Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OP([CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])(OCC)=O)C.[C:17]([C:19]1[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][CH:20]=1)#[N:18]>C1COCC1.CC(OC)(C)C.[NH4+].[Cl-]>[C:17]([C:19]1[CH:26]=[CH:25][C:22](/[CH:23]=[CH:9]/[C:10]([O:12][C:13]([CH3:14])([CH3:15])[CH3:16])=[O:11])=[CH:21][CH:20]=1)#[N:18]
Reactant: N#Cc1ccc(C=O)cc1
Reactant: CCOP(=O)(CC(=O)OC(C)(C)C)OCC
Agent: [Cl-]
Agent: [NH4+]
Solvent: COC(C)(C)C
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)/C=C/c1ccc(C#N)cc1
Temperature: 25 °C
Yield: 100 %

Procedure:
A flame dried three-neck flask equipped with a thermometer, an addition funnel and a N2 inlet was charged with NaH (3.96 g, 1.1 eqs) and anhydrous THF (120 mL). With moderate stirring at RT, a suspension was formed. To this suspension was added a solution of t-butyl diethylphosphonoacetate (23.2 mL 1.1 eq.) dissolved in anhydrous THF (20 mL), dropwise via the addition funnel over a period of 30 min. The suspension turned into a clear, light yellow colored solution. An exotherm from 25° C. to 35° C. was observed during the addition. After completion of the addition, the resulting mixture was stirred at RT for another 30 min. A solution of 4-cyanobenzaldehyde (11.3 g, 86.1 mmol, 1.0 eq) dissolved in anhydrous THF (20 mL) was added to the reaction mixture dropwise via the addition funnel over a period of 30 min. An exotherm from 25° C. to 35° C. was observed. The resulting mixture was stirred at RT for 1 h. Progress of the reaction was monitored by 1H NMR. Upon completion, the reaction mixture was diluted with MTBE (200 mL) and sat. NH4Cl solution (150 mL). The organic layer was separated and washed, sequentially, with 25 mL of H2O and 25 mL of sat. NH4Cl solution. After drying over MgSO4, the organic phase was evaporated to dryness to give 20.0 g 21A as a white solid (100% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.56 (s, 9H) 6.47 (d, 1H) 7.53-7.64 (m, 3H) 7.68 (d, 2H)
Reaction SMILES: [CH2:1]1[C@@H:6](O)[C@@H:5]([OH:8])[C@H:4]([OH:9])[CH2:3][C@@:2]1([C:11]([OH:13])=[O:12])[OH:10].[CH:14](=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[OH:10][C@@:2]12[CH2:1][C@@H:6]([O:13][C:11]1=[O:12])[C@H:5]1[C@H:4]([O:9][CH:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[O:8]1)[CH2:3]2
Reactant: O=C(O)[C@]1(O)C[C@@H](O)[C@@H](O)[C@H](O)C1
Reactant: O=Cc1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: O=C1O[C@@H]2C[C@@]1(O)C[C@H]1OC(c3ccccc3)O[C@@H]21
Temperature: -20 °C
Yield: 39.6 %

Procedure:
The procedure in J. Org. Chem. 1995, 50, 888-890 was followed. Briefly, a solution of quinic acid (20.0 g, 0.104 mol), benzaldehyde (16.6 g, 156 mmol) and para-toluenesulfonic acid monohydrate (1.0 g, 5.26 mmol) in toluene (350 mL) was refluxed for 10 hours in a flask equipped with a Dean-Stark trap. The reaction mixture was cooled, washed with saturated NaHCO3 solution and brine, dried (MgSO4). Filtered and concentrated. The concentrate was dissolved in 1:1 hexanes/ethyl acetate (100 mL) and cooled to −20° C. for 2 hours to provide 10.8 g (40%) of the desired product.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:16])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1.[H-].[Na+].[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>O1CCCC1.CN1CCCN(C)C1=O>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]([O:16][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[CH:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1
Reactant: O=C(Cn1cncn1)c1ccc(Cl)cc1Cl
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CN1CCCN(C)C1=O
Product: Clc1ccc(C(=Cn2cncn2)OCc2ccccc2)c(Cl)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 7.2 %

Procedure:
670 mg (2.62 mmol) of 1-(2,4-dichlorophenyl)-2-[1,2,4]triazol-1-yl-ethanone in 12 ml of tetrahydrofuran and 4 ml of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone were added to a suspension of 171 mg (3.92 mmol) of sodium hydride (55% in mineral oil) in 15 ml of tetrahydrofuran and 5 ml of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU) and stirred at room temperature for 3 hours. Thereafter, 396 mg (5.24 mmol) of benzyl bromide were added and the mixture was stirred at room temperature for a further 16 hours. The tetrahydrofuran was removed under a vacuum, the residue was added to 50 ml of water and extracted three times with 50 ml of diethyl ether each time. The combined organic phases were dried over magnesium sulphate and the diethyl ether was removed in a vacuum. The crude product was purified by column chromatography on silica gel (diethyl ether/pentane 1:4). In addition to mixed fractions with the C-alkylation product there were obtained 65 mg (7%) of pure 1-[2-(2,4-dichloro-phenyl)-2-benzyloxy-vinyl]-1H-[1,2,4]triazole as a colourless oil. [M+H]+=345, 347.
Reaction SMILES: [C:1]1([N:7]2[C:11](=[O:12])[CH2:10][C:9]([NH:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:20](OCC)(=[O:25])[CH2:21][C:22]([CH3:24])=O.C(O)(=O)C>O>[C:1]1([N:7]2[C:11](=[O:12])[C:10]3[C:22]([CH3:24])=[CH:21][C:20](=[O:25])[N:13]([C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:9]=3[NH:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCOC(=O)CC(C)=O
Reactant: O=C1CC(Nc2ccccc2)=NN1c1ccccc1
Solvent: O
Solvent: CC(=O)O
Product: Cc1cc(=O)n(-c2ccccc2)c2[nH]n(-c3ccccc3)c(=O)c12
Yield: 34.5 %

Procedure:
A mixture of 25 g of 1-phenyl-3-anilino-2-pyrazolin-5-one, 18 g of ethyl acetoacetate, and 150 ml of acetic acid was heat-refluxed for 6 hours. The reaction mixture was diluted with water, and the formed solid was crystallized from acetonitrile to obtain 10.9 g of 2,7-diphenyl-4-methylpyrazolo[3,4-b]pyridine-3,6-dione having a melting point of 145° to 147° C.
Reaction SMILES: [OH:1][C:2]1[CH:16]=[C:15]([OH:17])[CH:14]=[CH:13][C:3]=1[C:4]([O:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])=[O:5].[C:18]1(=[O:24])[O:23][C:21](=[O:22])[CH2:20][CH2:19]1>C(Cl)Cl>[C:21]([CH2:20][CH2:19][C:18]([O:17][C:15]1[CH:14]=[CH:13][C:3]([C:4]([O:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])=[O:5])=[C:2]([OH:1])[CH:16]=1)=[O:24])([OH:23])=[O:22]
Reactant: CCCCCCOC(=O)c1ccc(O)cc1O
Reactant: O=C1CCC(=O)O1
Solvent: ClCCl
Product: CCCCCCOC(=O)c1ccc(OC(=O)CCC(=O)O)cc1O
Reaction time: 8 h

Procedure:
n-Hexyl 2,4-dihydroxybenzoate (2 g) is dissolved in 25 mL of methylene chloride. To the solution, 0.85 g of succinic anhydride and 1.05 g of 4-N,N-dimethylpyridene are added. The reaction mixture is allowed to stir at ambient conditions overnight. The reaction mixture is extracted with 1 N HCl, water and saturated sodium chloride solution. The organic layer is dried over anhydrous sodium sulfate. Solvent is removed under reduced pressure to yield the product as an off-white powder.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.[CH3:7][C:8]([CH3:26])([C:12]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[C:14]([C:22]([F:25])([F:24])[F:23])[CH:13]=1)[C:9](O)=[O:10].Cl.[O:28]=[C:29]1[CH2:34][CH2:33][C:32]([NH2:41])([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:31][CH2:30]1.N1C=CC=CC=1.Cl>CN(C)C=O.ClCCl>[CH3:7][C:8]([CH3:26])([C:12]1[CH:17]=[C:16]([C:18]([F:19])([F:21])[F:20])[CH:15]=[C:14]([C:22]([F:24])([F:25])[F:23])[CH:13]=1)[C:9]([NH:41][C:32]1([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:31][CH2:30][C:29](=[O:28])[CH2:34][CH2:33]1)=[O:10]
Reactant: CC(C)(C(=O)O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: NC1(c2ccccc2)CCC(=O)CC1
Agent: Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(C)(C(=O)NC1(c2ccccc2)CCC(=O)CC1)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 41.4 %

Procedure:
Oxalyl chloride (5.8 mL, 66.6 mmol) was added slowly to a solution of α,α-dimethyl-3,5-bis(trifluoromethyl)benzeneacetic acid (Description 6, 10 g, 33.3 mmol) and dimethylformamide (1 drop) in dichloromethane (100 mL) and. the mixture was stirred at room temperature for 24 hours. The solvent was evaporated under reduced pressure and the residue was dissolved in dichloromethane (20 mL) and added slowly to a solution of 4-oxo-1-phenylcyclohexylamine hydrochloride (Description 18, 8.2 g, 43.4 mmol) and pyridine (5.7 mL, 66.3 mmol) in dichloromethane (100 mL). The mixture was stirred at room temperature for 24 hours, then hydrochloric acid (2M, 100 mL) was added. The layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatograph on silica gel, eluting with isohexane:EtOAc (75:25), to give the title compound as a colorless solid (6.5 g, 41%). 1H NMR (400 MHz, CDCl3) δ 7.83 (1H, s), 7.77 (2H, s), 7.35–7.26 (5H, m), 5.44 (1H, s), 2.70–2.66 (2H, m), 2.40–2.30 (6H, m), and 1.62 (6H, s).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11][C:12]2[C:20]([S:21](=[O:24])(=[O:23])[NH2:22])=[CH:19][C:15]([C:16]([OH:18])=[O:17])=[CH:14][C:13]=2[NH2:25])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[CH:26](=O)[C:27]1[O:31][CH:30]=[CH:29][CH:28]=1>COCCOCCOC>[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11][C:12]2[C:20]([S:21](=[O:24])(=[O:23])[NH2:22])=[CH:19][C:15]([C:16]([OH:18])=[O:17])=[CH:14][C:13]=2[NH:25][CH2:26][C:27]2[O:31][CH:30]=[CH:29][CH:28]=2)=[CH:7][CH:6]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Nc1ccc(Sc2c(N)cc(C(=O)O)cc2S(N)(=O)=O)cc1
Reactant: O=Cc1ccco1
Solvent: COCCOCCOC
Product: CC(=O)Nc1ccc(Sc2c(NCc3ccco3)cc(C(=O)O)cc2S(N)(=O)=O)cc1

Procedure:
The starting material is prepared as follows: The mixture of 2 g of 4-(4-acetamidophenylmercapto)-3-amino-5-sulfamoylbenzoic acid, 1 g of furfural and 20 ml of diethyleneglycol dimethyl ether is heated to 105° for 22 hours while stirring under nitrogen. It is evaporated under reduced pressure, the residue taken up in 75 ml of ethanol and 1 g of sodium borohydride is added portionwise while stirring at room temperature under nitrogen. After stirring overnight, 75 ml of water are added and the mixture is filtered. The filtrate is concentrated under reduced pressure, the concentrate acidified with concentrated hydrochloric acid and the precipitate formed filtered off, to yield the 4-(4-acetamidopheylmercapto)-3-furfurylamino-5-sulfamoylbenzoic acid.
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:8][C:9]([F:14])([F:13])[C:10]([OH:12])=[O:11].FC(F)(F)C(O)=O.[Cl:22][C:23]1[CH:24]=[N:25][C:26]2[NH:27][C:28]3[CH:29]=[N:30][CH:31]=[C:32]([CH:54]=3)[CH2:33][CH2:34][C:35]3[CH:43]=[C:39]([NH:40][C:41]=1[N:42]=2)[CH:38]=[CH:37][C:36]=3[NH:44][C:45](=[O:53])[CH2:46][CH:47]1[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1.[CH3:55][C:56]1[N:57]=[CH:58][S:59][C:60]=1[C:61](O)=[O:62]>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:8][C:9]([F:14])([F:13])[C:10]([OH:12])=[O:11].[Cl:22][C:23]1[CH:24]=[N:25][C:26]2[NH:27][C:28]3[CH:29]=[N:30][CH:31]=[C:32]([CH:54]=3)[CH2:33][CH2:34][C:35]3[CH:43]=[C:39]([NH:40][C:41]=1[N:42]=2)[CH:38]=[CH:37][C:36]=3[NH:44][C:45](=[O:53])[CH2:46][CH:47]1[CH2:52][CH2:51][N:50]([C:61]([C:60]2[S:59][CH:58]=[N:57][C:56]=2[CH3:55])=[O:62])[CH2:49][CH2:48]1
Reactant: O=C(CC1CCNCC1)Nc1ccc2cc1CCc1cncc(c1)Nc1ncc(Cl)c(n1)N2
Reactant: Cc1ncsc1C(=O)O
Solvent: O=C(O)C(F)(F)F
Product: Cc1ncsc1C(=O)N1CCC(CC(=O)Nc2ccc3cc2CCc2cncc(c2)Nc2ncc(Cl)c(n2)N3)CC1
Yield: 62 %

Procedure:
The desired compound was prepared according to the procedure of Example A27 using N-[6-chloro-2,4,8,18,22-pentaazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaen-12-yl]-2-piperidin-4-ylacetamide tris(trifluoroacetate) and 4-methyl-1,3-thiazole-5-carboxylic acid as starting materials in 62% yield. LCMS for C29H30ClN8O2S (M+H)+: m/z=589.2.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4](I)[CH:5]=[CH:6][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:28]([OH:31])[C:29]#[CH:30].C(N(C(C)C)CC)(C)C>[Cl-].[Na+].O.[Cu]I.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd].O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]([C:30]#[C:29][CH2:28][OH:31])[CH:5]=[CH:6][CH:7]=1
Reactant: Brc1cccc(I)c1
Reactant: C#CCO
Agent: [Cu]I
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: OCC#Cc1cccc(Br)c1
Temperature: 25 °C
Reaction time: 15 h

Procedure:
A mixture of 3-bromoiodobenzene (5.00 g), copper(I) iodide (67.4 mg), triphenylphosphine (232 mg), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (366 mg), propargyl alcohol (1.15 ml), diisopropylethylamine (12.3 ml) and tetrahydrofuran (90 ml) was stirred at room temperature for 15 hr. The reaction mixture was added to brine, and the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=98:2-70:30) to give the object product (3.42 g) as a brown oil.
Reaction SMILES: [O:1]=[C:2]1[N:8]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C@@H:18]([C:36](O)=[O:37])[CH2:19][C:20]3[CH:25]=[C:24]([CH3:26])[C:23]([O:27][CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[C:22]([CH3:35])[CH:21]=3)=[O:16])[CH2:11][CH2:10]2)[CH2:7][CH2:6][C:5]2[CH:39]=[CH:40][CH:41]=[CH:42][C:4]=2[NH:3]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C.[N:72]1([CH:78]2[CH2:83][CH2:82][N:81]([CH2:84][C:85]([O:87][CH2:88][CH3:89])=[O:86])[CH2:80][CH2:79]2)[CH2:77][CH2:76][NH:75][CH2:74][CH2:73]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[O:1]=[C:2]1[N:8]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C@H:18]([CH2:19][C:20]3[CH:21]=[C:22]([CH3:35])[C:23]([O:27][CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[C:24]([CH3:26])[CH:25]=3)[C:36]([N:75]3[CH2:76][CH2:77][N:72]([CH:78]4[CH2:83][CH2:82][N:81]([CH2:84][C:85]([O:87][CH2:88][CH3:89])=[O:86])[CH2:80][CH2:79]4)[CH2:73][CH2:74]3)=[O:37])=[O:16])[CH2:11][CH2:10]2)[CH2:7][CH2:6][C:5]2[CH:39]=[CH:40][CH:41]=[CH:42][C:4]=2[NH:3]1
Reactant: Cc1cc(C[C@@H](OC(=O)N2CCC(N3CCc4ccccc4NC3=O)CC2)C(=O)O)cc(C)c1OCc1ccccc1
Reactant: CCOC(=O)CN1CCC(N2CCNCC2)CC1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Agent: O=C([O-])[O-]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CCOC(=O)CN1CCC(N2CCN(C(=O)[C@@H](Cc3cc(C)c(OCc4ccccc4)c(C)c3)OC(=O)N3CCC(N4CCc5ccccc5NC4=O)CC3)CC2)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 2.80 g (4.90 mmol) (R)-2-(4-benzyloxy-3,5-dimethyl-phenyl)-1-carboxy-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate (Example 1g), 1.80 g (5.61 mmol) TBTU and 3.10 mL (22.08 mmol) triethylamine in 30 mL DMF was stirred for 1 h at RT. Then 2.00 g (5.48 mmol) ethyl (4-piperazin-1-yl-piperidin-1-yl)-acetate were added. The reaction mixture was stirred for 1 h at RT, poured onto 150 mL 15% K2CO3 solution and extracted with 200 mL EtOAc. The organic phase was extracted with 150 mL of 10% citric acid solution, the aqueous phase was made alkaline with 15% K2CO3 solution and extracted with 200 mL EtOAc. The organic phase was concentrated by evaporation i.vac. and the residue was purified by chromatography (silica gel, EtOH).
Reaction SMILES: ClCCl.[O:4]1[CH2:8][CH2:7][O:6][CH:5]1[CH:9]([CH2:13][CH2:14][O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:10][CH:11]=[CH2:12].[OH-:23].[Na+].OO>CCCCCC.O.C(O)C>[O:4]1[CH2:8][CH2:7][O:6][CH:5]1[CH:9]([CH2:13][CH2:14][O:15][CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[CH2:10][CH2:11][CH2:12][OH:23]
Reactant: [OH-]
Reactant: C=CCC(CCOCc1ccccc1)C1OCCO1
Agent: OO
Agent: [Na+]
Solvent: ClCCl
Solvent: CCO
Solvent: CCCCCC
Product: OCCCC(CCOCc1ccccc1)C1OCCO1
Temperature: 25 °C
Reaction time: 3 h
Yield: 74.6 %

Procedure:
A 1 M solution of borane-methyl sulfide complex in dichloromethane (27 mL, 27 mmol) was added dropwise to a stirred solution of the olefin 14 (21 g, 80.36 mmol), prepared according to Example 12, in hexane (60 mL) at 0° C. The mixture was stirred for 3 h at room temperature, then cooled to 0° C., and then absolute ethanol (15 mL) was added dropwise, followed by 15% NaOH (15 mL) and 30% H2O2 (15 mL). The reaction mixture was heated at reflux for 1 h. cooled to room temperature, and poured into water (200 mL). The organic layer was separated, and the aqueous layer was extracted with ether (3×75 mL). The organic layers were combined, dried over MgSO4, and concentrated under reduced pressure. The crude product was chromatographed on a silica gel column, eluting with 2% methanol in ether, to give the alcohol 15 (16.8 g, 74.6%) as a viscous liquid. IR (KBr)νmax 3442, 3034, 2952, 2878, 1458, 1407, 1364, 1206, 1103, 846, 742, 698 cm−1; 1HNMR (CDCl3) δ 1.36-1.39 (m, 1 H), 1.53-1.64 (m, 4 H), 1.79-1.90 (m, 3 H), 3.53-3.59 (m, 4 H), 3.79-3.92 (m, 4 H), 4.49 (s, 2H), 4.78 (d, J=3.6 Hz, 1 H), 7.25-7.32 (m, 5 H); 13CNMR (CDCl3) δ 25.38, 29.23, 30.17, 38.19, 62.76, 64.78, 64.84, 68.52, 72.72, 106.49, 127.39, 127.56, 128.23, 138.54: mass spectrum (EI), m/z (rel intensity) 280 (M+.0.02), 235(2.1), 220 (14), 219 (84), 218 (69), 172 (15), 146 (23), 127 (15), 91 (35), 84 (9), 73 (10), 65 (5.5).
Reaction SMILES: C[O-].[Na+].[CH:4](=[O:12])[C:5]1[C:6](=[CH:8][CH:9]=[CH:10][CH:11]=1)[OH:7].[Cl:13][CH2:14]/[CH:15]=[CH:16]/[CH2:17]Cl.Cl>O.C1(C)C=CC=CC=1.C(O)C>[Cl:13][CH2:14]/[CH:15]=[CH:16]/[CH2:17][O:7][C:6]1[CH:8]=[CH:9][CH:10]=[CH:11][C:5]=1[CH:4]=[O:12]
Reactant: ClC/C=C/CCl
Reactant: O=Cc1ccccc1O
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: O
Product: O=Cc1ccccc1OC/C=C/CCl

Procedure:
To 130 lt of ethanol, 12.1 kg of sodium methoxide are added while cooling and stirring, followed by 26.5 kg of salicylaldehyde at 30°. Thereupon 33.3 kg of trans-1,4-dichloro-2-butene are added and the mixture heated to 68° for 4 hours. It is combined with 156 lt of toluene, 187 lt of water and 9.4 kg of 36% hydrochloric acid while keeping the temperature at about 30°. The precipitate formed is filtered off and washed with 16 lt of toluene. The filtrate is separated, the organic layer washed 3 times with 27 lt of water, evaporated, the residue distilled and the fraction boiling at 170°/0.2 mmHg collected, to yield the 2-(4-chloro-trans-2-butenyloxy)-benzaldehyde.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=1.CCCCCC.C([Li])CCC.[CH2:20]([N:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29]([CH2:37][C:38](OCC)=[O:39])([OH:36])[C:28]1=[O:43])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>O1CCCC1.O>[CH2:20]([N:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29]([OH:36])([CH2:37][C:38]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=2)=[O:39])[C:28]1=[O:43])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: Cc1ccc(N)cc1
Reactant: CCOC(=O)CC1(O)C(=O)N(Cc2ccccc2)c2ccccc21
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Solvent: CCCCCC
Product: Cc1ccc(NC(=O)CC2(O)C(=O)N(Cc3ccccc3)c3ccccc32)cc1
Reaction time: 0.17 h
Yield: 45.3 %

Procedure:
To a solution of 0.254 g of p-toluidine in 10 ml of dry tetrahydrofuran was added dropwise 1.3 ml of a 1.59M hexane solution of n-butyl lithium at −78° C. under a nitrogen atmosphere, followed by stirring at that temperature for 10 minutes. To the mixture was added a solution of 0.299 g of 1-benzyl-3-(ethoxycarbonylmethyl)-3-hydroxyindolin-2-one in 5 ml of dry tetrahydrofuran at −78° C., followed by stirring at that temperature for 30 minutes. Water was added to the reaction mixture, and the product was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/1) to give 0.161 g (44%) of the title compound.
Reaction SMILES: [CH:1]1([C:4](Cl)=[O:5])[CH2:3][CH2:2]1.C[O:8][C:9]([C:11]1[CH:12]=[C:13]([CH3:35])[C:14]2[O:20][C:19]3[C:21]([Cl:31])=[CH:22][C:23]([N:25]4[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]4)=[CH:24][C:18]=3[CH2:17][S:16](=[O:33])(=[O:32])[C:15]=2[CH:34]=1)=[O:10]>ClCCl.N1C=CC=CC=1>[Cl:31][C:21]1[C:19]2[O:20][C:14]3[C:13]([CH3:35])=[CH:12][C:11]([C:9]([OH:10])=[O:8])=[CH:34][C:15]=3[S:16](=[O:32])(=[O:33])[CH2:17][C:18]=2[CH:24]=[C:23]([N:25]2[CH2:26][CH2:27][N:28]([C:4]([CH:1]3[CH2:3][CH2:2]3)=[O:5])[CH2:29][CH2:30]2)[CH:22]=1
Reactant: COC(=O)c1cc(C)c2c(c1)S(=O)(=O)Cc1cc(N3CCNCC3)cc(Cl)c1O2
Reactant: O=C(Cl)C1CC1
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cc1cc(C(=O)O)cc2c1Oc1c(Cl)cc(N3CCN(C(=O)C4CC4)CC3)cc1CS2(=O)=O
Reaction time: 0.75 h

Procedure:
A solution of cyclopropyl carbonyl chloride (0.22 mL, 2.4 mmol) in dichloromethane (2 mL) was added to a suspension of Example 104k (0.35 g, 0.8 mmol) in pyridine (3 mL)/dichloromethane (1 mL) at 10° C. The reaction mixture was stirred for 45 min, concentrated, treated with chilled water and dilute HCl to pH 6. The precipitated solid was filtered and dried to obtain the title compound. Yield: 0.372 g, (91.5%); 1H NMR (DMSO-d6): δ 0.76 (m, 4H, 2CH2); 2.06 (m, 1H, CH); 2.68 (s, 3H, CH3); 3.24 (s, 2H, CH2); 3.32 (s, 2H, CH2); 3.64 (S, 2H, CH2); 3.84 (s, 2H, CH2); 5.15 (s, 2H, CH2); 7.12 (d, 1H, Ar); 7.2 (d, 1H, Ar); 8.1 (s, 1H, Ar); 8.2 (s, 1H, Ar); 8.38 (s, 1H, OH). MS: m/e (ES+) 532 (M+1).
Reaction SMILES: [NH2:1][C@@H:2]1[C@@H:6]([C:7]([OH:9])=[O:8])[O:5][C@@H:4]([N:10]2[CH:18]=[N:17][C:16]3[C:11]2=[N:12][CH:13]=[N:14][C:15]=3[NH:19][C:20](=[O:27])[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C@@H:3]1[OH:28].O=C1[O:34][C:33](=O)[CH:32]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[O:31]1.C(O)(=O)[C@@H](C1C=CC=CC=1)O>>[C:20]([NH:19][C:15]1[N:14]=[CH:13][N:12]=[C:11]2[C:16]=1[N:17]=[CH:18][N:10]2[C@@H:4]1[O:5][C@H:6]([C:7]([OH:9])=[O:8])[C@@H:2]([NH:1][C:33](=[O:34])[C@@H:32]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[OH:31])[C@H:3]1[OH:28])(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: O=C1OC(=O)C(c2ccccc2)O1
Reactant: N[C@H]1[C@@H](O)[C@H](n2cnc3c(NC(=O)c4ccccc4)ncnc32)O[C@@H]1C(=O)O
Agent: O=C(O)[C@H](O)c1ccccc1
Product: O=C(Nc1ncnc2c1ncn2[C@@H]1O[C@H](C(=O)O)[C@@H](NC(=O)[C@H](O)c2ccccc2)[C@H]1O)c1ccccc1
Yield: 74.1 %

Procedure:
1-(6-Benzoylamino-9H-purin-9-yl)-3-D-mandelylamino-1,3-dideoxy-β-D-ribofuranuronic acid (300 mg) was prepared by reacting 1-(6-benzoylamino-9H-purin-9-yl)-1,3-dideoxy-3-amino-β-D-ribofuranuronic acid (300 mg) prepared in Example 1 with 2,4-dioxo-5-phenyl-1,3-dioxolane (253 mg), prepared from D-mandelic acid, according to a similar manner to that of Example 5, mp. 223°-227° C. (dec.).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][CH2:17][CH2:18]O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(P(CCCC)CCCC)CCC.[NH:33]1[CH:37]=[N:36][CH:35]=[N:34]1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1.O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][CH2:17][CH2:18][N:33]2[CH:37]=[N:36][CH:35]=[N:34]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCCCCc1ccc(OCc2ccccc2)cc1
Reactant: c1nc[nH]n1
Agent: CCCCP(CCCC)CCCC
Agent: CCOC(=O)N=NC(=O)OCC
Solvent: O
Solvent: C1CCOC1
Product: c1ccc(COc2ccc(CCCCn3cncn3)cc2)cc1
Yield: 81 %

Procedure:
To a solution of 4-(4-benzyloxyphenyl)butanol (3.55 g), tributyl phosphine (6.84 g) and 1,2,4-triazole (1.86 g) in tetrahydrofuran (75 ml) was added dropwise, at room temperature, diethyl azodicarboxylate (40% toluene solution, 11.8 g). The mixture was heated for two hours under reflux. The reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4), and concentrated under reduced pressure. The residue was subjected to a silica gel column chromatography. From the fraction eluted with ethyl acetate-hexane (1:2, v/v), 1-[4-(4-benzyloxyphenyl)butyl]-1,2,4-triazole (3.45 g, 83%) was obtained. Recrystallization from isopropyl ether gave colorless prisms, mp 68-69° C.