Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]1[C:6]2=[N:7][C:8]3[C:13]([C:14](Cl)=[C:5]2[C:4]([CH3:16])=[N:3]1)=[CH:12][CH:11]=[CH:10][CH:9]=3.[CH2:17]([NH2:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CS(C)=O>O>[CH3:1][N:2]1[C:6]2=[N:7][C:8]3[C:13]([C:14]([NH:24][CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[C:5]2[C:4]([CH3:16])=[N:3]1)=[CH:12][CH:11]=[CH:10][CH:9]=3
Reactant: Cc1nn(C)c2nc3ccccc3c(Cl)c12
Reactant: NCc1ccccc1
Solvent: O
Solvent: CS(C)=O
Product: Cc1nn(C)c2nc3ccccc3c(NCc3ccccc3)c12
Temperature: 25 °C

Procedure:
A mixture of 1,3-dimethyl-4-chloro-1H-pyrazolo[3,4-b]quinoline (1.2 g, 0.005 mol), benzylamine (1.2 ml) and DMSO (3 ml) was heated at 80°-90° C. for 3-4 hours. The reaction mixture was cooled to room temperature and then was poured into water. The mixture was extracted with CH2Cl2 (3×50 ml) and then the CH2Cl2 layers were combined and evaporated. The residue was purified by column chromatography on silca gel eluting with ethyl acetate to afford the product which was crystallized from ether/hexane to afford 1.2 g of 1,3-dimethyl-N-(phenylmethyl)-1H-pyrazolo[3,4-b]quinolin-4-amine, as a yellow solid, m.p. 105° C.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:13][C:12]3[N:14]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[N:15]=[C:16]([CH3:17])[C:11]=3[C:10](=[O:24])[CH:9]=2)=[CH:4][CH:3]=1.[N:25]1([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].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.[Fe+2]>[CH3:17][C:16]1[C:11]2[C:10](=[O:24])[CH:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([N:28]4[CH2:27][CH2:26][N:25]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:30][CH2:29]4)=[CH:3][CH:4]=3)[NH:13][C:12]=2[N:14]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:15]=1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: Cc1nn(-c2ccccc2)c2[nH]c(-c3ccc(Br)cc3)cc(=O)c12
Agent: [Fe+2]
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: Cc1nn(-c2ccccc2)c2[nH]c(-c3ccc(N4CCN(C(=O)OC(C)(C)C)CC4)cc3)cc(=O)c12
Temperature: 120 °C
Reaction time: 8 h

Procedure:
Into a 100 mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 6-(4-bromophenyl)-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridin-4(7H)-one (2500 mg, 6.58 mmol, 1.00 equiv) in toluene/DMF (30 ml/1 ml mL), tert-butyl piperazine-1-carboxylate (6130 mg, 32.96 mmol, 5.00 equiv), BINAP (410 mg, 0.65 mmol, 0.10 equiv), Pd2(dba)3 (602.9 mg, 0.66 mmol, 0.10 equiv), Cs2CO3 (3819 mg, 19.79 mmol, 3.00 equiv), dppf (270 mg). The resulting solution was stirred overnight at 120° C. in an oil bath. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (1:10) to yield tert-butyl 4-(4-(3-methyl-4-oxo-1-phenyl-4,7-dihydro-1H-pyrazolo[3,4-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate as a white solid.
Reaction SMILES: C([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[N:22]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[N:25]=3)=[CH:17][N:16]=2)=[CH:11][CH:10]=1)C1C=CC=CC=1.[H][H]>CO.O1CCCC1.[C].[Pd]>[F:29][C:26]([F:27])([F:28])[C:24]1[N:25]=[C:21]([C:18]2[CH:19]=[CH:20][C:15]([C:12]3[CH:11]=[CH:10][C:9]([OH:8])=[CH:14][CH:13]=3)=[N:16][CH:17]=2)[N:22]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:35])[CH3:36])[CH:23]=1
Reactant: C[Si](C)(C)CCOCn1cc(C(F)(F)F)nc1-c1ccc(-c2ccc(OCc3ccccc3)cc2)nc1
Reactant: [H][H]
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: C[Si](C)(C)CCOCn1cc(C(F)(F)F)nc1-c1ccc(-c2ccc(O)cc2)nc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 95.9 %

Procedure:
In methanol (8 mL) and tetrahydrofuran (6 mL) was dissolved 2-[4-(benzyloxy)-phenyl]-5-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]pyridine (0.77 g), and after adding palladium carbon (0.154 g) under nitrogen atmosphere, the atmosphere was replaced by hydrogen, and the mixture was stirred at room temperature for 5 hours. Insoluble material was filtered off by using a membrane filter, and the filtrate was concentrated under reduced pressure. The concentrate was diluted with methanol, activated charcoal was added thereto, and the mixture was filtered by using Celite. The filtrate was concentrated under reduced pressure and crystallized to obtain 4-{5-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)-ethoxy]methyl}-1H-imidazol-2-yl]pyridin-2-yl}phenol (0.612 g).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.C([Li])CCC.Br[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1>C1COCC1.[Cl-].[Zn+2].[Cl-]>[N:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[C:2]1[S:1][CH:5]=[CH:4][CH:3]=1
Reactant: c1ccsc1
Reactant: Brc1ccccn1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [Zn+2]
Solvent: C1CCOC1
Product: c1ccc(-c2cccs2)nc1
Reaction time: 3 h
Yield: 78.3 %

Procedure:
To a solution of thiophene (4.7 mL, 59.4 mmole) at 0° C. was added 2.5M n-butyllithium (24 mL, 59.4 mmole) dropwise via syringe. The solution was stirred 3 h and was transferred via cannula into a stirred solution of zinc chloride (8.6 g, 63.4 mmole) in 60 mL THF at room temperature. This solution was stirred for 1 h and was transferred via cannula into a stirred solution of 2-bromopyridine (3.8 mL, 39.6 mmole) and tetrakis-triphenylphosphine palladium (0.22 g, 0.2 mmole) in 100 mL of THF. The solution was stirred overnight at room temperature and was then quenched with saturate ammonium chloride solution (100 mL) and extracted with ether (3×100 mL). The ether extracts were washed with brine (1×100 mL), dried over MgSO4, filtered and concentrated to yield 8.4 g of crude residue. The material was chromatographed (silica gel, 10% ether/hexanes) to yield 5.0 g (78%) of a pale yellow solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]2[N:9]=[C:10]([C:12]#[N:13])[S:11][C:7]=2[C:6]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.[SH2:27]>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[C:8]2[N:9]=[C:10]([C:12](=[S:27])[NH2:13])[S:11][C:7]=2[C:6]([N:14]2[CH2:15][CH2:16][O:17][CH2:18][CH2:19]2)=[CH:5][CH:4]=1
Reactant: S
Reactant: COc1ccc(N2CCOCC2)c2sc(C#N)nc12
Solvent: c1ccncc1
Solvent: CCN(CC)CC
Product: COc1ccc(N2CCOCC2)c2sc(C(N)=S)nc12
Yield: 87 %

Procedure:
0.50 g 4-Methoxy-7-morpholin-4-yl-benzothiazole-2-carbonitrile and 5.46 ml triethylamine in 13 ml pyridine were stirred for 4 hours with about 5 ml hydrogen sulfide at room temperature. Solvent and excess hydrogen sulfide were removed and the residue chromatographed on siligagel with ethylacetate/heptane 1:1 to yield 0.49 g (87%) 4-methoxy-7-morpholin-4-yl-benzothiazole-2-carbothioic acid amide; M.p.: 238° C.; MS (ISP): m/e=310 (M+H+).
Reaction SMILES: C(O[N:9]=[C:10]1[CH2:15][CH2:14][N:13]([C:16]2[O:17][C:18]([CH3:21])=[N:19][N:20]=2)[CH2:12][CH2:11]1)C1C=CC=CC=1>N.CO.[Pd]>[CH3:21][C:18]1[O:17][C:16]([N:13]2[CH2:12][CH2:11][CH:10]([NH2:9])[CH2:15][CH2:14]2)=[N:20][N:19]=1
Reactant: Cc1nnc(N2CCC(=NOCc3ccccc3)CC2)o1
Agent: [Pd]
Agent: N
Solvent: CO
Product: Cc1nnc(N2CCC(N)CC2)o1
Yield: 109.1 %

Procedure:
To a solution of 1-(5-methyl-[1,3,4]oxadiazol-2-yl)-piperidin-4-one O-benzyl-oxime (2.32 g, 8.1 mmol)) in 7 M NH3 solution in MeOH (40.5 mL) was hydrogenated under an atmosphere of hydrogen in the presence of Palladium on charcoal (10%, 464 mg). The catalyst was filtered off and washed with MeOH. The filtrate was concentrated under reduced pressure to yield the title compound (1.61 g, 100%) as a yellow solid.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[CH3:12].[N:13]([O-])=O.[Na+].O.O.[Sn](Cl)Cl.[OH-].[Na+]>O.Cl>[NH:1]([C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[CH3:12])[NH2:13]
Reactant: COC(=O)c1ccc(N)c(C)c1
Reactant: O=N[O-]
Agent: Cl
Agent: Cl[Sn]Cl
Agent: [Na+]
Solvent: O
Product: COC(=O)c1ccc(NN)c(C)c1
Temperature: -15 °C
Reaction time: 4 h

Procedure:
50 ml of conc. hydrochloric acid are added to methyl 4-amino-3-methylbenzoate (10 g, 61 mmol) and the mixture is cooled down to −15° C. A solution of sodium nitrite (6.3 g, 91 mmol) in 50 ml of water is added dropwise in such a way that the temperature does not exceed −5° C. After stirring at −10° C. for 4 h, a solution of tin(II) chloride dihydrate in 50 ml of conc. hydrochloric acid is added dropwise to the suspension, with the reaction temperature not exceeding −5° C. The viscous suspension is stirred at RT for 15 h before it is adjusted to pH 14 with 200 ml of sodium hydroxide solution (10 N). The reaction mixture is filtered through kieselguhr and Extrelut® (60 g) and rinsed with 2 l of chloroform. The organic phase which is obtained is washed with water (2×200 ml), dried over sodium sulphate and evaporated in vacuo. The residue is stirred up with 120 ml of petroleum ether and filtered. Yield: 6.3 g
Reaction SMILES: [Li+].C[Si]([N-][Si](C)(C)C)(C)C.C(O)(=O)C.N1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[NH:17][CH:16]=1.[NH2:24][C:25]1C=CC=C[C:26]=1C#N>C1COCC1>[NH2:24][C:25]1[C:19]2[C:18](=[CH:23][CH:22]=[CH:21][CH:20]=2)[N:17]=[CH:16][CH:26]=1
Reactant: c1ccc2[nH]cnc2c1
Reactant: N#Cc1ccccc1N
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: Nc1ccnc2ccccc12
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
LiHMDS (3-4 eq) was added to the benzimidazole acetate (1.0 eq) in THF (at a constant temperature ranging from −78° C. to 0° C.). After 20 minutes, a solution of the 2-aminobenzonitrile (1.1 eq) in THF was then added. The resulting mixture was allowed to warm to room temperature, stirred for 1-3 hours and was then heated to approx. 40° C.-65° C.(1 hour to 12 hours). The mixture was cooled to 0° C. and quenched with NH4Cl (aq, saturated). The aqueous phase was extracted with Ch2Cl2 or EtOAc, and the organic extracts were collected, dried (Na2SO4), and filtered. Evaporation of the solvent under reduced pressure and purification of the residue by silica gel chromatography or HPLC provided the 4-amino quinoline products.
Reaction SMILES: [NH2:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([C@H:15]([NH:17][C:18]([C:20]2([NH:23]C(=O)C(F)(F)F)[CH2:22][CH2:21]2)=[O:19])[CH3:16])=[C:11]([F:30])[CH:10]=1.[OH-].[Na+]>CO>[NH2:23][C:20]1([C:18]([NH:17][C@@H:15]([C:12]2[CH:13]=[CH:14][C:9]([C:3]3[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=3[NH2:1])=[CH:10][C:11]=2[F:30])[CH3:16])=[O:19])[CH2:22][CH2:21]1
Reactant: C[C@@H](NC(=O)C1(NC(=O)C(F)(F)F)CC1)c1ccc(-c2cccc(F)c2N)cc1F
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: C[C@@H](NC(=O)C1(N)CC1)c1ccc(-c2cccc(F)c2N)cc1F
Temperature: 25 °C
Reaction time: 96 h

Procedure:
To a solution of N-[(1R)-1-(2′-amino-3,3′-difluoro-1,1′-biphenyl-4-yl)ethyl]-1-[(trifluoroacetyl)amino]cyclopropanecarboxamide (174 mg 0.407 mmol) in methanol (2 ml) was added 1.0N NaOH (2 ml, 2 mmol) and stirred at room temperature 4 days. This mixture was concentrated under vacuum to a 2 ml volume and extracted with methylene chloride (2×10 ml). The combined extracts were washed with water (1 ml), dried over MgSO4, filtered and the solvent removed in vacuo to give 1-amino-N-[(1R)-1-(2′-amino-3,3′-difluoro-1,1′-biphenyl-4-yl)ethyl]cyclopropanecarboxamide. Low resolution mass spectrometry: (M+H+)=332.3.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([F:9])[CH:8]=1)[NH2:5].O=[C:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]#[N:17].[Cl-].[Ca+2].[Cl-]>>[F:1][C:2]1[CH:3]=[C:4]([NH:5][C:11]2[CH2:15][CH2:14][CH2:13][C:12]=2[C:16]#[N:17])[CH:6]=[C:7]([F:9])[CH:8]=1
Reactant: N#CC1CCCC1=O
Reactant: Nc1cc(F)cc(F)c1
Agent: [Ca+2]
Agent: [Cl-]
Product: N#CC1=C(Nc2cc(F)cc(F)c2)CCC1

Procedure:
3,5-Difluoro-aniline (Aldrich Chemicals) (2.6 g, 20.0 mmol), 2-oxocyclopentane carbonitrile (Example 11) (2.2 g, 20.2 mmol), calcium chloride (2.5 g, 22.5 mmol) and T.H.F. were heated under reflux for 24 hours. After cooling the mixture was filtered and the solvent evaporated. Kugelrohr distillation (140° C., 0.3 mmHg) gave the product as pale yellow crystals.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:10]([O:12][CH3:13])=[O:11])[CH:3]=[CH:2]1.Br[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[CH:17]=1.[H-].[Na+]>CN(C=O)C>[F:23][C:22]([F:24])([F:25])[C:18]1[CH:17]=[C:16]([CH:21]=[CH:20][CH:19]=1)[CH2:15][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:10]([O:12][CH3:13])=[O:11])[CH:3]=[CH:2]1
Reactant: COC(=O)c1cccc2cc[nH]c12
Reactant: FC(F)(F)c1cccc(CBr)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)c1cccc2ccn(Cc3cccc(C(F)(F)F)c3)c12
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Methyl 1H-indole-7-carboxylate (1 g, 5.71 mmol) and 1-(bromomethyl)-3-(trifluoromethyl)benzene (956 ul, 6.28 mmol) were dissolved in DMF (16 ml), in an ice bath. 60% w/w NaH (251 mg, 6.28 mmol) was added portionwise. The ice bath was removed and the mixture stirred at RT for 30 min. The reaction mixture was quenched with NH4Cl(sat.) and extracted 3 times with ether. The organic layers were combined, washed with water and brine. The compound was purified by flash chromatography on silica gel. 1H NMR (500 MHz, DMSO-d6): δ 7.40 (d, 1H), 7.25 (s, 1H), 7.10 (m, 1H), 7.00 (m, 2H), 6.75 (s, 1H), 6.65 (t, 1H), 6.50 (d, 1H), 6.25 (s, 1H), 5.25 (s, 2H), 2.05 (d, 3H).
Reaction SMILES: Br[CH2:2][C:3](=[O:25])[C@@H:4]1[C@:21]2([CH3:22])[C@H:7]([C@H:8]3[C@H:18]([C:19](=[O:23])[CH2:20]2)[C@:16]2([CH3:17])[C@H:11]([CH2:12][C@H:13]([OH:24])[CH2:14][CH2:15]2)[CH2:10][CH2:9]3)[CH2:6][CH2:5]1.[NH:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]1=[S:32].[OH-].[Na+].O>O1CCCC1.CCOCC>[OH:24][C@@H:13]1[CH2:14][CH2:15][C@@:16]2([CH3:17])[C@@H:11]([CH2:10][CH2:9][C@@H:8]3[C@@H:18]2[C:19](=[O:23])[CH2:20][C@@:21]2([CH3:22])[C@H:7]3[CH2:6][CH2:5][C@@H:4]2[C:3](=[O:25])[CH2:2][S:32][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][N:26]=2)[CH2:12]1
Reactant: C[C@]12CC[C@@H](O)C[C@@H]1CC[C@H]1[C@@H]3CC[C@H](C(=O)CBr)[C@@]3(C)CC(=O)[C@@H]12
Reactant: S=c1cccc[nH]1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CCOCC
Product: C[C@]12CC[C@@H](O)C[C@@H]1CC[C@H]1[C@@H]3CC[C@H](C(=O)CSc4ccccn4)[C@@]3(C)CC(=O)[C@@H]12
Reaction time: 0.05 h
Yield: 22.4 %

Procedure:
A solution of 21-bromo-3α-hydroxy-5α-pregnane-11,20-dione (1.0 g.) in tetrahydrofuran (10 ml) was added to a solution of pyrid-2-thione (0.5 g) in 2N-aqueous sodium hydroxide (10 ml). After allowing the mixture to stand at room temperature for 3 mins., water and ether were added. The organic layer was washed with water, dried (Na2SO4) and evaporated. The residue was subjected to preparative t.l.c. and recrystallisation from methyl acetate/petrol to give title compound (240 mg.) as white needles m.p. 184° [α]D + 130° (c 0.9).
Reaction SMILES: [CH2:1]([N:8]1[C:21](=[O:22])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]2[CH:13]=[C:12]([CH:23]=O)[CH:11]=[CH:10][C:9]1=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[S:25]1[CH2:29][C:28](=[O:30])[NH:27][C:26]1=[O:31]>C1(C)C=CC=CC=1.C(O)(=O)C.N1CCCCC1>[CH2:1]([N:8]1[C:21](=[O:22])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]2[CH:13]=[C:12]([CH:23]=[C:29]3[S:25][C:26](=[O:31])[NH:27][C:28]3=[O:30])[CH:11]=[CH:10][C:9]1=2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1CSC(=O)N1
Reactant: O=Cc1ccc2c(c1)c1ccccc1c(=O)n2Cc1ccccc1
Solvent: Cc1ccccc1
Solvent: CC(=O)O
Solvent: C1CCNCC1
Product: O=C1NC(=O)C(=Cc2ccc3c(c2)c2ccccc2c(=O)n3Cc2ccccc2)S1
Yield: 79.7 %

Procedure:
592 mg of 5-benzyl-6-oxo-5,6-dihydrophenanthridine-2-carboxaldehyde and 221 mg of 2,4-thiazolidinedione were suspended in 10 ml of toluene. Two drops of acetic acid and two drops of piperidine were added to the suspension, followed by heating and refluxing overnight. The reaction liquid was cooled, and the solid thus obtained was collected by filtration. The collected solid was washed with toluene-diethyl ether, and dried, giving 620 mg (80% yield) of 5-[1-(5-benzyl-6-oxo-5,6-dihydrophenanthridin-2-yl)methylidene]thiazolidine-2,4-dione as a yellow solid.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][CH2:11][O:12]S(C1C=CC(C)=CC=1)(=O)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:23]([N:30]([CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[CH2:31][CH2:32]O)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[OH-].[Na+]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:34]([N:30]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH2:31][CH2:32][O:12][CH2:11][CH2:10][CH2:9][O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1
Reactant: OCCN(Cc1ccccc1)Cc1ccccc1
Reactant: Cc1ccc(S(=O)(=O)OCCCOCc2ccccc2)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S(=O)([O-])O
Agent: [Na+]
Product: c1ccc(COCCCOCCN(Cc2ccccc2)Cc2ccccc2)cc1
Yield: 53.3 %

Procedure:
Dibenzyl-[2-(3-benzyloxy-propoxy)-ethyl]-amine (860 mg) was prepared by following General Procedure W starting from toluene-4-sulfonic acid 3-benzyloxy-propyl ester (1.33 g), N,N-dibenzyl-2-aminoethanol (1.0 g), 50% aqueous sodium hydroxide solution (1.66 g in 1.66 mL of water), and tetrabutylammonium hydrogen sulfate (141 mg).
Reaction SMILES: N12CCCN=C1CCCCC2.[C:12]([O:16][C:17]([N:19]1[C:27]2[CH:26]=[CH:25][N:24]=[CH:23][C:22]=2[CH:21]=[C:20]1[CH2:28][N:29]1[CH2:34][CH2:33][N:32]([CH2:35][C:36]#[C:37][C:38]2[CH:39]=[N:40][CH:41]=[CH:42][C:43]=2[NH:44][C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:31][C:30]1=[O:52])=[O:18])([CH3:15])([CH3:14])[CH3:13]>CC#N>[C:12]([O:16][C:17]([N:19]1[C:27]2[CH2:26][CH2:25][NH:24][CH2:23][C:22]=2[CH:21]=[C:20]1[CH2:28][N:29]1[CH2:34][CH2:33][N:32]([CH2:35][C:36]2[N:44]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[C:43]3[CH:42]=[CH:41][N:40]=[CH:39][C:38]=3[CH:37]=2)[CH2:31][C:30]1=[O:52])=[O:18])([CH3:15])([CH3:14])[CH3:13]
Reactant: CC(C)(C)OC(=O)Nc1ccncc1C#CCN1CCN(Cc2cc3cnccc3n2C(=O)OC(C)(C)C)C(=O)C1
Solvent: C1CCC2=NCCCN2CC1
Solvent: CC#N
Product: CC(C)(C)OC(=O)n1c(CN2CCN(Cc3cc4cnccc4n3C(=O)OC(C)(C)C)CC2=O)cc2c1CCNC2
Temperature: 50 °C
Reaction time: 4 h
Yield: 107.5 %

Procedure:
1,8-Diazabicyclo[5.4.0]undec-7-ene (42 mg, 0.27 mmol) is added to a suspension containing 2-{4-[3-(4-tert-butoxycarbonylamino-pyridin-3-yl)-prop-2-ynyl]-2-oxo-piperazin-1-ylmethyl}-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester (77 mg, 0.14 mmol) in anhydrous CH3CN (10 mL) and the mixture is warmed to 50° C. After 4 h, the reaction mixture is concentrated to dryness and the residue is partitioned between CH2Cl2 (50 mL) and water (50 mL) and the layers are separated. The aqueous layer is extracted twice with CH2Cl2 (25 mL) and the combined organic phase is washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to provide 85 mg of the title compound as a crude solid which is used directly without further purification. 1H NMR (300 MHz, CDCl3) δ1.68 (s, 9H), 1.70 (s, 9H), 2.91 (m, 2H), 3.41 (s, 2H), 3.49 (m, 2H), 4.26 (s, 2H), 4.95 (d, J=1.1 Hz, 2H), 6.39 (d, J=0.7 Hz, 1H), 6.68 (d, J=0.7 Hz, 1H), 7.86 (m, 1H), 8.41 (m, 1H), 8.76 (br s, 1H), 8.82 (br s, 1H) ppm: MS (EI): m/z 561 (M+H).
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[CH:9][C:10]([CH3:13])=[N:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.OO.CC[O:18]CC.CCOC(C)=O>CC(O)=O.[Pd]>[C:1]1([C:7]2[CH:12]=[N+:11]([O-:18])[C:10]([CH3:13])=[CH:9][CH:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Cc1ccc(-c2ccccc2)cn1
Reactant: CCOCC
Agent: [Pd]
Agent: OO
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: Cc1ccc(-c2ccccc2)c[n+]1[O-]
Temperature: 70 °C

Procedure:
To a solution of 100 g 5-phenyl-2-picoline in 170 mL of glacial HOAc was added 30% H2O2 and the resulting solution was heated at 70° C. overnight. After the reaction mixture was cooled to room temperature, 1 g of 10% Pd/C was added to destroy any excess of H2O2. The reaction mixture was then filtered on celite, washed with toluene, and the filtrate was evaporated to dryness affording a yellow solid residue. The crude material was swished with a mixture of Et2O/EtOAc (10:1) and filtered to afford the pure title product as a white solid, m.p.: 91° C.
Reaction SMILES: [CH:1]1[C:6]2[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:5]=2[CH:4]=[CH:3][C:2]=1[OH:12].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:20][CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.O>CN(C=O)C>[CH:21]1([CH2:20][O:12][C:2]2[CH:3]=[CH:4][C:5]3[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:6]=3[CH:1]=2)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1
Reactant: BrCC1CCCCC1
Reactant: Oc1ccc2c(c1)CCCCC2
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: c1cc2c(cc1OCC1CCCCC1)CCCCC2
Temperature: 60 °C

Procedure:
To a mixture of 6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ol (Helvetica Chimica Acta 1947, 1883.) (9.9 g, 61.0 mmol) and Cs2CO3 (26.3 g, 73.2 mmol) in DMF (100 ML) was added (bromomethyl)cyclohexane (10.2 mL, 73.2 mmol). The mixture was heated to 60° C. for 18 h, dumped into water and extracted with ethyl acetate. The combined extracts were washed with water, dried over magnesium sulfate and concentrated to a solid. The solid was recrystallized from ethanol (13.0 g, 83%). m.p. 62-63° C.
Reaction SMILES: [Br:1][C:2]1[S:3][C:4]([Br:8])=[CH:5][C:6]=1I.[CH:9]#[C:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]>C(N(CC)CC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Br:1][C:2]1[S:3][C:4]([Br:8])=[CH:5][C:6]=1[C:9]#[C:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: Brc1cc(I)c(Br)s1
Reactant: C#CCCCCCCCC
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCN(CC)CC
Product: CCCCCCCCC#Cc1cc(Br)sc1Br
Temperature: 0 °C
Reaction time: 20 h

Procedure:
To a solution of the above prepared 2,5-dibromo-3-iodothiophene (3.43 grams, 9.3 mmol) and 1-decyne (1.45 grams, 10.5 mmol) in triethylamine (50 milliliters) were added dichlorobis(triphenylphosphine)palladium (II) (0.28 gram, 0.4 mmol) and copper(I) iodide (38 milligrams, 0.2 mmol) at 0° C. under argon. The reaction mixture was stirred at 0° C. for 6 hours and at room temperature for 20 hours under argon. After evaporation of the solvent, the product was purified by column chromatography on silica gel using hexane as eluent. 2,5-Dibromo-3-decynylthiophene was thus obtained as a colorless liquid was. Yield: 3.32 grams (94 percent).