Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].[C:19]([NH:27][C:28]1[CH:37]=[C:36](Br)[CH:35]=[CH:34][C:29]=1[C:30]([O:32]C)=[O:31])(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CN(C)C(=O)C>[C:19]([NH:27][C:28]1[CH:37]=[C:36]([C:2]2[O:1][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[CH:3]=2)[CH:35]=[CH:34][C:29]=1[C:30]([OH:32])=[O:31])(=[O:26])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: OB(O)c1cc2ccccc2o1
Reactant: COC(=O)c1ccc(Br)cc1NC(=O)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: O=C(Nc1cc(-c2cc3ccccc3o2)ccc1C(=O)O)c1ccccc1
Temperature: 90 °C
Reaction time: 22 h
Yield: 14.7 %

Procedure:
51 mg of benzofuran-2-boronic acid, 55 mg of sodium carbonate and 30 mg of polymer supported bis(acetato)triphenylphosphine palladium(II) were added to 2.5 mL of N,N-dimethylacetamide solution containing 70 mg of methyl 2-(benzamido)-4-bromobenzoate, and stirred at 90° C. for 22 hours. After the reaction mixture was cooled to room temperature, insoluble were removed by filtration and ethyl acetate and 1.2 mol/L hydrochloric acid were added. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with 1.0 mol/L hydrochloric acid and a saturated sodium chloride aqueous solution sequentially, and the solvent was evaporated under reduced pressure. 1.0 mL of 1.0 mol/L aqueous sodium hydroxide and 2.0 ml, of ethanol were added to the obtained residue and stirred at room temperature for 1 hour. 0.6 mol/L hydrochloric acid was added to the reaction mixture and a solid substance was separated by filtration to obtain 11 mg of 2-(benzamido)-4-(benzofuran-2-yl)benzoic acid as whine solid.
Reaction SMILES: C(CCN(C1C=C(C)N=C(N2C=CN=C2)N=1)[CH2:6][C:7]([NH:9][CH2:10][CH2:11][C:12]1[CH:20]=[CH:19][C:15]2[O:16][CH2:17][O:18][C:14]=2[CH:13]=1)=[O:8])#N.N>CO.[Ni]>[O:16]1[C:15]2[CH:19]=[CH:20][C:12]([CH2:11][CH2:10][NH:9][C:7](=[O:8])[CH3:6])=[CH:13][C:14]=2[O:18][CH2:17]1
Reactant: Cc1cc(N(CCC#N)CC(=O)NCCc2ccc3c(c2)OCO3)nc(-n2ccnc2)n1
Agent: [Ni]
Agent: N
Solvent: CO
Product: CC(=O)NCCc1ccc2c(c1)OCO2
Reaction time: 16 h

Procedure:
To 2-[(2-cyanoethyl)[2-(1H-imidazol-1-yl)-6-methyl-4-pyrimidinyl]amino]-N-[2-(1,3-benzodioxol-5-yl)ethyl]acetamide (2.5 g, 5.8 mmol) (a compound of formula (Yc3)) in MeOH (50 mL) was bubbled ammonia. Raney nickel (1.0 g of a 50% slurry) was added and the reaction was placed on a Parr hydrogenator at 50 psi. After shaking for 16 hours, the pressure was released and the reaction mixture was suction filtered through Celite. The solvent was removed in vacuo and the residue was chromatographed on silica gel (9:1 CH3CN/NH4OH) to afford 2-[(3-aminopropyl)[2-(1H-imidazol-1-yl)-6-methyl)-4-pyrimidinyl]amino]-N-[2-(1,3-benzodioxol-5-yl)ethyl]acetamide, a compound of formula (Yc6); as a white solid; NMR (DMSO-d6, 90° C.) 8.4 (s, 1), 7.8 (s, 1), 7.0 (s, 1), 6.75 (d, 1), 6.7 (s, 1), 6.6 (d, 1), 5.9 (s, 2), 4.1 (s, 2), 3.6 (br, 2), 3.3 (m, 2), 2.75 (t, 2), 2.6 (t, 2), 2.3 (s, 3), 1.8 (m, 2) ppm.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12](=[O:14])[CH3:13])=[CH:7][C:6]=1[F:15])(=[O:3])[CH3:2].[N+:16]([O-])([OH:18])=[O:17]>C(O)(=O)C>[C:1]([NH:4][C:5]1[CH:10]=[C:9]([N+:16]([O-:18])=[O:17])[C:8]([NH:11][C:12](=[O:14])[CH3:13])=[CH:7][C:6]=1[F:15])(=[O:3])[CH3:2]
Reactant: CC(=O)Nc1ccc(NC(C)=O)c(F)c1
Reactant: O=[N+]([O-])O
Solvent: CC(=O)O
Product: CC(=O)Nc1cc([N+](=O)[O-])c(NC(C)=O)cc1F
Temperature: 40 °C
Reaction time: 2 h

Procedure:
157.5 g (0.75 mol) of the 1,4-bisacetylamino-2-fluorobenzene obtained above under B. are initially introduced into 630 g of glacial acetic acid, and a mixture of 42 g of glacial acetic acid and 51 g of nitric acid (density 1.5) is added dropwise in the course of 2 hours. The mixture is subsequently stirred at 40° C. for a further 2 hours and cooled to 15° C. After the product which has precipitated has been filtered off, it is washed twice with 50 ml of glacial acetic acid each time and dried at 50° C. in a vacuum cabinet.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][C:8]1[CH:9]=[N:10][CH:11]=[C:12]([CH3:19])[C:13]=1[C:14](OCC)=[O:15]>C1COCC1>[CH3:7][C:8]1[CH:9]=[N:10][CH:11]=[C:12]([CH3:19])[C:13]=1[CH2:14][OH:15]
Reactant: CCOC(=O)c1c(C)cncc1C
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: Cc1cncc(C)c1CO
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 69.9 %

Procedure:
To a 0° C. mixture of lithium aluminum hydride (2.0 g, 53 mmol) in anhydrous THF (100 mL) was slowly added a solution of ethyl 3,5-dimethylpyridine-4-carboxylate (4.77 g, 26.6 mmol) in anhydrous THF (30 mL). The reaction mixture was stirred at 0° C. for 1.5 hours. The reaction was quenched with 5 N NaOH. Water (100 mL) and EtOAc (100 mL) were added. The mixture was stirred for 30 minutes. The solid material was removed by filtration. The organic layer was recovered. The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic extracts were dried over MgSO4, filtered, evaporated, and dried in vacuo, affording (3,5-dimethylpyridin-4-yl)methanol (2.55 g, 70% yield). The product was used without further purification.
Reaction SMILES: [Li]CCCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[O:13][CH3:14].[CH3:15][Sn:16](Cl)([CH3:18])[CH3:17]>C(OCC)C>[CH3:15][Sn:16]([CH3:18])([CH3:17])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[O:13][CH3:14]
Reactant: C[Sn](C)(C)Cl
Reactant: COc1ccccc1Br
Agent: [Li]CCCC
Solvent: CCOCC
Product: COc1ccccc1[Sn](C)(C)C
Temperature: -78 °C
Reaction time: 1 h
Yield: 76.6 %

Procedure:
To a stirring solution of n-BuLi (2.6 mL, 2.5M in hexane, 6.42 mmol) in diethyl ether (2.5 mL) at −78° C. was added 2-bromoanisole (1.0 g, 5.35 mmol) in diethyl ether (2 mL) dropwise. After stirring for 1 h at −78° C., trimethyltin chloride (6mL, 1.0M in THF, 6.42 mmol) was added dropwise. The mixture was allowed to stir an additional 2 h while slowly warming to room temperature. The mixture was then washed with saturated aqueous NaHCO3. The aqueous layer was extracted with diethyl ether (1×5 mL) and the organic layers were combined, dried (MgSO4), filtered and concentrate. The residue was purified by column chromatography (silica gel, hexane) to yield the title compound as a colorless oil (1.11 g, 76%). 1HNMR (400 MHz, CDCl3)δ7.47 (d, 1H), 7.40 (t, 1H), 7.05 (t, 1H), 6.90 (d, 1H), 3.36 (s, 3H), 0.34 (s, 9H).
Reaction SMILES: [C:1](Cl)(=[O:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].[OH:14][C@H:15]1[CH2:20][CH2:19][C@H:18]2[C@H:21]3[C@H:30]([CH2:31][CH2:32][C@:16]12[CH3:17])[C@@H:29]1[C:24](=[CH:25][C:26](=[O:33])[CH2:27][CH2:28]1)[CH2:23][C@H:22]3[CH3:34].OS(O)(=O)=O>>[CH3:34][C@@H:22]1[CH2:23][C:24]2[C@H:29]([CH2:28][CH2:27][C:26](=[O:33])[CH:25]=2)[C@@H:30]2[C@@H:21]1[C@H:18]1[C@@:16]([CH2:32][CH2:31]2)([CH3:17])[C@@H:15]([O:14][C:1](=[O:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[CH2:20][CH2:19]1
Reactant: CCCCCCCCCCC(=O)Cl
Reactant: C[C@@H]1CC2=CC(=O)CC[C@@H]2[C@H]2CC[C@]3(C)[C@@H](O)CC[C@H]3[C@@H]21
Agent: O=S(=O)(O)O
Product: CCCCCCCCCCC(=O)O[C@H]1CC[C@H]2[C@H]3[C@H](CC[C@]12C)[C@H]1CCC(=O)C=C1C[C@H]3C
Temperature: 0 °C
Reaction time: 8 h

Procedure:
A total of 2.23 grams of commercially available undecanoyl chloride were added to a stirred solution of 1.58 grams of (7α,17β)-17-hydroxy-7-methylestr-4-en-3-one at 0-5° C. reaction mixture was allowed to reach room temperature and stirred overnight. Thereafter, ice was added and after stirring for another 2 hours the reaction mixture was poured into ice-water, containing 4 ml of conc. H2SO4, followed by ethyl acetate extraction. The organic layers were washed with water, cold 1 N NaOH solution and brine, dried on sodium sulfate, filtered and evaporated in vacuo. The residue was chromatographed over silica. Elution with heptane-ethylacetate (4:1) and evaporation gave a greasy solid that was collected. Yield 1.42 g, [α]D20=+36° (c=1; dioxane), MS (ESI): 456.
Reaction SMILES: [OH:1][CH2:2][CH:3]1[CH2:10][CH:9]2[CH2:11][CH:5]([CH2:6][N:7](C(OC(C)(C)C)=O)[CH2:8]2)[CH2:4]1.[ClH:19].C(OCC)(=O)C>CO>[ClH:19].[CH:9]12[CH2:11][CH:5]([CH2:4][CH:3]([CH2:2][OH:1])[CH2:10]1)[CH2:6][NH:7][CH2:8]2
Reactant: CC(C)(C)OC(=O)N1CC2CC(CO)CC(C2)C1
Agent: Cl
Solvent: CO
Solvent: CCOC(C)=O
Product: OCC1CC2CNCC(C1)C2
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of 3-tert-butyl 7-hydroxymethyl-3-azabicyclo[3.3.1]nonane-3-carboxylate (7.78 g) in methanol (76 mL) was added 4M hydrogen chloride/ethyl acetate solution (76 mL). The reaction mixture was stirred at room temperature for 4 hr, and the solvent was evaporated under reduced pressure. The residue was dissolved in methanol (50 mL), and Amberlyst A-21 was added. The mixture was stirred at room temperature for 20 min, and the solid was removed by filtration. The solvent was evaporated under reduced pressure, and the residue was recrystallized from ethanol/ethyl acetate to give the title compound (5.22 g).
Reaction SMILES: Br[C:2]1[CH2:6][CH2:5][O:4][N:3]=1.NC1CCON=1.C([O:15][C:16](=[O:20])[CH2:17][NH:18][CH3:19])C>>[O:4]1[CH2:5][CH2:6][C:2]([N:18]([CH3:19])[CH2:17][C:16]([OH:20])=[O:15])=[N:3]1
Reactant: BrC1=NOCC1
Reactant: CCOC(=O)CNC
Agent: NC1=NOCC1
Product: CN(CC(=O)O)C1=NOCC1

Procedure:
2-((4,5-dihydroisoxazol-3-yl)(methyl)amino)acetic acid I-244a and I-244b were prepared in 2 steps according to the following procedure: racemic 3-bromo-4,5-dihydroisoxazole I-10 was converted to the corresponding 3-amino-4,5-dihydroisoxazole by reacting it with sarcosine ethyl ester under the same conditions as in Example 238. The ethyl ester was then hydrolyzed using the analogous conditions as in Example 119 to provide a mixture of racemic I-244. These compounds can be separated using chiral HPLC methods known in the art. For example, see chiral HPLC Method disclosed herein. [M−H]−=327.5 m/z. Activity: B
Reaction SMILES: [NH2:1][C@H:2]([C:7]([OH:9])=[O:8])[CH2:3][CH2:4][S:5][CH3:6].N[C@H:11](C(O)=O)[CH2:12]S.C(=O)([O-])O.[Na+].N[C@H](C(O)=O)CCCCN.Cl.P(=O)(O)(O)O>C(=O)([O-])[O-].[Na+].[Na+].O>[CH2:11]([O:8][C:7](=[O:9])[C@H:2]([CH2:3][CH2:4][S:5][CH3:6])[NH2:1])[CH3:12]
Reactant: CSCC[C@H](N)C(=O)O
Reactant: N[C@@H](CS)C(=O)O
Agent: Cl
Agent: NCCCC[C@H](N)C(=O)O
Agent: O=C([O-])O
Solvent: O
Product: CCOC(=O)[C@@H](N)CCSC
Temperature: 90 °C
Reaction time: 24 h

Procedure:
A solution of 2.2 g of L-lysine in 13.0 ml of ethyl alcohol and 1.6 ml of conc. sulfuric acid was heated under reflux at 90° C. for 5 hours, obtaining L-lysine ethyl ester in a yield of 76.5%. Separately, L-methionine ethyl ester was prepared from 0.8 g of L-methionine in the same manner as in Example 1. After 66 mg of papain and 6.6 mg of L-cysteine were dissolved in a solution of 1.8 g of sodium carbonate and 0.52 g of sodium hydrogen carbonate in 20 ml of water, 20 g of wheat gluten in limited amounts was added to the solution and mixed therewith. The previously prepared reaction solutions of L-lysine and L-methionine ethyl esters were all added to the protein system of wheat gluten, and the system was kept at 37° C. for 24 hours to effect plastein reaction. The rates of incorporation of L-lysine and L-methionine were 62.7% and 81.6%, respectively. At the end of the reaction, the reaction solution was diluted with water to a volume of 300 ml and adjusted to pH 7 with hydrochloric acid before it was subjected to repeated concentration operations for desalting and purification using a reverse osmosis membrane equipped small experimental apparatus (equipped with a DRS-10 flat membrane, manufactured by Daicell Chemical K.K.) under an operating pressure of 15 kg/cm2. The concentrate resulting from the reverse osmosis treatment was again diluted with water to a volume of 400 ml and adjusted to pH 2.0 with phosphoric acid. After 0.4 g of pepsin was added to the solution, the hydrolytic reaction was carried out for 3 hours. Thereafter, 0.4 g of orientase was added and the hydrolytic reaction was continued for an additional 30 hours. The reaction solution was heated to 90° C. for 10 minutes and then centrifuged under 2000G to remove the solids. The supernatant was freeze dried to yield 18.3 g of a low-molecular weight peptide mixture. This product had an average molecular weight of 350 and contained 8.9% of free amino acids, and the gel filtration showed that it contained 86.2% of compounds with a molecular weight of 700 or lower. Table 2 shows the amino acid composition of the starting protein, wheat gluten and the low-molecular weight peptide mixture produced therefrom. As seen from Table 2, the low-molecular weight peptide mixture had the increased contents of L-lysine and L-methionine as compared with the starting protein.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N+:8]([O-])=O.[CH:11]([Mg]Br)=[CH2:12].[Cl-].[NH4+]>O1CCCC1>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]2[C:3]=1[NH:8][CH:12]=[CH:11]2
Reactant: C=C[Mg]Br
Reactant: O=[N+]([O-])c1ccccc1Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: Brc1cccc2cc[nH]c12
Temperature: -40 °C
Reaction time: 0.33 h

Procedure:
1-bromo-2-nitrobenzene (6.000 g, 29.7 mmol) was added to tetrahydrofuran (65 mL) and cooled to −40° C. Vinylmagnesiumbromide (1M in tetrahydrofuran, 89 mL) was added quickly. The solution was stirred for 20 minutes and then poured into a saturated aqueous solution of ammonium chloride. The solution was extracted with diethyl ether and dried with brine and anhydrous sodium sulfate. The solution was concentrated and purified by flash column chromatography on silica gel with 5% ethyl acetate in hexanes to provide the title compound.
Reaction SMILES: [Si:1]([O:8][C@H]1CCC[C@@]2(C)[C@H]1CC[C@@H]2[C@H](C)CO)([C:4](C)(C)C)([CH3:3])[CH3:2].C[N+]1([O-])CCOCC1.[CH3:31][Si:32]([CH3:50])([CH3:49])OC(C)(C)[C@H](C)CS(C1C=CC=CC=1)(=O)=O>ClCCl.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC>[CH3:2][Si:1]([O:8][Si:32]([CH3:50])([CH3:49])[CH3:31])([CH3:4])[CH3:3]
Reactant: C[C@H](CS(=O)(=O)c1ccccc1)C(C)(C)O[Si](C)(C)C
Reactant: C[C@H](CO)[C@H]1CC[C@H]2[C@@H](O[Si](C)(C)C(C)(C)C)CCC[C@]12C
Agent: O=[Ru](=O)(=O)[O-]
Agent: CCC[N+](CCC)(CCC)CCC
Agent: C[N+]1([O-])CCOCC1
Solvent: ClCCl
Product: C[Si](C)(C)O[Si](C)(C)C
Temperature: 25 °C
Reaction time: 2 h

Procedure:
The compound of Example 10E (200 mg, 0.61 mmol) was dissolved in 2 mL of dichloromethane; 100 mg of 4 Å molecular sieves were added, followed by 15 mg of tetrapropylammonium perruthenate and 75 mg of 4-methylmorpholine N-oxide. The mixture was stirred for 2 hours at ambient temperature, and then filtered through diatomaceous earth to removed solids. The crude product was purified by silica gel chromatography using an Analogix IntelliFlash™ 40, eluting with a gradient of 5% to 30% ethyl acetate in hexanes. The compound of Example 10C (200 mg, 0.63 mmol) was combined with this aldehyde according to the coupling procedure described by Kutner et al. in J. Org. Chem. 1988, 53, 3450-3457. The named product was isolated as a mixture of trimethylsilyl ether (Fraction A) and hydroxyl (Fraction B) after chromatographic purification using an Analogix IntelliFlash 280™, eluting with a gradient of 0% to 50% ethyl acetate in hexanes. These products were combined and carried forward to the next step.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[C:8]([F:10])[C:7]([N+:11]([O-])=O)=[CH:6][C:3]=1[CH2:4][OH:5]>[Pt]=O.C(O)(=O)C>[Cl:1][C:2]1[CH:9]=[C:8]([F:10])[C:7]([NH2:11])=[CH:6][C:3]=1[CH2:4][OH:5]
Reactant: O=[N+]([O-])c1cc(CO)c(Cl)cc1F
Agent: O=[Pt]
Solvent: CC(=O)O
Product: Nc1cc(CO)c(Cl)cc1F
Yield: 96.5 %

Procedure:
In a Parr hydrogenation apparatus were placed 6.5 g (0.032 mole) of 2-chloro-4-fluoro-5-nitrobenzyl alcohol, 0.3 g of platinum oxide catalyst, and 100 ml of glacial acetic acid. Hydrogenation required 1.5 hours after which the catalyst was removed by filtration and the solvent was evaporated under reduced pressure, leaving 5.42 g of 2-chloro-4-fluoro-5-aminobenzyl alcohol as a tan solid. The nmr and ir spectra were consistent with the proposed structure.
Reaction SMILES: [ClH:1].[C:2]1([N:8]([CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[C:9]([C:11]2[CH:12]=[CH:13][C:14]3[S:18][C:17]([CH2:19][S:20][C:21]4[CH:26]=[CH:25][C:24]([C:27](=[NH:29])[NH2:28])=[CH:23][CH:22]=4)=[N:16][C:15]=3[CH:30]=2)=[O:10])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:38]O>C(O)(=O)C>[ClH:1].[C:2]1([N:8]([CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[C:9]([C:11]2[CH:12]=[CH:13][C:14]3[S:18][C:17]([CH2:19][S:20]([C:21]4[CH:26]=[CH:25][C:24]([C:27](=[NH:28])[NH2:29])=[CH:23][CH:22]=4)=[O:38])=[N:16][C:15]=3[CH:30]=2)=[O:10])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OO
Reactant: CCOC(=O)CCN(C(=O)c1ccc2sc(CSc3ccc(C(=N)N)cc3)nc2c1)c1ccccc1
Agent: Cl
Solvent: CC(=O)O
Product: CCOC(=O)CCN(C(=O)c1ccc2sc(CS(=O)c3ccc(C(=N)N)cc3)nc2c1)c1ccccc1
Temperature: 25 °C
Yield: 58 %

Procedure:
A solution of 0.15 g (0.27 mMol) of 2-[(4-amidinophenyl)thiomethyl]-benzothiazol-5-yl-carboxylic acid-N-phenyl-N-(2-ethoxycarbonylethyl)-amide-hydrochloride in 10 ml of acetic acid was mixed with 0.09 ml (about 0.81 mMol) of 30% hydrogen peroxide solution and stirred at room temperature. After 4 days a further 0.18 ml of hydrogen peroxide solution was added and the resulting mixture was stirred for a further two days. After removal of the solvent in vacuo the crude product obtained was purified by flash chromatography (silica gel; methylene chloride/ethanol=10:1 to 4:1). Yield: 58% of theory, C27H26N4O4S2 (534.66) Rf value: 0.24 (silica gel; methylene chloride/ethanol =4:1+a few drops of acetic acid) EKA mass spectrum: (M+H)+ =535
Reaction SMILES: [N+:1]([C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([O:14][CH:15]([C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH2:23])[CH:18]=2)[CH3:16])=[CH:6][CH:5]=1)([O-])=O.[H][H]>CO.CC(O)=O.[Pt]>[NH2:1][C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([O:14][CH:15]([C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH2:23])[CH:18]=2)[CH3:16])=[CH:6][CH:5]=1
Reactant: [H][H]
Reactant: CC(Oc1ccc([N+](=O)[O-])c2ccccc12)c1ccnc(N)c1
Agent: [Pt]
Solvent: CC(=O)O
Solvent: CO
Product: CC(Oc1ccc(N)c2ccccc12)c1ccnc(N)c1
Yield: 98.6 %

Procedure:
4-(1-(4-Nitronaphthalen-1-yloxy)ethyl)pyridin-2-amine (23) (91 mg, 0.294 mmol) in MeOH (15 mL) and AcOH (3.0 mL) was passed through a Thales H-cube (1.0 mL·min−1, 30° C., 55 mm 10% Pt/C Cat-Cart, full hydrogen mode). The volatiles were removed under reduced pressure, leaving a purple solid, which was then subjected to SCX capture and release to give 4-(1-(4-aminonaphthalen-1-yloxy)ethyl)pyridin-2-amine (24) (81 mg, 99%) as a purple oil: m/z 280 (M+H)+ (ES+).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:38]=[CH:37][C:6]([CH2:7][O:8][C:9]2[C:26]([O:27][CH2:28][C:29]3[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=3)=[CH:25][CH:24]=[CH:23][C:10]=2[C:11]([O:13]CC2C=CC(OC)=CC=2)=[O:12])=[CH:5][CH:4]=1>O1CCOCC1.[OH-].[Na+]>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][O:8][C:9]2[C:26]([O:27][CH2:28][C:29]3[CH:30]=[CH:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=3)=[CH:25][CH:24]=[CH:23][C:10]=2[C:11]([OH:13])=[O:12])=[CH:37][CH:38]=1
Reactant: COc1ccc(COC(=O)c2cccc(OCc3ccc(OC)cc3)c2OCc2ccc(OC)cc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: COc1ccc(COc2cccc(C(=O)O)c2OCc2ccc(OC)cc2)cc1

Procedure:
A solution of 19 (8.60 g, 16.71 mmol) in dioxane (84 mL) and 2N NaOH (42 mL) was stirred for 24 h at room temperature. The reaction mixture was concentrated in vacuo. The residue was stirred with H2O (100 mL) and then acidified to pH 2 with 1N HCl. The white solid was filtered, washed with hexane, and was recrystallised from EtOAc/hexanes to generate 5.93 g (90%) of 20 as a white crystalline solid, mp 129° C.: 1H NMR δ 3.8 (s, 3H), 3.85 (s, 3H), 5.12 (s, 2H), 5.20 (s, 2H), 6.83 (d, 2H, J=8.8), 6.96 (d, 2H, J=9.2), 7.18 (t, 2H, J=8.0), 7.22-7.27 (m, 2H), 7.41 (d, 2H, J=8.4), 7.73 (dd, 1H, J=1.2, 8.0); 13C NMR δ 55.36, 55.37, 55.44, 55.46, 71.42, 114.26, 119.12, 123.04, 124.37, 125.00, 126.87, 128.02, 129.73, 131.21, 147.17, 151.45, 159.94, 160.44, 165.45; HRMS m/z calcd for C23H22NaO6, 417.1332 (M+Na). found, 417.1332.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:10])/[CH:4]=[C:5](\[CH3:9])/[CH:6](O)[CH3:7].[Cl:11]P(Cl)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:10])/[CH:4]=[C:5](\[CH3:9])/[CH:6]([Cl:11])[CH3:7]
Reactant: COC(=O)/C=C(\C)C(C)O
Reactant: ClP(Cl)(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: ClCCl
Product: COC(=O)/C=C(\C)C(C)Cl
Temperature: 25 °C

Procedure:
To (E)-4-hydroxy-3-methyl-2-pentenoic acid methyl ester (1.00 g, 6.94 mmol) in methylene chloride cooled to -15° C. in a flame dried flask is added dichlorotriphenylphosphorane (2.47 g, 7.63 mmol). The reaction is warmed to ambient temperature, quenched by addition of ice (10 ml), extracted with methylene chloride (2×10 ml), washed with saline (10 ml), dried over sodium sulfate, concentrated in vacuo, and chromatographed on silica gel (230-400 mesh, 75 ml), eluting with hexane/ethyl acetate (95/5). The appropriate fractions are combined (Rf =0.55, TLC, hexane/ethyl acetate, 75/25) and concentrated in vacuo to give (E)-4-chloro-3-methyl-2-pentenoic acid methyl ester. 4-Amino-6-chloro-2-mercaptopyrimidine mesylate (0.30 g, 1.16 mmol) is dissolved in DMF (4 ml) and sodium hydride (0.06 g, 2.56 mmol) at ambient temperature followed by the addition of (E)-4-chloro-3-methyl-2-pentenoic acid methyl ester (0.19 g, 1.16 mmol). The reaction is stirred for 15 hours, quenched with excess water, extracted with ethyl acetate (3×15 ml). The extracts are combined, washed with saline (15 ml), dried over sodium sulfate, concentrated in vacuo and chromatographed on silica gel (230-400 mesh, 100 ml), eluting with hexane/ethyl acetate (85/15). The appropriate fractions are combined (Rf =0.18, TLC, hexane/ethyl acetate, 50/50) and concentrated in vacuo to give the title compound, mp 124-126° C.
Reaction SMILES: Cl[O-].[Ca+2].Cl[O-].[OH-].[Na+].[C:8](=[O:11])([O-])[O-:9].[Na+].[Na+].[O:14]1[C:19]2[CH:20]=[CH:21][C:22](C(C)=O)=[CH:23][C:18]=2[O:17][CH2:16][CH2:15]1>O>[CH2:15]1[CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([C:8]([OH:9])=[O:11])=[CH:20][C:19]=2[O:14]1
Reactant: O=C([O-])[O-]
Reactant: CC(=O)c1ccc2c(c1)OCCO2
Agent: [Ca+2]
Agent: [Na+]
Agent: [O-]Cl
Solvent: O
Product: O=C(O)c1ccc2c(c1)OCCO2
Temperature: 50 °C

Procedure:
A suspension of 80.1 g of calcium hypochlorite in 360 ml of water and a suspension of 6.72 g of sodium hydroxide and 56.4 g of sodium carbonate in 170 ml of water are combined and heated to 50° C. with stirring. The precipitate is removed by filtration and the solution obtained is combined with 25.0 g of 1,4-benzodioxan-6-yl-methylketone. The mixture is stirred for 15 h at 60° C., and after cooling to ambient temperature extracted with ethyl acetate. The aqueous phase is adjusted to a pH of 3 by the addition of concentrated hydrochloric acid while cooling with ice. The product precipitated is suction filtered, washed with water and dried at 90° C.