Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:15]=[CH:16][CH:17]=1)[O:6][CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])#[N:2].[C:18](OC)(=[O:26])[C:19]1[C:20](=[CH:22][CH:23]=[CH:24][CH:25]=1)[SH:21].C(N(CC)CC)C>C1(C)C=CC=CC=1>[O:26]=[C:18]1[C:19]2[CH:25]=[CH:24][CH:23]=[CH:22][C:20]=2[S:21][C:1]([C:3]2[CH:4]=[C:5]([CH:15]=[CH:16][CH:17]=2)[O:6][CH2:7][C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9])=[N:2]1
Reactant: CC(C)(C)OC(=O)COc1cccc(C#N)c1
Reactant: COC(=O)c1ccccc1S
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)COc1cccc(-c2nc(=O)c3ccccc3s2)c1
Yield: 19.8 %

Procedure:
A mixture of tert-butyl (3-cyanophenoxy)acetate (4.64 g, 20 mmol), methyl thiosalicylate (3.70 g, 24 mmol), triethylamine (2.54 g, 25 mmol) and toluene (15 ml) was heated and refluxed for 20 hours under a nitrogen flow. After the solvent was distilled off under reduced pressure, the residue was applied to column chromatography using silica gel. From the fractions eluted with hexane-ethyl acetate (3:1, v/v), the title compound (1.46 g, 20%) was obtained as crystals.
Reaction SMILES: [O:1]=[C:2]1[C:7]([CH:8]=[O:9])=[CH:6][CH:5]=[CH:4][NH:3]1.[F:10][C:11]([F:23])([F:22])[O:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.CCN(CC)CC>CC([O-])=O.CC([O-])=O.[Cu+2].CS(C)=O>[O:1]=[C:2]1[C:7]([CH:8]=[O:9])=[CH:6][CH:5]=[CH:4][N:3]1[C:16]1[CH:15]=[CH:14][C:13]([O:12][C:11]([F:10])([F:22])[F:23])=[CH:18][CH:17]=1
Reactant: O=Cc1ccc[nH]c1=O
Reactant: OB(O)c1ccc(OC(F)(F)F)cc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: O=Cc1cccn(-c2ccc(OC(F)(F)F)cc2)c1=O
Temperature: 25 °C
Yield: 22.9 %

Procedure:
In a microwave vial were placed 2-oxo-1,2-dihydropyridine-3-carbaldehyde 1-1 (200 mg, 1.62 mmol), 4-trifluoromethoxyphenylboronic acid 4-1 (660 mg, 3.25 mmol), and anhydrous Cu(OAc)2 (295 mg, 1.62 mmol). To the mixture was added DMSO (3.20 mL) followed by Et3N (0.45 mL, 3.25 mmol). The mixture was irradiated in microwave apparatus (Biotage) at 100° C. for 15 minutes and cooled to room temperature. The mixture was concentrated and the residue was purified by silica gel chromatography (0-20% EtOAc in hexane) to give 105 mg (25%) of 2-2 as a pale yellow solid: 1H NMR (300 MHz, CDCl3) δ 10.34 (1H, s), 8.13 (1H, dd, J=6.9, 2.1 Hz), 7.63 (1H, dd, J=6.9, 2.1 Hz), 7.47-7.36 (4H, m), 6.44 (1H, t, J=6.9 Hz); ESI-MS m/z 284 [C13H8F3NO3+H]+.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10](=[O:14])[C:11](Cl)=[O:12])=[CH:2]1.[CH2:15]([NH:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CC#N>[CH2:23]([N:22]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:11](=[O:12])[C:10]([C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][CH:2]=1)=[O:14])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: O=C(Cl)C(=O)c1c[nH]c2ccccc12
Reactant: c1ccc(CNCc2ccccc2)cc1
Solvent: CC#N
Product: O=C(C(=O)N(Cc1ccccc1)Cc1ccccc1)c1c[nH]c2ccccc12

Procedure:
N,N-Dibenzyl-2-(1H-indol-3-yl)-2-oxo-acetamide was synthesized following scheme I above starting from (1H-indol-3-yl)-oxo-acetyl chloride and dibenzylamine. Yield (58%). HPLC ret. time 3.52 min, 10-99% CH3CN, 5 min run; 1H NMR (400 MHz, DMSO-d6) δ 12.36 (d, J=2.1 Hz, 1H), 8.18 (d, J=3.3 Hz, 1H), 8.11 (d, J=7.6 Hz, 1H), 7.54 (m, 1H), 7.43-7.39 (m, 2H), 7.35-7.22 (m, 10H), 4.54 (s, 2H), 4.41 (s, 2H); ESI-MS 369.3 m/z (MH+).
Reaction SMILES: Cl[C:2]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:3]=1[C:4]#[N:5].[NH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CN1CCCC1.C(N(C(C)C)CC)(C)C>CCOC(C)=O>[N+:10]([C:7]1[CH:8]=[CH:9][C:2]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[C:3]([CH:6]=1)[C:4]#[N:5])([O-:12])=[O:11]
Reactant: N#Cc1cc([N+](=O)[O-])ccc1Cl
Reactant: Nc1ccccc1
Agent: CN1CCCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Product: N#Cc1cc([N+](=O)[O-])ccc1Nc1ccccc1
Yield: 88 %

Procedure:
2-Chloro-5-nitrobenzonitrile (Aldrich) (3.64 grams (hereinafter “g”), 20 millimoles (hereinafter “mmol”), aniline (2 milliliter (hereinafter “mL”), 22 mmol), N-methylpyrollidine (10 mL) and diisopropylethylamine (4 mL) were combined and heated to 120° under Ar for 18 hours (hereinafter “h”), cooled, poured into EtOAc (150 mL), washed with H2O (3×50 mL) and saturated aqueous (hereinafter “satd. aq.) NaCl (50 mL), dried (Na2SO4), concentrated, and the residue was triturated with hexane, filtered and the solid was washed with hexane and dried in vacuo to afford 4.23 g (88%) of the title compound as a light green solid. 1H NMR (400) MHz, δ: 8.45 (finely split doublet, 1), 8.19 (dd, 1), 7.48 (m,3), 7.28 (d,2), 7.06 (d, 1), 6.96 (br s,1).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][NH:7][CH3:8])=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH2:18](Br)[C:19]#[CH:20]>C1C=CC=CC=1>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][N:7]([CH2:20][C:19]#[CH:18])[CH3:8])=[CH:4][CH:3]=1
Reactant: C#CCBr
Reactant: CNCc1ccc(Cl)cc1
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: C#CCN(C)Cc1ccc(Cl)cc1

Procedure:
To a solution of 31.1 g (0.2 mole) N-(4-chlorobenzyl)-methylamine and 30.3 g (0.3 mole) triethylamine in 150 ml dry benzene are added in portions at room temperature while stirring 23.8 g (0.2 mole) propargyl bromide. The solution is heated for 17 hours with reflux. After filtering off the solid phase, the the solvent is distilled under vacuum and the remaining residue fractionally distilled under reduced pressure. One thus obtains 30.9 g N-(4-chlorobenzyl)-N-methyl-2-propinylamine (79% of the theory as colorless liquid of the boiling point 86°-106° C./2 Torr.
Reaction SMILES: [C:1]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][C:47]([OH:49])=O)(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].C(N(CC)CC)C.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[OH:68][CH2:69][C@@H:70]([C@@H:72]([C@@H:74]([CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH2:81][CH2:82][CH2:83][CH2:84][CH2:85][CH2:86][CH2:87][CH2:88][CH3:89])[OH:75])[OH:73])[NH2:71]>C(Cl)(Cl)Cl>[C:1]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][C:47]([NH:71][C@H:70]([C@@H:72]([C@@H:74]([CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH2:81][CH2:82][CH2:83][CH2:84][CH2:85][CH2:86][CH2:87][CH2:88][CH3:89])[OH:75])[OH:73])[CH2:69][OH:68])=[O:49])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCCCCCCCC[C@@H](O)[C@@H](O)[C@@H](N)CO
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)OCCCCCCCCCCCCCCCCCCCCCCCCCCC(=O)O
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: CCCCCCCC/C=C\CCCCCCCC(=O)OCCCCCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)[C@H](O)CCCCCCCCCCCCCC
Reaction time: 2 h
Yield: 29.6 %

Procedure:
A solution of 27-oleoyloxy-heptacosanoic acid (2 g; 2.89 mmoles) in chloroform (30 ml) and triethylamine (1.6 ml; 11.5 mmoles) was added in 30 minutes to a stirred solution of 0.5 grams of p-toluenesulphonyl chloride (0.5 g; 2.6 mmoles) in chloroform (40 ml) under nitrogen while keeping the temperature at 50° C. After stirring for 1 hour at 50° C. phytosphingosine (0.8 g; 2.52 mmoles) was added and stirring was continued for 2 hours at 50° C. After cooling the mixture was washed with 50 ml of 0.5N hydrochloric acid, 50 ml of water and brine respectively. The organic layer was evaporated in vacuum and the residue was crystallized from 50 ml of warm 2-propanol under nitrogen giving 2.03 grams of the impure title compound. Purification over 40 grams of silica gel (Flash 30-60 μm) with chloroform/methanol=9/1 and subsequent crystallization from 40 ml of hot isopropanol gave 0.74 g of the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]([C:11]1[O:12][C:13]2[CH:20]=[C:19](B3OC(C)(C)C(C)(C)O3)[CH:18]=[CH:17][C:14]=2[C:15]=1[CH3:16])=[O:10].Br[C:31]1[N:36]=[C:35]([C:37]([NH2:39])=[O:38])[CH:34]=[CH:33][CH:32]=1>>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]([C:11]1[O:12][C:13]2[CH:20]=[C:19]([C:31]3[N:36]=[C:35]([C:37]([NH2:39])=[O:38])[CH:34]=[CH:33][CH:32]=3)[CH:18]=[CH:17][C:14]=2[C:15]=1[CH3:16])=[O:10]
Reactant: Cc1c(C(=O)c2ccc(Cl)cc2Cl)oc2cc(B3OC(C)(C)C(C)(C)O3)ccc12
Reactant: NC(=O)c1cccc(Br)n1
Product: Cc1c(C(=O)c2ccc(Cl)cc2Cl)oc2cc(-c3cccc(C(N)=O)n3)ccc12

Procedure:
6-[2-(2,4-Dichloro-benzoyl)-3-methyl-benzofuran-6-yl]-pyridine-2-carboxylic acid amide was prepared via a Suzuki coupling of ((2,4-dichlorophenyl)-[3-methyl-6-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-benzofuran-2-yl]-methanone and 6-Bromo-pyridine-2-carboxylic acid amide as described in method 6 step 2. 1H-NMR (CD3OD) δ 8.42 (s, 1H), 8.23-8.17 (m, 2H), 8.09-8.02 (m, 2H), 7.92 (d, J=8 Hz 1H), 7.64 (d, J=2 Hz, 1H), 7.58-7.51 (m, 2H), 2.64 (s, 3H).
Reaction SMILES: C[O:2][C:3](=[O:33])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[N:17]([CH3:21])[C:16]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[C:15]3[CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])=[CH:8][CH:7]=1.[OH-].[K+]>C1COCC1.CO>[CH3:21][N:17]1[C:18]2[C:14](=[CH:13][C:12]([C:9]3[CH:10]=[CH:11][C:6]([O:5][CH2:4][C:3]([OH:33])=[O:2])=[CH:7][CH:8]=3)=[CH:20][CH:19]=2)[C:15]([CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])=[C:16]1[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: CCCCCc1c(-c2ccccc2)n(C)c2ccc(-c3ccc(OCC(=O)OC)cc3)cc12
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CCCCCc1c(-c2ccccc2)n(C)c2ccc(-c3ccc(OCC(=O)O)cc3)cc12

Procedure:
The desired product was prepared using a procedure similar to step 2 of example 4. Thus, [4-(1-methyl-3-pentyl-2-phenyl-1H-indol-5-yl)-phenoxy]-acetic acid methyl ester (0.184 g, 0.417 mmol) was reacted with 1N KOH (1.0 ml) in THF/MeOH (3 ml/2 ml) to give the product (0.104 g, 0.243 mmol, 58%) as a white solid, mp 146-148° C. 1H NMR (DMSO-d6) δ 0.73 (t, J=6.8 Hz, 3H), 1.10-1.19 (m, 4H), 1.47-1.54 (m, 2H), 2.62 (t, J=7.4 Hz, 2H), 3.52 (s, 3H), 4.66 (s, 2H), 6.96 (d, J=8.9 Hz, 2H), 7.37-7.46 (m, 5H), 7.51 (t, J=7.0 Hz, 2H), 7.57 (d, J=8.9 Hz, 2H), 7.69 (d, J=1.1 Hz, 1H), 12.96 (broad s, 1H); IR (solid) 3040, 2920, 2860, 1730, 1705, 1605, 1520, 1480, 1430, 1370, and 1230 cm−1; [ESI(−)], m/z 427 (M−H)−; Anal. Calcd. for C28H29NO3.0.25H2O: C, 77.84; H, 6.77; N, 3.24; Found: C, 78.13; H, 6.60; N, 3.19.
Reaction SMILES: [OH:1][C@H:2]([CH3:8])[CH2:3][C:4]([O:6][CH3:7])=[O:5].[CH3:9]I>>[OH:1][C@H:2]([CH3:8])[C@H:3]([CH3:9])[C:4]([O:6][CH3:7])=[O:5]
Reactant: COC(=O)C[C@@H](C)O
Reactant: CI
Product: COC(=O)[C@@H](C)[C@@H](C)O

Procedure:
This compound was prepared according to the procedure of Example 127, but the methyl 3-(R)-hydroxybutanoate was first alkylated with methyl iodide as described by Keck et al., (J. Org. Chem., 1985, 4317) to give methyl 3-(R)-hydroxy-2-(S)-methylbutanoate. The latter was transformed into the thiol according to the procedure of Example 127.
Reaction SMILES: Br[C:2]1[S:3][CH:4]=[CH:5][CH:6]=1.[Mg].II.Br[C:11]1[CH:16]=[CH:15][CH:14]=[C:13](Br)[CH:12]=1>C(OCC)C>[S:3]1[CH:4]=[CH:5][CH:6]=[C:2]1[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[C:2]1[S:3][CH:4]=[CH:5][CH:6]=1
Reactant: Brc1cccs1
Reactant: Brc1cccc(Br)c1
Agent: II
Agent: [Mg]
Solvent: CCOCC
Product: c1csc(-c2ccccc2-c2cccs2)c1
Reaction time: 1 h
Yield: 2.6 %

Procedure:
The Grignard was prepared by adding 2-bromothiophene (8.15 g, 0.05 m) in diethyl ether (10 ml) to magnesium turnings (1.22 g, 0.05 m) and iodine (trace) in diethyl ether (15 ml). After 1 h, the Grignard was slowly added to 1,3-dibromobenzene (5.0 g, 0.021 m) and catalyst in diethyl ether (20 ml). Workup after 24 h afforded a residue which crystallized from hot hexanes yielding a green solid (540 mg, 10% crude yield). The green solid (190 mg) was purified by column chromatography using petroleum ether as the eluant. A light green crystalline solid (136 mg, 7.6% yield) was separated; m.p. 83°-84° C., m/z 242 (M+); Found: C, 69.22; H, 4.04; S, 26.09; C14H10S2 requires: C,69.4; H, 4,1; S, 26.4H NMR(CDCl3) δ7.35 (dd, J=<1, 3 Hz, 2 H), δ7.085 (dd, J=5,3 Hz, 2H), δ7.29 (dd, J=<1, 5 Hz, 2H), δ7.81 (t, J=<1 Hz, 1H), δ7.38 (dd, J=8 Hz, 1H), δ7.51 (ddd, J=<1,2, 8 Hz, 2H).
Reaction SMILES: [O:1]1[C:5]2[C:6]3[C:7](=[CH:13][CH2:14][NH2:15])[CH2:8][CH2:9][C:10]=3[CH:11]=[CH:12][C:4]=2[N:3]=[CH:2]1.C(N(CC)CC)C.[C:23](OC(=O)C)(=[O:25])[CH3:24].C(=O)([O-])O.[Na+]>O1CCCC1>[O:1]1[C:5]2[C:6]3[C:7](=[CH:13][CH2:14][NH:15][C:23](=[O:25])[CH3:24])[CH2:8][CH2:9][C:10]=3[CH:11]=[CH:12][C:4]=2[N:3]=[CH:2]1
Reactant: CC(=O)OC(C)=O
Reactant: NCC=C1CCc2ccc3ncoc3c21
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(=O)NCC=C1CCc2ccc3ncoc3c21
Reaction time: 0.25 h
Yield: 53 %

Procedure:
2-(6,7-Dihydro-8H-indeno[5,4-d][1,3]oxazol-8-ylidene)ethanamine (30.0 mg, 0.148 mmol) was dissolved in tetrahydrofuran (1 mL), triethylamine (31.0 μL, 0.222 mmol) and acetic anhydride (16.8 μL, 0.178 mmol) were added under ice-cooling, and the mixture was stirred for 15 min. To the reaction solution was added saturated aqueous sodium hydrogencarbonate solution, and the mixture was extracted with ethyl acetate and washed with saturated brine. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/methanol=100/0→95/5) to give the title compound (19.0 mg, yield 53%).
Reaction SMILES: ClC(Cl)(Cl)COC(=O)[NH:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][C:14]2[CH:19]=[CH:18][C:17]([C:20](=[O:29])[NH:21][C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][N:23]=3)=[CH:16][C:15]=2[NH:30][C:31]2[C:32]3[CH:40]=[CH:39][C:38]([CH:41]([CH3:43])[CH3:42])=[N:37][C:33]=3[N:34]=[CH:35][N:36]=2)=[CH:9][CH:8]=1.[OH-].[Na+].Cl>O1CCCC1.O>[NH2:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][N:23]=3)=[O:29])=[CH:16][C:15]=2[NH:30][C:31]2[C:32]3[CH:40]=[CH:39][C:38]([CH:41]([CH3:43])[CH3:42])=[N:37][C:33]=3[N:34]=[CH:35][N:36]=2)=[CH:9][CH:8]=1
Reactant: CC(C)c1ccc2c(Nc3cc(C(=O)Nc4ccc(F)cn4)ccc3Sc3ccc(NC(=O)OCC(Cl)(Cl)Cl)cc3)ncnc2n1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)c1ccc2c(Nc3cc(C(=O)Nc4ccc(F)cn4)ccc3Sc3ccc(N)cc3)ncnc2n1
Temperature: 60 °C

Procedure:
To a solution of the product of Example 174B in tetrahydrofuran and water (1:1) was added 1 M NaOH (5 equiv). The solution was heated at 60° C. for 40 minutes, cooled, adjusted to pH 6 with 1N aqueous hydrochloric acid and extracted with ethyl acetate. The combined extracts were dried over magnesium sulfate, filtered and concentrated under vacuum. The resultant residue was purified by silica gel chromatography eluting with 2% methanol in dichloromethane to provide the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm: 1.34 (d, J=6.99 Hz, 6 H) 3.15-3.29 (m, J=6.89, 6.89, 6.89, 6.89 Hz, 1 H) 5.62 (s, 2 H) 6.65 (d, J=8.46 Hz, 2 H) 6.83 (d, J=8.46 Hz, 1 H) 7.15 (d, J=8.46 Hz, 2 H) 7.64 (d, J=8.46 Hz, 1 H) 7.79 (dt, J=8.64, 2.94 Hz, 1 H) 7.87 (dd, J=8.46, 1.84 Hz, 1 H) 8.04 (d, J=1.84 Hz, 1 H) 8.20 (dd, J=9.19, 4.04 Hz, 1 H) 8.38 (d, J=2.94 Hz, 1 H) 8.58 (s, 1 H) 8.89 (d, J=8.46 Hz, 1 H) 10.13 (s, 1 H) 10.85 (s, 1 H).
Reaction SMILES: [CH3:1][N:2]1[C:11]2[C:6](=[CH:7][C:8]([CH:12]3[CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13]3)=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]1=[O:24].[ClH:25].O1CCOCC1>C(Cl)Cl>[CH3:1][N:2]1[C:11]2[C:6](=[CH:7][C:8]([CH:12]3[CH2:16][CH2:15][NH:14][CH2:13]3)=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]1=[O:24].[ClH:25]
Reactant: Cn1c(=O)ccc2cc(C3CCN(C(=O)OC(C)(C)C)C3)ccc21
Agent: Cl
Solvent: C1COCCO1
Solvent: ClCCl
Product: Cn1c(=O)ccc2cc(C3CCNC3)ccc21
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A stirred solution of tert-butyl 3-(1-methyl-2-oxo-1,2-dihydroquinolin-6-yl)pyrrolidine-1-carboxylate (1 mg) in CH2Cl2 (2 mL) was treated with 4 M HCl in dioxane (1 mL, 4 mmol). The mixture was stirred at rt for 3 h and concentrated to leave 1-methyl-6-(pyrrolidin-3-yl)quinolin-2(1H)-one as its HCl salt (1 mg). LC-MS Method 1 tR=1.48 min, m/z=229.
Reaction SMILES: [N:1]1[CH:2]=[CH:3][N:4]2[C:9]([S:10][CH2:11][CH2:12][CH2:13][CH2:14][N:15]3[C:19](=[O:20])[CH2:18][S:17][C:16]3=[O:21])=[CH:8][CH:7]=[CH:6][C:5]=12.[CH:22](=O)[CH2:23][CH2:24][CH3:25].N1CCCCC1>C(O)C>[CH:22](=[C:18]1[S:17][C:16](=[O:21])[N:15]([CH2:14][CH2:13][CH2:12][CH2:11][S:10][C:9]2[N:4]3[CH:3]=[CH:2][N:1]=[C:5]3[CH:6]=[CH:7][CH:8]=2)[C:19]1=[O:20])[CH2:23][CH2:24][CH3:25]
Reactant: O=C1CSC(=O)N1CCCCSc1cccc2nccn12
Reactant: CCCC=O
Solvent: CCO
Solvent: C1CCNCC1
Product: CCCC=C1SC(=O)N(CCCCSc2cccc3nccn23)C1=O

Procedure:
To a solution of 1.61 g (5.0 mmol) of 3-[4-(imidazo[1,2-a]pyridin-5-ylthio)butyl]thiazolidine-2,4-dione and 0.45 ml (5.0 mmol) of n-butyraldehyde in 50 ml of ethanol, 0.05 ml (0.5 mmol) of piperidine was added, followed by refluxing for 2 hours. After the reaction mixture was cooled, the solvent was distilled off. The residue was dissolved in chloroform, washed with saturated aqueous sodium hydrogen carbonate and dried, after which the solvent was distilled off. The residue was purified by column chromatography (eluent, ethyl acetate) to yield 1.89 g (quant, light yellow oily substance) of the desired product.
Reaction SMILES: [CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][NH:2]1.[NH:11]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:13]=[C:12]1[CH2:20][N:21]([CH2:32][C:33]1[CH:40]=[CH:39][C:36]([CH:37]=O)=[CH:35][CH:34]=1)[CH:22]1[C:31]2[N:30]=[CH:29][CH:28]=[CH:27][C:26]=2[CH2:25][CH2:24][CH2:23]1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C1COCC1>[NH:11]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:13]=[C:12]1[CH2:20][N:21]([CH2:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37][N:2]2[CH2:3][CH2:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH2:1]2)=[CH:35][CH:34]=1)[CH:22]1[C:31]2[N:30]=[CH:29][CH:28]=[CH:27][C:26]=2[CH2:25][CH2:24][CH2:23]1
Reactant: O=Cc1ccc(CN(Cc2nc3ccccc3[nH]2)C2CCCc3cccnc32)cc1
Reactant: c1ccc2c(c1)CCNC2
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: c1ccc2c(c1)CCN(Cc1ccc(CN(Cc3nc4ccccc4[nH]3)C3CCCc4cccnc43)cc1)C2
Temperature: 25 °C
Reaction time: 2 h
Yield: 78.4 %

Procedure:
Using General Procedure B: To a stirred solution of 1,2,3,4-tetrahydroisoquinoline (49 mg, 0.37 mmol), 4-{[(1H-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzaldehyde (140 mg, 0.34 mmol), and AcOH 0.020 mL, 0.35 mmol) in THF (3.5 mL) was added NaBH(OAc)3 (94 mg, 0.44 mmol) and the mixture was stirred at room temperature for 2 h. Purification of the crude material by column chromatography on silica gel (500:5:1 CH2Cl2/MeOH/NH4OH) afforded a colourless foam (137 mg).
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]=1[C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=1)[CH:15]=[O:16].[BH4-].[Na+].Cl>COCCOC.O1CCCC1>[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]=1[C:12]1[CH:13]=[C:14]([CH2:15][OH:16])[CH:17]=[CH:18][CH:19]=1
Reactant: Cc1ccc2ccccc2c1-c1cccc(C=O)c1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: COCCOC
Product: Cc1ccc2ccccc2c1-c1cccc(CO)c1
Reaction time: 3 h
Yield: 81.4 %

Procedure:
3-(2-Methyl-1-naphthyl)benzaldehyde (2.39 g, 9.70 mmol) was dissolved in a mixed solvent of 1,2-dimethoxyethane (10 mL) and tetrahydrofuran (10 mL), and sodium borohydride (0.189 g, 5.00 mmol) was added under ice-cooling, and the mixture was stirred at the same temperature for 3 hr. Diluted hydrochloric acid was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (5%-30% ethyl acetate/hexane) to give the title compound (1.96 g, yield 81%) as a colorless viscous oil.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[CH:3]1.[Cl-].[CH:8](=[N+:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>>[CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[CH:8]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[N:15]1[CH2:16][CH2:17][CH2:18][CH2:19]1
Reactant: C(c1ccccc1)=[N+]1CCCC1
Reactant: Cn1cccc1
Agent: [Cl-]
Product: Cn1cccc1C(c1ccccc1)N1CCCC1

Procedure:
The preparation was carried out in accordance with general synthesis instructions 4 from 1-methyl-1H-pyrrole and 1-benzylidene-pyrrolidinium chloride.
Reaction SMILES: [O:1]1[CH2:5][CH2:4][O:3][CH:2]1[CH2:6][C:7]1([CH2:16][NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9][CH2:8]1.IC.[CH3:27][Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[CH2:6][C:7]1([CH2:16][N:17]([CH3:27])[C:18](=[O:24])[O:19][C:20]([CH3:21])([CH3:23])[CH3:22])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9][CH2:8]1
Reactant: CC(C)(C)OC(=O)NCC1(CC2OCCO2)CCc2ccccc21
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CI
Product: CN(CC1(CC2OCCO2)CCc2ccccc21)C(=O)OC(C)(C)C
Temperature: 25 °C

Procedure:
A solution of tert-butyl [1-(1,3-dioxolan-2-ylmethyl)-2,3-dihydro-1H-inden-1-yl]methylcarbamate (13.50 g, 38.9 mmole) in THF was cooled to 0° C. To this was added iodomethane (7.27 ml, 117 mmole) followed by 1M NaHMDS in THF (58 ml, 58 mmole). The reaction was then warmed to room temperature and stirred until no U16370/185/2 remained by TLC. The THF was evaporated and the residue dissolved in Et2O. The ether was washed with water and evaporated to afford 14.33 g of tert-butyl [1-(1,3-dioxolan-2-ylmethyl)-2,3-dihydro-1H-inden-1-yl]methyl(methyl)carbamate as a crude oil, which was used, with no further purification.