Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[C:2]1[C:3]2[C:8]([C:9]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[C:10]3[C:15]=1[CH:14]=[CH:13][CH:12]=[CH:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[Br:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=2)=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Na+].[Na+]>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.C1(C)C=CC=CC=1>[Br:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][C:32]([C:2]3[C:3]4[C:8]([C:9]([C:16]5[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=5)=[C:10]5[C:15]=3[CH:14]=[CH:13][CH:12]=[CH:11]5)=[CH:7][CH:6]=[CH:5][CH:4]=4)=[CH:31][CH:30]=2)=[CH:25][CH:24]=1
Reactant: OB(O)c1ccc(-c2ccc(Br)cc2)cc1
Reactant: Ic1c2ccccc2c(-c2ccccc2)c2ccccc12
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: [Na+]
Solvent: Cc1ccccc1
Product: Brc1ccc(-c2ccc(-c3c4ccccc4c(-c4ccccc4)c4ccccc34)cc2)cc1
Yield: 40.1 %

Procedure:
Into a 100 mL three-neck flask were put 2.8 g (7.2 mmol) of 9-iodo-10-phenylanthracene and 1.5 g (7.2 mmol) of 4′-bromobiphenyl-4-boronic acid, and the atmosphere in the flask was replaced with nitrogen. To the mixture, 40 mL of toluene and 10 mL (2.0 mol/L) of a sodium carbonate aqueous solution were added. The mixture was stirred under reduced pressure to be degassed. After the degassing, 120 mg (0.10 mmol) of tetrakis(triphenylphosphine)palladium(0) was added to the mixture. The mixture was stirred at 90° C. for 4 hours. After the stirring, about 50 mL of toluene was added to the mixture. The mixture was subjected to suction filtration through alumina, Celite (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 531-16855), and Florisil (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 540-00135). The solid obtained by condensation of the obtained filtrate was purified by high-performance liquid chromatography (the mobile phase: chloroform) to give a light yellow solid. The obtained solid was recrystallized with chloroform/hexane to give 1.4 g of a light yellow powdered solid, which was the object of the synthesis, in a yield of 40%.
Reaction SMILES: [C:1]1([CH2:7][C@@H:8]2[CH2:12][O:11][C:10](=[O:13])[NH:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li]CCCC.[C:19](Cl)(=[O:24])[CH2:20][CH2:21][CH:22]=[CH2:23]>C1COCC1.O>[CH2:7]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:19](=[O:24])[CH2:20][CH2:21][CH:22]=[CH2:23])[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: C=CCCC(=O)Cl
Reactant: O=C1N[C@H](Cc2ccccc2)CO1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Product: C=CCCC(=O)N1C(=O)OC[C@H]1Cc1ccccc1
Temperature: -78 °C
Reaction time: 1 h
Yield: 93 %

Procedure:
To a solution of (4R)-4-(phenylmethyl)-1,3-oxazolidin-2-one (50 g, 282 mmol) in THF (300 mL) was dropwise added n-BuLi in THF (2.4 M, 176 mL, 423 mmol) under nitrogen at −78° C., and the resulting mixture was stirred at −78° C. for 1 hour. Then 4-pentenoyl chloride (49 mL, 423 mmol) was dropwise added. After stirring at −78° C. for another 1 hour, the reaction mixture was allowed to warm up to room temperature and stirred overnight. After diluting with water, the mixture was extracted with ethyl acetate (2×400 mL). The combined ethyl acetate extracts were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by silica gel column chromatography (ethyl acetate:petroleum ether=1:10) to afford the title compound (68 g, 93%) as a light yellow oil. MS (ES+) C15H17NO3 requires: 259, found: 260 [M+H]+.
Reaction SMILES: [N:1]([C:4](=[CH:10][C:11]1[C:12]2[N:13]([C:17]([Br:20])=[CH:18][N:19]=2)[CH:14]=[CH:15][CH:16]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6])=[N+]=[N-].[K+].[Br-]>>[Br:20][CH:17]1[N:13]2[CH:14]=[CH:15][C:16]3[C:11]([CH:10]=[C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[N:1]=3)=[C:12]2[N:19]=[CH:18]1
Reactant: CCOC(=O)C(=Cc1cccn2c(Br)cnc12)N=[N+]=[N-]
Agent: [Br-]
Agent: [K+]
Product: CCOC(=O)c1cc2c3n(ccc-2n1)C(Br)C=N3

Procedure:
From 6j (yield: 92%); mp 280-282° C.; IR (KBr) 1707, 1178 cm−1; 1H NMR (400 MHz, DMSO-d6) δ 1.39 (t, 3H, J=7 Hz), 4.39 (q, 2H, J=7 Hz), 7.23 (d, 1H, J=7 Hz), 7.40 (s, 1H), 7.56 (s, 1H), 8.13 (d, 1H, J=7 Hz), 12.69 (brs, 1H); 13C NMR (100 MHz, DMSO-d6) δ 14.3, 60.6, 94.9, 102.9, 106.1, 113.5, 121.6, 126.4, 130.7, 132.9, 141.6, 160.5; MS m/z 309 (M++2, 57), 307 (M+, 57), 263 (100), 261 (88), 154 (58). Anal. Calcd for C12H10BrN3O2: C, 46.78; H, 3.27; N, 13.64. Found: C, 46.89; H, 3.40; N, 13.57.
Reaction SMILES: C1N=CN([C:6](N2C=NC=C2)=[O:7])C=1.[CH3:13][NH:14][C:15]1[C:16]([NH2:21])=[N:17][CH:18]=[CH:19][CH:20]=1.[Cl-].[Cl-].[Ca+2]>C1COCC1>[CH3:13][N:14]1[C:15]2[C:16](=[N:17][CH:18]=[CH:19][CH:20]=2)[NH:21][C:6]1=[O:7]
Reactant: CNc1cccnc1N
Reactant: O=C(n1ccnc1)n1ccnc1
Agent: [Ca+2]
Agent: [Cl-]
Solvent: C1CCOC1
Product: Cn1c(=O)[nH]c2ncccc21
Yield: 79.7 %

Procedure:
CDI (2.251 g) was added to a solution of N3-methylpyridine-2,3-diamine (1.14 g) in THF (dry) (50 mL) at room temperature. The mixture was stirred at room temperature under a dry atmosphere (CaCl2 tube) over weekend. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (silica gel, eluted with 0%-100% EtOAc in hexane) to give 1-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (1.1 g) as a white solid.
Reaction SMILES: Cl[C:2]1[C:11]([CH2:12][CH3:13])=[CH:10][C:9]2[C:4](=[C:5]([O:16][CH3:17])[CH:6]=[CH:7][C:8]=2[O:14][CH3:15])[N:3]=1.C(O)(=[O:20])C>O>[CH2:12]([C:11]1[C:2](=[O:20])[NH:3][C:4]2[C:9]([CH:10]=1)=[C:8]([O:14][CH3:15])[CH:7]=[CH:6][C:5]=2[O:16][CH3:17])[CH3:13]
Reactant: CC(=O)O
Reactant: CCc1cc2c(OC)ccc(OC)c2nc1Cl
Solvent: O
Product: CCc1cc2c(OC)ccc(OC)c2[nH]c1=O
Yield: 100 %

Procedure:
A solution of 200 mg (0.92 mmol) of 2-chloro-3-ethyl-5,8-dimethoxyquinoline in acetic acid (3 ml) and water (1 ml) was refluxed for 5 h. After evaporation of the solvent, the residue was dissolved in water, basified with 25% aqueous ammonium hydroxide and extracted with chloroform (3×25 ml). The combined chloroform layers were dried over sodium sulphate and evaporated, yielding 185 mg (100%) of 3-ethyl-5,8-dimethoxy-1H-quinolin-2-one.
Reaction SMILES: [OH:1][CH:2]([C@@H:14]([NH:24][C:25](=[O:41])[O:26][CH2:27][C:28]1([CH2:32][C:33]2[C:38]([F:39])=[CH:37][CH:36]=[CH:35][C:34]=2[F:40])[CH2:31][CH2:30][CH2:29]1)[CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]([NH:22][CH3:23])=[O:21])[C:3](=[O:13])[NH:4][C@@H:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:6].OC([C@@H](NC(=O)OCC1(CC2C=CC=CC=2)CCCCC1)CCCCNC(N1CCOCC1)=O)C(=O)N[C@@H](C1C=CC=CC=1)C>>[CH3:23][NH:22][C:20]([NH:19][CH2:18][CH2:17][CH2:16][CH2:15][C@H:14]([NH:24][C:25](=[O:41])[O:26][CH2:27][C:28]1([CH2:32][C:33]2[C:34]([F:40])=[CH:35][CH:36]=[CH:37][C:38]=2[F:39])[CH2:29][CH2:30][CH2:31]1)[C:2](=[O:1])[C:3](=[O:13])[NH:4][C@@H:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:6])=[O:21]
Reactant: CNC(=O)NCCCC[C@H](NC(=O)OCC1(Cc2c(F)cccc2F)CCC1)C(O)C(=O)N[C@H](C)c1ccccc1
Agent: C[C@@H](NC(=O)C(O)[C@H](CCCCNC(=O)N1CCOCC1)NC(=O)OCC1(Cc2ccccc2)CCCCC1)c1ccccc1
Product: CNC(=O)NCCCC[C@H](NC(=O)OCC1(Cc2c(F)cccc2F)CCC1)C(=O)C(=O)N[C@H](C)c1ccccc1

Procedure:
[1-(2,6-Difluorobenzyl)cyclobutyl]methyl(1S)-5-{[(methylamino)carbonyl]amino}-1-(oxo{[(1R)-1-phenylethyl]amino}acetyl)pentylcarbamate was prepared as in example 9j except that [1-(2,6-difluorobenzyl)cyclobutyl]methyl(1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)-5-{[(methylamino)carbonyl]amino}pentylcarbamate was substituted for (1-benzylcyclohexyl)methyl(1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)-5-[(4-morpholinylcarbonyl)amino]pentylcarbamate. 1H NMR (300 MHz, DMSO-d6) δ 9.19 (m, 1H), 7.58 (m, 1H), 7.05-7.43 (m, 8H), 5.86 (m, 1H), 5.65 (m, 1H), 4.98 (m, 1H), 4.76 (m, 1H), 3.95 (m, 2H). 3.25 under water peak (m, 3H), 2.96 (m, 2H), 2.78 (s, 2H), 1.60-1.90 (m, 6H), 1.25-1.50 (m, 9H). ES-LCMS m/z 571 (M−H).
Reaction SMILES: CC(C)([O-])C.[K+].[C:7]([CH2:9]P(=O)(OCC)OCC)#[N:8].[F:18][CH2:19][C:20]1([C:25]#[N:26])[CH2:23][C:22](=O)[CH2:21]1>O1CCCC1>[C:7]([CH:9]=[C:22]1[CH2:23][C:20]([CH2:19][F:18])([C:25]#[N:26])[CH2:21]1)#[N:8]
Reactant: N#CC1(CF)CC(=O)C1
Reactant: CCOP(=O)(CC#N)OCC
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: N#CC=C1CC(C#N)(CF)C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 1.0 M of potassium tert-butoxide in tetrahydrofuran (2.15 mL) at 0° C. was added dropwise a solution of diethyl cyanomethylphosphonate (0.364 mL, 0.00225 mol) in tetrahydrofuran (4 mL, 0.04 mol). The reaction was warmed to rt and then cooled to 0° C. again. To the reaction mixture was added a solution of 1-(fluoromethyl)-3-oxocyclobutanecarbonitrile (0.260 g, 0.00204 mol) in tetrahydrofuran (2 mL, 0.02 mol). The reaction was allowed to warm up to rt and stirred at rt overnight. After quenching with water, the mixture was extracted with ether. The combined organic layers were washed with water then brine, dried, and evaporated to dryness. The crude mixture was used directly in next step.
Reaction SMILES: [CH3:1][C:2]1([CH2:15][N:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[CH2:6][C:5]2[C:7]([CH3:14])=[C:8]([NH2:13])[C:9]([CH3:12])=[C:10]([CH3:11])[C:4]=2[O:3]1.[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][C:32]=1[O:33][CH3:34])[C:27](O)=[O:28]>>[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][C:32]=1[O:33][CH3:34])[C:27]([N:19]1[CH2:20][CH2:21][N:16]([CH2:15][C:2]2([CH3:1])[CH2:6][C:5]3[C:7]([CH3:14])=[C:8]([NH2:13])[C:9]([CH3:12])=[C:10]([CH3:11])[C:4]=3[O:3]2)[CH2:17][CH2:18]1)=[O:28]
Reactant: Cc1c(C)c2c(c(C)c1N)CC(C)(CN1CCNCC1)O2
Reactant: COc1ccc(C(=O)O)cc1OC
Product: COc1ccc(C(=O)N2CCN(CC3(C)Cc4c(C)c(N)c(C)c(C)c4O3)CC2)cc1OC
Yield: 74 %

Procedure:
Using 2,3-dihydro-2,4,6,7-tetramethyl-2-[(1-piperazinyl)methyl]-5-benzofuranamine and 3,4-dimethoxybenzoic acid, the procedure of Example 10, presented hereinafter, was otherwise followed to provide the title compound. Yield 74%.
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]1[CH2:13][S:12][C@H:11]2[N:8]([C:9](=[O:21])[C@H:10]2[NH:14][C:15]2[S:16][CH:17]=[C:18]([CH3:20])[N:19]=2)[C:7]=1[C:22]([O:24]C(C1C=CC=CC=1)C1C=CC=CC=1)=[O:23])(=[O:3])[CH3:2].FC(F)(F)C(O)=O.C1(OC)C=CC=CC=1>ClCCl>[C:1]([O:4][CH2:5][C:6]1[CH2:13][S:12][C@H:11]2[N:8]([C:9](=[O:21])[C@H:10]2[NH:14][C:15]2[S:16][CH:17]=[C:18]([CH3:20])[N:19]=2)[C:7]=1[C:22]([OH:24])=[O:23])(=[O:3])[CH3:2]
Reactant: CC(=O)OCC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)[C@@H](Nc3nc(C)cs3)[C@H]2SC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: COc1ccccc1
Product: CC(=O)OCC1=C(C(=O)O)N2C(=O)[C@@H](Nc3nc(C)cs3)[C@H]2SC1
Yield: 84.9 %

Procedure:
A mixture of 210 mg of (6R-trans)-3-[(acetyloxy)methyl]-7-[(4-methyl-2-thiazolyl)amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, diphenylmethyl ester, trifluoroacetic acid and anisole in dichloromethane was reacted as described in Example 11, giving 123 mg of the desired product.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[CH:13]([S:19][CH3:20])[CH:14]([C:16]([OH:18])=O)[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:21]([NH2:29])[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.Cl.C1C=C2N=NN(O)C2=CC=1.O.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[CH:13]([S:19][CH3:20])[CH:14]([C:16](=[O:18])[NH:29][CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH3:15])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: NCCc1ccccc1
Reactant: CSC(C(C)C(=O)O)C1CCCN1C(=O)OC(C)(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CSC(C(C)C(=O)NCCc1ccccc1)C1CCCN1C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 41.2 %

Procedure:
To a stirred solution of the crude 2-(2-carboxy-1-methylsulfanyl-propyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (223 mg) obtained above in CH2Cl2 (3 ml) was added phenethylamine(0.18 ml, 1.41 mmol), WSCI monohydrochloride(203 mg, 1.06 mmol), HOBt monohydrate(162 mg, 1.06 mmol) and diisopropylethylamine(0.37 ml, 2.12 mmol) at room temperature. After being stirred at room temperature for 4.5 hr, the mixture was quenched with 1N HCl (20 ml), extracted with AcOEt, dried (MgSO4) and concentrated in vacuo to give a crude oil, which was purified by flash column chromatography (hexane:AcOEt=3:1) to give 2-(1-methylsulfanyl-2-phenethylcarbamoyl-propyl)-pyrrolidine-1-carboxylic acid tert-butyl ester as an oil(123 mg, 43%).
Reaction SMILES: F[C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[CH3:11][S-:12].[Na+]>C1(C)C=CC=CC=1.CCOCC>[CH3:11][S:12][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5]
Reactant: C[S-]
Reactant: O=Cc1ccc(F)cc1F
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: CSc1cc(F)ccc1C=O
Temperature: 80 °C
Reaction time: 14 h
Yield: 75.3 %

Procedure:
A suspension of 2,4-difluorobenzaldehyde (16 mL, 146 mmol) and sodium thiomethoxide (14 g, 200 mmol) in toluene (200 mL) was stirred at 80° C. for 7 h and 14 h at room temperature. The reaction mixture was diluted with ether (300 mL), washed with water (100 mL), saturated aqueous NaHCO3 (100 mL) and brine (50 mL). The aqueous layers were combined and extracted with ether (2×100 mL). The organic layers were combined and dried over anhydrous Na2SO4, filtered and concentrated to give a viscous oil. This viscous oil was dissolved in ether/hexanes (1:1, v/v) and slowly concentrated on under vacuum. The precipitated white solid was separated by filteration and dried to give 2-methylthio-4-fluorobenzaldehyde (18.7 g, 75% yield). 1HNMR (500 MHz, CDCl3) δ: 10.11 (1H, s), 7.78 (1H, dd, J=8.55, 6.11 Hz), 6.97 (1H, dd, J=10.07, 2.44 Hz), 6.91 (1H, td, J=8.54, 2.44 Hz), 2.45 (3H, s). MS calcd for C8H7FOS (M+H): 171.2. found: 171.6.
Reaction SMILES: [CH:1]1([CH2:7][O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]([C:15]([O:17]C)=O)[N:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:19][C:20]#[N:21]>>[CH:1]1([CH2:7][O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]([C:15](=[O:17])[CH2:19][C:20]#[N:21])[N:10]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: COC(=O)c1nccc(OCC2CCCCC2)n1
Reactant: CC#N
Product: N#CCC(=O)c1nccc(OCC2CCCCC2)n1

Procedure:
CH3CN addition to methyl 4-(cyclohexylmethoxy)pyrimidine-2-carboxylate following the method described in Example 6 gives 3-(4-(cyclohexylmethoxy)pyrimidin-2-yl)-3-oxopropanenitrile.
Reaction SMILES: Br[CH2:2][C:3]1[C:4]([F:20])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17]([Cl:19])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1.[NH3:21]>C(Cl)Cl.CO>[NH2:21][CH2:2][C:3]1[C:4]([F:20])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17]([Cl:19])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1
Reactant: N#Cc1cc(Cl)cc(Oc2c(Cl)ccc(CBr)c2F)c1
Reactant: N
Solvent: ClCCl
Solvent: CO
Product: N#Cc1cc(Cl)cc(Oc2c(Cl)ccc(CN)c2F)c1
Reaction time: 2 h
Yield: 84 %

Procedure:
3-{[3-(Bromomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (1.0 g, 2.6 mmol) was dissolved in CH2Cl2 (5 mL) and added dropwise to ammonia in methanol (7N, 25 mL). The reaction mixture was stirred for 2 h then the solvent was evaporated. The resulting oil was purified by column chromatography (CH-2Cl2/MeOH) to afford the title compound (0.7 g, 84%). 1H NMR (400 MHz, DMSO-d6): δ ppm 7.79 (s, 2H), 7.45-7.56 (m, 4H), 7.42 (t, 1H), 3.75 (s, 2H). MS: m/z 311.1 (M+1).
Reaction SMILES: [C:1]1([C:11]2[CH:12]=[CH:13][CH:14]=[C:15]3[C:19]=2[C:18](=O)[CH:17]([CH2:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[CH2:16]3)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[BH4-].[Na+].CO.S(=O)(=O)(O)O>C1(C)C=CC=CC=1.O>[C:1]1([C:11]2[CH:12]=[CH:13][CH:14]=[C:15]3[C:19]=2[CH2:18][C:17]([CH2:21][CH:22]2[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]2)=[CH:16]3)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: O=C1c2c(cccc2-c2cccc3ccccc23)CC1CC1CCCCC1
Agent: O=S(=O)(O)O
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Solvent: Cc1ccccc1
Product: C1=C(CC2CCCCC2)Cc2c1cccc2-c1cccc2ccccc12
Temperature: 50 °C
Reaction time: 5 h
Yield: 94.1 %

Procedure:
24 g (68 mmole) 7-(1-Naphthyl)-2-cyclohexylmethyl-indan-1-one were dissolved in 85 ml toluene in a 500 ml-roundbottom flask equipped with a reflux condenser. 2.82 g (1.1 eq.) sodium borohydride were added. Then 11.8 ml (4.3 eq.) methanol were added at 50° C. and the mixture was stirred for 5 h at 50° C. 2M sulphuric acid was added until the gas evolution ceased. After addition of 100 ml water the layers were separated and the organic layer was washed two times with 2M sulphuric acid and once with a saturated sodium chloride solution. The solvent was evaporated and the crude indanol was dissolved in approx. 250 ml of toluene. After addition of 0.5 g p-toluene sulfonic acid the mixture was heated to reflux using a Dean-Stark-trap until TLC showed complete conversion (90 min). The solution was washed twice with a saturated NaHCO3-solution, once with water and once with a saturated sodium chloride solution. Drying over magnesium sulphate and evaporation of the solvent afforded 21.65 g (95%) of the desired indene as a slightly offwhite oil. 1H-NMR (400 MHz, CDCl3): δ=7.88 (m, 2H, aromatic), 7.73 (d, 1H, aromatic), 7.55-7.19 (m, 7H, aromatic), 6.10 (s, 1H, C═CH), 3.40 (s, 2H, benzylic) 2.25 (d, 2H CH2Cy), 1.67-0.80 (m, 11H, aliphatic) ppm.
Reaction SMILES: Cl.[NH2:2][C:3]1[C:12]2[N:13]=[C:14]([CH2:21][CH2:22][C:23]3([CH3:28])OCC[O:24]3)[N:15]([CH2:16][C:17]([CH3:20])([OH:19])[CH3:18])[C:11]=2[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[N:4]=1.[OH-].[Na+]>O>[NH2:2][C:3]1[C:12]2[N:13]=[C:14]([CH2:21][CH2:22][C:23](=[O:24])[CH3:28])[N:15]([CH2:16][C:17]([OH:19])([CH3:18])[CH3:20])[C:11]=2[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[N:4]=1
Reactant: CC(C)(O)Cn1c(CCC2(C)OCCO2)nc2c(N)nc3ccccc3c21
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC(=O)CCc1nc2c(N)nc3ccccc3c2n1CC(C)(C)O
Temperature: 25 °C
Reaction time: 2 h
Yield: 94 %

Procedure:
Concentrated hydrochloric acid (0.98 mL) was added dropwise to a stirred suspension of 1-{4-amino-2-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]-1H-imidazo[4,5-c]quinolin-1-yl}-2-methylpropan-2-ol (1.45 g, 3.91 mmol) in water (26 mL), and the resulting solution was stirred at room temperature for two hours and then adjusted to pH 11 with the addition of aqueous sodium hydroxide (20% w/w). A precipitate formed, and the suspension was stirred for several minutes. The precipitate was isolated by filtration and washed with water to provide 1.2 g of 4-[4-amino-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-2-yl]butan-2-one as a white powder.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:15](Br)[CH:16]=[CH2:17]>C(#N)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:17][CH:16]=[CH2:15])=[CH:4][CH:3]=1
Reactant: Oc1ccc(Cl)cc1
Reactant: C=CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: C=CCOc1ccc(Cl)cc1
Temperature: 50 °C
Reaction time: 5 h
Yield: 86.5 %

Procedure:
To a solution of 4-chlorophenol (30 g, 233 mmol) in acetonitrile (100 ml) was added potassium carbonate (48.1 g, 349 mmol, 1.5 eq) and allyl bromide (36.28 g, 299.9 mmol, 1.3 eq) dropwise with stirring for 5 hours at 50° C. in an oil bath. The solids were filtered out and the liquid was concentrated under vacuum to afford 1-chloro-4-(prop-2-en-1-yloxy)benzene as yellow oil (34 g, 86%); 1H NMR (300 MHz, CDCl3): δ 7.20-7.25 (m, 2H), 6.81-6.86 (m, 2H), 5.96-6.09 (m, 1H), 5.27-5.44 (m, 2H), 4.49-4.51 (m, 2H).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([C:6]2[N:11]=[C:10]([NH2:12])[CH:9]=[CH:8][CH:7]=2)=[CH:2]1.[CH2:13]([O:15][C:16]([N:18]=[C:19]=[S:20])=[O:17])[CH3:14]>O1CCOCC1>[CH2:13]([O:15][C:16](=[O:17])[NH:18][C:19]([NH:12][C:10]1[CH:9]=[CH:8][CH:7]=[C:6]([C:3]2[CH:4]=[CH:5][S:1][CH:2]=2)[N:11]=1)=[S:20])[CH3:14]
Reactant: Nc1cccc(-c2ccsc2)n1
Reactant: CCOC(=O)N=C=S
Solvent: C1COCCO1
Product: CCOC(=O)NC(=S)Nc1cccc(-c2ccsc2)n1
Yield: 73.3 %

Procedure:
A solution of 6-(3-thienyl)pyridin-2-amine (3.70 g; 21.0 mmol; 1.0 eq.) and ethoxycarbonyl isothiocyanate (2.73 mL; 24.1 mmol; 1.15 eq.) in dioxane (100 mL) was stirred at rt overnight. The precipitate formed was filtered and washed with c-Hex to give the title compound as a white solid (4.73 g; 73%). HPLC, Rt: 4.26 min. (purity 99.9%). LC/MS, M+(ESI): 308.3.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)=[CH:4][CH:3]=1.[C:17]1([N:23]2[C:35]3[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][C:30]=3[C:29]3[C:24]2=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(=O)([O-])[O-].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1.COCCOC>[O:9]1[C:10]2[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=2[N:12]=[C:8]1[C:5]1[CH:6]=[CH:7][C:2]([C:32]2[CH:33]=[CH:34][C:35]3[N:23]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[C:24]4[C:29]([C:30]=3[CH:31]=2)=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:3][CH:4]=1
Reactant: OB(O)c1ccc2c(c1)c1ccccc1n2-c1ccccc1
Reactant: Brc1ccc(-c2nc3ccccc3o2)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: COCCOC
Solvent: Cc1ccccc1
Product: c1ccc(-n2c3ccccc3c3cc(-c4ccc(-c5nc6ccccc6o5)cc4)ccc32)cc1
Temperature: 100 °C
Reaction time: 5 h

Procedure:
In a 100 mL three-neck flask were put 0.95 g (3.5 mmol) of 2-(4-bromophenyl)benzoxazole, 1.0 g (3.5 mmol) of 9-phenyl-9H-carbazole-3-boronic acid, and 0.074 g (0.24 mmol) of tri(ortho-tolyl)phosphine. To this mixture were added 15 mL of 1,2-dimethoxyethane (abbreviation: DME) and 5 mL of a 2M potassium carbonate aqueous solution. This mixture was degassed under reduced pressure, and then the atmosphere in the flask was replaced with nitrogen. To this mixture was added 7.8 mg (0.035 mmol) of palladium(II)acetate, and the resulting mixture was stirred at 100° C. for 5 hours. After that, toluene was added to this mixture, and this suspension was washed with a saturated aqueous sodium carbonate solution and saturated brine in that order. Then, magnesium sulfate was added to the organic layer to dry it. Next, this mixture was suction filtered, whereby a filtrate was obtained.
Reaction SMILES: C([O:3][C:4]([CH2:6][O:7][C:8]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:9]=1[CH2:10][CH2:11][CH2:12][CH:13]2[CH2:18][O:19][C:20]([NH:22][N:23]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:21])=[O:5])C.[OH-].[Na+]>O1CCOCC1>[C:4]([CH2:6][O:7][C:8]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:9]=1[CH2:10][CH2:11][CH2:12][CH:13]2[CH2:18][O:19][C:20]([NH:22][N:23]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:21])([OH:5])=[O:3]
Reactant: CCOC(=O)COc1cccc2c1CCCC2COC(=O)NN(c1ccccc1)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: O=C(O)COc1cccc2c1CCCC2COC(=O)NN(c1ccccc1)c1ccccc1
Yield: 50 %

Procedure:
A solution of 2-[(5-ethoxycarbonylmethoxy-1,2,3,4-tetrahydro-1-naphthyl)methoxycarbonyl]-1,1-diphenylhydrazine (0.17 g) and 1N-aqueous sodium hydroxide (1 ml) in dioxane (1.5 ml) was stirred at room temperature for 30 minutes and partitioned between 5% hydrochloric acid and ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and evaporated in vacuo. The residue was washed with isopropanol to afford 2-[(5-carboxymethoxy-1,2,3,4-tetrahydro-1-naphthyl)methoxycarbonyl]-1,1-diphenylhydrazine (0.08 g) as a colorless powder.