Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:17]([OH:19])=O)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[CH3:33][NH:34][O:35][CH3:36].C(N(CC)C(C)C)(C)C>ClCCl>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:17]([N:34]([O:35][CH3:36])[CH3:33])=[O:19])[CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)C(=O)O
Reactant: CNOC
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CON(C)C(=O)[C@H](Cc1ccccc1)NC(=O)OC(C)(C)C
Reaction time: 0.25 h

Procedure:
1000 mg (3.77 mmol) N-(tert-butoxycarbonyl)-L-phenylalanine was placed in 10 mL dichloromethane and mixed with 733 mg (4.52 mmol) 1,1′-carbonyldiimidazole. The batch was stirred for 15 min until the evolution of gas had stopped. Next the mixture was mixed with 441 mg (4.52 mmol) N,O-dimethylhydroxylamine hydrochloride and 657 μL (3.77 mmol) N,N-diisopropylethylamine and stirred for 1 hour at RT. Next the batch was diluted with dichloromethane and washed with distilled water, 0.5N hydrochloric acid and saturated sodium chloride solution in succession. The organic phase was separated and the combined aqueous phases were re-extracted with ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated in vacuo, yielding 1090 mg (93% of the theoretical) of the title compound.
Reaction SMILES: [CH:1]1[C:6](=[O:7])[C:5]([OH:8])=[CH:4][O:3][C:2]=1[CH2:9]O.S(Cl)([Cl:13])=O>C(#N)C>[CH:1]1[C:6](=[O:7])[C:5]([OH:8])=[CH:4][O:3][C:2]=1[CH2:9][Cl:13]
Reactant: O=S(Cl)Cl
Reactant: O=c1cc(CO)occ1O
Solvent: CC#N
Product: O=c1cc(CCl)occ1O
Reaction time: 0.25 h
Yield: 95.2 %

Procedure:
A 2-liter 3-neck round bottom flask was equipped with a mechanical stirrer. The flask was charged with kojic acid (0.25 kg, 1.759 mol) and 750 ml acetonitrile at 0° C. The kojic acid was insoluble in acetonitrile and stayed as a suspension. Thionyl chloride (140 ml, 1.919 mol) was added dropwise via a dropping funnel at ice bath temperature. The solid slowly dissolved to give a red clear solution. After 15 minutes, a white solid appeared. After 3 hrs at 0° C., the insoluble solid was filtered. The solid was filtered by suction filtration. The solid was mixed with water (0.5L) and then filtered. The acetonitrile mother liquor was reduced to 15% of the original volume and filtered. The solid was washed with water (200 ml) and then acetonitrile (50 ml). The combined solid was dried to constant weight (269 g, 95.2% yield). M.p. 166-1680° C. [lit value 166-167° C.]. 1H-NMR (DMSO-d6) δ: 4.66 (s, 2H, CH2Cl), 6.57 (s, 1H, CH), 8.12 (s, 1H, CH), 9.3 (br. s, 1H, OH).
Reaction SMILES: [C-:1]#[N:2].[Na+].Br[CH2:5][C:6]1[CH:15]=[CH:14][C:9]([C:10]([O:12][CH3:13])=[O:11])=[CH:8][CH:7]=1>CS(C)=O>[C:1]([CH2:5][C:6]1[CH:15]=[CH:14][C:9]([C:10]([O:12][CH3:13])=[O:11])=[CH:8][CH:7]=1)#[N:2]
Reactant: COC(=O)c1ccc(CBr)cc1
Reactant: [C-]#N
Agent: [Na+]
Solvent: CS(C)=O
Product: COC(=O)c1ccc(CC#N)cc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 55 %

Procedure:
A solution of sodium cyanide (20 g, 0.41 mol) in dimethylsulfoxide at 40° C. was treated dropwise with a solution of methyl 4-(bromomethyl)benzoate (52 g, 0.227 mol) in dimethylsulfoxide, stirred for 90 min., cooled to room temperature, quenched with saturated aqueous sodium chloride and extracted with ethyl acetate. The combined extracts were washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. Purification of the concentrate via column chromatography (silica, hexanes:ethyl acetate 0→5%) provided methyl 4-(cyanomethyl)benzoate (55%). 1H NMR (400 MHz, CDCl3): 8.05 (d, J=8 Hz, 2H); 7.42 (d, J=8 Hz, 2H); 3.93 (s, 3H); 3.81 (s, 2H). [M+H] 176
Reaction SMILES: C([N:8](C(OC(C)(C)C)=O)[C@H:9]1[CH2:13][C@@H:12]([N:14]2[CH:22]=[N:21][C:20]3[C:15]2=[N:16][C:17]([Cl:24])=[N:18][C:19]=3[Cl:23])[C@H:11]([OH:25])[C@@H:10]1[OH:26])(OC(C)(C)C)=O.[F:34][C:35]([F:40])([F:39])[C:36]([OH:38])=[O:37].N[C@H]1C[C@@H](N2C=NC3C2=NC(Cl)=NC=3N)[C@H](O)[C@@H]1O>>[F:34][C:35]([F:40])([F:39])[C:36]([OH:38])=[O:37].[NH2:8][C@H:9]1[CH2:13][C@@H:12]([N:14]2[CH:22]=[N:21][C:20]3[C:15]2=[N:16][C:17]([Cl:24])=[N:18][C:19]=3[Cl:23])[C@H:11]([OH:25])[C@@H:10]1[OH:26]
Reactant: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)[C@H]1C[C@@H](n2cnc3c(Cl)nc(Cl)nc32)[C@H](O)[C@@H]1O
Agent: Nc1nc(Cl)nc2c1ncn2[C@@H]1C[C@H](N)[C@@H](O)[C@H]1O
Solvent: O=C(O)C(F)(F)F
Product: N[C@H]1C[C@@H](n2cnc3c(Cl)nc(Cl)nc32)[C@H](O)[C@@H]1O

Procedure:
The title compound is prepared from (1S,2R,3S,5R)-3-(di-Boc-amino)-5-(2,6-dichloro-purin-9-yl)-cyclopentane-1,2-diol using a procedure analogous to that used to prepare (1S,2R,3S,5R)-3-amino-5-(6-amino-2-chloro-purin-9-yl)-cyclopentane-1,2-diol trifluoroacetate in Example 1. MS (ES+) m/e 304 (MH+).
Reaction SMILES: [OH-].[K+].Cl.[N:4]12[CH2:11][CH2:10][CH:7]([CH2:8][CH2:9]1)[C:6](=[O:12])[CH2:5]2.[N:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH:19]=O)[CH:14]=1.O>CO>[N:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH:19]=[C:5]2[C:6](=[O:12])[CH:7]3[CH2:10][CH2:11][N:4]2[CH2:9][CH2:8]3)[CH:14]=1
Reactant: O=Cc1cccnc1
Reactant: O=C1CN2CCC1CC2
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C1C(=Cc2cccnc2)N2CCC1CC2
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 76.2 %

Procedure:
Potassium hydroxide (56 g, 0.54 mole) was dissolved in methanol (420 mL). 3-Quinuclidinone hydrochloride (75 g, 0.49 mole) was added and the mixture was stirred for 30 min at ambient temperature. 3-Pyridinecarboxaldehyde (58 g, 0.54 mole) was added and the mixture stirred for 16 h at ambient temperature. The reaction mixture became yellow during this period, with solids caking on the walls of the flask. The solids were scraped from the walls and the chunks broken up. With rapid stirring, water (390 mL) was added. When the solids dissolved, the mixture was cooled at 4° C. ovemight. The crystals were collected by filtration, washed with water, and air dried to obtain 80 g of yellow solid. A second crop (8 g) was obtained by concentration of the filtrate to ˜10% of its former volume and cooling at 4° C. overnight. Both crops were sufficiently pure for further transformation (88 g, 82% yield).
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[N:9][CH:8]=[C:7]([Br:12])[CH:6]=2.C([Sn](CCCC)(CCCC)[CH:18]=[CH:19][O:20][CH2:21][CH3:22])CCC.[Li+].[Cl-].[F-].[K+]>C1(C)C=CC=CC=1.C(Cl)Cl.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>[Br:12][C:7]1[CH:8]=[N:9][C:10]2[C:5]([CH:6]=1)=[N:4][CH:3]=[C:2]([CH:18]=[CH:19][O:20][CH2:21][CH3:22])[CH:11]=2
Reactant: CCCC[Sn](C=COCC)(CCCC)CCCC
Reactant: Brc1cnc2cc(Br)cnc2c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cl-]
Agent: [F-]
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: CCOC=Cc1cnc2cc(Br)cnc2c1
Reaction time: 0.5 h
Yield: 55 %

Procedure:
A solution of 3,7-dibromo-1,5-naphthyridine (0.5 g, 1.74 mmol), tributyl-2-ethoxy-vinylstannane (1.91 mmol, 0.69 g), LiCl (8.7 mmol, 0.37 g) and 0.085 g of PdCl2(PPh3)2 in 50 mL of toluene was heated at 95° C. for 16 hr. After cooling off, 20 mL of a 2 M solution of KF was added to the mixture and stirring was continued for 0.5 hr. The mixture was diluted with 100 mL of CH2Cl2 and washed successively with a saturated solution of sodium bicarbonate, brine and water. The organic layer was dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was chromatographed using 5% MeOH in CH2Cl2 to give the desired material in 55% yield. 1H NMR (CDCl3, 300 MHz) δ 1.40 (m, 3H), 4.05 (m, 2H), 5.85 (s, 1H), 7.25 (s, 1H), 8.15 (m, 1H), 8.55 (m, 1H), 8.85 (m, 2H). MS (ESI) [M+H]+ at 280.
Reaction SMILES: [C:1]([O-:5])(=[O:4])[CH:2]=[CH2:3].[C:6](O)(=O)C=C.C(O)(=O)C=C.C(O)(=O)C=C.C(C(CO)(CO)C)O.C(O)(=O)C=C.C(O)(=O)C=C.C(C(CO)(CO)CC)O>>[C:1]([O-:5])(=[O:4])[CH:2]=[CH2:3].[C:1]([O-:5])(=[O:4])[C:2]([CH3:6])=[CH2:3]
Reactant: C=CC(=O)O
Agent: C=CC(=O)[O-]
Agent: CC(CO)(CO)CO
Agent: CCC(CO)(CO)CO
Product: C=C(C)C(=O)[O-]

Procedure:
The monomer or oligomer used in the invention is preferably a monomer or oligomer which has two or more ethylenic unsaturated double bonds and which is addition-polymerized by irradiation with light. The monomer or oligomer may be a compound having at least one addition-polymerizable ethylenic unsaturated group therein and having a boiling point of 100° C. or higher at a normal pressure. Examples thereof include: a monofunctional acrylate and a monofunctional methacryalte such as polyethylene glycol mono(meth)acrylate, polypropylene glycol mono(meth)acrylate and phenoxyethyl (meth)acrylate; polyethylene glycol di(meth)acrylate, polypropylene glycol di(meth)acrylate, trimethylolethane triacrylate, trimethylolpropane tri(meth)acrylate, trimethylolpropane diacrylate, neopentyl glycol di(meth)acrylate, pentaerythritol tetra(meth)acrylate, pentaerythritol tri(meth)acrylate, dipentaerythritol hexa(meth)acrylate, dipentaerythritol penta(meth)acrylate, hexanediol di(meth)acrylate, trimethylolpropane tri(acryloyloxypropyl)ether, tri(acryloyloxyethyl)isocyanurate, tri(acryloyloxyethyl)cyanurate, glycerin tri(meth)acrylate; a polyfunctional acrylate or polyfunctional methacrylate which may be obtained by adding ethylene oxide or propylene oxide to a polyfunctional alcohol such as polymethylolpropane or glycerin and converting the adduct into a (meth)acrylate.
Reaction SMILES: [CH3:1][N:2]([CH3:12])[C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-])=O)=[CH:5][N:4]=1.C([O-])(O)=O.[Na+]>CCO>[NH2:9][C:6]1[CH:5]=[N:4][C:3]([N:2]([CH3:12])[CH3:1])=[CH:8][CH:7]=1
Reactant: CN(C)c1ccc([N+](=O)[O-])cn1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: CN(C)c1ccc(N)cn1
Temperature: 80 °C
Reaction time: 0.58 h

Procedure:
A stirred mixture of the product from Step 1 (7.70 g, 0.0461 mol) and stannous chloride dihydrate (56.4 g, 0.250 mol) in absolute EtOH (100 ml) was warmed to 80° C. during 15 minutes and kept at that temperature for 35 minutes. The resulting mixture was kept at ambient temperature for 1 hour, poured onto ice (400 ml) and mixed with NaHCO3 (15 g). It was adjusted to a pH of 8-9 with saturated aqueous NaHCO3 and extracted with EtOAc; the extract was washed with water and brine dried (MgSO4) and concentrated to give 5.98 g of crude product. Pan of this was purified by silica gel chromatography, with 5% MeOH--0.25% NH4OH--CHCl3 to give the titled product.
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]2[CH:12]=[N:11][NH:10][C:7]2=[N:8][CH:9]=1.[CH3:13][Si:14]([CH3:21])([CH3:20])[CH2:15][CH2:16][O:17][CH2:18]Cl>C1COCC1.C(OCC)(=O)C>[Br:3][C:4]1[CH:5]=[C:6]2[CH:12]=[N:11][N:10]([CH2:18][O:17][CH2:16][CH2:15][Si:14]([CH3:21])([CH3:20])[CH3:13])[C:7]2=[N:8][CH:9]=1
Reactant: Brc1cnc2[nH]ncc2c1
Reactant: C[Si](C)(C)CCOCCl
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: C[Si](C)(C)CCOCn1ncc2cc(Br)cnc21
Reaction time: 8 h
Yield: 152.3 %

Procedure:
NaH (0.082 g, 2.06 mmol, 60% suspension in mineral oil) was added portionwise to a cold (0° C.) solution of 5-bromo-1H-pyrazolo[3,4-b]pyridine (0.204 g, 1.03 mmol) in dry THF (10 mL). The reaction mixture was stirred at 0° C. for 10 minutes before 2-(trimethylsilyl)ethoxymethyl chloride (0.31 mL, 0.292 mmol) was added dropwise via a syringe. The reaction mixture was left at room temperature overnight. The reaction mixture was diluted with ethyl acetate (50 mL) and carefully quenched with water (10 mL). The aqueous layer was separated and extracted with ethyl acetate (3×50 mL). The combined organic layers were dried, filtered and concentrated. The crude product was purified by column chromatography, eluting with hexanes/ethyl acetate (50:1) to give 5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridine (0.146 g, 43%) as an oil.
Reaction SMILES: [OH:1]C[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O.O.O.O.O.O.O.[Cl-].[Al+3:20].[Cl-].[Cl-].O.[C:24]([OH:36])(=[O:35])[CH2:25][C:26]([CH2:31][C:32]([OH:34])=[O:33])([C:28]([OH:30])=[O:29])[OH:27].[OH-].[Na+].[OH-].[OH:40][CH2:41][C@@H:42]([C@H:44]([C@@H:46]([C@@H:48]([CH2:50][OH:51])[OH:49])[OH:47])[OH:45])[OH:43].C([O-])(=O)CC(CC(O)=O)(C(O)=O)O.[Mg+2]>O.C(O)C>[OH-:1].[OH:51][CH2:50][C@@H:48]([C@H:46]([C@@H:44]([C@@H:42]([CH2:41][OH:40])[OH:43])[OH:45])[OH:47])[OH:49].[C:24]([O-:36])(=[O:35])[CH2:25][C:26]([CH2:31][C:32]([O-:34])=[O:33])([C:28]([OH:30])=[O:29])[OH:27].[Al+3:20]
Reactant: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: O=C([O-])CC(O)(CC(=O)O)C(=O)O
Agent: OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)CO
Agent: [Al+3]
Solvent: CCO
Solvent: O
Product: O=C([O-])CC(O)(CC(=O)[O-])C(=O)O

Procedure:
800 g of sorbitol, 600 g of aluminum chloride hexahydrate, and 250 g of citric acid monohydrate were dissolved in 3000 g of water at 70° C. with stirring to produce a solution. The pH of the solution was raised to about 8 by adding an aqueous solution containing 20 wt % of sodium hydroxide. After the addition of NaOH, a colorless and transparent nanocluster solution having a strong laser scattering characteristic was then obtained instantly. This strong laser scattering property indicated formation of magnesium citrate sorbitol hydroxide nanoclusters. The nanoclusters were further isolated by adding ethanol into the solution to precipitate the magnesium citrate sorbitol hydroxide nanoclusters. Or the nanoclusters were isolated from the solvent and free ions through a cross-flow membrane filtration device using a membrane with a molecular weight cut-off at 3500 Dalton. The isolated nanoclusters were further dried in an oven at 80° C. to form a solid.
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][C:5]([N:6]([CH3:8])[CH3:7])=[C:4]([F:11])[CH:3]=1.C(B(CC)[C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1)C>>[F:11][C:4]1[CH:3]=[C:2]([C:15]2[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=2)[CH:10]=[CH:9][C:5]=1[N:6]([CH3:8])[CH3:7]
Reactant: CN(C)c1ccc(Br)cc1F
Reactant: CCB(CC)c1ccncc1
Product: CN(C)c1ccc(-c2ccncc2)cc1F
Yield: 44 %

Procedure:
IDT330. 4-Bromo-2-fluoroaniline was methylated by treating it with dimethylsulphate to give a 26% yield of 4-Bromo-2-fluoro-N,N-dimethylaniline (XI) as a red oil. The resultant 4-Bromo-2-fluoro-N,N-dimethylaniline was coupled to diethyl (4-pyridyl) borane (I) using a tetrakis triphenyl phosphine palladium (0) catalyst to give 2-Fluoro-N,N-dimethyl-4-(pyridin-4-yl)aniline (XII) in a 44% yield. This was methylated by refluxing it in acetonitrile in the presence of methyl iodide and the product 4-(4-(dimethylamino)-3-fluorophenyl)-1-methylpyridinium iodide (XIII) IDT330 was obtained in a 21% yield.
Reaction SMILES: C[O:2][C:3]([CH:5]1[CH2:12][CH2:11][C:10]2([C:14]3[NH:22][C:21]4[C:20](=[O:23])[N:19]([CH2:24][CH2:25][CH3:26])[C:18](=[O:27])[N:17]([CH2:28][CH2:29][CH3:30])[C:16]=4[N:15]=3)[O:13][CH:6]1[CH2:7][CH2:8][CH2:9]2)=[O:4]>CO>[O:27]=[C:18]1[N:17]([CH2:28][CH2:29][CH3:30])[C:16]2[N:15]=[C:14]([C:10]34[O:13][CH:6]([CH2:7][CH2:8][CH2:9]3)[CH:5]([C:3]([OH:4])=[O:2])[CH2:12][CH2:11]4)[NH:22][C:21]=2[C:20](=[O:23])[N:19]1[CH2:24][CH2:25][CH3:26]
Reactant: CCCn1c(=O)c2[nH]c(C34CCCC(O3)C(C(=O)OC)CC4)nc2n(CCC)c1=O
Solvent: CO
Product: CCCn1c(=O)c2[nH]c(C34CCCC(O3)C(C(=O)O)CC4)nc2n(CCC)c1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
5-(2,6-Dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-9-oxa-bicyclo[3.3.1]nonane-2-carboxylic acid methyl ester (50 mg, from step 2) was taken in MeOH (5 ml) LiOH (15 mg) was added and stirred at rt overnight. Next day MeOH was removed under reduced pressure, diluted with water and extracted with ethyl acetate. Aqueous layer was acidified with 1N HCl, extracted with ethyl acetate (3×25 ml). Combined organic layer was washed with brine, and dried over Na2SO4. Concentration of the solvent gave a white solid, which was purified by crystallizing from ether. Mass (ES+ 405)
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[C:9]1([S:15](Cl)(=[O:17])=[O:16])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.O>N1C=CC=CC=1>[Br:8][C:6]1[CH:7]=[C:2]([NH:1][S:15]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)(=[O:17])=[O:16])[CH:3]=[N:4][CH:5]=1
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: Nc1cncc(Br)c1
Solvent: c1ccncc1
Solvent: O
Product: O=S(=O)(Nc1cncc(Br)c1)c1ccccc1
Temperature: 20 °C
Reaction time: 16 h
Yield: 100 %

Procedure:
To a solution of 3-amino-5-bromopyridine (0.500 g, 2.89 mmol) in pyridine (2 mL) was added benzenesulfonyl chloride (0.404 mL, 3.18 mmol) dropwise. The reaction mixture was stirred at room temperature (20° C.) for 16 h. After this time, water (5 mL) was added to the reaction mixture. The resulting crystalline solid was collected by filtration, washed with water and dried in the vacuum oven to afford the title compound (0.898 g, 2.89 mmol, quantitative). No further purification was required.
Reaction SMILES: [N:1]([CH2:4][C@@H:5]1[O:9][C:8](=[O:10])[N:7]([C:11]2[CH:16]=[CH:15][C:14]([I:17])=[C:13]([F:18])[CH:12]=2)[CH2:6]1)=[N+:2]=[N-:3].[CH3:19][Si:20]([C:23]#[CH:24])([CH3:22])[CH3:21]>C1COCC1>[F:18][C:13]1[CH:12]=[C:11]([N:7]2[CH2:6][C@H:5]([CH2:4][N:1]3[CH:24]=[C:23]([Si:20]([CH3:22])([CH3:21])[CH3:19])[N:3]=[N:2]3)[O:9][C:8]2=[O:10])[CH:16]=[CH:15][C:14]=1[I:17]
Reactant: [N-]=[N+]=NC[C@H]1CN(c2ccc(I)c(F)c2)C(=O)O1
Reactant: C#C[Si](C)(C)C
Solvent: C1CCOC1
Product: C[Si](C)(C)c1cn(C[C@H]2CN(c3ccc(I)c(F)c3)C(=O)O2)nn1
Temperature: 25 °C
Yield: 99.9 %

Procedure:
A solution of (5R)-5-azidomethyl-3-(3-fluoro-4-iodophenyl)-oxazolidin-2-one (1023, 248.0 g, 685.0 mmol) in anhydrous THF (600 mL) was treated with trimethylsilylacetylene (100.9 g, 145.2 mL, 1027.6 mmol, 1.5 equiv) at room temperature, and the resulting reaction mixture was warmed up to reflux for 12 h. When TLC and HPLC/MS showed that the cycloaddition reaction was complete, the reaction mixture was cooled down to room temperature before being concentrated in vacuo. The residue was further dried in vacuo to afford the crude, desired (5R)-3-(3-fluoro-4-iodo-phenyl)-5-(4-trimethylsilanyl-[1,2,3]triazol-1-ylmethyl)-oxazolidin-2-one (1024, 315.1 g, 315.1 g theoretical, 100%) as brown oil, which was directly used in the subsequent reaction without further purification. For 1024: 1H NMR (300 MHz, DMSO-d6) δ 0.01 (s, 9H, SiCH3), 3.67 (dd, 1H, J=6.4, 9.2 Hz), 4.01 (t, 1H, J=5.4 Hz), 4.59 (d, 2H, J=4.9 Hz), 4.91-4.94 (m, 1H), 6.88 (dd, 1H, J=2.4, 8.7 Hz), 7.22 (dd, 1H, J=2.4, 8.7 Hz), 7.58 (dd, 1H, J=7.5, 8.7 Hz), 7.73 (s, 1H, triazole-H); C15H18FIN4O2Si, LCMS (EI) m/e 461 (M++H).
Reaction SMILES: Cl[CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.[Na+].[I-].[CH3:19][NH2:20]>>[CH3:19][NH:20][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1
Reactant: CN
Reactant: CC(C)(C)OC(=O)N1CCN(CCCl)CC1
Agent: [I-]
Agent: [Na+]
Product: CNCCN1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 70 °C
Reaction time: 12 h

Procedure:
Into a 50-mL sealed tube, was placed tert-butyl 4-(2-chloroethyl)piperazine-1-carboxylate (300 mg, 1.21 mmol, 1.00 equiv), methanamine (in ethanol) (10 mL), NaI (100 mg). The resulting solution was stirred for 12 h at 70° C. in an oil bath. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 3 mL of water. The pH value of the solution was adjusted to 7-8 with sodium bicarbonate (5%). The resulting solution was extracted with 2×5 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 1×3 mL of water and 1×3 mL of brine. The resulting mixture was concentrated under vacuum. This resulted in 180 mg (crude) of tert-butyl 4-(2-(methylamino)ethyl)piperazine-1-carboxylate as brown oil
Reaction SMILES: ClC1C=C(Cl)C=CC=1C1C(C2NC=CN=2)=CN=C(CCN)N=1.Cl[C:24]1[N:29]=[C:28]([NH:30][C:31](=[O:33])[CH3:32])[C:27]([N+:34]([O-:36])=[O:35])=[CH:26][CH:25]=1.[Cl:37][C:38]1[CH:43]=[C:42]([Cl:44])[CH:41]=[CH:40][C:39]=1[C:45]1[C:50]([C:51]2[NH:52][CH:53]=[CH:54][N:55]=2)=[CH:49][N:48]=[C:47]([NH:56][CH2:57][CH2:58][NH:59]C2C=CC([N+]([O-])=O)=C(OC)N=2)[N:46]=1>>[Cl:37][C:38]1[CH:43]=[C:42]([Cl:44])[CH:41]=[CH:40][C:39]=1[C:45]1[C:50]([C:51]2[NH:55][CH:54]=[CH:53][N:52]=2)=[CH:49][N:48]=[C:47]([NH:56][CH2:57][CH2:58][NH:59][C:24]2[N:29]=[C:28]([NH:30][C:31](=[O:33])[CH3:32])[C:27]([N+:34]([O-:36])=[O:35])=[CH:26][CH:25]=2)[N:46]=1
Reactant: CC(=O)Nc1nc(Cl)ccc1[N+](=O)[O-]
Reactant: COc1nc(NCCNc2ncc(-c3ncc[nH]3)c(-c3ccc(Cl)cc3Cl)n2)ccc1[N+](=O)[O-]
Agent: NCCc1ncc(-c2ncc[nH]2)c(-c2ccc(Cl)cc2Cl)n1
Product: CC(=O)Nc1nc(NCCNc2ncc(-c3ncc[nH]3)c(-c3ccc(Cl)cc3Cl)n2)ccc1[N+](=O)[O-]

Procedure:
N-{6-[(2-{[4-(2,4-dichlorophenyl)-5-imidazol-2-ylpyrimidin-2-yl]amino}ethyl)amino]-3-nitro-2-pyridyl}acetamide was prepared from [4-(2,4-dichlorophenyl)-5-imidazol-2-ylpyrimidin-2-ylethylamine and N-(6-chloro-3-nitro-2-pyridyl)acetamide in accordance with the procedure described above for the preparation of [4-(2,4-dichlorophenyl)-5-imidazol-2-ylpyrimidin-2-yl]{2-[(6-methoxy-5-nitro(2-pyridyl))amino]ethyl}amine.
Reaction SMILES: [F:1][C:2]1[CH:33]=[CH:32][C:5]([NH:6][C:7]([NH:9][C:10]2[CH:31]=[CH:30][C:13]([O:14][C:15]3[C:24]4[C:19](=[CH:20][C:21]([O:28][CH3:29])=[C:22]([C:25]([OH:27])=[O:26])[CH:23]=4)[N:18]=[CH:17][CH:16]=3)=[CH:12][CH:11]=2)=[O:8])=[CH:4][CH:3]=1.Cl.C(N=C=N[CH2:40][CH2:41][CH2:42]N(C)C)C.C(N(CC)CC)C.CC(O)C>CN(C)C=O.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:6][C:7]([NH:9][C:10]2[CH:31]=[CH:30][C:13]([O:14][C:15]3[C:24]4[C:19](=[CH:20][C:21]([O:28][CH3:29])=[C:22]([C:25]([O:27][CH:41]([CH3:42])[CH3:40])=[O:26])[CH:23]=4)[N:18]=[CH:17][CH:16]=3)=[CH:12][CH:11]=2)=[O:8])=[CH:32][CH:33]=1
Reactant: COc1cc2nccc(Oc3ccc(NC(=O)Nc4ccc(F)cc4)cc3)c2cc1C(=O)O
Reactant: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COc1cc2nccc(Oc3ccc(NC(=O)Nc4ccc(F)cc4)cc3)c2cc1C(=O)OC(C)C
Yield: 15.8 %

Procedure:
After dissolving 4-(4-(((4-fluoroanilino)carbonyl)amino) phenoxy)-7-methoxy-6-quinolinecarboxylic acid (84 mg, 0.19 mmol) in dimethylformamide (1 ml), there were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (54 mg, 0.28 mmol), 1-hydroxy-1H-benzotriazolemonohydrate (38 mg, 0.28 mmol), triethylamine (0.079 ml, 0.56 mmol) and 2-propanol (0.15 ml) while stirring on ice, and the mixture was stirred overnight at room temperature. The reaction solution was directly subjected to silica gel column chromatography (eluent—ethyl acetate), the fraction containing the target substance was concentrated, suspended in ethyl acetate and diluted with hexane, and the crystals were filtered out and blow-dried to obtain the title compound (15.0 mg, 0.03 mmol, 16%) as white crystals.
Reaction SMILES: C1(C[C@@H]2NC(=O)[C@H](C(C)C)C[C@@H]2O)CCCCC1.[CH2:19]([C@H:26]1[CH2:31][C@H:30]([OH:32])[C@H:29]([CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[NH:28][C:27]1=[O:40])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>>[NH2:28][C@@H:29]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C@H:30]1[O:32][C:27](=[O:40])[C@@H:26]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:31]1
Reactant: O=C1N[C@@H](Cc2ccccc2)[C@@H](O)C[C@@H]1Cc1ccccc1
Agent: CC(C)[C@@H]1C[C@H](O)[C@H](CC2CCCCC2)NC1=O
Product: N[C@@H](Cc1ccccc1)[C@@H]1C[C@H](Cc2ccccc2)C(=O)O1

Procedure:
Following the procedure described in Example 7 and replacing the product of Example 6 with the product of Example 9 provides the title product.