Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C@@H]1(OC2C=CC=CC=2[C:18]2[CH:19]=[C:20]([CH:25]=[CH:26][CH:27]=2)[C:21]([O:23]C)=[O:22])O[C@@H](C)[C@@H](O)[C@@H](O)[C@@H]1O.O.[OH-].[Li+].Cl>C(#N)C>[C:21]([OH:23])(=[O:22])[C:20]1[CH:25]=[CH:26][CH:27]=[CH:18][CH:19]=1
Reactant: COC(=O)c1cccc(-c2ccccc2O[C@@H]2O[C@@H](C)[C@@H](O)[C@@H](O)[C@@H]2O)c1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: CC#N
Solvent: O
Product: O=C(O)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 120.7 %

Procedure:
Methyl 3-(2-(α-L-fucopyranosyloxy)phenyl)benzoate (0.44 g, 1.18 mmol) was dissolved in acetonitrile (8 ml) and treated with a solution of lithium hydroxide hydrate (60 mg, 1.41 mM, in 0.5 ml water) and the mixture was stirred overnight at room temperature. The mixture was then treated with 2N HCl to pH 3 to 4 and the volatiles were removed under reduced pressure. The residue was purified by HPLC (reverse-phase, gradient elution 5-50% acetonitrile in water, 0.1% trifluoroacetic acid, monitored at 254 nm) which gave 3-(2-α-L-fucopyranosyloxy)phenyl)benzoic acid (174 mg, 40%) as a white solid, m.p.: 92°-93° C.; 1H NMR (300 MHz, DMSO-d6): 8.07 (s, 1H), 7.88 (t, J=8.7, 2H),7.51 (t, J=7.7, 1H), 7.29-7.43 (comp, 2H), 7.27 (d, J=8, 1H), 7.09 (t, J=7.2, 1H), 5.49 (d, J=3, 1H), 3.05-3.90 (comp, 7H), 0.97 (d, J=6, 3H); IR (KBr): 3402, 2932, 1695, 1498, 1457, 1219, 1076, 960, 838, 750; analysis: calculated for C19H20O7.0.3[CF3CO2H].0.2[H2O]: 59.1% C; 5.2% H. found: 59.1% C; 5.5% H.
Reaction SMILES: [C:1]([O:4][C@H:5]1[C@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@@H:9]([CH2:15][O:16][C:17](=[O:19])[CH3:18])[O:8][C@@H:7]([O:20][C@@H:21]2[C@H:30]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C@@H:29]([O:39][CH2:40][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C@H:28]([CH3:47])[O:27][C@H:22]2[O:23]CC=C)[C@@H:6]1[NH:48][C:49](=[O:54])[C:50]([Cl:53])([Cl:52])[Cl:51])(=[O:3])[CH3:2]>O1CCCC1>[C:1]([O:4][C@H:5]1[C@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@@H:9]([CH2:15][O:16][C:17](=[O:19])[CH3:18])[O:8][C@@H:7]([O:20][C@@H:21]2[C@H:30]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C@@H:29]([O:39][CH2:40][C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=3)[C@H:28]([CH3:47])[O:27][C@H:22]2[OH:23])[C@@H:6]1[NH:48][C:49](=[O:54])[C:50]([Cl:53])([Cl:52])[Cl:51])(=[O:3])[CH3:2]
Reactant: C=CCO[C@@H]1O[C@@H](C)[C@H](OCc2ccccc2)[C@@H](OCc2ccccc2)[C@H]1O[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1NC(=O)C(Cl)(Cl)Cl
Solvent: C1CCOC1
Product: CC(=O)OC[C@H]1O[C@@H](O[C@@H]2[C@H](OCc3ccccc3)[C@@H](OCc3ccccc3)[C@H](C)O[C@H]2O)[C@H](NC(=O)C(Cl)(Cl)Cl)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 83.1 %

Procedure:
1,5-Cyclooctadiene-bis(methyldiphenylphosphine)iridium hexafluorophosphate (120 mg, 140 μmol) was dissolved tetrahydrofuran (10 mL), and the resulting red solution was degassed in an argon stream. Hydrogen was then bubbled through the solution, causing the colour to change to yellow. The solution was then degassed again in an argon stream. A solution of 317 (1.46 g, 1.75 mmol) in tetrahydrofuran (20 mL) was degassed and added. The mixture was stirred at rt overnight. The mixture was concentrated. The residue was taken up in acetone (27 mL), and water (3 mL) was added. Mercuric bromide (949 mg, 2.63 mmol) and mercuric oxide (761 mg, 3.5 mmol) were added to the mixture, protected from light. The mixture was stirred for 2 h at rt, then concentrated. The residue was taken up in CH2Cl2 and washed three limes with sat. aq. KI, then with brine. The organic phase was dried and concentrated. The residue was purified by column chromatography (cyclohexane-EtOAc 4:1) to give 318 (1.13 g, 81%) as a white foam. [α]D+4° (c 1, CHCl3). 1H NMR: δ 7.35-7.05 (m, 10H, Ph), 6.74 (d, 1H, J2,NH=8.5 Hz, NHD), 5.10 (d, 1H, J1,2=1.1 Hz, H-1A), 5.02 (m, 2H, H-3D, 4D), 4.80-4.50 (m, 4H, CH2Ph), 4.61 (d, 1H, J1,2=8.5 Hz, H-1D), 4.15-4.08 (m, 2H, J5,6=4.5, J6a,6b=12.3 Hz, H-6aD, 6bD), 4.00 (m, 1H, H-2D), 3.90 (dd, 1H, J2,3=3.3, H-2A), 3.86 (dd, 1H, J3,4=9.5 Hz, H-3A), 3.85 (dq, 1H, J4,5=9.5, J5,6=6.2 Hz, H-5A), 3.50 (m, 1H, H-5D), 3.30 (pt, 1H, H-4A), 2.85 (d, 1H, J1,OH=3.5 Hz, OH), 2.02, 1.97, 1.94 (3s, 9H, OAc), 1.23 (d, 3H, H-6A); 13C NMR: δ 171.1, 170.0, 169.6, 162.1 (C═O), 138.5-127.1 (Ph), 101.7 (C-1D), 94.1 (C-1A), 92.6 (CCl3), 81.4 (C-4A), 79.9 (C-2A), 77.3 (C-3A), 75.9, 74.1 (2C, CH2Ph), 72.7 (C-3D), 72.5 (C-5D), 68.6 (C-4D), 68.4 (C-5A), 62.2 (C-6D), 56.1 (C-2D), 21.1, 21.0, 20.9 (3C, OAc), 18.3 (C-6A). FAB-MS for C34H40Cl3NO13 (M, 775), m/z 789 [M+Na]+. Anal. Calcd for C34H40Cl3NO13: C, 52.55; H, 5.19; N, 1.80%. Found: C, 52.48; H, 5.37; N, 1.67%.
Reaction SMILES: [CH2:1]([O:8][C:9]([C@H:11]1[C@H:16]([OH:17])[C@H:15]([OH:18])[C@@H:14]([OH:19])[CH2:13][N:12]1[S:20]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=1)(=[O:22])=[O:21])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[C:32]1(C)[CH:37]=CC(S(O)(=O)=O)=C[CH:33]=1.C(OCC)(=O)C>CN(C=O)C>[CH2:1]([O:8][C:9]([C@H:11]1[C@@H:16]2[O:17][C:32]([CH3:37])([CH3:33])[O:18][C@@H:15]2[C@@H:14]([OH:19])[CH2:13][N:12]1[S:20]([C:23]1[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=1)(=[O:22])=[O:21])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1ccc(S(=O)(=O)N2C[C@H](O)[C@@H](O)[C@@H](O)[C@@H]2C(=O)OCc2ccccc2)cc1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(S(=O)(=O)N2C[C@H](O)[C@H]3OC(C)(C)O[C@H]3[C@@H]2C(=O)OCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 3585 %

Procedure:
The above compound (4) (7.4 g) was dissolved in DMF (80 mL) and DMP (17.6 g) and p-toluenesulfonic acid monohydrate (70 mg) were added, and then the mixture was stirred overnight at room temperature and further stirred at 60° C. for 1.5 hours. To the reaction solution was added ethyl acetate (150 mL) and, after washing with an aqueous saturated sodium hydrogencarbonate solution and saturated saline (×3), the organic layer was dried over magnesium sulfate and the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel medium pressure column chromatography (ethyl acetate:cyclohexane=1:3→1:2→1:1) to obtain the titled compound (6.3 g) as a syrup.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([S:9][CH3:10])[N:3]=1.C(NC(C)C)(C)C.[Li].[CH:19]1([CH:24]=[O:25])[CH2:23][CH2:22][CH2:21][CH2:20]1>C1COCC1>[CH:19]1([CH:24]([C:7]2[C:2]([Cl:1])=[N:3][C:4]([S:9][CH3:10])=[N:5][C:6]=2[Cl:8])[OH:25])[CH2:23][CH2:22][CH2:21][CH2:20]1
Reactant: CSc1nc(Cl)cc(Cl)n1
Reactant: O=CC1CCCC1
Agent: [Li]
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: CSc1nc(Cl)c(C(O)C2CCCC2)c(Cl)n1
Temperature: -78 °C
Reaction time: 0.33 h

Procedure:
4,6-Dichloro-2-methylsulfanyl-pyrimidine (8.0 g, 41.01 mmol) was dissolved in 500 mL dry THF and cooled to −78° C. Lithium diisopropylamine (36.9 mL of 2.0 M solution in hexanes) was added dropwise, and the reaction mixture was stirred for 20 minutes at −78° C. Cyclopentane-carboxaldehyde (8.05 g, 82.02 mmol was added, and the reaction mixture was stirred for 45 minutes at −78° C. The reaction was quenched by addition of saturated aqueous ammonium chloride. The aqueous mixture was extracted with ethyl acetate, and the combined organic layers were washed with water, washed with brine, dried (MgSO4), filtered, and evaporated under reduced pressure. The residue was purified by flash chromatography (5% to 40% EtOAc in hexanes) to yield 9.76 g of cyclopentyl-(4,6-dichloro-2-methylsulfanyl-pyrimidin-5-yl)-methanol. Mass Spec. M+H=294.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([C:30]3[CH:35]=[CH:34][N:33]=[C:32](SC)[N:31]=3)[C:10]3[C:11]([N:29]=2)=[N:12][C:13]([N:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)=[CH:14][CH:15]=3)=[CH:4][CH:3]=1.C1C=C(Cl)C=C(C(OO)=O)C=1.[C:49]1([C@@H:55]([NH2:57])[CH3:56])[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1>C(Cl)Cl.CC(O)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([C:30]3[CH:35]=[CH:34][N:33]=[C:32]([NH:57][C@H:55]([C:49]4[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=4)[CH3:56])[N:31]=3)[C:10]3[C:11]([N:29]=2)=[N:12][C:13]([N:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)=[CH:14][CH:15]=3)=[CH:4][CH:3]=1
Reactant: CSc1nccc(-n2c(-c3ccc(F)cc3)nc3nc(N4CCN(C(=O)OC(C)(C)C)CC4)ccc32)n1
Reactant: C[C@H](N)c1ccccc1
Agent: O=C(OO)c1cccc(Cl)c1
Solvent: CC(=O)O
Solvent: ClCCl
Product: C[C@H](Nc1nccc(-n2c(-c3ccc(F)cc3)nc3nc(N4CCN(C(=O)OC(C)(C)C)CC4)ccc32)n1)c1ccccc1
Temperature: 120 °C
Reaction time: 0.25 h
Yield: 35 %

Procedure:
2-(4-Fluorophenyl)-1-(2-methylthio-4-pyrimidinyl)-5-(4-tert.butoxycarbonyl-1-piperazinyl)imidazo[4,5-b]pyridine (106 mg, 0.2 mmol) is dissolved in CH2Cl2/HOAc 1:1 (10 ml), combined with mCPBA (113 mg 70%, 0.24 mmol) and stirred for 15 min. The reaction mixture is poured on water and extracted with CH2Cl2 three times. The combined organic phases are dried over Na2SO4. filtered and evaporated to dryness to yield the crude sulfoxide (100 mg), which is dissolved in 1-(S)-phenylethylamine (0.2 ml) and heated to 120° C. for 1 h. Purification over SiO2 (acetone/hexanes 1:1) yielded the title compound as colorless foam (45 mg 35%)
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]([CH2:19][C:20]1[C:29]2[C:24](=[CH:25][C:26]([O:38][CH2:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)=[C:27]([O:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH:28]=2)[CH2:23][CH2:22][N:21]=1)[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>C(O)C>[ClH:18].[CH2:1]([O:8][C:9]([N:11]([CH2:19][CH:20]1[C:29]2[C:24](=[CH:25][C:26]([O:38][CH2:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)=[C:27]([O:30][CH2:31][C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH:28]=2)[CH2:23][CH2:22][NH:21]1)[C:12]1[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(OCc1ccccc1)N(CC1=NCCc2cc(OCc3ccccc3)c(OCc3ccccc3)cc21)c1ccc(Cl)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: Cl
Product: O=C(OCc1ccccc1)N(CC1NCCc2cc(OCc3ccccc3)c(OCc3ccccc3)cc21)c1ccc(Cl)cc1
Reaction time: 3 h
Yield: 37.7 %

Procedure:
1-(N-Benzyloxycarbonyl-p-chloroanilinomethyl)-6,7-dibenzyloxy-3,4-dihydroisoquinoline (7.0 g) was added to 99% ethanol (160 ml) and to the solution was gradually added sodium borohydride (2.2 g) under ice cooling. The reaction temperature of the mixture was elevated to ambient temperature and the mixture was stirred for 3 hours. An insoluble material was filtered off from the reaction mixture and the filtrate was concentrated under reduced pressure. After water was added to the residue, the mixture was extracted with ethyl acetate. The extract was washed with water and dried. The solvent was distilled off from the solution and the residue was subjected to column chromatography on silica gel, washed with benzene and eluted with a mixture of chloroform and ethyl acetate. The eluate was concentrated and the residue was treated with ethanol containing hydrochloric acid. The crystals obtained were recrystallized from a mixture of 99% ethanol and ether to give 1-(N-benzyloxycarbonyl-p-chloroanilinomethyl)-6,7-dibenzyloxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (1.4 g), mp 139° to 142° C.
Reaction SMILES: C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:53]=[CH:52][C:29]3[N:30]([C:33]([C:46]4[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=4)([C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)[C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[N:31]=[N:32][C:28]=3[CH:27]=2)=[CH:22][C:21]=1[CH:54]=O.[C:56]([O:60][C:61]([N:63]1[CH2:67][CH2:66][CH2:65][C@@H:64]1[CH2:68][NH:69][CH2:70][C:71]1[CH:76]=[CH:75][C:74]([F:77])=[CH:73][CH:72]=1)=[O:62])([CH3:59])([CH3:58])[CH3:57]>ClC(Cl)C.ClCCl>[C:56]([O:60][C:61]([N:63]1[CH2:67][CH2:66][CH2:65][C@@H:64]1[CH2:68][N:69]([CH2:70][C:71]1[CH:76]=[CH:75][C:74]([F:77])=[CH:73][CH:72]=1)[CH2:54][C:21]1[CH:22]=[C:23]([C:26]2[CH:53]=[CH:52][C:29]3[N:30]([C:33]([C:46]4[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=4)([C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)[C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[N:31]=[N:32][C:28]=3[CH:27]=2)[CH:24]=[CH:25][C:20]=1[F:19])=[O:62])([CH3:59])([CH3:57])[CH3:58]
Reactant: O=Cc1cc(-c2ccc3c(c2)nnn3C(c2ccccc2)(c2ccccc2)c2ccccc2)ccc1F
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H]1CNCc1ccc(F)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(Cl)Cl
Solvent: ClCCl
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)N1CCC[C@@H]1CN(Cc1ccc(F)cc1)Cc1cc(-c2ccc3c(c2)nnn3C(c2ccccc2)(c2ccccc2)c2ccccc2)ccc1F
Temperature: 25 °C
Reaction time: 8 h
Yield: 51.1 %

Procedure:
Sodium triacetoxyborohydride (159 mg, 0.75 mmol) and acetic acid (36 mg, 0.6 mmol) were added to a mixture of 5-(4-fluoro-3-formylphenyl)-1-trityl-1H-benzotriazole (145 mg, 0.3 mmol) and (R)-2-[(4-fluoro-benzylamino)-methyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (111 mg, 0.36 mmol) and 4 angstrom molecular sieves in 5 mL of dichloroethane. The mixture was stirred at ambient temperature overnight, and then it was diluted with dichloromethane, and washed with saturated sodium bicarbonate solution and brine, dried over magnesium sulfate, filtered and concentrated to leave the crude product. Chromatography (elution with ethyl acetate/cyclohexane) provided 119 mg of product.
Reaction SMILES: F[C:2]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:3]=1[C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:14])[CH3:13])[CH2:8][CH2:7]1)=O.O.[NH2:21][NH2:22]>CCCCO>[F:19][C:17]1[CH:18]=[C:2]2[C:3]([C:4]([CH:6]3[CH2:11][CH2:10][N:9]([C:12](=[O:14])[CH3:13])[CH2:8][CH2:7]3)=[N:21][NH:22]2)=[CH:15][CH:16]=1
Reactant: NN
Reactant: CC(=O)N1CCC(C(=O)c2ccc(F)cc2F)CC1
Solvent: O
Solvent: CCCCO
Product: CC(=O)N1CCC(c2n[nH]c3cc(F)ccc23)CC1
Yield: 36 %

Procedure:
A solution of 1-[4-(2,4-difluoro-benzoyl)-piperidin-1-yl]-ethanone (1.7 g, 6.4 mmol), 6 mL of hydrazine hydrate and 13 mL of n-BuOH was refluxed for 48 hours. The reaction mixture was concentrated in vacuo, the residue was diluted with water (30 mL) and then extracted with ethyl acetate (50 mL). The solvent was removed in vacuo to yield the crude product as an oil. It was washed with heptane and the solvent was filtered to yield the title product (0.60 g, 2.3 mmol, 36% yield) as a white solid. MS (ESI) m/z 261.6 (M+H+); HPLC (Novapak 150×3.9 mm C-18 column: mobile phase: 35-90% acetonitrile/water with 0.1% TFA, at 2 mL/min over 2 min.) t 1.44 min.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[C:5]([N+:15]([O-])=O)=[CH:4][N:3]=1>CC(O)=O.O.[Fe]>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([NH2:15])=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[CH:7]=1
Reactant: CN1CCN(c2cc(Cl)ncc2[N+](=O)[O-])CC1
Agent: [Fe]
Solvent: CC(=O)O
Solvent: O
Product: CN1CCN(c2cc(Cl)ncc2N)CC1
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 99.5 %

Procedure:
1-(2-chloro-5-nitro-4-pyridyl)-4-methyl-piperazine (580 mg, 2.260 mmol) was dissolved in AcOH (20 mL)/Water (2 mL) and Fe (2.524 g, 45.20 mmol) was added. The resulting mixture was stirred at 50° C. for 30 minutes. The reaction was cooled to ambient temperature then loaded onto 50 g SCX-2 cartridge (pre-washed with MeOH). The cartridge was washed with DCM/MeOH mixtures, before the product was eluted with 2M NH3 in MeOH/DCM mixtures. The solvent was removed in vacuo to give 6-chloro-4-(4-methylpiperazin-1-yl)pyridin-3-amine as a purple solid (510 mg, 99% Yield). MS (ES+) 227.1.
Reaction SMILES: [O:1]1[CH2:16][CH:2]1[CH2:3][O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10](=[O:15])[CH:9]=[CH:8]2.[CH3:17][NH:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CO>[CH3:17][N:18]([CH2:16][CH:2]([OH:1])[CH2:3][O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10](=[O:15])[CH:9]=[CH:8]2)[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: CNCc1ccccc1
Reactant: O=c1ccc2cc(OCC3CO3)ccc2[nH]1
Solvent: CO
Product: CN(Cc1ccccc1)CC(O)COc1ccc2[nH]c(=O)ccc2c1
Yield: 32.5 %

Procedure:
A suspension of 6-(2,3-epoxypropoxy)carbostyril (15 g) and N-methylbenzylamine (11 g) in methanol (150 ml) is heated with refluxing for 2.5 hours. From the mixture, methanol is distilled off under reduced pressure, and to the resulting residue is added diethylether and the precipitated crystals are collected by filtration. The crystals thus obtained are purified by silica gel column chromatography (solvent; methanol:chloroform=1:100-1:25), and recrystallized from ethanol to give 6-[3-(N-methyl-N-benzylamino)-2-hydroxypropoxy]carbostyril (7.6 g), as white powder, m.p. 129°-132° C.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17].[CH2:18]1[O:24][P:22]([OH:25])(=[O:23])[CH2:21][O:20][C@H:19]1[CH2:26][N:27]1[C:32](=[O:33])[N:31]=[C:30]([NH2:34])[CH:29]=[CH:28]1>>[CH3:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][O:25][P:22]1([O:24][CH2:18][C@H:19]([CH2:26][N:27]2[C:32](=[O:33])[N:31]=[C:30]([NH2:34])[CH:29]=[CH:28]2)[O:20][CH2:21]1)=[O:23]
Reactant: Nc1ccn(C[C@H]2COP(=O)(O)CO2)c(=O)n1
Reactant: CCCCCCCCCCCCCCCCBr
Product: CCCCCCCCCCCCCCCCOP1(=O)CO[C@@H](Cn2ccc(N)nc2=O)CO1
Yield: 55 %

Procedure:
The title compound was prepared using the same procedure as described for Example 1 using 1-bromohexadecane and cyclic cidofovir.
Reaction SMILES: [Br:1][C:2]1[C:3]([Cl:11])=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1.CC1C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>ClCCl>[Br:1][C:2]1[C:3]([Cl:11])=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:13]1[CH2:14][CH2:15][CH2:16][CH2:17][O:12]1)[N:6]=[CH:5]2
Reactant: C1=COCCC1
Reactant: Clc1c(Br)ccc2[nH]ncc12
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: Clc1c(Br)ccc2c1cnn2C1CCCCO1
Temperature: 25 °C
Reaction time: 8 h
Yield: 81.5 %

Procedure:
To a mixture of 5-bromo-4-chloro-1H-indazole (8.0 g, 34.6 mmol) and 3,4-dihydro-2H-pyran (8.72 g, 0.104 mol) in dry dichloromethane (200 mL) was added p-TsOH (0.657 g, 3.46 mmol) at room temperature. The resulting mixture was stirred at room temperature overnight. Upon completion, saturated aqueous NaHCO3 (100 mL) was added slowly to the reaction mixture. The organic layer was separated, dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (0˜3% EtOAc in petroleum ether) affording the title compound (8.9 g). 1H NMR (300 MHz, DMSO-d6): δ 8.19 (s, 1H), 7.71 (m, 2H), 5.88 (dd, 1H), 3.89-3.84 (m, 1H), 3.79-3.73 (m, 1H), 2.42-2.32 (m, 1H), 2.05-1.95 (m, 2H), 1.75-1.70 (m, 1H), 1.60-1.54 (m, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[NH:9][NH2:10].[C:11](OC(=O)C)(=[O:13])[CH3:12]>C(OCC)(=O)C>[C:11]([NH:10][NH:9][C:3]1[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=1[Cl:1])(=[O:13])[CH3:12]
Reactant: CC(=O)OC(C)=O
Reactant: NNc1ccc(Cl)cc1Cl
Solvent: CCOC(C)=O
Product: CC(=O)NNc1ccc(Cl)cc1Cl

Procedure:
Generally in a process of condensing a hydrazonoyl derivative of formula (A) to form a compound of formula (I), the free hydrazine (1) as described above, for example, 2,4-dichlorophenylhydrazine (1) is reacted with acetic anhydride at a temperature of about 10° C. in an appropriate solvent such as ethyl acetate, yielding the corresponding 1acetyl-2-(2,4-dichlorophenyl)hydrazine (2). The hydrazine (2) is then chlorinated with phosphorous oxychloride at a temperature of about 110° C. in an appropriate solvent such as toluene, yielding the hydrazonoyl derivative of formula (A), N-(2,4-dichlorophenyl)ethanehydrozonoyl chloride. The hydrozonoyl chloride (A) is condensed with a ring forming agent, for example, potassium cyanate at a temperature of about 40° C. to about 65° C. in an appropriate solvent such as DMAC, yielding the corresponding compound of formula (I), 45-dihydro-1-(2,4-dichlorophenyl)-3-methyl-1,2,4-triazol-5(1H)-one. The condensing of hydrozonoyl chloride (A) to the compound of formula (I) in solvents such as DMAC is routinely aided by the presence of a catalyst, such as potassium fluoride. A detailed procedure for the preparation, and the potassium fluoride-catalized condensing of the hydrozonoyl chloride (A) with the ring forming agent potassium cyanate in DMAC to yield a compound of formula (I) is set forth in Example 1 hereinbelow.
Reaction SMILES: [CH3:1][C:2]1[C:22]([CH3:23])=[CH:21][C:5]2[N:6]([CH2:10][C:11]3[C:12]4[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][C:13]=4[S:14][CH:15]=3)[C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH2:30]([O:32][CH:33]=[CH:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH3:31].CO>C(OCC)(=O)C>[CH2:38]([O:37][C:35](=[O:36])[CH2:34][CH:33]([N:8]1[C:4]2[CH:3]=[C:2]([CH3:1])[C:22]([CH3:23])=[CH:21][C:5]=2[N:6]([CH2:10][C:11]2[C:12]3[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][C:13]=3[S:14][CH:15]=2)[C:7]1=[O:9])[O:32][CH2:30][CH3:31])[CH3:39]
Reactant: CCOC=CC(=O)OCC
Reactant: Cc1cc2[nH]c(=O)n(Cc3csc4cccc(C)c34)c2cc1C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: CCOC(C)=O
Product: CCOC(=O)CC(OCC)n1c(=O)n(Cc2csc3cccc(C)c23)c2cc(C)c(C)cc21
Temperature: 130 °C
Yield: 31.1 %

Procedure:
To a mixture of 5,6-Dimethyl-1-(4-methyl-benzo[b]thiophen-3-ylmethyl)-1,3-dihydro-benzimidazol-2-one (0.1 g, 0.31 mmol) and K2CO3 (86 mg, 0.62 mmol) in a microwave vial was added Ethyl 3-ethoxyacrylate (0.45 g, 3.1 mmol). The reaction mixture was heated to 130° C. for 20 min in a microwave. The reaction mixture was then diluted with ethyl acetate (since there was some insoluble material left, MeOH was added to the solution mixture to solubilize the material). This organic phase was washed with water (×2). The organic phase was dried over Na2SO4 and concentrated. The resulting residue was purified by silica gel prep TLC using 4:1 Hexane:ethyl acetate as an eluent to afford 45 mg of the desired product as an oily foam. LCMS (ESMS): m/z 467.32 (M+H+).
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].OC1C(O)=CC=CC=1C(NN)=O.CN([Si:28]([CH3:31])([CH3:30])[CH3:29])C(=O)C(F)(F)F>C(#N)C>[F:1][C:2]([F:7])([F:6])[C:3]([O:5][Si:28]([CH3:31])([CH3:30])[CH3:29])=[O:4]
Reactant: CN(C(=O)C(F)(F)F)[Si](C)(C)C
Reactant: O=C(O)C(F)(F)F
Agent: NNC(=O)c1cccc(O)c1O
Solvent: CC#N
Product: C[Si](C)(C)OC(=O)C(F)(F)F
Temperature: 40 °C
Reaction time: 1 h

Procedure:
(2,3-Dihydroxybenzoyl)hydrazine, trifluoroacetate salt (2.82 g) was suspended in 50 ml of acetonitrile and 13.5 g of N-methyl-N-(trimethylsilyl)trifluoroacetamide were added. After stirring for one hour at 40° C., the solvent and trifluoroacetic acid, trimethylsilyl ester formed were distilled off in vacuo. The remaining oil was dissolved again in 50 ml of dried acetonitrile, cooled to 0° C. and added dropwise to a solution of 3.48 g of an adduct of chlorosulfonylisocyanate and (S)-(2-oxo-3-azetidinyl)carbamic acid, phenylmethyl ester in 100 ml of acetonitrile at 0° C. with stirring. After continuous stirring overnight, the solvent was distilled off in vacuo and the residue stirred (1 hour) with 200 ml of isopropanol. (S)-3-[[(Phenylmethoxy)carbonyl]amino]-N-[[2-(2,3-dihydroxybenzoyl)hydrazino]sulfonyl]-2-oxo-1-azetidinecarboxamide precipitated from the solution. Isolation by filtration and washing with ether yielded 3.87 g of white powder.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)=[C:6]([CH:8]([NH2:11])[CH2:9][CH3:10])[CH:7]=1.[CH2:18]([O:20][C:21]1[CH:22]=[C:23]([CH2:32][C:33](O)=[O:34])[CH:24]=[CH:25][C:26]=1[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH3:19]>>[CH2:18]([O:20][C:21]1[CH:22]=[C:23]([CH2:32][C:33]([NH:11][CH:8]([C:6]2[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[N:12]2[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]2)[CH2:9][CH3:10])=[O:34])[CH:24]=[CH:25][C:26]=1[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH3:19]
Reactant: CCC(N)c1cc(Cl)ccc1N1CCCCC1
Reactant: CCOC(=O)c1ccc(CC(=O)O)cc1OCC
Product: CCOC(=O)c1ccc(CC(=O)NC(CC)c2cc(Cl)ccc2N2CCCCC2)cc1OCC

Procedure:
Prepared from 1-(5-chloro-2-piperidino-phenyl)-1-propylamine and 3-ethoxy-4-ethoxycarbonyl-phenylacetic acid.