Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:12]=[CH:13][C:14]=2[O:15][CH3:16])[CH:10]=[O:11])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:17][Mg]Br.[Cl-].[NH4+]>O1CCCC1>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:10]([OH:11])[CH3:17])[CH:12]=[CH:13][C:14]=2[O:15][CH3:16])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: C[Mg]Br
Reactant: COc1ccc(C=O)cc1OC1CCCC1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: COc1ccc(C(C)O)cc1OC1CCCC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 3-cyclopentyloxy-4-methoxybenzaldehyde (10.00 g, 45.40 mM) in dry tetrahydrofuran (100 ml) was cooled to 0° C., then a tetrahydrofuran solution of methyl magnesium bromide (136.20 mM) was dropwise added to the solution and the mixture was stirred at that temperature for 2 hours. An aqueous ammonium chloride was added to the solution obtained, which was then warmed to room temperature and extracted with ethyl acetate, then the extract was successively washed with brine and water. The organic solution was dried over anhydrous magnesium sulfate, and the solvent was evaporated in vacuo to obtain a crude product of 1-(3-cyclopentyloxy-4-methoxyphenyl)ethanol (10.67 g) as a light yellow oil. The crude product thus obtained of 1-(3-cyclopentyloxy-4-methoxyphenyl)ethanol (10.67 g) was dissolved in dry methylene chloride (200 ml), manganese dioxide (39.2 g) was added to the solution, then the solution was vigorously stirred at room temperature for 16 hours. The undissolved material in the solution was removed by filtration through Celite, and the filtrate was concentrated in vacuo to obtain a residue as a yellow oil. The residue was purified by flash chromatography (SiO2: eluted with 25% ethyl acetate/hexane). The solvent was removed in vacuo and the resultant product was dried to obtain 3-cyclopentyloxy-4-methoxyacetophenone 10.00 g (yield 94.4%) as a yellow oil.
Reaction SMILES: [C:1]([CH:4]1[CH2:8][CH2:7][C:6]([CH3:10])(O)[C:5]1=[CH2:11])([CH3:3])=[CH2:2].[CH3:12][CH:13]([CH3:18])[CH:14]=[CH:15][O:16]C>P(=O)(O)(O)O>[CH:15]([CH:14]([CH:13]([CH3:18])[CH3:12])[CH2:11][C:5]1[CH:4]([C:1]([CH3:3])=[CH2:2])[CH2:8][CH2:7][C:6]=1[CH3:10])=[O:16]
Reactant: C=C(C)C1CCC(C)(O)C1=C
Reactant: COC=CC(C)C
Agent: O=P(O)(O)O
Product: C=C(C)C1CCC(C)=C1CC(C=O)C(C)C
Yield: 45 %

Procedure:
According to the procedure described in Example 7, by the reaction of 30.4 g of 3-isopropenyl-1-methyl-2-methylene-cyclopentan-1-ol with 50 g of methyl (3-methyl-1-butenyl) ether in the presence of 7 drops of 85% phosphoric acid there was obtained 2-(2-formyl-3-methylbutyl)-3-isopropenyl-1-methyl-cyclopent-1-ene in 45% yield; boiling point 0.005 = 55°-56°C; nD20 = 1.4808; IRfilm : μmax = 3080, 2725, 1725, 1642, 1460/40, 1390/70 and 890 cm-1. The compound has a cedar-like, woody, remotely floral fragrance.
Reaction SMILES: [C:1]([CH:4]([CH:6]([C:8]([O-:10])=[O:9])[OH:7])[OH:5])([O-:3])=[O:2].[Sn+2:11]>[O-][99Tc](=O)(=O)=O.[Na+].C(O)C>[C:1]([CH:4]([CH:6]([C:8]([O-:10])=[O:9])[OH:7])[OH:5])([O-:3])=[O:2].[Sn+4:11].[C:1]([CH:4]([CH:6]([C:8]([O-:10])=[O:9])[OH:7])[OH:5])([O-:3])=[O:2]
Reactant: [Sn+2]
Agent: O=[99Tc](=O)(=O)[O-]
Agent: O=C([O-])C(O)C(O)C(=O)[O-]
Agent: [Na+]
Solvent: CCO
Product: [Sn+4]

Procedure:
4 mg of ligand, 1 ml of ethanol, 1 ml of an aqueous salt solution, not more than 0. 5 ml of an aqueous salt solution of 99mTcO4-- and 50 μg of tin(II) tartrate in solution are introduced in succession into a 10-ml flask. The reaction is carried out as in Example 3.1).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[CH:12]=[CH:13][C:14]([NH2:16])=[O:15].[Cl:17][CH2:18][C:19]([CH2:21]Cl)=O>C1(C)C=CC=CC=1>[Cl:17][CH2:18][C:19]1[N:16]=[C:14]([CH:13]=[CH:12][C:3]2[CH:4]=[CH:5][C:6]([C:8]([F:11])([F:10])[F:9])=[CH:7][C:2]=2[F:1])[O:15][CH:21]=1
Reactant: NC(=O)C=Cc1ccc(C(F)(F)F)cc1F
Reactant: O=C(CCl)CCl
Solvent: Cc1ccccc1
Product: Fc1cc(C(F)(F)F)ccc1C=Cc1nc(CCl)co1
Temperature: 25 °C
Yield: 23 %

Procedure:
4.00 g (17.1 mmol) 3-(2-Fluoro-4-trifluoromethyl-phenyl)-acrylamide, 2.60 g (21.3 mmol) 1,3-dichloroacetone and 40 ml toluene were kept at reflux temperature for 16 h with continuous removal of water by use of a water separator (Dean-Stark trap). After cooling to room temperature, two extractions with 100 ml water were performed, the organic phase was dried over sodium sulphate and the solvent removed in vacuo. Chromatography on silica gel (eluent: n-heptane/ethyl acetate 5:1) gave 1.20 g (23%) 4-chloromethyl-2-[2-(2-fluoro-4-trifluoromethyl-phenyl)-vinyl]-oxazole.
Reaction SMILES: [CH3:1][Si:2]([CH3:9])([CH3:8])[CH2:3][CH2:4][O:5][CH2:6]Cl.[Cl:10][C:11]1[CH:16]=[CH:15][N:14]=[CH:13][C:12]=1[S:17]([NH:20][C:21]1[C:26]([O:27][CH3:28])=[N:25][C:24]([CH3:29])=[CH:23][N:22]=1)(=[O:19])=[O:18].C(N(CC)C(C)C)(C)C.C(OCC)(=O)C>CN(C=O)C>[Cl:10][C:11]1[CH:16]=[CH:15][N:14]=[CH:13][C:12]=1[S:17]([N:20]([C:21]1[C:26]([O:27][CH3:28])=[N:25][C:24]([CH3:29])=[CH:23][N:22]=1)[CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:9])([CH3:8])[CH3:1])(=[O:18])=[O:19]
Reactant: COc1nc(C)cnc1NS(=O)(=O)c1cnccc1Cl
Reactant: C[Si](C)(C)CCOCCl
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COc1nc(C)cnc1N(COCC[Si](C)(C)C)S(=O)(=O)c1cnccc1Cl
Temperature: -5 °C

Procedure:
2-(Trimethylsilyl)ethoxymethyl chloride (0.22 ml) was added dropwise over 5 minutes to a stirred solution of 4-chloro-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (0.306 g) and N,N-diisopropylethylamine (0.21 ml) in dry DMF (1 ml) at −15° C. The resultant solution was allowed to warm to −5° C. over 40 minutes then ethyl acetate (30 ml) was added and the mixture was washed with 2M hydrochloric acid (30 ml), water (30 ml) and saturated sodium chloride solution and then dried (MgSO4). Volatile material was removed by evaporation and the residue was purified by gradient elution with 30-50% ethyl acetate/hexane through a silica gel Mega Bond Elut column to give 4-chloro-N-(3-methoxy-5-methylpyrazin-2-yl)-N-[2-(trimethylsilyl)ethoxymethyl]pyridine-3-sulphonamide (0.266 g) as an oil; 1H NMR (d6-DMSO): −0.1 (s, 9H), 0.7 (t, 2H), 2.45 (s, 3H), 3.6 (t, 2H), 3.85 (s, 3H), 5.2 (s, 2H), 7.8 (d, 1H), 8.0 (s, 1H), 8.8 (d, 1H), 9.1 (s, 1H); mass spectrum (+ve FAB, DMSO/Glycerol): 445 (M+H)+.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[CH:16]=[C:17]([CH:21]=[C:22]([O:33][CH2:34][CH2:35][OH:36])[C:23]=2[O:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([O:31][CH3:32])[CH:26]=2)[C:18](O)=[O:19])(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1>>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[CH:16]=[C:17]([C:18]([N:37]3[CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)=[O:19])[CH:21]=[C:22]([O:33][CH2:34][CH2:35][OH:36])[C:23]=2[O:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([O:31][CH3:32])[CH:26]=2)(=[O:12])=[O:13])=[CH:7][CH:6]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: COc1cccc(Oc2c(NS(=O)(=O)c3ccc(C(C)(C)C)cc3)cc(C(=O)O)cc2OCCO)c1
Reactant: C1COCCN1
Product: COc1cccc(Oc2c(NS(=O)(=O)c3ccc(C(C)(C)C)cc3)cc(C(=O)N3CCOCC3)cc2OCCO)c1

Procedure:
Analogously to Example 74, by condensing 3-(4-tert-butyl-benzenesulphonylamino)-5-(2-hydroxy-ethoxy)-4-(3-methoxy-phenoxy)-benzoic acid with morpholine there was obtained 4-tert-butyl-N-[3-(2-hydroxy-ethoxy)-2-(3-methoxy-phenoxy)-5-(morpholine-4-carbonyl)-phenyl]-benzenesulphonamide.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10]Cl)([O-:3])=[O:2].[NH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[S:19][CH2:20][C:21]1[N:25]=[CH:24][O:23][N:22]=1>C(Cl)(Cl)Cl>[N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10][NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[S:19][CH2:20][C:21]1[N:25]=[CH:24][O:23][N:22]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccccc1SCl
Reactant: Nc1ccccc1SCc1ncon1
Solvent: ClC(Cl)Cl
Product: O=[N+]([O-])c1ccccc1SNc1ccccc1SCc1ncon1
Reaction time: 8 h

Procedure:
A solution of 2-nitrophenylsulphenyl chloride (1.44 g, 7.5×10-3 mol) in chloroform was added dropwise to a solution of 3-(2-aminophenylthiomethyl)-1,2,4-oxadiazole in chloroform (20 ml). The yellow mixture was stirred overnight, the crude product collected by filtration and recrystallised from ethyl acetate/hexane to give 3-[2-(2-nitrophenylsulphenylamino)phenyl]thiomethyl-1,2,4-oxadiazole, m.p. 90° (dec.).
Reaction SMILES: [CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:10]1[C:11]2[CH:24]=[C:23]([CH2:25][CH3:26])[S:22][C:12]=2[N:13]=[C:14]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[N:15]=1>>[N:18]1[CH:19]=[CH:20][CH:21]=[C:16]([C:14]2[N:15]=[C:10]([NH:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:11]3[CH:24]=[C:23]([CH2:25][CH3:26])[S:22][C:12]=3[N:13]=2)[CH:17]=1
Reactant: CCc1cc2c(Cl)nc(-c3cccnc3)nc2s1
Reactant: NCc1ccccc1
Product: CCc1cc2c(NCc3ccccc3)nc(-c3cccnc3)nc2s1

Procedure:
With the procedure of Example 1, the reaction of benzylamine with 4-chloro-2-(pyridin-3-yl)-6-ethyl-thieno-[2,3-d]-pyrimidine yields 2-(pyridin-3-yl)-4-benzylamino-6-ethyl-thieno-[2,3-d]-pyrimidine.
Reaction SMILES: F[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[OH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:13][CH:12]=1.C([O-])([O-])=O.[K+].[K+].C([O-])(O)=O.[Na+]>CN(C)C(=O)C>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([O:10][C:11]2[CH:12]=[CH:13][C:14]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:15][CH:16]=2)=[CH:3][CH:4]=1)#[N:7]
Reactant: N#Cc1ccc(F)cc1
Reactant: CCOC(=O)Cc1ccc(O)cc1
Agent: O=C([O-])O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Product: CCOC(=O)Cc1ccc(Oc2ccc(C#N)cc2)cc1
Temperature: 155 °C

Procedure:
A mixture of 2.21 g of p-fluorobenzonitrile, 2.16 g of ethyl p-hydroxyphenylacetate and 2.07 g of K2CO3 in 20 ml of N,N-dimethylacetamide is stirred and heated at 155° C. for 18 hours. The mixture is chilled and poured into 40 ml of cold saturated NaHCO3 solution. The mixture is extracted with ether and the extracts washed with cold 2 N NaOH and saline. The extracts are dried (MgSO4) and concentrated under vacuum to give the product as a yellow oil.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([O:25][CH:26]([CH3:28])[CH3:27])=[C:13]([C:15]2[NH:24][C:18]3=[N+:19]([O-])[CH:20]=[CH:21][CH:22]=[C:17]3[N:16]=2)[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:29]([N:31](CC)CC)C.C[Si](C#N)(C)C>C(#N)C.O>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([O:25][CH:26]([CH3:28])[CH3:27])=[C:13]([C:15]2[NH:24][C:18]3=[N:19][C:20]([C:29]#[N:31])=[CH:21][CH:22]=[C:17]3[N:16]=2)[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCN(CC)CC
Reactant: CC(C)Oc1ccc(OCc2ccccc2)cc1-c1nc2ccc[n+]([O-])c2[nH]1
Agent: C[Si](C)(C)C#N
Solvent: CC#N
Solvent: O
Product: CC(C)Oc1ccc(OCc2ccccc2)cc1-c1nc2ccc(C#N)nc2[nH]1
Yield: 69 %

Procedure:
A solution (10 ml) of 2-[5-(benzyloxy)-2-isopropoxyphenyl]-3H-imidazo[4,5-b]pyridine 4-oxide, triethylamine (0.11 g) and trimethylsilyl cyanide (0.22 g) in acetonitrile was heated under reflux for 5 hr. The reaction mixture was diluted with water and extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate and concentrated. The obtained crude crystals were washed with diethyl ether to give the title compound (0.15 g, yield 69%) as colorless crystals. melting point 214-215° C. purity 93%. M+H: 385. 1H NMR (CDCl3) δ: 1.53 (6H, d, J=6.0 Hz), 4.77-4.85 (1H, m), 5.16 (2H, s), 7.06 (1H, d, J=9.0 Hz), 7.12-7.18 (1H, m), 7.32-7.50 (5H, m), 7.66 (1H, d, J=8.1 Hz), 8.12 (1H, d, J=8.1 Hz), 8.20 (1H, d, J=3.0 Hz).
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[C@@H:6]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)[CH2:5][C@@H:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[NH:3]1.S(=O)(=O)(O)O.[OH-].[Na+].N1CCCC1.[ClH:32].[N+:33]([O-])([OH:35])=[O:34]>CCOCC.C(O)C>[ClH:32].[ClH:32].[CH3:1][C:2]1([CH3:19])[C@@H:6]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)[CH2:5][C@@H:4]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([N+:33]([O-:35])=[O:34])[CH:14]=2)[NH:3]1
Reactant: O=[N+]([O-])O
Reactant: CC1(C)N[C@H](c2ccccc2)C[C@@H]1c1ccncc1
Agent: Cl
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CCOCC
Solvent: CCO
Solvent: C1CCNC1
Product: CC1(C)N[C@H](c2cccc([N+](=O)[O-])c2)C[C@@H]1c1ccncc1
Reaction time: 1 h

Procedure:
20 G. of 4-(cis-2,2-dimethyl-5-phenyl-3-pyrrolidinyl)-pyridine (racemate) are dissolved under cool temperatures (5°-10° C.) in concentrated nitric acid and 50 ml. of cool concentrated sulfuric acid are slowly added. Thereafter, the reaction mixture is stirred for about 1 hour at 10°-15° C. and then poured on ice. The pH of the reaction mixture is then adjusted to pH 8-9 with 3N sodium hydroxide, also in the cold, and exhaustively extracted with methylenechloride. The combined extracts are dried over sodium sulfate and evaporated in a water pump vacuum to dryness. The product thereby obtained is a mixture of pyrrolidine with para and meta nitrophenyl substituents. The mixture is dissolved in 400 ml. warm ethanol. After the addition of 25 ml. concentrated hydrochloric acid and some ether, a mixture of dihydrochlorides (m-nitrophenyl and p-nitrophenyl, 8 to 2) is obtained. Fractional crystallization from ethanol yields 4-[cis-2,2-dimethyl-5-(m-nitrophenyl)-3-pyrrolidinyl]-pyridine dihydrochloride (racemate) with a melting point of 229°-232° C. (decomp.).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[CH:4][N:3]=1.[N:9]1([C:15]([O:17][CH2:18][CH:19]([CH3:21])[CH3:20])=[O:16])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.C(N(CC)CC)C.CN(C=O)C>O>[Cl:8][C:6]1[N:5]=[CH:4][N:3]=[C:2]([N:12]2[CH2:11][CH2:10][N:9]([C:15]([O:17][CH2:18][CH:19]([CH3:21])[CH3:20])=[O:16])[CH2:14][CH2:13]2)[CH:7]=1
Reactant: CC(C)COC(=O)N1CCNCC1
Reactant: Clc1cc(Cl)ncn1
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(C)COC(=O)N1CCN(c2cc(Cl)ncn2)CC1
Temperature: 120 °C

Procedure:
A mixture of 4,6-dichloropyrimidine (0.25 g, 1.7 mmol), isobutyl piperazine-1-carboxylate (0.31 g, 1.7 mmol), triethylamine (0.23 mL, 1.8 mmol), and DMF (4.2 mL) was sealed in a microwave reactor vial and heated by microwave irradiation at 120° C. for 2 minutes. The reaction was cooled, diluted with water, and extracted with CH2Cl2. The combined extracts were dried over Na2SO4 and evaporated to obtain isobutyl 4-(6-chloropyrimidin-4-yl)piperazine-1-carboxylate. LC/MS: m/z 299.2 (M+H)+ at 3.10 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).
Reaction SMILES: Br[C:2]1[N:7]2[CH:8]=[C:9]([CH2:11][OH:12])[N:10]=[C:6]2[C:5]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:27]2[CH:28]=[CH:29][C:30]([N:33]3[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]3)=[N:31][CH:32]=2)O1.C([O-])([O-])=O.[K+].[K+]>>[OH:12][CH2:11][C:9]1[N:10]=[C:6]2[C:5]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:4][CH:3]=[C:2]([C:27]3[CH:28]=[CH:29][C:30]([N:33]4[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]4)=[N:31][CH:32]=3)[N:7]2[CH:8]=1
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc(B3OC(C)(C)C(C)(C)O3)cn2)CC1
Reactant: OCc1cn2c(Br)cnc(N3CCOCC3)c2n1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CC(C)(C)OC(=O)N1CCN(c2ccc(-c3cnc(N4CCOCC4)c4nc(CO)cn34)cn2)CC1

Procedure:
Compound 1e was subjected to Suzuki coupling conditions with tert-butyl 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)piperazine-1-carboxylate using the reaction conditions described in Example 1, Step G, and substituting K2CO3 as the base to obtain compound 23a. Mass Spectrum (LCMS, ESI pos.) Calcd. for C25H33N7O4: 496.3 (M+H). Found 496.3.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][CH2:10][N:11]2[C:15](=[O:16])[C:14]3=[CH:17][CH:18]=[CH:19][CH:20]=[C:13]3[C:12]2=[O:21])=[C:4]([C:22](=[O:29])[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:3]=1>[Ni].O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][N:11]2[C:15](=[O:16])[C:14]3=[CH:17][CH:18]=[CH:19][CH:20]=[C:13]3[C:12]2=[O:21])=[C:4]([C:22](=[O:29])[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:3]=1
Reactant: O=C(c1ccccc1)c1cc(Cl)ccc1C#CCN1C(=O)c2ccccc2C1=O
Agent: [Ni]
Solvent: C1CCOC1
Product: O=C(c1ccccc1)c1cc(Cl)ccc1CCCN1C(=O)c2ccccc2C1=O

Procedure:
A mixture of 2 g (5 mmole) of 1-[4-chloro-2-benzoylphenyl]-3-phthalimidopropyne and 1/2 teaspoonful of Raney nickel in 25 ml of tetrahydrofuran was hydrogenated at room temperature and atmospheric pressure. When 240 ml of hydrogen was absorbed, the catalyst was separated by filtration and the filtrate concentrated at reduced pressure to dryness. The residue was crystallized from a mixture of ether and petroleum to give crude product as a tan solid, mp 94°-97° C. Recrystallization from ether gave pale yellow prisms, mp 98°-99° C.
Reaction SMILES: Cl[CH2:2][C:3]1[S:7][C:6]2[CH:8]=[C:9]([O:12][C:13]3[S:14][C:15]4[CH:21]=[CH:20][CH:19]=[CH:18][C:16]=4[N:17]=3)[CH:10]=[CH:11][C:5]=2[CH:4]=1.CCN(C(C)C)C(C)C.[NH:31]1[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1>CC#N>[N:31]1([CH2:2][C:3]2[S:7][C:6]3[CH:8]=[C:9]([O:12][C:13]4[S:14][C:15]5[CH:21]=[CH:20][CH:19]=[CH:18][C:16]=5[N:17]=4)[CH:10]=[CH:11][C:5]=3[CH:4]=2)[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1
Reactant: C1CCNCC1
Reactant: ClCc1cc2ccc(Oc3nc4ccccc4s3)cc2s1
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: c1ccc2sc(Oc3ccc4cc(CN5CCCCC5)sc4c3)nc2c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 48.5 %

Procedure:
To a solution 2-(2-chloromethyl-benzo[b]thiophen-6-yloxy)-benzothiazole (86 mg, 0.26 mmol) in MeCN (3 mL) was added DIEA (0.014 mL, 11 mg, 0.8 mmol) followed by piperidine (0.051 mL, 44 mg, 0.52 mmol) and stirred (rt, 12 h). The reaction mixture was partitioned between DCM (15 mL) and saturated NaHCO3(5 mL). The organic layer was washed with saturated NH4Cl (10 mL), dried, filtered and concentrated in vacuo. The resulting residue was purified by reverse phase chromatography to provide the title compound as colorless solid (48 mg, 49%). MS (ESI): mass calcd. for C21H20N2OS2, 380.1; m/z found, 381.1[M+H]+. 1H NMR (400 MHz, CDCl3): 7.79 (d, J=2.3, 1H), 7.75-7.72 (m, 1H), 7.70 (d, J=8.6, 1H), 7.65 (dd, J=8.0, 0.7, 1H), 7.40-7.35 (m, 1H), 7.29 (dd, J=8.6, 2.3, 1H), 7.28-7.21 (m, 1H), 7.13 (5, 1H), 3.75 (5, 2H), 2.55-2.40 (m, 4H), 1.69-1.54 (m, 4H), 1.52-1.32 (m, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]([N:5]1[C@@H:13]2[C@@H:8]([C@@:9]([OH:23])([C:14]#[C:15][C:16]3[CH:17]=[C:18]([CH3:22])[CH:19]=[CH:20][CH:21]=3)[CH2:10][CH2:11][CH2:12]2)[CH2:7][CH2:6]1)=[O:4].[CH3:24][C:25]1[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=1[C:27](O)=[O:28]>>[CH3:24][C:25]1[CH:33]=[CH:32][CH:31]=[CH:30][C:26]=1[C:27]([O:23][C@@:9]1([C:14]#[C:15][C:16]2[CH:17]=[C:18]([CH3:22])[CH:19]=[CH:20][CH:21]=2)[CH2:10][CH2:11][CH2:12][C@@H:13]2[C@H:8]1[CH2:7][CH2:6][N:5]2[C:3]([O:2][CH3:1])=[O:4])=[O:28]
Reactant: COC(=O)N1CC[C@H]2[C@@H]1CCC[C@]2(O)C#Cc1cccc(C)c1
Reactant: Cc1ccccc1C(=O)O
Product: COC(=O)N1CC[C@@H]2[C@H]1CCC[C@]2(C#Cc1cccc(C)c1)OC(=O)c1ccccc1C

Procedure:
Synthesis in analogy to the General Method 1 starting from (3aS,4R,7aS)-4-hydroxy-4-m-tolylethynyl-octahydro-indole-1-carboxylic acid methyl ester and 2-methyl-benzoic acid to yield (3aR,4S,7aR)-methyl 4-(2-methylbenzoyloxy)-4-(m-tolylethynyl)octahydro-1H-indole-1-carboxylate. MS [M+H]=296 (ester eliminated ion); RT=4.217 min; HPLC Method III
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[CH2:9][OH:10].[Br:11][CH2:12][C:13](Br)=[O:14].C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[Br:11][CH2:12][C:13]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[CH2:9][OH:10])=[O:14]
Reactant: Nc1ccc(Cl)cc1CO
Reactant: O=C(Br)CBr
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: O=C(CBr)Nc1ccc(Cl)cc1CO
Reaction time: 0.08 h
Yield: 96 %

Procedure:
To a mixture of (2-amino-5-chlorophenyl)methanol (4.30 g, 27.3 mmol) in dichloromethane (220 ml) was added 2-bromoacetyl bromide (6.06 g, 2.61 ml, 30.0 mmol) at 0-5° C. Stirring for 5 minutes was followed by dropwise addition of aqueous 2 M sodium carbonate solution (130 ml) in approx. 10 minutes. The cooling bath was removed and stirring was continued for 2 h. The solvent was concentrated in vacuo. The aqueous residue was extracted with three 100 ml-portions of ethyl acetate. The combined organic layers were washed with one 50 ml-portion of brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give the title compound (7.30 g, 96%) as light grey solid which was used in the next step without purification. MS m/e: 276 ([M+1-1]+).
Reaction SMILES: [C:1]1([C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4])[OH:2].C([O-])(=O)C.[Eu+3:13].C([O-])(=O)C.C([O-])(=O)C>C1(C)C(C)=CC=CC=1>[C:1]1([C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[O-:4])[O-:2].[Eu+3:13].[C:1]1([C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[O-:4])[O-:2].[C:1]1([C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[O-:4])[O-:2].[Eu+3:13]
Reactant: Oc1ccccc1O
Agent: CC(=O)[O-]
Agent: [Eu+3]
Solvent: Cc1ccccc1C
Product: [O-]c1ccccc1[O-]
Temperature: 100 °C

Procedure:
A solution of catechol (3.30 g, 30 mmol) and xylene (45 ml) was dehydrated by distilling 5 mL of the solution. Thereafter, 6.58 g (20 mmol) of europium acetate was added to the solution while stirring. The mixed solution was refluxed for 1 hour, and then, while the distillation temperature was 132° C. or higher, distilled until the amount of the solution became half. After the distillation, solid content of the product was isolated by suction filtering using a membrane suction filter. The residual solid content was heated to 100° C. under vacuum using a vacuum dryer so that remaining volatile components were completely removed. The solid content (catechol-europium complex) was yellow in color. The yield amount was 6.28 g (20 mmol), and the yield percentage was 100%. 0.314 g of catechol-europium complex was dissolved into 10 mL of acetylacetone/toluene to produce a coating liquid.
Reaction SMILES: [CH3:1][CH:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][CH2:5][O:4][NH:3]1.[CH2:13](Br)[CH2:14][CH2:15][CH3:16].C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)C>[CH2:13]([N:3]1[O:4][CH2:5][CH2:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[CH:2]1[CH3:1])[CH2:14][CH2:15][CH3:16]
Reactant: CCCCBr
Reactant: CC1NOCCc2ccccc21
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOCC
Product: CCCCN1OCCc2ccccc2C1C
Temperature: 120 °C
Reaction time: 4 h

Procedure:
A mixture of 3.27 g. (0.02 mole) of 1-methyl-1,2,4,5-tetrahydro-3,2-benzoxazepine, 5.5 g. (0.04 mole) of butyl bromide and 3.18 g. (0.03 mole) of sodium carbonate was heated under stirring for 3 hours at 90° C. and for an additional four hours at 120° C. After cooling the reaction mixture was taken up with diethyl ether, and the inorganic residue filtered off. The filtrate was then evaporated in vacuo and the residue rectified by collecting the fraction boiling at 90° C./0.1 mm Hg. Yield 2.3 g. of 2-butyl-1-methyl-1,2,4,5-tetrahydro-3,2-benzoxazepine.