Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[CH:3]=1)[OH:2].[C:9]([CH2:13][C:14](OCC)=[O:15])(=O)[CH2:10][CH3:11].FC(F)(F)C(O)=O.S(=O)(=O)(O)O>>[CH2:10]([C:9]1[C:8]2[C:1](=[CH:3][C:4]([OH:5])=[CH:6][CH:7]=2)[O:2][C:14](=[O:15])[CH:13]=1)[CH3:11]
Reactant: CCOC(=O)CC(=O)CC
Reactant: Oc1cccc(O)c1
Agent: O=S(=O)(O)O
Solvent: O=C(O)C(F)(F)F
Product: CCc1cc(=O)oc2cc(O)ccc12
Temperature: 25 °C
Reaction time: 3 h
Yield: 42.4 %

Procedure:
Resorcinol (1.21 g, 11.0 mmol) was dissolved in hot ethyl propionylacetate (1.52 g, 10.0 mmol). To this stirred mixture at ice-water temperature was added dropwise a mixture of trifluoroacetic acid (1.70 mL, 22.0 mmol) and concentrated sulphuric acid (2.2 mL, 22.0 mmol) at such a rate that the reaction temperature was kept below 10° C. (about 30 min). The reaction mixture was then allowed to warm to room temperature and thereupon stirred for an additional 3 h before being quenched cautiously with ice-water. After stirring the suspension that formed for 1 h, the bright yellow precipitate was collected by suction filtration, washed exhaustively with water and then re-dissolved into acetone. The resulting solution was heated with activated charcoal, filtered and evaporated to give a light orange residue which was dried azeotropically with isopropyl alcohol. The crude product that obtained was purified by recrystallization from acetone/hexane (2:3) to give 3 as creamy crystals (806 mg, 4.24 mmol, 42%); mp 175-178° C. [Lit. [68] 177° C. (ethanol)]; δH (400 MHz, DMSO-d6) 1.22 (3H, t, J=7.3 Hz, CH3), 2.77 (2H, q, J=7.3 Hz, CH2), 6.09 (1H, s, C3-H), 6.71 (1H, d, JC6-H, C8-H=2.4 Hz, C8-H), 6.80 (1H, dd, JC8-H, C6-H=2.4 Hz and JC5-H, C6-H=8.4 Hz, C6-H), 7.64 (1H, d, JC6-H, C5-H=8.8 Hz, C5-H) and 10.53 (1H, s, exchanged with D2O, OH); MS (FAB+) m/z (rel. intensity) 190.8[100, (M+H)+]; MS (FAB−) m/z (rel. intensity) 342.8[60, (M−H+NBA)−], 188.8[100, (M−H)−]. Found: C, 69.4; H, 5.35; C11H10O3 requires C, 69.43; H, 5.30%.
Reaction SMILES: CO[C:3](=[O:21])[C:4]([C:6]1[C:16]2=[C:17]3[C:12](=[CH:13][CH:14]=[CH:15]2)[CH2:11][CH:10]([CH2:18][O:19][CH3:20])[CH2:9][N:8]3[CH:7]=1)=O.[F:22][C:23]1[CH:31]=[C:30]2[C:26]([C:27]([CH2:32][C:33]([NH2:35])=[O:34])=[CH:28][NH:29]2)=[CH:25][CH:24]=1>>[CH3:20][O:19][CH2:18][CH:10]1[CH2:11][C:12]2[C:17]3=[C:16]([C:6]([C:4]4[C:3](=[O:21])[NH:35][C:33](=[O:34])[C:32]=4[C:27]4[C:26]5[C:30](=[CH:31][C:23]([F:22])=[CH:24][CH:25]=5)[NH:29][CH:28]=4)=[CH:7][N:8]3[CH2:9]1)[CH:15]=[CH:14][CH:13]=2
Reactant: NC(=O)Cc1c[nH]c2cc(F)ccc12
Reactant: COCC1Cc2cccc3c(C(=O)C(=O)OC)cn(c23)C1
Product: COCC1Cc2cccc3c(C4=C(c5c[nH]c6cc(F)ccc56)C(=O)NC4=O)cn(c23)C1

Procedure:
Beginning with (5-methoxymethyl-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)oxoacetic acid methyl ester and (6-fluoro-1H-indol-3-yl)acetamide, the title compound was prepared essentially as described in Example 1.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]([CH3:12])[CH3:11])[C:5]=1[NH:13][C:14](=[O:22])[CH2:15][S:16]([CH2:19][CH2:20]Cl)(=[O:18])=[O:17])([CH3:3])[CH3:2].[C:23]1([N:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C1(C)C=CC=CC=1>C(OCC)(=O)C>[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]([CH3:12])[CH3:11])[C:5]=1[NH:13][C:14](=[O:22])[CH2:15][S:16]([CH2:19][CH2:20][N:32]1[CH2:33][CH2:34][N:29]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:30][CH2:31]1)(=[O:18])=[O:17])([CH3:3])[CH3:2]
Reactant: CC(C)c1cccc(C(C)C)c1NC(=O)CS(=O)(=O)CCCl
Reactant: c1ccc(N2CCNCC2)cc1
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: CC(C)c1cccc(C(C)C)c1NC(=O)CS(=O)(=O)CCN1CCN(c2ccccc2)CC1
Yield: 70.7 %

Procedure:
A mixture of 3.46 g of N-(2,6-diisopropylphenyl)-2(2-chloroethylsulfonyl)acetamide synthesized in (1) above, 1.62 g of N-phenylpiperazine, and 50 ml of toluene was heated under reflux for 4 hours. To the reaction mixture was added 100 ml of ethyl acetate, and the mixture was washed successively with a sodium hydrogencarbonate aqueous solution and a saturated sodium chloride aqueous solution, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was subjected to column chromatography using a mixture of ethyl acetate and hexane at a ratio varying from 1:1 to 1:0 as a developing solvent. The solvent was evaporated, and the residue was dissolved in ethyl acetate and crystallized from a 4N hydrochloric acid solution in ethyl acetate to obtain 3.33 g of the title compound as white powder (m.p.=197.0°-200.0° C.).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:17]=1)[C:12](Cl)=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:26]([O-])(=O)CC([O-])=O.C(C(CC)(O[Mg+2])C)C.S(=O)(=O)(O)O>C1C=CC=CC=1>[CH3:26][C:12]([C:11]1[CH:10]=[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:17]=[C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:15]=1)=[O:13]
Reactant: O=C(Cl)c1cc(OCc2ccccc2)cc(OCc2ccccc2)c1
Reactant: O=C([O-])CC(=O)[O-]
Agent: CCC(C)(CC)O[Mg+2]
Agent: O=S(=O)(O)O
Solvent: c1ccccc1
Product: CC(=O)c1cc(OCc2ccccc2)cc(OCc2ccccc2)c1
Temperature: 130 °C

Procedure:
70 g of 3,5-dibenzyloxy-benzoyl-chloride in dry benzene were slowly added to a solution of diethyl ethoxy-magnesium-malonate prepared in known manner. The reaction mixture was refluxed overnight, and after cooling 300 ml of benzene and 200 ml of 5-N sulphuric acid were added to hydrolyze the mixture. The benzene phase was washed three times with water and dried with magnesium sulphate. The benzene was evaporated and the excess of diethyl malonate distilled off under reduced pressure. To the residue 400 ml of dioxane, 80 ml of water and 40 ml of conc. hydrochloric acid were added. The reaction mixture was heated for 24 hours on an oil bath at 130° C. After evaporation a brown oil remained, which crystallized on standing. Recrystallized from ethanol: M.p. 60°-61° C.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][O:6][CH:7]2[C:12]([OH:14])=O.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:27][O:28][NH:29][CH3:30]>C(Cl)Cl>[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][O:6][CH:7]2[C:12]([N:29]([CH3:30])[O:28][CH3:27])=[O:14]
Reactant: CNOC
Reactant: O=C(O)C1OCCc2c(Br)cccc21
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: ClCCl
Product: CON(C)C(=O)C1OCCc2c(Br)cccc21
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A mixture of 5-bromo-3,4-dihydro-1H-isochromene-1-carboxylic acid (9.10 g, 35.4 mmol) and CDI (4.14 g, 42.5 mmol) in 200 mL of dry DCM was stirred at r.t. for 30 min and then O,N-dimethyl-hydroxylamine (5.99 g, 42.5 mmol) was added. The resulting mixture was stirred overnight. The solvents were removed under vacuum, and the residue was purified with silica gel column chromatography to give 5-bromo-N-methyl-N-(methyloxy)-3,4-dihydro-1H-isochromene-1-carboxamide. 1H-NMR (400 MHz, CDCl3) δ 7.40 (d, J=8.0 Hz, 1H), 6.99 (t, J=8.0 Hz, 1H), 6.93 (d, J=8.0 Hz, 1H), 5.63 (s, 1H), 4.23˜4.28 (m, 1H), 3.87˜3.92 (m, 1H), 3.71 (s, 3H), 3.19 (s, 3H), 2.71˜2.87 (m, 2H).
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]2[S:8][CH:9]=[CH:10][C:6]=2[CH:5]=1)([O-:3])=[O:2].Br[CH2:14][C:15]1[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][C:16]=1[O:25][CH3:26].O>ClCCl>[CH3:26][O:25][C:16]1[CH:17]=[C:18]([CH:23]=[CH:24][C:15]=1[CH2:14][C:10]1[C:6]2[CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:12]=[CH:11][C:7]=2[S:8][CH:9]=1)[C:19]([O:21][CH3:22])=[O:20]
Reactant: O=[N+]([O-])c1ccc2sccc2c1
Reactant: COC(=O)c1ccc(CBr)c(OC)c1
Solvent: O
Solvent: ClCCl
Product: COC(=O)c1ccc(Cc2csc3ccc([N+](=O)[O-])cc23)c(OC)c1

Procedure:
Stannic chloride (0.41 g.) was added to a stirred solution of 5-nitrobenzo[b]thiophene (0.28 g.) and methyl 4-bromomethyl-3-methoxybenzoate (B) (0.61 g.) in dichloromethane (5 ml.). The mixture was heated under reflux for 18 hours. The cooled mixture was poured into water (10 ml.) and extracted with dichloromethane (2×20 ml.). The combined extracts were dried (MgSO4) and evaporated. The oil was purified by flash chromatography on silica gel (100 ml.) eluting with 1:9 v/v ethyl acetate:hexane. The solid obtained was crystallized from hexane to give methyl 3-methoxy-4-(5-nitrobenzo[b]thien-3-ylmethyl)benzoate (I) as a solid (0.16 g., 30%): NMR: (250 MHz, CDCl3): 3.92 (s, 3 H, OCH3), 3.98 (s,3 H, OCH3), 4.28 (s,2 H, CH2 --Ar), 7.15 (d,1 H), 7.22 (s,1 H), 7.56 (m,2 H), 7.93 (d,1 H), 8.19 (dd, 1 H): 8.73 (d,1 H).
Reaction SMILES: [CH2:1]=[O:2].[OH-].[Na+].[CH:5](=[O:12])[CH:6]1[CH2:11][CH2:10][CH:9]=[CH:8][CH2:7]1>>[C:6]1([CH2:1][OH:2])([CH2:5][OH:12])[CH2:11][CH2:10][CH:9]=[CH:8][CH2:7]1
Reactant: C=O
Reactant: O=CC1CC=CCC1
Agent: [Na+]
Agent: [OH-]
Product: OCC1(CO)CC=CCC1
Temperature: 25 °C
Yield: 70 %

Procedure:
One hundred (100) parts by weight of a formaldehyde aqueous solution (37 wt. % formaldehyde) was charged to a reactor. To this solution, cooled externally with an ice-water bath, was added 118 parts of an aqueous sodium hydroxide solution (25 wt. % sodium hydroxide) by several portions and the temperature of the reaction content was maintained at 20 to 30° C. This was followed by a slow addition of 54 parts of 1,2,5,6-tetrahydrobenzaldehyde at such a rate that the reaction content temperature did not exceed 55° C. After the exotherm dissipated, it was heated at 55° C. for two hours with an external heating. The product precipitated out of the solution upon cooling and was collected by suction filtration. The wet-cake was washed thoroughly in the funnel with copious amount of water (5×100 parts). The crude product was allowed to dry in air overnight and purified by a recrystallization from toluene. The final product was an off-white colored crystalline material (yield 70%. m.p.: 92-93° C.).
Reaction SMILES: Cl[C:2]1[C:3](=[O:16])[NH:4][C:5]2[CH2:6][CH2:7][C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=3[C:10]=2[CH:11]=1.[CH3:17][NH2:18]>O>[CH3:17][NH:18][C:2]1[C:3](=[O:16])[NH:4][C:5]2[CH2:6][CH2:7][C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=3[C:10]=2[CH:11]=1
Reactant: O=c1[nH]c2c(cc1Cl)-c1ccccc1CC2
Reactant: CN
Solvent: O
Product: CNc1cc2c([nH]c1=O)CCc1ccccc1-2

Procedure:
Add 23.1 gm of 2-chloro-5,6-dihydro-benzo[f]quinolin-3(4H)-one to 100 ml of 40% aqueous methylamine and 250 ml of water. Heat the system in a steel bomb at 140° C. for 5 days. Stop the reaction and isolate 2-(N-methylamino)-5,6-dihydro-benzo[f]quinolin-3(4H)-one.
Reaction SMILES: [I:1]I.[Cl:3][C:4]1[CH:13]=[CH:12][C:11]([OH:14])=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8]([CH3:15])=[N:9]2.ICl>CO>[Cl:3][C:4]1[CH:13]=[C:12]([I:1])[C:11]([OH:14])=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8]([CH3:15])=[N:9]2
Reactant: Cc1ccc2c(Cl)ccc(O)c2n1
Reactant: II
Agent: ClI
Solvent: CO
Product: Cc1ccc2c(Cl)cc(I)c(O)c2n1
Reaction time: 3 h

Procedure:
Iodine monchloride (19.0 g) is added to a solution of 5-chloro-8-hydroxy-2-methylquinoline (21.5 g) in 250 mL of MeOH, and the resulting mixture is stirred for 3 h. Additional iodine monochloride (4.5 g) is then added, and the mixture is stirred for another 18 h. The reaction mixture is quenched with sat'd Na2SO3 (aq), then neutralized with sat'd NaHCO3 (aq). The solid precipitate is collected by filtration and dried under vacuum to give 31.22 g of the title compound as a pale green solid.
Reaction SMILES: [C:1]1([C:7]2[N:8]=[C:9]([NH:12][CH2:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[S:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br[CH2:24][C:25]1[CH:34]=[CH:33][C:28]([C:29]([O:31][CH3:32])=[O:30])=[CH:27][CH:26]=1.O>CN(C)C=O>[C:15]1([CH2:14][CH2:13][N:12]([CH2:24][C:25]2[CH:34]=[CH:33][C:28]([C:29]([O:31][CH3:32])=[O:30])=[CH:27][CH:26]=2)[C:9]2[S:10][CH:11]=[C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[N:8]=2)[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: COC(=O)c1ccc(CBr)cc1
Reactant: c1ccc(CCNc2nc(-c3ccccc3)cs2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(CN(CCc2ccccc2)c2nc(-c3ccccc3)cs2)cc1
Reaction time: 0.5 h
Yield: 47.9 %

Procedure:
To a solution of 4-phenyl-N-(2-phenylethyl)-1,3-thiazole-2-amine (4.63 g, 16.5 mmol) in N,N-dimethylformamide (50 mL) was added sodium hydride (60% in oil, 990 mg, 24.8 mmol) and the mixture was stirred for 30 min. Methyl 4-(bromomethyl)benzoate (4.54 g, 19.8 mmol) was added and the mixture was stirred at room temperature for 2 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with water, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (5%-50% ethyl acetate/hexane) to give the title compound (3.39 g, yield 48%) as a yellow oil.
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]2[CH:10]=[CH:9][C:8]([N+:11]([O-])=O)=[CH:7][C:5]=2[CH:6]=1.C(O)C.C([O-])=O.[NH4+]>[Pd].C1COCC1>[CH3:1][C:2]1[O:3][C:4]2[CH:10]=[CH:9][C:8]([NH2:11])=[CH:7][C:5]=2[CH:6]=1
Reactant: Cc1cc2cc([N+](=O)[O-])ccc2o1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CCO
Solvent: C1CCOC1
Product: Cc1cc2cc(N)ccc2o1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a 35° C. mixture of 50 g of 2-methyl-5-nitrobenzofuran, ethanol (250 mL), THF (250 mL) and wet 10% Pd/C (4 g) was added ammonium formate (53.4 g, 0.85 mol) over 50 min. After an additional 4 h, the reaction was cooled to room temperature and filtered through Celite. The filtrate was concentrated and the residue was taken up in methyl t-butyl ether. This mixture was filtered, concentrated and dried to provide 2-methyl-5-benzofuranamine which was converted to its hydrochloride salt or its oxalate salt. The oxalate was prepared as follows: To a solution of 2-methyl-5-benzofuranamine in TBME (415 mL) was added a solution of oxalic acid (25.4 g) in methanol (80 mL) dropwise. The precipitate was stirred for 2 h, collected, washed with methanol/TBME and dried to provide 2-methyl-5-benzofuranamine oxalate.
Reaction SMILES: Cl.[O:2]([NH2:4])[CH3:3].N1C=CC=CC=1.[C:11](Cl)(=[O:22])[O:12][C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][CH:14]=1>ClCCl>[CH3:3][O:2][NH:4][C:11](=[O:22])[O:12][C:13]1[CH:14]=[CH:15][C:16]([N+:19]([O-:21])=[O:20])=[CH:17][CH:18]=1
Reactant: CON
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Agent: Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CONC(=O)Oc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Yield: 36.1 %

Procedure:
Methoxylamine hydrochloride (1.00 g, 12.0 mmol) was suspended in a mixture of dry pyridine (0.97 mL, 12.0 mmol) and dichloromethane (24 mL), and a solution of 4-nitrophenyl chlorocarbonate (2.41 g, 12.0 mmol) in dichloromethane (12 mL) was added over 30 min with stirring. The resulting heavy white suspension was warmed to reflux, refluxed for 6 h, and cooled to room temperature. The suspension was diluted with dichloromethane and washed with 1M HCl, keeping the emulsion with the aqueous layer, and the aqueous layer was re-extracted with dichloromethane. The combined organic phase was washed with water, saturated aqueous sodium bicarbonate and brine, keeping any emulsions with the aqueous layer, and then dried over magnesium sulfate and concentrated under reduced pressure. The crude product was purified by chromatography (90 g silica gel, 20-40% EtOAc/hexanes) to give the title compound (0.92 g) as a white crystalline solid. A second set of less pure product fractions was isolated to give additional product (0.21 g) as a white solid.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C(OO)(=[O:18])C>ClCCl>[CH2:14]([O:13][C:11]([C:8]1[CH:9]=[C:10]2[C:5]([CH:4]=[CH:3][CH:2]=[N+:1]2[O-:18])=[CH:6][CH:7]=1)=[O:12])[CH3:15]
Reactant: CCOC(=O)c1ccc2cccnc2c1
Reactant: CC(=O)OO
Solvent: ClCCl
Product: CCOC(=O)c1ccc2ccc[n+]([O-])c2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 92.1 %

Procedure:
To a solution of ethyl quinoline-7-carboxylate (1.02 g, 5.05 mmol) in dichloromethane (20 mL) was added peracetic acid (2.13 mL, 10.1 mmol, 32 wt % in acetic acid). The reaction was stirred at room temperature overnight. The reaction was partitioned between water and dichloromethane. The layers were separated and the aqueous was extracted with dichloromethane (4×). The combined organics were washed with water and brine, dried over sodium sulfate, filtered, and concentrated. The solid was concentrated from heptanes and ethyl acetate several times, then dried under vacuum to give the title compound (1.01 g, 92%) as a yellow solid. +ESI (M+H) 218.2; 1H NMR (400 MHz, CDCl3, δ): 9.40 (s, 1H), 8.65 (d, J=6.05 Hz, 1H), 8.27 (dd, J=8.58, 1.56 Hz, 1H), 7.95 (d, J=8.39 Hz, 1H), 7.82 (d, J=8.58 Hz, 1H), 7.42 (dd, J=8.49, 6.15 Hz, 1H), 4.47 (q, J=7.02 Hz, 2H), 1.45 (t, J=7.1 Hz, 3H).
Reaction SMILES: Cl.Cl.[NH2:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]2[N:10]([CH2:18][C:19]([OH:21])=O)[N:11]=[C:12]([C:13]3[NH:14][CH:15]=[CH:16][N:17]=3)[C:5]=12.Cl.Cl.[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)=[CH:27][C:26]=1[O:37][CH3:38].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC(=CC1=2)Cl)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[NH2:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]2[N:10]([CH2:18][C:19]([N:34]3[CH2:33][CH2:32][N:31]([C:28]4[CH:29]=[CH:30][C:25]([Cl:24])=[C:26]([O:37][CH3:38])[CH:27]=4)[CH2:36][CH2:35]3)=[O:21])[N:11]=[C:12]([C:13]3[NH:17][CH:16]=[CH:15][N:14]=3)[C:5]=12
Reactant: Nc1ncnc2c1c(-c1ncc[nH]1)nn2CC(=O)O
Reactant: COc1cc(N2CCNCC2)ccc1Cl
Agent: CN(C)C(On1nnc2ccc(Cl)cc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COc1cc(N2CCN(C(=O)Cn3nc(-c4ncc[nH]4)c4c(N)ncnc43)CC2)ccc1Cl
Temperature: 25 °C
Reaction time: 3 h
Yield: 81.3 %

Procedure:
[4-Amino-3-(1H-imidazol-2-yl)pyrazolo[3,4-d]pyrimidin-1-yl]acetic acid dihydrochloride (79 g, 0.238 mol) and 1-(4-chloro-3-methoxyphenyl)piperazine dihydrochloride (71.3 g, 0.238 mol) were suspended in anhydrous DMF (793 mL) and cooled in an ice bath. N,N-diisopropylethylamine (290 mL, 1.67 mol) was added and the mixture was stirred at room temperature until all solids dissolved to form a brown solution. HCTU (113.23 g, 0.273 mol) was added in portions over 10 min while maintaining the internal temperature below 20° C. After 3 h, the reaction mixture was poured slowly into a flask of vigorously stirred ice water (6 L) to give a suspension, which was stirred for 1 h, filtered, and washed with saturated NaHCO3 (500 mL×2) and water (500 mL×2). The solid was purified by trituration in refluxing MeCN (2×500 mL) to provide 2-[4-amino-3-(1H-imidazol-2-yl)-pyrazolo[3,4-d]pyrimidin-1-yl]-1-[4-(4-chloro-3-methoxyphenyl)piperazin-1-yl]ethanone (90.5 g, 81% yield, >98% pure by LC-MS). 1H NMR (400 MHz, d6-DMSO) δ 13.0 (s, 1H), 10.14 (d, 1H, J=3.7 Hz), 8.16 (s, 1H), 7.95 (d, 1H, d, J=3.7 Hz), 7.25 (dd, 1H, J=1.03 and 1.36 Hz), 7.20 (d, 1H, J=8.8 Hz), 7.16 (s, 1H), 6.70 (d, 1H, J=2.4 Hz), 6.52 (dd, 1H, J=2.4 and 8.8 Hz), 5.37 (s, 2H), 3.83 (s, 3H), 3.74 (t, 2H, J=4.8 Hz), 3.58 (t, 2H, J=4.8 Hz), 3.28 (t, 2H, J=4.8 Hz), 3.17 (t, 2H, J=4.8 Hz). 13C NMR (100.6 MHz, d6-DMSO) δ 165.3, 159.0, 157.3, 155.7, 155.5, 151.6, 141.2, 136.6, 130.3, 128.7, 119.0, 111.9, 109.0, 101.9, 98.0, 56.7, 49.4, 48.9, 48.8, 44.7, 42.1; IR (KBr) 3219, 2937, 1682, 1638, 1594, 1567 cm−1; MS (ES) m/z 468.1 (M+H+). Anal. Calcd for C21H22N9O2Cl-0.85 H2O: C, 52.20; H, 4.94; N, 26.09; Cl, 7.34. Found: C, 51.92; H, 4.68; N, 26.44; Cl, 7.18.
Reaction SMILES: [NH2:1][C:2]1[CH:37]=[CH:36][C:5]([CH2:6][N:7]2[C:13](=[O:14])[C@H:12]3[CH2:15][CH2:16][CH2:17][C@H:11]3[N:10]([C:18](=[O:31])[CH2:19][N:20]3[C:24](=[O:25])[C:23]4=[CH:26][CH:27]=[CH:28][CH:29]=[C:22]4[C:21]3=[O:30])[C:9]3[CH:32]=[CH:33][CH:34]=[CH:35][C:8]2=3)=[CH:4][CH:3]=1.[C:38]1([C@H:44]([N:46]=[C:47]=[O:48])[CH3:45])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C(OCC)(=O)C.C(OCC)C>[C:38]1([C@H:44]([NH:46][C:47](=[O:48])[NH:1][C:2]2[CH:3]=[CH:4][C:5]([CH2:6][N:7]3[C:13](=[O:14])[C@H:12]4[CH2:15][CH2:16][CH2:17][C@H:11]4[N:10]([C:18](=[O:31])[CH2:19][N:20]4[C:21](=[O:30])[C:22]5=[CH:29][CH:28]=[CH:27][CH:26]=[C:23]5[C:24]4=[O:25])[C:9]4[CH:32]=[CH:33][CH:34]=[CH:35][C:8]3=4)=[CH:36][CH:37]=2)[CH3:45])[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1
Reactant: C[C@@H](N=C=O)c1ccccc1
Reactant: Nc1ccc(CN2C(=O)[C@H]3CCC[C@H]3N(C(=O)CN3C(=O)c4ccccc4C3=O)c3ccccc32)cc1
Solvent: CCOCC
Solvent: CCOC(C)=O
Product: C[C@@H](NC(=O)Nc1ccc(CN2C(=O)[C@H]3CCC[C@H]3N(C(=O)CN3C(=O)c4ccccc4C3=O)c3ccccc32)cc1)c1ccccc1
Yield: 54 %

Procedure:
Using (3aR*,10aS*)-9-(4-aminobenzyl)-4-(phthalimidoacetyl)-2,3,3a,4,9,10a-hexahydrobenzo[b]cyclopenta[e][1,4]diazepin-10(1H)-one and (R)-1-phenylethyl isocyanate, the title compound was synthesized in otherwise the same manner as Example 26. Yield 54%, m.p. 158°-163° C. (ethyl acetate-diethyl ether).
Reaction SMILES: Br[CH2:2][C:3]1[C:8]([N+:9]([O-:11])=[O:10])=[CH:7][CH:6]=[CH:5][N:4]=1.[Cl:12][C:13]1[CH:14]=[C:15]([OH:20])[CH:16]=[CH:17][C:18]=1[Cl:19]>>[Cl:12][C:13]1[CH:14]=[C:15]([CH:16]=[CH:17][C:18]=1[Cl:19])[O:20][CH2:2][C:3]1[C:8]([N+:9]([O-:11])=[O:10])=[CH:7][CH:6]=[CH:5][N:4]=1
Reactant: Oc1ccc(Cl)c(Cl)c1
Reactant: O=[N+]([O-])c1cccnc1CBr
Product: O=[N+]([O-])c1cccnc1COc1ccc(Cl)c(Cl)c1
Yield: 72 %

Procedure:
In accordance with the same procedures as in Step 3 of Preparation 1, except for using 2-bromomethyl-3-nitropyridine prepared in Step 2 of Preparation 1 and 3,4-dichlorophenol, the titled compound was obtained as yellow solid. (Yield: 72%)
Reaction SMILES: C(N(CC)CC)C.[CH3:8][O:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[C:15](=[O:21])[O:14][CH:13]2[PH2](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[N:41]1[CH:46]=[CH:45][C:44]([CH:47]=O)=[CH:43][CH:42]=1>C(Cl)Cl>[CH3:8][O:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[C:15](=[O:21])[O:14][C:13]2=[CH:47][C:44]1[CH:45]=[CH:46][N:41]=[CH:42][CH:43]=1
Reactant: O=Cc1ccncc1
Reactant: COc1cc2c(cc1OC)C([PH2](c1ccccc1)(c1ccccc1)c1ccccc1)OC2=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1cc2c(cc1OC)C(=Cc1ccncc1)OC2=O
Yield: 60.9 %

Procedure:
Triethylamine (20 ml, 145 mmoles) was dropwise added to a suspension of 5,6-dimethoxy-3-(triphenyl-λ6-phosphanyl)-3H-isobenzofuran-1-one (78 g, 145 mmoles), obtained as described in example 3, and 4-pyridincarboxaldehyde (13 ml, 145 mmoles) in CH2Cl2 (1 l), at room temperature under stirring. After 1.5 hours the mixture was filtered and evaporated and the residue was treated with ethanol under reflux, cooled and filtered. The mother liquors were chromatographed (eluent: 100% CH2Cl2, then with 1% CH3OH) and the residue was brought to dryness and joined to the above filtrate to give 25 g of the title compound.
Reaction SMILES: [Na].[N:2]([C@@H:5]1[C@@H:12]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[C@H:11]([O:23]C(C2C(C3C=CC=CC=3)=CC=CC=2)=O)[C@@H:10]([CH2:38][O:39][Si:40]([C:53]([CH3:56])([CH3:55])[CH3:54])([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[O:9][C@H:6]1[S:7][CH3:8])=[N+:3]=[N-:4]>CO.C1COCC1>[N:2]([C@@H:5]1[C@@H:12]([O:13][CH2:14][C:15]2[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=2)[C@H:11]([OH:23])[C@@H:10]([CH2:38][O:39][Si:40]([C:53]([CH3:56])([CH3:55])[CH3:54])([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[O:9][C@H:6]1[S:7][CH3:8])=[N+:3]=[N-:4]
Reactant: COc1ccc(CO[C@@H]2[C@@H](N=[N+]=[N-])[C@H](SC)O[C@H](CO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)[C@H]2OC(=O)c2ccccc2-c2ccccc2)cc1
Agent: [Na]
Solvent: C1CCOC1
Solvent: CO
Product: COc1ccc(CO[C@H]2[C@H](O)[C@@H](CO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)O[C@@H](SC)[C@@H]2N=[N+]=[N-])cc1
Temperature: 40 °C
Reaction time: 0.5 h
Yield: 91.1 %

Procedure:
Sodium (89 mg) was reacted in dry MeOH (50 mL) then a solution of methyl 2-azido-4-O-biphenylcarbonyl-6-O-tert-butyldiphenylsilyl-2-deoxy-3-O-(4-methoxybenzyl)-1-thio-β-D-glucopyranoside (11) (3 g, 3.88 mmol) in THF (25 mL) was added. The reaction mixture was stirred at 40° C. for 30 minutes, then cooled to room temperature. The solution was neutralized by Amberlite IR 120 (H+) ion exchange resin. The suspension was filtered, the filtrate was evaporated. The residue was purified by chromatography using EtOAc—hexane 1:4 as the mobile phase to give methyl 2-azido-6-O-tert-butyldiphenylsilyl-2-deoxy-3-O-(4-methoxybenzyl)-1-thio-β-D-glucopyranoside (10) (2.1 g, 91%)