Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[CH:2]=[CH:3][C:4]([OH:28])=[C:5]([C:7]2[N:8]=[C:9]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:26]=3[OH:27])N(C3C=CC(C(O)=O)=CC=3)N=2)[CH:6]=1.C(Cl)(=O)C1C(=CC=CC=1)[OH:32].C(N)(=O)C1C(=CC=CC=1)O>>[OH:28][C:4]1[CH:3]=[CH:2][CH:1]=[CH:6][C:5]=1[C:7]1[O:27][C:26]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[C:9](=[O:32])[N:8]=1
Reactant: O=C(O)c1ccc(-n2nc(-c3ccccc3O)nc2-c2ccccc2O)cc1
Reactant: O=C(Cl)c1ccccc1O
Agent: NC(=O)c1ccccc1O
Product: O=c1nc(-c2ccccc2O)oc2ccccc12

Procedure:
U.S. Pat. No. 6,465,504 discloses a process for preparing Deferasirox wherein the process includes reacting salicyloyl chloride with salicylamide at 170° C. to obtain 2-(2-hydroxyphenyl)benz[e][1,3]oxazin-4-one, and further crystallization in ethanol to obtain slight yellow color crystals of 2-(2-hydroxyphenyl)benz[e][1,3]oxazin-4-one. 2-(2-hydroxyphenyl)benz[e][1,3]oxazin-4-one which is further reacted with 4-hydrazinebenzoic acid in presence of ethanol to give Deferasirox. Major drawback of this process is preparation of 2-(2-hydroxyphenyl)benz[e][1,3]oxazin-4-one at high temperature and in the absence of solvent which causes formation of several impurities which is difficult to avoid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[NH:9][CH2:10][C:11]1[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=1.[CH3:17][S:18](Cl)(=[O:20])=[O:19].C(=O)([O-])[O-].[K+].[K+]>ClCCl>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[N:9]([CH2:10][C:11]1[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=1)[S:18]([CH3:17])(=[O:20])=[O:19]
Reactant: CS(=O)(=O)Cl
Reactant: Clc1ccc(NCc2cccnc2)c(Cl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: CS(=O)(=O)N(Cc1cccnc1)c1ccc(Cl)cc1Cl

Procedure:
A 2.7 g. portion of 3-(2,4-dichlorophenylaminomethyl)pyridine was dissolved in dichloromethane and reacted with 0.9 ml. of methanesulfonyl chloride in the presence of 1.4 g. of potassium carbonate at ambient temperature for several days. The reaction mixture was worked up as described in Example 4 to obtain 3.2 g. of oil, which was triturated with petroleum ether and then diethyl ether and filtered to obtain 2.8 g. of solid. The solid was triturated with chloroform, filtered and dried to obtain 0.9 g. of the desired product, m.p. 180°-186°. Its elemental analysis was as follows.
Reaction SMILES: O=P(Cl)(Cl)[Cl:3].[C:6]([C:10]1[N:15]=[C:14](O)[C:13]([C:17]([O:19][CH3:20])=[O:18])=[CH:12][N:11]=1)([CH3:9])([CH3:8])[CH3:7]>CCN(CC)CC>[C:6]([C:10]1[N:15]=[C:14]([Cl:3])[C:13]([C:17]([O:19][CH3:20])=[O:18])=[CH:12][N:11]=1)([CH3:9])([CH3:8])[CH3:7]
Reactant: COC(=O)c1cnc(C(C)(C)C)nc1O
Reactant: O=P(Cl)(Cl)Cl
Solvent: CCN(CC)CC
Product: COC(=O)c1cnc(C(C)(C)C)nc1Cl
Temperature: 40 °C
Reaction time: 1 h
Yield: 87 %

Procedure:
To ice cold (0-5° C.) POCl3 (35 mL) was added dropwise Et3N (0.4 mL), followed by methyl 2-t-butyl-4-hydroxypyrimidine-5-carboxylate (3.45 g, 16.4 mmol). The mixture was then warmed to 40° C. and stirred under Ar for 1 h, then concentrated and diluted with CHCl3 (100 mL) and poured carefully onto ice (˜300 g) and stirred at RT until the ice all melted. The organic phase was separated, washed with NaHCO3 (100 mL), H2O (100 mL), dried (Na2SO4), concentrated and dried to yield methyl 2-t-butyl-4-chloropyrimidine-5-carboxylate (3.28 g, 87% yield). 1H NMR (400 MHz, DMSO-d6): δ 1.35 (s, 9H), 3.90 (s, 3H), 9.14 (s, 1H).
Reaction SMILES: [CH:1]([CH:4]1[CH2:9][CH2:8][CH:7]([OH:10])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[C:11](O)(=[O:14])[CH:12]=[CH2:13].C(OOC(C)(C)C)(C)(C)C>>[CH:1]([CH:4]1[CH2:9][CH2:8][C:7]2([O:10][C:11](=[O:14])[CH2:12][CH2:13]2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2]
Reactant: CC(C)C1CCC(O)CC1
Reactant: C=CC(=O)O
Agent: CC(C)(C)OOC(C)(C)C
Product: CC(C)C1CCC2(CCC(=O)O2)CC1

Procedure:
To 1247 g of 4-isopropylcyclohexanol at 143°-150° C. was added in 6 hrs a mixture of 71.1 g (1.0 m) acrylic acid, 142 g (1.0 m) 4-isopropylcyclohexanol and 14.6 g (0.1 m) di-tert-butylperoxide. After an additional hour at 143°-150° the mixture was distilled at reduced pressure yielding 142.1 g. Bp:125°-141° C. (1.0 mm Hg). Odor:woody, milky-lactone, dry. Analysis:99% pure by VPC: 44% cis (odor:nonalactone, celery-lactone) 56% trans (odor:strong woody, cinnamic, urine)
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([NH:9][C:10](=[O:21])[C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[C:13](F)[CH:12]=2)[CH:5]=[CH:6][C:7]=1[CH3:8].[OH:22][CH2:23][CH2:24][NH2:25].C([O-])(O)=O.[Na+]>CN(C=O)C>[CH3:1][C:2]1[CH:3]=[C:4]([NH:9][C:10](=[O:21])[C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[C:13]([NH:25][CH2:24][CH2:23][OH:22])[CH:12]=2)[CH:5]=[CH:6][C:7]=1[CH3:8]
Reactant: NCCO
Reactant: Cc1ccc(NC(=O)c2ccc([N+](=O)[O-])c(F)c2)cc1C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1ccc(NC(=O)c2ccc([N+](=O)[O-])c(NCCO)c2)cc1C
Temperature: 120 °C

Procedure:
A mixture of N-(3,4-dimethyl-phenyl)-3-fluoro-4-nitrobenzamide (65 mg), 2-hydroxy-1-ethylamine (0.225 mL of 2M THF solution) in DMF (1 mL) was heated at 120° C. under microwave radiation for 5 min. Then saturated NaHCO3 aqueous solution was added. The aqueous layer was extracted with EtOAc. The organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to give N-(3,4-dimethyl-phenyl)-3-(2-hydroxy-ethylamino)-4-nitrobenzamide as a yellow oil: MS (m/z) 300 (M+1); 1H NMR (CDCl3, 400 MHz) δ 8.24 (d, 1H), 8.06 (s, 1H), 7.78 (s, 1H), 7.42 (d, 2H), 7.35 (d, 1H), 7.13 (d, 1H), 6.95 (d, 1H), 3.09 (d, 3H), 2.28 (s, 3H), 2.25 (s, 3H), 1.58 (s, 1H).
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([N-]C(C)C)(C)C.[Li+].C([Li])CCC.CCCCCC.C(NC(C)C)(C)C.[O:45]1[CH2:50][CH2:49][CH2:48][CH2:47][CH:46]1[CH2:51][CH:52]=[O:53]>O1CCCC1>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[CH:12]=[C:11]2[CH:52]([OH:53])[CH2:51][CH:46]2[CH2:47][CH2:48][CH2:49][CH2:50][O:45]2)(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=CCC1CCCCO1
Reactant: O=S(=O)(c1ccccc1)n1ccc2cccnc21
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Solvent: CCCCCC
Product: O=S(=O)(c1ccccc1)n1c(C(O)CC2CCCCO2)cc2cccnc21
Temperature: -78 °C
Reaction time: 0.08 h
Yield: 60 %

Procedure:
To a suspension of 1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridine (5.0 g, 19.4 mmol) in dry tetrahydrofuran (125 mL) at −78° C. was added freshly prepared lithium diisopropylamide [prepared by adding 1.6 M n-butyllithium in n-hexane (18 mL, 29 mmol) to a 0° C. solution of diisopropylamine (4.4 mL, 31 mmol) in dry tetrahydrofuran (17 mL)] dropwise. The mixture was stirred at −78° C. for 5 min and then treated with (tetrahydro-pyran-2-yl)-acetaldehyde (4.6 g, 26 mmol) dropwise. The resulting mixture was stirred at −78° C. for 1 h and quenched with brine. The mixture was extracted with ethyl acetate (2×150 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash column chromatography (QingDao silica gel, 200-300 mesh, 25% ethyl acetate/hexanes) afforded 1-(1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-(tetrahydro-pyran-2-yl)-ethanol (4.5 g, 60%) as a colorless oil: LC/MS m/e calcd for C20H22N2O4S [M+H]+ 387.47, observed 387.2.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:37]=[CH:36][C:12]([NH:13][C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[C:21]([C:24]4[O:28][C:27]([CH:29]=[CH:30][C:31]([O:33]CC)=[O:32])=[CH:26][CH:25]=4)[CH:22]=3)[N:17]=[CH:16][N:15]=2)=[CH:11][C:10]=1[Cl:38])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>C1COCC1.C(O)C>[CH2:1]([O:8][C:9]1[CH:37]=[CH:36][C:12]([NH:13][C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[C:21]([C:24]4[O:28][C:27]([CH:29]=[CH:30][C:31]([OH:33])=[O:32])=[CH:26][CH:25]=4)[CH:22]=3)[N:17]=[CH:16][N:15]=2)=[CH:11][C:10]=1[Cl:38])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)C=Cc1ccc(-c2ccc3ncnc(Nc4ccc(OCc5ccccc5)c(Cl)c4)c3c2)o1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: O=C(O)C=Cc1ccc(-c2ccc3ncnc(Nc4ccc(OCc5ccccc5)c(Cl)c4)c3c2)o1
Yield: 102.4 %

Procedure:
Prepared according to Procedure H utilizing ethyl 3-(5-{4-[4-(benzyloxy)-3-chloroanilino]-6-quinazolinyl}-2-furyl)-2-propenoate (0.65 g) and aqueous sodium hydroxide (2M, 4 mL) in THF (8 mL) and ethanol (4 mL) to afford the title compound (0.63 g). Electrospray MS m/z 498 (MH+).
Reaction SMILES: [C:1]1([CH3:22])[CH:6]=[CH:5][C:4]([P:7]([C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=2)[C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)=[CH:3][CH:2]=1.[CH2:23]([I:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.P(=O)(O)(O)O>C1(C)C=CC=CC=1>[I-:30].[CH2:23]([P+:7]([C:4]1[CH:5]=[CH:6][C:1]([CH3:22])=[CH:2][CH:3]=1)([C:15]1[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=1)[C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: ICc1ccccc1
Reactant: Cc1ccc(P(c2ccc(C)cc2)c2ccc(C)cc2)cc1
Agent: O=P(O)(O)O
Solvent: Cc1ccccc1
Product: Cc1ccc([P+](Cc2ccccc2)(c2ccc(C)cc2)c2ccc(C)cc2)cc1
Product: [I-]
Temperature: 35 °C

Procedure:
Into a 50 milliliter glass reactor equipped with a thermometer connected to a temperature controller, a heating mantle, a condenser and a magnetic stirring bar, is charged 5 gms (0.0164 mole) of tri-p-tolylphosphine and 23 gms of toluene. The slurry is heated to 35° C. then 4.3 gms (0.0177 mole) of benzyl iodide is added. This reaction mass is heated to 40° C. in 15 minutes and maintained for 16 hours then cooled to 26° C. and the resulting phosphonium salt collected by filtration, then vacuum dried. There is obtained 3.6 gms of catalyst which has a melting point of 210° C.-218° C. and a chemical shift of 28.5 ppm (phosphoric acid reference).
Reaction SMILES: Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([Cl:8])[N:3]=1.[C-]#N.[K+].C[N:13]([CH:15]=[O:16])C>O>[Cl:8][C:4]1[N:3]=[C:2]([C:15]([NH2:13])=[O:16])[CH:7]=[N:6][CH:5]=1
Reactant: CN(C)C=O
Reactant: Clc1cncc(Cl)n1
Agent: [C-]#N
Agent: [K+]
Solvent: O
Product: NC(=O)c1cncc(Cl)n1
Temperature: 100 °C
Reaction time: 3 h
Yield: 32 %

Procedure:
To a solution of 2,6-dichloropyrazine (50 mg, 0.34 mmol) in DMF (1 mL) was added a solution of potassium cyanide (24 mg, 0.37 mmol) in H2O (1 mL). After stirring for 3 h at 100° C., the reaction mixture was cooled to r.t., poured into H2O (10 mL) and extracted with EtOAc three times. The combined organic layer was dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography (silica gel, EtOAc:Hexane, 3:7) to give 15 mg of the desired product. Yield: 32%.
Reaction SMILES: [CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.[F:7][C:8]([F:13])([F:12])[C:9]([OH:11])=[O:10]>[Cu]>[CH:1]1([O:11][C:9](=[O:10])[C:8]([F:13])([F:12])[F:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: C1=CCCCC1
Reactant: O=C(O)C(F)(F)F
Agent: [Cu]
Product: O=C(OC1CCCCC1)C(F)(F)F

Procedure:
Both experiments with copper metal deposited the white precipitate. During the course of the second experiment, solution samples were taken for analysis. Cyclohexene was found to be the major reaction product (ester/olefin=0.2) which slowly reacted with trifluoroacetic acid to form cyclohexyltrifluoroacetate. Thus, elimination of cyclohexene from a cyclohexyl-copper complex is the predominant reaction pathway under our conditions.
Reaction SMILES: [NH2:1][C:2]1[N:3]=[C:4]([CH:7]2[CH2:12][CH2:11][N:10]([C:13](=[O:25])[CH2:14][N:15]3[C:19]([CH3:20])=[CH:18][C:17]([C:21]([F:24])([F:23])[F:22])=[N:16]3)[CH2:9][CH2:8]2)[S:5][CH:6]=1.C(N(C(C)C)CC)(C)C.[CH:35]1([C:45](Cl)=[O:46])[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:38][CH2:37][CH2:36]1>ClCCl>[CH3:20][C:19]1[N:15]([CH2:14][C:13]([N:10]2[CH2:11][CH2:12][CH:7]([C:4]3[S:5][CH:6]=[C:2]([NH:1][C:45]([CH:35]4[C:44]5[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=5)[CH2:38][CH2:37][CH2:36]4)=[O:46])[N:3]=3)[CH2:8][CH2:9]2)=[O:25])[N:16]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:18]=1
Reactant: O=C(Cl)C1CCCc2ccccc21
Reactant: Cc1cc(C(F)(F)F)nn1CC(=O)N1CCC(c2nc(N)cs2)CC1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cc(C(F)(F)F)nn1CC(=O)N1CCC(c2nc(NC(=O)C3CCCc4ccccc43)cs2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 48.2 %

Procedure:
To a solution of 1-[4-(4-amino-thiazol-2-yl)-piperidin-1-yl]-2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethanone (120 mg, 0.32 mmol) and diisopropylethylamine (0.2 mL, 0.96 mmol) in dichloromethane (5 mL) is added dropwise a solution of 1,2,3,4-tetrahydro-naphthalene-1-carbonyl chloride (74 mg, 0.38 mmol) in dichloromethane (3 mL) at 0° C. After stirring overnight at RT, the solvent is evaporated and the residue is purified by flash chromatography on silica gel (ethylacetate/cyclohexane 1:1) to give 1,2,3,4-tetrahydro-naphthalene-1-carboxylic acid (2-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-thiazol-4-yl)amide (Compound No. 1.g.011, 82 mg, 48%). M.p.=179.2-181.3° C. 1H-NMR (400 MHz, CDCl3): δ=1.60-1.75 (m, 3H), 1.81-1.89 (m, 2H), 2.05-2.15 (m, 2H), 2.31 (s, 3H), 2.32-2.40 (m, 1H), 2.77-2.94 (m, 3H), 3.05-3.18 (m, 1H), 3.19-3.29 (m, 1H), 3.87 (t, 1H), 3.95-4.04 (m, 1H), 4.50-4.59 (m, 1H), 4.90-5.06 (2d, 2H, diastereotopic protons), 6.32 (s, 1H), 7.25-7.30 (m, 4H), 7.49 (s, 1H), 7.79 (br, 1H). MS: m/z=532 (M+1).
Reaction SMILES: CC(C)([O-])C.[K+].[N+:7]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=1)([O-:9])=[O:8].ClC1C=CC(O[CH2:24][C:25]#[N:26])=CC=1.Cl>CN(C=O)C>[CH3:17][O:16][C:13]1[CH:14]=[CH:15][C:10]([N+:7]([O-:9])=[O:8])=[C:11]([CH2:24][C:25]#[N:26])[CH:12]=1
Reactant: N#CCOc1ccc(Cl)cc1
Reactant: COc1ccc([N+](=O)[O-])cc1
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1ccc([N+](=O)[O-])c(CC#N)c1
Temperature: -10 °C
Reaction time: 0.5 h
Yield: 39.3 %

Procedure:
24.0 g (214 mmol) potassium-tert-butoxide in 100 mL DMF were slowly added dropwise to a solution of 13.17 g (86.0 mmol) 4-nitroanisole and 18.0 g (107 mmol) 4-chlorophenoxyacetonitrile in 50 mL DMF. The reaction mixture was stirred for 30 min at −10° C. and then poured into 300 g of a 1:1 mixture of conc. HCl and ice. After extraction with EtOAc the organic phase was washed with water, dried and concentrated to dryness by rotary evaporation in vacuo with gentle heating. The residue was treated with a 1:1 mixture of PE/EtOAc and the product that crystallised out was suction filtered. After washing with a 1:1 mixture of PE/EtOAc the crystals were dried in the air. 6.5 g of the desired product was obtained.
Reaction SMILES: [CH2:1]([N:4]([CH2:19][CH2:20][CH3:21])[CH:5]1[CH2:14][CH2:13][C:12]2[C:7](=[C:8]([O:15][CH2:16][CH2:17][NH2:18])[CH:9]=[CH:10][CH:11]=2)[CH2:6]1)[CH2:2][CH3:3].[C:22](=[O:25])([O-])[O-].[K+].[K+].[CH3:28][S:29](Cl)(=[O:31])=[O:30].C(OC(C)C)(C)C.C(O)C>C1(C)C=CC=CC=1>[CH2:19]([N:4]([CH2:1][CH2:2][CH3:3])[CH:5]1[CH2:14][CH2:13][C:12]2[C:7](=[C:8]([O:15][CH2:16][CH2:17][NH:18][S:29]([CH3:28])(=[O:31])=[O:30])[CH:9]=[CH:10][CH:11]=2)[CH:6]1[CH:22]=[O:25])[CH2:20][CH3:21]
Reactant: CS(=O)(=O)Cl
Reactant: CCCN(CCC)C1CCc2cccc(OCCN)c2C1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)OC(C)C
Solvent: Cc1ccccc1
Solvent: CCO
Product: CCCN(CCC)C1CCc2cccc(OCCNS(C)(=O)=O)c2C1C=O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
1.45 g (5 mmol) of 2-dipropylamino-8-(2-aminoethoxy)-1,2,3,4-tetrahydronaphthalene and 1.38 g (10 mmol) of potassium carbonate were initially introduced into 20 ml of toluene. 0.63 g (5.5 mmol) of methanesulphonyl chloride was then added dropwise, and the mixture was subsequently stirred for 3 h at room temperature. The mixture was then filtered and evaporated. The residue obtained was stirred with petroleum ether and filtered off under suction. The product, obtained by chromatography over silica gel 60, 40-63 μm, using diisopropyl ether/ethanol, 3:2, was recrystallized from petroleum ether with activated charcoal.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:13]=[CH:12][C:6]2[CH2:7][NH:8][CH2:9][CH2:10][S:11][C:5]=2[CH:4]=1.Cl[C:15]1[CH:24]=[C:23]([Cl:25])[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([CH3:26])[CH:21]=2)[N:16]=1>C(O)CCC>[Cl:25][C:23]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([CH3:26])[CH:21]=2)[N:16]=[C:15]([N:8]2[CH2:7][C:6]3[CH:12]=[CH:13][C:3]([O:2][CH3:1])=[CH:4][C:5]=3[S:11][CH2:10][CH2:9]2)[CH:24]=1
Reactant: COc1ccc2c(c1)SCCNC2
Reactant: Cc1ccc2nc(Cl)cc(Cl)c2c1
Solvent: CCCCO
Product: COc1ccc2c(c1)SCCN(c1cc(Cl)c3cc(C)ccc3n1)C2
Temperature: 160 °C
Reaction time: 2.5 h
Yield: 49.7 %

Procedure:
A mixture of 8-methoxy-2,3,4,5-tetrahydro-1,4-benzothiazepine (0.63 g, 3.2 mmol), 2,4-dichloro-6-methylquinoline (0.68 g, 3.2 mmol) and n-butanol (4 mL) was heated with stirring in a 5 mL of microwave process vial for 2.5 hours at 160° C. under microwave irradiation. The solvent was removed by concentration in vacuo. The residue was dissolved in a mixture solvent of ethanol and dichloromethane and then concentrated in vacuo to remove dichloromethane. The formed precipitate was collected by filtration, which was washed with diethyl ether and petroleum ether, dried in vacuo to afford 0.59 g of the product as a pale white solid (yield was 50%). MS obsd. (ESI+) [(M+H)+] 371.
Reaction SMILES: [C:1]([O:4][CH2:5][CH:6]=[CH:7][S:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])(=[O:3])[CH3:2].[Br:15]Br.C(N(CC)CC)C>CCOCC.O>[C:1]([O:4][CH2:5][CH:6]=[C:7]([Br:15])[S:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])(=[O:3])[CH3:2]
Reactant: BrBr
Reactant: CCCCCCSC=CCOC(C)=O
Solvent: CCN(CC)CC
Solvent: O
Solvent: CCOCC
Product: CCCCCCSC(Br)=CCOC(C)=O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 3-hexylthio-2-propenyl acetate (1.3 g, 6.0 mmol) in 10 ml of ether cooled to -10° is added bromine (1.05 g, 0.34 ml, 6.6 mmol). The mixture is stirred at ambient temperature for 30 min., then cooled to 0° and triethylamine (3.0 g, 4.18 ml, 30.0 mmol) is added. The reaction mixture is stirred overnight at RT, then diluted with water and extracted with hexane. The extract is washed with 2N H2SO4, water, saturated NaHCO3 and brine and is dried. The crude product is purified by prep. TLC on silica gel eluting with 20% ethyl acetate/hexane. The upper band is collected to give 3-bromo-3-hexylthio-2-propenyl acetate. The lower band is collected to give 2-bromo-3-hexylthio-2propenyl acetate.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[C:9]([N:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)(=[O:11])[CH3:10]>>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([N:15]2[CH2:16][CH2:17][N:12]([C:9](=[O:11])[CH3:10])[CH2:13][CH2:14]2)=[N:3][CH:4]=1
Reactant: Brc1ccc(Br)nc1
Reactant: CC(=O)N1CCNCC1
Product: CC(=O)N1CCN(c2ccc(Br)cn2)CC1

Procedure:
Prepared from 2,5-dibromopyridine and 1-acetylpiperazine by the method of Example 13 (b).
Reaction SMILES: [ClH:1].C(OCC)(=O)C.C(OC([NH:15][CH2:16][C:17]([NH:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][CH:21]=1)=[O:18])=O)(C)(C)C>>[ClH:1].[NH2:15][CH2:16][C:17]([NH:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][CH:21]=1)=[O:18]
Reactant: CC(C)(C)OC(=O)NCC(=O)Nc1ccc(C#N)cc1
Agent: Cl
Solvent: CCOC(C)=O
Product: N#Cc1ccc(NC(=O)CN)cc1
Reaction time: 18 h

Procedure:
45.5 ml of a solution of 4N-hydrogen chloride/ethyl acetate was added to 10 g of 2-(tert-butoxycarbonylamino)-N-(4-cyanophenyl)acetamide in a closed vessel and stirred for 18 hours. The crystals formed were removed by filtration, washed with ethyl acetate and then dried under a reduced pressure to obtain 7.7 g of 2-amino-N-(4-cyanophenyl)acetamide hydrochloride. 58.8 ml of an 5 aqueous saturated solution of sodium hydrogencarbonate and 20 ml of water were added to 3.7 g of the hydrochloride and stirred for 1 hour. The crystals thus formed were taken out by filtration and dried under a reduced pressure to obtain 2.5 g of 2-amino-N-(4-cyanophenyl)acetamide.
Reaction SMILES: NC1C=C([C:15]2[C:20]([C:21](N)=[O:22])=[CH:19][CH:18]=[CH:17][CH:16]=2)C(C2C=CC(N)=CC=2)=CC=1.[N+:24]([C:27]1[CH:28]=[C:29]([NH2:42])[C:30]([C:33]2[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][CH:34]=2)=[CH:31][CH:32]=1)([O-:26])=[O:25].C(Cl)(=O)C1C=CC=CC=1>CN(C1C=CN=CC=1)C.CN1CCCC1=O>[C:21]([N:42]=[C:29]1[CH2:28][C:27]([N+:24]([O-:26])=[O:25])=[CH:32][CH:31]=[C:30]1[C:33]1[CH:34]=[CH:35][C:36]([N+:39]([O-:41])=[O:40])=[CH:37][CH:38]=1)(=[O:22])[C:20]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: Nc1cc([N+](=O)[O-])ccc1-c1ccc([N+](=O)[O-])cc1
Reactant: NC(=O)c1ccccc1-c1cc(N)ccc1-c1ccc(N)cc1
Agent: CN(C)c1ccncc1
Solvent: CN1CCCC1=O
Solvent: O=C(Cl)c1ccccc1
Product: O=C(N=C1CC([N+](=O)[O-])=CC=C1c1ccc([N+](=O)[O-])cc1)c1ccccc1

Procedure:
A method for preparing 4,4'-diaminobiphenyl-2-benzamide which consists essentially of the steps of reacting 4,4'-dinitro-2-biphenylamine with benzoyl chloride in the presence of 4-dimethylamine pyridine in N-methyl-2-pyrrolidinone (NMP) to give 2-(N-benzoylimino)-4,4'-dinitrobiphenyl, and hydrogenating said 2-(N-benzoylimino)-4,4:dinitrobiphenyl.
Reaction SMILES: [CH:1]1[CH2:6][CH:5]=[CH:4][CH2:3][CH:2]=1.C([C:9]1[C:15](=O)[C:14](Cl)=[C:13](Cl)[C:11](=[O:12])[C:10]=1C#N)#N>>[C:1]1([CH:10]2[CH2:9][CH2:15][CH2:14][CH2:13][C:11]2=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Reactant: C1=CCC=CC1
Product: O=C1CCCCC1c1ccccc1
Yield: 56 %

Procedure:
Rh2(S-DOSP)4-catalyzed decomposition of the cyclic vinyldiazoacetate 58 in the presence of 1,3-cyclohexadiene 40 resulted in the formation of the 1,4-cyclohexadiene 59 in 73% yield and 97% ee. The absolute configuration of compound 59 was determined by DDQ oxidation and ozonolysis to afford the 2-phenylcyclohexanone in a 56% yield. Found [α]26D=−17 (c=1.66, PhH) . Lit. value: [α]24D=−113.5 (c=0.60, PhH), S-isomer. (Berti et al., J. Chem. Soc., pp. 3371-3377 (1971), which is hereby incorporated by reference.) Similarly, decomposition of the dienyldiazoacetate 60 in the presence of 1,3-cyclohexadiene 40 resulted in the formation of 61 (60% yield and 99% ee), in which both diene components have moved out of conjugation.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][O:9][C:10]2[CH:18]=[C:17]3[C:13]([C:14]([C:21]4[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=4)=[C:15](Br)[C:16]3=[O:19])=[CH:12][CH:11]=2)[CH2:3][CH2:2]1.O1CCN(CCOC2C=C3C(C(C4C=CC=CC=4)=C(Br)C3=O)=CC=2)CC1.[N:57]1[CH:62]=[C:61](B(O)O)[CH:60]=[N:59][CH:58]=1>>[O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][O:9][C:10]2[CH:18]=[C:17]3[C:13]([C:14]([C:21]4[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=4)=[C:15]([C:61]4[CH:62]=[N:57][CH:58]=[N:59][CH:60]=4)[C:16]3=[O:19])=[CH:12][CH:11]=2)[CH2:3][CH2:2]1
Reactant: O=C1C(Br)=C(c2ccc(C(F)(F)F)cc2)c2ccc(OCCN3CCOCC3)cc21
Reactant: OB(O)c1cncnc1
Agent: O=C1C(Br)=C(c2ccccc2)c2ccc(OCCN3CCOCC3)cc21
Product: O=C1C(c2cncnc2)=C(c2ccc(C(F)(F)F)cc2)c2ccc(OCCN3CCOCC3)cc21
Yield: 25 %

Procedure:
The procedure of Step 7 of Example 1 was repeated except for using 6-(2-morpholinoethoxy)-2-bromo-3-(4-(trifluoromethyl)phenyl)-1H-inden-1-one obtained in Step 6 of Example 32 as a starting material instead of 6-(2-morpholinoethoxy)-2-bromo-3-phenyl-1H-inden-1-one, 5-pyrimidinylboronic acid instead of 3-pyridinylboronic acid, and being purified by prep HPLC (CH3CN/H2O=7:3) to obtain the title compound (25%).
Reaction SMILES: [Li]CCCC.C(NC(C)C)(C)C.[Cl:13][C:14]1[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=1.[CH2:20]([O:22]C=O)C>O1CCCC1.O>[Cl:13][C:14]1[CH:19]=[CH:18][N:17]=[CH:16][C:15]=1[CH:20]=[O:22]
Reactant: Clc1ccncc1
Reactant: CCOC=O
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Solvent: O
Product: O=Cc1cnccc1Cl
Temperature: 0 °C
Reaction time: 0.75 h

Procedure:
35.8 ml of n-BuLi (1.6 M in hexane; 57 mmol, 1 eq.) is added to a solution of 7.5 ml of N,N-diisopropylamine in 100 ml of tetrahydrofuran at −60° C. in nitrogen. The mixture is then left under stirring at 0° C. for 45 min before being cooled to −90° C. To this solution, a solution of 6.5 g of 4-chloropyridine (57 mmol, 1 eq.) in 25 ml of tetrahydrofuran is added drop by drop such that the temperature remains between −70 and −60° C. The mixture is left under stirring at −70° C. for 3 hrs. Then, a solution of 5.1 ml of ethylformate (63 mmol, 1.1 eq.) in 10 ml of tetrahydrofuran is added. The mixture is left under stirring for 1 hr at −65/−70° C. and the reaction mixture is then returned to −10° C. and hydrolysed with water. The organic phase is separated and the aqueous phase is extracted 3 times with ethyl acetate. The combined organic phases are dried on Na2SO4 and the solvent is evaporated.