Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[Si]([C:5]#[C:6][C:7]1[N:11]2[C:12]3[C:17]([N:18]=[C:19]([NH:20][CH2:21][CH2:22][CH2:23][OH:24])[C:10]2=[N:9][CH:8]=1)=[CH:16][C:15]([C:25]([F:28])([F:27])[F:26])=[CH:14][CH:13]=3)(C)C.C(=O)([O-])[O-].[K+].[K+]>ClCCl.CO.[Cl-].[Na+].O>[C:6]([C:7]1[N:11]2[C:12]3[C:17]([N:18]=[C:19]([NH:20][CH2:21][CH2:22][CH2:23][OH:24])[C:10]2=[N:9][CH:8]=1)=[CH:16][C:15]([C:25]([F:26])([F:27])[F:28])=[CH:14][CH:13]=3)#[CH:5]
Reactant: C[Si](C)(C)C#Cc1cnc2c(NCCCO)nc3cc(C(F)(F)F)ccc3n12
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [K+]
Solvent: O
Solvent: ClCCl
Solvent: CO
Product: C#Cc1cnc2c(NCCCO)nc3cc(C(F)(F)F)ccc3n12
Temperature: 25 °C
Reaction time: 1 h
Yield: 91.2 %

Procedure:
To a solution of 3-({1-[(trimethylsilyl)ethynyl]-7-(trifluoromethyl)imidazo[1,2-a]quinoxalin-4-yl}amino)propan-1-ol (80 mg, 0.20 mmol) in dichloromethane (1 mL) and methanol (1 mL) was added potassium carbonate (136 mg, 0.98 mmol). The heterogeneous mixture was stirred under argon at room temperature for 1 h and then diluted with brine and dichloromethane. The organic layer was washed three times with brine and the combined aqueous layers were extracted three times with dichoromethane. The combined organic extracts were dried over sodium sulfate, filtered and evaporated to afford the title compound (61 mg, 91%) as a yellow solid. The crude product was used without further purification.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)(=[O:11])=[O:10])[CH:5]=[N:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Cl[C:43]1[N:48]=[C:47]2[S:49][C:50]([NH:52][C:53](=[O:55])[CH3:54])=[N:51][C:46]2=[CH:45][CH:44]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CN(C=O)C.O1CCOCC1>[F:18][C:15]1[CH:16]=[CH:17][C:12]([S:9]([NH:8][C:4]2[CH:3]=[C:2]([C:43]3[N:48]=[C:47]4[S:49][C:50]([NH:52][C:53](=[O:55])[CH3:54])=[N:51][C:46]4=[CH:45][CH:44]=3)[CH:7]=[N:6][CH:5]=2)(=[O:11])=[O:10])=[CH:13][CH:14]=1
Reactant: CC(=O)Nc1nc2ccc(Cl)nc2s1
Reactant: O=S(=O)(Nc1cncc(Br)c1)c1ccc(F)cc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: CC(=O)[O-]
Solvent: C1COCCO1
Solvent: CN(C)C=O
Product: CC(=O)Nc1nc2ccc(-c3cncc(NS(=O)(=O)c4ccc(F)cc4)c3)nc2s1
Temperature: 90 °C
Reaction time: 19 h
Yield: 8.2 %

Procedure:
To a 25 mL round-bottomed flask was added N-(5-bromopyridin-3-yl)-4-fluorobenzenesulfonamide (0.15 g, 0.45 mmol), bis(pinacolato)diboron (0.17 g, 0.68 mmol, Aldrich, St. Louis. MO), potassium acetate (0.18 g, 1.8 mmol) and 1,4-dioxane (4.0 ml). The mixture was carefully evacuated and backfilled with N2 and then dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.033 g, 0.045 mmol, Strem, Newburyport, Mass.) was added. The mixture was carefully evacuated and backfilled with N2 again. The mixture was stirred at 90° C. for 19 hours and then allowed to cool to rt. To the mixture was added DMF (4.0 ml), N-(5-chlorothiazolo[5,4-b]pyridin-2-yl)acetamide (0.075 g, 0.33 mmol) and 2 M sodium carbonate (0.82 ml, 1.7 mmol). The mixture was carefully evacuated and backfilled with N2 and then trans-dichlorobis(triphenylphosphine)palladium (II) (0.023 g, 0.033 mmol, Strem) was added. The mixture was carefully evacuated and backfilled with N2 and then stirred at 90° C. for 18 h. The mixture was allowed to cool to room temperature and then poured into water (100 mL) and extracted with 25% iPrOH/CHCl3 (4×50 mL). The combined extracts were dried (Na2SO4) and concentrated. The residue was taken up in CH2Cl2/MeOH and concentrated onto silica. Purification by silica gel chromatography (3.0 to 10% MeOH (2 M in NH3)/CH2Cl2) afforded a brown solid. This was further purified by Prep-HPLC (Phenomenex Synergi 4u MAX-RP 80A 150×21.20 nm n, 00F-4337-P0, 2 to 100% CH3CN (0.1% TFA)/H2O (0.1% TFA) over 15 min then 100% CH3CN for 5 minutes at 20 ml/min) with the fractions containing suspected product concentrated to afford the title compound as a tan solid (0.012 g, 6.3% yield). MS (ESI pos. ion) m/z: 444 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.55 (s, 1H), 10.71 (s, 1H), 9.00 (d, J=1.8 Hz, 1H), 8.36 (d, J=2.5 Hz, 1H), 8.17-8.22 (m, 2H), 8.07 (d, J=8.6 Hz, 1H), 7.85-7.90 (m, 2H), 7.39-7.45 (m, 2H), 2.24 (s, 3H).
Reaction SMILES: [OH-].[Na+].[CH3:3][C:4]1[O:8][C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:6][C:5]=1[CH2:15][O:16][C:17]1[CH:39]=[CH:38][C:20]([CH2:21][O:22]/[N:23]=[C:24](/[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=2)\[CH2:25][CH2:26][C:27]([O:29]CC)=[O:28])=[CH:19][CH:18]=1.CO.Cl>O1CCCC1>[CH3:3][C:4]1[O:8][C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:6][C:5]=1[CH2:15][O:16][C:17]1[CH:39]=[CH:38][C:20]([CH2:21][O:22]/[N:23]=[C:24](/[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=2)\[CH2:25][CH2:26][C:27]([OH:29])=[O:28])=[CH:19][CH:18]=1
Reactant: CCOC(=O)CC/C(=N\OCc1ccc(OCc2nc(-c3ccccc3)oc2C)cc1)c1ccccn1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: Cc1oc(-c2ccccc2)nc1COc1ccc(CO/N=C(\CCC(=O)O)c2ccccn2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 86.6 %

Procedure:
A 1N aqueous saturated solution of sodium hydroxide (5 ml) was added to a solution of ethyl E-4-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyloxyimino]-4-(2-pyridyl)butyrate (520 mg) in tetrahydrofuran (10 ml)-methanol (5 ml) and stirred at room temperature for 1 hour. 1N hydrochloric acid (5.5 ml) was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The residue was recrystallized from ethyl acetate-hexane to obtain E-4-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyloxyimino]-4-(2-pyridyl)butyric acid (425 mg, yield 87%) as colorless crystals. m.p. 116-117° C.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][NH:8]2)=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].Cl[C:15]1[C:24]2[C:19](=[CH:20][C:21]([O:27][CH3:28])=[C:22]([O:25][CH3:26])[CH:23]=2)[N:18]=[CH:17][N:16]=1>CN1CCCC1=O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][N:8]2[C:15]2[C:24]3[C:19](=[CH:20][C:21]([O:27][CH3:28])=[C:22]([O:25][CH3:26])[CH:23]=3)[N:18]=[CH:17][N:16]=2)=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12]
Reactant: O=[N+]([O-])c1cc2c(cc1Cl)NCC2
Reactant: COc1cc2ncnc(Cl)c2cc1OC
Solvent: CN1CCCC1=O
Product: COc1cc2ncnc(N3CCc4cc([N+](=O)[O-])c(Cl)cc43)c2cc1OC
Yield: 24 %

Procedure:
Utilizing a procedure analogous to that described in Example 47 this product was prepared in 24% yield from 6-chloro-5-nitro-indoline (1.1 eq.), and 4-chloro-6,7-dimethoxy-quinazoline (1.0 eq) in N-methyl-pyrrolidinone. (M.P. 276°-278° C.; LC-MS: 387 (MH+); anal. RP18-HPLC RT: 4.48 min.).
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[O:10]=[C:11]([CH2:17][CH3:18])[CH2:12][C:13]([O:15][CH3:16])=[O:14].N1CCCCC1>C1C=CC=CC=1.CCOCC.CC(O)=O>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[C:12]([C:11](=[O:10])[CH2:17][CH3:18])[C:13]([O:15][CH3:16])=[O:14])=[CH:4][CH:3]=1
Reactant: CCC(=O)CC(=O)OC
Reactant: O=Cc1ccc(F)cc1
Solvent: CC(=O)O
Solvent: CCOCC
Solvent: c1ccccc1
Product: CCC(=O)C(=Cc1ccc(F)cc1)C(=O)OC
Temperature: 25 °C
Yield: 70 %

Procedure:
A mixture of para-fluorobenzaldehyde (37.98 gm, 306 mmol), 3-oxopentanoic acid, methyl ester (39.78 gm, 306 mmol), piperidine (2.60 gm, 30.6 mmol) and HOAc (0.555 gm, 9.2 mmol) was allowed to reflux in benzene (150 ml) 7 hours under argon. The solution was cooled to room temperature, then diluted with ether and washed with 2% HCl, saturated NaHCO3, water, and brine, then dried over MgSO4, filtered and concentrated to give a yellow oil. The oil was purified by distillation (bp=144° C. at 2.7 mm Hg) to give the title compound as a yellow oil (50.612 gm, 70%).
Reaction SMILES: [CH3:1][C:2]1[C:3]([CH2:8][S:9][CH2:10][CH2:11][NH2:12])=[N:4][CH:5]=[CH:6][CH:7]=1.[C:13]1([S:19]([NH:22][C:23](=[NH:26])SC)(=[O:21])=[O:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C(#N)C>[C:13]1([S:19]([NH:22][C:23]([NH2:26])=[N:12][CH2:11][CH2:10][S:9][CH2:8][C:3]2[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][N:4]=2)(=[O:20])=[O:21])[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: Cc1cccnc1CSCCN
Reactant: CSC(=N)NS(=O)(=O)c1ccccc1
Solvent: CC#N
Product: Cc1cccnc1CSCCN=C(N)NS(=O)(=O)c1ccccc1

Procedure:
A solution of 3-methyl-2-((2-aminoethyl)thiomethyl)pyridine (6.3 g) and N-benzenesulphonyl-S-methylisothiourea (8.0 g) in acetonitrile (100 ml) was heated under reflux for 24 hours. Concentration, followed by chromatographic purification on a column of silica gel and recrystallisation afforded N-benzenesulphonyl-N"-[2-((3-methyl-2-pyridyl)methylthio)ethyl]guanidine.
Reaction SMILES: O=[C:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:9]=[CH:10][C:11](=[O:14])[NH:12][CH:13]=2)[CH2:4][CH2:3]1.[NH:15]1[CH2:18][CH:17]([NH:19][C:20]([CH2:22][NH:23][C:24](=[O:35])[C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=2)=[O:21])[CH2:16]1>>[O:14]=[C:11]1[NH:12][CH:13]=[C:8]([CH:5]2[CH2:6][CH2:7][CH:2]([N:15]3[CH2:18][CH:17]([NH:19][C:20]([CH2:22][NH:23][C:24](=[O:35])[C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:32])[F:33])[CH:26]=4)=[O:21])[CH2:16]3)[CH2:3][CH2:4]2)[CH:9]=[CH:10]1
Reactant: O=C1CCC(c2ccc(=O)[nH]c2)CC1
Reactant: O=C(CNC(=O)c1cccc(C(F)(F)F)c1)NC1CNC1
Product: O=C(CNC(=O)c1cccc(C(F)(F)F)c1)NC1CN(C2CCC(c3ccc(=O)[nH]c3)CC2)C1

Procedure:
The title compounds were prepared as white solids from the reductive amination of 5-(4-oxo-cyclohexyl)-1H-pyridin-2-one (as prepared in the previous step) and N-(azetidin-3-ylcarbamoylmethyl)-3-trifluoromethyl-benzamide using the procedure described in Step F of Example 1.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][C:6]12[CH2:17][CH2:16][CH2:15][C:13]3[C:14]1=[C:9]([CH:10]=[CH:11][CH:12]=3)[NH:8][C:7]2=[O:18].[CH3:19][O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:19][O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[N:27]1[CH2:32][CH2:31][N:30]([CH2:2][CH2:3][CH2:4][CH2:5][C:6]23[CH2:17][CH2:16][CH2:15][C:13]4[C:14]2=[C:9]([CH:10]=[CH:11][CH:12]=4)[NH:8][C:7]3=[O:18])[CH2:29][CH2:28]1
Reactant: O=C1Nc2cccc3c2C1(CCCCBr)CCC3
Reactant: COc1ccccc1N1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1ccccc1N1CCN(CCCCC23CCCc4cccc(c42)NC3=O)CC1
Yield: 94.4 %

Procedure:
2a-(4-Bromobutyl)-2a,3,4,5-tetrahydrobenz[cd]indole-2(1H)-one (220 mg, 0.72 mmol), 4-(2-methoxyphenyl)piperazine (150 mg, 0.79 mmol) and potassium carbonate (150 mg, 1.1 mmol) were stirred in anhydrous N,N-dimethylformamide (5 ml) at 50° C. for 4 hours. The solvent was evaporated under a reduced pressure, and the thus obtained residue was mixed with ethyl acetate and water. The reaction product was extracted with ethyl acetate, washed with saturated brine and dried with anhydrous sodium sulfate. Then the compound obtained by the evaporation of the solvent under a reduced pressure was separated and purified by a silica gel column chromatography to obtain 280 mg of the title compound (0.68 mmol, 94% in yield).
Reaction SMILES: [CH3:1][CH:2]1[C:7]([CH3:19])([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[N:15]=[N:16][NH:17][CH:18]=3)[CH:9]=2)[CH2:6][CH2:5][NH:4][CH2:3]1.Br[CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([CH3:29])[CH:24]=1.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH3:1][CH:2]1[C:7]([CH3:19])([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[N:15]=[N:16][NH:17][CH:18]=3)[CH:9]=2)[CH2:6][CH2:5][N:4]([CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([CH3:29])[CH:24]=2)[CH2:3]1
Reactant: CC1CNCCC1(C)c1cccc(-c2c[nH]nn2)c1
Reactant: Cc1cccc(CCBr)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1cccc(CCN2CCC(C)(c3cccc(-c4c[nH]nn4)c3)C(C)C2)c1
Reaction time: 8 h
Yield: 12.9 %

Procedure:
To a solution of 3,4-dimethyl-4-(3-(1H-1,2,3-triazol-4-yl)phenyl)piperidine (Preparation 44, 80 mg, 0.31 mmol) in N,N-dimethyl-formamide (6 mL) was added 1-(2-bromoethyl)-3-methylbenzene (Preparation 46, 67 mg, 0.31 mmol) and sodium hydrogencarbonate (40 mg, 0.47 mmol). The resultant mixture was heated to 80° C. and stirred overnight. The reaction mixture was cooled, poured onto saturated aqueous sodium hydrogencarbonate solution (100 mL) and extracted with ethyl acetate (3×20 mL). The combined extracts were dried over MgSO4, filtered and concentrated in vacuo to give an off-white gum. The crude product was partially purified by column chromatography on a 5 g silica Waters Sep-Pak3 eluting with dichloromethane and then 5% methanol in dichloromethane. The pure fractions were collected to give the title compound as a clear oil (15 mg, 12.8%).
Reaction SMILES: C1CCCCC1.C([Li])(CC)C.[F:12][C:13]1[CH:14]=[C:15]([C:19]2[CH:28]=[CH:27][C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=2)[CH:16]=[CH:17][CH:18]=1.[I:29]I>O.C1COCC1>[F:12][C:13]1[CH:14]=[C:15]([C:19]2[CH:28]=[CH:27][C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=2)[CH:16]=[CH:17][C:18]=1[I:29]
Reactant: II
Reactant: Fc1cccc(-c2ccc3ccccc3c2)c1
Agent: [Li]C(C)CC
Solvent: C1CCCCC1
Solvent: O
Solvent: C1CCOC1
Product: Fc1cc(-c2ccc3ccccc3c2)ccc1I
Temperature: 25 °C
Reaction time: 1 h
Yield: 78.2 %

Procedure:
A 50.21 ml cyclohexane solution of sec-butyl lithium in a concentration of 1.01M was dropped into a 200 ml THF solution of 4.90 g (=22.05 mmol) of the above 2-(3-fluorophenyl)naphthalene at −70° C. After the dropping was finished, the reaction solution was stirred at the same temperature for 1 hour, added with a 200 ml THF solution of 12.87 g (=50.71 mmol) of iodine through dropping and then slowly heated to room temperature. After being stirred for 18 hours, the reaction solution was added into iced water dissolved with Na2S2O3.5H2O, and then the reaction mixture was extracted twice with toluene. The extract was washed thrice with water and then dried with anhydrous MgSO4. After the solvent was evaporated under a reduced pressure, the obtained orange solid of 8.61 g was purified with silica gel chromatography using heptane/toluene in a ratio of 5:1 as the eluent to obtain a pinkish solid of 7.86 g, which was recrystallized with a mixed solvent of Solumix/heptane/toluene in a ratio of 5:5:1 to obtain 6.00 g of 2-(3-fluoro-4-iodophenyl)naphthalene as yellowish crystals.
Reaction SMILES: [C:1]([O:5][C@@H:6]([C:11]1[C:12]([C:25]2[CH2:32][CH2:31][C:28]3([CH2:30][CH2:29]3)[CH2:27][CH:26]=2)=[C:13]2[C:18](=[CH:19][C:20]=1[CH3:21])[N:17]=[C:16]([CH:22]([F:24])[F:23])[CH:15]=[CH:14]2)[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Li+]>O1CCCC1.CO.O.C(#N)C>[C:1]([O:5][C@@H:6]([C:11]1[C:12]([C:25]2[CH2:32][CH2:31][C:28]3([CH2:29][CH2:30]3)[CH2:27][CH:26]=2)=[C:13]2[C:18](=[CH:19][C:20]=1[CH3:21])[N:17]=[C:16]([CH:22]([F:23])[F:24])[CH:15]=[CH:14]2)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(C(F)F)ccc2c1C1=CCC2(CC1)CC2
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: CC#N
Solvent: O
Product: Cc1cc2nc(C(F)F)ccc2c(C2=CCC3(CC2)CC3)c1[C@H](OC(C)(C)C)C(=O)O
Temperature: 50 °C
Yield: 67.3 %

Procedure:
To a solution of (S)-methyl 2-tert-butoxy-2-(2-(difluoromethyl)-7-methyl-5-(spiro[2.5]oct-5-en-6-yl)quinolin-6-yl)acetate (44.7 mg, 0.101 mmol) in tetrahydrofuran:methanol:water (2:2:1, 2 mL) was added lithium hydroxide (12 mg, 0.504 mmol) and the reaction was heated to 50° C. overnight. The reaction was diluted with acetonitrile and purified by reverse phase HPLC (Gemini, 15 to 95 ACN/H2O+0.1% TFA) and the desired product was lyophilized to give a white powder (29.2 mg). 1H-NMR: 400 MHz, (CD3CN) δ: 8.49 (d, J=8.8 Hz, 1 H), 7.85 (s, 1 H), 7.69 (d, J=8.4 Hz, 1 H), 6.84 (t, =55.2 Hz, 1 H), 5.93 (s, 1 H), 5.68 (s, 1 H), 2.67 (m, 1 H), 2.62 (s, 3 H), 2.46 (m, 1 H), 2.28-2.24 (m, 2 H), 1.66 (m, 2 H), 1.23 (s, 9 H), 0.54-0.40 (m, 4 H). LCMS-ESI+ (m/z): [M+H]+ calcd for C25H30F2NO3: 430.21. found: 430.32.
Reaction SMILES: [C:1]([C:5]1[CH:26]=[CH:25][C:8]([O:9][CH:10]([C:16]2[CH:21]=[CH:20][C:19]3[O:22][CH2:23][O:24][C:18]=3[CH:17]=2)[C:11]([O:13]CC)=[O:12])=[C:7]([CH2:27][CH2:28][CH3:29])[CH:6]=1)([O:3][CH3:4])=[O:2].[OH-].[Na+].C(Cl)Cl.CO.[NH4+].[OH-]>CO>[C:1]([C:5]1[CH:26]=[CH:25][C:8]([O:9][CH:10]([C:16]2[CH:21]=[CH:20][C:19]3[O:22][CH2:23][O:24][C:18]=3[CH:17]=2)[C:11]([OH:13])=[O:12])=[C:7]([CH2:27][CH2:28][CH3:29])[CH:6]=1)([O:3][CH3:4])=[O:2]
Reactant: CCCc1cc(C(=O)OC)ccc1OC(C(=O)OCC)c1ccc2c(c1)OCO2
Agent: [NH4+]
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CO
Product: CCCc1cc(C(=O)OC)ccc1OC(C(=O)O)c1ccc2c(c1)OCO2
Yield: 96.4 %

Procedure:
To a nitrogen flushed 5 L 3 neck round bottom flask equipped with a mechanical stirrer, a dropping funnel, and a nitrogen inlet was charged with 697.3 g (1.68 mol) of the crude product of Step A and 2 L of methanol. 500 mL of 5.0N (1.5 eq) aqueous sodium hydroxide was added over a 20-minute period via an addition funnel. The reaction mixture was stirred at room temperature for an additional 1 hr at which point TLC analysis (CH2Cl2 -MeOH-NH4OH 90:10:1) indicated that the starting material had been consumed. The reaction mixture neutralized with 420 mL of 6N HCl, and the bulk of the organic solvent was removed in vacuo. The residue was dissolved in ether and extracted with a combination of aqueous NaOH and NaHCO3. The aqueous layer was extracted with ether and the combined organic layer was washed with aqueous NaHCO3. The aqueous layer was acidified with HCl and extracted with ether. The ether solution was dried with magnesium sulfate, filtered, and concentrated to afford 708.9 g (theoretical 625 g) of the title compound as a viscous orange oil. NMR indicated that it was ca. 85% product by weight (15% ether) thus providing a corrected yield of 602.6 g (96.4% yield)
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[N:11]=[C:10]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([N:26]4[C:34]5[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=5[C:28]5[CH:35]=[N:36][CH:37]=[CH:38][C:27]4=5)[N:21]=3)[CH:9]=2)=[CH:4][CH:3]=1.[CH:39]1[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH:42]=[CH:41][C:40]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1>C(Cl)(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C>[CH:47]1[C:48]2[C:43](=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH:44]=[CH:45][C:46]=1[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[N:11]=[C:10]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([N:26]4[C:34]5[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=5[C:28]5[CH:35]=[N:36][CH:37]=[CH:38][C:27]4=5)[N:21]=3)[CH:9]=2)=[CH:4][CH:3]=1
Reactant: Brc1ccc(-c2cc(-c3ccccn3)nc(-c3cccc(-n4c5ccccc5c5cnccc54)n3)c2)cc1
Reactant: OB(O)c1ccc2ccccc2c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CCO
Solvent: ClC(Cl)Cl
Product: c1ccc(-c2cc(-c3ccc(-c4ccc5ccccc5c4)cc3)cc(-c3cccc(-n4c5ccccc5c5cnccc54)n3)n2)nc1
Temperature: 25 °C
Reaction time: 6 h
Yield: 71.5 %

Procedure:
To 4.6 g of the 4′-(4-bromophenyl)-6-(5H-pyrido[4,3-b]indol-5-yl)-[2,2′;6′,2″]terpyridine obtained in Example 4 were added 1.4 g of 2-naphthaleneboronic acid, 0.5 g of tetrakis(triphenylphosphine)palladium, 21 mL of a 2 M aqueous potassium carbonate solution, 72 mL of toluene, and 18 mL of ethanol, followed by heating with reflux while stirring for 6 hours. After cooling to room temperature, a precipitate was collected by filtration. To the precipitate, 200 mL of o-dichlorobenzene was added and insoluble matter was removed by filtration. The filtrate was concentrated under a reduced pressure to obtain a concentrate. The concentrate was dissolved in chloroform and subjected to adsorptive purification with NH silica gel. Thereafter, the filtrate was concentrated under a reduced pressure to obtain a crude product. The crude product was washed with ethyl acetate to obtain 3.5 g (yield, 69%) of 4′-(4-naphthalen-2-yl-phenyl)-6-(5H-pyrido[4,3-b]indol-5-yl)-[2,2′;6′,2″]terpyridine (Compound 134) as a white powder.
Reaction SMILES: [CH3:1][C:2]1[C:6]([CH2:7][C:8]2[C:16]3[O:15][CH2:14][C:13](=[O:17])[C:12]=3[CH:11]=[CH:10][C:9]=2[O:18][CH3:19])=[C:5]([CH3:20])[NH:4][N:3]=1.[NH:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23]([CH:30]=O)=[N:22]1.N1CCCCC1>CO>[NH:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](/[CH:30]=[C:14]2\[O:15][C:16]3[C:8]([CH2:7][C:6]4[C:2]([CH3:1])=[N:3][NH:4][C:5]=4[CH3:20])=[C:9]([O:18][CH3:19])[CH:10]=[CH:11][C:12]=3[C:13]\2=[O:17])=[N:22]1
Reactant: COc1ccc2c(c1Cc1c(C)n[nH]c1C)OCC2=O
Reactant: O=Cc1n[nH]c2ccccc12
Solvent: C1CCNCC1
Solvent: CO
Product: COc1ccc2c(c1Cc1c(C)n[nH]c1C)O/C(=C\c1n[nH]c3ccccc13)C2=O
Temperature: 60 °C
Reaction time: 2 h
Yield: 61.7 %

Procedure:
A solution of 7-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-6-methoxybenzofuran-3(2H)-one (0.0427 g, 0.157 mmol) in methanol (0.6 mL) was added with 1H-indazole-3-carboxaldehyde (0.0229 g, 0.157 mmol) and piperidine (0.0107 g, 0.126 mmol), and the mixture was stirred at 60° C. for 2 hours. The reaction mixture was cooled to room temperature, and the precipitated solid was collected by filtration to obtain (Z)-2-[(1H-indazol-3-yl)methylene]-7-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-6-methoxybenzofuran-3(2H)-one (0.0388 g, 61%).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:23]=[O:24])[S:5][C:6]=1[C:7]1[S:8][C:9]([C:12]2[S:13][C:14]([C:17]3[S:18][CH:19]=[CH:20][C:21]=3[CH3:22])=[CH:15][CH:16]=2)=[CH:10][CH:11]=1.[BH4-].[Na+]>C(O)C>[CH3:1][C:2]1[CH:3]=[C:4]([CH2:23][OH:24])[S:5][C:6]=1[C:7]1[S:8][C:9]([C:12]2[S:13][C:14]([C:17]3[S:18][CH:19]=[CH:20][C:21]=3[CH3:22])=[CH:15][CH:16]=2)=[CH:10][CH:11]=1
Reactant: Cc1ccsc1-c1ccc(-c2ccc(-c3sc(C=O)cc3C)s2)s1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: Cc1ccsc1-c1ccc(-c2ccc(-c3sc(CO)cc3C)s2)s1
Reaction time: 0.5 h
Yield: 97.1 %

Procedure:
To a suspension of 4MT-CHO (1.35 g, 3.5 mmol) in 30 mL dry ethanol was added 265 mg (7 mmol) sodium borohydride in small portions. The reaction mixture quickly changed color from orange to yellow and the stirring was continued for 30 min. Removal of the solvent under reduced pressure followed by purification with flash silica gel column chromatography using chloroform as eluent yielded yellow crystals (1.32 g, 97.2%).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:17]=[C:16]2[C:11]([CH2:12][CH2:13][C:14](=[O:18])[NH:15]2)=[CH:10][CH:9]=1.[CH2:19]([CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH2:19]([CH:26]1[CH2:31][CH2:30][N:29]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][O:7][C:8]2[CH:17]=[C:16]3[C:11]([CH2:12][CH2:13][C:14](=[O:18])[NH:15]3)=[CH:10][CH:9]=2)[CH2:28][CH2:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: c1ccc(CC2CCNCC2)cc1
Reactant: O=C1CCc2ccc(OCCCCCBr)cc2N1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: O=C1CCc2ccc(OCCCCCN3CCC(Cc4ccccc4)CC3)cc2N1
Yield: 88 %

Procedure:
2.7 Grams of 7-(5-bromopentoxy)-3,4-dihydrocarbostyril, 2.0 g of 4-benzylpiperidine and 1.5 g of triethylamine were mixed with 30 ml of dimethylformamide and the mixture was heated at 60°-70° C. for 6 hours. The reaction mixture was then concentrated under a reduced pressure to dryness, and to the residue thus obtained was added a 5%-sodium hydrogencarbonate aqueous solution and stirred. The insoluble matters thus formed were collected by filtration, washed with water and dried. Recrystallization from ligroin to obtain 3.6 g (yield: 88%) of 7-[5-(4-benzyl-1-piperidyl)pentoxy]-3,4-dihydrocarbostyril as in the form of colorless plate-like crystals. Melting point: 100°-102° C.