Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O=[C:2]1[C:7]2[CH:8]=[CH:9][C:10]([OH:15])=[C:11]([CH2:12][CH2:13][CH3:14])[C:6]=2[O:5][C:4]([CH2:23][CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])([CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:3]1>C(O)(=O)C.[H][H].[Pd]>[CH2:12]([C:11]1[C:6]2[O:5][C:4]([CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])([CH2:23][CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:3][CH2:2][C:7]=2[CH:8]=[CH:9][C:10]=1[OH:15])[CH2:13][CH3:14]
Reactant: [H][H]
Reactant: CCCc1c(O)ccc2c1OC(CCC(=O)OCC)(CCC(=O)OCC)CC2=O
Agent: [Pd]
Solvent: CC(=O)O
Product: CCCc1c(O)ccc2c1OC(CCC(=O)OCC)(CCC(=O)OCC)CC2
Reaction time: 8 h
Yield: 19.8 %

Procedure:
The title product of Example 1 (4.19 g, 10.3 mmol) was dissolved in 50 ml of acetic acid, and then hydrogenated at 70° C. using 60 psi of hydrogen and 10% palladium on carbon as catalyst. After eight hours, the mixture was allowed to cool, and insolubles were removed by filtration. The filtrate was concentrated under reduced pressure. The residue was chromatographed on silicagel column. Elution with 20% ethyl acetate/hexane afforded the title compound (0.80 g).
Reaction SMILES: [C:1]1([C:11](OCC)=[O:12])([C:6](OCC)=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C(OCC)C.O>O1CCCC1>[OH:7][CH2:6][C:1]1([CH2:11][OH:12])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CCOC(=O)C1(C(=O)OCC)CCCC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: O
Product: OCC1(CO)CCCC1
Temperature: 25 °C
Reaction time: 17 h
Yield: 91.5 %

Procedure:
A solution of diethyl cyclopentane-1,1-dicarboxylate (23.3 g) in dry tetrahydrofuran (50 cm3) was added to a stirred suspension of lithium aluminium hydride (2.3 g) in dry tetrahydrofuran (150 cm3) at 0° C. under an atmosphere of nitrogen. The mixture was allowed to warm to the ambient temperature then stood for 17 hours; GLC analysis of a withdrawn sample indicated the presence of starting ester at this time. Two further portions of lithium aluminium hydride (0.5 g and 3.0 g) were added and the mixture stirred for a total of 2.5 hours. After this time GLC analysis showed no starting material. The mixture was poured into a mixture of diethyl ether and water. The aqueous layer was separated and extracted twice with diethyl ether. The combined organic layers were washed with brine and dried over anhydrous magnesium sulphate. Evaporation of the solvent under reduced pressure gave the title compound (12.95 g) in 89% purity (by GLC analysis) as an off-white solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[OH:9].[Br:10][CH2:11][CH2:12]Br.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[Br:10][CH2:11][CH2:12][O:9][C:3]1[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=1[F:8]
Reactant: BrCCBr
Reactant: Oc1c(F)cccc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: Fc1cccc(F)c1OCCBr
Temperature: 60 °C
Reaction time: 8 h
Yield: 22.8 %

Procedure:
A suspension of 2,6-difluoro phenol (18 g, 0.385 mol), 1,2-dibromoethane (71.6 ml, 0.83 mol) and K2CO3 (47.86 g, 0.3463 mol) in dry acetonitrile (190 ml) was stirred at 60° C. overnight under nitrogen atmosphere. The reaction mixture was filtered and solvent concentrated under reduced pressure. The residue was purified by column chromatography over silica gel using 7% ethyl acetate in petroleum ether as eluent to give the title compound (20.8 g) as colorless oil.
Reaction SMILES: [C:1]1([CH2:7][C:8]([NH:10][CH:11]2[C:38](=[O:39])[N:13]3[C:14]([C:22]([O:24][CH:25]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[O:23])=[C:15]([CH2:19][S:20][CH3:21])[CH2:16][S:17](=O)[C@H:12]23)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(=CC)C.C(Br)(=O)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl.O>[C:1]1([CH2:7][C:8]([NH:10][CH:11]2[C:38](=[O:39])[N:13]3[C:14]([C:22]([O:24][CH:25]([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)[C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)=[O:23])=[C:15]([CH2:19][S:20][CH3:21])[CH2:16][S:17][C@H:12]23)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CSCC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)C(NC(=O)Cc3ccccc3)[C@H]2S(=O)C1
Agent: CC(=O)Br
Agent: CC=C(C)C
Agent: O=C([O-])O
Solvent: ClCCl
Solvent: O
Product: CSCC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)C(NC(=O)Cc3ccccc3)[C@H]2SC1
Yield: 92 %

Procedure:
To a solution of benzhydryl 7-(2-phenylacetamido)-3-methylthiomethyl-3-cephem-4-carboxylate-1-oxide (15.1 g) in methylene chloride (150 ml) was added 2-methyl-2-butene (5.7 ml), followed by adding dropwise acetyl bromide (5.2 ml) under ice-cooling and stirring for half an hour. After addition of water, the mixture was adjusted to pH about 5 with an aqueous solution of sodium bicarbonate, washed three times with an aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and then evaporated under reduced pressure to give benzhydryl 7-[2-phenylacetamido)-3-methylthiomethyl-3-cephem-4-carboxylate (13.5 g).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][NH:4][C:3]2[CH:7]=[N:8][CH:9]=[CH:10][C:2]1=2.Br[CH2:12][C:13]([C:15]1[CH:20]=[C:19]([Br:21])[C:18]([OH:22])=[C:17]([Br:23])[CH:16]=1)=[O:14].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Br:21][C:19]1[CH:20]=[C:15]([C:13](=[O:14])[CH2:12][N:4]2[CH2:5][CH2:6][O:1][C:2]3[CH:10]=[CH:9][N:8]=[CH:7][C:3]2=3)[CH:16]=[C:17]([Br:23])[C:18]=1[OH:22]
Reactant: c1cc2c(cn1)NCCO2
Reactant: O=C(CBr)c1cc(Br)c(O)c(Br)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: O=C(CN1CCOc2ccncc21)c1cc(Br)c(O)c(Br)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 58.4 %

Procedure:
In a 10 ml flask, (3,4-dihydro-2H-pyrido[4,3-b][1,4]oxazine (60 mg, 0.44 mmol) was dissolved in anhydrous acetonitrile (5 ml). At room temperature, 2-bromo-1-(3,5-dibromo-4-hydroxy-phenyl)-ethanone (164 mg, 0.44 mmol) and potassium carbonate (121 mg, 0.88 mmol) were added thereto and then stirred at room temperature for 16 hours. The reaction mixture was filtered and the resulting white solid was recrystallized from methanol to obtain the target compound 54 as white solid (110 mg, 58.5%).
Reaction SMILES: C([Mg]Br)C.[Mg].C(Br)C.[CH2:9]([OH:12])[C:10]#[CH:11].Cl[CH2:14]/[CH:15]=[CH:16]\[CH2:17]/[CH:18]=[CH:19]\[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]>C1COCC1>[CH2:9]([OH:12])[C:10]#[C:11][CH2:14]/[CH:15]=[CH:16]\[CH2:17]/[CH:18]=[CH:19]\[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]
Reactant: C#CCO
Reactant: CCCCC/C=C\C/C=C\CCl
Agent: CC[Mg]Br
Agent: [Mg]
Solvent: CCBr
Solvent: C1CCOC1
Product: CCCCC/C=C\C/C=C\CC#CCO
Temperature: 23 °C
Yield: 98.5 %

Procedure:
A solution off ethylmagnesium bromide in THF (10 ml) was prepared from magnesium (1.4 g, 57.7 mmol) and ethyl bromide (7.7 g, 71 mmol). Propargyl alcohol (1.53 g, 27.4 mmol) in dry THF (6 ml) was then added dropwise to the above ethylmagnesium bromide solution at 5° C. with vigorous stirring. The resulting viscous mixture was stirred at 23° C. under argon for twenty minutes. Cuprous chloride (0.14 g) was added and the reaction mixture was further stirred for twenty minutes. A solution of (Z,Z)-1-chloro-2,5-undecadiene (3.4 g, 18.2 mmol) in THF (2.0 ml) was then added dropwise to the above mentioned mixture over a period of twenty five minutes, at 20° C. The reaction mixture was stirred at 50° C. under argon for 18 h. The THF was removed at ~35° C. on a rotary evaporator and the resulting residue was treated with cold 1.5N H2SO4 (150 ml). It was extracted with ether, washed with water, and dried over Na2SO4. Evaporation of ether at reduced pressure gave 3.7 g of light yellow oil which was chromatographed on 70 g of silica gel. Elution with ether-petroleum ether (1:3) gave 2.3 g (61%) of (Z,Z)-5,8-tetradecadien-2-yl-1-ol which was evaporatively distilled at 137°-140° C./0.3 mm Hg as a colorless liquid.
Reaction SMILES: [N+:1]([C:4]1[C:12]2[C:7](=[CH:8][C:9]([Cl:14])=[C:10]([Cl:13])[CH:11]=2)[NH:6][C:5]=1[C:15]([O:17][CH2:18][CH3:19])=[O:16])([O-])=O.O.O.[Sn](Cl)Cl.C(=O)([O-])[O-].[K+].[K+].C(=O)=O>C(O)C.O.C(OCC)(=O)C>[NH2:1][C:4]1[C:12]2[C:7](=[CH:8][C:9]([Cl:14])=[C:10]([Cl:13])[CH:11]=2)[NH:6][C:5]=1[C:15]([O:17][CH2:18][CH3:19])=[O:16]
Reactant: CCOC(=O)c1[nH]c2cc(Cl)c(Cl)cc2c1[N+](=O)[O-]
Agent: Cl[Sn]Cl
Agent: O=C([O-])[O-]
Agent: O=C=O
Solvent: CCOC(C)=O
Solvent: CCO
Solvent: O
Product: CCOC(=O)c1[nH]c2cc(Cl)c(Cl)cc2c1N
Temperature: 25 °C

Procedure:
Dissolve 3-nitro-2-carbethoxy-5,6-dichloroindole (38.1 g) in ethanol (1 L) and add tin (II) chloride dihydrate (163 g). Warm to between 65° and 75° C. for 4 to 5 hours. Cool to room temperature and pour into a mixture of ethyl acetate (3 L) and water (2 L). Add solid potassium carbonate and stir occasionally until the carbon dioxide evolution ceases. Filter throught diatomaceous earth and separate the organic phase of the filtrate. Dry (MgSO4) and evaporate the solvent in vacuo to give the title compound.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:24])[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[C:8]([O:16]CC2C=CC=CC=2)[CH:7]=1)[CH3:2]>CO.[Pd]>[CH2:1]([O:3][C:4](=[O:24])[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[C:8]([OH:16])[CH:7]=1)[CH3:2]
Reactant: CCOC(=O)Cc1cc(OCc2ccccc2)cc2ccccc12
Agent: [Pd]
Solvent: CO
Product: CCOC(=O)Cc1cc(O)cc2ccccc12
Temperature: 25 °C
Reaction time: 14 h

Procedure:
(3-Benzyloxy-naphthalen-1-yl)-acetic acid ethyl ester (2.43 g, 7.58 mmol) is dissolved in MeOH (50 ml). Palladium on charcoal (807 mg) is added, and the reaction mixture is stirred at RT under an atmosphere of hydrogen (1 atm) for 14 h. The reaction mixture is filtered. Concentration yields the pure title compound. 1H NMR (DMSO, 400 MHz) δ 1.18 (t, J=7.2 Hz, 3H), 4.05 (s, 2H), 4.10 (q, J=7.2 Hz, 2H), 7.04 (d, J=1.8 Hz, 1H), 7.06 (d, J=1.8, 1H), 7.30 (t, J=7.8, 1H), 7.40 (t, J=7.8, 1H), 7.70 (d, J=7.8, 1H), 7.80 (d, J=7.8 Hz, 1H); ES-MS: 230 [M+H]+.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[C:6]([NH:11][CH:12]3[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]3)[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.[CH2:19]([NH2:22])[CH2:20][CH3:21].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl.CO>CO>[CH:1]1[C:10]2[C:5](=[C:6]([NH:11][CH:12]3[CH2:17][CH2:16][CH:15]([NH:22][CH2:19][CH2:20][CH3:21])[CH2:14][CH2:13]3)[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1
Reactant: O=C1CCC(Nc2cccc3cnccc23)CC1
Reactant: CCCN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: CCCNC1CCC(Nc2cccc3cnccc23)CC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 25.4 %

Procedure:
4-(5-Isoquinolylamino)-1-cyclohexanone (intermediate 4) (60 mg) and propylamine (30 mg) were dissolved in methanol (1 ml), and sodium triacetoxyborohydride (105 mg) was added by portions to the solution at room temperature. The reaction mixture was stirred at room temperature for 18 hr. Hydrochloric acid-methanol was then added thereto, and the reaction mixture was stirred and was then concentrated. The residue was purified by HPLC [0.5% aqueous trifluoroacetic acid solution/acetonitrile]. A saturated aqueous sodium hydrogencarbonate solution (2 ml) was then added to fractions containing respective compounds, followed by extraction with chloroform-propanol (3/1). The organic layers were dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure to give an anti-form compound (18 mg) and a syn-form compound (22 mg).
Reaction SMILES: [H-].[Na+].[C:3]1([C:9]2[CH:10]=[C:11]([OH:21])[CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:14]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Br[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29].O>CN(C)C=O>[C:3]1([C:9]2[CH:10]=[C:11]([CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:14]=2)[O:21][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: Oc1cc(-c2ccccc2)cc(-c2ccccc2)c1
Reactant: CCOC(=O)CCCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)CCCCCOc1cc(-c2ccccc2)cc(-c2ccccc2)c1
Temperature: 25 °C
Reaction time: 5 h
Yield: 31.7 %

Procedure:
To a suspension of 0.78 g of sodium hydride (55 % w/w dispersion in mineral oil) in 300 cc of dimethylformamide was added a solution of 2 g of 3,5-diphenyl-phenol in 10 cc of dimethylformamide, The mixture was stirred for 5 hours at room temperature until effervescence had stopped. 2.2 g of ethyl 6-bromohexanoate was then added and the resultant mixture stirred at room temperature overnight. The mixture was then heated for 20 hours to 40° C. After cooling, the resultant mixture was poured into 100 cc of cold water and extracted with ethyl acetate (3#100 cc). The combined extracts were washed with water, dried (Na2SO4) and concentrated in vacuo. The resultant residue was flash chromatographed on silica gel (30-60 mm; eluent: 92:8 n-hexane/ethyl acetate) to give 1 g of ethyl 6-(3,5-diphenyl-phenoxy)hexanoate as a oil, used without further purification in the next step.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[C:15](=[O:19])[CH2:14][CH2:13][CH2:12]3)[CH:5]=[CH:4][N:3]=[CH:2]1.[CH:20]([C:22]1[S:23][CH:24]=[CH:25][N:26]=1)=[O:21].OS(O)(=O)=O>CC(O)=O.O>[OH:21][CH:20]([C:22]1[S:23][CH:24]=[CH:25][N:26]=1)[CH:14]1[CH2:13][CH2:12][C:11]2[C:16](=[CH:17][CH:18]=[C:9]([O:8][CH2:7][CH2:6][N:1]3[CH:5]=[CH:4][N:3]=[CH:2]3)[CH:10]=2)[C:15]1=[O:19]
Reactant: O=Cc1nccs1
Reactant: O=C1CCCc2cc(OCCn3ccnc3)ccc21
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CC(=O)O
Product: O=C1c2ccc(OCCn3ccnc3)cc2CCC1C(O)c1nccs1
Yield: 74.6 %

Procedure:
6-(2-Imidazole-1-yl-ethoxy)-3,4-dihydro-2H-naphthalen-1-one (0.200 g, 0.78 mmol) was reacted with 2-formylthiazole (0.107 g, 0.94 mmol) in a mixture of HOAc (1 mL) and concentrated H2SO4 (0.100 mL) at room temperature overnight. The resulting biphasic reaction mixture was diluted with water and then extracted with EtOAc. The aqueous portion was made to pH 10 with 50% NaOH and extracted with EtOAc (3×50 mL). The pooled organic extracts were washed well with water, dried, filtered, and concentrated to afford 0.215 g (74%) of the title compound as a golden oil: APCI-MS m/e 370.2 M++1).
Reaction SMILES: CS[C:3]1[NH:4][C:5](=[O:14])[C:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:7][N:8]=1.[NH:15]1[C:23]2[C:18](=[CH:19][CH:20]=[C:21]([NH2:24])[CH:22]=2)[CH:17]=[N:16]1>C(O)C>[NH:15]1[C:23]2[C:18](=[CH:19][CH:20]=[C:21]([NH:24][C:3]3[NH:4][C:5](=[O:14])[C:6]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:7][N:8]=3)[CH:22]=2)[CH:17]=[N:16]1
Reactant: Nc1ccc2cn[nH]c2c1
Reactant: CCOC(=O)c1cnc(SC)[nH]c1=O
Solvent: CCO
Product: CCOC(=O)c1cnc(Nc2ccc3cn[nH]c3c2)[nH]c1=O
Temperature: 80 °C
Yield: 45.4 %

Procedure:
The mixture of ethyl 2-(methylthio)-6-oxo-1,6-dihyropyrimidine-5-carboxylate (358 mg, 1.671 mmol) and 1-H-indazol-6-amine (222 mg, 1.671 mmol) were dissolved in 10 mL of ethanol and heated at 80° C. overnight. After heating, the solution was run on thin layer chromatography and filtered. The precipitate was collected and stored. 1H-NMR confirmed the product (227 mg, 45.4% yield).
Reaction SMILES: [SH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH2:21][CH2:20][CH2:19][N:11]3[C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:29][O:30][CH2:31]Br>C(Cl)Cl>[CH3:29][O:30][CH2:31][S:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]3[CH2:21][CH2:20][CH2:19][N:11]3[C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[CH:6][CH:7]=1
Reactant: Sc1ccc(-c2nc3n(c2-c2ccncc2)CCC3)cc1
Reactant: COCBr
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COCSc1ccc(-c2nc3n(c2-c2ccncc2)CCC3)cc1
Temperature: 25 °C

Procedure:
To an ice bath cooled solution containing 1.0 q (3.4mmole) of 2-(4-mercaptophenyl)-3-(4-pyridyl)-6,7-dihydro-[5H]-pyrrolo[1,2-a]imidazole prepared as in Example 16 and 0.5 ml (3.6 mmole) of triethylamine in 10ml of methylene chloride is added 0.27 ml (3.5 mmole) of bromomethyl methyl ether. The reaction is allowed to warm to room temperature and stirred at room temperature for several hours. Workup and chromatography in a manner analogous to that outlined in example 18 affords the desired titled compound.
Reaction SMILES: [C:1]1(=[O:12])[O:11][C@H:8]([CH2:9][OH:10])[C@@H:6]([OH:7])[C@H:4]([OH:5])[C@H:2]1[OH:3].[NH2:13]CCCN>CO>[O:12]=[C:1]([NH2:13])[C@@H:2]([C@H:4]([C@@H:6]([C@@H:8]([CH2:9][OH:10])[OH:11])[OH:7])[OH:5])[OH:3]
Reactant: O=C1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Reactant: NCCCN
Solvent: CO
Product: NC(=O)[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Temperature: 40 °C
Reaction time: 8 h
Yield: 240.8 %

Procedure:
A 100 ml round bottom flask equipped with a condenser, addition funnel, thermometer and mechanical stirrer was charged with D-glucono-1,5-lactone (5.4 g, 0.03 mole) and methanol (7 g). The suspension was heated to 40° C. over 15 minutes and the heating mantle removed. Soya-aminopropylamine (10.0 g, 0.03 mole) was added dropwise over 15 minutes with rapid stirring. The reaction mixture was cooled and placed in a refrigerator at 0° C. overnight. The white product was filtered, washed with cold isopropanol (3×100 ml) and dried under vacuum at 35° C. giving 14.1 g (92% yield) of soyaaminopropyl D-gluconamide with a melting point of 97°-100° C.
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH2:10][CH2:11]Br.[ClH:13].Cl.[CH3:15][N:16]([CH3:25])[CH2:17][CH2:18][CH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.[OH-].[Na+].Br.Cl>CCOCC.C(O)(=O)C.CN(C=O)C.C(N(CC)CC)C>[ClH:13].[ClH:13].[CH3:25][N:16]([CH3:15])[CH2:17][CH2:18][CH:19]1[CH2:24][CH2:23][N:22]([CH2:11][CH2:10][O:9][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[OH:2])[CH2:21][CH2:20]1
Reactant: CN(C)CCC1CCNCC1
Reactant: COc1ccccc1OCCBr
Agent: Br
Agent: Cl
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: CC(=O)O
Product: CN(C)CCC1CCN(CCOc2ccccc2O)CC1
Temperature: 0 °C

Procedure:
A mixture of 2-bromoethyl 2-methoxyphenyl ether (7.5 g), 4-(2-dimethylaminoethyl)piperidine dihydrochloride (7.44 g), triethylamine (18.1 ml) and DMF (50 ml) was heated on a steam bath for 18 hours. The mixture was poured into ice/water (500 ml) and basified with 2M sodium hydroxide. The product was extracted into dichloromethane to give an oil. The oil was triturated with ether. The ether was decanted off and evaporated to give crude 4-(2-dimethylaminoethyl)-1-[2-(2-methoxyphenoxy)ethyl]piperidine (4.58 g) which was added to glacial acetic acid (17 ml) and 48% hydrobromic acid (57 ml). The mixture was heated on a steam bath for 4 hours and then evaporated to dryness. The residue was dissolved in water, basified with 2M sodium hydroxide solution and extracted with dichloromethane to give an oil. The oil was dissolved in ether and acidified with ethereal hydrogen chloride The precipitate was collected by filtration and recrystallised from propan-2-ol to give 2-{2-[4-(2-dimethylaminoethyl)piperidino]ethoxy}phenol dihydrochloride m.p. 273°-275° C.
Reaction SMILES: [CH:1](=O)[CH2:2][CH2:3][CH:4]=C.[C:7]([OH:13])(=[O:12])[CH2:8][C:9](O)=O.N1CCCCC1.Cl>N1C=CC=CC=1>[C:7]([OH:13])(=[O:12])/[CH:8]=[CH:9]/[CH2:4][CH2:3][CH:2]=[CH2:1]
Reactant: C=CCCC=O
Reactant: O=C(O)CC(=O)O
Agent: Cl
Solvent: c1ccncc1
Solvent: C1CCNCC1
Product: C=CCC/C=C/C(=O)O
Temperature: 90 °C
Reaction time: 5 h

Procedure:
4-Pentenal (4.45 g, 51.4 mmol) and malonic acid (6.41 g, 61.6 mmol) were dissolved in pyridine (9.9 mL). To the solution, piperidine (1.9 mL) was added, and the mixture was then stirred at 90° C. for 5 hours. The mixture was allowed to cool and then made acidic by the addition of 2 N hydrochloric acid, followed by extraction with diethyl ether. The organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate, and the filtrate was then concentrated under reduced pressure. The residue was distilled under reduced pressure to obtain the compound of interest as a colorless oil substance (3 mmHg, 110-116° C., 3.27 g, 50%).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[N:11]=[C:10]2[C:6]([N:7]=[CH:8][N:9]2[C@H:12]2[C@H:16]([OH:17])[C@H:15]([OH:18])[C@@H:14]([CH2:19][O:20][CH3:21])[O:13]2)=[C:5]([NH:22][CH2:23][CH:24]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:4]=1.[CH:37]1([CH:43]=O)[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[CH:37]1([CH2:43][NH:1][CH2:2][C:3]2[N:11]=[C:10]3[C:6]([N:7]=[CH:8][N:9]3[C@H:12]3[C@H:16]([OH:17])[C@H:15]([OH:18])[C@@H:14]([CH2:19][O:20][CH3:21])[O:13]3)=[C:5]([NH:22][CH2:23][CH:24]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:4]=2)[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1
Reactant: O=CC1CCCCC1
Reactant: COC[C@H]1O[C@@H](n2cnc3c(NCC(c4ccccc4)c4ccccc4)nc(CN)nc32)[C@H](O)[C@@H]1O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Product: COC[C@H]1O[C@@H](n2cnc3c(NCC(c4ccccc4)c4ccccc4)nc(CNCC4CCCCC4)nc32)[C@H](O)[C@@H]1O
Yield: 46.9 %

Procedure:
The title compound was prepared by a similar method to example 5 from (2R,3R,4S,5R)-2-{2-(aminomethyl)-6-[(2,2-diphenylethyl)amino]-9H-purin-9-yl}-5-(methoxymethyl)tetrahydro-3,4-furandiol (example 1) (110 mg, 0.22 mmol), cyclohexanecarboxaldehyde (22 mg, 0.20 mmol) and sodium tnacetoxyborohydnde (70 mg, 0.33 mmol) to afford the title compound as a solid (55 mg). MS: 587 (MH+).
Reaction SMILES: [N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]=1[S:10][CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:21]=1[N:20]([CH2:22][CH3:23])[CH2:19][CH2:18][C:17]2=O.Cl.[NH2:26][OH:27].C([O-])(=O)C.[Na+]>C(O)C.O>[N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]=1[S:10][CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:21]=1[N:20]([CH2:22][CH3:23])[CH2:19][CH2:18][C:17]2=[N:26][OH:27]
Reactant: NO
Reactant: CCN1CCC(=O)c2cccc(CSc3nc4ccccc4[nH]3)c21
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CCN1CCC(=NO)c2cccc(CSc3nc4ccccc4[nH]3)c21
Yield: 60 %

Procedure:
8-(2-Benzimidazolyl)thiomethyl-1-ethyl-4-oxo-1,2,3,4-tetrahydroquinoline (1.5 g), hydroxylamine hydrochloride (458 mg) and sodium acetate (1.7 g) were dissolved in a mixed solvent (23 ml) of ethanol-water (20:3), and the solution was refluxed for 3 hours. After completion of the reaction, the solvent was distilled off and the resulting residue was poured into water. The precipitated crystals were collected by filtration and recrystallized from methanol to give 8-(2-benzimidazolyl)thiomethyl-1-ethyl-4-hydroxyimino-1,2,3,4-tetrahydroquinoline (0.94 g).
Reaction SMILES: [CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:40]([NH:42][S:43]([N:46]([CH2:48]C(OC)OC)[CH3:47])(=[O:45])=[O:44])=[O:41])=[CH:12][C:13]=3[N:14]3[C:21]=2[C:20]2[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=2[O:18][CH2:17][C@H:16]([N:26]([CH3:39])[C@H:27]2[CH2:31][CH2:30][N:29]([C:32](OC(C)(C)C)=O)[CH2:28]2)[CH2:15]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CCN(CC)CC.[BH3-]C#N.[Na+].CC(O)=O>C(Cl)Cl.C(O)(C(F)(F)F)=O.CO>[CH:1]1([C:7]2[C:8]3[C:13]4=[CH:12][C:11](=[CH:10][CH:9]=3)[C:40](=[O:41])[NH:42][S:43](=[O:45])(=[O:44])[N:46]([CH3:47])[CH2:48][CH2:32][N:29]3[CH2:28][C@H:27]([CH2:31][CH2:30]3)[N:26]([CH3:39])[C@@H:16]3[CH2:15][N:14]4[C:21]=2[C:20]2[C:19]([O:18][CH2:17]3)=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: COC(CN(C)S(=O)(=O)NC(=O)c1ccc2c(C3CCCCC3)c3n(c2c1)C[C@@H](N(C)[C@H]1CCN(C(=O)OC(C)(C)C)C1)COc1ccccc1-3)OC
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Solvent: CC(=O)O
Product: CN1[C@H]2CCN(CCN(C)S(=O)(=O)NC(=O)c3ccc4c(C5CCCCC5)c5n(c4c3)C[C@@H]1COc1ccccc1-5)C2
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A 0.05M solution of tert-butyl (3S)-3-[{(7R)-14-cyclohexyl-11-[({[(2,2-dimethoxyethyl)(methyl)amino]sulfonyl}amino)carbonyl]-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocin-7-yl}(methyl)amino]pyrrolidine-1-carboxylate in DCM/TFA 3:1 was stirred at RT for 1.5 h. The residue obtained by evaporation was dissolved in MeOH, NEt3 (5 eq) was added, followed by NaCNBH3 (3 eq) and AcOH (10 eq) and the mixture was stirred for 4 h at RT.