Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[C:4](Cl)[N:3]=1.C(N(CC)CC)C.[NH2:17][C:18]([CH3:22])([CH3:21])[CH2:19][OH:20]>C(#N)C>[Cl:1][C:2]1[N:3]=[C:4]([NH:17][C:18]([CH3:22])([CH3:21])[CH2:19][OH:20])[CH:5]=[C:6]([Cl:8])[N:7]=1
Reactant: Clc1cc(Cl)nc(Cl)n1
Reactant: CC(C)(N)CO
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CC(C)(CO)Nc1cc(Cl)nc(Cl)n1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
To a solution of 2,4,6-trichloropyrimidine (20.0 g, 109 mmol) in acetonitrile (500 mL) was added triethylamine (11.03 g, 109 mmol) at 0° C. After 5 min at room temperature, 2-amino-2-methylpropan-1-ol (9.72 g, 109 mmol) was added portionwise. The reaction mixture was stirred for another 1 h at room temperature, filtered and concentrated. Purification via silica gel column (ethyl acetate/petroleum ether=1/10 to 1/1) afforded the title product.
Reaction SMILES: [Cl:1][C:2]1[C:3]([NH:22][C:23](=[O:31])[CH2:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([N:12]1[CH2:16][CH2:15][C@@H:14](OS(C)(=O)=O)[CH2:13]1)[CH:6]=[CH:5]2.[CH3:32][NH2:33]>C(O)C>[Cl:1][C:2]1[C:3]([NH:22][C:23](=[O:31])[CH2:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([N:12]1[CH2:16][CH2:15][C@H:14]([NH:33][CH3:32])[CH2:13]1)[CH:6]=[CH:5]2
Reactant: CS(=O)(=O)O[C@@H]1CCN(c2ccc3c(NC(=O)CC4CCCCC4)c(Cl)ccc3n2)C1
Reactant: CN
Solvent: CCO
Product: CN[C@H]1CCN(c2ccc3c(NC(=O)CC4CCCCC4)c(Cl)ccc3n2)C1

Procedure:
Prepared according to the method of example 33(b), using N-[6-Chloro-2-[(3R)-3-[(methylsulfonyl)oxy]-1-pyrrolidinyl]-5-quinolinyl]-cyclohexaneacetamide (Example 35(a)) (0.2 g) and 8M methylamine in ethanol (3 mL) to afford the title compound (0.063 g).
Reaction SMILES: O[CH2:2][C:3]1[CH:4]=[C:5]([CH:10]=[C:11]([CH3:13])[CH:12]=1)[C:6]([O:8][CH3:9])=[O:7].CS(Cl)(=O)=O.[CH3:19][NH:20][CH2:21][CH2:22][CH2:23][CH3:24]>C(Cl)Cl>[CH2:21]([N:20]([CH2:2][C:3]1[CH:4]=[C:5]([CH:10]=[C:11]([CH3:13])[CH:12]=1)[C:6]([O:8][CH3:9])=[O:7])[CH3:19])[CH2:22][CH2:23][CH3:24]
Reactant: COC(=O)c1cc(C)cc(CO)c1
Reactant: CCCCNC
Agent: CS(=O)(=O)Cl
Solvent: ClCCl
Product: CCCCN(C)Cc1cc(C)cc(C(=O)OC)c1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To methyl 3-(hydroxymethyl)-5-methylbenzoate prepared by the method in Example SP-177 (1.1 g, 6.1 mmol), in anhydrous methylene chloride (10 mL) is added methanesulfonyl chloride (663 μL, 8.6 mmol) at −30° C., and the reaction is warmed to 0° C. The reaction stirred 1 h, then filtered. The filtrate is added to N-methylbutylamine (2.1 mL, 18.3 mmol), and the reaction stirred at room temperature 16 h. The solution is concentrated under reduced pressure. Purification by flash chromatography affords the title compound in pure form. ESI MS m/z 250.2 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[C:3]2[CH:12]=[CH:11][CH:10]=[CH:9][C:4]=2[Se:5][C:6]=1[C:7]#[N:8].C([OH:15])C>[OH-].[Na+]>[NH2:1][C:2]1[C:3]2[CH:12]=[CH:11][CH:10]=[CH:9][C:4]=2[Se:5][C:6]=1[C:7]([NH2:8])=[O:15]
Reactant: CCO
Reactant: N#Cc1[se]c2ccccc2c1N
Agent: [Na+]
Agent: [OH-]
Product: NC(=O)c1[se]c2ccccc2c1N
Temperature: 7.5 °C
Yield: 60 %

Procedure:
To a suspension of 3-aminobenzo[b]selenophene-2-carbonitrile (5.0 g) in aqueous sodium hydroxide solution (100 mL, 10%) was added ethanol (60 mL) and the mixture refluxed for 1 h. Ethanol was distilled off under vacuum (appr. 25 mL) and the mixture was allowed to cool to 5-10° C. The separated crystals were filtered off, washed with cold water and dried to give the product as a off-white color solid (3 g, 60%), mp 180-182° C. 1H NMR (400 MHz, DMSO-d6): δ 7.99-8.01 (1H, m, H-7), 7.92-7.94 (1H, m, H-4), 7.40-7.42 (2H, m, H-5,6), 7.21 (2H, s, —CONH2), 6.97 (2H, s, —NH2); LC-MS (positive ion mode): m/z 261, 263 (M+Na)+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:22](O)[C:10]3[N:11]=[C:12]([CH3:21])[N:13]([CH2:14][CH2:15][C:16]4[N:17]=[CH:18][NH:19][CH:20]=4)[C:9]=3[CH:8]=[CH:7][C:6]=2[CH:24]=1.[CH3:25][N:26]1[CH:33]=[CH:32][C:30](=[O:31])[NH:29][C:27]1=[O:28]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:22]([C:32]3[C:30](=[O:31])[NH:29][C:27](=[O:28])[N:26]([CH3:25])[CH:33]=3)[C:10]3[N:11]=[C:12]([CH3:21])[N:13]([CH2:14][CH2:15][C:16]4[N:17]=[CH:18][NH:19][CH:20]=4)[C:9]=3[CH:8]=[CH:7][C:6]=2[CH:24]=1
Reactant: Cn1ccc(=O)[nH]c1=O
Reactant: Cc1nc2c(n1CCc1c[nH]cn1)C=Cc1cc(Cl)ccc1C2O
Product: Cc1nc2c(n1CCc1c[nH]cn1)C=Cc1cc(Cl)ccc1C2c1cn(C)c(=O)[nH]c1=O

Procedure:
The subtitle product was prepared from the product of step (ii) and 1-methyluracil (0.36 g) according to the method of example 42 step (iv). Purification was by biotage chromatography on silica eluting with 5% methanol in dichloromethane with 1% 0.880 ammonia present to give a white solid.
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C:7]([OH:9])=[O:8].S(=O)(=O)(O)O.[CH3:15]O>>[CH3:1][C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C:7]([O:9][CH3:15])=[O:8]
Reactant: Cc1ccsc1C(=O)O
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)c1sccc1C
Yield: 97 %

Procedure:
To a solution of 3-Methylthiophene-2-carboxylic acid (15 g, 105 mmol, 1.0 eq) in methanol (150 mL) was added cone sulfuric acid (7.5 mL) drop wise and refluxed for 12 h. The solvent was evaporated under vacuum and the residue was taken into ethyl acetate (200 mL), washed with water (2×50 mL), saturated aqueous sodium bicarbonate solution (2×50 mL), brine (50 mL), dried (Na2SO4) and filtered. The filtrate was evaporated under vacuum to afford 20 g (97%) of the desired product as a oil. 1HNMR (400 MHz, CDCl3) δ 7.38 (d, J=5.0 Hz, 1H), 6.91 (d, J=5.0 Hz, 1H), 3.85 (s, 3H), 2.55 (s, 3H); ESI-MS [(m/z) 157 (MH)+]
Reaction SMILES: [CH3:1][C:2]1([CH3:12])[CH2:7][S:6](=[O:9])(=[O:8])[CH2:5][C:4]([CH3:11])([CH3:10])[NH:3]1.[Cl:13][O-].[Na+]>O.Cl>[Cl:13][N:3]1[C:2]([CH3:12])([CH3:1])[CH2:7][S:6](=[O:9])(=[O:8])[CH2:5][C:4]1([CH3:11])[CH3:10]
Reactant: [O-]Cl
Reactant: CC1(C)CS(=O)(=O)CC(C)(C)N1
Agent: Cl
Agent: [Na+]
Solvent: O
Product: CC1(C)CS(=O)(=O)CC(C)(C)N1Cl
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
19.1 g (0.1 mole) of 2,2,6,6-tetramethyl-1-aza-4-thiacyclohexane 4,4-dioxide is dissolved in 100 ml of water and 10 ml of 10N hydrochloric acid. The resulting solution is cooled to 0° C and within 90 minutes an addition made dropwise at between 0° and 5° C, with stirring, of 125 ml of a freshly prepared sodium hypochlorite solution (36 g of sodium hydroxide is dissolved in 300 ml of water, and at 0° C24 g of chlorine introduced). The reaction mixture is further stirred for 10 minutes at 0°-5° C; the precipitate is filtered off with suction, washed with water, dried, and crystallised from ligroin to yield 1-chloro-2,2,6,6-tetramethyl-1-aza-4-thiacyclohexane-4,4-dioxide (13) as colourless crystals, M.P. 163° C.
Reaction SMILES: [F:1][CH:2]([F:23])[O:3][C:4]1[C:5]([OH:22])=[C:6]([C:12]2[CH:20]=[CH:19][CH:18]=[C:17]3[C:13]=2[CH2:14][CH2:15][C:16]3=[O:21])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11].C(=O)([O-])[O-].[K+].[K+].Br[CH2:31][C:32]1([CH2:36][OH:37])[CH2:35][O:34][CH2:33]1>C(#N)C>[F:1][CH:2]([F:23])[O:3][C:4]1[C:5]([O:22][CH2:31][C:32]2([CH2:36][OH:37])[CH2:35][O:34][CH2:33]2)=[C:6]([C:12]2[CH:20]=[CH:19][CH:18]=[C:17]3[C:13]=2[CH2:14][CH2:15][C:16]3=[O:21])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11]
Reactant: COc1ccc(-c2cccc3c2CCC3=O)c(O)c1OC(F)F
Reactant: OCC1(CBr)COC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COc1ccc(-c2cccc3c2CCC3=O)c(OCC2(CO)COC2)c1OC(F)F
Temperature: 80 °C
Yield: 19 %

Procedure:
To a stirring solution of 4-(3-(difluoromethoxy)-2-hydroxy-4-methoxyphenyl)-2,3-dihydro-1H-inden-1-one (80 mg, 0.25 mmol) in acetonitrile (10 mL) was added potassium carbonate (102 mg, 0.75 mmol) and (3-bromomethyl-oxetan-3-yl)-methanol (68 mg, 0.375 mmol) and the resultant reaction mixture was heated to 80° C. for 16 h. The reaction mixture was cooled to RT, filtered through celite and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 0-40% ethyl acetate in pet ether) to afford the title compound as a solid (20 mg, 19%).
Reaction SMILES: C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]#[N:11])[CH:5]=1.O.[NH2:14][NH2:15]>C(O)C>[C:10]([C:6]1[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=1)[C:3]([NH:14][NH2:15])=[O:2])#[N:11]
Reactant: NN
Reactant: COC(=O)c1cccc(C#N)c1
Solvent: O
Solvent: CCO
Product: N#Cc1cccc(C(=O)NN)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 52.7 %

Procedure:
A mixture of 3-cyano-benzoic acid methyl ester (2 g, 12 mmol) and hydrazine monohydrate (0.60 mL, 12 mmol) in ethanol (10 mL) was stirred at room temperature overnight. The reaction mixture was concentrated and then the residue was triturated with diethyl ether to afford 3-cyano-benzoic acid hydrazide (1.02 g, 51%, pink solid). 1H NMR (DMSO) □ (ppm): 10.31 (s, 1H), 8.21 (m, 1H), 8.11 (m, 1H), 7.99 (m, 1H), 7.70 (m, 1H), 4.50 (s, 1H).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:26]=[C:27]([O:30][CH2:31][CH3:32])[C:28]=1[F:29])[CH2:7][N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:25])[C:16]2[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[C:18]([OH:24])[CH:17]=2)[CH2:10][CH2:9]1)[CH3:2].[CH3:33][S:34](Cl)(=[O:36])=[O:35].C(N(C(C)C)C(C)C)C>C(Cl)Cl>[CH2:31]([O:30][C:27]1[CH:26]=[C:6]([CH:5]=[C:4]([O:3][CH2:1][CH3:2])[C:28]=1[F:29])[CH2:7][N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]([C:16]2[CH:17]=[C:18]([O:24][S:34]([CH3:33])(=[O:36])=[O:35])[CH:19]=[C:20]([O:22][CH3:23])[CH:21]=2)=[O:25])[CH2:10][CH2:9]1)[CH3:32]
Reactant: CCOc1cc(CN2CCC(NC(=O)c3cc(O)cc(OC)c3)CC2)cc(OCC)c1F
Reactant: CS(=O)(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CCOc1cc(CN2CCC(NC(=O)c3cc(OC)cc(OS(C)(=O)=O)c3)CC2)cc(OCC)c1F

Procedure:
In analogy to the procedure described in example 72a), N-[1-(3,5-diethoxy-4-fluoro-benzyl)-piperidin-4-yl]-3-hydroxy-5-methoxy-benzamide (example 257) was reacted with methanesulfonyl chloride, N-ethyl-diisopropylamine in CH2Cl2 at rt to yield the title compound as colorless solid. MS: 525.2 (MH+).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:8]2[O:12][CH2:11][CH2:10][O:9]2)[CH:5]=[CH:6][CH:7]=1.[C:13](B1OC(C)(C)C(C)(C)O1)([CH3:15])=[CH2:14].C(=O)([O-])[O-].[Na+].[Na+].O>C(COC)OC.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:13]([C:2]1[CH:3]=[C:4]([CH:8]2[O:12][CH2:11][CH2:10][O:9]2)[CH:5]=[CH:6][CH:7]=1)([CH3:15])=[CH2:14]
Reactant: C=C(C)B1OC(C)(C)C(C)(C)O1
Reactant: Brc1cccc(C2OCCO2)c1
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: O
Solvent: COCCOC
Product: C=C(C)c1cccc(C2OCCO2)c1
Temperature: 90 °C
Yield: 66.3 %

Procedure:
A degassed solution of 2-(3-bromo-phenyl)-[1,3]dioxolane (3.46 ml, 22.6 mmol) in dimethoxyethane (60 ml) was added into a tube which has been charged with a mixture of 2-isopropenyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (3.8 g, 22.6 mmol) and an aqueous solution of sodium carbonate (1M, 20 ml); tetrakis(triphenylphosphine)palladium(0) (0.266 g) is then added, the tube is sealed and heated to 90° C. overnight. After cooling of the reaction mixture, water (20 ml) was added, the aqueous layer separated and extracted with dichloromethane (3×20 ml). The combined organic layers were dried over sodium sulphate and evaporated. The crude product was purified by chromatography on silica gel using cyclohexane as the eluent. There were obtained 2.85 g (68% of theory) of the 2-(3-isopropenyl-phenyl)-[1,3]dioxolane.
Reaction SMILES: Br[C:2]1[C:3]([NH:22][CH2:23][CH2:24][OH:25])=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[N:26]1[CH:31]=[CH:30][CH:29]=[C:28](B(O)O)[CH:27]=1>>[OH:25][CH2:24][CH2:23][NH:22][C:3]1[C:2]([C:28]2[CH:27]=[N:26][CH:31]=[CH:30][CH:29]=2)=[CH:21][C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=2)=[O:8])=[CH:5][N:4]=1
Reactant: OB(O)c1cccnc1
Reactant: O=C(Nc1ccc(OC(F)(F)F)cc1)c1cnc(NCCO)c(Br)c1
Product: O=C(Nc1ccc(OC(F)(F)F)cc1)c1cnc(NCCO)c(-c2cccnc2)c1

Procedure:
The title compound was prepared in an analogous fashion to that described in Example 152 using 5-bromo-6-((2-hydroxyethyl)amino)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 159.1) and pyridin-3-ylboronic acid. LC-MS (Condition 6) tR=0.88 min, m/z=419.0 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[C:3](=[O:20])[NH:4][N:5]=[C:6]([O:9][CH2:10][CH2:11][CH2:12][S:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:7]=1Cl.[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][NH2:28])[CH:22]=1>O.O1CCOCC1>[Cl:1][C:2]1[C:3](=[O:20])[NH:4][N:5]=[C:6]([O:9][CH2:10][CH2:11][CH2:12][S:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:7]=1[NH:28][CH2:27][C:23]1[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=1
Reactant: NCc1cccnc1
Reactant: O=c1[nH]nc(OCCCSc2ccccc2)c(Cl)c1Cl
Solvent: C1COCCO1
Solvent: O
Product: O=c1[nH]nc(OCCCSc2ccccc2)c(NCc2cccnc2)c1Cl
Yield: 74.8 %

Procedure:
After 0.3 g of 4,5-dichloro-6-[3-(phenylthio)propyloxy]-3(2H)-pyridazinone and 0.243 g of 3-picolylamine were dissolved in a solvent mixture of water-dioxane (1:1), the mixture was heated to reflux for 8 hours. After completion of the reaction, the reaction mixture was poured onto water and extracted with ethyl acetate. After washing with water and drying, the solvent was distilled off. The resulting crystals were recrystallized from isopropanol to give 0.273 g of the objective compound. Yield, 73%, Melting point, 152°-155° C.
Reaction SMILES: [CH:1]([O:4][CH2:5][CH2:6][N:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[NH:16][CH:17]1[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18]1)([CH3:3])[CH3:2].[IH:30].C(O)C>C(OCC)C>[IH:30].[CH:1]([O:4][CH2:5][CH2:6][N:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[NH:16][CH:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)([CH3:3])[CH3:2]
Reactant: CC(C)OCCn1c(NC2CCN(C(=O)OC(C)(C)C)CC2)nc2ccccc21
Agent: I
Solvent: CCO
Solvent: CCOCC
Product: CC(C)OCCn1c(NC2CCNCC2)nc2ccccc21
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Combine (1-(2-(isopropoxy)ethyl)-1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine (2.97 g, 7.38 mmol), aqueous hydriodic acid (5 mL, 57%), and ethanol (10 mL). Heat to reflux. After 1 hour, cool to ambient temperature and pour the reaction mixture into diethyl ether (350 mL) and stir to give a solid. After 1 hour, collect the solid by filtration, rinse with diethyl ether, and dry in vacuo to give the title compound.
Reaction SMILES: [I:1]I.[CH2:3]([O:10][C:11]1[CH:16]=[C:15]([O:17][CH2:18][CH2:19][CH3:20])[CH:14]=[CH:13][C:12]=1[CH2:21][CH3:22])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>C(Cl)(Cl)Cl.FC(F)(F)C([O-])=O.[Ag+]>[CH2:3]([O:10][C:11]1[CH:16]=[C:15]([O:17][CH2:18][CH2:19][CH3:20])[C:14]([I:1])=[CH:13][C:12]=1[CH2:21][CH3:22])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: CCCOc1ccc(CC)c(OCc2ccccc2)c1
Reactant: II
Agent: [Ag+]
Agent: O=C([O-])C(F)(F)F
Solvent: ClC(Cl)Cl
Product: CCCOc1cc(OCc2ccccc2)c(CC)cc1I
Reaction time: 1 h

Procedure:
A solution of iodine (2.82 g, 11.1 mmol) dissolved in CHCl3 (80 mL) was added dropwise to a stirred mixture of 2-benzyloxy-1-ethyl-4-propoxy-benzene (3 g, 11.1 mmol), silver trifluoroacetate (2.45 g, 11.1 mmol) in CHCl3 (20 mL). After the addition was complete the reaction mixture was stirred for 1 hour. The mixture was filtered through a pad of celite washing with CH2Cl2. The filtrate was washed with satd Na2S2O3, brine, dried over Na2SO4 and concentrated to a pale yellow solid (4.04 g, 92%). 1H NMR (400 MHz, CDCl3): δ 1.07 (t, J=7.3 Hz, 3 H), 1.17 (t, J=7.6 Hz, 3 H), 1.81 (m, 2 H), 2.59 (q, J=7.6 Hz, 2 H), 3.90 (t, J=6.3 Hz, 2 H), 5.05 (s, 2 H), 6.43 (s, 1 H), 7.31-7.45 (m, 5 H), 7.49 9s, 1 H).
Reaction SMILES: Cl.[CH:2]12[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:10][CH:4]([CH2:5]3)[C:3]1=O)[CH2:9]2.[CH:13]([NH2:16])([CH3:15])[CH3:14].C([BH3-])#N.C([N+](CCCC)(CCCC)CCCC)CCC>ClCCl>[CH:2]12[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:10][CH:4]([CH2:5]3)[CH:3]1[NH:16][CH:13]([CH3:15])[CH3:14])[CH2:9]2
Reactant: CC(C)N
Reactant: O=C1C2CC3CC(C2)CC1C3
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: Cl
Agent: [BH3-]C#N
Solvent: ClCCl
Product: CC(C)NC1C2CC3CC(C2)CC1C3
Temperature: 25 °C

Procedure:
Methanolic HCl (2.5 M; 13.3 mmol) is added to a solution of 2-adamantanone (1.00 g, 6.7 mmol) in dichloromethane (25 mL) and then isopropylamine (2.5 mL, 29.4 mmol) is added, followed by tetrabutylammonium cyanoborohydride (1.41 g, 5 mmol) and approximately 1 g of 4A molecular sieves. The reaction mixture is stirred at room temperature until the reaction is complete, as judged by TLC. Then the mixture is filtered and the filtrate is acidified to pH 1 with 1 M HCl, and the solvent is evaporated. The residue is taken up in water and extracted with ether. The aqueous layer is made basic to pH 10 with NaOH solution and the resulting mixture is extracted several times with ether. The combined ether layers are washed with water and brine, dried (magnesium sulfate), filtered, and evaporated to give adamantan-2-yl-isopropyl-amine.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:43])[CH2:5][CH2:6][C:7]([C:9]1[CH:10]=[C:11]2[C:19](=[CH:20][CH:21]=1)[N:18]([CH2:22][CH:23]([CH2:28][CH3:29])[CH2:24][CH2:25][CH2:26][CH3:27])[C:17]1[C:12]2=[CH:13][C:14]([C:34](=[O:42])[C:35]2[CH:40]=[CH:39][C:38](F)=[CH:37][CH:36]=2)=[C:15]2[CH:33]=[CH:32][CH:31]=[CH:30][C:16]2=1)=[O:8])[CH3:2].C([O-])([O-])=O.[K+].[K+].[CH:50]1[C:62]2[NH:61][C:60]3[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=3)[C:54]=2[CH:53]=[CH:52][CH:51]=1.O>CS(C)=O>[CH2:1]([O:3][C:4](=[O:43])[CH2:5][CH2:6][C:7]([C:9]1[CH:10]=[C:11]2[C:19](=[CH:20][CH:21]=1)[N:18]([CH2:22][CH:23]([CH2:28][CH3:29])[CH2:24][CH2:25][CH2:26][CH3:27])[C:17]1[C:12]2=[CH:13][C:14]([C:34](=[O:42])[C:35]2[CH:40]=[CH:39][C:38]([N:61]3[C:62]4[CH:50]=[CH:51][CH:52]=[CH:53][C:54]=4[C:55]4[C:60]3=[CH:59][CH:58]=[CH:57][CH:56]=4)=[CH:37][CH:36]=2)=[C:15]2[CH:33]=[CH:32][CH:31]=[CH:30][C:16]2=1)=[O:8])[CH3:2]
Reactant: CCCCC(CC)Cn1c2ccc(C(=O)CCC(=O)OCC)cc2c2cc(C(=O)c3ccc(F)cc3)c3ccccc3c21
Reactant: c1ccc2c(c1)[nH]c1ccccc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: CCCCC(CC)Cn1c2ccc(C(=O)CCC(=O)OCC)cc2c2cc(C(=O)c3ccc(-n4c5ccccc5c5ccccc54)cc3)c3ccccc3c21
Temperature: 150 °C
Reaction time: 8 h

Procedure:
To 4-(11-(2-ethylhexyl)-5-(4-fluoro-benzoyl)-11H-benzo[a]carbazol-8-yl]-4-oxo-butyric acid ethyl ester (1.01 g, 1.75 mmol) in dimethylsulfoxide (DMSO) (10 mL) are added K2CO3 (738 mg, 5.33 mmol) and carbazole (297 mg, 1.77 mmol). The reaction mixture is heated to 150° C. and stirred overnight. After cooling to room temperature, the reaction mixture is poured into water, and the crude product is extracted with CH2Cl2. The organic layer is washed with water and brine, dried over MgSO4. After concentration, the crude product is purified by column chromatography on silica gel eluting with CH2Cl2 to obtain a brown resin (760 mg; 60%). The structure is confirmed by 1H-NMR spectrum (CDCl3). δ [ppm]: 0.84 (t), 0.92 (t), 1.20-1.52 (m), 2.28-2.36 (m), 2.82 (t), 3.48 (t), 4.16 (q), 4.74-4.21 (m), 7.33 (t), 7.46 (t), 7.60 (d), 7.63 (d), 7.68 (t), 7.72 (t), 7.77 (d), 8.15 (t), 8.19 (d), 8.22 (d), 8.50 (s), 8.58 (d), 8.67 (d), 8.81 (s).
Reaction SMILES: C(N(CC)CC)C.[CH3:8][C:9]1([CH3:16])[O:13][CH:12]([CH2:14][NH2:15])[CH2:11][O:10]1.[CH2:17]([O:24][C:25]1[CH:34]=[C:33]2[C:28]([C:29](Cl)=[C:30]([N+:35]([O-:37])=[O:36])[CH:31]=[N:32]2)=[CH:27][CH:26]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>ClCCl>[CH2:17]([O:24][C:25]1[CH:34]=[C:33]2[C:28]([C:29]([NH:15][CH2:14][CH:12]3[CH2:11][O:10][C:9]([CH3:16])([CH3:8])[O:13]3)=[C:30]([N+:35]([O-:37])=[O:36])[CH:31]=[N:32]2)=[CH:27][CH:26]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: CC1(C)OCC(CN)O1
Reactant: O=[N+]([O-])c1cnc2cc(OCc3ccccc3)ccc2c1Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC1(C)OCC(CNc2c([N+](=O)[O-])cnc3cc(OCc4ccccc4)ccc23)O1
Temperature: 25 °C
Reaction time: 6 h
Yield: 96.2 %

Procedure:
Triethylamine (31.88 mL, 228.77 mmol) followed by 2,2-dimethyl-1,3-dioxolan-4-methanamine (20.0 g, 152.51 mmol) were added to a solution of 7-benzyloxy-4-chloro-3-nitroquinoline (48.00 g, 152.51 mmol) in dichloromethane (400 mL), which was then stirred at ambient temperature for 6 hours. The crude reaction mixture was concentrated under reduced pressure, and the resulting solid was treated with water. The mixture was stirred for 1 hour. The solid was collected by filtration, washed with water, dried, suspended in diethyl ether (400 mL), sonicated, and the resulting precipitate material was collected by filtration. The product was dried under vacuum at 40° C. for 12 hours to afford 60.1 g of (7-benzyloxy-3-nitro-quinolin-4-yl)[(2,2-dimethyl[1,3]dioxolan-4-yl)methyl]amine as a yellow solid, mp 154-155° C.
Reaction SMILES: [N+](C1C=CC(O[C:11](=[O:30])/[CH:12]=[CH:13]/[CH:14]=[C:15]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)=CC=1)([O-])=O.[N:31]1[CH:36]=[CH:35][CH:34]=[C:33]([CH2:37][CH2:38][CH2:39][CH2:40][NH2:41])[CH:32]=1>O1CCCC1>[F:29][C:25]1[CH:24]=[C:23]([C:15]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=2)=[CH:14]/[CH:13]=[CH:12]/[C:11]([NH:41][CH2:40][CH2:39][CH2:38][CH2:37][C:33]2[CH:32]=[N:31][CH:36]=[CH:35][CH:34]=2)=[O:30])[CH:28]=[CH:27][CH:26]=1
Reactant: O=C(/C=C/C=C(c1cccc(F)c1)c1cccc(F)c1)Oc1ccc([N+](=O)[O-])cc1
Reactant: NCCCCc1cccnc1
Solvent: C1CCOC1
Product: O=C(/C=C/C=C(c1cccc(F)c1)c1cccc(F)c1)NCCCCc1cccnc1
Yield: 90 %

Procedure:
As in Example 134, a solution of (E)-5,5-bis(3-fluorophenyl)-2,4-pentadienoic acid 4-nitrophenyl ester (25.85 g) and 3-pyridinebutanamine (10 g) in tetrahydrofurane (100 mL) was stirred for 18 hours at room temperature and was worked up in the usual manner. The crude product was purified by HPLC (ethyl acetate) and then crystallized from ethyl acetate-hexane to afford 23.9 g of (E)-5,5-bis(3-fluorophenyl)- N-[4-(3-pyridinyl)butyl]-2,4-pentadienamide mp 103°-104° C.
Reaction SMILES: [O:1]=[CH:2][C:3]1[CH:11]=[CH:10][C:7]([O:8][CH3:9])=[C:5]([OH:6])[CH:4]=1.C(=O)([O-])[O-].[K+].[K+].[CH:18]1(Br)[CH2:22][CH2:21][CH2:20][CH2:19]1.C1(C)C=CC=CC=1>CN(C)C=O.[I-].[K+]>[CH:18]1([O:6][C:5]2[CH:4]=[C:3]([CH:11]=[CH:10][C:7]=2[O:8][CH3:9])[CH:2]=[O:1])[CH2:22][CH2:21][CH2:20][CH2:19]1
Reactant: BrC1CCCC1
Reactant: COc1ccc(C=O)cc1O
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Product: COc1ccc(C=O)cc1OC1CCCC1
Temperature: 65 °C
Reaction time: 24 h
Yield: 80.5 %

Procedure:
A solution of 100 g (0.66 mol) of isovanillin, 136.2 g (0.99 mol) of anhydrous potassium carbonate, and 3 g of potassium iodide in 650 ml of anhydrous dimethylformamide was stirred at 65° C. 127.3 g (0.85 mol) of cyclopentyl bromide was slowly added dropwise for 1 hour to the solution. This solution was stirred at 65° C. for 1 day and, then, its temperature was lowered to a room temperature. It was diluted by 2.0 L of toluene and was washed with 1M sodium hydroxide (2×1.5 L). The aqueous layer was extracted with 0.5 L of toluene, and the organic layer was washed with distilled water (2×1.5 L). The organic layer was dried and concentrated to obtain 117 g of light brown oily title compound. 1H NMR(CDCl3,d): 9.84(s, 1H) 7.42(m, 2H) 6.95(d, 1H, J=9 Hz) 4.87(m, 1H) 3.93(s, 3H) 2.1-6(m, 8H)