Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([CH3:14])([CH3:13])[C:10](=[O:15])[C:9]=2[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Cl[CH2:31][C:32]1[CH:41]=[CH:40][C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[N:33]=1>C(#N)C>[CH3:23][O:22][C:19]1[CH:18]=[CH:17][C:16]([C:9]2[C:10](=[O:15])[C:11]([CH3:13])([CH3:14])[O:12][C:8]=2[C:5]2[CH:4]=[CH:3][C:2]([O:1][CH2:31][C:32]3[CH:41]=[CH:40][C:39]4[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=4)[N:33]=3)=[CH:7][CH:6]=2)=[CH:21][CH:20]=1
Reactant: COc1ccc(C2=C(c3ccc(O)cc3)OC(C)(C)C2=O)cc1
Reactant: ClCc1ccc2ccccc2n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COc1ccc(C2=C(c3ccc(OCc4ccc5ccccc5n4)cc3)OC(C)(C)C2=O)cc1
Temperature: 80 °C
Reaction time: 16 h
Yield: 0.1 %

Procedure:
To a stirred solution of 5-(4-hydroxyphenyl)-4-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-one (600 mg, 1.93 mol) in acetonitrile (50 mL) was added K2CO3 (800 mg, 5.8 mol). 2-Chloromethyl quinoline (500 mg, 2.32 mol) was added dropwise under an inert atmosphere. The reaction mixture was stirred at 80° C. for 16 h and then partitioned between water and EtOAc (200 mL). The organic layer was separated, washed with water, dried over Na2SO4 and then concentrated in vacuo to obtain a residue. The residue was purified via silica gel column chromatography to afford 4-(4-methoxyphenyl)-2,2-dimethyl-5-(4-(quinolin-2-ylmethoxy)phenyl)furan-3(2H)-one (0.51 g, 58%) as a white solid. 1H NMR (500 MHz, d6-DMSO): δ 8.45 (d, J=7.2 Hz, 1 H), 8.02-7.97 (m, 2 H), 7.85-7.77 (m, 1 H), 7.76-7.68 (m, 2 H), 7.59-7.51 (m, 2 H), 7.19-7.11 (m, 4 H), 6.95 (d, J=7.4 Hz, 2 H), 5.41 (s, 2 H), 3.75 (s, 3 H), 1.45 (s, 6 H). MS: M+H: m/z=452.1.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=O)[CH2:10][CH2:11][C:12]([OH:14])=[O:13])=[CH:5][CH:4]=1.C(O)(=O)C>[C].[Pd].C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:9][CH2:10][CH2:11][C:12]([OH:14])=[O:13])=[CH:7][CH:8]=1
Reactant: COc1ccc(C(=O)CCC(=O)O)cc1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: COc1ccc(CCCC(=O)O)cc1
Reaction time: 9 h

Procedure:
After 4-(4-methoxyphenyl)-4-oxobutanoic acid (40 g) was added to (not completely dissolved in) a mixed solvent of acetic acid (100 ml) and THF (100 ml), 10% palladium-carbon (50%-wet) (4 g) was added thereto and the resulting mixture was stirred for 9 hours under a hydrogen atmosphere (0.4 MPa). The catalyst was removed by filtration through Celite and toluene was added to the residue. The solvent was distilled off under reduced pressure to obtain 4-(4-methoxy-phenyl)butanoic acid quantitatively.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:10])[CH3:9].Br[CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[C:8]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[O:1][CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])(=[O:10])[CH3:9]
Reactant: CCOC(=O)CBr
Reactant: CC(=O)c1ccccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)COc1ccccc1C(C)=O
Yield: 67.6 %

Procedure:
A mixture of 136 g of o-hydroxyacetophenone, 167 g of ethyl bromoacetate and 205 g of potassium carbonate was refluxed in 3 l of acetone for 6 hours under heating with stirring. The insoluble materials were filtered from the reaction mixture and the acetone was evaporated from the filtrate. Further, the mixture was distilled to obtain a fraction having a boiling point of 132° C/2 mmHg which was then recrystallized from ligroin to obtain 150 g of the product.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:13]=[C:12]2[C:7]([C:8](=O)[CH2:9][CH:10]=[N:11]2)=[CH:6][CH:5]=1.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH:26]([CH3:28])[NH:25][CH2:24][CH:23]1[CH3:29])=[O:21])([CH3:18])([CH3:17])[CH3:16]>CN(C=O)C>[C:15]([O:19][C:20]([N:22]1[CH:23]([CH3:29])[CH2:24][N:25]([C:8]2[C:7]3[C:12](=[CH:13][C:4]([Cl:3])=[CH:5][CH:6]=3)[N:11]=[CH:10][CH:9]=2)[CH:26]([CH3:28])[CH2:27]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]
Reactant: O=C1CC=Nc2cc(Cl)ccc21
Reactant: CC1CN(C(=O)OC(C)(C)C)C(C)CN1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC1CN(c2ccnc3cc(Cl)ccc23)C(C)CN1C(=O)OC(C)(C)C
Temperature: 80 °C
Reaction time: 1 h
Yield: 25 %

Procedure:
Sodium hydride (72 mg, 3 mmol) is added to a solution of 7-chloro-4-quinolone (359 mg, 2 mmol) in DMF. After 1 h at 40° C. N-phenyl(trifluoromethylsulfon)imide (1.0 g, 2.8 mmol) and, 1 h later, 1-tert-butoxycarbonyl-2,5-dimethylpiperazine (1.8 g, 8 mmol) is added. The reaction mixture is stirred at 80° C. for 2 days, concentrated, diluted with EtOAc, washed with water and brine, dried (Na2SO4), and concentrated. The residue is purified by reversed phase HPLC with water-MeCN-TFA to give 4-[4-(tert-butoxycarbonyl)-2,5-dimethylpiperazin-1-yl]-7-chloroquinoline (188 mg, 0.5 mmol) which is deprotected with TFA in CH2Cl2 and transformed after being washed with base into the product with 4-fluorophenyl isocyanate (31 μL, 0.27 mmol) according to method C giving the title product as a colorless solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[N+:12]([O-:14])=[O:13])[C:6](O)=[O:7].S(Cl)([Cl:17])=O>C(CC(C)(C)C)(C)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[N+:12]([O-:14])=[O:13])[C:6]([Cl:17])=[O:7]
Reactant: COc1cc(C(=O)O)ccc1[N+](=O)[O-]
Reactant: O=S(Cl)Cl
Solvent: CC(C)CC(C)(C)C
Product: COc1cc(C(=O)Cl)ccc1[N+](=O)[O-]
Temperature: 25 °C

Procedure:
A stirred suspension of 1.0 g of 3-methoxy-4-nitrobenzoic acid and 1.40 ml of thionyl chloride is heated to reflux for 2 hours. The mixture is cooled to room temperature, 2 ml of iso-octane added and the mixture evaporated in vacuo to a solid residue. The residue is washed with iso-octane (2×2 ml), dried in vacuo to give 1.08 g of cream colored solid.
Reaction SMILES: [OH-].[Li+].[CH2:3]([O:7][C:8]1[CH:13]=[C:12](/[CH:14]=[C:15](\[O:20][CH3:21])/[C:16]([O:18]C)=[O:17])[CH:11]=[CH:10][C:9]=1[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([NH:28][C:29]([NH:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])=[O:30])[CH:23]=1)[CH2:4][CH2:5][CH3:6].O.Cl>O1CCCC1>[CH2:3]([O:7][C:8]1[CH:13]=[C:12](/[CH:14]=[C:15](\[O:20][CH3:21])/[C:16]([OH:18])=[O:17])[CH:11]=[CH:10][C:9]=1[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([NH:28][C:29]([NH:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])=[O:30])[CH:23]=1)[CH2:4][CH2:5][CH3:6]
Reactant: CCCCCCCNC(=O)Nc1cccc(-c2ccc(/C=C(\OC)C(=O)OC)cc2OCCCC)c1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CCCCCCCNC(=O)Nc1cccc(-c2ccc(/C=C(\OC)C(=O)O)cc2OCCCC)c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 82.9 %

Procedure:
1.3 mL (1.3 mmol) of aqueous 1 N lithium hydroxide solution are added to a solution of 423 mg (0.87 mmol) of methyl (Z)-3-[2-butoxy-3′-(3-heptylureido)biphenyl-4-yl]-2-methoxyacrylate in 10 mL of tetrahydrofuran. The reaction mixture is stirred for 24 hours at room temperature. After addition of 20 mL of water and acidification with 1 N hydrochloric acid, the reaction medium is extracted with ethyl acetate. The organic phases are combined, washed with saturated sodium chloride solution and dried over sodium sulfate. The solvents are evaporated off and the residue is then recrystallized from 5 mL of acetonitrile. 348 mg (85%) of (Z)-3-[2-butoxy-3′-(3-heptylureido)biphenyl-4-yl]-2-methoxyacrylic acid are obtained in the form of a white powder. (m.p.=137° C.).
Reaction SMILES: [H-].[Na+].[CH:3]1([C:9]2[C:17]3[C:12](=[CH:13][C:14]([C:18]([O:20][CH3:21])=[O:19])=[CH:15][CH:16]=3)[NH:11][C:10]=2[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH:28]=[CH2:29])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.[H][H].Br[CH2:33][C:34](=[CH2:38])[C:35]([OH:37])=[O:36]>C1COCC1.CN(C=O)C>[CH:3]1([C:9]2[C:17]3[C:12](=[CH:13][C:14]([C:18]([O:20][CH3:21])=[O:19])=[CH:15][CH:16]=3)[N:11]([CH2:38][C:34](=[CH2:33])[C:35]([OH:37])=[O:36])[C:10]=2[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH:28]=[CH2:29])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1
Reactant: [H][H]
Reactant: C=Cc1ccccc1-c1[nH]c2cc(C(=O)OC)ccc2c1C1CCCCC1
Reactant: C=C(CBr)C(=O)O
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: C=Cc1ccccc1-c1c(C2CCCCC2)c2ccc(C(=O)OC)cc2n1CC(=C)C(=O)O
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 45.9 %

Procedure:
Sodium hydride (155 mg of a 95% dispersion in mineral oil, 6.13 mmol) was added in portions during 5 min to a stirred and cooled solution (ice-water bath) of 7 (1.0 g, 2.79 mmol) in THF (7 mL). When the evolution of hydrogen subsided DMF (2 mL) was added followed by a solution of bromomethylacrylic acid (505 mg, 3.06 mmol) in THF (1.5 mL). Stirring was continued with cooling (10 min) and then at 22° C. for 30 min. The mixture was concentrated and the residue partitioned between ethyl acetate and water. The organic layer was washed (water, brine), dried (sodium sulfate) and concentrated. The residue was chromatographed on silicic acid (15 g) using the flash technique and eluting with methylene chloride:ethyl acetate:acetic acid (10:1:0.005). The product containing fraction was concentrated on a rotary evaporator to leave 2-((3-cyclohexyl-6-(methoxycarbonyl)-2-(2-vinylphenyl)-1H-indol-1-yl)methyl)acrylic acid (568 mg, 40%) as a yellow gum. A sample (142 mg) was further purified on a Shimadzu preparatory liquid chromatograph. The fraction containing the product was concentrated to leave 13 (R=H) as a granular solid. ESI-MS m/z 433 (MH+), 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 1.07-1.37 (m, 3H) 1.58-1.88 (m, 7 H) 2.41-2.53 (m, 1 H) 3.93 (s, 3 H) 4.50 (d, J=18.31 Hz, 1 H) 4.84 (d, J=18.31 Hz, 1 H) 4.89 (s, 1 H) 5.13 (d, J=10.99 Hz, 1 H) 5.29 (s, 1 H) 5.68 (d, J=17.70 Hz, 1 H) 6.19 (s, 1 H) 6.36 (dd, J=17.55, 11.14 Hz, 1 H) 7.15 (d, J=7.63 Hz, 1 H) 7.31 (t, J=7.48 Hz, 1 H) 7.45 (t, J=7.63 Hz, 1 H) 7.70 (d, J=7.93 Hz, 1 H) 7.76-7.87 (m, 2H) 7.96 (s, 1 H).
Reaction SMILES: [OH:1][N:2]=[C:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[O:12][C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1)[C:4]#[N:5].[C:20](=O)([O-])[O-].[K+].[K+].COS(OC)(=O)=O.CCOCC>CN(C)C=O>[CH3:20][O:1][N:2]=[C:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[O:12][C:13]1[CH:14]=[CH:15][C:16]([Cl:19])=[CH:17][CH:18]=1)[C:4]#[N:5]
Reactant: O=C([O-])[O-]
Reactant: N#CC(=NO)c1ccccc1Oc1ccc(Cl)cc1
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOCC
Solvent: COS(=O)(=O)OC
Product: CON=C(C#N)c1ccccc1Oc1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 94.4 %

Procedure:
α-hydroxyimino-2-(4-chlorophenoxy)phenylacetonitrile (a mixture of E- and Z-isomers) (1.36 g, 0.005 mole) was dissolved in dried dimethylformamide (10 ml) and potassium carbonate (0.90 g, 0.0065 mole) was added to the mixture. Further, dimethylsulfate (0.76 g, 0.006 mole) was added to the mixture under ice cooling, followed by stirring at room temperature for 1 hour. Then, ether (150 ml) was added to the mixture, which was washed twice with water. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and then the resulting residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to obtain α-methoxyimino-2-(4-chlorophenoxy)phenylacetonitrile (1.35 g, yield: 94.4%) as a pale yellow oil.
Reaction SMILES: [N:1]([CH:4]1[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:5]1)=[C:2]=[S:3].[CH3:14][C:15]1[O:19][C:18]([CH2:20][NH:21][C:22]2[C:23]([NH2:28])=[CH:24][CH:25]=[CH:26][CH:27]=2)=[CH:17][CH:16]=1>O1CCCC1>[CH3:14][C:15]1[O:19][C:18]([CH2:20][NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[NH:28][C:2]([NH:1][CH:4]2[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:5]2)=[S:3])=[CH:17][CH:16]=1
Reactant: Cc1ccc(CNc2ccccc2N)o1
Reactant: CCOC(=O)N1CCC(N=C=S)C1
Solvent: C1CCOC1
Product: CCOC(=O)N1CCC(NC(=S)Nc2ccccc2NCc2ccc(C)o2)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 100 %

Procedure:
A mixture of 80 parts of ethyl 3-isothiocyanato-1-pyrrolidinecarboxylate, 88.8 parts of N1 -[(5-methyl-2-furanyl)methyl]-1,2-benzenediamine and 560 parts of tetrahydrofuran was stirred for 2 hours at reflux temperature. After cooling to room temperature, the reaction mixture was evaporated, yielding 144.9 parts (100%) of ethyl 3-[[[[2-[[(5-methyl-2-furanyl)methyl]amino]phenyl]amino]thioxomethyl]amino]-1-pyrrolidinecarboxylate as a residue (interm. 7). In a similar manner there were also prepared:
Reaction SMILES: [NH2:1][CH2:2][CH:3]([OH:16])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][N:13]([CH3:15])[CH3:14])[CH:7]=1.C([O:20][CH2:21][C:22]([N:24]=[C:25]([N:28]([CH3:37])[N:29]=CC1C=CC=CC=1)SC)=O)(=O)C.[CH2:38]([C:42](C)=O)[CH:39](C)C>>[OH:16][CH:3]([CH2:4][O:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][N:13]2[CH2:14][CH2:42][CH2:38][CH2:39][CH2:15]2)[CH:7]=1)[CH2:2][NH:1][C:25]1[N:28]([CH3:37])[N:29]=[C:22]([CH2:21][OH:20])[N:24]=1
Reactant: CN(C)Cc1cccc(OCC(O)CN)c1
Reactant: CSC(=NC(=O)COC(C)=O)N(C)N=Cc1ccccc1
Reactant: CC(=O)CC(C)C
Product: Cn1nc(CO)nc1NCC(O)COc1cccc(CN2CCCCC2)c1

Procedure:
Similarly prepared by this procedure from 1-amino-3-[3-(dimethylaminomethyl)phenoxy]-2-propanol (1.5 g) and compound B (2.25 g) except that the methyl isobutyl ketone extract was evaporated to give a solid which was washed with diethyl ether and then recrystallised from methyl acetate was 5-[[3-[3-(dimethylaminomethyl)phenoxy]-2-hydroxy-propyl]amino]-1-methyl-1H-1,2,4-triazole-3-methanol (250 mg) m.p. 104°-109°.
Reaction SMILES: C(OC([N:8]1[C:12]2[CH:13]=[CH:14][C:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[S:23]([CH2:26][CH2:27][OH:28])(=[O:25])=[O:24])=[CH:16][C:11]=2[N:10]=[C:9]1[CH2:29]Br)=O)(C)(C)C.[F:31][C:32]([F:44])([F:43])[S:33]([C:36]1[CH:41]=[CH:40][C:39]([OH:42])=[CH:38][CH:37]=1)(=[O:35])=[O:34].C([O-])([O-])=O.[Na+].[Na+].[Na+].[I-]>CN(C=O)C>[F:44][C:32]([F:43])([F:31])[S:33]([C:36]1[CH:37]=[CH:38][C:39]([O:42][CH2:29][C:9]2[NH:8][C:12]3[CH:13]=[CH:14][C:15]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=4[S:23]([CH2:26][CH2:27][OH:28])(=[O:25])=[O:24])=[CH:16][C:11]=3[N:10]=2)=[CH:40][CH:41]=1)(=[O:34])=[O:35]
Reactant: CC(C)(C)OC(=O)n1c(CBr)nc2cc(-c3ccccc3S(=O)(=O)CCO)ccc21
Reactant: O=S(=O)(c1ccc(O)cc1)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=S(=O)(CCO)c1ccccc1-c1ccc2[nH]c(COc3ccc(S(=O)(=O)C(F)(F)F)cc3)nc2c1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
A mixture of 2-bromomethyl-5-[2-(2-hydroxy-ethanesulfonyl)-phenyl]-benzoimidazole-1-carboxylic acid tert-butyl ester (0.030 g, 0.0606 mmol), 4-trifluoromethanesulfonyl-phenol (0.027 g, 0.121 mmol), Na2CO3 (0.026 g, 0.242 mmol), and NaI (0.036 g, 0.242 mmol) in DMF (1 mL) was stirred for 12 hours at room temperature. The reaction mixture was concentrated under reduced pressure and the resulting residue was dissolved in CH2Cl2 (1 mL) followed by an addition of TFA (0.3 mL) and the mixture was stirred at rt for 3 hours. The reaction mixture was concentrated, and the residue was purified by chromatography (silica, CH2Cl2: MeOH, 5:1) to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD) δ (ppm): 8.17 (dd, 1H, J=8.0 Hz, J=1.2 Hz), 8.03 (d, 2H, J=8.8 Hz), 7.76-7.62 (m, 4H), 7.48-7.45 (m, 3H), 7.35 (d, 1H, J=8.4 Hz), 5.57 (s, 2H), 3.63 (t, 2H, J=6.4 Hz), 2.91 (t, 2H, J=6.6 Hz). Mass Spectrum (LCMS, ESI pos.) Calcd. For C25H23F3N3O6S2: 582.5 (M+MeCN+H), Found 582.2.
Reaction SMILES: I[CH2:2][CH2:3][CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:8][CH:7]=1.[OH:20][CH2:21][CH2:22][C:23]1[NH:24][CH:25]=[CH:26][N:27]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH2:13]([O:12][C:9]1[CH:10]=[CH:11][C:6]([CH2:5][CH2:4][CH2:3][CH2:2][N:24]2[CH:25]=[CH:26][N:27]=[C:23]2[CH2:22][CH2:21][OH:20])=[CH:7][CH:8]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: OCCc1ncc[nH]1
Reactant: ICCCCc1ccc(OCc2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: OCCc1nccn1CCCCc1ccc(OCc2ccccc2)cc1
Yield: 80.4 %

Procedure:
Benzyl 4-(4-iodobutyl)phenyl ether (14.29 g), 2-(2-hydroxyethyl)imidazole (13.1 g) and potassium carbonate (5.39 g) were stirred in DMF (390 ml) at 60° C. for 16 hours. After cooling, the insoluble matter was filtered off; the filtrate was concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with water and saturated brine. Under reduced pressure, the solvent was distilled off; the residue was purified by column chromatography (eluent:ethyl acetate:methanol=19:1 to 9:1). The eluate was recrystallized from ethyl acetate-methanol to give the titled compound (10.99 g) as colorless crystals.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:6]=1[CH:7]=[CH:8][N+:9]([O-])=[CH:10]2)=[O:4].FC(F)(F)C1C=CC=CC=1.[C:26]([NH2:30])([CH3:29])([CH3:28])[CH3:27].C1(C)C=CC(S(OS(C2C=CC(C)=CC=2)(=O)=O)(=O)=O)=CC=1>C(OCC)(=O)C>[C:26]([NH:30][C:10]1[C:11]2[CH:12]=[CH:13][CH:14]=[C:5]([C:3]([O:2][CH3:1])=[O:4])[C:6]=2[CH:7]=[CH:8][N:9]=1)([CH3:29])([CH3:28])[CH3:27]
Reactant: COC(=O)c1cccc2c[n+]([O-])ccc12
Reactant: CC(C)(C)N
Agent: Cc1ccc(S(=O)(=O)OS(=O)(=O)c2ccc(C)cc2)cc1
Solvent: CCOC(C)=O
Solvent: FC(F)(F)c1ccccc1
Product: COC(=O)c1cccc2c(NC(C)(C)C)nccc12
Yield: 62.9 %

Procedure:
5-(Methoxycarbonyl)isoquinoline 2-oxide (2.0 g, 9.84 mmol) obtained in Step (4) above and trifluorotoluene (20 mL) were mixed and stirred. The reaction solution was slowly added with t-butylamine (3.6 g, 49.25 mmol) and p-toluenesulfonic acid anhydride (6.42 g, 19.68 mmol) at about 5° C., and stirred for about 2 hours at the same temperature (˜5° C.). The reaction mixture was diluted with ethyl acetate, and washed with a saturated aqueous sodium bicarbonate solution and saline. The organic layer thus obtained was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the title compound (1.6 g, 64%).
Reaction SMILES: C(NC(C)C)(C)C.[Li]CCCC.[CH3:13][CH2:14][O:15][C:16]([CH3:18])=[O:17].[CH2:19]([O:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([CH:33]=[CH:34][N+:35]([O-:37])=[O:36])[CH:28]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1COCC1>[CH2:14]([O:15][C:16](=[O:17])[CH2:18][CH:33]([C:29]1[CH:30]=[CH:31][CH:32]=[C:27]([O:26][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:28]=1)[CH2:34][N+:35]([O-:37])=[O:36])[CH3:13]
Reactant: CCOC(C)=O
Reactant: O=[N+]([O-])C=Cc1cccc(OCc2ccccc2)c1
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: CCOC(=O)CC(C[N+](=O)[O-])c1cccc(OCc2ccccc2)c1
Temperature: -78 °C

Procedure:
To a dry round bottom flask was added 2.7 mL of diisopropylamine and 20 mL THF. The mixture was cooled to −78° C. with stirring. A solution of n-BuLi (11.4 mL, 1.6 M) was added dropwise and the resulting solution was stirred for 20 min. EtOAc (1.5 mL) was added slowly to quench and the mixture was stirred for an additional 20 min. 1-Benzyloxy-3-(2-nitrovinyl)benzene (3.4 g, 13 mmol) in 50 mL THF was then added and the solution was stirred for 2 h. The mixture was warmed to r.t., quenched with sat. NH4Cl solution (50 mL), extracted with EtOAc, washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel to give 3.2 g of the desired product.
Reaction SMILES: CC(C)=O.C(=O)=O.C([O:15][CH2:16][C@@H:17]([CH2:28][N:29]1[CH:34]=[C:33]([CH3:35])[C:32](=[O:36])[N:31](C(=O)C2C=CC=CC=2)[C:30]1=[O:45])[C@H:18]([O:20][Si](C(C)(C)C)(C)C)[CH3:19])C1C=CC=CC=1.B(Cl)(Cl)Cl>ClCCl>[CH3:35][C:33]1[C:32](=[O:36])[NH:31][C:30](=[O:45])[N:29]([CH2:28][C@@H:17]([C@H:18]([OH:20])[CH3:19])[CH2:16][OH:15])[CH:34]=1
Reactant: Cc1cn(C[C@H](COCc2ccccc2)[C@@H](C)O[Si](C)(C)C(C)(C)C)c(=O)n(C(=O)c2ccccc2)c1=O
Agent: ClB(Cl)Cl
Agent: O=C=O
Solvent: ClCCl
Solvent: CC(C)=O
Product: Cc1cn(C[C@H](CO)[C@@H](C)O)c(=O)[nH]c1=O
Temperature: 25 °C
Reaction time: 6 h
Yield: 70.7 %

Procedure:
To a cold (−77° C., acetone/dry ice bath) solution of 5 (2.0 g, 3.72 mmol) in 100 ml of anhydrous dichloromethane was added (via syringe) 38 ml of 1M BCl3 in dichloromethane over 5 min. The reaction was stirred for 6 hrs until no more changes were observed by HPLC analysis and then quenched by adding a mixture of pyridine (26 ml) and methanol (54 ml) over 5 min. The reaction mixture was allowed to warm up to room temperature and concentrated. The resultant material was re-dissolved in methanol (100 ml) and co-evaporated twice with triethylamine (10 ml) to remove pyridine. The residue was suspended in dichloromethane and filtered to remove some triethylammonium chloride. The solid were washed with dichloromethane and the combined filtrates were concentrated and then chromatographed on silica eluting with 10% methanol in dichloromethane. Concentration of the pure product fractions afforded 0.6 g (70%) of nucleoside 6. 1H NMR (DMSO-d6): δ 11.19 (s, 1H), 7.46 (s, 1H), 4.56 (d, J=4.8 Hz, 1H), 4.50 (t, J=5.1 Hz, 1H), 3.83 (m, 1H), 3.73 (m, 1H), 3.57 (m, 1H), 3.38 (m, 2H), 1.75 (s, 3H), 1.73 (m, 1H). 1.10 (d, J=6.3 Hz, 3H).
Reaction SMILES: [CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9]([O-:12])([O-])=O.[K+].[K+].[C:15]1([CH:23]=[CH:22][CH:21]=[C:19]([OH:20])[C:17]=1O)[OH:16]>>[CH2:1]([O:20][C:19]1[CH:21]=[CH:22][CH:23]=[C:15]([O:16][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:17]=1[O:12][CH2:9][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Oc1cccc(O)c1O
Reactant: BrCc1ccccc1
Reactant: O=C([O-])[O-]
Agent: [K+]
Product: c1ccc(COc2cccc(OCc3ccccc3)c2OCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 81.8 %

Procedure:
Lowe, W. et al., Arch. Pharm. (Weinheim) 327:255 (1994). Benzyl bromide (57 mL, 0.481 mol) and then K2CO3 (100 g, 0.725 mol) were added to a solution of pyrogallol (20 g, 0.1 59 mol) in 200 mL dry, degassed acetone under Ar. This reaction mixture was subsequently stirred for 30 min at room temperature and then for 24 h at reflux under Ar. A solution of NaOH (1.6 g) in MeOH (32 mL) was then added and the reaction refluxed for an additional 30 min. After cooling to room temperature, solids were filtered and washed with acetone. The filtrate was concentrated and the residue recrystallized from MeOH to afford 8 (52 g, 83%) as an off-white solid. mp 67-68° C. 1H NMR (CDCl3): δ7.44-7.19 (m, 15 H), 6.85 (dd, J=9, 9 Hz, 1 H), 6.57 (d, J=8.2 Hz, 2 H), 5.05 (s, 2 H), 5.02 (s, 4 H). 13C NMR (CDCl3): δ152.9, 138.4, 137.8, 137.0, 128.4, 128.3, 128.0, 127.8, 127.6 (2), 127.3, 127.2, 123.5, 107.7, 75.0, 70.9.
Reaction SMILES: [C:1]1([O:7][S:8]([C:11]2[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=2)(=[O:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:18]1([S:36](Cl)(=[O:38])=[O:37])[C:27]2[C:22](=[CH:23][C:24]([S:28](Cl)(=[O:30])=[O:29])=[CH:25][CH:26]=2)[CH:21]=[C:20]([S:32](Cl)(=[O:34])=[O:33])[CH:19]=1.[OH2:40]>N1C=CC=CC=1>[C:1]1([O:7][S:8]([C:11]2[CH:12]=[CH:13][C:14]([NH:17][S:28]([C:24]3[CH:23]=[C:22]4[C:27](=[CH:26][CH:25]=3)[C:18]([S:36]([NH:17][C:14]3[CH:13]=[CH:12][C:11]([S:8]([O:7][C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=5)(=[O:9])=[O:40])=[CH:16][CH:15]=3)(=[O:38])=[O:37])=[CH:19][C:20]([S:32]([NH:17][C:14]3[CH:13]=[CH:12][C:11]([S:8]([O:7][C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)(=[O:9])=[O:10])=[CH:16][CH:15]=3)(=[O:34])=[O:33])=[CH:21]4)(=[O:30])=[O:29])=[CH:15][CH:16]=2)(=[O:9])=[O:10])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=S(=O)(Cl)c1ccc2c(S(=O)(=O)Cl)cc(S(=O)(=O)Cl)cc2c1
Reactant: Nc1ccc(S(=O)(=O)Oc2ccccc2)cc1
Reactant: O
Solvent: c1ccncc1
Product: O=S(=O)(Nc1ccc(S(=O)(=O)Oc2ccccc2)cc1)c1ccc2c(S(=O)(=O)Nc3ccc(S(=O)(=O)Oc4ccccc4)cc3)cc(S(=O)(=O)Nc3ccc(S(=O)(=O)Oc4ccccc4)cc3)cc2c1
Temperature: 25 °C

Procedure:
To a solution of 11.2 g of the above amine in 50 ml of pyridine is added 6.35 g of 1,3,6-naphthalenetrisulfonyl chloride. The resulting solution is heated on a steam bath for one hour, cooled to room temperature and poured into cold water with separation of an oil. The mixture is extracted with methylene chloride. The methylene chloride extract is washed with 0.5N hydrochloric acid, then with water and dried over magnesium sulfate. The solvent is removed and the resulting oil is dissolved in benzene:acetone (7:3) and passed through a bed of magnesol on a sintered glass funnel. The cake is washed with additional benzene:acetone (7:3). The filtrate and washings are combined and evaporated and dried in vacuo to yield 11.9 g of the product of the example as a cream colored solid.