Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:7]([I:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[N:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CS(C)=O>[I:8][C:7]1[C:2]([O:22][C:19]2[CH:18]=[CH:17][C:16]([NH:15][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][N:9]=3)=[CH:21][CH:20]=2)=[N:3][CH:4]=[CH:5][CH:6]=1
Reactant: Clc1ncccc1I
Reactant: Oc1ccc(Nc2ccccn2)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CS(C)=O
Solvent: O
Product: Ic1cccnc1Oc1ccc(Nc2ccccn2)cc1
Temperature: 80 °C

Procedure:
To a 250-mL round-bottomed flask was added 2-chloro-3-iodopyridine (5.32 g, 22.22 mmol), 4-(pyridin-2-ylamino)phenol (4.96 g, 26.6 mmol) and cesium carbonate (11.27 g, 34.6 mmol) in DMSO (100 mL) and the reaction was heated at 80° C. overnight. The reaction was cooled to rt and poured into water (400 mL). The solution was extracted with EtOAc (4×100 mL) and the combined organic layers were washed with brine and dried over Na2SO4. The solution was filtered, evaporated onto silica gel and purified by flash chromatography (Isco, (330 gram)) eluting with 2M NH3 in MeOH:CH2Cl2 (0:1→1:19). The material was dissolved in MeOH, evaporated onto silica gel and further purified by flash chromatography (Isco (330 gram)) eluting with EtOAc:hexanes (0:1→3:1) to give a white amorphous solid. MS (ESI, pos. ion) m/z: 389.9. IC50 (uM)=0.2284.
Reaction SMILES: [C:1]1([CH2:7][O:8][C:9]2[CH:10]=[CH:11][CH2:12][C:13]3[C:17]=2[N:16]=[C:15]2[CH2:18][CH2:19][CH2:20][CH2:21][C:14]=32)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[F:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29]Cl)=[CH:27][CH:26]=1>CN(C)C=O>[C:1]1([CH2:7][O:8][C:9]2[CH:10]=[CH:11][CH:12]([CH2:29][C:28]3[CH:31]=[CH:32][C:25]([F:24])=[CH:26][CH:27]=3)[C:13]3[C:17]=2[N:16]=[C:15]2[CH2:18][CH2:19][CH2:20][CH2:21][C:14]=32)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: C1=CC(OCc2ccccc2)=C2N=C3CCCCC3=C2C1
Reactant: Fc1ccc(CCl)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Fc1ccc(CC2C=CC(OCc3ccccc3)=C3N=C4CCCCC4=C32)cc1
Yield: 75.3 %

Procedure:
A solution of 1,2,3,4-tetrahydro-6-(phenylmethoxy)-9H-dibenzo[b,d]pyrrole (2.77 g) in dimethylformamide (20 mL) was stirred under argon at room temperature and treated with a 55% oil dispersion of sodium hydride in mineral oil (0.48 g). After stirring for ten minutes, a solution of 4-fluorobenzyl chloride (1.73 g) in dimethylformamide (5 mL) was added and the mixture was stirred for an additional 30 minutes. The solvent was removed by evaporation and the residue was mixed with water and extracted with dichloromethane. The organic phase was dried over sodium sulfate, concentrated and the residue was purified by HPLC chromatography (eluting system: dichloromethane-hexane 1:2) and crystallization from ether-hexane to produce 2.9 g (75%) of 1,2,3,4-tetrahydro-6-(phenylmethoxy)-9-[(4-fluorophenyl)methyl]-9H-dibenzo[b,d]pyrrole, mp 134°-135° C.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:21])[C:5]([C:10]1[CH:15]=[CH:14][C:13]([NH2:16])=[C:12]([NH:17][CH3:18])[C:11]=1[C:19]#[N:20])([CH3:9])[C:6](=[O:8])[CH3:7])[CH3:2].[F:22][C:23]1[CH:28]=[CH:27][C:26]([N:29]=[C:30]=S)=[C:25]([CH3:32])[CH:24]=1>C1COCC1>[CH2:1]([O:3][C:4](=[O:21])[C:5]([C:10]1[CH:15]=[CH:14][C:13]2[N:16]=[C:30]([NH:29][C:26]3[CH:27]=[CH:28][C:23]([F:22])=[CH:24][C:25]=3[CH3:32])[N:17]([CH3:18])[C:12]=2[C:11]=1[C:19]#[N:20])([CH3:9])[C:6](=[O:8])[CH3:7])[CH3:2]
Reactant: CCOC(=O)C(C)(C(C)=O)c1ccc(N)c(NC)c1C#N
Reactant: Cc1cc(F)ccc1N=C=S
Solvent: C1CCOC1
Product: CCOC(=O)C(C)(C(C)=O)c1ccc2nc(Nc3ccc(F)cc3C)n(C)c2c1C#N
Temperature: 25 °C
Reaction time: 48 h
Yield: 56.5 %

Procedure:
To a glass scintillation vial was added 2-(4-amino-2-cyano-3-methylamino-phenyl)-2-methyl-3-oxo-butyric acid ethyl ester (0.247 g, 0.854 mmol), followed by THF (5 mL) and a magnetic stir bar. To the resulting solution was added 4-fluoro-1-isothiocyanato-2-methyl-benzene (0.191 g, 1.14 mmol) and the solution was stirred at room temperature for 48 h. To the solution was then added mercuric oxide (0.222 g, 1.02 mmol), and stirring was continued at room temperature for 24 h. The brown suspension was then filtered through a ½ inch thick pad of silica, washed with THF, and concentrated to dryness. The resulting deep red solid was further purified by silica gel chromatography, eluting with ethyl acetate:hexane (0% -100%) to provide 2-[4-cyano-2-(4-fluoro-2-methyl-phenylamino)-3-methyl-3H-benzoimidazol-5-yl]-2-methyl-3-oxo-butyric acid ethyl ester (0.204 g, 56%) as a deep red solid. ESMS (m/z): (M+1)+ found, 423.
Reaction SMILES: NC1C=C(C=CC=1)OC1C=CN=C(C(N)=O)C=1.[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=1.[Si:26]([O:33][CH2:34][CH2:35][NH:36][C:37]([C:39]1[C:44](Cl)=[CH:43][CH:42]=[CH:41][N:40]=1)=[O:38])([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27]>>[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][C:43]2[CH:42]=[CH:41][N:40]=[C:39]([C:37]([NH:36][CH2:35][CH2:34][O:33][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:27])[CH3:28])=[O:38])[CH:44]=2)=[CH:21][CH:20]=1
Reactant: CC(C)(C)[Si](C)(C)OCCNC(=O)c1ncccc1Cl
Reactant: Nc1ccc(O)cc1
Agent: NC(=O)c1cc(Oc2cccc(N)c2)ccn1
Product: CC(C)(C)[Si](C)(C)OCCNC(=O)c1cc(Oc2ccc(N)cc2)ccn1

Procedure:
4-(4-Aminophenoxy)-N-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)pyridine-2-carboxamide was prepared by a method analogous to that described for 4-(3-aminophenoxy) pyridine-2-carboxamide (Intermediate 2C), starting from 4-aminophenol and N-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)chloropyridine-2-carboxamide MS ES: 388 (M+H)+, calcd 388, RT=3.60 min.
Reaction SMILES: [CH2:1]([NH:8][C:9]1[N:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[NH:15][CH:14]=[C:13]([C:19]([OH:21])=O)[C:12]2=[O:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.ClC(OCC)=O.[CH2:36]([NH2:40])[CH2:37][CH2:38][CH3:39].[Cl-].[Na+]>CN(C)C=O>[CH2:36]([NH:40][C:19]([C:13]1[C:12](=[O:22])[C:11]2[C:16](=[CH:17][CH:18]=[C:9]([NH:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[N:10]=2)[NH:15][CH:14]=1)=[O:21])[CH2:37][CH2:38][CH3:39]
Reactant: O=C(O)c1c[nH]c2ccc(NCc3ccccc3)nc2c1=O
Reactant: CCCCN
Agent: CCOC(=O)Cl
Agent: [Cl-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCCCNC(=O)c1c[nH]c2ccc(NCc3ccccc3)nc2c1=O
Temperature: 0 °C
Reaction time: 1 h
Yield: 69.9 %

Procedure:
To a solution of 6-benzylamino-4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxylic acid (53 mg, 0.2 mmol) and triethylamine (59 ml, 0.42 mmol) in N,N-dimethylformamide (1 mL) at 0° C. was added ethyl chloroformate (39 mL, 0.41 mmol). After stirring at 0° C. for 1 h, n-butylamine 99 mL, 1.0 mmol) was added. The reaction mixture was stirred an additional 2 h at 0° C., then poured into saturated aqueous sodium chloride. The mixture was cooled in an ice bath, the precipitate collected, rinsed with water and ether, then dried to afford 49 mg of N-n-butyl 6-benzylamino-4-oxo-1,4-dihydro-1,5-naphthyridine-3-carboxamide as a brown solid. Compound 1. An alternate name for this compound is: N-butyl(4-oxo-6-(benzylamino)(3-hydro-5-azaquinolyl))formamide.
Reaction SMILES: CC([C:4]1[C:12]2[O:11][C@@H:10]3[CH2:13][C@H:14]([OH:26])[C@@H:15]([NH:16][S:17]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)(=[O:19])=[O:18])[C@@H:9]3[C:8]=2[CH:7]=[CH:6][CH:5]=1)=O.C(=O)([O-])O.[Na+].ClC1C=CC=[C:35]([C:39]([O:41]O)=[O:40])C=1.S([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[C:39]([O:41][C:4]1[C:12]2[O:11][C@@H:10]3[CH2:13][C@H:14]([OH:26])[C@@H:15]([NH:16][S:17]([C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)(=[O:18])=[O:19])[C@@H:9]3[C:8]=2[CH:7]=[CH:6][CH:5]=1)(=[O:40])[CH3:35]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CC(=O)c1cccc2c1O[C@@H]1C[C@H](O)[C@@H](NS(=O)(=O)c3ccccc3)[C@H]21
Agent: O=C([O-])O
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: CC(=O)Oc1cccc2c1O[C@@H]1C[C@H](O)[C@@H](NS(=O)(=O)c3ccccc3)[C@H]21
Temperature: 25 °C
Reaction time: 5 h

Procedure:
(1S, 2S, 3aR, 8bS)-1-benzenesulfonamido-2-hydroxy-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofuran-5-yl methyl ketone (112) (1.57 g) was dissolved in methylene chloride (30 ml) followed by the addition of sodium hydrogencarbonate (2.12 g) and metachloroperbenzoic acid (potency: 70%, 4.61) and stirring for 5 hours at room temperature. A 4% aqueous solution of sodium sulfite (100 ml) was added to the reaction mixture followed by extraction with methylene chloride (100 ml+50 ml×2). The organic layer was washed with saturated brine (50 ml×2) and concentrated to a solid after drying with anhydrous magnesium sulfate. The residue was purified with column chromatography (silica gel: n-hexane/ethyl acetate 1:1-1:2) to obtain (1S, 2S, 3aR, 8bS)-1-benzenesulfonamido-2-hydroxy- 2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofuran-5-yl acetate (1.26 g).
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13](/[C:16](/[C:29]3[CH:33]=[CH:32][S:31][CH:30]=3)=[CH:17]/[CH2:18][N:19]([CH2:21][C:22]([O:24]C(C)(C)C)=[O:23])[CH3:20])=[CH:12][CH:11]=2)=[CH:6][CH:5]=1)([CH3:3])[CH3:2].CO>C(O)=O>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([C:10]2[CH:15]=[CH:14][C:13](/[C:16](/[C:29]3[CH:33]=[CH:32][S:31][CH:30]=3)=[CH:17]/[CH2:18][N:19]([CH2:21][C:22]([OH:24])=[O:23])[CH3:20])=[CH:12][CH:11]=2)=[CH:8][CH:9]=1)([CH3:3])[CH3:2]
Reactant: CC(C)c1ccc(-c2ccc(/C(=C/CN(C)CC(=O)OC(C)(C)C)c3ccsc3)cc2)cc1
Solvent: O=CO
Solvent: CO
Product: CC(C)c1ccc(-c2ccc(/C(=C/CN(C)CC(=O)O)c3ccsc3)cc2)cc1
Temperature: 40 °C

Procedure:
(Z)-N-(1-(4-(4-Isopropylphenyl)phenyl)-1-(3-thienyl)prop-1-en-3-yl)sarcosine, t-butyl ester F(i) (18.62 g, 40.3 mmol) was dissolved in 96% formic acid (200 mL). The solution was warmed at 40° C. overnight, then concentrated. The residue was co-evaporated twice with CH2Cl2. Column chromatography (2-15% MeOH/CH2Cl2) provided a pale yellow solid. Trituration with methanol (MeOH) provided pure (Z)-N-(1-(4-(4-isopropylphenyl)phenyl)-1-(3-thienyl)prop-1-en-3-yl)sarcosine G(i) (11.38 g, 70%) as a white solid. 1H NMR (300 MHz, methanol-d4) 1.23 (d, 6H), 2.47 (s, 3H), 2.92 (hept, 1H), 3.26 (s, 2H), 3.50 (d, 2H), 6.22 (t, 1H), 6.94 (d, 1H), 7.32 (d, 4H), 7.46 (d, 1H), 7.57-7.65 (m, 5H).
Reaction SMILES: Cl.[CH3:2][O:3][C:4](=[O:18])[CH2:5][CH2:6][NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][CH:10]=1.C(N(CC)CC)C.[CH2:26]([O:28][C:29]([CH2:31][C:32](Cl)=[O:33])=[O:30])[CH3:27]>C(Cl)Cl>[CH2:26]([O:28][C:29](=[O:30])[CH2:31][C:32](=[O:33])[N:7]([CH2:8][C:9]1[CH:10]=[CH:11][C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=1)[CH2:6][CH2:5][C:4]([O:3][CH3:2])=[O:18])[CH3:27]
Reactant: COC(=O)CCNCc1ccc([N+](=O)[O-])cc1
Reactant: CCOC(=O)CC(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)CC(=O)N(CCC(=O)OC)Cc1ccc([N+](=O)[O-])cc1
Reaction time: 1 h
Yield: 96.4 %

Procedure:
N-(p-Nitrobenzyl)-β-alanine methyl ester hydrochloride (32.66 g) and triethylamine (38 ml) are dissolved in methylene chloride (200 ml), and a solution of ethoxycarbonylacetyl chloride (20.0 g) in methylene chloride (100 ml) is added dropwise to the mixture under ice-cooling. The mixture is stirred at the same temperature for one hour, and the mixture is filtered to remove precipitates (triethylamine hydrochloride). The filtrate is washed with 2% HCl, water, 2% NaOH and water, dried and then distilled to remove the solvent to give ethyl[N-(p-nitrobenzyl)-N-(methoxycarbonylethyl)carbamoyl]acetate (40.4 g, 96.4%) as yellow oil.
Reaction SMILES: [CH2:1]([N:5]([CH2:51][CH2:52][CH2:53][CH3:54])[C:6]([C:8]1[C:12]([Cl:13])=[C:11]([CH2:14][CH2:15][OH:16])[N:10]([C:17]2[CH:22]=[CH:21][C:20]([C:23](=[O:38])[NH:24][S:25]([C:28]3[CH:37]=[CH:36][C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH:29]=3)(=[O:27])=[O:26])=[CH:19][C:18]=2[C:39]([N:41]2[CH2:50][CH2:49][C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[CH2:42]2)=[O:40])[N:9]=1)=[O:7])[CH2:2][CH2:3][CH3:4].CC(C)=[O:57].OS(O)(=O)=O.O=[Cr](=O)=O>CC(C)=O>[Cl:13][C:12]1[C:8]([C:6](=[O:7])[N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[CH2:51][CH2:52][CH2:53][CH3:54])=[N:9][N:10]([C:17]2[CH:22]=[CH:21][C:20]([C:23](=[O:38])[NH:24][S:25]([C:28]3[CH:37]=[CH:36][C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH:29]=3)(=[O:27])=[O:26])=[CH:19][C:18]=2[C:39]([N:41]2[CH2:50][CH2:49][C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[CH2:42]2)=[O:40])[C:11]=1[CH2:14][C:15]([OH:57])=[O:16]
Reactant: CCCCN(CCCC)C(=O)c1nn(-c2ccc(C(=O)NS(=O)(=O)c3ccc4ccccc4c3)cc2C(=O)N2CCc3ccccc3C2)c(CCO)c1Cl
Reactant: CC(C)=O
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Product: CCCCN(CCCC)C(=O)c1nn(-c2ccc(C(=O)NS(=O)(=O)c3ccc4ccccc4c3)cc2C(=O)N2CCc3ccccc3C2)c(CC(=O)O)c1Cl
Temperature: 25 °C
Reaction time: 0.42 h
Yield: 21.9 %

Procedure:
To N,N-dibutyl-4-chloro-5-(2-hydroxyethyl)-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamide (Example 170, 27 mg, 0.035 mmol) in acetone (640 μL) was added Jones reagent (39 μL, 0.11 mmol). The resulting reaction mixture was stirred at room temperature for 25 min. Additional Jones reagent (39 μL, 0.11 mmol) was added and stirring was continued for 1.5 h. The reaction mixture was then quenched with i-PrOH followed by water. The aqueous layer was extracted with EtOAc (3×), and the combined organics were washed with sat. aq. NaCl solution and dried over Na2SO4. After filtering through a pipette containing a small plug of CELITE®, concentration in vacuo afforded a yellow oil. The crude oil was purified by preparative HPLC to give the title compound (6 mg, 22%) as a white solid after lyophilization. 1H NMR (CD3OD, 2:1 mixture of amide rotamers) δ 8.56 (s, 1H), 8.19 (ddd, J=8.4 Hz, 3.2, 1.9 1H), 8.12 (d, J=1.8 Hz, 1H), 8.04-7.99 (m, 2H), 7.96-7.90 (m, 2H), 7.85 (dd, J=12.8, 8.4 Hz, 1H), 7.63-7.54 (m, 2H), 7.25-7.06 (m, 3.5H), 6.94 (d, J=7.0 Hz, 0.5H), 4.77-4.41 (m, 1.5H), 4.09 (br s, 0.5H), 3.79-3.38 (m, 5H), 3.24-2.67 (m, 5H), 1.60-0.84 (m, 11H), 0.78 (t, J=7.3 Hz, 2H), 0.71-0.65 (m, 1H); MS(ESI+) m/z 784.3 (M+H)+.
Reaction SMILES: CC(C)[N:3]=C=NC(C)C.[CH3:10][C:11]1[C:16]([NH:17][C:18]([C:20]2[S:24][C:23]([NH:25][C:26]3[CH:27]=[C:28]([N:33]4[CH2:38][CH2:37][N:36]([CH2:39][CH2:40][OH:41])[CH2:35][CH2:34]4)[N:29]=[C:30]([CH3:32])[N:31]=3)=[N:22][CH:21]=2)=[O:19])=[C:15]([Cl:42])[CH:14]=[CH:13][CH:12]=1.[NH:43](C(OC(C)(C)C)=O)[C@H:44]([C:48]([OH:50])=O)[CH:45]([CH3:47])[CH3:46].C1(C)C=CC(S([O-])(=O)=O)=CC=1.CN(C)C1C=C[NH+]=CC=1>C(Cl)Cl.CN(C=O)C>[CH3:10][C:11]1[C:16]([NH:17][C:18]([C:20]2[S:24][C:23]([NH:25][C:26]3[CH:27]=[C:28]([N:33]4[CH2:38][CH2:37][N:36]([CH2:39][CH2:40][OH:41])[CH2:35][CH2:34]4)[N:29]=[C:30]([CH3:32])[N:31]=3)=[N:22][CH:21]=2)=[O:19])=[C:15]([Cl:42])[CH:14]=[CH:13][CH:12]=1.[NH2:43][C@H:44]([C:48]([NH2:3])=[O:50])[CH:45]([CH3:47])[CH3:46]
Reactant: CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: CC(C)N=C=NC(C)C
Agent: CN(C)c1cc[nH+]cc1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: Cc1nc(Nc2ncc(C(=O)Nc3c(C)cccc3Cl)s2)cc(N2CCN(CCO)CC2)n1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(C)[C@H](N)C(N)=O
Temperature: 25 °C
Reaction time: 5 h

Procedure:
DIC (302 mg, 2.4 mmol) was added with stirring to a DMF (4 mL) solution of dasatinib (196 mg, 0.4 mmol), Boc-Val-OH (104 mg, 0.48 mmol), and DPTS (124 mg, 0.4 mmol). The resulting mixture was stirred at room temperature for five hours. After this period, DCM (100 mL) was added to the reaction mixture which was allowed to stir for an additional 20 minutes. The mixture was transferred into a separatory funnel and washed with 5% NaCl (100 mL×3). The organic phase was dried over Na2SO4 and the solvent removed under reduced pressure. The resulting residue was purified by column chromatography (biotage: DCM/CH3OH, CH3OH, 5-10%, 20 CV). The obtained solid was redissolved in 5.0 mL of TFA/DCM (2:3) and the solution was stirred at room temperature for one hour. TFA and DCM were removed under reduced pressure. The residue was dissolved in 150 mL of DCM and the resulting solution was washed with 5% Na2CO3 and then 5% NaCl. The desired product was obtained (160 mg, yield: 68%) as a white solid; 1H NMR (500 MHz, CD3OD). δ 0.96 (d, 3H), 0.99 (d, 3H), 2.03 (m, 1H), 2.32 (s, 3H), 2.47 (s, 3H), 2.59 (t, 4H), 2.71 (t, 2H), 3.64 (t, 4H), 4.32 (m, 2H), 6.00 (s, 1H), 7.22 (m, 2H), 7.34 (d, 1H), 8.14 (s, 1H); LC-MS (m/z) calcd., 586.2, found 587.2 [M+H]+.
Reaction SMILES: CC(P(C(C)(C)C)C1[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:10][CH:9]=[CH:8][CH:7]=1)(C)C.C(N(CC)CC)C.[C:29]1([C:35]#[C:36][P:37](=[O:42])([OH:41])[O:38][CH2:39][CH3:40])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C(C1C=CC=CC=1)CCC#C>[Au].ClC(Cl)C>[C:29]1([C:35]#[C:36][P:37](=[O:41])([O:42][C:8]([CH2:9][CH2:10][CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[CH2:7])[O:38][CH2:39][CH3:40])[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1
Reactant: CC(C)(C)P(c1ccccc1-c1ccccc1)C(C)(C)C
Reactant: CCOP(=O)(O)C#Cc1ccccc1
Agent: [Au]
Agent: C#CCCCc1ccccc1
Solvent: CCN(CC)CC
Solvent: CC(Cl)Cl
Product: C=C(CCCc1ccccc1)OP(=O)(C#Cc1ccccc1)OCC
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 74 %

Procedure:
A gold (Ag(I)) catalyst {[Au(JohnPhos)NCCH3]|SbF6—} [JohnPhos:(2-biphenyl)di-tert-butylphosphine] (11.3 mg, 0.015 mmol) and triethylamine (Et3N) (3.0 mg, 0.03 mmol) were put into a reaction container, and dichloroethane (0.4 mL) was put thereinto. After stirring at room temperature for 5 minutes, ethyl hydrogen phenylethynylphosphonate) (63.0 mg, 0.3 mmol) diluted with 0.5 mL of dichloroethane was added thereto, and finally, pent-4-ynylbenzene (86.5 mg, 0.6 mmol) was put thereinto. Then, when all of the starting materials disappeared in the TLC, the reaction was allowed to be completed. After the solvent was removed under low atmospheric pressure, the product was separated by chromatography to obtain ethyl 5-phenylpent-1-en-2-yl phenylethynylphosphonate (78.7 mg, 74%) which is a title compound.
Reaction SMILES: [C:1]([C:4]1[C:5]2[N:6]([CH:41]=[N:42][N:43]=2)[C:7]([CH2:32][C:33]2[C:38]([Cl:39])=[CH:37][CH:36]=[CH:35][C:34]=2[Cl:40])=[N:8][C:9]=1[NH:10][C:11]1[C:16]([F:17])=[CH:15][C:14]([N:18]2[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19]2)=[C:13]([F:31])[CH:12]=1)(=[O:3])[NH2:2].FC(F)(F)C(O)=O>ClCCl>[Cl:39][C:38]1[CH:37]=[CH:36][CH:35]=[C:34]([Cl:40])[C:33]=1[CH2:32][C:7]1[N:6]2[CH:41]=[N:42][N:43]=[C:5]2[C:4]([C:1]([NH2:2])=[O:3])=[C:9]([NH:10][C:11]2[CH:12]=[C:13]([F:31])[C:14]([N:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)=[CH:15][C:16]=2[F:17])[N:8]=1
Reactant: CC(C)(C)OC(=O)N1CCN(c2cc(F)c(Nc3nc(Cc4c(Cl)cccc4Cl)n4cnnc4c3C(N)=O)cc2F)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: NC(=O)c1c(Nc2cc(F)c(N3CCNCC3)cc2F)nc(Cc2c(Cl)cccc2Cl)n2cnnc12
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of the product of Example 15G (230 mg, 0.36 mmol) in dichloromethane (8 mL) was added trifluoroacetic acid (2 mL) dropwise. The mixture was stirred at ambient temperature for 4 hours and concentrated. The solid was washed with ethanol and dried under vacuum to give the title compound. 1H NMR (DMSO-d6, 300 MHz): δ 12.38 (d, J=1.5 Hz, 1H), 9.71 (s, 1H), 8.95 (d, J=2.1 Hz, 1H), 8.76 (br. s, 2H), 8.14 (d, J=2.1 Hz, 1H), 7.56-7.54 (m, 2H), 7.45-7.40 (m, 1H), 7.25-7.17 (m, 1H), 7.05-6.99 (m, 1H), 4.96 (s, 2H), 3.24-3.23 (m, 4H), 3.15-3.11 (m, 4H). MS: 533 (M+H+).
Reaction SMILES: [CH2:1]1[C:13]2[NH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH2:4][CH2:3][NH:2]1.[CH:14](=O)[CH2:15][CH3:16].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[CH2:14]([N:2]1[CH2:3][CH2:4][C:5]2[C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[NH:12][C:13]=2[CH2:1]1)[CH2:15][CH3:16]
Reactant: CCC=O
Reactant: c1ccc2c3c([nH]c2c1)CNCC3
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: CCCN1CCc2c([nH]c3ccccc23)C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 91.4 %

Procedure:
2,3,4,9-Tetrahydro-1H-beta-carbolin (2.5 g, 14.5 mmol) and propionaldehyde (1.06 ml, 14.5 mmol) were dissolved in THF (100 ml). Acetic acid (1.25 ml, 21.8 mmol) and sodium trisacetoxyborohydride (4.615 g, 21.8 mmol) were sequentially added to the reaction mixture and stirred for 1 h at room temperature. The reaction mixture was concentrated and the residue was dissolved in H2O (10 ml) and ethyl acetate (50 ml). The pH was adjusted to 9 by adding NaOH (2M). The organic phase was separated, dried over magnesium sulfate, filtered, and evaporated to dryness to yield the title product (2.84 g, 91%).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([OH:15])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[Cl:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[S:32](Cl)(=[O:34])=[O:33]>C=Cl.C(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([O:15][S:32]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[Cl:25])(=[O:34])=[O:33])[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Oc1cccc(OCc2ccccc2)c1
Reactant: O=S(=O)(Cl)c1ccccc1Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=S(=O)(Oc1cccc(OCc2ccccc2)c1)c1ccccc1Cl
Temperature: 0 °C
Reaction time: 2 h
Yield: 95.2 %

Procedure:
To a solution of 3-benzyloxyphenol (2.97 g, 15 mmol), as prepared in the preceding step, in methylene chlorine (50 mL) at 0° C., was added N,N-diisopropylethylamine (2 mL) and 2-chlorobenzenesulfonyl chloride (3.27 g, 15.5 mmol). The reaction mixture was stirred at 0° C. for 2 h and at room temperature for 2 h. The reaction mixture was diluted with methylene chloride (200 mL), washed sequentially with saturated NaHCO3 (2×50 mL) and brine (2×50 mL), dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography (1:1 hexane:methylene chloride) to give the title compound as a colorless liquid (5.35 g, 95%). 1H-NMR (300 MHz, CDCl3) δ 4.97 (s, 2H), 6.71 (dd, 1H), 6.78 (t, 1H), 6.85 (dd, 1H), 7.17 (t, 1H), 7.37 (m, 5H) 7.58 (m, 2H), 7.91 (dd, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]([NH:13][C:14](=[O:18])OCC)=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH3:19])[CH:9]=2)[N:4]=1.[N+:20]([C:23]1[CH:28]=[CH:27][C:26]([N:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)=[CH:25][CH:24]=1)([O-:22])=[O:21]>>[CH3:1][O:2][C:3]1[C:12]([NH:13][C:14]([N:32]2[CH2:33][CH2:34][N:29]([C:26]3[CH:25]=[CH:24][C:23]([N+:20]([O-:22])=[O:21])=[CH:28][CH:27]=3)[CH2:30][CH2:31]2)=[O:18])=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH3:19])[CH:9]=2)[N:4]=1
Reactant: CCOC(=O)Nc1nc2cc(C)ccc2nc1OC
Reactant: O=[N+]([O-])c1ccc(N2CCNCC2)cc1
Product: COc1nc2ccc(C)cc2nc1NC(=O)N1CCN(c2ccc([N+](=O)[O-])cc2)CC1
Yield: 86 %

Procedure:
Ethyl N-(2-methoxy-6-methylquinoxalin-3-yl)carbamate and 1-(4-nitrophenyl)piperazine were reacted by the same way with the example 43 to obtain the titled compound (yield, 86%). 1H NMR (300 MHz, CDCl3): δ 2.46 (s, 3H), 3.52-3.58 (m, 4H), 3.82 (s, 3H), 4.09-4.13 (m, 4H), 6.85 (d, 7=9.2 Hz, 2H), 7.03-7.15 (m, 1H), 7.41 (m, 1H), 7.52-7.58 (m, 2H), 8.16 (d, 1=9.2 Hz, 2H).