Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].N1C=CC=CC=1.[NH2:11][C:12]1[C:17]([F:18])=[CH:16][C:15]([F:19])=[CH:14][C:13]=1[S:20][CH2:21][C:22]#[N:23]>C1COCC1>[C:22]([CH2:21][S:20][C:13]1[CH:14]=[C:15]([F:19])[CH:16]=[C:17]([F:18])[C:12]=1[NH:11][C:1](=[O:3])[CH3:2])#[N:23]
Reactant: N#CCSc1cc(F)cc(F)c1N
Reactant: CC(=O)Cl
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: CC(=O)Nc1c(F)cc(F)cc1SCC#N
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
Acetyl chloride (575 μl, 8 mmol) in THF (2 ml) and subsequently pyridine (645 μl, 8 mmol) in THF (2 ml) were added to a stirred solution of (2-amino-3,5-difluorophenylsulfanyl)acetonitrile (1.53 g) in THF (20 ml) at 0° C. The mixture was stirred at 0° C. for 15 min, then at ambient temperature for 1 h. Additional amounts of acetyl chloride (57 μl) and pyridine (65 μl) were added, and stirring was continued for 1 h. Then the solvent was removed in vacuo and the residue was triturated with water (25 ml). The precipitate was filtered off and dried. Recrystallization from 96% ethanol gave the title compound. Yield 1.16 g (63%), mp 148.5-149° C. An additional crop of the title compound (0.25 g, 13%) was obtained from the mother liqueor; 1H-NMR (DMSO-d6), δ (ppm): 9.65 (s, 1H, NH), 7.40-7.20 (m, 2H, Ar—H), 4.34 (s, 2H, CH2), 2.09 (s, 3H, CH3).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.C([O-])([O-])=O.[Na+].[Na+].I[C:19]1[CH:20]=[CH:21][C:22](C)=[C:23](O)[CH:24]=1.COCCOC>CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:5][CH:4]=1
Reactant: Cc1ccc(I)cc1O
Reactant: COc1ccc(B(O)O)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: CCOC(C)=O
Product: COc1ccc(-c2ccccc2)cc1
Yield: 50.8 %

Procedure:
A mixture of 4-methoxyphenylboronic acid (4.55 g, 21.38 mmol), Na2CO3 (32.1 ml 2 N aqueous, 64.2 mmol), Pd(PPh3)4 (1.24 g, 1.07 mmol), 5-iodo-2-methylphenol (Hodgson, Moore J. Chem. Soc. 1926, 2038) (5.0 g, 21.38 mmol), and ethylene glycol dimethyl ether (225 ml) was heated to reflux overnight. The reaction was cooled, diluted with EtOAc and the layers separated. The organic layer was dried over anhydrous Na2SO4, passed through a silica plug and concentrated. Chromatography (30% EtOAc/hexanes) afforded 1.64 g (36%) product as a white solid and 2 g 4-methoxy biphenyl as an undesired by-product: mp 146–147° C.; 1H NMR (300 MHz, DMSO-d6): δ 2.13 (3H, s), 3.78 (3H, s), 6.94 (1H, dd, J=8.1 Hz, 2.7 Hz), 7.00 (3H, m), 7.09 (1H, d, J=8.1 Hz), 7.48 (1H, d, J=9.5 Hz), 9.36 (1H, s).
Reaction SMILES: [CH3:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([C:10]2[CH:15]=[C:14]([CH3:16])[CH:13]=[CH:12][C:11]=2[C:17]2[CH:18]=[N:19][N:20]([CH3:22])[CH:21]=2)=[O:9])[C@@H:3]1[CH2:23][NH:24][C:25]1[CH:30]=[CH:29][C:28]([C:31](F)(F)F)=[CH:27][N:26]=1.ClC1N=CC=CC=1C#[N:39]>>[CH3:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8](=[O:9])[C:10]2[CH:15]=[C:14]([CH3:16])[CH:13]=[CH:12][C:11]=2[C:17]2[CH:18]=[N:19][N:20]([CH3:22])[CH:21]=2)[C@@H:3]1[CH2:23][NH:24][C:25]1[N:26]=[CH:27][CH:28]=[CH:31][C:30]=1[C:29]#[N:39]
Reactant: Cc1ccc(-c2cnn(C)c2)c(C(=O)N2CCC[C@@H](C)[C@H]2CNc2ccc(C(F)(F)F)cn2)c1
Reactant: N#Cc1cccnc1Cl
Product: Cc1ccc(-c2cnn(C)c2)c(C(=O)N2CCC[C@@H](C)[C@H]2CNc2ncccc2C#N)c1

Procedure:
The title compound was synthesized following the same general protocol as described for ((2S,3R)-3-methyl-2-(((5-(trifluoromethyl)pyridin-2-yl)amino)methyl)piperidin-1-yl)(5-methyl-2-(1-methyl-1H-pyrazol-4-yl)phenyl)methanone in Example A1, using 2-chloronicotinonitrile. ESI-MS (m/z): 429 [M+1]+.
Reaction SMILES: [CH3:1][S:2]([OH:5])(=[O:4])=[O:3].[CH3:6][C:7]1[CH:8]=[C:9]([CH:26]=[CH:27][C:28]=1[N+:29]([O-])=O)[C:10]([O:12][C:13]1[CH:22]=[CH:21][C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:23](=[NH:25])[NH2:24])[CH:19]=2)[CH:14]=1)=[O:11].[CH3:32][S:33]([OH:36])(=[O:35])=[O:34].[H][H]>[Pd].CN(C=O)C>[CH3:1][S:2]([OH:5])(=[O:4])=[O:3].[CH3:32][S:33]([OH:36])(=[O:35])=[O:34].[NH2:29][C:28]1[CH:27]=[CH:26][C:9]([C:10]([O:12][C:13]2[CH:22]=[CH:21][C:20]3[C:15](=[CH:16][CH:17]=[C:18]([C:23](=[NH:24])[NH2:25])[CH:19]=3)[CH:14]=2)=[O:11])=[CH:8][C:7]=1[CH3:6]
Reactant: [H][H]
Reactant: Cc1cc(C(=O)Oc2ccc3cc(C(=N)N)ccc3c2)ccc1[N+](=O)[O-]
Agent: [Pd]
Agent: CS(=O)(=O)O
Solvent: CN(C)C=O
Product: Cc1cc(C(=O)Oc2ccc3cc(C(=N)N)ccc3c2)ccc1N

Procedure:
To 25 ml of DMF (anhydrous), were added 2.2 g of 6-amidino-2-naphthyl 3-methyl-4-nitrobenzoate methanesulfonate, 0.63 g of methanesulfonic acid, and 0.23 g of 10% Pd-C. Into the mixture, while being vigorously stirred, was introduced hydrogen. After removal of Pd-C by filtration, the reaction mixture was mixed with ethyl ether to separate an oily substance which was washed with ether and recrystallized from an ethanol-ethyl ether mixture to obtain 2.8 g of a white to pale brown powder of 6-amidino-2-naphthyl 4-amino-3-methylbenzoate dimethanesulfonate.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][C:24]3[N:25]=[C:26]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[O:27][C:28]=3[CH3:29])=[CH:18][CH:17]=2)=[C:7]([CH2:9][C:10]([O:12]C)=[O:11])[CH:8]=1.O1CCCC1.[OH-].[Na+].Cl>O.CO>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][C:24]3[N:25]=[C:26]([C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=4)[O:27][C:28]=3[CH3:29])=[CH:18][CH:17]=2)=[C:7]([CH2:9][C:10]([OH:12])=[O:11])[CH:8]=1
Reactant: COC(=O)Cc1cc(OC)ccc1OCc1ccc(OCc2nc(-c3ccccc3)oc2C)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: COc1ccc(OCc2ccc(OCc3nc(-c4ccccc4)oc3C)cc2)c(CC(=O)O)c1
Temperature: 50 °C
Reaction time: 15 h
Yield: 94.6 %

Procedure:
To a mixture of methyl 2-[5-methoxy-2-[-4-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]benzyloxy]phenyl]acetate (0.98 g), tetrahydrofuran (4 mL) and methanol (4 mL) was added a 1N aqueous sodium hydroxide solution (4.2 mL) and the mixture was stirred at 50° C. for 15 hrs. 1N Hydrochloric acid (4.2 mL) and water were added to the reaction mixture, and the precipitated solid was collected by filtration and dried with air to give crystals (0.90 g, 94%) of 2-[5-methoxy-2-[4-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]benzyloxy]phenyl]acetic acid. Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 134-136° C.
Reaction SMILES: [C:1]([C@@H:5]1[CH2:10][CH2:9][C@H:8]([OH:11])[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[CH3:12][O:13][C:14]([C:16]1[CH:25]=[CH:24][C:23]2[C:18](=[CH:19][CH:20]=[C:21](O)[CH:22]=2)[CH:17]=1)=[O:15].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(C)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[C:1]([C@H:5]1[CH2:6][CH2:7][C@H:8]([O:11][C:21]2[CH:22]=[C:23]3[C:18](=[CH:19][CH:20]=2)[CH:17]=[C:16]([C:14]([O:13][CH3:12])=[O:15])[CH:25]=[CH:24]3)[CH2:9][CH2:10]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)[C@H]1CC[C@@H](O)CC1
Reactant: COC(=O)c1ccc2cc(O)ccc2c1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: COC(=O)c1ccc2cc(O[C@H]3CC[C@H](C(C)(C)C)CC3)ccc2c1

Procedure:
A mixture of cis-4-tert-butylcyclohexanol (927 mg, 0.00593 mol), 6-hydroxy-naphthalene-2-carboxylic acid methyl ester (1.00 g, 0.00494 mol) and triphenylphosphine (1560 mg, 0.00593 mol) in toluene (10 mL, 0.1 mol) was heated to reflux, and diisopropyl azodicarboxylate (1.17 mL, 0.00593 mol) was added dropwise and was stirred and refluxed for 6 hours. The mixture was taken up into dichloromethane and was purified via column chromatography with ethyl acetate:hexane (0:100 to 40:60) to give methyl 6-(trans-4-tert-butylcyclohexyloxy)-2-naphthoate as a white solid (0.95 g, 56%). 1H NMR (400 MHz, CDCl3) δ 8.52 (s, 1H), 8.01 (dd, J=8.7, 1.7 Hz, 1H), 7.84 (d, J=9.6 Hz, 1H), 7.73 (d, J=8.7 Hz, 1H), 7.17 (m, 2H), 4.34 (m, 1H), 3.97 (s, 3H), 2.30 (m, 2H), 1.92 (m, 2H), 1.52-1.14 (m, 5H), 0.91 (s, 9H).
Reaction SMILES: C(N(C(C)C)CC)(C)C.[NH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH2:23][CH:24]([NH:26][CH2:27][C@@H:28]([C:30]2[CH:31]=[C:32]([OH:36])[CH:33]=[CH:34][CH:35]=2)[OH:29])[CH3:25])=[CH:17][CH:16]=1.I.[NH2:38][C:39]1[C:40]([C:47]([NH:49][C:50](=[NH:53])SC)=[O:48])=[N:41][C:42]([Cl:46])=[C:43]([NH2:45])[N:44]=1>C(O)C>[NH2:38][C:39]1[C:40]([C:47]([NH:49][C:50](=[NH:53])[NH:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]2[CH:16]=[CH:17][C:18]([CH2:21][CH2:22][CH2:23][CH:24]([NH:26][CH2:27][C@H:28]([OH:29])[C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([OH:36])[CH:31]=3)[CH3:25])=[CH:19][CH:20]=2)=[O:48])=[N:41][C:42]([Cl:46])=[C:43]([NH2:45])[N:44]=1
Reactant: CC(CCCc1ccc(CCCCN)cc1)NC[C@H](O)c1cccc(O)c1
Reactant: CSC(=N)NC(=O)c1nc(Cl)c(N)nc1N
Agent: I
Solvent: CCO
Solvent: CCN(C(C)C)C(C)C
Product: CC(CCCc1ccc(CCCCNC(=N)NC(=O)c2nc(Cl)c(N)nc2N)cc1)NC[C@H](O)c1cccc(O)c1
Temperature: 75 °C
Reaction time: 4.5 h
Yield: 30.4 %

Procedure:
Diisopropylethylamine (0.45 mL, 2.58 mmol) was added to a mixture of amino alcohol 142 (0.63 g, 1.69 mmol) and 1-(3,5-diamino-6-chloropyrazine-2-carbonyl)-2-methylisothiourea hydriodide (0.66 g, 2.58 mmol) in absolute ethanol (10 mL). The mixture was stirred at 75° C. (oil bath) for 4.5 h. After this time the mixture was cooled to rt and the solvent was removed by rotary evaporation. Purification by column chromatography (silica gel, a gradient of 5:95 to 10:90 methanol/dichloromethane, followed by a gradient of 5:95 to 10:90 (10% concentrated aqueous ammonium hydroxide/methanol)/dichloromethane) and subsequent drying in a 40° C. vacuum oven for 88 h afforded the phenol derivative 143 (0.30 g, 30% yield) as a yellow solid: mp 82-86° C.; 1H NMR (500 MHz, DMSO-d6) δ 0.93 (dd, 3H, J=6.0, 3.5 Hz), 1.21-1.28 (m, 1H), 1.32-1.40 (m, 1H), 1.49-1.60 (m, 6H), 1.75 (s, 1H), 2.49-2.66 (m, 5H), 3.11-3.19 (m, 2H), 4.44-4.48 (m, 1H), 5.17 (br s, 1H), 6.59-6.72 (m, 6H), 7.06-7.11 (m, 5H), 9.09 (br s, 1H); m/z (ESI) 583 [C29H39ClN8O3+H]+.
Reaction SMILES: [H-].[Na+].[N+:3]([C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[CH:8]=[CH:9][NH:10]2)([O-:5])=[O:4].[Cl:15][CH2:16][CH2:17]OS(C1C=CC(C)=CC=1)(=O)=O>O1CCCC1>[Cl:15][CH2:16][CH2:17][N:10]1[C:11]2[C:7](=[C:6]([N+:3]([O-:5])=[O:4])[CH:14]=[CH:13][CH:12]=2)[CH:8]=[CH:9]1
Reactant: Cc1ccc(S(=O)(=O)OCCCl)cc1
Reactant: O=[N+]([O-])c1cccc2[nH]ccc12
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=[N+]([O-])c1cccc2c1ccn2CCCl
Yield: 31.6 %

Procedure:
Into a flask of 500 ml capacity fitted with a stirrer and cooling tube, there were introduced 7.2 g (corresponding to 0.21 mol) of an NaH oil dispersion, and 50 ml of tetrahydrofuran. The mixture was stirred on an ice-water bath. To this mixture was added, dropwise, little by little, a solution of 34.02 g of 4-nitroindole (0.21 mol) dissolved in 100 ml of tetrahydrofuran. After completion of the dropwise addition, the ice-water bath was removed and the mixture was stirred for one hour at room temperature. Then, 49.29 g (0.21 mol) of 2-chloroethyl-p-toluenesulfonate were added, and was reacted for 10 hours while stirring, heating under reflux. After completion of the reaction, the insoluble material was removed by filtration, and concentration was performed under reduced pressure. Further, this reaction mixture was purified by column chromatography using silica gel, to obtain 14.9 g of 1-(2-chloroethyl)-4-nitroindole.
Reaction SMILES: P(Cl)(Cl)([Cl:3])=O.[N+:6]1([O-])[CH:11]=[CH:10][CH:9]=[C:8]2[CH2:12][CH2:13][CH:14]([C:15]([O:17][CH3:18])=[O:16])[C:7]=12.O>CN(C=O)C.C(Cl)(Cl)Cl>[Cl:3][C:11]1[N:6]=[C:7]2[CH:14]([C:15]([O:17][CH3:18])=[O:16])[CH2:13][CH2:12][C:8]2=[CH:9][CH:10]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: COC(=O)C1CCc2ccc[n+]([O-])c21
Solvent: ClC(Cl)Cl
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)C1CCc2ccc(Cl)nc21
Temperature: 25 °C
Yield: 62.2 %

Procedure:
To a cooled (0° C.) solution of 0.21 mL (2.28 mmol) of phosphorous oxychloride in 0.2 mL of anhydrous DMF was added a solution of 1.1 g (5.69 mmol) of methyl 6,7-dihydro-5H-cyclopenta[b]pyridine-7-carboxylate 1-oxide from Step B above in 15 mL chloroform dropwise over 10 min. The resulting solution was allowed to warm to ambient temperature and then refluxed for 4 h. The mixture was cooled and poured into 30 mL of cold water. The aqueous solution was extracted with diethyl ether (3×30 mL) followed by a single extraction with 30 mL of dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and evaporated in vacuo. The resulting brown residue was purified by silica gel chromatography eluting with 50% ethyl acetate in hexane to afford the title compound as a light brown solid (0.30 g, 25%). LC-MS: m/z (E/S) 212.0 (MH)+.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=[CH:11][CH:12]=[O:13])=[CH:2]1.[CH2:14]([CH:16]1[O:18][CH2:17]1)Br.[OH-].[K+].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O>[OH:18][CH2:17][CH2:16][CH2:14][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=[CH:11][CH:12]=[O:13])=[CH:2]1
Reactant: BrCC1CO1
Reactant: O=CC=Cc1c[nH]c2ccccc12
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=CC=Cc1cn(CCCO)c2ccccc12
Temperature: 25 °C
Reaction time: 2 h

Procedure:
In a 10 mL Pyrex-glass vessel is mixed 3-(1H-indol-3-yl)acrylaldehyde (171 mg, 1 mmol), epibromohydrin (137 mg, 1 mmol), KOH (224 mg, 4 mmol) and anhydrous K2CO3 (553 mg, 4 mmol) in 1 mL DMF. This mixture is subjected to microwave irradiation at 350 W in successive 30 s periods, with 30 s periods at room temperature between each irradiation to avoid overheating the reaction. After the reaction has reached completion as monitored by TLC (5:1-hexanes:EtOAc) the reaction mixture is allowed to cool to room temperature and then is quenched by the addition of 10 mL 1M NaOH under vigorous stirring. The mixture is stirred for an additional 2 hrs, whereupon it is poured into 50 mL of ice-cold water. The precipitated solids are removed by filtration and washed 3×25 mL with water. The resulting solids are dried under vacuum and then recrystallized from ethanol to afford colorless crystals.
Reaction SMILES: Cl[C:2]1[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[N:10][C:9]2[C:4](=[CH:5][C:6]([Cl:19])=[C:7]([Cl:18])[CH:8]=2)[N:3]=1.Cl.Cl.[C:22]1([CH:28]([NH2:38])[CH2:29][CH2:30][CH2:31][N:32]2[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(N(CC)CC)C>C1(C)C=CC=CC=1>[Cl:18][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][C:6]=1[Cl:19])[N:3]=[C:2]([NH:38][CH:28]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:29][CH2:30][CH2:31][N:32]1[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37]1)[C:11]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1)=[N:10]2
Reactant: Clc1cc2nc(Cl)c(-c3ccccn3)nc2cc1Cl
Reactant: NC(CCCN1CCCCC1)c1ccccc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: Clc1cc2nc(NC(CCCN3CCCCC3)c3ccccc3)c(-c3ccccn3)nc2cc1Cl
Yield: 63.3 %

Procedure:
To a solution 2,6,7-trichloro-3-pyridin-2-yl-quinoxaline (0.31 g) and alpha-phenyl-1-piperdine-butylamine dihydrochloride (0.31 g) in toluene (25 mL) was added triethylamine (0.50 mL). The resulting mixture was refluxed under nitrogen atmosphere for 36 hours. After refluxing, the reaction mixture was cooled, filtered, and concentrated under vacuum. The residue was purified by flash chromatography (silica gel, 1:9 methanol/dichloromethane) to give a yellow solid. Recrystallization from methanol and water gave the product as a fluffy yellow powder (0.32 g); mp 125-127° C.
Reaction SMILES: C[O:2][C:3]1[C:8]([O:9]C)=[C:7]([O:11]C)[CH:6]=[CH:5][C:4]=1[CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][N:18]([C:21]([S:23][CH3:24])=[S:22])[CH2:17][CH2:16]1.O.C(=O)([O-])O.[Na+]>ClCCl.B(Br)(Br)Br>[OH:2][C:3]1[C:8]([OH:9])=[C:7]([OH:11])[CH:6]=[CH:5][C:4]=1[CH2:13][CH2:14][N:15]1[CH2:16][CH2:17][N:18]([C:21]([S:23][CH3:24])=[S:22])[CH2:19][CH2:20]1
Reactant: COc1ccc(CCN2CCN(C(=S)SC)CC2)c(OC)c1OC
Agent: BrB(Br)Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: CSC(=S)N1CCN(CCc2ccc(O)c(O)c2O)CC1
Reaction time: 8 h
Yield: 31.7 %

Procedure:
In 14 ml of dry dichloromethane was dissolved 1 ml of boron tribromide. 9.3 ml of the resulting solution containing 665 mmol. of boron tribromide was chilled to -50° C. in a nitrogen atmosphere. To the chilled solution was dropwise added a solution of 0.73 g of methyl 4-{2-(2,3,4-trimethoxyphenyl)ethyl}-1-piperazinecarbodithioate in 25 ml of dry dichloromethane for 15 min. The resulting mixture was left to reach room temperature, and then stirred overnight. To the mixture was added 3 ml of water, and further added a saturated aqueous sodium hydrogen carbonate solution until the mixture had pH 8. The mixture was then extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and placed under reduced pressure to distill off the solvent, yielding 205 mg of the desired compound as a grayish powder, m.p. 156°-158° C. (decomp.), yield 31.5%.
Reaction SMILES: [C:1]([NH:4][C@H:5]1[C@@H:14]([O:15]C(=O)C)[C@H:13]([O:19]C(=O)C)[C@@H:12]([CH2:23][N:24]=[N+:25]=[N-:26])[O:11][C@@H:6]1[O:7][CH2:8][CH:9]=[CH2:10])(=[O:3])[CH3:2]>CO>[C:1]([NH:4][C@H:5]1[C@@H:14]([OH:15])[C@H:13]([OH:19])[C@@H:12]([CH2:23][N:24]=[N+:25]=[N-:26])[O:11][C@@H:6]1[O:7][CH2:8][CH:9]=[CH2:10])(=[O:3])[CH3:2]
Reactant: C=CCO[C@H]1O[C@H](CN=[N+]=[N-])[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H]1NC(C)=O
Solvent: CO
Product: C=CCO[C@H]1O[C@H](CN=[N+]=[N-])[C@@H](O)[C@H](O)[C@@H]1NC(C)=O
Yield: 99 %

Procedure:
Allyl 2-acetamido-3,4-di-O-acetyl-6-azido-2,6-dideoxy-α-D-mannopyranoside, prepared as described above, (0.5 mg) was dissolved in 10 mL methanol containing 0.2 M MeONa. After five minutes Dowex 50 cation exchange resin was added to the mixture to neutralize. The resin was filtered and the filtrate was concentrated to yield allyl 2-acetamido-6-azido-2,6-dideoxy-α-D-mannopyranoside (99 percent).
Reaction SMILES: [CH2:1]([OH:12])[C@H:2]([C@H:4]([C@@H:6]([C@@H:8]([CH2:10][OH:11])[OH:9])[OH:7])[OH:5])[OH:3].[CH3:13][C:14]([CH3:16])=O>>[CH3:13][C:14]1([CH3:16])[O:9][CH:8]([CH:6]2[O:7][C:2]([CH3:4])([CH3:1])[O:5][CH:4]2[CH:2]2[O:3][C:8]([CH3:10])([CH3:6])[O:12][CH2:1]2)[CH2:10][O:11]1
Reactant: OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Reactant: CC(C)=O
Product: CC1(C)OCC(C2OC(C)(C)OC2C2COC(C)(C)O2)O1

Procedure:
1,2:3,4:5,6-Tri-o-isopropylidene-d-mannitol is prepared by rapidly stirring with a mechanical stirrer, of 40 g of mannitol and 500 ml of anhydrous acetone in the presence of 4.0 ml of concentrated (18M) sulfuric acid as a catalyst for 24 hours in a 2 liter flask. The sulfuric acid is neutralized with about 6.8 g anhydrous sodium carbonate and the acetone is evaporated by vacuum distillation at about 30° C. The remaining yellowish oil is diluted with an equal volume of cold water in order to provide the crystalline product. The crystals are filtered, dried, and used without further purification.
Reaction SMILES: COC(C1CC(=O)[N:7](C2C=CC(O)=CC=2)[CH2:6]1)=O.COC1C=CC=CC=1CBr.C[O:29][C:30]([CH:32]1[CH2:36][C:35](=[O:37])[N:34]([C:38]2[CH:43]=[CH:42][C:41]([O:44][CH2:45][C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=3[O:52][CH3:53])=[CH:40][CH:39]=2)[CH2:33]1)=O>C(O)C>[CH3:6][NH2:7].[CH3:6][NH:7][C:30]([CH:32]1[CH2:36][C:35](=[O:37])[N:34]([C:38]2[CH:43]=[CH:42][C:41]([O:44][CH2:45][C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=3[O:52][CH3:53])=[CH:40][CH:39]=2)[CH2:33]1)=[O:29]
Reactant: COC(=O)C1CC(=O)N(c2ccc(OCc3ccccc3OC)cc2)C1
Reactant: COC(=O)C1CC(=O)N(c2ccc(O)cc2)C1
Agent: COc1ccccc1CBr
Solvent: CCO
Product: CN
Product: CNC(=O)C1CC(=O)N(c2ccc(OCc3ccccc3OC)cc2)C1

Procedure:
The title compound is prepared by alkylation of the (RS)-1-(4-hydroxyphenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester with 2-methoxybenzylbromide giving the (RS)-1-[4-(2-methoxy-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methyl ester as a light yellow oil [83% of theory, MS:m/e=355 (M+H)+ which, thereupon, by treatment with methylamine in ethanol at 80° C. yields the (RS)-1-[4-(2-methoxybenzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methylamide. Yield: 47% of theory as a white solid. MS: m/e=355 (M+H)+.
Reaction SMILES: [CH3:1][N:2]([CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[NH2:3].C([O:21][C@@H:22]1[C@H:26]([O:27]C(=O)C2C=CC=CC=2)[C@@H:25]([CH2:36][O:37]C(=O)C2C=CC=CC=2)[O:24][C@H:23]1[N:46]1[CH:54]=[N:53][C:52]2[C:47]1=[N:48][C:49]([Cl:56])=[N:50][C:51]=2Cl)(=O)C1C=CC=CC=1.C(N(CC)CC)C.N>O1CCOCC1>[Cl:56][C:49]1[N:50]=[C:51]([NH:3][N:2]([CH3:1])[CH2:4][CH2:5][O:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:52]2[N:53]=[CH:54][N:46]([C:47]=2[N:48]=1)[C@@H:23]1[O:24][C@H:25]([CH2:36][OH:37])[C@@H:26]([OH:27])[C@H:22]1[OH:21]
Reactant: CN(N)CCOc1ccccc1
Reactant: O=C(OC[C@H]1O[C@@H](n2cnc3c(Cl)nc(Cl)nc32)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1)c1ccccc1
Agent: N
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: CN(CCOc1ccccc1)Nc1nc(Cl)nc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Yield: 47 %

Procedure:
The title compound was prepared according to method A by reacting 1-methyl-1-(2-phenoxyethyl)hydrazine (prepared by the general method described in example 1) (0.80 g, 4 mmol) and 9-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (2.53 g, 4 mmol) and triethylamine (1.11 ml, 8 mmol) in dioxan (25 ml), followed by debenzoylation of the purified product using methanolic ammonia to provide the title 2-chloro-N-(N-methyl-N-(2-phenoxyethyl)amino)adenosine (0.84 g, 47%) (after column chromatography) obtained as a solid, mp 166°-8° C., 1H NMR (DMSO-d6)γ 2.70 (3H, s, --CH3), 3.22 (2H, br t, --CH2 --), 3.51-3.58 (1H, m, H-5'a), 3.62-3.69 (1H, m, H-5'a), 3.95 (1H, q, H-4'), 4.05-4.15 (3H, m, --CH2 -- and H-3' ), 4.50 (1H, q, H-2'), 5.06 (1H, t, 5'-OH), 5.21, 5.49 (2H, 2d, 2'- and 3--OH), 5.81 (1H, H-1'), 6.79-7.25 (5H, m, Ar-H), 8.41 (1H, s, H-8), 9.41 (1H, br s, N-H).
Reaction SMILES: C(OC([N:8]1[C@@H:12]([CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:30])[C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=3)=[CH:17][CH:16]=2)[CH2:11][O:10]C1(C)C)=O)(C)(C)C.O.FC(F)(F)C(O)=O.[OH-].[Na+]>C(#N)C>[NH2:8][C@H:12]([CH2:11][OH:10])[CH2:13][CH2:14][C:15]1[CH:16]=[CH:17][C:18]([NH:21][C:22](=[O:30])[C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)=[CH:19][CH:20]=1
Reactant: CC(C)(C)OC(=O)N1[C@@H](CCc2ccc(NC(=O)c3ccc(Cl)cc3)cc2)COC1(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Solvent: CC#N
Solvent: O
Product: N[C@H](CO)CCc1ccc(NC(=O)c2ccc(Cl)cc2)cc1
Temperature: 80 °C
Yield: 83.8 %

Procedure:
To a solution of (S)-4-{2-[4-(4-chloro-benzoylamino)-phenyl]-ethyl}-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (438 mg) in acetonitrile (5 ml) were added water (4 ml) and trifluoroacetic acid (0.29 ml). The mixture was heated at 80° C. for 4.5 h. The mixture was then cooled to room temperature and poured into 1 M aq. NaOH and extracted twice with EtOAc/THF. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to afford N-[4-((S)-3-amino-4-hydroxy-butyl)-phenyl]-4-chloro-benzamide (255 mg, 84%) a white solid. MS (ISP): 321.2 ([{37Cl}M+H]+), 319.2 ([{35Cl}M+H]).