Agent: [Li]
Solvent: C1CCOC1
Solvent: CI
Product: CCOC(=O)C(C)n1ncc(C)cc1=O
Temperature: -78 °C
Reaction time: 0.25 h

Procedure:
To ethyl [4-methyl-6-oxopyridazin-1(6H)-yl]acetate (0.132 g, 0.673 mmol) in tetrahydrofuran (4 mL) at −78° C. was added 1M lithium hexamethyldisilazane solution (0.74 mL). The reaction mixture was stirred at −78° C. for 15 min then was added methyl iodide (0.046 mL, 0.74 mmol). After being stirred at −78° C. for 2 h, the reaction mixture was allowed to warm to ambient temperature over 0.5 h. Removal of the volatiles in vacuo followed by purification using a Biotage Horizon® system (0-50% ethyl acetate/hexanes mixture) gave ethyl 2-[4-methyl-6-oxopyridazin-1(6H)-yl]propanoate as oil. To 88 mg (0.42 mmol) of the above oil in tetrahydrofuran (0.3 mL), water (0.2 mL) and methanol (0.2 mL) was added 5 N sodium hydroxide solution (0.2 mL). The reaction mixture was stirred at ambient temperature for 3 h then neutralized with 2 N hydrochloric acid and purified by reverse phase HPLC (TMC Pro-Pac C18; 0-40% 0.1% trifluoroacetic acid in acetonitrile/0.1% trifluoroacetic acid in water gradient). Removal of the volatiles in vacuo afforded the title compound as a white solid. LC/MS 183.2 (M+1).
Reaction SMILES: [O:1]1[CH:5]=[CH:4][C:3]([CH2:6]O)=[CH:2]1.C1(P([N:22]=[N+:23]=[N-:24])(C2C=CC=CC=2)=O)C=CC=CC=1.CCCCCCC=CCCC>C1(C)C=CC=CC=1>[N:22]([CH2:6][C:3]1[CH:4]=[CH:5][O:1][CH:2]=1)=[N+:23]=[N-:24]
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Reactant: OCc1ccoc1
Agent: CCCC=CCCCCCC
Solvent: Cc1ccccc1
Product: [N-]=[N+]=NCc1ccoc1
Temperature: 25 °C
Yield: 94.8 %

Procedure:
To a 50 mL round-bottomed flask equipped with a magnetic stirbar was added 3-furan methanol (1.00 g, 10.2 mmol) and a solution of diphenyl phosphoryl azide (3.37 g, 12.2 mmol) in toluene (30 mL). The stirring solution is allowed to cool to 0° C., in which 1, 8 Diazabycyclo [5.4.0.]undec-7-ene (1.86 g, 12.2 mmol) was added dropwise. The reaction is allowed to slowly warm to ambient temperature for an additional 16 hours of stirring. After this period, the reaction mixture is washed with water (2×20 mL) and then with 5% HCl (20 mL). Volatiles are evaporated under reduced pressure. The resulting residue is then purified by column chromatography (1:9 ethyl acetate/hexane) providing 3-azidomethyl furan (1.19 g, 95%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.46 (d, 1H), δ 7.44 (s, 1H), δ 6.42 (d, 1H), δ 4.20 (s, 2H). ppm; 13C NMR (75 MHz, CDCl3) δ 144.1, 141.1, 110.4, 92.1, 45.8 ppm; LRMS (EI) Calcd for C5H5N3O (M+) 123, found 123.
Reaction SMILES: [C:1]([NH:4][C:5]1[C:10]([F:11])=[CH:9][C:8]([Cl:12])=[C:7]([N+:13]([O-])=O)[CH:6]=1)(=[O:3])[CH3:2]>C(O)(=O)C.C(OCC)(=O)C.[Fe]>[C:1]([NH:4][C:5]1[C:10]([F:11])=[CH:9][C:8]([Cl:12])=[C:7]([NH2:13])[CH:6]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Nc1cc([N+](=O)[O-])c(Cl)cc1F
Agent: [Fe]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CC(=O)Nc1cc(N)c(Cl)cc1F
Temperature: 90 °C
Yield: 60.4 %

Procedure:
Iron powder (31.9 g) were suspended in a 5% acetic acid solution (60 ml), and the suspension was heated to 90° C. A solution of 4-(N-acetylamino)-1-chloro-5-fluoro-2-nitrobenzene (13.3 g) in acetic acid (100 l ml) and ethyl acetate (70 ml) was dropwise added thereto, and the resultant mixture was refluxed at 80° C. for 2 hours. The reaction mixture was filtered by celite. The filtrate was extracted with ethyl acetate, and the extract was neutralized with a saturated sodium hydrogen carbonate solution. The organic layer was washed with water, dried and concentrated under reduced pressure to give 7.0 g of 4-(N-acetylamino)-2-amino-1-chloro-5-fluorobenzene. M.P., 140.5°-141.5° C.
Reaction SMILES: [ClH:1].CN.[O:4]1[CH2:9][CH2:8][C:7](=O)[CH2:6][CH2:5]1.[CH2:11]([N:13](CC)CC)C>[Pd].CO>[ClH:1].[CH3:11][NH:13][CH:7]1[CH2:8][CH2:9][O:4][CH2:5][CH2:6]1
Reactant: CCN(CC)CC
Reactant: O=C1CCOCC1
Agent: [Pd]
Agent: CN
Agent: Cl
Solvent: CO
Product: CNC1CCOCC1
Temperature: 60 °C
Reaction time: 3 h
Yield: 273.3 %

Procedure:
A mixture of methylamine hydrochloride (5.4 g), terahydro-4H-pyran-4-one (8 g), triethylamine (2.4 g), 5% palladium on carbon (400 mg) and methanol (56 ml) were stirred at 60° C. for 3 hours under a hydrogen atmosphere. The palladium on carbon was removed by filtration through diatomaceous earth (Celite®) and the resultant filtrate evaporated in vacuo to a cream solid. To this solid were added propan-2-ol (39 ml), methanol (10 ml) and diethyl ether (20 ml), the resultant suspension then allowed to stir at room temperature for 1 hour, the solid was collected by filtration, washed with diethyl ether (10 ml) and dried in vacuo at room temperature to give N-methyl-N-(tetrahydropyran-4-yl)amine hydrochloride (9.83 g) as a white solid; NMR Spectrum: (DMSOd6) 1.62 (m, 2H); 1.94 (m, 2H); 2.53 (m, 3H); 3.14 (m, 1H); 3.3 (m, 2H); 3.91 (m, 2H); 9.24 (s, 2H).