Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[NH:13][C:12]3=[CH:14][S:15][CH:16]=[C:11]3[C:10](=[O:17])[NH:9][C:8]=2[CH:18]=1)([O-])=O.N1C=CC=CC=1>[Pd].CO>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]2[NH:13][C:12]3=[CH:14][S:15][CH:16]=[C:11]3[C:10](=[O:17])[NH:9][C:8]=2[CH:18]=1
Reactant: O=C1Nc2cc([N+](=O)[O-])ccc2Nc2cscc21
Agent: [Pd]
Solvent: c1ccncc1
Solvent: CO
Product: Nc1ccc2c(c1)NC(=O)c1cscc1N2

Procedure:
A 7.8 g. portion of 4,9-dihydro-7-nitro-10H-thieno[3,4-b][1,5]benzodiazepin-10-one in a mixture of 200 ml. of pyridine and 50 ml. of methanol with 200 mg. of 10% palladium on carbon catalyst was shaken for 2 hours in a Parr hydrogenator. The catalyst was filtered and the solvents were removed under vacuum on the steam bath. The residue was dissolved in dilute hydrochloric acid, filtered, and the filtrate was made alkaline with sodium hydroxide. The crystals which form are recovered by filtration and air dried given the desired product as a brown powder, m.p. 212°-215° C.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH2:14]([O:21][C:22](=[O:28])[C@@H:23]1[CH2:27][CH2:26][CH2:25][NH:24]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[CH2:14]([O:21][C:22](=[O:28])[C@@H:23]1[CH2:27][CH2:26][CH2:25][N:24]1[C:10](=[O:12])[CH2:9][NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: CC(C)(C)OC(=O)NCC(=O)O
Reactant: O=C(OCc1ccccc1)[C@@H]1CCCN1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)NCC(=O)N1CCC[C@H]1C(=O)OCc1ccccc1
Reaction time: 2 h
Yield: 97.7 %

Procedure:
N-t-butyloxycarbonylglycine (21.02 g, 120 mmole), L-proline benzylester hydrochloride (29.01 g, 120 mmole) and HOBt (1.62 g, 12 mmole) were dissolved in methylene chloride (400 ml), and triethylamine (12.14 g, 120 mmole) and WSC hydrochloride (23.00 g, 120 mmole) were added to the solution at -30° C. The mixture was stirred for 2 hours at less than 0° C., and then overnight at room temperature. The solution was washed with 5% aqueous sodium bicarbonate (400 ml, twice), 5% aqueous citric acid (400 ml, twice) and water (400 ml) in the order given, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to give N-t-butyloxycarbonylglycyl-l-proline benzylester(yield 42.50 g, 97.7%).
Reaction SMILES: [CH2:1]([OH:34])[C@H:2]1[O:7][CH:6]([O:8][CH2:9][C@H:10]2[O:15][CH:14]([O:16][C@:17]3([CH2:26][OH:27])[O:21][C@H:20]([CH2:22][OH:23])[C@@H:19]([OH:24])[C@@H:18]3[OH:25])[C@H:13]([OH:28])[C@@H:12]([OH:29])[C@@H:11]2[OH:30])[C@H:5]([OH:31])[C@@H:4]([OH:32])[C@H:3]1[OH:33].O.O.O.O.O>CN(C)C=O>[CH2:1]([OH:34])[C@H:2]1[O:7][C@H:6]([O:8][CH2:9][C@H:10]2[O:15][C@H:14]([O:16][C@:17]3([CH2:26][OH:27])[O:21][C@H:20]([CH2:22][OH:23])[C@@H:19]([OH:24])[C@@H:18]3[OH:25])[C@H:13]([OH:28])[C@@H:12]([OH:29])[C@@H:11]2[OH:30])[C@H:5]([OH:31])[C@@H:4]([OH:32])[C@H:3]1[OH:33]
Reactant: OC[C@H]1OC(OC[C@H]2OC(O[C@]3(CO)O[C@H](CO)[C@@H](O)[C@@H]3O)[C@H](O)[C@@H](O)[C@@H]2O)[C@H](O)[C@@H](O)[C@H]1O
Solvent: O
Solvent: CN(C)C=O
Product: OC[C@H]1O[C@H](OC[C@H]2O[C@H](O[C@]3(CO)O[C@H](CO)[C@@H](O)[C@@H]3O)[C@H](O)[C@@H](O)[C@@H]2O)[C@H](O)[C@@H](O)[C@H]1O
Yield: 311.1 %

Procedure:
A solution of 2.0 g of D-raffinose pentahydrate in 50 ml of absolute dimethylformamide was stirred at 60° C. for 20 hours in the presence of 10.3 g of sulphur trioxide-trimethylamine complex, whereby a precipitate separated. The solvent was decanted off. The residue was washed with methanol, dissolved in 64 ml of aqueous 10% sodium acetate solution and concentrated. The residue was taken up several times in water and evaporated to remove trimethylamine. The residue was gel-chromatographed (Sephadex® LH 20) in order to remove salts. After freeze-drying there were obtained 5.28 g of sulfated raffinose, S=19.89%, AS (average degree of sulfation) about 2.8.
Reaction SMILES: [C:1]([O:9][C:10]1[CH:11]=[C:12](C2C(O)=CC=CC=2)[C:13](O)=[CH:14][CH:15]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N+:24]([O-:27])(O)=[O:25]>C(O)(=O)C>[C:1]([O:9][C:10]1[CH:15]=[CH:14][C:13]([C:2]2[CH:7]=[CH:6][C:5]([N+:24]([O-:27])=[O:25])=[CH:4][CH:3]=2)=[CH:12][CH:11]=1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=[N+]([O-])O
Reactant: O=C(Oc1ccc(O)c(-c2ccccc2O)c1)c1ccccc1
Solvent: CC(=O)O
Product: O=C(Oc1ccc(-c2ccc([N+](=O)[O-])cc2)cc1)c1ccccc1
Temperature: 85 °C

Procedure:
4-Benzoyloxybiphenol (40 g) is mixed with 310 ml of glacial acetic acid and heated to 85° C. Fuming nitric acid (100 ml) is added slowly while maintaining the reaction medium temperature between 85°-90° C. After complete addition, the reaction is cooled to room temperature.
Reaction SMILES: CO[C:3]([C:5]1[C:6]([OH:36])=[C:7]2[C:12](=[C:13]([C:15]3[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=3)[N:14]=1)[N:11]([C@@H:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH3:22])[C:10](=[O:29])[C:9]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[CH:8]2)=[O:4].[NH2:37][CH2:38][CH2:39][C:40]([OH:42])=[O:41].C[O-].[Na+]>C([O-])(O)=O.[Na+]>[OH:36][C:6]1[C:5]([C:3]([NH:37][CH2:38][CH2:39][C:40]([OH:42])=[O:41])=[O:4])=[N:14][C:13]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)=[C:12]2[C:7]=1[CH:8]=[C:9]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:10](=[O:29])[N:11]2[C@@H:21]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[CH3:22]
Reactant: COC(=O)c1nc(-c2cccnc2)c2c(cc(-c3ccccc3)c(=O)n2[C@H](C)c2ccccc2)c1O
Reactant: NCCC(=O)O
Agent: C[O-]
Agent: O=C([O-])O
Agent: [Na+]
Product: C[C@H](c1ccccc1)n1c(=O)c(-c2ccccc2)cc2c(O)c(C(=O)NCCC(=O)O)nc(-c3cccnc3)c21
Temperature: 25 °C
Yield: 22 %

Procedure:
A mixture of (R)-5-hydroxy-2-oxo-3-phenyl-1-(1-phenyl-ethyl)-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (30 mg, 0.063 mmol), β-alanine (560 mg, 6.3 mmol) and NaOMe solution (9.5 mL, 4.7 mmol, 0.5 M in MeOH) was refluxed for 16 h. After the mixture was cooled to r.t., the solvent was evaporated in vacuo. The residue was partitioned between EtOAc and water. 1 M HCl was added with vigorous stirring until pH was about 3-4. The aqueous layer was extracted with additional EtOAc, and the organic layers were combined, dried over MgSO4 and concentrated. The residue was dissolved in saturated NaHCO3 and washed several times with ether. The aqueous layer was acidified to pH about 3-4 with 6 M HCl, and the resulting precipitate was isolated by filtration. The crude solid was purified by silica gel chromatography (10-100% EtOAc/hexanes+1% AcOH). The product isolated was dissolved in saturated NaHCO3 and washed several times with ether. The aqueous layer was acidified to pH about 3-4 with 6 M HCl, and the resulting precipitate was isolated by filtration to give 7.4 mg of the title compound. MS: (+) m/z 535.33 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][CH:3]=1.[C:9]([O:15][CH3:16])(=[O:14])[CH2:10][CH2:11][C:12]#[CH:13]>C(NCC)C.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.[Cu]I>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:13]#[C:12][CH2:11][CH2:10][C:9]([O:15][CH3:16])=[O:14])=[CH:4][CH:3]=1
Reactant: C#CCCC(=O)OC
Reactant: Clc1ccc(I)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCNCC
Product: COC(=O)CCC#Cc1ccc(Cl)cc1
Yield: 48.1 %

Procedure:
A mixture of 1-chloro-4-iodobenzene (56 g, 235 mmol), dichlorobis(triphenylphosphine)palladium (II) (6.9 g, 9.8 mmol) and copper (I) iodide (1.9 g, 9.8 mmol) in diethylamine (200 mL) was degassed with bubbling nitrogen. Methyl 4-pentynoate (Description 1, 22.0 g, 196 mmol) was added dropwise and the mixture was degassed with bubbling nitrogen. The mixture was heated under reflux for 24 h., cooled and poured into saturated aqueous ammonium chloride. The mixture was extracted with ethyl acetate and the combined organic fractions were washed with saturated aqueous ammonium chloride. The solvent was evaporated under reduced pressure and the residue was triturated with hexane. The mixture was filtered, dried (MgSO4) and concentrated under reduced pressure. The mixture was refrigerated and the solid was collected and dried in vacuo to give the title compound as pale brown solid (21.0 g, 48%). 1H NMR (360 MHz, CDCl3) δ 7.31 (2H, d, J 7.5 Hz), 7.25 (2H, d, J 7.5 Hz), 3.72 (3H, s), 2.73 (2H, t, J 7.3 Hz), and 2.62 (2H, t, J 7.3 Hz).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[N:3][N:2]=1.C(OO)(=[O:13])C>C(O)(=O)C>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[N:3][N+:2]=1[O-:13]
Reactant: CC(=O)OO
Reactant: c1ccc2cnncc2c1
Solvent: CC(=O)O
Product: [O-][n+]1cc2ccccc2cn1
Temperature: 80 °C

Procedure:
Phthalazine (0.40 moles) was dissolved in 200 ml of glacial acetic acid. Under nitrogen, 10 ml portions of a 32% solution of peracetic acid in acetic acid were added until 0.44 mole had been added and then the mixture was heated to 80° C. for 1 hour. The resulting reaction mixture was cooled to room temperature and the acetic acid was removed using a rotary evaporator. The solid residue was suspended/dissolved in 500 ml water and treated with 50 ml of 50% sodium hydroxide and extracted 5 times with 500 ml of dichloromethane. The organic extracts were combined, dried over magnesium sulfate, crystallized from dichloromethane-hexane, and vacuum-dried to yield 50.1 g of phthalazine N-oxide (0.34 mole), mp (DSC)=149° C. GC analysis showed the desired product contained less than 0.5% phthalazine.
Reaction SMILES: Cl.[NH2:2][OH:3].[OH:4][CH2:5][CH:6]1[O:10][C:9](=[O:11])[N:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18](=O)[CH3:19])=[CH:14][CH:13]=2)[CH2:7]1>N1C=CC=CC=1.C(O)C>[OH:4][CH2:5][CH:6]1[O:10][C:9](=[O:11])[N:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18](=[N:2][OH:3])[CH3:19])=[CH:14][CH:13]=2)[CH2:7]1
Reactant: CC(=O)c1ccc(N2CC(CO)OC2=O)cc1
Reactant: NO
Agent: Cl
Solvent: c1ccncc1
Solvent: CCO
Product: CC(=NO)c1ccc(N2CC(CO)OC2=O)cc1
Temperature: 25 °C
Yield: 86.7 %

Procedure:
Hydroxylamine hydrochloride (5 g) was added to a solution of 5 g 5-hydroxymethyl-3-(4-acetylphenyl)-2-oxazolidinone in 40 ml of 1:1 pyridine/ethanol. The mixture was stirred at reflux under nitrogen for 4 hours. After cooling to room temperature, the mixture was evaporated and the residue was triturated with water and dilute aqueous hydrochloric acid and collected. Recrystallization from aqueous ethanol gave 4.61 g pure 5-hydroxymethyl-3-[4-(1-hydroxyiminoethyl)phenyl]-2-oxazolidinone, m.p. 189.5°-190° C.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]([I:19])=[C:11]([N:20]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21][CH2:22][CH2:23][CH:24]=C)[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC[O:35]C(C)=O>C1COCC1.O>[CH2:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]([I:19])=[C:11]([N:20]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21][CH2:22][CH2:23][CH:24]=[O:35])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(C)=O
Reactant: C=CCCCN(C(=O)OC(C)(C)C)c1cc(OCc2ccccc2)c2ccccc2c1I
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N(CCCC=O)c1cc(OCc2ccccc2)c2ccccc2c1I
Temperature: 25 °C
Reaction time: 6 h
Yield: 80 %

Procedure:
A solution of 81 (44 mg, 81 μmol) in THF (3 mL) was treated sequentially with a solution of NaIO4 (35 mg, 162 μmol, 2 equiv) in 0.5 mL H2O and a solution of OSO4 (7.5 mM in THF, 0.53 mL, 4 μmol, 0.05 equiv). The reaction mixture was stirred for 6 h at 25° C. EtOAc (20 mL) was added and the organic layer was dried (Na2SO4), filtered through Celite, and the solvent removed under vacuum. Chromatography (SiO2, 1×15 cm, 15% EtOAc-hexane) afforded 110 (35 mg, 80%) as an oil: 1H NMR (CDCl3, 400 MHz) δ 9.73 (t, J=1.3 Hz, 1H), 8.32 (d, J=8.2 Hz, 1H), 8.20 (d, J=8.4 Hz, 1H), 7.61-7.49 (m, 4H), 7.42-7.32 (m, 3H), 6.77 and 6.72 (two s, 1H), 5.32-5.25 (m, 2H), 3.86 (ddd, J=14.0, 8.6 Hz, 6.7 Hz, 1H), 3.47 (m, 1H), 2.48 (m, 2H), 1.93-1.75 (m, 2H), 1.29 and 1.23 (two s, 9H); IR (film) νmax 3064, 3032, 2975, 2930, 2722, 1638, 1616, 1590, 1407, 1160 cm31 1; FABHRMS (NBA-CsI) m/z 678.0095 (M+Cs+, C26H28INO4 requires 678.0117).
Reaction SMILES: [CH:1]([C@H:3]1[CH2:5][C@@:4]1([CH2:12][N:13]([CH3:23])[S:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)(=[O:16])=[O:15])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=O.[CH2:24]([N:26]([CH:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1)[C:27](=[O:36])[O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH3:25]>>[CH2:24]([N:26]([CH:37]1[CH2:42][CH2:41][N:40]([CH2:1][C@H:3]2[CH2:5][C@@:4]2([CH2:12][N:13]([CH3:23])[S:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)(=[O:16])=[O:15])[C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH2:39][CH2:38]1)[C:27](=[O:36])[O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH3:25]
Reactant: CCN(C(=O)OCc1ccccc1)C1CCNCC1
Reactant: CN(C[C@@]1(c2ccccc2)C[C@@H]1C=O)S(=O)(=O)c1ccccc1
Product: CCN(C(=O)OCc1ccccc1)C1CCN(C[C@H]2C[C@@]2(CN(C)S(=O)(=O)c2ccccc2)c2ccccc2)CC1

Procedure:
N-{[(1S,2S)-2-formyl-1-phenylcyclopropyl]methyl}-N-methylbenzenesulfonamide and benzyl ethyl(piperidin-4-yl)carbamate (incorporating by reference as needed Bioorg. and Med. Chem. Lett., 11 (2001), 2475) were reacted as per Preparation 10 to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ 7.67-7.55 (m, 5H), 7.39-7.21 (m, 10H), 5.07 (s, 2H), 3.67 (m, 1H), 3.57 (d, J=13.3 Hz, 1H), 3.17 (q, J=6.6 Hz, 2H), 2.99-2.93 (m, 1H), 2.76 (d, J=13.3 Hz, 1H), 2.75-2.68 (m, 1H), 2.52 (s, 3H), 2.29-2.19 (m, 1H), 1.87-1.38 (m, 7H), 1.11 (m, 1H), 1.04 (t, J=6.6 Hz, 3H), 1.07-1.03 (m, 1H), 0.90 (m, 1H). ES-LCMS m/z 576.2 (M+H).
Reaction SMILES: [Na].[CH:2]1([N:7]2[C:11]([NH2:12])=[C:10]([C:13]([NH2:15])=[O:14])[C:9]([CH2:16][CH3:17])=[N:8]2)[CH2:6][CH2:5][CH2:4][CH2:3]1.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27]([O-])=O)=[CH:22][CH:21]=1.O>C(O)C>[CH:2]1([N:7]2[C:11]3=[N:12][C:27]([CH2:26][C:23]4[CH:24]=[CH:25][C:20]([O:19][CH3:18])=[CH:21][CH:22]=4)=[N:15][C:13](=[O:14])[C:10]3=[C:9]([CH2:16][CH3:17])[NH:8]2)[CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: CCc1nn(C2CCCC2)c(N)c1C(N)=O
Reactant: COc1ccc(CC(=O)[O-])cc1
Agent: [Na]
Solvent: O
Solvent: CCO
Product: CCc1[nH]n(C2CCCC2)c2nc(Cc3ccc(OC)cc3)nc(=O)c1-2
Yield: 56.1 %

Procedure:
Sodium spheres (207 mg) were dissolved in ethanol (15 ml) and 1-cyclopentyl-3-ethyl-5-amino-1H-pyrazole-4-carboxamide (1.0 g) was added, followed by 4-methoxyphenylacetate (1.62 g, 9 mmol) The reaction mixture was refluxed for 16 hours, the solvent was stripped, water was added to the residue, and the product was collected by filtration and recrystallized from ether to afford 0.89 g of 1-cyclopentyl-3-ethyl-6-(4-methoxyphenylmethyl)pyrazolo [3,4-d]pyrimidin-4-one, m.p. 172-173° C.
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:17](Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C(O)C>[CH2:17]([O:10][C:7]1[CH:8]=[CH:9][C:4]([CH2:3][CH2:2][OH:1])=[CH:5][CH:6]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: BrCc1ccccc1
Reactant: OCCc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: OCCc1ccc(OCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 4-(2-hydroxy-ethyl)-phenol (50 g, 0.36 mol) in ethanol (400 ml) is added potassium carbonate (75 g, 0.54 mol, 1.5 eq) and benzyl bromide (47.2 ml, 0.39 mol, 1.1 eq), the reaction mixture is stirred at RT overnight. The reaction mixture is then filtered off through celite and concentrated under vacuum. 2-(4-Benzyloxy-phenyl)-ethanol is isolated after crystallization with diethyl ether.
Reaction SMILES: I[C:2]1[N:3]=[C:4]([CH3:16])[N:5]([C:8]2[CH:13]=[CH:12][N:11](C)[C:10](=[O:15])[CH:9]=2)[C:6]=1[CH3:7].[C:17]([C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH3:26])[CH:20]=1)#[CH:18]>>[CH3:26][O:25][C:21]1[CH:20]=[C:19]([C:17]#[C:18][C:2]2[N:3]=[C:4]([CH3:16])[N:5]([C:8]3[CH:13]=[CH:12][NH:11][C:10](=[O:15])[CH:9]=3)[C:6]=2[CH3:7])[CH:24]=[CH:23][CH:22]=1
Reactant: Cc1nc(I)c(C)n1-c1ccn(C)c(=O)c1
Reactant: C#Cc1cccc(OC)c1
Product: COc1cccc(C#Cc2nc(C)n(-c3cc[nH]c(=O)c3)c2C)c1

Procedure:
The title compound, light brown solid, MS: m/e=320.1 (M+H+), was prepared in accordance with the general method of example 1c from 4-(4-iodo-2,5-dimethyl-imidazol-1-yl)-1-methyl-1H-pyridin-2-one and 1-Ethynyl-3-methoxy-benzene.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([OH:10])[CH:5]=[CH:6][C:7]=1[O:8]C.N.OO.Cl.Cl.[C:16]1([NH2:23])[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=1>CC(C)=O.O>[NH2:1][C:2]1[C:7](=[O:8])[CH:6]=[C:5]([NH:22][C:19]2[CH:20]=[CH:21][C:16]([NH2:23])=[CH:17][CH:18]=2)[C:4](=[O:10])[CH:3]=1
Reactant: Nc1ccc(N)cc1
Reactant: COc1ccc(O)cc1N
Agent: Cl
Agent: N
Agent: OO
Solvent: O
Solvent: CC(C)=O
Product: NC1=CC(=O)C(Nc2ccc(N)cc2)=CC1=O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
0.75 mole (10.5 g) of 3-amino-4-methoxy phenol is dissolved in 50 cc of acetone to which have been added 50 cc of ammonia (22° Be) and 250 cc of H2O2 (20 volumes). To this solution there is immediately added 0.05 mole (9.0 g) of paraphenylene diamine dihydrochloride in solution in 100 cc of water. The resulting reaction mixture is agitated for two hours at ambient temperature at which time the reaction mixture is filtered to recover the precipitate which has formed. After recrystallizing the precipitate in ethylacetate and washing the recrystallized product initially with a little methyl cellosolve and then with a little ether, 2-amino-5-[4'-(amino)anilino]-1,4-benzoquinone is obtained which is chromatographically pure and which melts with decomposition above 260° C.
Reaction SMILES: [O:1]([CH2:24][CH2:25][O:26][CH2:27][CH2:28][O:29][C:30]1[C:37]([O:38][CH2:39][CH2:40][O:41][CH3:42])=[CH:36][C:33]([C:34]#[N:35])=[C:32]([N+:43]([O-])=O)[CH:31]=1)[CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][C:8]1[C:15]([O:16][CH2:17][CH2:18][O:19][CH3:20])=[CH:14][C:11]([C:12]#[N:13])=[C:10]([N+:21]([O-])=O)[CH:9]=1>CC(O)=O.CC(O)C.[Fe]>[O:1]([CH2:24][CH2:25][O:26][CH2:27][CH2:28][O:29][C:30]1[C:37]([O:38][CH2:39][CH2:40][O:41][CH3:42])=[CH:36][C:33]([C:34]#[N:35])=[C:32]([NH2:43])[CH:31]=1)[CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][C:8]1[C:15]([O:16][CH2:17][CH2:18][O:19][CH3:20])=[CH:14][C:11]([C:12]#[N:13])=[C:10]([NH2:21])[CH:9]=1
Reactant: COCCOc1cc(C#N)c([N+](=O)[O-])cc1OCCOCCOCCOCCOc1cc([N+](=O)[O-])c(C#N)cc1OCCOC
Agent: [Fe]
Solvent: CC(C)O
Solvent: CC(=O)O
Product: COCCOc1cc(C#N)c(N)cc1OCCOCCOCCOCCOc1cc(N)c(C#N)cc1OCCOC
Temperature: 25 °C
Yield: 81 %

Procedure:
To a solution of 4,4′-((((oxybis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))-bis(oxy))bis(5-(2-methoxyethoxy)-2-nitrobenzonitrile) (0.3 g) in AcOH (10 mL) and i-PrOH (10 mL) was added iron powder (0.75 g). The resulting mixture was heated to reflux for 1 h. After reaction finished, the mixture was cooled to room temperature, filtered, the precipitate washed with EA (10 mL). The combined washings and filtrate were concentrated under reduced pressure and purification by silica chromatography to give 0.22 g of 4,4′-((((oxybis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))-bis(oxy))bis(2-amino-5-(2-methoxyethoxy)benzonitrile). 1H-NMR (400 MHz, CDCl3): δ: 6.88 (s, 2H), 6.33 (s, 2H), 4.28 (br, 4H), 4.15-4.12 (m, 4H), 4.05-4.02 (m, 4H), 3.86-3.83 (m, 4H), 3.72-3.68 (m, 8H), 3.66-3.64 (m, 4H), 3.42 (s, 6H).
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9](I)=[CH:8][CH:7]=1)=[O:4].NC1C=CC([C:22](=[O:28])[CH2:23][CH2:24][CH2:25][CH2:26][Br:27])=CC=1>>[Br:27][CH2:26][CH2:25][CH2:24][CH2:23][C:22]([C:9]1[CH:10]=[CH:11][C:6]([NH:5][C:3](=[O:4])[C:2]([F:14])([F:13])[F:1])=[CH:7][CH:8]=1)=[O:28]
Reactant: Nc1ccc(C(=O)CCCCBr)cc1
Reactant: O=C(Nc1ccc(I)cc1)C(F)(F)F
Product: O=C(CCCCBr)c1ccc(NC(=O)C(F)(F)F)cc1

Procedure:
The title compound was synthesized in a manner analogous to that described for Intermediate 32, using Intermediate 43 as a substrate. ES/MS calcd. for C13H14BrF3NO2+ 352.0. Found m/z=352.1 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[N:6][C:5]([Cl:8])=[C:4]2[NH:9][CH:10]=[CH:11][C:3]=12.[H-].[Na+].FC(F)(F)S(O[Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])(=O)=O>O1CCCC1>[Br:1][C:2]1[CH:7]=[N:6][C:5]([Cl:8])=[C:4]2[N:9]([Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])[CH:10]=[CH:11][C:3]=12
Reactant: Clc1ncc(Br)c2cc[nH]c12
Reactant: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)n1ccc2c(Br)cnc(Cl)c21
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 4-bromo-7-chloro-1H-pyrrolo[2,3-c]pyridine (1.64 g) in dry tetrahydrofuran (80 ml) at 0° C. under an atmosphere of nitrogen was added portionwise sodium hydride (60% dispersion in mineral oil, 625 mg). After addition, the solution was stirred at room temperature for 30 minutes. The solution was then recooled to 0° C. and a solution of tert-butyldimethylsilyl trifluoromethanesulphonate (3.75 g) in dry tetrahydrofuran (20 ml) was added dropwise. The solution was partitioned between ethyl acetate (100 ml) and water (100 ml) and washed with water until the pH of the aqueous was neutral. The organic layer was dried (MgSO4) and evaporated to give a brown oil. The residue was purified by Biotage chromatography over silica gel (10 g), eluting with 10% ethyl acetate/isohexane to give the title compound as a red oil. (1.63 g).
Reaction SMILES: [C:1](=[O:4])([O-])[O-:2].[Na+].[Na+].[C:7]([N:12]1[C:16](=[O:17])[C:15]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:14]2[C:13]1=[O:22])(OCC)=O>O>[C:13]1(=[O:22])[N:12]([C@@H:7]([CH2:13][CH2:14][CH2:15][CH2:16][OH:17])[C:1]([OH:2])=[O:4])[C:16](=[O:17])[C:15]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:14]12
Reactant: O=C([O-])[O-]
Reactant: CCOC(=O)N1C(=O)c2ccccc2C1=O
Agent: [Na+]
Solvent: O
Product: O=C(O)[C@H](CCCCO)N1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of (+)-L-ε-hydroxynorleucine [prepared according to the procedure of Bodanszky et al., J. Med Chem., 1978, 21, 1030-1035] (1.030 g., 7.0 mmol.) and sodium carbonate (745 mg., 7.0 mmol.) in water (12 ml.) was treated with N-carbethoxy-phthalimide (1.495 g., 7.0 mmol.) and the mixture was stirred at room temperature for 2 hours. The solution was filtered, cooled to 0° C., and acidified with 6N hydrochloric acid to afford a white precipitate. The solid was collected by filtration and dried in vacuo at 80° C. for one hour to give 1.297 g. of the title compound; m.p. 162°-1630° C.; [α]D =-35.7° (c=1.3, methanol).
Reaction SMILES: C(N(CC)CC)C.[C:8]([Si:10]([CH3:13])([CH3:12])[CH3:11])#[CH:9].Br[C:15]1[C:16]([C:22]#[N:23])=[N:17][CH:18]=[C:19]([Cl:21])[CH:20]=1>[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd].CN(C)C=O>[Cl:21][C:19]1[CH:20]=[C:15]([C:9]#[C:8][Si:10]([CH3:13])([CH3:12])[CH3:11])[C:16]([C:22]#[N:23])=[N:17][CH:18]=1
Reactant: N#Cc1ncc(Cl)cc1Br
Reactant: C#C[Si](C)(C)C
Agent: [Cu]I
Agent: [Pd]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: C[Si](C)(C)C#Cc1cc(Cl)cnc1C#N
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 39.9 %

Procedure:
A pressure vessel was charged with triethylamine (7.65 mL, 55.2 mmol), ethynyltrimethylsilane (2.32 mL, 16.6 mmol), copper (I) iodide (0.263 g, 1.380 mmol), palladium (0) tetrakis(triphenylphosphine) (0.558 g, 0.483 mmol), 3-bromo-5-chloropicolinonitrile (3.0 g, 13.8 mmol), and N,N-dimethylformamide (50 ml). The vessel was flushed with argon, sealed, stirred at ambient temperature for 15 minutes, and then heated at 50° C. for 4 hours. The solution was diluted with water and extracted with ethyl acetate. The combined organic layers were concentrated, and the residue was purified by silica-gel chromatography, eluting 0-50% ethyl acetate in hexane, to afford the title compound (1.3 g, 5.5 mmol). MS m/z=235 (M+H).