Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([S:3]([CH2:6][CH2:7][C:8]12[CH2:15][CH2:14][C:11]([C:16]([NH:18][CH3:19])=O)([CH2:12][CH2:13]1)[CH2:10][CH2:9]2)(=[O:5])=[O:4])[CH3:2].C(Cl)(=O)C(Cl)=O.[F:26][C:27]([F:40])([F:39])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[C:34]1NN=[N:36][N:35]=1>C(Cl)Cl.CN(C=O)C>[CH2:1]([S:3]([CH2:6][CH2:7][C:8]12[CH2:15][CH2:14][C:11]([C:16]3[N:18]([CH3:19])[C:34]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=4[C:27]([F:26])([F:40])[F:39])=[N:35][N:36]=3)([CH2:12][CH2:13]1)[CH2:10][CH2:9]2)(=[O:5])=[O:4])[CH3:2]
Reactant: CCS(=O)(=O)CCC12CCC(C(=O)NC)(CC1)CC2
Reactant: FC(F)(F)c1ccccc1-c1nnn[nH]1
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CCS(=O)(=O)CCC12CCC(c3nnc(-c4ccccc4C(F)(F)F)n3C)(CC1)CC2
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Methyl amide 10-5 (220 mg, 0.77 mmol) was dissolved in anhydrous methylene chloride (2 mL) and treated with oxalyl chloride (2M in methylene chloride, 0.77 mL, 1.54 mmol) and DMF (2 drops). The solution was stirred at room temperature for 1 h, then solvent removed by evaporation under diminished pressure. The residue was redissolved in anhydrous toluene (2 mL) and treated with 5[2-(trifluoromethyl)phenyl]1H-tetrazole (214 mg, 1 mmol). The mixture was refluxed for 18 h. The reaction was cooled to room temperature and the cream-colored precipitate was filtered and washed to give 300 mg of crude product as the HCl salt. The salt was taken up in methylene chloride/1N HCl and the aqueous layer was washed with two additional portions of methylene chloride. The organic layers were combined and evaporated and the residue was chromatographed by flash silica gel chromatography. Elution was carried out with a gradient ranging from 0 to 5% methanol/methylene chloride. The appropriate fractions were combined and evaporated to give 3-{4-[2-(ethylsulfonyl)ethyl]bicyclo[2.2.2]oct-1-yl}-4-methyl-5-[2-(trifluoromethyl)phenyl]4H-1,2,4-triazole (10-6) as a white powder. MS (ESI+)=456.2 (M+1); 1H NMR (500 MHz, CDCl3): δ 1.46 (3H, t, J=7.3 Hz), 1.63 (6H, m), 1.78 (2H, m), 2.19 (6H, m), 2.96 (2H,m), 3.05 (2H, q, J=7.2 Hz), 3.50 (3H, s), 7.56 (1H, m), 7.72 (2H, m), 7.87 (1H, m) ppm.
Reaction SMILES: [C:1]([O:4][C:5]1[C:14]2[O:13][CH2:12][C:11](=O)[N:10]([CH2:16][CH2:17][O:18][CH:19]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:9]=2[CH:8]=[CH:7][CH:6]=1)(=[O:3])[CH3:2].B.C1COCC1.O>C1COCC1>[C:1]([O:4][C:5]1[C:14]2[O:13][CH2:12][CH2:11][N:10]([CH2:16][CH2:17][O:18][CH:19]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:9]=2[CH:8]=[CH:7][CH:6]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Oc1cccc2c1OCC(=O)N2CCOC(c1ccccc1)c1ccccc1
Agent: B
Solvent: O
Solvent: C1CCOC1
Product: CC(=O)Oc1cccc2c1OCCN2CCOC(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 90.3 %

Procedure:
8-acetoxy-4-(2-(diphenylmethoxy)ethyl)-3-oxo-3,4-dihydro-2H-1,4-benzooxazine (630 mg) was dissolved in THF (10 ml), and a 1.0M borane THF solution (4.5 ml) was added to the resultant solution at 0° C., followed by stirring at room temperature for 4 hours. After water was added to the reaction solution to terminate reaction, the reaction solution was extracted with ethyl acetate. The resultant organic layer was washed with water, saturated sodium bicarbonate water, water and saturated brine, dried over sodium sulfate, and then concentrated. The residue was purified by medium-pressure column chromatography (solvent:ethyl acetate/cyclohexane=1/5) to obtain the colorless oily object compound (550 mg, yield 90%).
Reaction SMILES: [NH:1]1[C:10](=[O:11])[C:9]2[NH:8][CH:7]=[N:6][C:5]=2[N:4]=[C:2]1[NH2:3].[O:12]1[CH:18]2[CH:13]1[CH:14]=[CH:15][CH2:16][CH2:17]2.CO>[Pd].O1CCCC1>[OH:12][CH:13]1[CH2:18][CH2:17][CH:16]([N:6]2[CH:7]=[N:8][C:9]3[C:10](=[O:11])[NH:1][C:2]([NH2:3])=[N:4][C:5]2=3)[CH:15]=[CH:14]1
Reactant: C1=CC2OC2CC1
Reactant: Nc1nc2nc[nH]c2c(=O)[nH]1
Agent: [Pd]
Solvent: CO
Solvent: C1CCOC1
Product: Nc1nc2c(ncn2C2C=CC(O)CC2)c(=O)[nH]1
Yield: 25.1 %

Procedure:
7.56 g (50 mmol) of guanine are reacted with 2 mol % of the palladium(0) catalyst prepared in situ as above and one equivalent of 3,4-epoxycyclohexene in tetrahydrofuran first at 0° C. and then for 8 hours under reflux temperature, and the mixture is then poured into methanol. The reaction mixture is concentrated and the residue is taken up in 2-propanol and filtered off with suction. The residue is recrystallized first from ethanol with active charcoal and then from water. 3.1 g (25.1% of theory) of 9-[(1RS,4SR)-4-hydroxy-cyclohex-2-en-1-yl]guanine of melting point >300° C. are obtained. 1H NMR (270 MHz, d6 -DMSO); δ[ppm]: 10.57 (s, 1H), 7.60 (s, 1H), 6.46 (s, 2H), 6.05 (m, 1H), 5.77 (m, 1H), 4.91 (d, 1H), 4.79 (m, 1H), 4.06 (m, 1H), 1.95-1.75 (m, 3H), 1.53 (m, 1H).
Reaction SMILES: C(OC([N:8]1[CH2:17][CH2:16][C:15]2[NH:14][N:13]=[C:12]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=3)[C:11]=2[CH2:10][CH2:9]1)=O)(C)(C)C.Cl[CH:26]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1.C(OC(N1CCC2NN(C3CCCCCCC3)C(C3C=CC(Cl)=CC=3)C=2CC1)=O)(C)(C)C>>[Cl:24][C:21]1[CH:20]=[CH:19][C:18]([C:12]2[C:11]3[CH2:10][CH2:9][NH:8][CH2:17][CH2:16][C:15]=3[N:14]([CH:26]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)[N:13]=2)=[CH:23][CH:22]=1
Reactant: CC(C)(C)OC(=O)N1CCc2[nH]nc(-c3ccc(Cl)cc3)c2CC1
Reactant: ClC1CCCCCCC1
Agent: CC(C)(C)OC(=O)N1CCC2=C(CC1)C(c1ccc(Cl)cc1)N(C1CCCCCCC1)N2
Product: Clc1ccc(-c2nn(C3CCCCCCC3)c3c2CCNCC3)cc1
Yield: 43.8 %

Procedure:
The title compound (47 mg) was prepared from 3-(4-chloro-phenyl)-4,5,7,8-tetrahydro-1H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 103, Step B; 0.30 mmol) using chloro-cyclooctane (1.0 mmol) in place of chloro-cyclobutane according to Example 238. The reaction sequence also yielded 3-(4-chloro-phenyl)-2-cyclooctyl-1,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester in the alkylation step. MS (ESI): exact mass calculated for C21H28ClN3, 357.20; found, m/z 358.5 [M+H]+. 1H NMR (500 MHz, CD3OD): 7.50-7.44 (m, 4H), 4.49-4.45 (m, 1H), 3.51-3.48 (m, 2H), 3.38-3.36 (m, 2H), 3.33-3.32 (m, 2H), 3.05-3.04 (m, 2H), 2.21-2.18 (m, 2H), 1.97-1.88 (m, 4H), 1.72-1.64 (m, 8H).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C:2]1=[O:10].[N:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1)=O.C([O-])(=O)C.[NH4+]>C(O)(=O)C>[N:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1)=[C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][C:2]1=[O:10]
Reactant: O=C1Cc2ccccc2N1
Reactant: O=C(c1ccccn1)c1ccccn1
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CC(=O)O
Product: O=C1Nc2ccccc2C1=C(c1ccccn1)c1ccccn1
Temperature: 100 °C
Yield: 78.8 %

Procedure:
To 50 ml of acetic acid were poured 4.2 g of 97% oxindole, 5.0 g of di-2-pyridylketone, and 20.9 g of ammonium acetate. The mixture was heated for 12 hours at 100° C. Thereafter, the solvent was evaporated, and the residue was extracted with ethyl acetate. The extract was washed with water, saturated sodium bicarbonate water, and saturated brine, and subsequently dried over sodium sulfate. The resultant crude product was purified by silica gel column chromatography (ethyl acetate), to thereby obtain 6.4 g (yield 78.8%) of the title compound in the form of yellow crystals. The melting point and elementary analysis data are shown in Table 17, and NMR and MS spectrum data are shown in Table 18.
Reaction SMILES: C(S[S:4][C:5]#[N:6])#N.[NH2:7][C:8]1[C:17]2[C:12](=[C:13]([N+:18]([O-:20])=[O:19])[CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10][CH:9]=1.[OH-].[NH4+]>O>[NH2:7][C:8]1[C:17]2[C:12](=[C:13]([N+:18]([O-:20])=[O:19])[CH:14]=[CH:15][CH:16]=2)[C:11]([S:4][C:5]#[N:6])=[CH:10][CH:9]=1
Reactant: N#CSSC#N
Reactant: Nc1cccc2c([N+](=O)[O-])cccc12
Agent: [NH4+]
Agent: [OH-]
Solvent: O
Product: N#CSc1ccc(N)c2cccc([N+](=O)[O-])c12
Reaction time: 1 h

Procedure:
The cold thiocyanogen solution was added to the stirred solution of 1-amino-5-nitronaphthalene, maintaining the temperature at 5°-15° C. The mixture was stirred a further one hour at 5°-15° C. and then made just alkaline (pH 7-8) by addition of concentrated ammonium hydroxide solution. The reaction mixture, after filtering from a small amount of insoluble material, was evaporated to dryness. The solid obtained was stirred with water, filtered, washed and dried.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]([NH:7][C:8]2[CH:9]=[C:10]([OH:14])[CH:11]=[CH:12][CH:13]=2)[S:5][CH:6]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:22][CH:23]=[C:24]([CH3:26])[CH3:25]>CC(C)=O>[CH3:1][C:2]1[N:3]=[C:4]([NH:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([O:14][CH2:22][CH:23]=[C:24]([CH3:26])[CH3:25])[CH:9]=2)[S:5][CH:6]=1
Reactant: CC(C)=CCBr
Reactant: Cc1csc(Nc2cccc(O)c2)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CC(C)=CCOc1cccc(Nc2nc(C)cs2)c1
Yield: 59 %

Procedure:
Following the procedure general for O-alkylation, Method A, a mixture of 3-(4-methylthiazol-2-ylamino)phenol (74 mg, 0.36 mmol) and K2CO3 (55 mg, 0.39 mmol) in acetone (3.6 mL) was treated with 4-bromo-2-methyl-2-butene (0.05 mL, 0.43 mmol). The reaction mixture was heated at reflux for 4 h. The title compound was obtained after purification by flash chromatography on silica gel (hexane:EtOAc 7/3) in 59% yield (58 mg).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][C:9](=[O:12])[CH2:10]Cl.[H-].[Na+].Cl.C(OCC)C>CN(C)C=O>[O:8]1[C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[O:1][CH2:10][C:9]1=[O:12]
Reactant: O=C(CCl)Oc1ccccc1O
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: O=C1COc2ccccc2O1
Reaction time: 3 h

Procedure:
161.5 g (0.87 mole) of chloroacetic acid 2-hydroxyphenyl ester were dissolved in 300 ml of anhydrous dimethylformamide. 20.88 g (0.87 mole) of sodium hydride were added portion by portion with indirect ice refrigeration. After the ending of the addition, heating was carried out for 3 hours at 35° C. followed by hydrolysis in which the reaction mixture was distributed between 600 ml 1N hydrochloric acid and 600 ml diethyl ether. The organic phase was dried with sodium sulfate and was concentrated by evaporation. 117.6 g (90% of the theoretical amount) of raw 3-H-benzo-1,4-dioxin-2-one were obtained. The light-brown oil which was accumulated at first was crystallized in the course of time (melting point 45°-53° C.2).
Reaction SMILES: [CH2:1]([CH:3]1[CH2:11][C:10]2[C:5](=[C:6]([Cl:14])[C:7]([Cl:13])=[C:8]([OH:12])[CH:9]=2)[C:4]1=[O:15])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:23][C:24]#[N:25].[I-].[K+]>CC(C)=O>[O:15]=[C:4]1[C:5]2[C:10](=[CH:9][C:8]([O:12][CH2:23][C:24]#[N:25])=[C:7]([Cl:13])[C:6]=2[Cl:14])[CH2:11][CH:3]1[CH2:1][CH3:2]
Reactant: N#CCCl
Reactant: CCC1Cc2cc(O)c(Cl)c(Cl)c2C1=O
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCC1Cc2cc(OCC#N)c(Cl)c(Cl)c2C1=O

Procedure:
A mixture of 2-ethyl-5-hydroxy-6,7-dichloroindanone (24.5 g., 0.1 mole), anhydrous potassium carbonate (13.8 g., 0.10 mole), chloroacetonitrile (7.55 g., 0.10 mole) and potassium iodide (1.66 g.) in acetone (0.5 l.) is refluxed for 18 hours. The product which precipitates upon addition of water to the reaction mixture (20 g., 71%) melts at 139°-141° C. after recrystallization from butyl chloride.
Reaction SMILES: [C:1](OC)(=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].Cl[Sn](Cl)(Cl)Cl.[Si](Cl)(Cl)(Cl)Cl>ClC1C=CC=CC=1>[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH:9]=[CH:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)OC
Agent: Cl[Si](Cl)(Cl)Cl
Agent: Cl[Sn](Cl)(Cl)Cl
Solvent: Clc1ccccc1
Product: CCCCCCCCC=CCCCCCCCC
Yield: 16 %

Procedure:
Several other runs were carried out to demonstrate the use of embodiment A for the disproportionation of unsaturated esters. In run 201, 21 mmoles of methyl oleate, 0.22 mmoles of (methoxyphenylcarbene)pentacarbonyltungsten(O), 2.2 mmoles of SnCl4, and 2.2 mmoles of SiCl4 in about 18 ml of chlorobenzene were stirred at 55° C. for 72 hours. The reaction product mixture contained a 16% yield of 9-octadecene and about a 10% yield of dimethyl 9-octadecen-1,18-dioate. The yield of 9-octadecene is increased over the yield of run 168 which did not use SiCl4.
Reaction SMILES: [CH:1]1([N:7]([CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:8](=[O:20])[NH:9][C:10]2[S:11][C:12]([S:15][CH2:16][C:17]([OH:19])=[O:18])=[CH:13][N:14]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C1(=O)CCCCC1>C(OC(=O)C)C>[CH:23]12[CH2:28][CH:27]([CH2:25][CH2:24]1)[CH2:26][CH:22]2[CH2:21][N:7]([CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)[C:8](=[O:20])[NH:9][C:10]1[S:11][C:12]([S:15][CH2:16][C:17]([OH:19])=[O:18])=[CH:13][N:14]=1
Reactant: O=C(O)CSc1cnc(NC(=O)N(CCc2ccccc2)C2CCCCC2)s1
Solvent: O=C1CCCCC1
Solvent: CCOC(C)=O
Product: O=C(O)CSc1cnc(NC(=O)N(CC2CC3CCC2C3)C2CCCCC2)s1

Procedure:
Prepared as described for the synthesis of [2-(3-cyclohexyl-3-phenethyl-ureido)-thiazol-5-ylsulfanyl]-acetic acid, from c-bicyclo[2.2.1]hept-2-yl-methylamine, cyclohexanone and 2-amino-thiazol-5-ylsulfanyl)-acetic acid ethyl ester.
Reaction SMILES: [CH:1]1[CH:6]=[CH:5][C:4]([NH:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([Br:14])[CH:9]=2)=[CH:3][CH:2]=1.[C:15](Cl)([Cl:17])=[O:16].CCCCCC.C(OCC)(=O)C>C1(C)C=CC=CC=1>[Br:14][C:10]1[CH:9]=[C:8]([N:7]([C:4]2[CH:3]=[CH:2][CH:1]=[CH:6][CH:5]=2)[C:15]([Cl:17])=[O:16])[CH:13]=[CH:12][CH:11]=1
Reactant: Brc1cccc(Nc2ccccc2)c1
Reactant: O=C(Cl)Cl
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: Cc1ccccc1
Product: O=C(Cl)N(c1ccccc1)c1cccc(Br)c1
Temperature: 90 °C

Procedure:
A solution of 15.0 g (60.4 mmole) of 3-bromodiphenylamine [i.e., N-(3-bromophenyl)aniline] [S. Kurzepa and J. Cieslak, Roczniki Chem., 34, 111 (1960)] in 30 ml of toluene and 50 ml (116 mmole) of 1.93M phosgene in toluene were combined and heated at 90° C. under nitrogen for 2 hours with stirring. The red orange colored solution was cooled, flushed with nitrogen for 2 hours to remove excess Phosgene and concentrated in vacuo to 18.0 g (58.0 mmole, 96%) of red orange oil which was homogeneous by TLC (4:1 hexane-ethyl acetate, Rf =0.80).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](=O)[CH3:10])=[CH:4][CH:3]=1.[ClH:12].[CH2:13]([NH2:15])[CH3:14].C([BH3-])#N.[Na+]>CO>[ClH:12].[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([NH:15][CH2:13][CH3:14])[CH3:10])=[CH:4][CH:3]=1
Reactant: CC(=O)Cc1ccc(Br)cc1
Reactant: CCN
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: CCNC(C)Cc1ccc(Br)cc1
Temperature: 22 °C
Reaction time: 16 h
Yield: 58 %

Procedure:
A mixture of 1-(4-bromophenyl)propan-2-one (5 grams, 23.5 mmole), ethylamine hydrochloride (19 grams, 0.23 mole) and sodium cyanoborohydride (2.22 grams, 0.035 mole) in methanol (100 ml) was stirred at 22° C. for 16 hours. The mixture was concentrated under reduced pressure and the residue was partitioned between 1.0N sodium hydroxide (25 ml) and ethyl ether (60 ml). The organic phase was dried (anhydrous magnesium sulfate) and concentrated under reduced pressure. The oily base was converted to the hydrochloride salt and recrystallized from ethanol/ethyl ether to give [2-(4-bromophenyl)-1-methylethyl]ethylamine hydrochloride (3.8 grams, 58%), m.p. 175-176° C.
Reaction SMILES: [Na].[F:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]#[N:11].[N:12]([C:15]1[CH:23]=[CH:22][CH:21]=[CH:20][C:16]=1[C:17]([OH:19])=O)=[N+:13]=[N-:14]>C(O)C>[F:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:10]2=[N:11][C:17](=[O:19])[C:16]3[C:15]([N:12]2[NH:13][N:14]=1)=[CH:23][CH:22]=[CH:21][CH:20]=3
Reactant: [N-]=[N+]=Nc1ccccc1C(=O)O
Reactant: N#CCc1ccccc1F
Agent: [Na]
Solvent: CCO
Product: O=c1nc2c(-c3ccccc3F)n[nH]n2c2ccccc12
Reaction time: 0.25 h
Yield: 99.7 %

Procedure:
Sodium (0.55 g, 24 mmol) was dissolved in dry ethanol (25 ml) at room temperature under nitrogen. 2-Fluorophenylacetonitrile (1.9 ml, 15 mmol) was added and the orange solution was stirred for 15 min, followed by dropwise addition of a solution of 2-azidobenzoic acid (1.97 g, 12.1 mmol) in diy ethanol (20 ml). The thick, white gel was stirred at room temperature for 45 min then refluxed for 18 h. Solvent was removed by evaporation and water (40 ml) was added. The yellow suspension was acidified with aqueous citric acid (1 M). The precipitate was collected, washed with water and dried in vacuo at room temperature to give 3-(2-fluorophenyl)-1,2,3-triazolo[1,5-α]quinazolin-5-one (3.38 g, 100%) as an off-white powder, m.p. 238-241° C. (DMF). Found: C, 64.33; H, 3.06; N, 20.29. C15H9FN4O requires C, 64.28; H, 3.24; N, 19.99%. δH (360 MHz; DMSO) 7.33-7.38 (2H, m), 7.46-7.55 (1H, m), 7.69-7.73 (2H, m), 8.02 (1H, ddd, J=9, 9 and 1), 8.24 (1H, dd, J=8 and 1), 8.38 (1H, d, J=8) and 12.40 (1H, br s); m/z (ES+) 821 (M+H+).
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]2[C:18](=[O:19])[C:13]3[NH:14][CH2:15][CH:16]=[CH:17][C:12]=3[CH2:11][CH2:10][C:9]=2[CH:20]=1)(=[O:4])=[O:3].[CH3:21][N:22]1[CH2:27][CH2:26][CH:25](Cl)[CH2:24][CH2:23]1.[Mg].C1COCC1>C(Cl)Cl>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]2[C:18]([CH:25]3[CH2:26][CH2:27][N:22]([CH3:21])[CH2:23][CH2:24]3)([OH:19])[C:13]3=[N:14][CH:15]=[CH:16][CH:17]=[C:12]3[CH2:11][CH2:10][C:9]=2[CH:20]=1)(=[O:4])=[O:3]
Reactant: CS(=O)(=O)c1ccc2c(c1)CCC1=C(NCC=C1)C2=O
Reactant: CN1CCC(Cl)CC1
Agent: [Mg]
Solvent: C1CCOC1
Solvent: ClCCl
Product: CN1CCC(C2(O)c3ccc(S(C)(=O)=O)cc3CCc3cccnc32)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 61 %

Procedure:
8-Methylsulfonyl-5,6-dihydro-1H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-one (1 g) was dissolved in 30 ml of methylene chloride, followed by the dropwise gradual addition of a Grignard reagent under ice cooling. The Grignard reagent had been prepared from 0.07 g of N-methyl-4-chloropiperidine, 0.012 g of magnesium and 10 ml of THF. After the resultant mixture was stirred for 1 hour at the same temperature, it was stirred for additional 1 hour at room temperature. The reaction mixture was then treated in a similar manner to Referential Example 2, whereby 0.82 g of the target compound, 8-methylsulfonyl-6,11-dihydro-11-(1-methyl-4-piperidyl)-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ol was obtained (yield: 61%).
Reaction SMILES: Cl.Cl.Cl.[O:4]1[C:12]2[CH:11]=[CH:10][N:9]=[C:8]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([NH2:27])[CH2:23][CH2:22]4)[CH2:15][CH2:14]3)[C:7]=2[CH:6]=[CH:5]1.CCN(CC)CC.[CH3:35][S:36](Cl)(=[O:38])=[O:37].O>C(Cl)Cl>[O:4]1[C:12]2[CH:11]=[CH:10][N:9]=[C:8]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([NH:27][S:36]([CH3:35])(=[O:38])=[O:37])[CH2:23][CH2:22]4)[CH2:15][CH2:14]3)[C:7]=2[CH:6]=[CH:5]1
Reactant: CS(=O)(=O)Cl
Reactant: N[C@H]1CC[C@H](CCN2CCN(c3nccc4occc34)CC2)CC1
Agent: Cl
Solvent: O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)N[C@H]1CC[C@H](CCN2CCN(c3nccc4occc34)CC2)CC1
Temperature: 0 °C

Procedure:
trans-4-[2-(4-Furo[3,2-c]pyridin-4-yl-piperazin-1-yl)-ethyl]-cyclohexylamine trihydrochloride (intermediate A) (150 mg, 0.34 mmol) was dissolved in CH2Cl2 (1.5 ml) and the solution was cooled to 0° C. Et3N (139 mg, 1.37 mmol) and methanesulfonyl chloride (78 mg, 0.68 mmol) were added and the reaction mixture was stirred over night at room temperature. H2O was added and the product was extracted with CH2Cl2. The organic layer was dried (Na2SO4) and the solvent was evaporated. Purification by flash chromatography over silica gel (CH2Cl2/MeOH/25% NH3 aq 140:10:1) yielded the title compound as a white solid (78 mg, 56%), MS (ISP) m/z=407.2 [(M+H)+].
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(N(CCCC)CCCC)CCC>>[C:3]1(/[CH:2]=[CH:1]/[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C=Cc1ccccc1
Reactant: Clc1ccccc1
Solvent: CCCCN(CCCC)CCCC
Product: C(=C/c1ccccc1)\c1ccccc1

Procedure:
Styrene (1.2 mmol), chlorobenzene (1 mmol), LDH-Pd0 (3 mol %), tri-n-butyl amine (222mg, 1.2 mmol) and NAIL (3.23 g, 10 mmol) were taken in a teflon vessel, closed and irradiated in a Miele Electronic M270 microwave oven at 400W and 130° C. for 0.5–1 h. After completion of the reaction, the LDH-Pd0 catalyst was filtered and washed with water and dichloromethane. After removing the solvent, the crude material was chromatographed on silica gel to afford the trans-stilbene.
Reaction SMILES: C(O[CH:4]=[C:5]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7])C.[CH3:16][C:17]1[N:22]=[C:21]([NH2:23])[CH:20]=[CH:19][CH:18]=1>C1(C)C=CC=CC=1>[CH2:14]([O:13][C:11](=[O:12])[C:5](=[CH:4][NH:23][C:21]1[CH:20]=[CH:19][CH:18]=[C:17]([CH3:16])[N:22]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:15]
Reactant: Cc1cccc(N)n1
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Solvent: Cc1ccccc1
Product: CCOC(=O)C(=CNc1cccc(C)n1)C(=O)OCC
Yield: 106.4 %

Procedure:
Add diethyl ethoxymethylenemalonate (10.0 ml, 55.0 mmol) to a solution of 6-methyl-pyridin-2-ylamine (5.41 g, 50.0 mmol) in toluene (100 ml). Heat the mixture under reflux overnight. Evaporate the solvent in vacuo to provide 2-[(6-methyl-pyridin-2-ylamino)-methylene]-malonic acid diethyl ester (14.8 g) as a white solid. MS (ES+): 279 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]([CH2:19][CH:20]([CH3:22])[CH3:21])[C:11](=[O:23])[CH2:10][CH2:9]1.[Cl:24]N1C(=O)CCC1=O.C(OC(=O)C)C>CN(C)C=O>[Cl:24][C:16]1[CH:17]=[CH:18][C:13]2[N:12]([CH2:19][CH:20]([CH3:21])[CH3:22])[C:11](=[O:23])[CH2:10][CH2:9][CH:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])[C:14]=2[CH:15]=1
Reactant: O=C1CCC(=O)N1Cl
Reactant: CC(C)CN1C(=O)CCC(c2ccccc2Cl)c2ccccc21
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(C)CN1C(=O)CCC(c2ccccc2Cl)c2cc(Cl)ccc21
Yield: 80.1 %

Procedure:
A solution of 5-(2-chlorophenyl)-1-isobutyl-2,3,4,5-tetrahydro-1H-[1]-benzazepin-2-one (2.7 g) and N-chlorosuccinimide (1.65 g) in dimethylformamide (10 ml) was stirred for 7 hours at 70° C. To the reaction mixture was added acetic acid ethyl ester (100 ml), which was washed with dilute hydrochloric acid and a saturated aqueous solution of sodium hydrogencarbonate, followed by drying over anhydrous sodium sulfate. The solvent was removed, and the residue was recrystallized from hexane/acetic acid ethyl ester to give 2.39 g of colorless crystals, m.p. 152°-154° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]2[C:10](=[CH:18][N:19]([CH3:22])[C:20]=2[CH3:21])[N:11]([CH3:17])[C:12](=[O:16])[CH:13]([OH:15])[N:14]=1.[C:23](Cl)(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(N(CC)CC)C.O>C1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]2[C:10](=[CH:18][N:19]([CH3:22])[C:20]=2[CH3:21])[N:11]([CH3:17])[C:12](=[O:16])[CH:13]([O:15][C:23]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:30])[N:14]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: Cc1c2c(cn1C)N(C)C(=O)C(O)N=C2c1ccccc1Cl
Solvent: O
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: Cc1c2c(cn1C)N(C)C(=O)C(OC(=O)c1ccccc1)N=C2c1ccccc1Cl

Procedure:
A mixture of 5-(2-chlorophenyl)-1,7-dihydro-3-hydroxy-1,6,7-trimethyl-pyrrolo[3,4-e][1,4]diazepin-2(3H)-one (4.75 g, 0.0149 mole), benzoyl chloride (2.45 g, 0.0174 mole) and triethylamine (4.5 g, 0.0445 mole) in benzene (100 ml) is refluxed for about 2 hours. Benzene is then boiled off under vacuum and the residue is taken up with a small amount of water and filtered. The raw material thus obtained is crystallized from ethanol yielding 4.9 g of the compound of the title. M.p. 228°-29° C.