Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[O:8][C:7]([C:9]([OH:11])=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1.[N:37]1([CH2:43][C:44]2[CH:45]=[C:46]([CH:60]=[CH:61][CH:62]=2)[O:47][CH2:48]/[CH:49]=[CH:50]\[CH2:51][NH:52][C:53](=[O:59])[CH2:54][S:55][CH2:56][CH2:57][NH2:58])[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1>ClCCl>[N:37]1([CH2:43][C:44]2[CH:45]=[C:46]([CH:60]=[CH:61][CH:62]=2)[O:47][CH2:48]/[CH:49]=[CH:50]\[CH2:51][NH:52][C:53](=[O:59])[CH2:54][S:55][CH2:56][CH2:57][NH:58][C:9]([C:7]2[O:8][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)=[O:11])[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1
Reactant: O=C(O)c1ccc([N+](=O)[O-])o1
Reactant: NCCSCC(=O)NC/C=C\COc1cccc(CN2CCCCC2)c1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Solvent: ClCCl
Product: O=C(CSCCNC(=O)c1ccc([N+](=O)[O-])o1)NC/C=C\COc1cccc(CN2CCCCC2)c1
Reaction time: 0.5 h
Yield: 10.6 %

Procedure:
There was suspended 1.67 g (0.011 mol) of 5-nitro-2-furoic acid in 85 ml of dichloromethane and added 1.62 g (0.011 mol) of HOBt and 2.26 g (0.011 mol) of DCC under cooling with ice, and the mixture was stirred for 30 minutes. Thereto was added 4.0 g (0.011 mol) of N-[4-[3-(piperidinomethyl) phenoxy]-cis-2-butenyl]-2-(2-aminoethylthio)acetamide and the mixture was stirred for 18 hours at room temperature. The precipitate was filtrated off, and the filtrate was washed with 10% aqueous solution of sodium hydroxide and with water and dried over Glauber's salt. Then the solvent was removed under reduced pressure and the residue was purified by ilica gel column chromatography (chloroform:methanol=10:1) to give 0.60 g of the titled compound as oily matter.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([OH:11])[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].[CH2:12](O)[CH2:13][CH3:14].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([O:11][CH2:12][CH2:13][CH3:14])[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9]
Reactant: CCCO
Reactant: O=[N+]([O-])c1ccc(O)cc1F
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CCCOc1ccc([N+](=O)[O-])c(F)c1

Procedure:
To a solution of the 3-fluoro-4-nitrophenol (32 mmol, 5.0 g), 1-propanol (48 mmol, 3.9 mL), and triphenylphosphine (64 mmol, 16.8 g) in CH2Cl2 (160 mL) at 0° C. was added DIAD (64 mmol, 12 mg). The reaction mixture was concentrated in vacuo. The product was isolated by flash chromatography on silica eluting with 5% EtOAc in hexanes. H1 NMR (500 MHz, CDCl3): δ 8.13 (t, J=8.7 Hz, 1H), 6.81-6.75 (m, 2H), 4.05 (d, J=6.4 Hz, 2H), 1.90 (m, 2H), 1.10 (t, J=7.3 Hz, 3H).
Reaction SMILES: [CH2:1]([C:8]1[C:20](=[O:21])[N:19]([CH:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)[C:11]2[N:12]=[C:13](S(C)=O)[N:14]=[CH:15][C:10]=2[CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][N:37]([C:40]2[CH:41]=[N:42][C:43]([NH2:46])=[CH:44][CH:45]=2)[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28]>C1(C)C=CC=CC=1>[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][N:37]([C:40]2[CH:41]=[N:42][C:43]([NH:46][C:13]3[N:14]=[CH:15][C:10]4[CH:9]=[C:8]([CH2:1][C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=5)[C:20](=[O:21])[N:19]([CH:22]5[CH2:26][CH2:25][CH2:24][CH2:23]5)[C:11]=4[N:12]=3)=[CH:44][CH:45]=2)[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:28])[CH3:29]
Reactant: CS(=O)c1ncc2cc(Cc3ccccc3)c(=O)n(C3CCCC3)c2n1
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc(N)nc2)CC1
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1CCN(c2ccc(Nc3ncc4cc(Cc5ccccc5)c(=O)n(C5CCCC5)c4n3)nc2)CC1
Yield: 19.9 %

Procedure:
6-Benzyl-8-cyclopentyl-2-methanesulfinyl-8H-pyrido[2,3-d]pyrimidin-7-one (0.64 g, 1.74 mmol) and 4-(6-Amino-pyridin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester (0.87 g, 2.96 mmol) in toluene (10 ml) were heated to 95° C. for 28 hours. The reaction mixture was allowed to cool then chromatographed on silica gel using a gradient of 20 to 50% ethyl acetate in hexane. The product-containing fractions were evaporated and the residue was triturated with acetonitrile to give a solid. This solid was collected by filtration and dried in vacuo to provide 4-[6-(6-benzyl-8-cyclopentyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)-pyridin-3-yl]-piperazine-1-carboxylic acid tert-butyl ester (0.201 g, 19.8%). MS (APCI) M++1: Calc'd, 582.31. Found, 582.3.
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[C:5](Cl)(=[O:7])[CH3:6].[NH:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][C:10]1=[O:18]>C(=S)=S>[C:5]([C:14]1[CH:13]=[C:12]2[C:17](=[CH:16][CH:15]=1)[NH:9][C:10](=[O:18])[CH2:11]2)(=[O:7])[CH3:6]
Reactant: CC(=O)Cl
Reactant: O=C1Cc2ccccc2N1
Agent: [Al+3]
Agent: [Cl-]
Solvent: S=C=S
Product: CC(=O)c1ccc2c(c1)CC(=O)N2
Reaction time: 0.08 h

Procedure:
To 95 ml. of carbon disulfide was added 27 g. (0.202 mole) of aluminum chloride, followed by the dropwise addition of a solution of 3 ml. (0.042 mole) of acetyl chloride in 5 ml. of carbon disulfide, with stirring. Stirring was continued for 5 minutes and then 4.4 g. (0.033 mole) of 2-oxindole was added. The resulting mixture was heated under reflux for 4 hours and cooled. The carbon disulfide was removed by decantation and the residue was triturated under water and recovered by filtration. After drying, 3.2 g. of the title compound was obtained, m.p. 225°-227° C.
Reaction SMILES: O.O.[Sn](Cl)Cl.[CH3:6][O:7][C:8]1[CH:9]=[C:10]([C:19](=[O:21])[CH3:20])[CH:11]=[C:12]([N+:16]([O-])=O)[C:13]=1[O:14][CH3:15].C(=O)([O-])O.[Na+].C(Cl)Cl>C(O)C>[NH2:16][C:12]1[C:13]([O:14][CH3:15])=[C:8]([O:7][CH3:6])[CH:9]=[C:10]([C:19](=[O:21])[CH3:20])[CH:11]=1
Reactant: COc1cc(C(C)=O)cc([N+](=O)[O-])c1OC
Agent: Cl[Sn]Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCO
Solvent: O
Product: COc1cc(C(C)=O)cc(N)c1OC
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
11.3 g of tin dichloride dihydrate are added to 2.25 g of 3',4'-dimethoxy-5'-nitroacetophenone dissolved in 50 ml of ethanol, where upon the mixture is stirred at 75° for 30 minutes. Thereupon, the reaction mixture is poured on to 100 g of ice, neutralized with about 300 ml of saturated sodium hydrogen carbonate solution and treated with 150 ml of methylene chloride. The mixture is filtered and the methylene chloride phase is separated. This is dried over sodium sulfate and evaporated, and the residue is recrystallized from ether/petroleum ether. There is obtained 5'-amino-3',4'-dimethoxyacetophenone of m.p. 63°-65°.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[CH2:4][NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:12][CH:13]=[CH2:14].[CH3:16][C:17]([C:19]1[CH:24]=[CH:23][C:22]([N:25]=[C:26]=[O:27])=[CH:21][CH:20]=1)=O.Cl.[NH2:29][OH:30].C(OC)(OC)OC>C1COCC1.N1C=CC=CC=1>[OH:30][N:29]=[C:17]([C:19]1[CH:24]=[CH:23][C:22]([NH:25][C:26]([N:5]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[CH2:12][CH:13]=[CH2:14])[CH2:4][C:3]([O:2][CH3:1])=[O:15])=[O:27])=[CH:21][CH:20]=1)[CH3:16]
Reactant: NO
Reactant: CC(=O)c1ccc(N=C=O)cc1
Reactant: C=CCc1ccccc1NCC(=O)OC
Agent: Cl
Solvent: C1CCOC1
Solvent: COC(OC)OC
Solvent: c1ccncc1
Product: C=CCc1ccccc1N(CC(=O)OC)C(=O)Nc1ccc(C(C)=NO)cc1
Reaction time: 3 h

Procedure:
A solution of 0.02 mol N-(2-allylphenyl)glycine methyl ester in 40 mL of THF is added dropwise to a solution of 0.02 mol of 4-isocyanatoacetophenone and 5 mL of pyridine in 40 mL of THF, and the reaction mixture is stirred for 3 hours. The solvent is then removed by rotary evaporator. The residue is dispersed in 50 mL of CH3OH, and 0.022 mol of hydroxylamine hydrochloride and 0.06 mol of trimethyl orthoformate are added. The reaction mixture is heated to reflux for 1 hour. The solvent is removed by rotary evaporator to give the product, N-[4-(1-hydroxyiminoethyl)phenyl]-N'-(2 -allylphenyl)-N'-methoxycarbonylmethylurea.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C:11]#[N:12].[C:13]([O-:16])(=[O:15])C.[Na+].[CH2:18](O)[CH3:19]>>[C:11]([C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([C:13]([O:16][CH2:18][CH3:19])=[O:15])[CH:3]=2)[NH:7][CH:6]=1)#[N:12]
Reactant: N#Cc1c[nH]c2ccc(Br)cc12
Reactant: CC(=O)[O-]
Reactant: CCO
Agent: [Na+]
Product: CCOC(=O)c1ccc2[nH]cc(C#N)c2c1
Temperature: 70 °C
Reaction time: 24 h
Yield: 41 %

Procedure:
To a solution of 5-bromo-1H-indole-3-carbonitrile (2.61 g, 11.8 mmol) in ethanol (50 mL) in a 500 mL Parr bottle was added sodium acetate (2.90 g, 35.6 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium (II) dichloride dichloromethane complex (1.93 g, 2.36 mmol). The reaction mixture was evacuated and back filled with nitrogen three times. The reaction vessel was then pressurized with 25 psi carbon monoxide. The reaction was heated to 70° C. and when the desired temperature was reached the pressure of the vessel was increased to 40 psi. The reaction was agitated at 70° C. for 24 hours. The mixture was filtered through Celite, rinsing with ethanol. The filtrate was concentrated under reduced pressure and then diluted with dichloromethane. The mixture was filtered to remove the insoluble solids. The filtrate was concentrated and purified by flash column chromatography (20-80% ethyl acetate/heptanes). The resulting solid was triturated with dichloromethane and a small amount of heptanes to give ethyl 3-cyano-1H-indole-5-carboxylate (1.05 g, 41%) 1H NMR (400 MHz, DMSO-d6, δ): 12.54 (br. s., 1 H), 8.41 (d, J=2.7 Hz, 1 H), 8.25 (d, J=1.6 Hz, 1 H), 7.89 (dd, J=8.6, 1.6 Hz, 1 H), 7.66 (dd, J=8.6, 0.6 Hz, 1 H), 4.34 (q, J=7.0 Hz, 2 H), 1.35 (t, J=7.1 Hz, 3 H).
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[C:9]([C:11]2[CH2:15][C:14]([C:20]3[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]([Cl:27])[CH:21]=3)([C:16]([F:19])([F:18])[F:17])[O:13][N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[F:28][C:29]([F:33])([F:32])[CH2:30][NH2:31].Cl.C(N(CC)CCCN=C=NCC)C>C(Cl)(Cl)Cl.CN(C1C=CN=CC=1)C>[NH2:1][C:2]1[CH:10]=[C:9]([C:11]2[CH2:15][C:14]([C:20]3[CH:21]=[C:22]([Cl:27])[CH:23]=[C:24]([Cl:26])[CH:25]=3)([C:16]([F:17])([F:18])[F:19])[O:13][N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4]([NH:31][CH2:30][C:29]([F:33])([F:32])[F:28])=[O:6]
Reactant: NCC(F)(F)F
Reactant: Nc1cc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)ccc1C(=O)O
Agent: CCN=C=NCCCN(CC)CC
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClC(Cl)Cl
Product: Nc1cc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)ccc1C(=O)NCC(F)(F)F
Temperature: 25 °C
Reaction time: 20 h
Yield: 19.6 %

Procedure:
In a solution of 0.60 g of crude 2-amino-4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]benzoic acid in 6 ml of chloroform, 0.20 g of 2,2,2-trifluoroethylamine, 0.02 g of 4-(N,N-dimethylamino)pyridine and 0.33 g of 1-[3-(diethylamino)propyl]-3-ethylcarbodiimide hydrochloride were added, and stirred at room temperature for 20 hours. After the completion of the reaction, the reaction mixture was subjected to purification with medium-pressure preparative liquid chromatography (Yamazen Corporation, medium pressure preparative system; YFLC-Wprep) that was eluted with ethyl acetate-hexane (1:4), and 0.14 g of the aimed product was obtained as pale yellow crystal.
Reaction SMILES: [C:1]([NH:4][C@@H:5]1[C@H:12]([OH:13])[C@H:11]([CH3:14])[O:10][C@H:7]([O:8][CH3:9])[CH2:6]1)(=[O:3])[CH3:2].[CH2:15](I)[CH3:16]>CN(C)C=O.[Ag]=O>[C:1]([NH:4][C@@H:5]1[C@H:12]([O:13][CH2:15][CH3:16])[C@H:11]([CH3:14])[O:10][C@H:7]([O:8][CH3:9])[CH2:6]1)(=[O:3])[CH3:2]
Reactant: CCI
Reactant: CO[C@@H]1C[C@H](NC(C)=O)[C@H](O)[C@H](C)O1
Agent: O=[Ag]
Solvent: CN(C)C=O
Product: CCO[C@H]1[C@@H](NC(C)=O)C[C@@H](OC)O[C@H]1C
Reaction time: 17 h

Procedure:
5.0 g of methyl 3-acetamido-2,3,6-trideoxy-β-L-lyxohexopyranoside were heated at 45° C. in the dark in a mixture of 25 ml of ethyl iodide and 20 ml of dimethylformamide containing 10 g of silver oxide. After 17 hours, the mixture was filtered through Celite and the filtrate was evaporated. The gum obtained was purified by column chromatography to give 3.4 g of methyl 3-acetamido-2,3,6-trideoxy-4-O-ethyl-β-L-lyxohexopyranoside in the form of colourless crystals of melting point 199°-200° C.; [α]D20 =-75.0° (c=0.5% in methanol).
Reaction SMILES: C(N(CC)CC)C.C(Cl)(Cl)Cl.[NH2:12][C:13]1[C:14]([S:20][CH3:21])=[N:15][C:16]([CH3:19])=[CH:17][CH:18]=1.[Br:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]Cl.[OH2:33]>>[Br:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31]([NH:12][C:13]1[C:14]([S:20][CH3:21])=[N:15][C:16]([CH3:19])=[CH:17][CH:18]=1)=[O:33]
Reactant: O
Reactant: ClCCCCCCCCCBr
Reactant: CSc1nc(C)ccc1N
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CSc1nc(C)ccc1NC(=O)CCCCCCCCBr
Temperature: 25 °C
Reaction time: 17 h
Yield: 27 %

Procedure:
Triethylamine (607 mg, 6.0 mmol) was added to a chloroform (10 ml) solution of 3-amino-6-methyl-2-methylthiopyridine (685 mg, 4.44 mmol), and a chloroform (3 ml) solution of 9-bromononanyl chloride (1,281 mg, 5 mmol) was then slowly added thereto dropwise while being cooled with ice. The mixture was stirred at room temperature for 17 hours. The reaction mixture was diluted with water, and then extracted with ethyl acetate. The organic layer was washed with water and then with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate. Subsequently, the solvent was distilled off, and the resulting crude product was purified through silica gel chromatography (silica gel 75 g, eluent—hexane:ethyl acetate=10:1→4:1) to obtain 433 mg (yield 27%) of 9-bromo-N-(6-methyl-2-methylthio-3-pyridyl)nonanamide as a colorless crystal (melting point: 80 to 82° C.).
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[CH:8]=[C:9]([CH:16]=[CH:17][C:18]=2[CH3:19])[C:10]([NH:12][CH:13]2[CH2:15][CH2:14]2)=[O:11])[CH:5]=[N:4][C:3]=1[C:20]#[N:21].[CH:22]1([Mg]Br)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.C1C[O:33][CH2:32]C1>C(OCC)(=O)C.O>[CH:22]1([C:20]2[N:21]=[C:32]([OH:33])[N:1]=[C:2]3[C:3]=2[N:4]=[CH:5][N:6]3[C:7]2[CH:8]=[C:9]([CH:16]=[CH:17][C:18]=2[CH3:19])[C:10]([NH:12][CH:13]2[CH2:14][CH2:15]2)=[O:11])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1
Reactant: Cc1ccc(C(=O)NC2CC2)cc1-n1cnc(C#N)c1N
Reactant: C1CCOC1
Reactant: Br[Mg]C1CCCCC1
Solvent: O
Solvent: CCOC(C)=O
Product: Cc1ccc(C(=O)NC2CC2)cc1-n1cnc2c(C3CCCCC3)nc(O)nc21
Reaction time: 4 h
Yield: 57 %

Procedure:
To a solution of 3-(5-amino-4-cyano-imidazol-1-yl)-N-cyclopropyl-4-methyl-benzamide (28 mg, 0.1 mmol, see Example 2A) in dry THF (5 ml) under nitrogen was added a 1 M solution of cyclohexylmagnesium bromide in THF (2M, 0.25 mL, 0.5 mmol) at room temperature. After the reaction of mixture was stirred at that temperature for 4 hours, 5 mL of water was added. The mixture was extracted with ethyl acetate (3×20 mL), washed with water and dried over MgSO4, and concentrated. The crude product was dissolved in 2 mL of methylene chloride. And then 1,1-carbonyldiimidazole (32 mg, 0.2 mmol) was added. After being stirred at room temperature for 1 hour, the mixture was diluted with 50 mL of ethyl acetate and water, and the ethyl acetate layer was separated, washed with water, brine and then dried over MgSO4. After filtration and concentration, the crude product was purified by preparatory HPLC to give a solid (22 mg, 57%). HPLC tR=1.94 min; MS m/z 392 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[C:7]([N+:8]([O-])=O)=[C:6]([Cl:11])[N:5]=[C:4]([S:12][CH3:13])[N:3]=1.O.O.Cl[Sn]Cl>CCO>[Cl:1][C:2]1[C:7]([NH2:8])=[C:6]([Cl:11])[N:5]=[C:4]([S:12][CH3:13])[N:3]=1
Reactant: CSc1nc(Cl)c([N+](=O)[O-])c(Cl)n1
Agent: Cl[Sn]Cl
Solvent: O
Solvent: CCO
Product: CSc1nc(Cl)c(N)c(Cl)n1
Temperature: 90 °C
Reaction time: 2 h
Yield: 81.9 %

Procedure:
To a solution of 4,6-dichloro-2-methylsulfanyl-5-nitro-pyrimidine (1.0 g, 4.2 mmol) in EtOH (20 mL) was added SnCl2.2H2O (3.8 g, 17 mmol). The mixture was heated to 90° C. After 2 h, the reaction mixture was cooled and the solution was concentrated. The residue was treated with saturated (satd.) aqueous (aq.) NaHCO3 until pH 8. The resulting mixture was then extracted with EtOAc (3×100 mL). The combined organic extracts were dried, filtered, and concentrated. The residue was purified by FCC to afford a colorless solid (723 mg, 87%). MS (ESI): mass calcd. for C5H5Cl2N3S, 208.9; m/z found, 210.3 [M+H]+. 1H NMR ((CD3)2SO): 5.89 (s, 2H), 2.45 (s, 3H).
Reaction SMILES: I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[CH:16]=[CH:15][C:14]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[CH:9]=2)[N:4]([S:23]([C:26]2[CH:32]=[CH:31][C:29]([CH3:30])=[CH:28][CH:27]=2)(=[O:25])=[O:24])[CH:3]=1.[F:33][C:34]1[CH:35]=[C:36]([CH:54]=[CH:55][CH:56]=1)[CH2:37][N:38]1[C:42]([CH3:43])=[C:41](B2OC(C)(C)C(C)(C)O2)[C:40]([CH3:53])=[N:39]1.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1(C)C=CC=CC=1.C(O)C.O>[F:33][C:34]1[CH:35]=[C:36]([CH:54]=[CH:55][CH:56]=1)[CH2:37][N:38]1[C:42]([CH3:43])=[C:41]([C:2]2[C:10]3[C:5](=[N:6][CH:7]=[C:8]([C:11]4[CH:16]=[CH:15][C:14]([N:17]5[CH2:22][CH2:21][O:20][CH2:19][CH2:18]5)=[CH:13][CH:12]=4)[CH:9]=3)[N:4]([S:23]([C:26]3[CH:32]=[CH:31][C:29]([CH3:30])=[CH:28][CH:27]=3)(=[O:25])=[O:24])[CH:3]=2)[C:40]([CH3:53])=[N:39]1
Reactant: Cc1nn(Cc2cccc(F)c2)c(C)c1B1OC(C)(C)C(C)(C)O1
Reactant: Cc1ccc(S(=O)(=O)n2cc(I)c3cc(-c4ccc(N5CCOCC5)cc4)cnc32)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: O
Product: Cc1ccc(S(=O)(=O)n2cc(-c3c(C)nn(Cc4cccc(F)c4)c3C)c3cc(-c4ccc(N5CCOCC5)cc4)cnc32)cc1
Yield: 58.7 %

Procedure:
Using similar reaction conditions as described in step-ii of example-1, 4-(4-(3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)morpholine (intermediate 43) (150 mg, 0.268 mmol) was coupled with 1-(3-fluorobenzyl)-3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (intermediate 16) (133 mg, 0.402 mmol) in sodium carbonate (86 mg, 0.805 mmol), Pd(PPh3)2Cl2 (10 mg, 0.0134 mmol), Toluene/ethanol/water (5/5/5 ml) to afford 100 mg (58.82% yield) of titled compound. MS: m/z=636.1 (M+1).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:11])[CH3:10].C[O-].[Na+].[OH:15][C:16]1C=CC=C2C=1N=CC=C2.O>CO.C(OCC)(=O)C>[C:9]([NH:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[O:15][CH3:16])(=[O:11])[CH3:10]
Reactant: CC(=O)Nc1ccccc1Br
Reactant: Oc1cccc2cccnc12
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: CCOC(C)=O
Solvent: O
Product: COc1ccccc1NC(C)=O
Yield: 945.4 %

Procedure:
Then, 2.14 g of the 2-bromo-1-acetylaminobenzene was added to a solution containing 2.3 ml of a 28% methanol solution of sodium methoxide, 100 mg of cuprous chloride, and 145 mg of 8-hydroxyquinoline in 40 ml of methanol, and the mixture was heated under reflux for 50 minutes. After cooling with water, ethyl acetate was added thereto, and the resulting mixture was washed with water and dried over Glauber's salt. The solvent was distilled off, and the obtained crude crystals were recrystallized from an n-hexane/ethyl acetate solvent mixture, to obtain 1.56 g (yield: 95%) of the desired compound. The spectrum data of the compound was in agreement with the spectrum data of the separately synthesized reference compound.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[CH3:16][C:17]1[CH:22]=[C:21]([OH:23])[C:20]([C:24]([CH3:26])=[O:25])=[CH:19][C:18]=1[Cl:27].O>CN(C)C1C=CN=CC=1.ClC1C=CC=CC=1Cl>[Cl:27][C:18]1[C:17]([CH3:16])=[CH:22][C:21]([O:23][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][CH:3]=2)=[C:20]([C:24](=[O:25])[CH3:26])[CH:19]=1
Reactant: CC(=O)c1cc(Cl)c(C)cc1O
Reactant: COc1cc2nccc(Cl)c2cc1OC
Agent: CN(C)c1ccncc1
Solvent: Clc1ccccc1Cl
Solvent: O
Product: COc1cc2nccc(Oc3cc(C)c(Cl)cc3C(C)=O)c2cc1OC
Temperature: 150 °C
Reaction time: 2 h
Yield: 42.7 %

Procedure:
4-Chloro-6,7-dimethoxyquinoline (100 mg), 5-chloro-2-hydroxy-4-methylacetophenone (248 mg), and 4-dimethylaminopyridine (164 mg) were suspended in o-dichlorobenzene (6 ml), and the suspension was stirred at 150° C. for 2 hr. The reaction solution was cooled to room temperature, water was then added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed therefrom by distillation under the reduced pressure, and the residue was purified by column chromatography using acetone-chloroform to give the title compound (71 mg, yield 45%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([OH:14])[C@@H:11]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH2:23][CH2:24][O:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[N+:32]([O-:34])=[O:33])=[CH:17][CH:16]=2)[C@H:10]([O:35][CH2:36][C@H:37]2[CH2:41][O:40][C:39]([CH3:43])([CH3:42])[O:38]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[CH2:45][C:46]1[CH:47]=[C:48]([O:56][CH3:57])[C:49]2[C:54]([CH:55]=1)=[CH:53][CH:52]=[CH:51][CH:50]=2>>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([O:14][CH2:45][C:46]2[CH:47]=[C:48]([O:56][CH3:57])[C:49]3[C:54](=[CH:53][CH:52]=[CH:51][CH:50]=3)[CH:55]=2)[C@@H:11]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH2:23][CH2:24][O:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[N+:32]([O-:34])=[O:33])=[CH:17][CH:16]=2)[C@H:10]([O:35][CH2:36][C@H:37]2[CH2:41][O:40][C:39]([CH3:43])([CH3:42])[O:38]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: COc1cc(CCl)cc2ccccc12
Reactant: CC(C)(C)OC(=O)N1C[C@H](O)[C@@H](c2ccc(OCCCOc3ccccc3[N+](=O)[O-])cc2)[C@H](OC[C@H]2COC(C)(C)O2)C1
Product: COc1cc(CO[C@H]2CN(C(=O)OC(C)(C)C)C[C@@H](OC[C@H]3COC(C)(C)O3)[C@@H]2c2ccc(OCCCOc3ccccc3[N+](=O)[O-])cc2)cc2ccccc12

Procedure:
In analogy to the procedure described in example 1) (f) the (3S,4R,5R)-3-[(4S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-5-hydroxy-4-[4-[3-(2-nitro-phenoxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester was reacted with 3-chloromethyl-1-methoxy-naphthalene [example 1) (α)]to yield the (3S,4R,5R)-3-[(4S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-5-(4-methoxy-naphthalen-2-ylmethoxy)-4-[4-[3-(2-nitro-phenoxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester as colorless oil; MS: 773 (M+H)+.
Reaction SMILES: C(N(CCCC)CCCC)CCC.FC(F)(F)S(O[C:20]1[C:21]([C:26]([O:28][CH3:29])=[O:27])=[N:22][CH:23]=[CH:24][CH:25]=1)(=O)=O.[F:32][C:33]1[CH:40]=[CH:39][C:36]([CH:37]=[CH2:38])=[CH:35][CH:34]=1>CN(C=O)C.[Cu]I>[F:32][C:33]1[CH:40]=[CH:39][C:36]([CH:37]=[CH:38][C:20]2[C:21]([C:26]([O:28][CH3:29])=[O:27])=[N:22][CH:23]=[CH:24][CH:25]=2)=[CH:35][CH:34]=1
Reactant: C=Cc1ccc(F)cc1
Reactant: COC(=O)c1ncccc1OS(=O)(=O)C(F)(F)F
Agent: [Cu]I
Solvent: CN(C)C=O
Solvent: CCCCN(CCCC)CCCC
Product: COC(=O)c1ncccc1C=Cc1ccc(F)cc1
Temperature: 90 °C

Procedure:
Tributylamine (24.6 ml) was added to a stirred mixture of methyl 3-(trifluoromethanesulfonyloxy)pyridin-2-carboxylate (19.6 g), bis (triortho-tolylphosphine)palladium(II) chloride (1.08 g), copper (I) iodide (0.1 3 g) and 4-fluorostyrene (12.3 ml) in DMF (300 ml). The solution was heated under an inert atmosphere at 90° C. for 26 hours then cooled to ambient temperature and concentrated under reduced pressure. The residue was dissolved in dichloromethane (300 ml), the solid filtered and the filtrate washed with 1M. citric acid (3×100 ml), saturated aqueous sodium bicarbonate (150 ml), dried and concentrated under reduced pressure. The brown oil obtained was pre-absorbed onto silica then purified on a silica flash column eluting with ethyl acetate/iso-hexane (4:6) to give methyl 3-[2-(4-fluorophenyl)ethenyl]pyridin-2-carboxylate as a pale yellow solid (12.4 g).