Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1](/[C:9]1[N:10]=[C:11]2[CH:17]=[CH:16][N:15]([S:18]([C:21]3[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=3)(=[O:20])=[O:19])[C:12]2=[N:13][CH:14]=1)=C\C1C=CC=CC=1.I([O-])(=O)(=O)=[O:29].[Na+].[O-]S([O-])(=S)=O.[Na+].[Na+].CCOC(C)=O>O1CCOCC1.O.[Os](=O)(=O)(=O)=O>[S:18]([N:15]1[C:12]2=[N:13][CH:14]=[C:9]([CH:1]=[O:29])[N:10]=[C:11]2[CH:17]=[CH:16]1)([C:21]1[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=1)(=[O:20])=[O:19]
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: Cc1ccc(S(=O)(=O)n2ccc3nc(/C=C/c4ccccc4)cnc32)cc1
Agent: O=[Os](=O)(=O)=O
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: Cc1ccc(S(=O)(=O)n2ccc3nc(C=O)cnc32)cc1
Reaction time: 24 h
Yield: 79.9 %

Procedure:
To a solution of (E)-2-styryl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (1.2 g, 3.2 mmol) in 1,4-dioxane (20 mL) and water (2.0 mL) was added sodium periodate (2.73 g, 12.8 mmol) followed by osmium tetroxide (2.5% in t-BuOH, 4.01 mL, 0.320 mmol). After about 1 day at ambient temperature, additional sodium periodate (2.73 g, 12.78 mmol) and osmium tetroxide (2.5% in t-BuOH, 4.01 mL, 0.320 mmol) were added. After about 2 days, a solution of aqueous Na2S2O3 (100 mL) and EtOAc (100 mL) was added. The organic layer was separated, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The resulting solid was triturated with heptane to remove benzaldehyde. The resulting solid was dried in vacuo to provide 5-tosyl-5H-pyrrolo[2,3-b]pyrazine-2-carbaldehyde as a brown solid (0.77 g, 80%): LC/MS (Table 2, Method a) Rt=2.01 min; MS m/z: 334 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]([O:11][CH2:12][CH2:13][O:14][CH3:15])[N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([O:25][CH3:26])[N:6]2[CH2:16][C:17]1[CH:24]=[CH:23][C:20]([C:21]#N)=[CH:19][CH:18]=1.C1C[O:30]CC1>>[NH2:1][C:2]1[N:10]=[C:9]([O:11][CH2:12][CH2:13][O:14][CH3:15])[N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([O:25][CH3:26])[N:6]2[CH2:16][C:17]1[CH:18]=[CH:19][C:20]([CH:21]=[O:30])=[CH:23][CH:24]=1
Reactant: COCCOc1nc(N)c2nc(OC)n(Cc3ccc(C#N)cc3)c2n1
Reactant: C1CCOC1
Product: COCCOc1nc(N)c2nc(OC)n(Cc3ccc(C=O)cc3)c2n1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
The product of example 5 (100 mg) is dissolved in dry THF (3 mL) and cooled to 0° C. under argon. The reagent generated in example 6 (0.72 mL) is added to the reaction flask and the mixture is stirred at 0-5° C. for 1 h and then quenched by addition of 3 M HCl. The mixture is then extracted with ethyl acetate and then dichloromethane and concentrated in vacuo to yield 85 mg. NMR is consistent with structure assignment.
Reaction SMILES: [I:1][C:2]1[CH:10]=[C:6]([C:7](O)=[O:8])[C:5]([NH2:11])=[CH:4][CH:3]=1.C([O-])([O-])OC.C([O-])(=O)C.[NH4+:21].[CH3:22]O>O>[I:1][C:2]1[CH:10]=[C:6]2[C:5](=[CH:4][CH:3]=1)[N:11]=[CH:22][NH:21][C:7]2=[O:8]
Reactant: CO
Reactant: Nc1ccc(I)cc1C(=O)O
Reactant: [NH4+]
Agent: CC(=O)[O-]
Agent: COC([O-])[O-]
Solvent: O
Product: O=c1[nH]cnc2ccc(I)cc12
Temperature: 25 °C
Reaction time: 3 h
Yield: 93 %

Procedure:
In a 10-mL volume stainless steel pressure-resistant vessel were placed 1.0 g (3.8 mmol) of 5-iodoanthranilic acid, 0.81 g (7.6 mmol) of methyl orthoformate, 0.59 g (7.6 mmol) of ammonium acetate, and 4.0 mL of methanol. The reaction was carried out at 120° C. for 3 hours. After the reaction was complete, the reaction mixture was cooled to room temperature, and 40 mL of water was added to the reaction mixture. The resulting aqueous mixture was stirred for 15 minutes and filtered to give 0.97 g (isolated yield: 93%) of 6-iodoquinazolin-4-one as a pale gray crystalline product.
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][O:7][C:8]2[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=2[CH:10]=[N:11][OH:12])=[CH:4][CH:3]=1.[Cl:19]Cl>CCOCC.C(Cl)Cl>[Cl:19][C:10](=[N:11][OH:12])[C:9]1[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=1[O:7][CH2:6][C:5]1[CH:17]=[CH:18][C:2]([Cl:1])=[CH:3][CH:4]=1
Reactant: ON=Cc1ccccc1OCc1ccc(Cl)cc1
Reactant: ClCl
Solvent: ClCCl
Solvent: CCOCC
Product: ON=C(Cl)c1ccccc1OCc1ccc(Cl)cc1

Procedure:
2-(4-Chlorobenzyloxy)benzaldehyde oxime (26.17 g) was dissolved in ether (200 ml) and methylene chloride (50 ml), and chlorine (6.0 ml) was introduced at -10° C. or below, and then the temperature was raised from -10° C. to room temperature over 2 hours. After completion of the reaction, the mixture was concentrated under reduced pressure to give crude α-chloro-2-(4-chlorobenzyloxy)benzaldehyde oxime. The resulting crude product was dissolved in acetonitrile (150 ml), a mixture of imidazole (17.02 g) and acetonitrile (100 ml) was added at room temperature over 15 minutes, and then the resulting mixture was stirred at 65° to 70° C. for 2 hours. After completion of the reaction, water and methylene chloride were added. The resulting crystals were separated by filtration to give 2-(4-chlorobenzyloxy)-α-(1-imidazolyl)benzaldehyde oxime (11.05 g) as colorless crystals. mp. 196°-197° C.
Reaction SMILES: [OH:1][CH:2]1[C:6]([CH3:8])([CH3:7])[CH2:5]C[C:3]1=[O:9].[CH:10]1([NH2:16])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.O.C1(C)C(S(O)(=O)=[O:25])=CC=CC=1>CCO>[CH:10]1([NH:16][C:3](=[O:9])[CH:2]([OH:1])[C:6]([CH3:7])([CH3:8])[CH2:5][OH:25])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1
Reactant: NC1CCCCC1
Reactant: Cc1ccccc1S(=O)(=O)O
Reactant: CC1(C)CCC(=O)C1O
Solvent: CCO
Solvent: O
Product: CC(C)(CO)C(O)C(=O)NC1CCCCC1
Temperature: 150 °C
Reaction time: 1 h

Procedure:
Place 2-hydroxy-3,3-dimethyl-cyclopentanone (1.044 g, 7.86 mmol), cyclohexylamine (1.91 ml, 16.51 mmol) and toluenesulfonic acid monohydrate (0.152 g, 0.1 mmol) in EtOH (4 mL) in a microwave reactor. Stir for 1 hour at 150° C. Quench with 1N HCl and extract with ethyl acetate. Wash the extract with NaHCO3, brine. Dry over magnesium sulfate, filter, and concentrate to afford N-cyclohexyl-2,4-dihydroxy-3,3-dimethyl-butyramide.
Reaction SMILES: [I:1][C:2]1[C:3]([O:25][CH3:26])=[C:4]([C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=[C:14](I)[C:13]=2[O:23][CH3:24])[C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.[CH2:27]([Li])CCC.CI>C1COCC1.[Cl-].[NH4+]>[CH3:26][O:25][C:3]1[C:2]([I:1])=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]=1[C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[C:14]([CH3:27])[C:13]=1[O:23][CH3:24]
Reactant: COc1c(I)cc2ccccc2c1-c1c(OC)c(I)cc2ccccc12
Reactant: [Li]CCCC
Agent: [Cl-]
Agent: [NH4+]
Solvent: CI
Solvent: C1CCOC1
Product: COc1c(C)cc2ccccc2c1-c1c(OC)c(I)cc2ccccc12
Temperature: 25 °C

Procedure:
To a −80° C. solution of (+/−)-3,3′-diiodo-2,2′-dimethoxy-1,1′-binaphthyl (2.016 g, 3.6 mmol) in THF (dry, distilled, 80 mL, 0.044 M) was added n-butyl lithium (2.8 mL, 3.9 mmol) dropwise. The reaction mixture turned yellow and was stirred for 1 h before the addition of methyl iodide (dry, distilled, 0.35 mL, 5.6 mmol). The reaction mixture was allowed to gradually warm to room temperature. After stirring for a further 3 h saturated aqueous ammonium chloride solution (4 drops) was added. The reaction mixture was evaporated to dryness, the residue taken up in diethyl ether and washed with water. The organic layer was dried (MgSO4), filtered and the filtrate evaporated to dryness to give a pale yellow solid. Purification of the crude material by flash column chromatography (4% ethyl acetate/hexane) yielded (+/−)-2,2′-dimethoxy-3-iodo-3′-methyl-1,1′-binaphthyl.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH2:21]>C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[C:13](=[O:21])[CH2:12][CH2:11][CH2:10][C@H:9]1[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: O
Reactant: CC(C)(C)OC(=O)[C@@H]1CCCCN1C(=O)OC(C)(C)C
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)[C@@H]1CCCC(=O)N1C(=O)OC(C)(C)C
Reaction time: 4 h

Procedure:
To a vigorously stirred solution of RuCl3.H2O (2.39 g, 11.5 mmol) and NaIO4 (24.6 g, 115.0 mmol) in water (250 mL) was added (S)-piperidine-1,2-dicarboxylic acid di-tert-butyl ester (8.22 g, 28.8 mmol) in ethyl acetate (250 mL) at room temperature. After stirring for 4 h, the reaction mixture was partitioned and the aqueous layer washed with ethyl acetate. To the combined organic layers was added iPrOH (2.5 mL) and stirring was continued for 2 hours in order to destroy excess RuO4. The precipitate was removed by filtration through a pad of celite and the filtrate was evaporated under reduced pressure. The residue was purified by flash chromatography (30% ethyl acetate in hexane) to afford the title compound as a pale yellow oil, which crystallized upon standing (6.69 g, 78%): 1H NMR (400 MHz, CDCl3) δ 1.49 (9H, s), 1.52 (9H, s), 1.75-1.82 (2H, m), 1.97-2.06 (1H, m), 2.15-2.21 (1H, m), 2.41-2.61 (2H, m), 4.59 (1H, dd, J 3.5 Hz) Method I:
Reaction SMILES: [F:1][C:2]1[CH:14]=[C:13]2[C:5]([C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:11]=3[NH:12]2)=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].[OH-].[K+].I[CH:21]([CH3:23])[CH3:22].O>C(#N)C>[F:1][C:2]1[CH:14]=[C:13]2[C:5]([C:6]3[CH:7]=[CH:8][CH:9]=[C:10]([CH:21]([CH3:23])[CH3:22])[C:11]=3[NH:12]2)=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16]
Reactant: CC(C)I
Reactant: O=[N+]([O-])c1cc2c(cc1F)[nH]c1ccccc12
Agent: [K+]
Agent: [OH-]
Solvent: CC#N
Solvent: O
Product: CC(C)c1cccc2c1[nH]c1cc(F)c([N+](=O)[O-])cc12
Reaction time: 8 h
Yield: 42.9 %

Procedure:
3-Fluoro-benzohydrazine (3.3 g) and cyclohexanone (2.2 g) were added to ethanol (30 ml) and the mixture was stirred for 2 hours under reflux. The reaction mixture was concentrated and the resulting residue was recrystallized from hexane to obtain 7-fluoro-carbazole (1.81 g, 48%). Then, concentrated sulfuric acid (20 ml) was cooled to 0° C. and added with 7-fluoro-carbazole (2.1 g) and sodium nitrate (900 mg), and then the mixture was stirred for 10 minutes. The reaction mixture was poured on an ice layer and filtered to obtain 7-fluoro-6-nitro-carbazole (1.1 g, 42%). The resulting 7-fluoro-6-nitro-carbazole (500 mg) and KOH (200 mg) were stirred in acetonitrile as a solvent, and then the mixture was added dropwise with 2-iodopropane (500 mg) and stirred for 8 hours. The reaction mixture was added with water and extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by column chromatography (adsorbent: silica gel, developing solvent: ethyl acetate/hexane) to obtain 7-fluoro-1-isopropyl-6-nitro-carbazole (254 mg, 43%). The resulting 7-fluoro-1-isopropyl-6-nitro-carbazole (500 mg) and Fe (400 mg) were stirred in i-PrOH/water solvent (1:1) under reflux. The reaction mixture was extracted with ethyl acetate and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by column chromatography (adsorbent: silica gel, developing solvent: ethyl acetate/hexane) to obtain 6-amino-7-fluoro-isopropyl-carbazole (290 mg, 65%). The resulting amino compound (500 mg) was dissolved in chloroform (10 ml), and the solution was added dropwise with phenyl chloroformate (190 mg) and stirred for 2 hours. The reaction mixture was added with water and extracted. The extract was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by column chromatography (adsorbent: silica gel, developing solvent: ethyl acetate/hexane) to obtain phenylurethane (263 mg, 61%).
Reaction SMILES: [NH2:1][C:2]1[C:3]2[C:10](I)=[CH:9][N:8]([C@H:12]3[CH2:15][C@H:14]([CH2:16][OH:17])[CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[C:18]1([C:24]2[CH:33]=[CH:32][C:31]3[C:26](=[CH:27][C:28](B4OC(C)(C)C(C)(C)O4)=[CH:29][CH:30]=3)[N:25]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C([O-])([O-])=O.[Na+].[Na+].O>CN(C=O)C.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>[NH2:1][C:2]1[C:3]2[C:10]([C:28]3[CH:27]=[C:26]4[C:31]([CH:32]=[CH:33][C:24]([C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=5)=[N:25]4)=[CH:30][CH:29]=3)=[CH:9][N:8]([C@H:12]3[CH2:15][C@H:14]([CH2:16][OH:17])[CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: CC1(C)OB(c2ccc3ccc(-c4ccccc4)nc3c2)OC1(C)C
Reactant: Nc1ncnc2c1c(I)cn2[C@H]1C[C@H](CO)C1
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: CN(C)C=O
Solvent: O
Product: Nc1ncnc2c1c(-c1ccc3ccc(-c4ccccc4)nc3c1)cn2[C@H]1C[C@H](CO)C1

Procedure:
Following the general procedure for the Suzuki coupling, trans-[3-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-cyclobutyl]-methanol (139.2 mg, 0.4045 mmol) was reacted with 2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-quinoline (141 mg, 0.426 mmol), Na2CO3 (107 mg, 1.01 mmol) and Pd(PPh3)4 (30 mg, 0.026 mmol) in DMF (10 mL)/water (2 mL). The crude material was purified by column chromatography on silica gel [Jones Flashmaster, 10 g/70 mL cartridge, eluting with CH2Cl2 (1-7)→2% MeOH in CH2Cl2 (8-22)→5% MeOH in CH2Cl2 (23-41)→7% MeOH in CH2Cl2 (42-51)], yielding the title compound. 1H NMR (CDCl3, 400 MHz) δ 2.42-2.60 (m, 3H), 2.60-2.73 (m, 3H), 3.88 (d, J=6.4 Hz, 2H), 5.19 (brs, 2H), 5.44-5.53 (mc, 1H), 7.39 (s, 1H), 7.46-7.52 (m, 1H), 7.52-7.58 (m, 2H), 7.71 (dd, J=1.7, 8.3 Hz, 1H), 7.92 (d, J=8.5 Hz, 1H), 7.94 (d, J=7.7 Hz, 1H), 8.17-8.22 (m, 2H), 8.27 (d, J=8.5 Hz, 1H), 8.29-8.32 (m, 1H), 8.36 (s, 1H). 13C NMR (CDCl3, 100.6 MHz, DEPT135) δ 30.62 (+), 32.16 (2C1-), 46.70 (+), 65.12 (−), 101.04 (Cquart), 116.13 (Cquart), 118.88 (+), 120.64 (+), 125.82 (Cquart), 127.27 (+), 127.45 (2C, +), 128.17 (+), 128.21 (+), 128.71 (2C, +), 129.40 (+), 136.23 (Cquart), 136.49 (+), 139.23 (Cquart), 148.28 (Cquart), 150.47 (Cquart), 151.57 (+), 157.09 (Cquart) 157.97 (Cquart). MS (ES+): m/z 422.1 (51) [MH+], 338.2 (39) [MH+-cyclobutene-CH2OH]. HPLC: tR=2.4 min (OpenLynx, polar—5 min).
Reaction SMILES: [F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6](=[O:13])[NH:7]2.[H-].[Na+].[CH2:16]([O:23][C:24]([NH:26][C@@H:27]1[CH2:32][CH2:31][N:30]([CH2:33][CH2:34]OS(C)(=O)=O)[CH2:29][C@H:28]1[C:40]([O:42][CH3:43])=[O:41])=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(OC(=O)NC1CCN(CCN2C3C(=CC=C(F)C=3F)C=CC2=O)CC1)(C)(C)C>>[CH2:16]([O:23][C:24]([NH:26][C@@H:27]1[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][N:7]2[C:8]3[C:3](=[C:2]([F:1])[CH:11]=[C:10]([F:12])[CH:9]=3)[CH:4]=[CH:5][C:6]2=[O:13])[CH2:29][C@H:28]1[C:40]([O:42][CH3:43])=[O:41])=[O:25])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: O=c1ccc2c(F)cc(F)cc2[nH]1
Reactant: COC(=O)[C@@H]1CN(CCOS(C)(=O)=O)CC[C@H]1NC(=O)OCc1ccccc1
Agent: CC(C)(C)OC(=O)NC1CCN(CCn2c(=O)ccc3ccc(F)c(F)c32)CC1
Agent: [H-]
Agent: [Na+]
Product: COC(=O)[C@@H]1CN(CCn2c(=O)ccc3c(F)cc(F)cc32)CC[C@H]1NC(=O)OCc1ccccc1

Procedure:
5,7-Difluoroquinolin-2(1H)-one (Intermediate 25) (350 mg, 1.93 mmol) was deprotonated with sodium hydride (85 mg, 60% in oil, 2.13 mmol) and alkylated with methyl (3R,4R)-4-{[(benzyloxy)carbonyl]amino}-1-{2-[(methylsulfonyl)oxy]ethyl}piperidine-3-carboxylate (Intermediate 40) (1.93 mmol) as described for Intermediate 20 to give the product as a colorless hard foam, 538 mg (56%).
Reaction SMILES: [CH2:1]([P:3]([CH2:6][CH3:7])[CH2:4][CH3:5])[CH3:2].[I:8]C.[CH3:10]CCCCC>C1(C)C=CC=CC=1>[I-:8].[CH2:1]([P+:3]([CH2:6][CH3:7])([CH2:4][CH3:5])[CH3:10])[CH3:2]
Reactant: CI
Reactant: CCCCCC
Reactant: CCP(CC)CC
Solvent: Cc1ccccc1
Product: CC[P+](C)(CC)CC
Product: [I-]

Procedure:
To 236 g (0.5 mol) of a commercially available 25% solution of triethylphosphine (product name: HISHICOLIN (registered trademark) P-2, manufactured by Nippon Chemical Industrial Co., Ltd.) in toluene, 71 g (0.5 mol) of iodomethane (reagent, manufactured by Tokyo Chemical Industry Co., Ltd.) was added dropwise under a nitrogen atmosphere, and the mixture was reacted at 30 to 40° C. for 5 hours with stirring. After the reaction was completed, 100 ml of hexane was added to the reaction mixture to precipitate crystals. The resulting crystals were filtered and vacuum dried under a degree of vacuum of 0.5 kPa at 80° C. for 3 hours to obtain triethylmethylphosphonium iodide. Thereby, 116 g of triethylmethylphosphonium iodide was obtained (yield 89%). To 78 g (0.3 mol) of the resulting triethylmethylphosphonium iodide, 78 g of pure water was added to form a 50% aqueous solution. Thereto, was added 86 g (0.3 mol) of lithium bis(trifluoromethylsulfonyl)imide (reagent, manufactured by Kanto Chemical Co., Inc.) to allow them to react with each other, followed by stirring for 2 hours at room temperature (25° C.) to complete the reaction. After the completion of the stirring, precipitated crystals were separated by filtration and dissolved in acetone, followed by adding hexane thereto to recrystallize the crystals. The resulting crystals were filtered and vacuum dried under a degree of vacuum of 0.5 kPa at 80° C. for 3 hours. The structure of the resulting product was examined by 1H-NMR, 13C-NMR, 19F-NMR, and 31P-NMR. The product was identified as triethylmethylphosphonium bis(trifluoromethylsulfonyl)imide (TEMP-TFSI), and it had a purity of 99%. The resulting TEMP-TFSI was a white solid at room temperature (25° C.), which had a moisture content determined by the Karl Fischer titration method of 98 ppm and a chlorine content determined by ion chromatography of 13 ppm. The amount of the product yielded was 105 g (yield 85%).
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[C:8]([O:10][C:11]2[CH:16]=[CH:15][C:14]([CH2:17][OH:18])=[CH:13][C:12]=2[F:19])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[H-].[Na+].Cl[C:23]1[CH:24]=[C:25]2[N:32]([CH3:33])[CH2:31][CH2:30][N:26]2[C:27](=[O:29])[N:28]=1>C1COCC1>[Cl:1][C:2]1[CH:9]=[C:8]([O:10][C:11]2[CH:16]=[CH:15][C:14]([CH2:17][O:18][C:23]3[CH:24]=[C:25]4[N:32]([CH3:33])[CH2:31][CH2:30][N:26]4[C:27](=[O:29])[N:28]=3)=[CH:13][C:12]=2[F:19])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]
Reactant: CN1CCn2c1cc(Cl)nc2=O
Reactant: N#Cc1ccc(Oc2ccc(CO)cc2F)cc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CN1CCn2c1cc(OCc1ccc(Oc3ccc(C#N)c(Cl)c3)c(F)c1)nc2=O

Procedure:
Prepared in a manner similar to that described for E1 using 2-chloro-4-(2-fluoro-4-(hydroxymethyl)phenoxy)benzonitrile (100 mg, 0.360 mmol) in THF (8 mL), sodium hydride (21.6 mg, 0.540 mmol) and 7-chloro-1-methyl-2,3-dihydroimidazo[1,2-c]pyrimidin-5(1H)-one (66.8 mg, 0.360 mmol).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:14]3[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=3)[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:30]2[CH:31]=[N:32][NH:33][CH:34]=2)O1>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>[NH:32]1[CH:31]=[C:30]([C:2]2[CH:7]=[CH:6][C:5]([C:8]3([C:14]4[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=4)[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]3)=[CH:4][CH:3]=2)[CH:34]=[N:33]1
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Reactant: N#Cc1ccc(C2(c3ccc(Cl)cc3)CCNCC2)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Product: N#Cc1ccc(C2(c3ccc(-c4cn[nH]c4)cc3)CCNCC2)cc1
Temperature: 100 °C

Procedure:
4-[4-(4-chloro-phenyl)-piperidin-4-yl]-benzonitrile was reacted with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole following the procedure set out in Example 1, but using tetrakis(triphenylphosphine)palladium (0) as the catalyst and heating at 100° C. for 15 minutes, to obtain the title compound. LCMS (PS-A3) Rt 6.68 min [M+H]+ 329. 1H NMR (Me-d3-OD) δ 2.65-2.73 (4H, m), 2.77-2.85 (4H, m), 3.75 (3H, s), 7.46 (2H, d), 7.59 (2H, d), 7.68 (2H, d), 7.71 (2H, d), 8.42 (2H, br.s).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=1)[CH:6]=[CH:5]2.[C:19]1(B(O)O)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+].C(Cl)Cl>O1CCOCC1.O.O>[CH3:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][N:7]2[C:8]3[C:4](=[CH:3][C:2]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:10][CH:9]=3)[CH:5]=[CH:6]2)=[CH:13][CH:14]=1
Reactant: Cc1ccc(Cn2ccc3cc(Br)ccc32)cc1
Reactant: OB(O)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: O
Solvent: C1COCCO1
Product: Cc1ccc(Cn2ccc3cc(-c4ccccc4)ccc32)cc1
Temperature: 70 °C
Reaction time: 48 h
Yield: 48.5 %

Procedure:
A mixture of 5-bromo-1-(4-methylbenzyl)-1H-indole (1.0 g, 3.33 mmol), benzeneboronic acid (0.621 g, 5.0 mmol), potassium carbonate (0.691 g, 5.0 mmol), and [1′1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with methylenechloride (1:1) (0.816 g, 1.0 mmol) in dioxane-water (10:1, 16.5 mL) was stirred at 70° C. for 2 day. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic extract was washed with water and brine, and then concentrated to an oil. The residue was purified by flash column chromatography using hexane/ethyl acetate (96:4) as an eluant to give the title compound as a semi-solid (0.48 g, 49%). Mass spectrum (+ESI, [M+H]+) m/z 298. 1HNMR (300 MHz, DMSO-d6): δ 7.80 (s, 1H), 7.63 (d, 2H, J=8.4 Hz), 7.48 (d, 2H, J=11.1 Hz), 7.38-7.45 (m, 3H), 7.11 (m, 4H), 6.52 (d, 2H, J=2.8 Hz), 5.38 (s, 2H), and 2.22 ppm (s, 3H).
Reaction SMILES: C(OC1[CH:12]=[CH:11][C:8]([CH:9]=[CH2:10])=[CH:7][CH:6]=1)(=O)C.C(O[C:18]([O:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=O)(C)(C)C.C(=O)([O-])[O-].[K+].[K+].C1COCC1>C(Cl)Cl>[C:24]([O:23][C:21]([O:20][C:18]1[CH:10]=[CH:9][C:8]([CH:11]=[CH2:12])=[CH:7][CH:6]=1)=[O:22])([CH3:25])([CH3:26])[CH3:27]
Reactant: C=Cc1ccc(OC(C)=O)cc1
Reactant: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: C1CCOC1
Product: C=Cc1ccc(OC(=O)OC(C)(C)C)cc1
Reaction time: 22 h

Procedure:
In 200 mL of methylene chloride was dissolved 6.91 g (0.043 m) of 4-acetoxystyrene and 13.10 g (0.060 m) of di-t-butyldicarbonate under nitrogen. To the solution at room temperature was added 14.0 g (0.101 m) of potassium carbonate and the mixture was vigorously stirred for 22 hours, following the reaction by thin layer chromatography. After 22 hours at room temperature 100 mL of THF was added and the reaction was further stirred for 142 hours. It was worked up as in the above Examples. There was a very low yield (less than 10 %) of the product, 4-(t-butoxycarbonyloxy)styrene, under these conditions as analyzed by NMR, HPLC and TLC.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([CH:13]=O)[CH:7]=[CH:6]2.[NH:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1.[Na]>O1CCCC1.C(O)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([CH2:13][N:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1)[CH:7]=[CH:6]2
Reactant: COc1ccc2cc(C=O)ccc2c1
Reactant: C1CCNC1
Agent: [Na]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: COc1ccc2cc(CN3CCCC3)ccc2c1
Temperature: 0 °C
Reaction time: 7 h
Yield: 100.1 %

Procedure:
To a solution of 6-methoxy-2-naphthaldehyde (3.00 g, 16.1 mmol) and pyrrolidine (2.69 ml, 32.2 mmol) in tetrahydrofuran (32 ml) and acetic acid (16 ml) was added sodium triacetoxyhydroborate. (6.83 g, 32.2 mmol) at 0° C., and the mixture was stirred at room temperature for 7 hours. The solvent was distilled off under reduced pressure, 1N hydrochloric acid was added to the resulting oil, and the mixture was washed with diethyl ether. An 8N aqueous sodium hydroxide solution was added to the aqueous layer, followed by extraction with ethyl acetate. The extract was washed with an aqueous saturated sodium chloride solution, and dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure to obtain the titled compound (3.89 g).