Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(N(CC)CC)C.[C:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:16]1[CH:21]=[CH:20][C:19]([CH2:22][NH:23][CH2:24][CH2:25][CH3:26])=[CH:18][CH:17]=1)#[N:9].[Cl-].[CH3:28][O:29][C:30](=[O:39])[CH2:31][C:32]([CH3:38])([CH3:37])[CH2:33][C:34]([OH:36])=O>C(Cl)Cl>[C:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:16]1[CH:17]=[CH:18][C:19]([CH2:22][N:23]([CH2:24][CH2:25][CH3:26])[C:34](=[O:36])[CH2:33][C:32]([CH3:38])([CH3:37])[CH2:31][C:30]([O:29][CH3:28])=[O:39])=[CH:20][CH:21]=1)#[N:9]
Reactant: COC(=O)CC(C)(C)CC(=O)O
Reactant: CCCNCc1ccc(-c2ccccc2C#N)cc1
Agent: [Cl-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCN(Cc1ccc(-c2ccccc2C#N)cc1)C(=O)CC(C)(C)CC(=O)OC
Temperature: 25 °C
Reaction time: 2 h

Procedure:
1.83 ml of triethylamine are added to a solution of 2.19 g of N-(2'-cyanobiphenyl-4-ylmethyl)-N-propyl-amine and 2.37 g of 3,3-dimethylglutaric acid monomethyl ester monochloride in 100 ml of CH2Cl2 and the mixture is stirred at room temperature for 2 hours. Extraction twice with 50 ml of water each time and extraction of the aqueous phase with 40 ml of CH2Cl2 produces an organic phase which, after being concentrated by evaporation, yields by the customary procedure 3,3-dimethyl-4-methoxycarbonyl-butanoic acid N-(2'-cyanobiphenyl-4-ylmethyl)-N-propyl-amide that has an Rf value of 0.66 [CH2Cl2 /CH3OH (95:5)].
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[C:5]([CH3:7])[N:4]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[N:3]=1.[CH3:24][O:25][S:26]([C:29]1[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=1)(=[O:28])=[O:27]>>[C:32]1([CH3:35])[CH:31]=[CH:30][C:29]([S:26]([O-:28])(=[O:25])=[O:27])=[CH:34][CH:33]=1.[CH2:8]([N+:4]1[N:3]([CH3:24])[C:2]([CH3:1])=[CH:6][C:5]=1[CH3:7])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23]
Reactant: COS(=O)(=O)c1ccc(C)cc1
Reactant: CCCCCCCCCCCCCCCCn1nc(C)cc1C
Product: CCCCCCCCCCCCCCCC[n+]1c(C)cc(C)n1C
Product: Cc1ccc(S(=O)(=O)[O-])cc1

Procedure:
Reaction of 3,5-dimethyl-1-hexadecyl-pyrazole with toluene-4-sulfonic acid-methyl ester yields 1-hexadecyl-2,3,5-trimethylpyrazolium p-toluene sulfonate; m.p. 113°-114° C.
Reaction SMILES: [C:1]1([O:7][CH2:8][CH2:9][Br:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:11]1([P:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C1(O)C=CC=CC=1>CCOCC>[Br-:10].[O:7]([CH2:8][CH2:9][P+:17]([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: BrCCOc1ccccc1
Solvent: CCOCC
Solvent: Oc1ccccc1
Product: [Br-]
Product: c1ccc(OCC[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Temperature: 90 °C
Reaction time: 48 h

Procedure:
A mixture of 2-bromoethyl phenyl ether (20.0 g), triphenylphosphine (26.2 g) and phenol (200 g) was heated at 90° C. with stirring for 48 hours. The mixture was cooled to approximately 40° C. and added to ether (1500 ml). The ether was decanted off and the residual oil was triturated with ether until a solid was obtained. The solid was collected by filtration to give (2-phenoxyethyl)triphenylphosphonium bromide.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[Cl-].[Al+3].[Cl-].[Cl-].[NH:9]1[C:17]2[CH:16]=[CH:15][CH:14]=[C:13]3[CH2:18][CH2:19][CH2:20][CH:11]([C:12]=23)[C:10]1=[O:21].[CH:22]([O:25][CH:26]([CH3:28])[CH3:27])([CH3:24])[CH3:23]>C(OCC)(=O)C.C(=S)=S>[CH3:1][OH:3].[CH:22]([O:25][CH:26]([CH3:28])[CH3:27])([CH3:24])[CH3:23].[C:1]([C:14]1[CH:15]=[CH:16][C:17]2[NH:9][C:10](=[O:21])[CH:11]3[CH2:20][CH2:19][CH2:18][C:13]=1[C:12]=23)(=[O:3])[CH3:2]
Reactant: CC(=O)Cl
Reactant: O=C1Nc2cccc3c2C1CCC3
Agent: [Al+3]
Agent: [Cl-]
Solvent: S=C=S
Solvent: CCOC(C)=O
Solvent: CC(C)OC(C)C
Product: CC(=O)c1ccc2c3c1CCCC3C(=O)N2
Product: CO
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A 3.1 ml (43.4 mmol) portion of acetyl chloride was added to a carbon disulfide suspension (100 ml) of aluminum chloride (11.5 g, 86.7 mmol) and stirred at a room temperature for 30 minutes. Thereto was added dropwise a carbon disulfide solution (150 ml) of 2a,3,4,5-tetrahydrobenz[cd]indole-2(1H)-one (5.0 g, 28.9 mmol) spending 2 hours. After 2 hours of heating under reflux and confirmation of the disappearance of the material by a thin layer chromatography, this was returned to a room temperature and mixed with isopropyl ether. The supernatant fluid was discarded by decantation, and the remaining rubber-like substance was dissolved in ethyl acetate and washed with water. The water layer was extracted with ethyl acetate, the organic layers were combined and dried (Na2SO4), and then the solvent was evaporated under a reduced pressure. By recrystallizing the thus obtained oily substance from ethyl acetate-isopropyl ether and then from methanol-isopropyl ether, 3.5 g of the title compound was obtained (yield, 56%).
Reaction SMILES: N1[C:6]2[CH2:7][CH2:8][CH2:9][CH2:10][C:5]=2[N:4]=[C:3]([C:11]([O:13][CH2:14][CH3:15])=[O:12])N=1.C(O)(=O)[C:17]1[C:18](=[CH:20][CH:21]=[CH:22][CH:23]=1)N.N(OCCC(C)C)=O>O1CCOCC1.C(OCC)C>[CH2:7]1[C:6]2[C:5](=[N:4][C:3]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:17]3[C:18]=2[CH:20]=[CH:21][CH:22]=[CH:23]3)[CH2:10][CH2:9][CH2:8]1
Reactant: CCOC(=O)c1nnc2c(n1)CCCC2
Reactant: Nc1ccccc1C(=O)O
Agent: CC(C)CCON=O
Solvent: C1COCCO1
Solvent: CCOCC
Product: CCOC(=O)c1nc2c(c3ccccc13)CCCC2

Procedure:
Analogously to the method described by Gonsalves et al. (Tetrahedron 1992, 48, 6821) a solution of 3.90 g of ethyl 5,6,7,8-tetrahydro-benzo[1,2,4]triazine-3-carboxylate (Sagi et al., Heterocycles 1989, 29, 2253) is refluxed in 20 ml of dioxane. Then 8.22 g anthranilic acid and 7.02 g isoamyl nitrite, in each case dissolved in 20 ml dioxane, are simultaneously added dropwise within 25 minutes using two dropping funnels. The reaction mixture is refluxed for a further 30 minutes. For working up the cooled dark brown reaction solution is diluted with 150 ml diethyl ether, washed with 100 ml of 2 N sodium hydroxide solution and with water, dried over magnesium sulphate and evaporated down. The brown, oily flask residue is chromatographed through a silica gel column with ethyl acetate/petroleum ether (20:80 to 50:50) as eluant. The product obtained is still somewhat contaminated but is further reacted without any further purification.
Reaction SMILES: [NH2:1][C:2]1[C:3]2[C:8]([N:9]=[C:10]3[C:15]=1[CH:14]([OH:16])[CH2:13][CH2:12][CH2:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.OS(O)(=O)=O>CC(O)=O>[OH2:16].[NH2:1][C:2]1[C:3]2[C:8]([N:9]=[C:10]3[C:15]=1[CH:14]=[CH:13][CH2:12][CH2:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[NH2:1][C:2]1[C:3]2[C:8]([N:9]=[C:10]3[C:15]=1[CH:14]=[CH:13][CH2:12][CH2:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2
Reactant: Nc1c2c(nc3ccccc13)CCCC2O
Agent: O=S(=O)(O)O
Solvent: CC(=O)O
Product: Nc1c2c(nc3ccccc13)CCC=C2
Product: O
Temperature: 0 °C

Procedure:
In 50 ml of HOAc was dissolved 3.00 g of 9-amino-1,2,3,4-tetrahydroacridin-1-ol. To this mechanically stirred solution at room temperature was added 0.75 ml (1 eq) of H2SO4. The reaction mixture was warmed on a steam bath causing a precipitate to form. After 0.5 hour of heating, the reaction was complete based on thin layer chromatography. The reaction mixture was poured into excess ice/10% NaOH and the precipitate was collected. The precipitate was dissolved in dichloromethane, dried over MgSO4, filtered, and evaporated to a solid which was purified by silica gel chromatography to yield a solid. Two recrystallizations from dichloromethane/hexanes yielded 1.40 g (75% crude yield prior to chromatography) of a powder, melting point 178°-179° C.
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[N:9]1[O:10][N:11]=[C:12]2[CH:17]=[C:16]([C:18](Cl)=[O:19])[CH:15]=[CH:14][C:13]=12>>[CH3:1][N:2]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)[C:18]([C:16]1[CH:15]=[CH:14][C:13]2=[N:9][O:10][N:11]=[C:12]2[CH:17]=1)=[O:19]
Reactant: O=C(Cl)c1ccc2nonc2c1
Reactant: CNc1ccccc1
Product: CN(C(=O)c1ccc2nonc2c1)c1ccccc1

Procedure:
Prepared from N-methylaniline and [2,1,3]-benzoxadiazole-5-carbonylchloride using the procedure described for Example 7. N-Methyl-N-phenyl-[2,1,3]-benzoxadiazole-5-carboxamide was isolated as a yellow oil. LC-MS, MH+=254; 1H NMR (300 MHz, CDCl3) δ 7.74 (s, 1H); 7.64 (d, 1H, J=9.6 Hz); 7.34(d, 1H, J=9.6 Hz); 7.29-7.09 (m, 5H); 3.54 ppm is (s, 3H).
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: mp 173°-174° C.; 1H NMR (80 MHz, CDCl3)δ(TMS) 8.05 (s, 1H, CH=N), 7.78 (s, 1H, CH=N), 8.0-7.0 (m, 6H, arom), 4.89 (AB system, Δv=0.42, J=14.5 Hz, 2H, CH2 -Tr), 3.87 (AB system, Δv=0.30, J=14 Hz, 2H, CH2NH). Anal calcd. for C17H14C14N4O3S: C 41.15%; H 2.84%; N 11.29%. Found: C 40.86%; H 3.06%; N 11.28%.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:8]2[CH2:12][CH2:11][CH2:10][NH:9]2)[CH:7]=1.N1C=CC=CC=1.[CH3:19][S:20](Cl)(=[O:22])=[O:21]>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:8]2[CH2:12][CH2:11][CH2:10][N:9]2[S:20]([CH3:19])(=[O:22])=[O:21])[CH:7]=1
Reactant: CS(=O)(=O)Cl
Reactant: Brc1cncc(C2CCCN2)c1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CS(=O)(=O)N1CCCC1c1cncc(Br)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 79 %

Procedure:
To a stirred solution of 3-bromo-5-(2-pyrrolidinyl)pyridine (0.2 g, 0.881 mmol) and pyridine (0.157 mL, 1.937 mmol) in DCM (1 mL) is added methanesulfonyl chloride in DCM (1 mL) dropwise. The mixture is stirred at room temperature for 2 h. The mixture is concentrated. The resulting crude product is purified by normal phase chromatography using 0-3% MeOH in DCM as the gradient to afford 3-bromo-5-(1-methanesulfonyl-pyrrolidin-2-yl)-pyridine (211.2 mg, 79% yield).
Reaction SMILES: [CH3:1][C:2]1[C:3]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:4][O:5][C:6]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8].C1C(=O)N([Br:25])C(=O)C1.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.C(Cl)(Cl)(Cl)Cl>C(Cl)Cl>[Br:25][CH2:1][C:2]1[C:3]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:4][O:5][C:6]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8]
Reactant: CCOC(=O)c1onc(-c2ccccc2)c1C
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Solvent: ClCCl
Product: CCOC(=O)c1onc(-c2ccccc2)c1CBr
Yield: 79.3 %

Procedure:
Ethyl 4-methyl-3-phenylisoxazole-5-carboxylate (0.2 g, 0.87 mmol), NBS (0.17 g, 0.95 mmol), and benzoyl peroxide (21 mg, 0.087 mmol) were added to 5 mL of carbon tetrachloride and the mixture was refluxed for 16 h. The mixture was diluted with CH2Cl2, and 5 g of silica gel was added. The solvent was removed in vacuo and the crude was purified by flash chromatography (0-20% EtOAc/hexanes) to give 214 mg of the title compound. MS: (+) m/z 310.31, 312.28 (M+1, 79Br/81Br).
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.OO.S([O-])([O-])(=O)=[O:11].[Al+3].S([O-])([O-])(=O)=[O:17].S([O-])([O-])(=O)=O.[Al+3]>CC(C)CC(=O)C>[C:1]1([C:6](=[CH:5][CH:4]=[CH:3][CH:2]=1)[OH:11])[OH:7].[C:1]1([CH:6]=[CH:5][C:4]([OH:17])=[CH:3][CH:2]=1)[OH:7]
Reactant: O=S(=O)([O-])[O-]
Reactant: Oc1ccccc1
Agent: OO
Agent: [Al+3]
Solvent: CC(=O)CC(C)C
Product: Oc1ccc(O)cc1
Product: Oc1ccccc1O

Procedure:
With 10 g. (106 m. moles) of phenol were admixed the indicated ratios of 60 percent hydrogen peroxide and 4-methyl-2-pentanone in Table 5 and to the resulting mixture was added 0.070 g. of aluminum sulfate (Al2 (SO4)3.18H2O). The resulting mixture was reacted to 100° C. for 30 minutes in the same manner as in Example 1. Yields of catechol and hydroquinone are shown in Table 5.
Reaction SMILES: [C:1]([O:5][C:6](=[O:29])[C:7]([O:10]/[N:11]=[C:12](/[C:16]1[N:17]=[C:18]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[S:19][CH:20]=1)\[C:13]([OH:15])=O)([CH3:9])[CH3:8])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:63][C@@H:64]1[C:67](=[O:68])[NH:66][C@@H:65]1[CH2:69][C:70]1[N:71]=[N:72][N:73]([CH2:75][CH2:76][NH:77][C:78](=[O:84])[O:79][C:80]([CH3:83])([CH3:82])[CH3:81])[CH:74]=1>C(Cl)Cl.CN(C=O)C>[C:80]([O:79][C:78]([NH:77][CH2:76][CH2:75][N:73]1[CH:74]=[C:70]([CH2:69][C@@H:65]2[C@H:64]([NH:63][C:13](=[O:15])/[C:12](=[N:11]\[O:10][C:7]([CH3:8])([CH3:9])[C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:29])/[C:16]3[N:17]=[C:18]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[S:19][CH:20]=3)[C:67](=[O:68])[NH:66]2)[N:71]=[N:72]1)=[O:84])([CH3:83])([CH3:81])[CH3:82]
Reactant: CC(C)(C)OC(=O)NCCn1cc(C[C@H]2NC(=O)[C@H]2N)nn1
Reactant: CC(C)(C)OC(=O)Nc1nc(/C(=N/OC(C)(C)C(=O)OC(C)(C)C)C(=O)O)cs1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)NCCn1cc(C[C@H]2NC(=O)[C@H]2NC(=O)/C(=N\OC(C)(C)C(=O)OC(C)(C)C)c2csc(NC(=O)OC(C)(C)C)n2)nn1

Procedure:
Prepared in analogous manner to example 82 step 7, using (Z)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acid (18.55 mg, 0.043 mmol), HATU (17.7 mg, 0.047 mmol), DCM:DMF (1:3, 800 μl), DIPEA (18.86 μl, 0.108 mmol), tert-butyl (2-(4-(((2R,3S)-3-amino-4-oxoazetidin-2-yl)methyl)-1H-1,2,3-triazol-1-yl)ethyl)carbamate (11.17 mg, 0.036 mmol). 6.5 mg. LCMS: Rt=0.971 min, m/z=722.4 (M+1). Method 2m_acidic. 1H NMR (400 MHz, Methanol-d4) δ 7.82 (s, 1H), 7.32 (s, 1H), 5.34 (d, J=4.9 Hz, 1H), 4.43 (t, J=5.9 Hz, 3H), 4.19 (dt, J=9.3, 4.5 Hz, 1H), 4.09 (q, J=7.1 Hz, 1H), 3.54-3.45 (m, 3H), 3.13 (ddd, J=15.0, 11.8, 6.0 Hz, 2H), 2.93 (dd, J=15.2, 9.6 Hz, 1H), 2.01 (s, 2H), 1.53 (d, J=1.4 Hz, 14H), 1.49 (s, 7H), 1.46 (d, J=1.7 Hz, 15H), 1.38 (s, 14H), 1.23 (t, J=7.1 Hz, 3H).
Reaction SMILES: [CH3:1][C:2]1[C:11]2[C:10](=O)[CH2:9][CH:8]([C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)[CH2:7][C:6]=2[N:5]=[CH:4][CH:3]=1.[C:19]([NH:22][NH2:23])([NH2:21])=[NH:20].[ClH:24].Cl.O>C(O)C>[ClH:24].[NH:22]([N:23]=[C:10]1[CH2:9][CH:8]([C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)[CH2:7][C:6]2[N:5]=[CH:4][CH:3]=[C:2]([CH3:1])[C:11]1=2)[C:19]([NH2:21])=[NH:20]
Reactant: Cc1ccnc2c1C(=O)CC(c1ccncc1)C2
Reactant: N=C(N)NN
Agent: Cl
Solvent: CCO
Solvent: O
Product: Cc1ccnc2c1C(=NNC(=N)N)CC(c1ccncc1)C2
Yield: 93.6 %

Procedure:
A mixture of 4-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydroquinolin-5-one (0.1 g), aminoguanidine hydrochloride (0.049 g), concentrated hydrochloric acid (0.15 ml), water (0.15 ml) and ethanol (10 ml) was refluxed for 6 hours. Under reduced pressure, the solvent was evaporated, and the residue was dissolved in water. The solution was washed with ethyl acetate. Under reduced pressure, the solvent was evaporated, and the residue was recrystallized from ethanol-water to give 5-guanidinoimino-4-methyl-7-(4-pyridyl)-5,6,7,8-tetrahydroquinoline hydrochloride (Compound 76) (0.13 g) as colorless crystals.
Reaction SMILES: [CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12](=O)[C:13]([Cl:19])=[C:14]([Cl:18])[C:15]([OH:17])=[O:16])=[C:4]1[CH3:21])[CH3:2].[CH3:22][C:23]1[NH:24][C:25]2[C:30]([CH:31]=1)=[CH:29][CH:28]=[CH:27][CH:26]=2>C(OC(=O)C)(=O)C>[CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]2([C:31]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[NH:24][C:23]=3[CH3:22])[O:17][C:15](=[O:16])[C:14]([Cl:18])=[C:13]2[Cl:19])=[C:4]1[CH3:21])[CH3:2]
Reactant: Cc1cc2ccccc2[nH]1
Reactant: CCn1c(C)c(C(=O)C(Cl)=C(Cl)C(=O)O)c2ccccc21
Solvent: CC(=O)OC(C)=O
Product: CCn1c(C)c(C2(c3c(C)[nH]c4ccccc34)OC(=O)C(Cl)=C2Cl)c2ccccc21
Temperature: 25 °C

Procedure:
A mixture of 10.0 g (0.047 mole) of 4-(1-ethyl-2-methyl-3-indolyl)-2,3-dichloro-4-oxo-2-butenoic acid, 4.0 g (0.030 mole) of 2-methylindole and 150 ml of acetic anhydride was stirred at ambient temperature in an atmosphere of air for approximately seventeen hours and the solid which formed was collected by filtration. After drying in vacuo at 60° C there was obtained 5-(1-ethyl-2-methyl-3-indolyl)-5-(2-methyl-3-indolyl)-3,4-dichloro-2(5H)-furanone (Formula V: R=CH3CH2 ; R1 =R3 =CH3 ; R2 =Y=Y1 =H) as a blue-colored solid which melted over the range of 282°-285° C.
Reaction SMILES: I.[CH2:2]([N:9]1[CH2:13][C:12](=[O:14])[N:11]=[C:10]1SC)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[N:17]1([CH2:23][C:24]2[CH:25]=[C:26]([CH:32]=[CH:33][CH:34]=2)[O:27][CH2:28][CH2:29][CH2:30][NH2:31])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.C(N(CC)CC)C.[ClH:42]>C(O)C>[ClH:42].[ClH:42].[N:17]1([CH2:23][C:24]2[CH:25]=[C:26]([CH:32]=[CH:33][CH:34]=2)[O:27][CH2:28][CH2:29][CH2:30][NH:31][C:10]2[N:9]([CH2:2][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)[CH2:13][C:12](=[O:14])[N:11]=2)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1
Reactant: CSC1=NC(=O)CN1Cc1ccccc1
Reactant: NCCCOc1cccc(CN2CCCCC2)c1
Agent: Cl
Agent: I
Solvent: CCN(CC)CC
Solvent: CCO
Product: O=C1CN(Cc2ccccc2)C(NCCCOc2cccc(CN3CCCCC3)c2)=N1

Procedure:
1-Benzyl-2-methylthio-2-imidazolin-4-one hydroiodide (2.09 g) from the previous stage, 3-(3-piperidinomethylphenoxy)propylamine (1.49 g) and triethylamine (1.27 g) were refluxed in ethanol (35 ml) for 7 hours with stirring. The solution was allowed to cool overnight and evaporated under reduced pressure to give a residue. This residue was dissolved in 2N hydrochloric acid (30 ml), and extracted with chloroform (3×20 ml). The aqueous layer was taken to pH 10 with 2N sodium hydroxide and extracted with chloroform (3×30 ml). The latter chloroform extracts were dried (MgSO4) and evaporated under reduced pressure. The residue was washed thoroughly with cold diethyl ether and treated with dilute ethanolic HCL. Excess solvent was evaporated and the residue recrystallised from isopropanolacetone to afford 2-[3-(3-piperidinomethylphenoxy)propylamino]-1-benzylimidazolin-4-one dihydrochloride, m.p. 95°-98° C.
Reaction SMILES: [Mg].Cl[CH:3]1[CH2:8][CH2:7][N:6]([CH3:9])[CH2:5][CH2:4]1.II.C1([Mg]Cl)CCCCC1.[NH2:20][C:21]1[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=1[C:23]#N.C1C[O:32]CC1>>[NH2:20][C:21]1[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=1[C:23]([CH:3]1[CH2:8][CH2:7][N:6]([CH3:9])[CH2:5][CH2:4]1)=[O:32]
Reactant: C1CCOC1
Reactant: CN1CCC(Cl)CC1
Reactant: N#Cc1ccccc1N
Agent: Cl[Mg]C1CCCCC1
Agent: II
Agent: [Mg]
Product: CN1CCC(C(=O)c2ccccc2N)CC1
Temperature: 45 °C
Yield: 7 %

Procedure:
To a suspension of magnesium (1.8 g, 74 mmol) in dry THF (50 mL) in a flame-dried round bottomed flask under nitrogen was added 4-chloro-1-methylpiperidine (9.0 g, 68 mmol). A crystal of iodine and a catalytic amount of cyclohexylmagnesium chloride was added and the mixture was heated to reflux for 2 h. A gray precipitate formed, which was removed via vacuum filtration under a nitrogen atmosphere. To the filtrate was added a solution of 2-aminobenzonitrile (1.6 g, 14 mmol) in dry THF (15 mL). The stirred mixture was heated to 45° C. for 2 h. Ice was added and the reaction was quenched with 1 M sulfuric acid. The mixture was extracted with ethyl acetate and the acidic aqueous layer was then neutralized with 1 N sodium hydroxide, concentrated on a rotary evaporator and extracted with ethyl acetate. The combined organics were dried over sodium sulfate, filtered and concentrated to afford (2-aminophenyl)(1-methylpiperidin-4-yl)methanone as a yellow oil (1.0 g, 7%).
Reaction SMILES: [CH2:1]([N:9]1[C:18]2[C:13](=[C:14]([CH3:24])[C:15]([CH2:20][C:21](=[O:23])N)=[C:16]([CH3:19])[CH:17]=2)[CH2:12][CH2:11][CH2:10]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[OH-].[Na+].[CH2:27]([OH:30])[CH2:28]C>O>[CH2:1]([N:9]1[C:18]2[C:13](=[C:14]([CH3:24])[C:15]([CH2:20][C:21]([O:30][CH2:27][CH3:28])=[O:23])=[C:16]([CH3:19])[CH:17]=2)[CH2:12][CH2:11][CH2:10]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCCCCN1CCCc2c1cc(C)c(CC(N)=O)c2C
Reactant: CCCO
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCCCCCCCN1CCCc2c1cc(C)c(CC(=O)OCC)c2C
Temperature: 130 °C
Reaction time: 20 h

Procedure:
1-Octyl-6-carbamoylmethyl-5,7-dimethyl-1,2,3,4-tetrahydroquinoline (2.5 g) was dissolved in n-propanol (50 ml) and a solution of NaOH (3.0 g) in water (30 ml) was added, which was followed by stirring at 130° C. for 20 hr under nitrogen. The organic layer of the reaction mixture was separated and the solvent was evaporated under reduced pressure. The residue was dissolved in water (300 ml) and washed with ethyl acetate (100 ml). The aqueous layer was adjusted to pH 1-2 with 6N hydrochloric acid and extracted with chloroform (200 ml). The chloroform layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained 1-octyl-6-carboxymethyl-5,7-dimethyl-1,2,3,4-tetrahydroquinoline was dissolved in ethanol (50 ml), and conc. hydrochloric acid (4 ml) was added, which was followed by stirring at 70° C. for 1 hr. The solvent was evaporated under reduced pressure. The residue was neutralized with saturated aqueous solution of sodium hydrogencarbonate and extracted with chloroform (100 ml). After washing with water, the chloroform layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: benzene) to give 1.0 g of oily 1-octyl-6-ethoxycarbonylmethyl-5,7-dimethyl-1,2,3,4-tetrahydroquinoline.
Reaction SMILES: [Si:1]([CH:18]([OH:25])[C@H:19]1[O:23][C:22](=[O:24])[CH2:21][CH2:20]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Si](Cl)(C)(C)C.[C:41]1([Se:47]Br)[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>C1COCC1.CCOCC>[Si:1]([CH:18]([OH:25])[C@H:19]1[O:23][C:22](=[O:24])[C@H:21]([Se:47][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH2:20]1)([C:14]([CH3:17])([CH3:15])[CH3:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Br[Se]c1ccccc1
Reactant: CC(C)(C)[Si](c1ccccc1)(c1ccccc1)C(O)[C@@H]1CCC(=O)O1
Agent: C[Si](C)(C)Cl
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: CC(C)(C)[Si](c1ccccc1)(c1ccccc1)C(O)[C@@H]1C[C@@H]([Se]c2ccccc2)C(=O)O1
Temperature: -78 °C
Reaction time: 1 h
Yield: 58.7 %

Procedure:
To a solution of 4 (5 g, 14.1 mmol) in anhydrous THF (50 mL) at −78° C. was added lithium bis(trimethylsilyl)amide (1 M solution in THF, 15.8 mL, 15.8 mmol) over a period of 10 min. After stirring at −78° C. for 1 h, Me3SiCl (1.918 g, 17.65 mmol) was added dropwise, and the reaction mixture was allowed to warm to room temperature. After being stirred at room temperature for 30 min, the mixture was cooled to −78° C., and a solution of PhSeBr (5 g, 21.19 mmol) in anhydrous THF (25 mL) was added rapidly. The mixture was diluted with ether (50 mL), washed with water until the color of organic layer changed from dark brown to light yellow, dried (Na2SO4), filtered, and evaporated. The resulting oily residue [containing 3R(α, 5) and 3S(β) isomers; TLC: hexane/EtOAc, 10:1; Rf=0.42 and 0.28, respectively] was purified by flash chromatography on silica gel eluting with hexane/EtOAc (99:1 to 95:5) to give the title compound 5 as a light yellow oil (4.22 g, 59/%). 1H NMR (CDCl3) δ7.69–7.60 (m, 6H, arom.), 7.46–7.30 (m, 9H, arom.), 4.37–4,34 (m, 1H, H-5), 4.12–4.08 (m, 1H, H-3), 3.86–3.82 (dd, J=3 & 11 Hz, 1H, CH2OH), 3.62–3.59 (dd, J=3 & 11 Hz, 1H, CH2OH), 2.73–2.67 (m, 1H, H-4), 2.32–2.28 (m, 1H, H-4), 1.02 (s, 9H, t-Bu).