Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [I:1][C:2]1[C:10]([I:11])=[CH:9][C:8]([I:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[C:13]([O:18][CH2:19][CH2:20]O)(=[O:17])[C:14]([CH3:16])=[CH2:15].C1(N=C=NC2CCCCC2)CCCCC1>CCOCC>[C:13]([O:18][CH2:19][CH2:20][O:5][C:4](=[O:6])[C:3]1[CH:7]=[C:8]([I:12])[CH:9]=[C:10]([I:11])[C:2]=1[I:1])(=[O:17])[C:14]([CH3:16])=[CH2:15]
Reactant: C=C(C)C(=O)OCCO
Reactant: O=C(O)c1cc(I)cc(I)c1I
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CCOCC
Product: C=C(C)C(=O)OCCOC(=O)c1cc(I)cc(I)c1I

Procedure:
2,3,5-triiodobenzoic acid (25 g), 2-hydroxyethyl methacrylate (7.2 g), 1,3-dicyclohexylcarbodiimide (11.5 g) and 4-pyrrilidinopyridine (0.75 g) were stirred in ether suspension (250 ml) at room temperature for 24 hr. The solid was filtered off and the residue washed with fresh ether. The ether solution was extracted with dilute HCl (0.2M) and then with saturated sodium bicarbonate solution. The organic phase was dried (MgSO4) and the solvent removed under reduced pressure. The residue (21.1 g) was recrystallised from ethyl acetate to give a pure material as white crystals m.pt.94° C.
Reaction SMILES: C(OC([NH:8][C@H:9]([C:29]([NH:31][CH2:32][C:33]([O:35][C:36](=[O:50])[C@H:37]([CH:39]([CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C:40]([O-:42])=[O:41])[NH2:38])=[O:34])=[O:30])[CH2:10][CH2:11][CH2:12][NH:13][C:14](=[NH:28])[NH:15][S:16]([C:19]1[C:24]([CH3:25])=[CH:23][C:22]([CH3:26])=[CH:21][C:20]=1[CH3:27])(=[O:18])=[O:17])=O)(C)(C)C.[ClH:51].O1CCOCC1>O1CCOCC1>[ClH:51].[C:24]1([CH3:25])[CH:23]=[C:22]([CH3:26])[CH:21]=[C:20]([CH3:27])[C:19]=1[S:16]([NH:15][C:14](=[NH:28])[NH:13][CH2:12][CH2:11][CH2:10][C@@H:9]([C:29]([NH:31][CH2:32][C:33]([O:35][C:36](=[O:50])[C@H:37]([CH:39]([CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C:40]([OH:42])=[O:41])[NH2:38])=[O:34])=[O:30])[NH2:8])(=[O:18])=[O:17]
Reactant: Cc1cc(C)c(S(=O)(=O)NC(=N)NCCC[C@H](NC(=O)OC(C)(C)C)C(=O)NCC(=O)OC(=O)[C@@H](N)C(Cc2ccccc2)C(=O)[O-])c(C)c1
Agent: Cl
Solvent: C1COCCO1
Product: Cc1cc(C)c(S(=O)(=O)NC(=N)NCCC[C@H](N)C(=O)NCC(=O)OC(=O)[C@@H](N)C(Cc2ccccc2)C(=O)O)c(C)c1
Reaction time: 1 h

Procedure:
1.5 g (2.1 mmol) of compound (III) was dissolved in 30 ml of purified dioxane and 30 ml of 4N HCl/dioxane was added thereto. The mixture was stirred for 1 hour. After concentrating to dryness, the product was crystallized by adding dry ether. The crystals were centrifuged, washed with dry ether several times and dried. Thus 1.3 g of the titled compound was obtained.
Reaction SMILES: ClCCl.[OH:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]1[C:20]([OH:21])=[C:19]([O:22][CH3:23])[C:18]([O:24][CH3:25])=[CH:17][C:16]=1[CH3:26].[O:27]=O>C1C=C(C=NCCN=CC2C([O-])=CC=CC=2)C([O-])=CC=1.[Co+2]>[OH:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]1[C:20](=[O:21])[C:19]([O:22][CH3:23])=[C:18]([O:24][CH3:25])[C:17](=[O:27])[C:16]=1[CH3:26]
Reactant: COc1cc(C)c(CCCCCCCCCCO)c(O)c1OC
Reactant: O=O
Agent: [Co+2]
Agent: [O-]c1ccccc1C=NCCN=Cc1ccccc1[O-]
Solvent: ClCCl
Product: COC1=C(OC)C(=O)C(CCCCCCCCCCO)=C(C)C1=O
Reaction time: 72 h

Procedure:
To a dichloromethane solution (30 ml) of 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methylphenol (1.4 g) is added bis(salicylidene)ethylenediiminocobalt(II) (0.06 g), and the mixture is stirred in oxygen streams at 20° C. and atmospheric pressure for 72 hours. After the reaction has been completed, the reaction mixture is passed through a bed of a small quantity of silica gel (about 15 g) to remove the catalyst. The solvent is then distilled off and the residue is recrystallized from ether-hexane (1:4). The above procedure yields 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (1.01 g) as orange-yellow needles melting at 51° C.-52° C.
Reaction SMILES: [N+](C1C=CC(C([O:10][CH2:11][C@H:12]2[O:16][C@@:15](C(=O)COC3C=CC=CC=3)([N:17]3[C:31]4[N:30]=[C:24]([NH:25]C(C)(C)C)[NH:23][C:21](=[O:22])[C:20]=4[N:19]=[CH:18]3)[CH2:14][C@@H:13]2[OH:42])=O)=CC=1)([O-])=O.ClCCl.C(#N)C.C(N(P(N(C(C)C)C(C)C)OCCC#N)C(C)C)(C)C.N1[C-]=NN=N1.C([NH2+]C(C)C)(C)C>ClCCl>[C@@H:15]1([N:17]2[C:31]3[N:30]=[C:24]([NH2:25])[NH:23][C:21](=[O:22])[C:20]=3[N:19]=[CH:18]2)[O:16][C@H:12]([CH2:11][OH:10])[C@@H:13]([OH:42])[CH2:14]1
Reactant: CC(C)(C)Nc1nc2c(ncn2[C@@]2(C(=O)COc3ccccc3)C[C@H](O)[C@@H](COC(=O)c3ccc([N+](=O)[O-])cc3)O2)c(=O)[nH]1
Agent: CC(C)N(C(C)C)P(OCCC#N)N(C(C)C)C(C)C
Agent: CC(C)[NH2+]C(C)C
Agent: [c-]1nnn[nH]1
Solvent: ClCCl
Solvent: CC#N
Product: Nc1nc2c(ncn2[C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]1
Reaction time: 2 h

Procedure:
5′-O-p-nitrobenzoyl-2-N-t-butylphenoxyacetyldeoxyguanosine (1 eq) is dried in a dichloromethane/acetonitrile mixture and reacted with 1.2 eq of bisdiisopropylaminocyanoethoxyphosphine and 0.5 eq of diisopropylammoniumtetrazolide in anhydrous dichloromethane. After reacting for 2 hours, the reaction mixture is diluted and washed successively with 0.5 M sodium bicarbonate and saturated sodium chloride. The organic phase is evaporated to dryness. After redissolution in chloroform and precipitation in hexane, the product is dried under vacuum and stored under argon. This amidite is soluble in acetonitrile, a solvent in which oligonucleotide syntheses are conventionally carried out.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[C:11]1(=[O:17])[O:16][C:14](=[O:15])[CH2:13][CH2:12]1.[Cl-].[Al+3].[Cl-].[Cl-]>ClC(Cl)C.O.Cl>[CH:9]1[C:10]2[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=2)[CH:6]=[CH:7][C:8]=1[C:11](=[O:17])[CH2:12][CH2:13][C:14]([OH:16])=[O:15]
Reactant: c1ccc2ccccc2c1
Reactant: O=C1CCC(=O)O1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: CC(Cl)Cl
Product: O=C(O)CCC(=O)c1ccc2ccccc2c1
Temperature: 25 °C
Yield: 41.6 %

Procedure:
Naphthalene (5.0 gm, 0.039 moles) and succinic anhydride (4.68 gm, 0.0468 moles) were taken up in dichloroethane (50 ml). Aluminium chloride (11.44 g, 0.0858 moles) was added at room temperature and the resulting mixture heated under reflux for 1 hr with stirring. The reaction mixture was cooled to room temperature, diluted with 25 ml of 1:1 mixture of water and Conc. hydrochloric acid. After stirring for 10 min the separated solid was filtered under suction, washed with water and dilute hydrochloric acid. Subsequent column chromatography gave a buff coloured solid. Subsequent chromatography gave 3.7 gm (41%) the title compound, mp 173-174° C.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[N+]([O-])([O-])=O.[NH4+].[Br:17]N1C(=O)CCC1=O.CCOC(C)=O>CC#N>[Br:17][C:6]1[CH:5]=[C:4]([CH:1]([CH3:3])[CH3:2])[CH:9]=[CH:8][C:7]=1[O:10][CH3:11]
Reactant: COc1ccc(C(C)C)cc1
Reactant: O=C1CCC(=O)N1Br
Agent: O=[N+]([O-])[O-]
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: CC#N
Product: COc1ccc(C(C)C)cc1Br
Yield: 99.7 %

Procedure:
A solution of 20.0 g of 1-isopropyl-4-methoxy benzene, 1.07 g of ammonium nitrate, and 23.7 g of N-bromosuccinimide in MeCN (66.5 ml) was stirred at room temperature for one hour. To the reaction solution was added EtOAc and a saturated aqueous solution of NaHCO3, liquid separation was performed, and the aqueous layer was extracted with EtOAc. The combined organic layer was washed with saturated brine and dried over MgSO4, then, the drying agent was separated by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silicagel 60; mobile phase: EtOAc/n-hexane=1/9, v/v) to obtain 30.4 g of the title compound.
Reaction SMILES: [CH3:1][C:2]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:6]=[CH:5][CH2:4][N:3]1[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[OH2:20].[OH-].[Na+].OO>C1COCC1>[OH:20][CH:5]1[CH2:4][N:3]([C:7]([O:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:8])[C:2]([CH3:1])([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:6]1
Reactant: O
Reactant: CC(C)(C)OC(=O)N1CC=CC1(C)c1ccccc1
Agent: OO
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CC(O)CC1(C)c1ccccc1
Temperature: 0 °C

Procedure:
A solution of 20-4 (0.50 g, 1.9 mmol) in anhydrous THF (80 mL) at 0° C. was treated with BH3:THF (1.93 mL, 1.9 mmol) then stirred for 1 hour. at 25° C. Water (0.35 mL, 19.2 mmol) was added, followed by 3 N NaOH (0.23 mL, 5.8 mmol). The resulting solution was cooled to 0° C. prior to the addition of 30% H2O2 (0.22 mL, 1.9 mmol). The reaction was partitioned between sat. aq. NaHCO3 (100 mL) and EtOAc (2×100 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column (SiO2, O-100% EtOAc/Hexanes gradient) to yield tert-butyl 4-hydroxy-2-methyl-2-phenylpyrrolidine-1-carboxylate, 20-5: LRMS m/z (M+H) 278.2 found, 278.1 required.
Reaction SMILES: [H-].[Na+].[CH2:3]([C:5]1[N:14]=[C:13]([CH2:15][CH3:16])[CH:12]=[C:11]2[C:6]=1[CH:7]=[CH:8][C:9](=[O:17])[NH:10]2)[CH3:4].Br[CH2:19][C:20]1[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][CH:21]=1.O>CN(C=O)C>[CH2:3]([C:5]1[N:14]=[C:13]([CH2:15][CH3:16])[CH:12]=[C:11]2[C:6]=1[CH:7]=[CH:8][C:9](=[O:17])[N:10]2[CH2:19][C:20]1[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][CH:21]=1)[CH3:4]
Reactant: CCc1cc2[nH]c(=O)ccc2c(CC)n1
Reactant: COC(=O)c1ccc(CBr)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCc1cc2c(ccc(=O)n2Cc2ccc(C(=O)OC)cc2)c(CC)n1
Yield: 72.1 %

Procedure:
Sodium hydride (50% dispersion in oil; 1.05 g) was added to a stirred solution of 5,7-diethyl-1,6-naphthyridin-2(1H)-one (4.0 g) in DMF (75 ml) and the mixture was stirred until effervescence ceased. Methyl 4-bromomethylbenzoate (4.58 g) was added and the mixture was stirred under argon for 4 hours. The mixture was then poured into water and extracted twice with ethyl acetate. The combined organic extracts were washed with saturated sodium chloride solution, dried (MgSO4) and solvent was removed by evaporation. The resultant solid was purified by flash chromatography, eluting with ethyl acetate/petroleum ether (3:1 v/v gradually increasing to 1.0 v/v) to give methyl 4-[(5,7-diethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-1-yl)-methyl]benzoate as a solid (5.0 g); m.p. 128°-130° C.; NMR (d6 -DMSO): 1.15(t, 3H), 1.25(t, 3H), 2.69(q, 2H), 3.06(q, 2H), 3.83(s, 3H), 5.56(s, 2H), 6.71(d, 1H), 7.04(s, 1H), 7.35(d, 2H), 7.91(d, 2H), 8.22(d, 1H); mass spectrum (+ve FAB, methanol/DMSO/NBA): 351 (M+H)+ ; microanalysis, found: C, 71.8; H, 6.3; N, 8.2%; C21H22N2O3 requires: C, 72.0; H, 6.3; N, 8.0%.
Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9](CO)[OH:10])[OH:8])[OH:6])[OH:4].O=C[C@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O.OCC([C@H]([C@@H]([C@@H](CO)O)O)O)=O.OCC([C@@H]([C@H]([C@@H](CO)O)O)O)=O.OCC([C@H]([C@H]([C@@H](CO)O)O)O)=O.OCC([C@@H]([C@@H]([C@@H](CO)O)O)O)=O.C(O)[C@H]1O[C@H](O[C@]2(CO)O[C@H](CO)[C@@H](O)[C@@H]2O)[C@H](O)[C@@H](O)[C@@H]1O>O[Mo](O)(=O)=O.[O-][Mo]([O-])(=O)=O.[Na+].[Na+].[O-][Mo]([O-])(=O)=O.O>[O:1]=[CH:2][C@@H:3]([C@H:5]([C@H:7]([CH2:9][OH:10])[OH:8])[OH:6])[OH:4]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: O=[Mo](=O)(O)O
Agent: O=[Mo](=O)([O-])[O-]
Agent: O=C(CO)[C@@H](O)[C@@H](O)[C@H](O)CO
Solvent: O
Product: O=C[C@H](O)[C@@H](O)[C@@H](O)CO

Procedure:
It is also known that both D-glucose and D-mannose can be epimerized in an aqueous solution containing about 17% by weight of D-glucose or D-mannose, based on total solution weight (i.e., 20% by weight of glucose, based on the weight of water) and a small amount of molybdic acid catalyst producing a solution containing 25 percent D-mannose, remainder D-glucose on the dry basis. This epimerization is described by V. Bilik, Chem. Zvesti, 26, 183-186 (1972) and in Czech patent 149,051 (June 15, 1973). No reaction took place when sodium molybdate was used as the catalyst. Bilik and co-workers have also found that various other sugars can be epimerized in the presence of molybdate ions in aqueous solution. For example, D-fructose gives a mixture of D-sorbose, D-tagatose, and D-psicose, and sucrose gives a mixture of D-mannose and D-sorbose in a similar reaction. [Chemical Abstracts, 80, 146433s (1974)]. Also, L-arabinose gives a mixture of L-arabinose and L-ribose [Czechoslovakian Patent 149,472, July 15, 1973; C.A. 81, 78189k (1974)]; L-mannose gives a mixture of L-glucose and L-mannose [C.A. 81, 91887f (1974)]; and D-galactose gives a mixture of D-talose and D-gulose in addition to D-galactose [C.A. 81, 152523h (1974)].
Reaction SMILES: C(NC1C=CN([C@@H]2O[C@H](CO)[C@@H](O)[C@@H]2O)C(=O)N=1)(=O)CCCCCCCCCCCCC.C(NC1C=CN([C@@H]2O[C@H](CO)[C@@H](O)[C@@H]2O)C(=O)N=1)(=O)CCCCCCCCCCC.C(NC1C=CN([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)C(=O)N=1)(=O)CCCCCCCCCCCCC.C(NC1C=CN([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)C(=O)N=1)(=O)CCCCCCCCCCC.[C:125]([NH:142][C:143]1[CH:157]=[CH:156][N:146]([C@@H:147]2[O:155][C@H:152]([CH2:153][OH:154])[C@@H:150]([OH:151])[C@H:148]2[OH:149])[C:145](=[O:158])[N:144]=1)(=[O:141])[CH2:126][CH2:127][CH2:128][CH2:129][CH2:130][CH2:131][CH2:132][CH2:133][CH2:134][CH2:135][CH2:136][CH2:137][CH2:138][CH2:139][CH3:140]>>[C:125]([NH:142][C:143]1[CH:157]=[CH:156][N:146]([C@@H:147]2[O:155][C@H:152]([CH2:153][OH:154])[C@@H:150]([OH:151])[C@@H:148]2[OH:149])[C:145](=[O:158])[N:144]=1)(=[O:141])[CH2:126][CH2:127][CH2:128][CH2:129][CH2:130][CH2:131][CH2:132][CH2:133][CH2:134][CH2:135][CH2:136][CH2:137][CH2:138][CH2:139][CH3:140]
Reactant: CCCCCCCCCCCCCCCC(=O)Nc1ccn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c(=O)n1
Agent: CCCCCCCCCCCC(=O)Nc1ccn([C@@H]2O[C@H](CO)[C@@H](O)[C@@H]2O)c(=O)n1
Agent: CCCCCCCCCCCC(=O)Nc1ccn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c(=O)n1
Agent: CCCCCCCCCCCCCC(=O)Nc1ccn([C@@H]2O[C@H](CO)[C@@H](O)[C@@H]2O)c(=O)n1
Product: CCCCCCCCCCCCCCCC(=O)Nc1ccn([C@@H]2O[C@H](CO)[C@@H](O)[C@@H]2O)c(=O)n1

Procedure:
By following the same procedure as above using N4 -myristoyl-1-β-D-arabinofuranosylcytosine, N4 -lauroyl-1-β-D-arabinofuranosylcytosine, N4 -myristoylcytidine, N4 -lauroylcytidine and N4 -palmitoylcytidine, respectively in place of N4 -palmitoyl-1-β-D-arabinofuranosylcytosine, the following products were obtained:
Reaction SMILES: [F:1][C:2]([F:27])([F:26])[CH2:3][N:4]1[C:8]([C:9]2[N:10]=[C:11]3[C:17]4[CH:18]=[C:19]([C:22](O)=[O:23])[CH:20]=[CH:21][C:16]=4[O:15][CH2:14][CH2:13][N:12]3[CH:25]=2)=[N:7][CH:6]=[N:5]1.[CH:28]([N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1)([CH3:30])[CH3:29]>>[CH:28]([N:31]1[CH2:36][CH2:35][N:34]([C:22]([C:19]2[CH:20]=[CH:21][C:16]3[O:15][CH2:14][CH2:13][N:12]4[CH:25]=[C:9]([C:8]5[N:4]([CH2:3][C:2]([F:27])([F:1])[F:26])[N:5]=[CH:6][N:7]=5)[N:10]=[C:11]4[C:17]=3[CH:18]=2)=[O:23])[CH2:33][CH2:32]1)([CH3:30])[CH3:29]
Reactant: O=C(O)c1ccc2c(c1)-c1nc(-c3ncnn3CC(F)(F)F)cn1CCO2
Reactant: CC(C)N1CCNCC1
Product: CC(C)N1CCN(C(=O)c2ccc3c(c2)-c2nc(-c4ncnn4CC(F)(F)F)cn2CCO3)CC1

Procedure:
Following the procedure for 109, 2-(1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-10-carboxylic acid and 1-isopropylpiperazine gave 120. MS: (ESI+)=490.2. 1H NMR (400 MHz, DMSO) δ 8.38 (d, J=2.0 Hz, 1H), 8.10 (d, J=5.4 Hz, 2H), 7.37 (dd, J=8.4, 2.1 Hz, 1H), 7.12 (d, J=8.4 Hz, 1H), 5.87 (q, J=8.8 Hz, 2H), 4.57 (s, 4H), 3.49 (s, 4H), 2.68 (dt, J=13.0, 6.6 Hz, 1H), 2.45 (s, 4H), 0.97 (d, J=6.5 Hz, 6H)
Reaction SMILES: [CH2:1]([O:8][C@H:9]1[C@H:15]2[CH2:16][N:17]([C:18]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[O:19])[C@@H:10]1[C@H:11]([O:14]2)[O:12]C)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>O>[CH2:1]([O:8][C@H:9]1[C@H:15]([OH:14])[CH2:16][N:17]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[C@@H:10]1[CH:11]=[O:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CO[C@H]1O[C@@H]2CN(C(=O)OCc3ccccc3)[C@H]1[C@H]2OCc1ccccc1
Solvent: O=C(O)C(F)(F)F
Solvent: O
Product: O=C[C@@H]1[C@@H](OCc2ccccc2)[C@H](O)CN1C(=O)OCc1ccccc1
Yield: 91.5 %

Procedure:
Methyl 3-O-benzyl-N-benzyloxycarbonyl-2,5-dideoxy-2,5-imino-α-D-lyxofuranoside (14α) (1.015 g, 2.77 mmol) was stirred in a 1:1 mixture of trifluoroacetic acid and water (20 ml). Once all the starting material had dissolved, the solvents were evaporated (without heat) and purification by flash chromatography (ethyl acetate-hexane 1:2) gave 3-O-benzyl-N-benzyloxycarbonyl-2,5-dideoxy-2,5-imino-D-lyxose (901 mg, 92%) as a clear oil, [α]20 D -24.2° (c, 1.39 in chloroform); νmax (film) 3400 (OH), 1700 (2×CO), 1425, 1360, 1195 and 700 cm-1 ; δH 2.55 (1H, bs, OH); 3.65 (1H, 2×d, H-5); 3.79 (1H, 2×dd, H-5'); 4.03, 4.31 (2H, 2×bs, H-2, H-3); 4.44, 4.55 (1H, bs and dd, H-4); 4.51-4.71 (2H, m, CH2Ph); 5.09-5.20 (2H, m, CH2 -Z); 7.29-7.40 (10H, m, H-Ph); 9.49, 4.59 (1H, 2×d, H-1, J1,2 0.7 Hz). m/z: 91 (100%), 108 (68%), 230 (50%), 356 (M+H+, 20%). (Found C, 67.76; H, 6.48; N, 3.77. C20H21NO5 requires C, 67.59; H, 5.96; N, 3.94). Methyl 3-O-benzyl-N-benzyloxycarbonyl-2,5-dideoxy-2,5-imino-β-D-lyxofuranoside (14β) (976 mg, 2.64 mmol) reacted similarly: it afforded the title compound (15) (820 mg, 87%), spectroscopically identical to that prepared above, under the same reaction conditions.
Reaction SMILES: CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:34]1([C:40]([OH:42])=O)[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1.[Br:43][C:44]1[CH:53]=[CH:52][C:47]2[N:48]=[C:49]([NH2:51])[S:50][C:46]=2[CH:45]=1>C(Cl)Cl>[Br:43][C:44]1[CH:53]=[CH:52][C:47]2[N:48]=[C:49]([NH:51][C:40]([CH:34]3[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39]3)=[O:42])[S:50][C:46]=2[CH:45]=1
Reactant: Nc1nc2ccc(Br)cc2s1
Reactant: O=C(O)C1CCCCC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C(Nc1nc2ccc(Br)cc2s1)C1CCCCC1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 78.4 %

Procedure:
A mixture of Hunig's base (286 μl, 1637 μmol), HATU (830 mg, 2182 μmol) and cyclohexanecarboxylic acid (147 mg, 1146 μmol) was dissolved in 2.0 mL CH2Cl2 and stirred at room temperature for 10 min. 6-bromobenzo[d]thiazol-2-amine (250 mg, 1091 μmol) was added, and stirring was continued overnight. The solids were filtered and washed with CH2Cl2. The filtrate was concentrated, dissolved in CH2Cl2 and purified by silica gel chromatography using 100% CH2Cl2 to provide N-(6-bromobenzo[d]thiazol-2-yl)cyclohexanecarboxamide (290 mg, 78% yield) as a white solid. MS (ESI pos. ion) m/z calc'd for C14H15BrN2OS: 339.3/341.3. found 339.0/341.0.
Reaction SMILES: C[N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]3[CH:15]=[CH:14][CH:13]=[CH:12][C:10]3=2)[CH:5]=[CH:4][CH:3]1[OH:16].[N:17]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]3[CH:30]=[CH:29][CH:28]=[CH:27][C:25]3=2)[CH:20]=[CH:19][CH:18]=1.[CH2:31]1[CH2:37][S:34](=[O:36])(=[O:35])[O:33][CH2:32]1.CI>>[N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]3[CH:15]=[CH:14][CH:13]=[CH:12][C:10]3=2)[CH:5]=[CH:4][CH:3]=1.[CH3:3][O:16][C:22]1[CH:23]=[C:24]2[CH:30]=[CH:29][CH:28]=[CH:27][C:25]2=[C:26]2[C:21]=1[CH:20]=[CH:19][CH2:18][N:17]2[CH2:32][CH2:31][CH2:37][S:34]([OH:33])(=[O:36])=[O:35]
Reactant: O=S1(=O)CCCO1
Reactant: CN1c2c(ccc3ccccc23)C=CC1O
Agent: c1ccc2c(c1)ccc1cccnc12
Solvent: CI
Product: COc1cc2ccccc2c2c1C=CCN2CCCS(=O)(=O)O

Procedure:
Compound 13 was synthesized according to the procedure outlined above in Example 3 for the synthesis of the N-methyl-hydroxybenzoquinoline derivative 15. Compound 13 was then alkylated according to the general amino group alkylation procedure described above in Example 3, this time using 1,3-propane sultone as the alkylating agent rather than MeI, to give a 5-methoxybenzoquinoline-N-propanesulfonic acid intermediate 16 (1HNMR: CD3OD d 7.94 (d, 1H, J=8.7 Hz), 7.65 (d, 1H, J=8.4 Hz), 7.32 (t, 1H), 7.27 (t, 1H), 6.85 (s, 1H), 4.89 (s, 3H), 3.20 (m, 2H), 3.08 (bt, 2H, J=6 Hz), 2.91 (m, 2H), 2.72 (t, 2H, J=6.6 Hz), 2.33 (m, 2H), 1.89 (m, 2H). Subsequent methoxy group deprotection of compound 16 by the general boron tribromide procedure described above in Example 1 resulted in the 3-(5-hydroxybenzoquinolin-1-yl) propanesulfonic acid 17.
Reaction SMILES: [NH2:1][C:2]1[NH:7][C:6]2[C:8]3[CH2:14][CH2:13][CH2:12][CH2:11][C:9]=3[S:10][C:5]=2[C:4](=O)[N:3]=1.CN(C)C1C=CC=CC=1.O=P(Cl)(Cl)[Cl:27]>[Cl-].C([N+](CC)(CC)CC)C.C(#N)C>[Cl:27][C:4]1[C:5]2[S:10][C:9]3[CH2:11][CH2:12][CH2:13][CH2:14][C:8]=3[C:6]=2[N:7]=[C:2]([NH2:1])[N:3]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: Nc1nc(=O)c2sc3c(c2[nH]1)CCCC3
Agent: CC[N+](CC)(CC)CC
Agent: [Cl-]
Solvent: CC#N
Solvent: CN(C)c1ccccc1
Product: Nc1nc(Cl)c2sc3c(c2n1)CCCC3
Temperature: 110 °C
Yield: 40.8 %

Procedure:
In a 15 mL flask, 2-amino-6,7,8,9-tetrahydro-1H-benzo[4,5]thieno[3,2-d]pyrimidin-4-one (0.2 g, 0.9 mmol) and tetraethyl ammonium chloride (0.3 g, 1.8 mmol) were dried under vacuum at 100° C. for 12 h. Addition of acetonitrile (1.80 mL), dimethylaniline (0.12 mL, 0.9 mmol) and POCl3 (0.50 mL, 5.42 mmol) followed, and the reaction mixture was heated to 110° C. for 15 min. The solution was concentrated and ice was added along with CHCl3 (5 mL). The aqueous layer pH was adjusted to pH=7 with saturated (satd.) aq. NaHCO3 and extraction from that layer proceeded with CHCl3 (3×20 mL). The combined organic layers were dried (Na2SO4) and concentrated. The resultant residue was purified by FCC (50% EtOAc/hexanes) to afford the desired product as a pale yellow solid (88 mg). Certain substrates were found to be unstable at higher temperatures, in which case prolonged heating at lower temperature (in a range such as from about 50° C. to about 60° C.) sufficed. MS: 240.0. 1H NMR (400 MHz, CDCl3) δ ppm 5.08 (s, 2H), 2.90-2.83 (m, 2H), 2.74-2.67 (m, 2H), 1.98-1.91 (m, 2H), 1.91-1.83 (m, 2H).
Reaction SMILES: [BH4-].[Li+].[CH2:3]([O:10][C:11]1[C:12]([CH2:24][CH:25]([CH3:27])[CH3:26])=[N+:13]([O-:23])[C:14]([O:21][CH3:22])=[C:15]([C:17](OC)=[O:18])[N:16]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl>C(OCC)C.O>[CH2:3]([O:10][C:11]1[C:12]([CH2:24][CH:25]([CH3:27])[CH3:26])=[N+:13]([O-:23])[C:14]([O:21][CH3:22])=[C:15]([CH2:17][OH:18])[N:16]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: COC(=O)c1nc(OCc2ccccc2)c(CC(C)C)[n+]([O-])c1OC
Agent: Cl
Agent: [BH4-]
Agent: [Li+]
Solvent: O
Solvent: CCOCC
Product: COc1c(CO)nc(OCc2ccccc2)c(CC(C)C)[n+]1[O-]
Yield: 30.5 %

Procedure:
2.4 Milligrams of lithium borohydride was added to 1 ml of a solution of 12.5 mg of 3-benzyloxy-2-isobutyl-6-methoxy-5-methoxycarbonylpyrazine 1-oxide dissolved in anhydrous diethyl ether. The mixture was refluxed for 6 hours in an argon gas stream with stirring, then 0.2 ml of 1N hydrochloric acid was added to the reaction mixture with ice cooling, and the mixture was diluted with water. The reaction mixture was extracted with ethyl acetate and the extract was washed with an aqueous solution saturated with NaCl solution and dried over magnesium sulfate, and the solvent was removed by evaporation. The residue was purified by a thin layer chromatography (developing solvent: dichloromethane/methanol=40/1) to obtain 3.5 mg of 3-benzyloxy-5-hydroxymethyl-6-methoxy-2-isobutylpyrazine 1-oxide (Compound B-24) as colorless needle-like crystals having a melting point of 68.0°-69.2° C.
Reaction SMILES: [CH:1]1([N:7]([CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[C:8](=[O:17])[C:9]2[CH:14]=[CH:13][C:12](Br)=[C:11]([CH3:16])[CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C([Li])(C)(C)C.CN(C)[CH:30]=[O:31]>C1COCC1>[CH:1]1([N:7]([CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[C:8](=[O:17])[C:9]2[CH:14]=[CH:13][C:12]([CH:30]=[O:31])=[C:11]([CH3:16])[CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Cc1cc(C(=O)N(C2CCCCC2)C2CCCC2)ccc1Br
Reactant: CN(C)C=O
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Product: Cc1cc(C(=O)N(C2CCCCC2)C2CCCC2)ccc1C=O

Procedure:
To a cold (-70° C.), stirred solution of 4-bromo-3-methylbenzoic acid N-cyclohexyl-N-cyclopentyl amide (4 g, 0.011 mol) in THF (40 mL) was added t-butyl lithium (13 mL of 1.7 M solution) via syringe over 10 min. The originally colorless solution became a dark red. Dimethylformamide (DMF) (884 mg) was added. The cold bath was removed and the reaction allowed to warm to 0° , during the course of which, the reaction became much lighter in color. The reaction was diluted with ethyl acetate, washed with 0.5 N KHSO4 and the organic layer was dried (Na2SO4). The drying agent was filtered, the filtrate concentrated in vacuo and the crude product purified by chromatography on silica gel using mixtures of ethyl acetate and hexane as eluents to give title compound of Step(a), m.p. 57°-59° C. Anal. Calcd for C20H27NO2 : C, 76.64; H, 8.68; N, 4.47. Found: C, 76.21; H, 8.71; N, 4.11.