Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:18]=2[NH:24]C(=O)OC(C)(C)C)=[O:16])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>ClCCl>[NH2:24][C:18]1[C:19]([F:23])=[CH:20][CH:21]=[CH:22][C:17]=1[C:15]([NH:14][CH:11]1[CH2:12][CH2:13][N:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:9][CH2:10]1)=[O:16]
Reactant: CC(C)(C)OC(=O)Nc1c(F)cccc1C(=O)NC1CCN(Cc2ccccc2)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Nc1c(F)cccc1C(=O)NC1CCN(Cc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of tert-butyl 2-(1-benzylpiperidin-4-ylcarbamoyl)-6-fluorophenylcarbamate (67.0 g, 157 mmol) in dichloromethane (700 mL) at 0° C. was added trifluoroacetic acid (100 mL). The ice bath was removed and the reaction stirred at room temperature overnight. The reaction was concentrated and partitioned between ethyl acetate and saturated sodium bicarbonate. The aqueous was extracted with ethyl acetate (2×), which were washed with water (3×), then brine, dried over magnesium sulfate, and concentrated to give 47.6 g (93%) as a white solid which was used without purification. Mass spec.: 328.33 (MH)+.
Reaction SMILES: [CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[CH:3]=1.[F:11][C:12]1[C:16]([F:17])=[CH:15][NH:14][CH:13]=1.B(F)(F)F>C(Cl)Cl>[F:11][C:12]1[C:16]([F:17])=[C:15]2[C:1]([C:2]3[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[CH:3]=3)=[C:15]3[N:14]=[C:13]([C:1]([C:2]4[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[CH:3]=4)=[C:15]4[NH:14][C:13](=[C:1]([C:2]5[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[CH:3]=5)[C:13]5[C:12]([F:11])=[C:16]([F:17])[C:15](=[C:1]([C:2]6[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[CH:3]=6)[C:13]=1[NH:14]2)[N:14]=5)[C:12]([F:11])=[C:16]4[F:17])[C:12]([F:11])=[C:16]3[F:17]
Reactant: Fc1c[nH]cc1F
Reactant: COc1cccc(C=O)c1
Agent: FB(F)F
Solvent: ClCCl
Product: COc1cccc(-c2c3nc(c(-c4cccc(OC)c4)c4[nH]c(c(F)c4F)c(-c4cccc(OC)c4)c4nc(c(-c5cccc(OC)c5)c5[nH]c2c(F)c5F)C(F)=C4F)C(F)=C3F)c1
Reaction time: 0.5 h
Yield: 19.2 %

Procedure:
m-Anisaldehyde (0.3 mL, 2.5 mmol), 3,4-difluoropyrrole (215 mg, 2.1 mmol), and 100 mL of dry CH2Cl2 were placed under N2 in a 250 mL round-bottom flask equipped with a magnetic stir bar. The reaction was stirred while BF3 etherate (0.9 mL, 7.1 mmol) was added via syringe. To monitor the reaction, aliquots were periodically removed from the reaction vessel, oxidized with DDQ, neutralized with pyridine, and chromatographed by silica gel TLC using CHCl3 as eluent. After 30 minutes, DDQ (1 g) and pyridine (3 mL) were added. The reaction was stirred for 12 hours and filtered through a short silica gel column using CH3Cl3 as eluent, and the solvent was evaporated. A rough purification was done using a silica gel column with CHCl3 as eluent. The solvent was removed, and the product was further purified on silica gel using chloroform/hexane (1:4). The pure fractions were combined and concentrated to afford 88.8 mg of pure 2,3,7,8,12,13,17,18-octafluoro-5,10,15,20-tetrakis(3-methoxyphenyl)porphyrin in 20% yield. The product is characterized by the following data: 1H NMR (360 MHz, CDCl3) δ 7.65 (t, 12H), 7.30 (m, 4H), 4.02 (s, 12H), -4.14 (s, 2H); 19F δ (500 MHz, CDCl3, -50° C.) δ -140.9 (s, 4F), -146.0 (s, 4F); UV-vis (CH2Cl2) 406 (5.31), 500 (4.22), 533 (3.67), 581 (3.57), 636 (3.56); low-resolution FAB MS 878 (calcd 878). Anal. Calcd for C48H30F8N4O4 : C, 65.61; H, 3.44; N, 6.38. Found: C, 64.49-H, 3.46; N, 5.61.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[C:10]=2[Cl:16])=[C:4]([CH2:17][F:18])[N:3]=1.NC1N=C(N)C(C2C=C([Cl:33])C=C(Cl)C=2Cl)=C(CO)N=1>>[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([C:9]2[CH:14]=[C:13]([Cl:33])[CH:12]=[C:11]([Cl:15])[C:10]=2[Cl:16])=[C:4]([CH2:17][F:18])[N:3]=1
Reactant: Nc1nc(N)c(-c2cccc(Cl)c2Cl)c(CF)n1
Reactant: Nc1nc(N)c(-c2cc(Cl)cc(Cl)c2Cl)c(CO)n1
Product: Nc1nc(N)c(-c2cc(Cl)cc(Cl)c2Cl)c(CF)n1

Procedure:
This compound was prepared in an analogous manner to the compound of Example 18 from 2,4-diamino-5-(2,3,5-trichlorophenyl )-6-hydroxymethylpyrimidine, mp. 215°-217° C.
Reaction SMILES: C(O)(=O)C.Cl[C:6]1[NH:11][C:10](=[O:12])[N:9]=[C:8]([N:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[CH2:15][CH2:14]2)[N:7]=1>[OH-].[Pd+2].[OH-].O>[F:25][C:22]1[CH:23]=[CH:24][C:19]([N:16]2[CH2:15][CH2:14][N:13]([C:8]3[N:7]=[CH:6][NH:11][C:10](=[O:12])[N:9]=3)[CH2:18][CH2:17]2)=[CH:20][CH:21]=1
Reactant: O=c1nc(N2CCN(c3ccc(F)cc3)CC2)nc(Cl)[nH]1
Agent: [Pd+2]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Product: O=c1nc(N2CCN(c3ccc(F)cc3)CC2)nc[nH]1
Temperature: 25 °C
Reaction time: 72 h
Yield: 98.5 %

Procedure:
An acetic acid (15 mL)-water (35 mL) mixed solution of 6-chloro-4-[4-(4-fluorophenyl)piperazin-1-yl]-1,3,5-triazin-2(1H)-one (1.00 g, 3.23 mmol) synthesized in Reference Synthesis Example 2 and palladium hydroxide-activated carbon catalyst (100 mg) was stirred under hydrogen atmosphere at room temperature for 3 days. After completion of the reaction, the reaction solution was filtered with Celite and the filtered residue was washed with methanol, followed by concentrating the obtained solution under reduced pressure. Toluene was added to the residue and the mixture was azeotropically dehydrated four times. The obtained residue was dried under reduced pressure to obtain the title compound (876 mg, yield 99%).
Reaction SMILES: [OH:1][CH2:2][C@@H:3]1[CH2:8][CH2:7][C@H:6]([C:9]([O:11][CH2:12][CH2:13][CH2:14][CH3:15])=[O:10])[CH2:5][CH2:4]1.C(N(CC)CC)C.[CH3:23][S:24](Cl)(=[O:26])=[O:25]>C(Cl)Cl>[CH3:23][S:24]([O:1][CH2:2][C@@H:3]1[CH2:4][CH2:5][C@H:6]([C:9]([O:11][CH2:12][CH2:13][CH2:14][CH3:15])=[O:10])[CH2:7][CH2:8]1)(=[O:26])=[O:25]
Reactant: CS(=O)(=O)Cl
Reactant: CCCCOC(=O)[C@H]1CC[C@@H](CO)CC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCOC(=O)[C@H]1CC[C@@H](COS(C)(=O)=O)CC1
Reaction time: 18 h

Procedure:
To a solution of butyl cis-4-(hydroxymethyl)cyclohexanecarboxylate (25.06 g, 117 mmol) and triethylamine (24.3 ml, 17.8 g, 176 mmol) in methylene chloride (600 ml) under nitrogen, cooled in an ice-bath, was added dropwise over 20 minutes methane-sulfonyl-chloride (13.6 ml, 16.1 g, 140 mmol). The solution was stirred 18 hours while warming from 0° C. to ambient temperature. Additional triethylamine (2 ml, 1.5 g, 14 mmol) and methane-sulfonyl-chloride (1 ml, 1.5 g, 13 mmol) were added and the mixture was stirred four hours at ambient temperature. The mixture was diluted with methylene chloride (300 ml), washed with IN hydrochloric acid (300 ml), water (300 ml), and half-saturated sodium carbonate solution (300 ml), dried (sodium sulfate), filtered, and the solvent was evaporated under reduced pressure to give crude butyl cis-4-{[(methylsulfonyl)oxy]methyl}cyclohexanecarboxylate (35.31 g) as an orange oil: 1H NMR (CDCl3) 4.08 (4H, m), 3.00 (3H, s), 2.59 (1H, m), 2.05 (2H, m), 1.86 (1H, m) 1.52-1.69 (6H, m), 1.31-1.43 (4H, m), 0.94 (3H, m). MS.: 293.3 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]2[CH2:15][C:14]3[CH:16]=[CH:17][CH:18]=[CH:19][C:13]=3[NH:12][C:11](=[O:20])[C@H:10]2[CH3:21])=[CH:5][CH:4]=1.[H-].[Na+].[CH3:24][N:25]([CH2:27][CH2:28][Cl:29])[CH3:26].C1(C)C=CC=CC=1>CN(C)C=O>[ClH:29].[CH3:24][N:25]([CH3:26])[CH2:27][CH2:28][N:12]1[C:13]2[CH:19]=[CH:18][CH:17]=[CH:16][C:14]=2[CH2:15][C@H:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[C@H:10]([CH3:21])[C:11]1=[O:20]
Reactant: CN(C)CCCl
Reactant: COc1ccc([C@H]2Cc3ccccc3NC(=O)[C@H]2C)cc1
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Product: COc1ccc([C@H]2Cc3ccccc3N(CCN(C)C)C(=O)[C@H]2C)cc1
Product: Cl
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A solution of (cis)-1,3,4,5-tetrahydro-4-(4-methoxyphenyl)-3-methyl-2H-1-benzazepin-2-one (0.37 g, 1.32 mmol) in 13 ml of dry dimethylformamide was treated with sodium hydride (0.035 g, 1.45 mmol, room temperature, argon) and stirring at room temperature was continued for one-half hour. N,N-Dimethyl-2-chloroethylamine (0.92 ml of a 2.15M solution in toluene 1.97 mmol) was introduced and the reaction was carried out for 3 hours (85° C. oil bath). TLC indicated that reaction progress had stopped after 11/2 hours. More sodium hydride (0.02 g, 0.83 mmol) was added (room temperature) followed by more N,N-dimethyl-2-chloroethylamine solution (0.46 ml, 0.99 mmol). The reaction was continued at 85° C. (oil bath temperature) for 31/2 hours. Dimethylformamide was removed in vacuo. Ethyl acetate and water were added, the water layer was washed with ethyl acetate, the combined ethyl acetate layers were washed with water (2 times), brine, dried over sodium sulfate and evaporated in vacuo to yield 0.42 g of a yellow oil. Acidification with saturated hydrogen chloride/ether solution followed by evaporation in vacuo and subsequent trituration with ether (1 crop) yielded 0.37 g of an off-white solid. TLC of the mother liquor revealed the presence of unconsumed starting material. Recrystallization from ethyl acetate/methanol (2 crops) yielded 0.22 g of an off-white solid, melting point 211°-216° C., dec. (foaming).
Reaction SMILES: C([Li])(C)(C)C.Br[C:7]1[CH:17]=[C:16]([C:18]([CH3:21])([CH3:20])[CH3:19])[C:10]2[O:11][CH2:12][C:13]([CH3:15])([CH3:14])[C:9]=2[CH:8]=1.CN(C)[CH:24]=[O:25]>C1COCC1>[C:18]([C:16]1[C:10]2[O:11][CH2:12][C:13]([CH3:15])([CH3:14])[C:9]=2[CH:8]=[C:7]([CH:24]=[O:25])[CH:17]=1)([CH3:21])([CH3:20])[CH3:19]
Reactant: CC(C)(C)c1cc(Br)cc2c1OCC2(C)C
Reactant: CN(C)C=O
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Product: CC(C)(C)c1cc(C=O)cc2c1OCC2(C)C
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 28.1 %

Procedure:
t-Butyllithium (11.9 mL, 20.3 mmol, 1.7M in pentane) is added dropwise to a solution of 5-bromo-7-tert-butyl-2,3-dihydro-3,3-dimethylbenzo[b]furan (3.60 g, 12.7 mmol) in 50 mL of anhydrous THF at -78° C.; the resulting reaction mixture is stirred at -78° C. for 15 min and N,N-dimethylformamide (1.0 mL, 13.0 mmol) is introduced. The reaction mixture is kept at -78° C. for 0.5 h, quenched with water, warmed to room temperature, and extracted with ether. The extract is washed with water, dried over anhydrous magnesium sulfate, and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (10%→20% ether-hexane) gives 0.83 g (28%) of 7-tert-butyl-2,3-dihydro-3,3-dimethyl-5-formylbenzo[b]furan as a yellowish oil.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[N:19]=[CH:18][C:17]([CH2:20][C:21]([NH2:23])=[O:22])=[C:16]([NH:24][CH2:25][CH:26]4[CH2:30][CH2:29][CH2:28][NH:27]4)[CH:15]=3)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.[C:31](OC(=O)C)(=[O:33])[CH3:32].N1C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.O>[C:31]([N:27]1[CH2:28][CH2:29][CH2:30][CH:26]1[CH2:25][NH:24][C:16]1[CH:15]=[C:14]([NH:13][C:10]2[CH:11]=[CH:12][C:7]([N:4]3[CH2:3][CH2:2][O:1][CH2:6][CH2:5]3)=[CH:8][CH:9]=2)[N:19]=[CH:18][C:17]=1[CH2:20][C:21]([NH2:23])=[O:22])(=[O:33])[CH3:32]
Reactant: NC(=O)Cc1cnc(Nc2ccc(N3CCOCC3)cc2)cc1NCC1CCCN1
Reactant: CC(=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Solvent: ClCCl
Solvent: O
Product: CC(=O)N1CCCC1CNc1cc(Nc2ccc(N3CCOCC3)cc2)ncc1CC(N)=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 87.7 %

Procedure:
30.3 mg of 6-[(4-morpholinophenyl)amino]-4-[(pyrrolidin-2-ylmethyl)amino]pyridine-3-carboxyamide (the compound of Example 358) was dissolved in 2 mL of methylene chloride, to which 9.4 mg of acetic anhydride and 9.1 mg of pyridine were sequentially added, and stirred at room temperature for 2 hours. To the reaction mixture saturated sodium bicarbonate in water was added, extracted with chloroform:methanol=10:1, the extract was washed with saturated saline, and dried on anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by silica gel thin layer chromatography (chloroform:ammonia methanol=8:1), recrystallized from chloroform-ether to obtain the title compound (29.3 mg, 87%) as a light yellow crystalline powder.
Reaction SMILES: [CH:1]1(/[CH:7]=[CH:8]/[C:9]2[S:13][CH:12]=[C:11]([CH:14]=[O:15])[CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:16][C:17]#[N:18]>>[CH:1]1(/[CH:7]=[CH:8]/[C:9]2[S:13][CH:12]=[C:11]([CH:14]([OH:15])[CH2:16][C:17]#[N:18])[CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CC#N
Reactant: O=Cc1csc(/C=C/C2CCCCC2)c1
Product: N#CCC(O)c1csc(/C=C/C2CCCCC2)c1

Procedure:
Addition of CH3CN to (E)-5-(2-cyclohexylvinyl)thiophene-3-carbaldehyde following the method used in Example 3 gave (E)-3-(5-(2-cyclohexylvinyl)thiophen-3-yl)-3-hydroxypropanenitrile as a yellow oil which was used in the next step without further purification. Yield (0.47 g, quant.).
Reaction SMILES: Cl[C:2]1C=C(C(OO)=O)C=CC=1.CS[C:14]1[CH:15]=[N:16][CH:17]=[C:18]([C:20]#[C:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:19]=1.[S:28]([O-:31])([O-:30])=S.[Na+].[Na+]>ClCCl>[CH3:2][S:28]([C:14]1[CH:15]=[N:16][CH:17]=[C:18]([C:20]#[C:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:19]=1)(=[O:31])=[O:30]
Reactant: CSc1cncc(C#Cc2ccccc2)c1
Reactant: [O-]S([O-])=S
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: [Na+]
Solvent: ClCCl
Product: CS(=O)(=O)c1cncc(C#Cc2ccccc2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 64 %

Procedure:
Add 3-chlorobenzenecarboperoxoic acid (79.2 mg, 0.46 mmol) to a solution of 3-methylsulfanyl-5-phenylethynyl-pyridine, (prepared as described in EXAMPLE 128), (34.4 mg, 0.15 mmol) in dichloromethane (1 mL) at 0° C., warm to room temperature and stir for 2 h. Dilute with a 5% aqueous solution of sodium thiosulfite and dichloromethane. After separating the layers, sequentially wash the organic layer with a 5% aqueous solution of sodium thiosulfite and an aqueous saturated solution of sodium chloride, dry (magnesium sulfate), filter and concentrate. Purify the residue by silica gel chromatography, eluting with 100:0 to 100:50 hexanes:ethyl acetate, to give the title compound (24.8 mg, 64%).
Reaction SMILES: [CH2:1]([C:3]1[CH:4]=[C:5]([NH:9][C:10]#[N:11])[CH:6]=[CH:7][CH:8]=1)[CH3:2].Cl.[C:13]1([NH2:23])[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][CH:14]=1>ClC1C=CC=CC=1>[C:13]1([NH:23][C:10]([NH:9][C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([CH2:1][CH3:2])[CH:4]=2)=[NH:11])[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][CH:14]=1
Reactant: Nc1cccc2ccccc12
Reactant: CCc1cccc(NC#N)c1
Agent: Cl
Solvent: Clc1ccccc1
Product: CCc1cccc(NC(=N)Nc2cccc3ccccc23)c1
Temperature: 25 °C
Yield: 6.4 %

Procedure:
A solution of m-ethylphenylcyanamide (730 mg, 2.99 mmol) and 1-naphthylamine hydrochloride (900 mg, 5.05 mmol) in chlorobenzene (20 ml) was heated at 140°-145° C. for 12 hours. It was allowed to cool to room temperature, concentrated and the residue was partitioned between dichloromethane and 10% NaOH solution. The organic layer was concentrated and the resulting residue was recrystallized from abs. EtOH-H2O to give N-(1-naphthyl)-N'-(m-ethylphenyl)guanidine (55 mg, 4%) as off-white needles. mp 96°-98° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)=[CH:9][CH2:10][CH2:11][N:12]2[CH2:30][CH2:29][C:15]3([O:19][C:18](=[O:20])[N:17]([CH:21]4[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]4)[C:16]3(O)[CH3:27])[CH2:14][CH2:13]2)=[CH:4][CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[OH-].[Na+]>C1(C)C(C)=CC=CC=1>[F:37][C:34]1[CH:35]=[CH:36][C:31]([C:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)=[CH:9][CH2:10][CH2:11][N:12]2[CH2:30][CH2:29][C:15]3([O:19][C:18](=[O:20])[N:17]([CH:21]4[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]4)[C:16]3=[CH2:27])[CH2:14][CH2:13]2)=[CH:32][CH:33]=1
Reactant: CC1(O)N(C2CCCCC2)C(=O)OC12CCN(CCC=C(c1ccc(F)cc1)c1ccc(F)cc1)CC2
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: Cc1ccccc1C
Product: C=C1N(C2CCCCC2)C(=O)OC12CCN(CCC=C(c1ccc(F)cc1)c1ccc(F)cc1)CC2
Yield: 90.3 %

Procedure:
20.4 g of 8-[4,4-bis(4-fluorophenyl)-3-butenyl]-3-cyclohexyl-4-hydroxy-4-methyl-2-oxo-1-oxa-3,8-diazaspiro[4,5]decane are boiled with 1.52 g of p-toluenesulfonic acid monohydrate in 204 ml of xylene while stirring in an apparatus fitted with a water-trap and azeotropically distilling off the water formed in the reaction. After the termination of the reaction (about 2 hours) the reaction mixture is cooled down and its pH value is adjusted to 9-10 by adding 5% by weight aqueous sodium hydroxide solution. Then, the organic phase is washed with water to neutral, dried over anhydrous sodium sulfate and evaporated under reduced pressure. After recrystallizing the residue from a mixture of benzene and ethanol, the title product is obtained in 90.3% yield, m.p.: 145°-146° C.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1Cl.[CH2:9]([CH:11]([CH2:15][CH2:16][CH2:17][CH3:18])[CH2:12][Mg]Br)[CH3:10].Cl>Cl[Ni]1(Cl)[P](C2C=CC=CC=2)(C2C=CC=CC=2)CCC[P]1(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)C>[CH2:9]([CH:11]([CH2:15][CH2:16][CH2:17][CH3:18])[CH2:12][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:12][CH:11]([CH2:9][CH3:10])[CH2:15][CH2:16][CH2:17][CH3:18])[CH3:10]
Reactant: Clc1ccccc1Cl
Reactant: CCCCC(CC)C[Mg]Br
Agent: Cl[Ni]1(Cl)[P](c2ccccc2)(c2ccccc2)CCC[P]1(c1ccccc1)c1ccccc1
Agent: Cl
Solvent: CCOCC
Product: CCCCC(CC)Cc1ccccc1CC(CC)CCCC
Temperature: 0 °C
Reaction time: 1 h
Yield: 62 %

Procedure:
A dry 2-L three-neck flask equipped with a 500-mL addition funnel, a condenser, a stir bar, and a nitrogen outlet was charged with 1,2-dichlorobenzene (540 mmol), Ni(dppp)Cl2 (6 mmol), and diethyl ether (200 mL). The addition funnel was charged with 3M 2-ethylhexylmagnesium bromide (400 mL). The reaction flask was cooled to 0° C. and the 2-ethylhexylmagnesium bromide was slowly added to the reaction. After the addition of Grignard reagent was completed, the reaction mixture was stirred at 0° C. for 1 hour. The reaction mixture was then warmed to gentle reflux for 12 hours. The reaction mixture was cooled to room temperature and poured onto ice and 100 mL of 10% HCl with vigorous stirring. The organic phase was separated and the aqueous phase was extracted with chloroform (3×500 mL). The combined organic phases were dried over anhydrous magnesium sulfate and excess solvent was removed by rotary evaporation. The volatile impurities were removed by distillation and the residue was purified by column chromatography (hexanes). The product was isolated as colorless oil (101 g, 62%).
Reaction SMILES: Cl[CH2:2][C:3]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([O:18][CH3:19])[CH:12]=2)[CH2:7][CH2:6]1)=[O:4].[CH3:20][N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1>>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([N:8]2[CH2:9][CH2:10][N:5]([C:3](=[O:4])[CH2:2][N:24]3[CH2:25][CH2:26][N:21]([CH3:20])[CH2:22][CH2:23]3)[CH2:6][CH2:7]2)=[CH:12][C:13]=1[O:18][CH3:19]
Reactant: CN1CCNCC1
Reactant: COc1cc(N2CCN(C(=O)CCl)CC2)ccc1Cl
Product: COc1cc(N2CCN(C(=O)CN3CCN(C)CC3)CC2)ccc1Cl

Procedure:
In a 4 mL vial was added 2-chloro-1-[4-(4-chloro-3-methoxy-phenyl)-piperazin-1-yl]-ethanone (1) (200 mg, 0.66 mmol, 1.0 equiv) and 1-methylpiperazine (725 μL, 6.60 mmol, 10.00 equiv). A stir bar was placed in the vial and the vial was then capped. The resultant mixture stirred at 60° C. overnight. The crude product was purified by reversed phase HPLC (acetonitrile —H2O with 0.1% TFA as the eluent) to yield 1-[4-(4-chloro-3-methoxy-phenyl)-piperazin-1-yl]-2-(4-methyl-piperazin-1-yl)-ethanone (25): HPLC retention time, 0.32 minutes (Agilent Zorbax SB-C18, 2.1×50 mm, 5μ, 35° C.) using 1 ml/min flow rate, a 2.5 minute gradient of 20% to 100% B with a 1.1 minute wash at 100% B (A=0.1% formic acid/5% acetonitrile/94.9% water, B=0.1% formic acid/5% water/94.9% acetonitrile); MS (ES) M+H expected, 367.5, found, 367.9.
Reaction SMILES: [BH4-].[Na+].[C:3]([OH:6])(=O)[CH3:4].Cl.[OH2:8]>>[O:8]=[CH:4][C@@H:3]([C@H:4]([C@@H:3]([C@@H:4]([CH2:3][OH:6])[OH:8])[OH:6])[OH:8])[OH:6].[CH2:3]([OH:6])[C@@H:4]([C@H:3]([C@@H:4]([C@@H:4]([CH2:3][OH:6])[OH:8])[OH:8])[OH:6])[OH:8]
Reactant: O
Reactant: CC(=O)O
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Product: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Product: OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)CO
Reaction time: 3 h

Procedure:
To a mixture of 30 μl of the sample, 100 μl of 0.3% sodium borohydride in water was added. After standing for 3 hours at room temperature, 50 μl of 2M acetic acid was added to the solution to decompose excess reducing reagent. The lyophilized sample was methanolyzed with 0.5 ml of 1.5N anhydrous methanolic hydrochloric acid at 90° C. for 4 hours. The methanolysate was evaporated in vacuo, and the residue was trimethylsilyated in pyridine with hexamethyldisilazane and trimethylsilyl chloride for 1 hour at room temperature. The column for gas-liquid chromatography was packed with 2% OV-17 on Chromosorb W, 80-100 mesh (0.5×300 cm). The temperature was programmed from 120° C. to 185° C. at the rate of 4° C. increment per min. Using maltose operated in the same manner as standard, the number of glucose of 1, 2, 3, 4 and 5 in each fraction were obtained from the molar ratio of glucose to glucitol. From this, the number of glucose units in the oligosaccharide of 3, 4, 5, 6 and 7 was determined (hereinafter referred to as "FG3, FG4, FG5, FG6 and FG7", respectively).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[Li]CCCC.[C:13]([N:20]1[CH2:25][CH2:24][CH:23](C#N)[CH2:22][CH2:21]1)([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].C1C[O:31][CH2:30]C1>O>[N:3]1[CH:4]=[CH:5][C:6]([C:30]([CH:25]2[CH2:24][CH2:23][CH2:22][CH2:21][N:20]2[C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])=[O:31])=[CH:7][CH:2]=1
Reactant: Brc1ccccn1
Reactant: C1CCOC1
Reactant: CC(C)(C)OC(=O)N1CCC(C#N)CC1
Agent: [Li]CCCC
Solvent: O
Product: CC(C)(C)OC(=O)N1CCCCC1C(=O)c1ccncc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 18 %

Procedure:
To a solution of 2-bromopyridine (3.60 g, 22.5 mmol) in THF (100 mL) at −78° C. was added n-BuLi (1.6 M in hexanes, 20.0 mL, 22.5 mmol) and stirred for 1.5 h. Added a solution of 1-N-Boc-4-cyanopiperidine (4.60 g, 21.9 mmol) in THF (50 mL) and stirred for 18 h whilst warming to room temperature. The reaction was diluted with water (400 mL) and extracted with EtOAc (2×400 mL). The combined organic extracts were dried over MgSO4, concentrated under vacuum and purified by column chromatography using 0 to 40% EtOAc in hexanes to afford 6 a clear pale yellow oil (1.01 g, 18%); 1H-nmr (400 MHz, CDCl3) δ 8.68 (d, J=5.0 Hz, 1H), 8.04 (d, J=8.0 Hz, 1H), 7.85 (td, J=8.0, 1.5 Hz, 1H), 7.48 (dd, J=8.0, 1.5 Hz, 1H), 4.21-4.07 (m, 2H), 4.02 (tt, J=11.0, 3.5 Hz, 1H), 2.93 (t, J=11.0 Hz, 2H), 1.89 (d, J=9.5 Hz, 2H), 1.71-1.60 (m, 2H), 1.48 (s, 9H); m/z 232.8 [M-tBu].
Reaction SMILES: [CH:1]1[N:5]2[C:6]3[CH2:17][C:16]4[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=4[C:7]=3[NH:8][C:9](=[O:10])[C:4]2=[N:3][CH:2]=1.CS(C)=O.[H-].[Na+].[N:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]([CH:34]=O)=[CH:26][CH:25]=1>C(O)(=O)C.O>[N:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]([CH:34]=[C:17]2[C:6]3[N:5]4[CH:1]=[CH:2][N:3]=[C:4]4[C:9](=[O:10])[NH:8][C:7]=3[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:16]2=3)=[CH:26][CH:25]=1
Reactant: O=Cc1ccnc2ccccc12
Reactant: O=c1[nH]c2c(n3ccnc13)Cc1ccccc1-2
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Solvent: CS(C)=O
Product: O=c1[nH]c2c3ccccc3c(=Cc3ccnc4ccccc34)c2n2ccnc12
Yield: 80.1 %

Procedure:
The procedure is performed as in Example 28, but starting with 3 g of 5H,10H-imidazo[1,2-a]indeno-[1,2-e]pyrazin-4-one, 60 ml of dimethyl sulphoxide, 0.96 g of 80% sodium hydride and 3.18 g of 4-quinolincarboxaldehyde. After treating with water and acetic acid, the suspension obtained is filtered and the solid thus isolated is washed with 2×30 ml of water and then 4×30 ml of acetone and dried at 100° C. under vacuum (2 mmHg; 0.26 kPa). 3.9 g of 10-(4-quinolylmethylene)-5H,10H-imidazo[1,2-a]indeno-[1,2-e]pyrazin-4-one are obtained, in the form of an orange solid melting above 260° C. (Analysis % calculated C: 76.23, H: 3.89, N: 15.46, O: 4.41, % found C: 75.9, H: 4.2, N: 15.4).