Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:3][C:4](=[O:49])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[C:26]([C:28]3[CH:32]=[CH:31][S:30][CH:29]=3)[CH:25]=[C:24]([C:33]3[CH:41]=[CH:40][C:36]4[O:37][CH2:38][O:39][C:35]=4[CH:34]=3)[CH:23]=2)[C:10]=1[CH2:42][CH2:43][C:44]([O:46]CC)=[O:45])C.[OH-].[Na+]>C(O)C.C(OC(C)C)(=O)C>[O:37]1[C:36]2[CH:40]=[CH:41][C:33]([C:24]3[CH:23]=[C:22]([CH:27]=[C:26]([C:28]4[CH:32]=[CH:31][S:30][CH:29]=4)[CH:25]=3)[O:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][C:11]3[C:10]([CH2:42][CH2:43][C:44]([OH:46])=[O:45])=[C:9]([CH:14]=[CH:13][CH:12]=3)[O:8][CH2:7][CH2:6][CH2:5][C:4]([OH:49])=[O:3])=[CH:34][C:35]=2[O:39][CH2:38]1
Reactant: CCOC(=O)CCCOc1cccc(CCCCCCOc2cc(-c3ccsc3)cc(-c3ccc4c(c3)OCO4)c2)c1CCC(=O)OCC
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: CC(=O)OC(C)C
Product: O=C(O)CCCOc1cccc(CCCCCCOc2cc(-c3ccsc3)cc(-c3ccc4c(c3)OCO4)c2)c1CCC(=O)O
Temperature: 52.5 °C
Reaction time: 5 h
Yield: 67.9 %

Procedure:
To a solution of the 4-{3-[6-(3-benzo[1,3]dioxol-5-yl-5-thiophen-3-yl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy}-butyric acid ethyl ester (649 mg, 0.944 mmol) in ethanol (40 mL) was added aqueous 1.0 N sodium hydroxide (35 mL) at room temperature. The resulting suspension was heated to 50-55° C. and the mixture was stirred for 5 h. Then, the reaction mixture was concentrated and the residue was diluted with water (20 mL) and extracted with diethyl ether (50 mL) to remove any neutral impurities. The aqueous layer was acidified with 1.0 N hydrochloric acid and the precipitated white organic compound was extracted into ethyl acetate (2×100 mL). The combined ethyl acetate extracts were washed with brine solution (100 mL) and the organic layers were dried over anhydrous magnesium sulfate. Filtration and removal of the solvent afforded the crude product which was dissolved in hot iso-propyl acetate (10 mL) and then diluted with hexanes (5 mL). The resulting light yellow solution was stored in the refrigerator for 2 days. The white solids were collected by filtration and washed with hexanes. After air-drying, 4-{3-[6-(3-benzo[1,3]dioxol-5-yl-5-thiophen-3-yl-phenoxy)-hexyl]-2-(2-carboxy-ethyl)-phenoxy}-butyric acid (404 mg, 68%) was isolated as a white solids, mp=110-112° C.: ES(+)-HRMS m/e calculated for C36H38O8S (M+Na)+ 653.2179, found 653.2183. Elemental analysis: (C36H38O8S): C=68.49 (calcd, 68.55), H=5.93 (6.07), S=5.15 (5.08).
Reaction SMILES: C([O:8][C:9]1[C:34]([O:35][CH3:36])=[CH:33][C:12]([CH2:13][C:14]2[C:22]3[C:17](=[N:18][CH:19]=[CH:20][CH:21]=3)[N:16]([Si:23]([CH:30]([CH3:32])[CH3:31])([CH:27]([CH3:29])[CH3:28])[CH:24]([CH3:26])[CH3:25])[CH:15]=2)=[C:11]([F:37])[CH:10]=1)C1C=CC=CC=1>CO.O1CCCC1.[Pd]>[F:37][C:11]1[C:12]([CH2:13][C:14]2[C:22]3[C:17](=[N:18][CH:19]=[CH:20][CH:21]=3)[N:16]([Si:23]([CH:27]([CH3:29])[CH3:28])([CH:24]([CH3:26])[CH3:25])[CH:30]([CH3:32])[CH3:31])[CH:15]=2)=[CH:33][C:34]([O:35][CH3:36])=[C:9]([OH:8])[CH:10]=1
Reactant: COc1cc(Cc2cn([Si](C(C)C)(C(C)C)C(C)C)c3ncccc23)c(F)cc1OCc1ccccc1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: COc1cc(Cc2cn([Si](C(C)C)(C(C)C)C(C)C)c3ncccc23)c(F)cc1O
Reaction time: 1 h
Yield: 85.6 %

Procedure:
3-(4-Benzyloxy-2-fluoro-5-methoxy-benzyl)-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (657, 0.831 g, 1.60 mmol) was dissolved in methanol (40 mL) and tetrahydrofuran (40 mL). 10% Palladium on carbon (3.41 g) was added. The reaction was shaken at 50 psi for 1 hour. The reaction was filtered through Celite and washed with methanol. The organic portion was passed through celite several times until a clear solution was obtained. The organic portion was concentrated under reduced pressure to provide the desired compound as an off-white solid (649, 587 mg, 86%). MS (ESI) [M+H+]+=429.5.
Reaction SMILES: [CH2:1]1[CH:13]2[CH:5]([C:6]3[C:11]([NH:12]2)=[CH:10][CH:9]=[CH:8][CH:7]=3)[CH2:4][CH2:3][CH2:2]1.[Cl:14][CH2:15][CH2:16][C:17](Cl)=[O:18]>CC(C)=O>[Cl:14][CH2:15][CH2:16][C:17]([N:12]1[CH:13]2[CH:5]([CH2:4][CH2:3][CH2:2][CH2:1]2)[C:6]2[C:11]1=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:18]
Reactant: c1ccc2c(c1)NC1CCCCC21
Reactant: O=C(Cl)CCCl
Solvent: CC(C)=O
Product: O=C(CCCl)N1c2ccccc2C2CCCCC21
Yield: 111.7 %

Procedure:
To a solution of 10 g 1,2,3,4,4a,9a-hexahydrocarbazole in 30 ml acetone was added a solution of 8.3 g 3-chloropropionyl chloride in 30 ml acetone dropwise at ambient temperature and the mixture was refluxed for 1 hour. The solvent was then distilled off under reduced pressure and the residue was dissolved in 100 ml of dichloromethane and washed with 10% hydrochloric acid twice. The solution was dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure to provide about 17 g of 9-(3-chloropropionyl)-1,2,3,4,4a,9a-hexahydrocarbazole as a viscous oil. This oil was not purified but submitted directly to the next reaction.
Reaction SMILES: [NH2:1][C:2]1[C:11]2[C:6](=[C:7](I)[C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[N:5]=[N:4][C:3]=1[C:15]([NH:17][CH2:18][CH2:19][CH3:20])=[O:16].[C:21]1(B(O)O)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>>[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[N:5]=[N:4][C:3]=1[C:15]([NH:17][CH2:18][CH2:19][CH3:20])=[O:16]
Reactant: CCCNC(=O)c1nnc2c(I)c(OC)ccc2c1N
Reactant: OB(O)c1ccccc1
Product: CCCNC(=O)c1nnc2c(-c3ccccc3)c(OC)ccc2c1N
Yield: 51.4 %

Procedure:
Using Method F, 4-amino-7-methoxy-8-iodo-N-propyl-cinnoline-3-carboxamide (311 mg, 0.81 mmol) and phenylboronic acid (394 mg, 3.24 mmol) were reacted (refluxed overnight) to afford the title compound (140 mg, 52% yield) as a white solid. 1H NMR (300 MHz, CDCl3) δ 8.51 (bm, 1H), 7.90 (d, J=9.2 Hz, 1H), 7.52 (d, J=9.2 Hz, 1H), 7.36-7.50 (m, 5H), 3.92 (s, 3H), 3.43 (apparent q, J=6.4 Hz, 2H), 1.63 (apparent sextet, J=7.2 Hz, 2H), 0.98 (t, J=7.4 Hz, 3H). MS APCI, m/z=337 (M+H) HPLC 1.76 min.
Reaction SMILES: [I-].[K+].[CH2:3]([O:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][CH:10]=1)[C:4]([CH3:7])([CH3:6])[CH3:5].[Br:18]Br>O>[Br:18][C:14]1[CH:13]=[C:12]([N+:15]([O-:17])=[O:16])[CH:11]=[CH:10][C:9]=1[O:8][CH2:3][C:4]([CH3:7])([CH3:6])[CH3:5]
Reactant: CC(C)(C)COc1ccc([N+](=O)[O-])cc1
Reactant: BrBr
Agent: [I-]
Agent: [K+]
Solvent: O
Product: CC(C)(C)COc1ccc([N+](=O)[O-])cc1Br
Reaction time: 5 h
Yield: 84.2 %

Procedure:
Subsequently, a catalytic amount of potassium iodide was added to 4-neopentyloxynitrobenzene (69 g), and bromine (66 g) was added dropwise at 60° C. The mixture was stirred for 5 h. The reaction mixture was poured into water and extracted with toluene. The organic layer was washed with aqueous sodium sulfite solution, dried over anhydrous magnesium sulfate, after which the solvent was evaporated under reduced pressure. The residue was recrystallized from n-hexane to give 3-bromo-4-neopentyloxynitrobenzene (80 g), melting point: 86–88° C.
Reaction SMILES: [O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([C:11]([NH2:19])([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH3:12])[CH2:7][CH2:6]2)OCC1.Cl.ClCCl>CC(C)=O>[NH2:19][C:11]([CH:8]1[CH2:7][CH2:6][C:5](=[O:1])[CH2:10][CH2:9]1)([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH3:12]
Reactant: CC(N)(c1ccccc1)C1CCC2(CC1)OCCO2
Agent: Cl
Solvent: CC(C)=O
Solvent: ClCCl
Product: CC(N)(c1ccccc1)C1CCC(=O)CC1
Reaction time: 5 h

Procedure:
Crude 1-(1,4-dioxa-spiro[4.5]dec-8-yl)-1-phenyl-ethylamine (26, 2.5 g) was dissolved in acetone (40 mL) and treated with 6M aqueous hydrochloric acid (21.1 mL). After 5 hours stirring the mixture was evaporated at less than 20° C. to give a residue which was treated with dichloromethane, washed with saturated sodium bicarbonate solution, dried and filtered to give a solution of crude product which was used immediately. Rt=0.7 min (Method 5). Detected mass: 218.3 (M+H+).
Reaction SMILES: [CH:1]1([S:7]([CH2:10][S:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][C:21](=[O:23])[CH3:22])=[CH:16][CH:15]=2)(=[O:13])=[O:12])(=[O:9])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C1(C)C=CC(S([N:33]=[N+:34]=[N-])(=O)=O)=CC=1.C1CCN2C(=NCCC2)CC1.Cl>ClCCl>[CH:1]1([S:7]([C:10]([S:11]([C:14]2[CH:15]=[CH:16][C:17]([O:20][C:21](=[O:23])[CH3:22])=[CH:18][CH:19]=2)(=[O:12])=[O:13])=[N+:33]=[N-:34])(=[O:8])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Cc1ccc(S(=O)(=O)N=[N+]=[N-])cc1
Reactant: CC(=O)Oc1ccc(S(=O)(=O)CS(=O)(=O)C2CCCCC2)cc1
Agent: Cl
Solvent: ClCCl
Solvent: C1CCC2=NCCCN2CC1
Product: CC(=O)Oc1ccc(S(=O)(=O)C(=[N+]=[N-])S(=O)(=O)C2CCCCC2)cc1
Reaction time: 0.17 h
Yield: 34 %

Procedure:
The cyclohexylsulfonyl(4-acetyloxyphenylsulfonyl)methane in Synthesis Example 12, 5 g (0.014 mol), was dispersed in 100 g of dichloromethane. To the dispersion was added 2.3 g (0.015 mol) of p-toluenesulfonylazide. With stirring under ice cooling, 2.9 g (0.015 mol) of DBU was added to the dispersion, and after 10 minutes, 55 g of a 0.2N aqueous hydrochloric acid was added to stop reaction. The organic layer was separated and washed with 50 g of water. The organic layer was concentrated and 6 g of the residue was purified by silica gel column chromatography using dichloromethane as an elute. The thus obtained oily product was combined with 20 g of hexane for crystallization, followed by filtration and vacuum drying. There was obtained 2 g (yield 34%) of fine yellow crystals.
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[C:12]([NH:15][CH2:16][CH2:17][NH2:18])(=[O:14])[CH3:13].C(=O)([O-])[O-].[Na+].[Na+]>CC(C)CCO>[N:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH:10]=[CH:11][C:2]=1[NH:18][CH2:17][CH2:16][NH:15][C:12](=[O:14])[CH3:13]
Reactant: Clc1ccc2ccccc2n1
Reactant: CC(=O)NCCN
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(C)CCO
Product: CC(=O)NCCNc1ccc2ccccc2n1
Yield: 116.5 %

Procedure:
A mixture of 2-chloroquinoline (10.00 g, 0.061 mol), N-acetylethylenediamine (6.24 g, 0.061 mol), sodium carbonate (6.48 g, 0.061 mol), and 3-methyl-1-butanol (125 mL) was heated under reflux for 3 days. The mixture was cooled, filtered, and the filtrate was concentrated to give 16.3 g (>100%) of a yellow oil. Purification by flash chromatography (eluent 5% MeOH/CHCl3 ; 10% MeOH/1% Et3N/CHCl3) gave 6.8 g (49%) of a yellow oil.
Reaction SMILES: [C:1]1([CH2:6][SH:7])[S:5][CH:4]=[CH:3][CH:2]=1.C(N1C(=O)C2=CC=CC=[C:12]2[C:11]1=[S:20])C>>[CH2:11]([S:20][S:7][CH2:6][C:1]1[S:5][CH:4]=[CH:3][CH:2]=1)[CH3:12]
Reactant: SCc1cccs1
Reactant: CCN1C(=O)c2ccccc2C1=S
Product: CCSSCc1cccs1

Procedure:
Starting from thenylmercaptan and N-ethylthiophthalimide there is obtained ethyl-thenyl-disulphide.
Reaction SMILES: Cl[Si](C)(C)[CH3:3].[Cl:6][C:7]1[C:15]([N+:16]([O-:18])=[O:17])=[C:14]([CH3:19])[C:13]([F:20])=[CH:12][C:8]=1[C:9]([OH:11])=[O:10]>CO.O>[CH3:3][O:10][C:9](=[O:11])[C:8]1[CH:12]=[C:13]([F:20])[C:14]([CH3:19])=[C:15]([N+:16]([O-:18])=[O:17])[C:7]=1[Cl:6]
Reactant: Cc1c(F)cc(C(=O)O)c(Cl)c1[N+](=O)[O-]
Reactant: C[Si](C)(C)Cl
Solvent: CO
Solvent: O
Product: COC(=O)c1cc(F)c(C)c([N+](=O)[O-])c1Cl
Temperature: 20 °C
Reaction time: 16 h

Procedure:
A solution of chlorotrimethylsilane (200 mL) in methanol (300 mL) was treated with 2-chloro-5-fluoro-4-methyl-3-nitrobenzoic acid (Preparation 1c, 65.5 g) portionwise under nitrogen. The resulting solution was stirred at 20° C. for 16 h. Further chlorotrimethylsilane (100 mL) was added and the reaction heated at 50° C. for 6 h. The reaction mixture was evaporated to afford crude product which was diluted with water and extracted with ethyl acetate (300 mL). The organic extract was dried (MgSO4), filtered and evaporated to afford the subtitle compound (53.4 g).
Reaction SMILES: C(Cl)(Cl)Cl.[OH:5][CH2:6][C:7]1[CH:16]=[C:15]2[C:10]([CH2:11][CH2:12][C:13](=[O:17])[NH:14]2)=[CH:9][CH:8]=1.[CH3:18][C:19](OC(C)=O)=[O:20].C([O-])(O)=O.[Na+]>CN(C1C=CN=CC=1)C.CCN(CC)CC>[C:19]([O:5][CH2:6][C:7]1[CH:16]=[C:15]2[C:10]([CH2:11][CH2:12][C:13](=[O:17])[NH:14]2)=[CH:9][CH:8]=1)(=[O:20])[CH3:18]
Reactant: O=C1CCc2ccc(CO)cc2N1
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccncc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: CC(=O)OCc1ccc2c(c1)NC(=O)CC2
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
To a CHCl3 (30.0 mL) solution, the compound (670 mg) obtained in Step 52-1, Ac2O (536 μL), DMAP (20.0 mg) and Et3N (1.05 mL) were added under ice cooling and the mixture was stirred at room temperature for 45 minutes. To the reaction mixture, a saturated aqueous NaHCO3 solution was added and the solution was extracted three times with CHCl3. The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel 60 N, mobile phase: MeOH/CHCl3=0/100 to 10/90; v/v) to obtain (2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)methyl acetate (767 mg, a light yellow solid).
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=1.[C:8]([O:11][C@@H:12]1[C@@H:26]([O:27][C:28](=[O:30])[CH3:29])[C@H:25]([O:31][C:32](=[O:34])[CH3:33])[CH2:24][S:23][C@H:13]1[O:14][C:15]1[C:16]([F:22])=[N:17][CH:18]=[C:19](Br)[CH:20]=1)(=[O:10])[CH3:9]>>[C:8]([O:11][C@@H:12]1[C@@H:26]([O:27][C:28](=[O:30])[CH3:29])[C@H:25]([O:31][C:32](=[O:34])[CH3:33])[CH2:24][S:23][C@H:13]1[O:14][C:15]1[C:16]([F:22])=[N:17][CH:18]=[C:19]([C:2]2[CH:3]=[N:4][CH:5]=[N:6][CH:7]=2)[CH:20]=1)(=[O:10])[CH3:9]
Reactant: Brc1cncnc1
Reactant: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cc(Br)cnc1F
Product: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cc(-c2cncnc2)cnc1F

Procedure:
By carrying out the operation analogously to the first part of example 137, 5-(pinacolatoboryl)pyrimidine is prepared from 5-bromopyrimidine and is reacted immediately in the same reactor with 5-bromo-2-fluoro-3-pyridinyl 2,3,4-tri-O-acetyl-5-thio-β-D-xylopyranoside, obtained according to preparation VIII, under conditions analogous to those applied in the preparation of example 177. The expected product is thus obtained in the form of a yellow solid (yield=40%).
Reaction SMILES: [NH2:1][CH2:2][C@@H:3]1[C@@H:7]([F:8])[CH2:6][N:5]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:4]1.NCC1CN(C(O[CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=O)CC=1.C(=O)C1C=CC=CC=1.Cl.[OH-].[Na+]>CO>[CH2:29]([NH:1][CH2:2][C@@H:3]1[C@@H:7]([F:8])[CH2:6][N:5]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:4]1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: NCC1=CCN(C(=O)OCc2ccccc2)C1
Reactant: NC[C@H]1CN(C(=O)OCc2ccccc2)C[C@@H]1F
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O=Cc1ccccc1
Solvent: CO
Product: O=C(OCc1ccccc1)N1C[C@H](CNCc2ccccc2)[C@@H](F)C1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
The mixture (310 mg) of (3S,4R)-3-aminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine and 3-aminomethyl-1-benzyloxycarbonyl-3-pyrroline was dissolved in methanol (4 mL). To this solution, molecular sieves 4A (130 mg) and then benzaldehyde (0.13 mL) were added and the mixture was stirred at room temperature for 1 hour. Subsequently, a borane/pyridine complex (0.19 mL) was added and the reaction mixture was further stirred at room temperature for 4 hours. 6 mol/L hydrochloric acid (2 mL) was then added and the mixture was stirred at room temperature for 1 hour, followed by addition of a 30% aqueous solution of sodium hydroxide to make the mixture basic. The mixture was then extracted with diethyl ether (3×10 mL) The diethyl ether layers were combined and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluant: dichloromethane:methanol=10:1) to give (3S,4R)-3-benzylaminomethyl-1-benzyloxycarbonyl-4-fluoropyrrolidine as a pale yellow oil (177 mg).
Reaction SMILES: [CH:1]([O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11]([CH3:15])=[CH:10][CH:9]=[CH:8]2)([CH3:3])[CH3:2].[Br:16]N1C(=O)CCC1=O>>[Br:16][CH2:15][C:11]1[C:12]2[C:7](=[CH:6][C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[CH:14][CH:13]=2)[CH:8]=[CH:9][CH:10]=1
Reactant: Cc1cccc2cc(OC(C)C)ccc12
Reactant: O=C1CCC(=O)N1Br
Product: CC(C)Oc1ccc2c(CBr)cccc2c1

Procedure:
Using general procedure A (Exp. 1.3.), 6-isopropoxy-1-methyl-naphthalene was reacted with N-bromosuccinimide to give 1-bromomethyl-6-isopropoxy-naphthalene as colorless oil. MS: 279.1 ([M−H]−).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:14][C:13]([CH:15]=O)=[CH:12][CH:11]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[NH2:17][CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=1.[BH4-].[Na+].[ClH:28]>CO>[ClH:28].[ClH:28].[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:14][C:13]([CH2:15][NH:17][CH2:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=3)=[CH:12][CH:11]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: O=Cc1ccc(-c2ccc([N+](=O)[O-])cc2)o1
Reactant: NCCc1ccccn1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: O=[N+]([O-])c1ccc(-c2ccc(CNCCc3ccccn3)o2)cc1
Yield: 87 %

Procedure:
A mixture of 54 g (0.25 mole) of 5-(4-nitrophenyl)-2-furaldehyde and 30.5 g (0.25 mole) of 2-(2-aminoethyl)pyridine in 300 ml of methanol was heated under reflux for 21/2 hours. The resulting solution was cooled to 25°, and 9.5 g (0.25 mole) of sodium borohydride was added in portions over 1 hour at 25°-30°. The solution was heated under reflux for 15 min, and the solvent was removed on a rotary evaporator. The residual solid was partitioned between water and chloroform. The chloroform layer (400 ml) was separated, dried over MgSO4, and concentrated on a rotary evaporator to give 81 g of a reddish brown, oily residue which solidified on standing. The residual solid was dissolved in 400 ml of absolute methanol and treated with 200 ml of absolute methanol saturated with hydrogen chloride with cooling in ice. The yellow solid which was deposited was collected by filtration using a rubber dam and dried in a vacuum oven at oil pump pressure at 100° C. for 8 hr to give 86 g (87%) of product. Two additional recrystallizations from absolute methanol gave an analytical sample, m.p. 173°-177°.
Reaction SMILES: Cl[CH2:2][C:3]([C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:14]=1[N:13]=[CH:12][CH:11]=[CH:10]2)=[O:4].[N-:15]=[N+:16]=[N-:17].[Na+]>CS(C)=O.CCOC(C)=O>[N:15]([CH2:2][C:3]([C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:14]=1[N:13]=[CH:12][CH:11]=[CH:10]2)=[O:4])=[N+:16]=[N-:17]
Reactant: [N-]=[N+]=[N-]
Reactant: O=C(CCl)c1cccc2cccnc12
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Product: [N-]=[N+]=NCC(=O)c1cccc2cccnc12
Reaction time: 2 h

Procedure:
To a solution of 2-chloro-1-quinolin-8-yl-ethanone (5.85 g, 28.5 mmol) in DMSO (60 mL), as prepared in the last step, was added NaN3 (2.2 g, 33.9 mmol). After 2 hours, the reaction was diluted with EtOAc (250 mL) and washed with H2O (3×100 mL). The organic phase was washed with brine (100 mL), dried over Na2SO4 and concentrated in vacuo. Purification via SiO2 chromatography (20% EtOAc/hexanes) affored the product as a pale yellow solid (4.95 g). 1H NMR (300 Hz, CDCl3) δ 9.0-8.97 (m, 1H), 8.26-8.22 (m, 2H), 8.04-8.02 (m, 1H), 7.68-7.63 (m, 1H), 7.52-7.48 (m, 1H), 5.12 (s, 2H).
Reaction SMILES: C(CCCCCCCCCCN)C=C.C(N(CC)C(C)C)(C)C.ClC([O:27][CH2:28][CH:29]1C2C=CC=CC=2C2C1=CC=CC=2)=O.[C:42]([NH:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69]CC=C)([O:44][CH2:45][CH:46]1[C:58]2[C:53](=[CH:54][CH:55]=[CH:56][CH:57]=2)[C:52]2[C:47]1=[CH:48][CH:49]=[CH:50][CH:51]=2)=[O:43]>ClCCl>[C:42]([N:59]([CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH3:69])[CH2:29][CH:28]=[O:27])([O:44][CH2:45][CH:46]1[C:47]2[C:52](=[CH:53][CH:54]=[CH:55][CH:48]=2)[C:51]2[C:58]1=[CH:57][CH:56]=[CH:49][CH:50]=2)=[O:43]
Reactant: O=C(Cl)OCC1c2ccccc2-c2ccccc21
Reactant: C=CCCCCCCCCCCCNC(=O)OCC1c2ccccc2-c2ccccc21
Agent: C=CCCCCCCCCCCCN
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCCCCCCCCCN(CC=O)C(=O)OCC1c2ccccc2-c2ccccc21
Temperature: 5 °C

Procedure:
A three-necked, 500 mL round bottom flask equipped with a thermometer, mechanic stirrer and an addition funnel was purged with nitrogen and charged with N-allyldecylamine (˜0.11 mol) in dichloromethane from step a (210 mL) and N,N-diisopropylethylamine (20.0 mL, 14.8 g, 0.113 mol). The mixture was cooled in a 5° C. ice bath and a solution of 9-fluorenylmethyl chloroformate (25.6 g, 0.099 mol) dissolved in dichloromethane (50 mL) was added dropwise (total volume approximately 330 mL). The reaction was exothermic and the internal temperature was controlled below 10° C. throughout the 9-fluorenylmethyl chloroformate addition. The reaction mixture was warmed to 21° C. when the addition was finished, and monitored by the disappearance of 9-fluorenylmethyl chloroformate and the formation of N-FMOC-N-allyldecylamine using HPLC (retention time for FMOC-chloride=3.08 min; retention time for product=7.96 min). The reaction mixture was washed with 0.01 N HCl (100 mL). The organic layer was collected and used without further purification.
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]([C@H:13]([CH3:17])[C:14]([OH:16])=[O:15])[CH:7]=[CH:6]2.[CH2:18]([O:25][CH2:26][C@H:27]([OH:30])[CH2:28]O)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C@H:13]([CH3:17])[C:14]([O:16][CH2:28][C@H:27]([OH:30])[CH2:26][O:25][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:15])[CH:7]=[CH:6]2
Reactant: COc1ccc2cc([C@H](C)C(=O)O)ccc2c1
Reactant: OC[C@@H](O)COCc1ccccc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: COc1ccc2cc([C@H](C)C(=O)OC[C@H](O)COCc3ccccc3)ccc2c1

Procedure:
A solution of (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 3.70 g, 16.1 mmol), (R)-(+)-3-benzyloxy-1,2-propanediol (2.92 g, 19.0 mmol), N,N-dimethylaminopyridine (DMAP, 0.40 g, 3.3 mmol) and 1,3-dicyclohexylcarbodiimide (3.61 g, 17.5 mmol) in CH2Cl2 (120 mL) was stirred at ambient temperature overnight. The byproduct, dicyclohexyl urea, was removed by filtration. The reaction mixture was partitioned between HCl (3N, 50 mL) and CH2Cl2 (50 mL×2). The combined organic extracts were back washed with water, brine, dried over Na2SO4, filtered, concentrated and dried under vacuum. The product was separated by silica gel column chromatography eluting with EtOAc:hexane (1:2, Rf=0.23) to give a mixture of the 1- and 2-glycerol ester isomers (88:12, 3.87 g). 1H NMR (300 MHz, CDCl3) δ 7.69-7.64 (m, 3H), 7.40-7.03 (m, 8H), 5.34 (s, 2H), 4.17-4.14 (m, 2H), 3.88 (s, 3H), 3.9-3.85 (m, 2H), 3.33-3.28 (m, 2H), 2.45 (br. d, 1H), 1.56 (d, J=7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 174.6, 157.6, 137.6, 135.4, 133.6, 129.6, 129.2, 128.8, 128.3, 127.7, 127.61, 127.55, 127.1, 126.1, 125.9, 119.0, 105.5, 73.3, 70.6, 68.8, 65.5, 62.2, 55.2, 45.3, 18.3. Mass spectrum (API-TIS) m/z 412 (M+NH4)+.
Reaction SMILES: [CH:1]1([C:4]2[N:8]([CH3:9])[C:7]3[CH:10]=[C:11]([N:14]4[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][C:15]4=[O:21])[CH:12]=[CH:13][C:6]=3[N:5]=2)[CH2:3][CH2:2]1.[S:22]1[CH:26]=[CH:25][C:24]([CH2:27]O)=[CH:23]1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1COCC1>[CH:1]1([C:4]2[N:8]([CH3:9])[C:7]3[CH:10]=[C:11]([N:14]4[CH:19]=[CH:18][C:17]([O:20][CH2:27][C:24]5[CH:25]=[CH:26][S:22][CH:23]=5)=[CH:16][C:15]4=[O:21])[CH:12]=[CH:13][C:6]=3[N:5]=2)[CH2:2][CH2:3]1
Reactant: Cn1c(C2CC2)nc2ccc(-n3ccc(O)cc3=O)cc21
Reactant: OCc1ccsc1
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: C1CCOC1
Product: Cn1c(C2CC2)nc2ccc(-n3ccc(OCc4ccsc4)cc3=O)cc21
Temperature: 50 °C
Reaction time: 1 h

Procedure:
To a solution of 1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one (100 mg), 3-thienylmethanol (67 μl) and tributylphosphine (258 μl) in THF (10 ml) was added 1,1′-(azodicarbonyl)dipiperidine (264 mg). The mixture was stirred under sonication at 50° C. for 1 h. The reaction mixture was then cooled to room temperature, and concentrated in vacuo. The crude residue was diluted with DCM (100 ml), and the DCM layer was washed with water (100 ml), brine (30 ml), dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography (MeOH/DCM) to give the title compound (50 mg) as an off-white solid.