Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([N:13]2[CH2:18][CH2:17][N:16]3[CH:19]=[N:20][C:21]([C:22]([O:24]C)=[O:23])=[C:15]3[CH2:14]2)(=[O:12])=[O:11])=[C:5]([CH3:26])[CH:4]=1.[Li+].[OH-]>CO.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH3:26])[C:6]([S:10]([N:13]2[CH2:18][CH2:17][N:16]3[CH:19]=[N:20][C:21]([C:22]([OH:24])=[O:23])=[C:15]3[CH2:14]2)(=[O:11])=[O:12])=[C:7]([CH3:9])[CH:8]=1
Reactant: COC(=O)c1ncn2c1CN(S(=O)(=O)c1c(C)cc(OC)cc1C)CC2
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COc1cc(C)c(S(=O)(=O)N2CCn3cnc(C(=O)O)c3C2)c(C)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 63 %

Procedure:
A mixture of methyl 7-(4-methoxy-2,6-dimethylphenylsulfonyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxylate (0.13 mmol, 1 equiv.), MeOH/H2O (1:1, 4 ml), and LiOH (0.551 mmol, 6 equiv.) was stirred for 16 h at 25° C. The organic solvent was removed in vacuo, and the resulting suspension was diluted with water (5 ml) and adjusted to an acidic pH value with 1N HCl at 0° C. Extraction with ethyl acetate (2×15 ml) was then carried out, and the combined organic phases were washed with sat. NaCl solution. The organic phase was dried over Na2SO4 and concentrated in vacuo to yield the product in the form of a light-yellow solid. This was used in the following stage without further purification. Yield: 63%
Reaction SMILES: C[CH:2]([OH:11])[CH2:3][CH2:4][CH2:5][C:6]([CH3:10])=[C:7]([F:9])[F:8].[CH3:12][S:13](Cl)(=[O:15])=[O:14].C(N(CC)CC)C>O1CCCC1>[CH3:12][S:13]([O:11][CH2:2][CH2:3][CH2:4][CH2:5][C:6]([CH3:10])=[C:7]([F:9])[F:8])(=[O:15])=[O:14]
Reactant: CS(=O)(=O)Cl
Reactant: CC(CCCC(C)O)=C(F)F
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(CCCCOS(C)(=O)=O)=C(F)F
Temperature: 25 °C
Reaction time: 1 h
Yield: 99.6 %

Procedure:
To 100 ml of tetrahydrofuran, 5.00 g (33 mmol) of methyl 6,6-difluoro-5-methyl-5-hexenol and 4.20 g (37 mmol) of methanesulfonyl chloride were dissolved, followed by drop-wisely adding 4.40 g (44 mmol) of triethylamine under ice-cooling. After the end of the drop-wise addition, the reaction liquid was stirred at room temperature for 1 hour. Hydrochloric acid salt of triethylamine was filtered, followed by adding water to the filtrate and extracting with ethyl acetate. The organic layer was washed with water and a saturated saline solution in this order, followed by drying over anhydrous magnesium sulfate and concentrating under reduced pressure to obtain 7.50 g (yield: 99%) of 6,6-difluoro-5-methyl-5-hexenyl methanesulfonate.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[C:12]1([CH3:22])[CH:17]=[CH:16][CH:15]=[C:14]([S:18](Cl)(=[O:20])=[O:19])[CH:13]=1>CN(C1C=CN=CC=1)C>[CH3:22][C:12]1[CH:13]=[C:14]([S:18]([NH:1][C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:11]=2[N:10]=[CH:9][CH:8]=[CH:7]3)(=[O:20])=[O:19])[CH:15]=[CH:16][CH:17]=1
Reactant: Nc1cccc2cccnc12
Reactant: Cc1cccc(S(=O)(=O)Cl)c1
Agent: CN(C)c1ccncc1
Product: Cc1cccc(S(=O)(=O)Nc2cccc3cccnc23)c1
Yield: 64.5 %

Procedure:
In the similar fashion using route 14 general procedure 27, 8-aminoquinoline (200 mg, 1.38 mmol), m-toluenesulfonyl chloride (260 mg, 1.3 mmol) and DMAP (cat.) gave the title compound (250 mg, 60%) after purification by column chromatography with DCM as the eluent.
Reaction SMILES: [CH2:1]([C:4]1[N:5]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22](O)=[O:23])[C:6]2[C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N:9]=[CH:8][C:7]=2[N:16]=1)[CH2:2][CH3:3].C(Cl)(=O)C(Cl)=O.[NH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1>ClCCl>[N:31]1([C:22](=[O:23])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][N:5]2[C:6]3[C:15]4[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=4[N:9]=[CH:8][C:7]=3[N:16]=[C:4]2[CH2:1][CH2:2][CH3:3])[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1
Reactant: C1COCCN1
Reactant: CCCc1nc2cnc3ccccc3c2n1CCCCCC(=O)O
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Product: CCCc1nc2cnc3ccccc3c2n1CCCCCC(=O)N1CCOCC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 99.2 %

Procedure:
A solution of 6-(2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)hexanoic acid (3.0 g, 9.2 mmol) in anhydrous dichloromethane (50 mL) was cooled to 0° C. Oxalyl chloride (1.44 mL, 16.6 mmol) was added dropwise over a period of 15 minutes. The resulting solution was allowed to warm to ambient temperature and stirred for one hour and then concentrated under reduced pressure. The residue was dissolved in dichloromethane (50 mL), and morpholine (2.41 mL, 27.6 mmol) was added. The reaction was stirred overnight, washed sequentially with saturated aqueous sodium bicarbonate and brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide 3.6 g of 1-(6-morpholin-4-yl-6-oxohexyl)-2-propyl-1H-imidazo[4,5-c]quinoline.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]=[CH:10][C:11]([OH:13])=[O:12]>CCO.O=[Pt]=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]([OH:13])=[O:12]
Reactant: O=C(O)C=Cc1ccc(F)cc1F
Agent: O=[Pt]=O
Solvent: CCO
Product: O=C(O)CCc1ccc(F)cc1F
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 5.0 g (27.15 mmol) of 3-(2,4-difluorophenyl)acrylic acid in EtOH (50 mL) is hydrogenated over PtO2 catalyst under atmospheric pressure and stirred overnight at RT. After filtration to remove the catalyst, the filtrate is concentrated in vacuo to afford 3-(2,4-difluorophenyl)propanoic acid as a white solid: m.p. 104° C. 1H NMR (CDCl3, 400 MHz) δ 2.67 (t, 2H, J=7.6 Hz), 2.94 (t, 2H, J=7.6 Hz), 6.80 (m, 2H), 7.18 (dd, 1H, J=14.8 Hz and 8.0 Hz). The title A compound, (2,4-difluorophenyl)piperazin-1-yl-propanone hydrochloride is obtained analogously to the title B compound of Example 4 as a white solid: m.p=221° C. LC/MS (M+1=255.1). 1H NMR (DMSO-d6, 400 MHz) δ 2.66 (t, 2H, J=7.6 Hz), 2.81 (t, 2H, J=7.6 Hz), 3.01 (m, 2H), 3.05 (m, 2H), 3.69 (m, 4H), 7.02 (dt, 1H, J=8.4 Hz and 2.4 Hz), 7.18 (dt, 1H, J=10.0 Hz and 28 Hz), 7.29 (dd, 1H, J=15.6 Hz and 8.8 Hz), 9.65 (br s, NH). Anal. calculated for (Cl3H16F2N2O HCl+0.2H2O): C, 53.05; H, 5.96; Cl, 12.04; F, 12.91; N, 9.52; O, 6.52. Found C, 53.01; H, 5.96; N, 9.74.
Reaction SMILES: [CH:1]1[C:6]2[C:7](=O)[NH:8][C:9]3[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=3[O:11][C:5]=2[CH:4]=[CH:3][CH:2]=1.[CH3:17][CH:18]1[CH2:23][NH:22][CH2:21][CH:20]([CH3:24])[NH:19]1.[OH-].[NH4+]>C1(C)C=CC=CC=1.Cl[Ti](Cl)(Cl)Cl>[CH3:17][CH:18]1[NH:19][CH:20]([CH3:24])[CH2:21][N:22]([C:7]2[C:6]3[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=3[O:11][C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[N:8]=2)[CH2:23]1
Reactant: CC1CNCC(C)N1
Reactant: O=C1Nc2ccccc2Oc2ccccc21
Agent: Cl[Ti](Cl)(Cl)Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: Cc1ccccc1
Product: CC1CN(C2=Nc3ccccc3Oc3ccccc32)CC(C)N1
Temperature: 25 °C
Yield: 60.4 %

Procedure:
To a stirred solution of 10,11-dihydro-dibenz[b,f][1,4]oxazepin-11-one (0.4 g; 1.9 mmol; Aldrich) in dry toluene (20 mL) at room temperature was added 2,6-dimethyl piperazine (0.99 g; 8.7 mmol; Aldrich) followed by the dropwise addition of TiCl4 (1M in toluene, 2.27 mL; 2.27 mmol). The reaction mixture was refluxed for 2 hours, cooled to room temperature and then poured into an ammonium hydroxide solution (30%, 50 mL). The resulting mixture was extracted with dichloromethane (4×75 mL), and the combined organic phases were then dried (K2CO3) and concentrated. Purification of the product was conducted on silica gel using CHCl3 :MeOH (94:6) eluant to give 0.353 g (60%) of 11-(3,5-dimethyl-l-piperazinyl)-dibenz [b,f][1,4]oxazepine as a pale yellow solid; m.p. 112°-114° C.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([OH:9])[CH:6]=[CH:7][CH:8]=1)#[N:2].[ClH:10].[H][H]>[Pd].CO>[ClH:10].[OH:9][C:5]1[CH:4]=[C:3]([CH2:1][NH2:2])[CH:8]=[CH:7][CH:6]=1
Reactant: N#Cc1cccc(O)c1
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: CO
Product: NCc1cccc(O)c1
Reaction time: 1 h
Yield: 80.9 %

Procedure:
Methanol (100 mL) and 10% palladium on carbon (2 g) were charged to a 250 mL Parr bottle followed by 3-cyanophenol (19.0 g, 0.1595 mol) and concentrated HCl (16.66 mL, 0.2 mol). The mixture was hydrogenated at room temperature and 50 psi until the uptake of hydrogen stopped (about 10 h). The reaction was filtered through a bed of Celite and the filter cake was washed with methanol (3×25 mL). The combined filtrates were evaporated under reduced pressure. Remaining volatiles were removed by evaporating the residue twice from 50 mL portions of absolute ethanol. The crude amine hydrochloride, essentially free of residual HCl, was dissolved with warming in a minimum amount of absolute ethanol (80 mL) and the stirred solution was diluted with anhydrous diethyl ether (500 mL). The mixture was stirred in an ice bath for 1 h then the colorless crystalline product was filtered off, washed with anhydrous diethyl ether (3×50 mL) and dried in vacuo to furnish (3-hydroxyphenyl)methylamine hydrochloride salt (20.6 g, 80.9%), mp 146-148° C.
Reaction SMILES: [BH4-].[Na+].[CH3:3][CH:4]1[CH:9]([N:10]2[CH:14]=[CH:13][N:12]=[CH:11]2)[C:8](=[O:15])[C:7]2[CH:16]=[CH:17][CH:18]=[CH:19][C:6]=2[O:5]1.O>CO>[CH3:3][CH:4]1[CH:9]([N:10]2[CH:14]=[CH:13][N:12]=[CH:11]2)[CH:8]([OH:15])[C:7]2[CH:16]=[CH:17][CH:18]=[CH:19][C:6]=2[O:5]1
Reactant: CC1Oc2ccccc2C(=O)C1n1ccnc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CC1Oc2ccccc2C(O)C1n1ccnc1
Reaction time: 2 h
Yield: 99.1 %

Procedure:
NaBH4 (0.6 g) was added portionwise to a solution of 2-methyl-3-(1-imidazolyl)-2,3-dihydro-4H-1-benzopyran-4 one (1.3 g) in MeOH (70 ml) at room temperature. The mixture, stirred for 2 hours, added with water (300 ml), extracted with CHCl3, dried and evaporated to dryness gave 2-methyl-3-(1-imidazolyl)-2.3-dihydro-4H-1-benzopyran-4-ol (1.3 g); m.p.=160°-175° C.;
Reaction SMILES: [Cl:1][C:2]1[CH:35]=[CH:34][C:5]([CH2:6][NH:7][C:8]([C:10]2[S:11](=[O:33])(=[O:32])[N:12]([CH3:31])[C:13]3[CH:20]=[CH:19][C:18]([C:21]#[C:22][CH2:23][O:24]C4CCCCO4)=[CH:17][C:14]=3[C:15]=2[OH:16])=[O:9])=[CH:4][CH:3]=1.CC1C=CC(S(O)(=O)=O)=CC=1.O>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[S:11](=[O:33])(=[O:32])[N:12]([CH3:31])[C:13]3[CH:20]=[CH:19][C:18]([C:21]#[C:22][CH2:23][OH:24])=[CH:17][C:14]=3[C:15]=2[OH:16])=[O:9])=[CH:34][CH:35]=1
Reactant: CN1c2ccc(C#CCOC3CCCCO3)cc2C(O)=C(C(=O)NCc2ccc(Cl)cc2)S1(=O)=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Solvent: O
Product: CN1c2ccc(C#CCO)cc2C(O)=C(C(=O)NCc2ccc(Cl)cc2)S1(=O)=O
Temperature: 55 °C
Yield: 63.7 %

Procedure:
To a solution of N-(4-chlorobenzyl)-4-hydroxy-1-methyl-6-(3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl)-1H-2,1-benzothiazine-3-carboxamide 2,2-dioxide (Preparation 53, 0.30 g) in CH3OH (30 mL) is added p-TsOH.H2O (30 mg). The reaction mixture is heated to 55° C. for 2 h. The solvent is evaporated in vacuo and the residue is diluted with Et2O (20 mL) and sonicated. The resulting precipitate is filtered and washed with Et2O to afford 0.16 g (61%) of the title compound as a white solid. Physical characteristics: m.p. 167-168° C.; 1H NMR (300 MHz, CDCl3) δ15.82, 8.21, 7.93, 7.69, 7.36, 7.17, 4.60, 4.53, 3.49, 2.21; IR (diffuse reflectance) 3344, 1615, 1579, 1554, 1540, 1490, 1392, 1385, 1325, 1310, 1293, 1279, 1160, 1093, 1031 cm−1; MS (ESI+) m/z 433 (MH+); HRMS (FAB) m/z 433.0614 (C20H17ClN2O5S+H). Anal. Found: C, 54.57; H, 4.16; N, 6.10.
Reaction SMILES: [Cl:1][C:2]1[C:9]([C:10]#[C:11][Si](C)(C)C)=[C:8](F)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[CH3:17][S:18][CH2:19][C@H:20]([NH2:22])[CH3:21]>>[Cl:1][C:2]1[C:3]([C:4]#[N:5])=[CH:6][CH:7]=[C:8]2[C:9]=1[CH:10]=[CH:11][N:22]2[C@H:20]([CH3:21])[CH2:19][S:18][CH3:17]
Reactant: C[Si](C)(C)C#Cc1c(F)ccc(C#N)c1Cl
Reactant: CSC[C@@H](C)N
Product: CSC[C@@H](C)n1ccc2c(Cl)c(C#N)ccc21

Procedure:
Synthesized in a manner similar to Example 36 using 2-chloro-4-fluoro-3-((trimethylsilyl)ethynyl)benzonitrile (Example 32B) and (R)-1-(methylthio)propan-2-amine (Example 27C): MS (ESI): m/z 265 (M+H).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[C:9]([C:11]2[O:12][C:13]([C:23](O)=[O:24])=[C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[Cl:22])[N:15]=2)[C:8]([CH3:26])=[CH:7][N:6]=1)(=[O:3])[CH3:2].C[N:28](C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.N>C(Cl)Cl>[C:1]([NH:4][C:5]1[CH:10]=[C:9]([C:11]2[O:12][C:13]([C:23]([NH2:28])=[O:24])=[C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[Cl:22])[N:15]=2)[C:8]([CH3:26])=[CH:7][N:6]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Nc1cc(-c2nc(-c3ccccc3Cl)c(C(=O)O)o2)c(C)cn1
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Agent: N
Solvent: ClCCl
Product: CC(=O)Nc1cc(-c2nc(-c3ccccc3Cl)c(C(N)=O)o2)c(C)cn1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 14.7 %

Procedure:
To a round bottom flask was added 2-[2-(acetylamino)-5-methylpyridin-4-yl]-4-(2-chlorophenyl)-1,3-oxazole-5-carboxylic acid (0.12 g, 0.33 mmol), DCM (4 mL), TBTU (0.42 g, 1.3 mmol), and TEA (0.35 mL, 2.5 mmol). The mixture was allowed to stir for 5 min at rt, and then ammonia (0.5M in dioxane, 32 mL) was added. The resulting mixture was allowed to stir at rt overnight and then concentrated. DCM and water were added. The organic solution was separated, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography to give 2-[2-(acetylamino)-5-methylpyridin-4-yl]-4-(2-chlorophenyl)-1,3-oxazole-5-carboxamide (0.018 g, 15%). LCMS (FA): m/z=371.4 (M+H).
Reaction SMILES: Cl[CH2:2][C:3]([CH:5]1[CH2:9][CH2:8][CH2:7][O:6]1)=[O:4].[SH:10][C@H:11]1[NH:14][C:13](=[O:15])[C@H:12]1[NH:16][C:17](=[O:26])[CH2:18][O:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(OCC)(=O)C>[O:19]([CH2:18][C:17]([NH:16][C@H:12]1[C@@H:11]([S:10][CH2:2][C:3]([CH:5]2[CH2:9][CH2:8][CH2:7][O:6]2)=[O:4])[NH:14][C:13]1=[O:15])=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: O=C(COc1ccccc1)N[C@@H]1C(=O)N[C@@H]1S
Reactant: O=C(CCl)C1CCCO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=C(COc1ccccc1)N[C@@H]1C(=O)N[C@@H]1SCC(=O)C1CCCO1
Yield: 59 %

Procedure:
(RS)-2-Chloroacetyltetrahydrofuran (2.46 g, 16.5 mmol), (3R,4R)-4-mercapto-3-phenoxyacetamidoazetidin-2-one (4.157 g, 16.5 mmol) and potassium carbonate (2.227 g 16.5 mmol) in DMF (10 ml) were stirred for 2 h, diluted with ethyl acetate, washed twice with water and with brine, dried concentrated and flash chromatographed eluting with 40, 30, 20, 10 and 0% hexane in ethyl acetate to give the title compound as a foam (3.547 g, 59%); νmax (CH2Cl2) 3405, 1785, 1693, 1520, 1496 and 1240 cm-1 ; δ(CDCl3, 250 MHz) 1.9-2.3 (4 H, m), 3.42 and 3.62, 3.46 and 3.56 (together 2 H, 2 ABq, J15.8 Hz, 15.4 Hz), 3.85-4.0 (2 H, m), 4.4-4.5 (1 H, m), 4.58 (2 H, s), 5.01, 5.04 (together 1 H, 2 d, J4.7 Hz), 5.59 (1 H, dd, J 8.8, 4.5 Hz) 6.62, 6.68 (together 1 H, 2 s), 6.9-7.4 (5 H, m) and 7.45, 7.47 (together 1 H, 2 d, J8.8 Hz). [Mass spectrum: M+ (364)].
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH2:11][CH2:10][C:9]1=[CH:13][C:14]1C=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH3:23])[CH:15]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(O)C.[Pt].[H][H]>[CH2:1]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[CH:14]=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: [H][H]
Reactant: COc1ccc(C=C2CCCN2Cc2ccccc2)cc1OC
Agent: [Pt]
Solvent: CCO
Product: COc1ccc(C2CCCN2Cc2ccccc2)cc1OC

Procedure:
Dissolve 3 g of 1-benzyl-2-(3,4-dimethoxybenzylidene)pyrrolidine in ethanol and hydrogenate with platinum/hydrogen. Distil the hydrogenated product under a vacuum to obtain 2.3 g (77% of theory) of title compound (b.p. 173° at 0.007 mm of Hg).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]2[C:6]([O:10][CH:11]([CH2:23]C(C)C)[CH2:12][CH2:13][N:14]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH3:15])=[CH:7][CH:8]=[CH:9][C:2]1=2.[CH2:27](N(C)CCC(O)CCCC)[C:28]1C=CC=C[CH:29]=1>>[S:1]1[CH:5]=[CH:4][C:3]2[C:6]([O:10][CH:11]([CH2:23][CH2:27][CH2:28][CH3:29])[CH2:12][CH2:13][N:14]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH3:15])=[CH:7][CH:8]=[CH:9][C:2]1=2
Reactant: CCCCC(O)CCN(C)Cc1ccccc1
Reactant: CC(C)CC(CCN(C)Cc1ccccc1)Oc1cccc2sccc12
Product: CCCCC(CCN(C)Cc1ccccc1)Oc1cccc2sccc12

Procedure:
Using a method similar to that for [3-(Benzo[b]thiophen-4-yloxy)-5-methyl-hexyl]-benzyl-methyl-amine, 1-(benzyl-methyl-amino)-heptan-3-ol affords the title compound: mass spectrum (ion spray) m/z=368 (M+1); 1H NMR (CDCl3) δ 8 7.45-7.41 (m, 2H), 7.29-7.19 (m, 7H), 6.80 (d, 1H), 4.56-4.51 (m, 1H), 3.47 (s, 2H), 2.55 (t, 2H), 2.20 (s, 3H), 2.01-1.91 (m, 2H), 1.90-1.63 (m, 3H), 1.45-1.29 (m, 4H), 0.89 (t, 3H).
Reaction SMILES: [CH3:1][C:2]1([CH2:13][N:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][C:27]([NH:30]C(OC(C)(C)C)=O)=[CH:26][CH:25]=3)=[O:21])[CH2:16][CH2:15]2)[O:6][C:5]2=[N:7][C:8]([N+:10]([O-:12])=[O:11])=[CH:9][N:4]2[CH2:3]1.FC(F)(F)C(O)=O.C(=O)([O-])O.[Na+]>C(Cl)Cl>[CH3:1][C:2]1([CH2:13][N:14]2[CH2:15][CH2:16][N:17]([C:20]([O:22][CH2:23][C:24]3[CH:25]=[CH:26][C:27]([NH2:30])=[CH:28][CH:29]=3)=[O:21])[CH2:18][CH2:19]2)[O:6][C:5]2=[N:7][C:8]([N+:10]([O-:12])=[O:11])=[CH:9][N:4]2[CH2:3]1
Reactant: CC(C)(C)OC(=O)Nc1ccc(COC(=O)N2CCN(CC3(C)Cn4cc([N+](=O)[O-])nc4O3)CC2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC1(CN2CCN(C(=O)OCc3ccc(N)cc3)CC2)Cn2cc([N+](=O)[O-])nc2O1
Temperature: 25 °C
Reaction time: 2 h
Yield: 36.4 %

Procedure:
A mixture of 4-(tert-butoxycarbonylamino)-benzyl 4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylate (340 mg, 0.66 mmol), trifluoroacetic acid (2 ml) and methylene chloride (10 ml) was stirred at room temperature for 2 hours, and then neutralized with a saturated sodium hydrogencarbonate solution. The organic phase was washed with water and a saturated saline solution in this order, dried over magnesium sulfate and then filtered. The filtrate was concentrated under reduced pressure. To the residue, diethyl ether was added, and the precipitates were filtered off to afford 4-aminobenzyl 4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylate (100 mg, yield 37%) as a light yellow powder.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:18])([CH2:16][NH2:17])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1.[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=1[S:27](Cl)(=[O:29])=[O:28]>>[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=1[S:27]([NH:17][CH2:16][C:9]([C:3]1[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=1[Cl:1])([OH:18])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1)(=[O:29])=[O:28]
Reactant: O=S(=O)(Cl)c1cc(Cl)ccc1Cl
Reactant: NCC(O)(Cn1cncn1)c1ccc(Cl)cc1Cl
Product: O=S(=O)(NCC(O)(Cn1cncn1)c1ccc(Cl)cc1Cl)c1cc(Cl)ccc1Cl

Procedure:
Following the procedure described in the preceeding examples but using 2-(2,4-dichlorophenyl)-3-amino-1-(1H-1,2,4-triazol-1-yl)propan-2-ol and 2,5-dichlorobenzenesulfonylchloride, the title compound was obtained in a similar yield:
Reaction SMILES: [NH:1]([C:3]1[CH:8]=[CH:7][NH:6][C:5](=[O:9])[CH:4]=1)[NH2:2].[CH2:10]([CH2:17][C:18](=O)[CH3:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[CH3:19][C:18](=[N:2][NH:1][C:3]1[CH:8]=[CH:7][NH:6][C:5](=[O:9])[CH:4]=1)[CH2:17][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: CC(=O)CCc1ccccc1
Reactant: NNc1cc[nH]c(=O)c1
Product: CC(CCc1ccccc1)=NNc1cc[nH]c(=O)c1

Procedure:
In accordance with the same procedures as in Step 2 of Preparation 1, except for using 4-hydrazino-1H-pyridin-2-one (5.39 g, 43.1 mmol) prepared in Step 1 of Preparation 1 and benzylacetone (9.70 ml, 64.6 mmol), the titled compound was obtained as a white solid. (Yield: 66.5%) The product was used in the subsequent reaction without further purification.
Reaction SMILES: [C:1]([C:4]1[NH:5][C:6]2[C:11]([C:12]=1[CH2:13][CH:14]([CH3:16])[CH3:15])=[CH:10][CH:9]=[C:8]([C:17]([O:19][CH3:20])=[O:18])[CH:7]=2)(=[O:3])[CH3:2].[Cl:21][C:22]1[CH:29]=[CH:28][CH:27]=[CH:26][C:23]=1[CH2:24]Br>>[C:1]([C:4]1[N:5]([CH2:24][C:23]2[CH:26]=[CH:27][CH:28]=[CH:29][C:22]=2[Cl:21])[C:6]2[C:11]([C:12]=1[CH2:13][CH:14]([CH3:16])[CH3:15])=[CH:10][CH:9]=[C:8]([C:17]([O:19][CH3:20])=[O:18])[CH:7]=2)(=[O:3])[CH3:2]
Reactant: COC(=O)c1ccc2c(CC(C)C)c(C(C)=O)[nH]c2c1
Reactant: Clc1ccccc1CBr
Product: COC(=O)c1ccc2c(CC(C)C)c(C(C)=O)n(Cc3ccccc3Cl)c2c1

Procedure:
Methyl 2-acetyl-1-(2-chlorobenzyl)-3-isobutylindole-6-carboxylate (71.4 mg) was prepared from methyl 2-acetyl-3-isobutylindole-6-carboxylate (58 mg) and 2-chlorobenzyl bromide (0.04 ml) in a similar manner to that of Example 1.
Reaction SMILES: [NH2:1][C:2]1[C:3]([I:29])=[C:4]([CH2:24][O:25][C:26](=[O:28])[CH3:27])[C:5]([I:23])=[C:6]([C:21]=1[I:22])[C:7]([NH:9][CH2:10][CH:11]([O:17][C:18](=[O:20])[CH3:19])[CH2:12][O:13][C:14](=[O:16])[CH3:15])=[O:8].[C:30]([O:33][CH2:34][C:35](Cl)=[O:36])(=[O:32])[CH3:31].C(=O)([O-])O.[Na+]>CN(C)C(=O)C>[C:30]([O:33][CH2:34][C:35]([NH:1][C:2]1[C:3]([I:29])=[C:4]([CH2:24][O:25][C:26](=[O:28])[CH3:27])[C:5]([I:23])=[C:6]([C:21]=1[I:22])[C:7]([NH:9][CH2:10][CH:11]([O:17][C:18](=[O:20])[CH3:19])[CH2:12][O:13][C:14](=[O:16])[CH3:15])=[O:8])=[O:36])(=[O:32])[CH3:31]
Reactant: CC(=O)OCc1c(I)c(N)c(I)c(C(=O)NCC(COC(C)=O)OC(C)=O)c1I
Reactant: CC(=O)OCC(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: CC(=O)OCC(=O)Nc1c(I)c(COC(C)=O)c(I)c(C(=O)NCC(COC(C)=O)OC(C)=O)c1I
Reaction time: 8 h
Yield: 99.4 %

Procedure:
5-Amino-3-acetoxymethyl-N-(2,3-diacetoxypropyl)-2,4,6-triiodobenzamide (3.0 g, 4.03 mmol) was dissolved in dry N,N-dimethylacetamide (8 ml) at ambient temperature. With efficient stirring acetoxyacetyl chloride (4.39 ml, 40.3 mmol) was added dropwise, and the mixture was stirred overnight. The mixture was then added slowly with stirring into a saturated solution of sodium hydrogen carbonate (80 ml). The precepitate formed was filtered off and dissolved in chloroform (80 ml). The organic solution was washed with an aqueous saturated solution of NaHCO3 (25 ml), and then evaporated to dryness. The solid residue was dissolved in acetone and filtered through a pad of alumina with acetone as eluent. Evaporation of the solvent gave 3.38 g (100%) of a white crystalline product.
Reaction SMILES: [O:1]=[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:12]([F:15])([F:14])[F:13])[CH:8]=2)[N:3]1[CH2:16][C:17]([O:19]C)=[O:18].O[Li].O.Cl>C1COCC1.O>[O:1]=[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:12]([F:14])([F:13])[F:15])[CH:8]=2)[N:3]1[CH2:16][C:17]([OH:19])=[O:18]
Reactant: COC(=O)Cn1c(=O)ccc2cc(C(F)(F)F)ccc21
Agent: Cl
Agent: [Li]O
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)Cn1c(=O)ccc2cc(C(F)(F)F)ccc21
Reaction time: 8 h
Yield: 94.4 %

Procedure:
To a stirring solution of methyl 2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetate (4.8 g, 16.8 mmol) in THF/water (25 mL/5 mL, 5:1) was added LiOH.H2O (3.52 g, 84.2 mmol). The resulting mixture was stirred overnight. The crude mixture was slowly acidified with 1N HCl and then extracted with EtOAc. The organic phase was dried (MgSO4), filtered and concentrated under vacuum to give 2-(2-oxo-6-(trifluoromethyl)quinolin-1(2H)-yl)acetic acid (4.3 g). Retention time (min)=3.005, method [7], MS (ESI) 272.1 (M+H).