Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:15]=[CH:14][C:11]([CH:12]=[O:13])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[Br-].[Cl-].[NH4+].[CH2:19]1COC[CH2:20]1>>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:15]=[CH:14][C:11]([CH:12]([OH:13])[C:19]#[CH:20])=[CH:10][CH:9]=2)[CH2:4][CH2:3]1
Reactant: CN1CCN(c2ccc(C=O)cc2)CC1
Reactant: C1CCOC1
Agent: [Br-]
Agent: [Cl-]
Agent: [NH4+]
Product: C#CC(O)c1ccc(N2CCN(C)CC2)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 84.2 %

Procedure:
To a solution of 4-(4-methyl-piperazin-1-yl)-benzaldehyde (28.9 mmol) in THF (100 ml), ethnylmagnesium bromide (0.5M solution in THF) (43.4 mmol) is added at −78° C. The solution is then stirred at room temperature for 18 h. The reaction mixture is treated with saturated ammonium chloride and extracted with ethyl acetate. The organic layer is washed with brine, dried over magnesium sulfate and evaporated down. CH2Cl2 is added to the residue to afford a precipitate, which is collected by filtration. yield 84.2%, Rf=0.23 (CH2Cl2:MeOH=9:1).
Reaction SMILES: [OH:1][C:2]1[C:7](=[O:8])[CH:6]=[CH:5]O[C:3]=1[CH3:9].[CH:10]1([NH2:16])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.C>O>[CH:10]1([N:16]2[CH:5]=[CH:6][C:7](=[O:8])[C:2]([OH:1])=[C:3]2[CH3:9])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1
Reactant: NC1CCCCC1
Reactant: Cc1occc(=O)c1O
Solvent: O
Product: Cc1c(O)c(=O)ccn1C1CCCCC1
Reaction time: 0.5 h

Procedure:
1-Cyclohexyl-3-hydroxy-2-methylpyrid-4-one was prepared by dissolving 10.0 g of 3-hydroxy-2-methylpyr-4-one (Maltol) and 3 equivalents (~27 ml) of cyclohexylamine (99+ %) in 200 ml of water. Decolorizing charcoal was added and the mixture was stirred for 0.5 hours. The aqueous mixture was filtered through a course frit then concentrated in vacuo, leaving an oily residue. Crystallization from hot water yielded crystals of the desired product. m.p. 199° C.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:21]=[C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:19]=[CH:18][C:10]=1[O:11][CH2:12][C:13](OCC)=[O:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH3:30].CO>O>[CH2:1]([O:8][C:9]1[CH:21]=[C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:19]=[CH:18][C:10]=1[O:11][CH2:12][C:13]([NH2:30])=[O:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: N
Reactant: CCOC(=O)COc1ccc(OCc2ccccc2)cc1OCc1ccccc1
Solvent: CO
Solvent: O
Product: NC(=O)COc1ccc(OCc2ccccc2)cc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A mixture of ethyl (2,4-dibenzyloxyphenoxy)acetate (2 g), concentrated ammonia (25 mL) and methanol (50 mL) is stirred at room temperature for 18 hours. The reaction mixture is diluted with water (50 mL) then evaporated to low bulk and filtered. The solid is washed with water and dried to give 2-(2,4-dibenzyloxyphenoxy)acetamide (1.1 g) as a white powder, m.p. 120° C. [Elemental analysis:- C,73.1; H,5.78; N,3.79%. Calculated:- C,72.7; H,5.83; N,3.85%].
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][C:10]=1[C:16]1[CH:21]=[C:20](Cl)[N:19]=[C:18]([NH2:23])[N:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:24][C:25]1[CH:30]=[CH:29][C:28]([CH2:31][CH2:32][OH:33])=[CH:27][CH:26]=1>>[NH2:23][C:18]1[N:19]=[C:20]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([CH2:31][CH2:32][OH:33])=[CH:27][CH:26]=2)[CH:21]=[C:16]([C:10]2[CH:11]=[C:12]([Cl:15])[CH:13]=[CH:14][C:9]=2[O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[N:17]=1
Reactant: Nc1ccc(CCO)cc1
Reactant: Nc1nc(Cl)cc(-c2cc(Cl)ccc2OCc2ccccc2)n1
Product: Nc1nc(Nc2ccc(CCO)cc2)cc(-c2cc(Cl)ccc2OCc2ccccc2)n1
Yield: 71 %

Procedure:
Following the method described in Example 72, 4-(2-benzyloxy-5-chloro-phenyl)-6-chloro-pyrimidin-2-ylamine and 2-(4-amino-phenyl)-ethanol provided the title compound (71% yield). 1H NMR (CD3OD) δ 2.85 (t, 2H, J=6.9 Hz, CH2), 3.78 (t, 2H, J=6.9 Hz, CH2), 5.27 (s, 2H, CH2), 6.42 (s, 1H, Ar), 7.28-7.30 (m, 2H, Ar), 7.32-7.36 (m, 2H, Ar), 7.39 (d, 4H, J=6.3 Hz, Ar), 7.58 (d, 2H, J=8.4 Hz, Ar), 7.68-7.70 (m, 2H, Ar).
Reaction SMILES: Br[CH2:2][C:3]([NH:5][C:6]1[CH:14]=[CH:13][C:9]([CH2:10][C:11]#[N:12])=[CH:8][CH:7]=1)=[O:4].[F:15][C:16]1[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=1[NH2:18]>CN(C=O)C>[F:15][C:16]1[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=1[NH:18][CH2:2][C:3]([NH:5][C:6]1[CH:14]=[CH:13][C:9]([CH2:10][C:11]#[N:12])=[CH:8][CH:7]=1)=[O:4]
Reactant: Nc1ccccc1F
Reactant: N#CCc1ccc(NC(=O)CBr)cc1
Solvent: CN(C)C=O
Product: N#CCc1ccc(NC(=O)CNc2ccccc2F)cc1
Temperature: 0 °C
Yield: 73.5 %

Procedure:
A solution of 4-((bromoacetyl)amino)benzyl cyanide (8.5 g, 33.6 mmol) and 2-fluoroaniline (9.03 g, 81.3 mmol) in anhydrous DMF (60 mL) was heated to 90°-100° C. for 2 days with stirring under N2. The solution was cooled, poured into 500 mL of ice-water, and then extracted with CH2Cl2 (200 mL). The separated organic layer was dried (MgSO4) and filtered, a small amount of silica gel was added to the CH2Cl2 solution, and then the mixture was concentrated. Purification by chromatography, eluting with hexane-ethyl acetate (2:1), afforded 7.0 g (73.5%) of the title compound, mp 111°-113° C.: 1H NMR (DMSO-d6) δ10.09 (s, 1H), 7.61 (d, J=8.4, 2H), 7.27 (d, J=8.8, 2H), 7.05 (ddd, J=9.6, J=8.0, J=1.6, 1H), 6.94 (t, J=7.1, 1H), 6.63-6.58 (m, 2H), 5.76 (bt, J=6.0, 1H): 3.96 (s, 2H), 3.93 (d, J=6.0, 2H); 13C NMR (DMSO-d6) δ168.92, 150.87 (d, J=236), 138.18, 136.37 (d, J=11.0), 128.47, 125.85, 124.72 (d, J=3.0), 119.61, 119.32, 116.24 (d, J=6.8), 114.37 (d, J=17), 112.13, 46.62, 21.79; MS (El, m/z) 283 (M+).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]2[C:11](=[O:28])[NH:12][C:13](=[O:27])[C:14]=2[C:15]2[C:25]3=[C:26]4[C:21](=[CH:22][CH:23]=[CH:24]3)S[CH2:19][CH2:18][N:17]4[CH:16]=2)=[CH:2]1.ClC1C=CC=C(C(OO)=O)C=1.[S:40](=[O:43])(O)[O-:41].[Na+].C(=O)(O)[O-].[Na+]>ClCCl>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]2[C:11](=[O:28])[NH:12][C:13](=[O:27])[C:14]=2[C:15]2[C:25]3=[C:26]4[C:21](=[CH:22][CH:23]=[CH:24]3)[S:40](=[O:43])(=[O:41])[CH2:19][CH2:18][N:17]4[CH:16]=2)=[CH:2]1
Reactant: O=S([O-])O
Reactant: O=C1NC(=O)C(c2cn3c4c(cccc24)SCC3)=C1c1c[nH]c2ccccc12
Agent: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: O=C1NC(=O)C(c2cn3c4c(cccc24)S(=O)(=O)CC3)=C1c1c[nH]c2ccccc12
Reaction time: 24 h
Yield: 23.8 %

Procedure:
To a solution of 3-(1H-indol-3-yl)-4-(4,5-dihydro-3H-5-thia-2a-aza-acenaphthylen-1-yl)pyrrole-2,5-dione (0.50 g, 1.3 mmol) in dichloromethane was added meta-chloroperbenzoic acid (0.671 g, 3.89 mmol) at 0° C. After 24 hrs at room temperature, a saturated solution of sodium bisulfite and sodium bicarbonate was added, and the mixture was extracted with ethyl acetate. The organic layer was subjected to silica gel chromatography, eluting with ethyl acetate/hexane (4:1) to give 0.120 g (23.8%) of the title compound.
Reaction SMILES: [CH3:1][N:2]([CH3:31])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[N:9][C:10]([C:13]2[CH:14]=[C:15]([CH:28]=[CH:29][CH:30]=2)[CH2:16][N:17]2[C:22](=[O:23])[CH:21]=[CH:20][C:19]([C:24]([NH:26][OH:27])=[NH:25])=[N:18]2)=[N:11][CH:12]=1.N1C=CC=CC=1.Cl[C:39](OCC)=[O:40]>CN(C=O)C>[CH3:31][N:2]([CH3:1])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[N:9][C:10]([C:13]2[CH:14]=[C:15]([CH:28]=[CH:29][CH:30]=2)[CH2:16][N:17]2[C:22](=[O:23])[CH:21]=[CH:20][C:19]([C:24]3[NH:25][C:39](=[O:40])[O:27][N:26]=3)=[N:18]2)=[N:11][CH:12]=1
Reactant: CCOC(=O)Cl
Reactant: CN(C)CCCOc1cnc(-c2cccc(Cn3nc(C(=N)NO)ccc3=O)c2)nc1
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: CN(C)CCCOc1cnc(-c2cccc(Cn3nc(-c4noc(=O)[nH]4)ccc3=O)c2)nc1

Procedure:
500 mg (1.18 mmol) of 1-{3-[5-(3-dimethylaminopropoxy)pyrimidin-2-yl]-benzyl}-N-hydroxy-6-oxo-1,6-dihydropyridazine-3-carboxamidine are dissolved in 15 ml of DMF, and 286 μl (3.54 mmol) of pyridine are added. 124 μl (1.30 mmol) of ethyl chloroformate are subsequently added with stirring, and the solution is stirred at 80° C. for 15 and subsequently at 100° C. for 72 h. The reaction mixture is evaporated, and the residue is purified by means of preparative HPLC; yield: 21.2 mg of “A227” trifluoroacetate; HPLC: Rt=2.07 min; LC-MS: 450 (M+H).
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].[Si](C=[N+]=[N-])(C)(C)[CH3:15]>C1C=CC=CC=1.CO>[N+:11]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:2]=1[OH:1])[C:6]([O:8][CH3:15])=[O:7])([O-:13])=[O:12]
Reactant: O=C(O)c1ccc(O)c([N+](=O)[O-])c1
Reactant: C[Si](C)(C)C=[N+]=[N-]
Solvent: CO
Solvent: c1ccccc1
Product: COC(=O)c1ccc(O)c([N+](=O)[O-])c1
Reaction time: 8 h
Yield: 75.2 %

Procedure:
To a stirred solution of 4-hydroxy-3-nitrobenzoic acid (5.18 g, 28.29 mmol) in benzene-MeOH (4:1, v/v, 140 mL) was added TMSCHN2 (14.10 mL, 28.20 mmol, 2 M solution in hexane) at room temp, and the resulting mixture was stirred overnight. The mixture was evaporated and the residue was purified by column chromatography on silica-gel with CHCl3 as eluent to give 4.18 g (75%) methyl 3-nitro-4-hydroxybenzoate as a yellow crystalline solid. 1H-NMR (CDCl3) d 3.95 (s, 3H), 7.22 (d, 1H, J=8.8 Hz), 8.24 (dd, 1, J=2.0, 8.8 Hz), 8.83 (d, 1H, J=2.0 Hz), 10.89 (s, 1H).
Reaction SMILES: [CH:1]1([NH2:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:8][C:9](N)=[O:10].N>O>[CH:1]1([NH:7][C:9]([NH2:8])=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: NC1CCCCC1
Reactant: NC(N)=O
Agent: N
Solvent: O
Product: NC(=O)NC1CCCCC1
Yield: 89.7 %

Procedure:
495 g (5 mols) of cyclohexylamine and 390 g (6.5 mols) of urea are heated under reflux in 750 ml of water. After the splitting-off of ammonia is complete, the mixture is cooled down and the product is filtered off with suction. After washing and drying, 638 g of N-cyclohexylurea (90% of theory) are obtained.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][CH3:9])=[CH:4][N:3]=1.O.[NH2:11][NH2:12]>CO>[NH:11]([C:2]1[N:7]=[CH:6][C:5]([CH2:8][CH3:9])=[CH:4][N:3]=1)[NH2:12]
Reactant: NN
Reactant: CCc1cnc(Cl)nc1
Solvent: O
Solvent: CO
Product: CCc1cnc(NN)nc1
Temperature: 50 °C
Reaction time: 16 h
Yield: 79 %

Procedure:
To a solution of 2-chloro-5-ethylpyrimidine (0.31 g, 2.2 mmol) in MeOH (5 mL) was added hydrazine monohydrate (1.0 mL, 20.6 mmol). After stirring for 16 h at 50° C., the solution was cooled to room temperature and purified by reverse phase HPLC to give 0.24 g (80%) of the title compound as a white solid. MH+139.
Reaction SMILES: C([O:4][C:5]1[CH:41]=[CH:40][C:8]([C:9]([N:11]([CH:37]([CH3:39])[CH3:38])[C:12]2[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:13]=2[CH:20]2[CH2:29][CH2:28][C:27]3[CH:26]=[C:25]([O:30][C:31](=[O:36])[C:32]([CH3:35])([CH3:34])[CH3:33])[CH:24]=[CH:23][C:22]=3[CH2:21]2)=[O:10])=[CH:7][C:6]=1[F:42])(=O)C.O.C(=O)([O-])[O-].[K+].[K+]>CO>[F:42][C:6]1[CH:7]=[C:8]([CH:40]=[CH:41][C:5]=1[OH:4])[C:9]([N:11]([CH:37]([CH3:39])[CH3:38])[C:12]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:13]=1[CH:20]1[CH2:29][CH2:28][C:27]2[CH:26]=[C:25]([O:30][C:31](=[O:36])[C:32]([CH3:33])([CH3:34])[CH3:35])[CH:24]=[CH:23][C:22]=2[CH2:21]1)=[O:10]
Reactant: COc1ccc(C2CCc3cc(OC(=O)C(C)(C)C)ccc3C2)c(N(C(=O)c2ccc(OC(C)=O)c(F)c2)C(C)C)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: COc1ccc(C2CCc3cc(OC(=O)C(C)(C)C)ccc3C2)c(N(C(=O)c2ccc(O)c(F)c2)C(C)C)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 62.5 %

Procedure:
To a solution of pivalic acid 6-{2-[(4-acetoxy-3-fluorobenzoyl)isopropylamino]-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-yl ester (1.1 g) in methanol (18 ml) were sequentially added water (2 ml) and potassium carbonate (321 mg), and the solution was stirred for 1 hour at room temperature. Water was added thereto, the solution was extracted with ethyl acetate, then washed with brine, dried over anhydrous magnesium sulfate, and then the solvent was evaporated in vacuo. The residue was purified by silica gel column chromatography (hexane-ethyl acetate system) to provide the title compound (637 mg).
Reaction SMILES: [CH2:1]1[C:14]2[C:13]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[NH:7][C:6]=2[CH:5]([C:15]([O:17]CC)=O)[CH2:4][NH:3][CH2:2]1.Cl.[CH3:21][NH2:22].CN>C1COCC1>[CH3:21][NH:22][C:15]([CH:5]1[C:6]2[NH:7][C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:13]=3[C:14]=2[CH2:1][CH2:2][NH:3][CH2:4]1)=[O:17]
Reactant: CCOC(=O)C1CNCCc2c1[nH]c1ccccc21
Reactant: CN
Agent: Cl
Solvent: C1CCOC1
Product: CNC(=O)C1CNCCc2c1[nH]c1ccccc21
Temperature: 80 °C
Yield: 65.8 %

Procedure:
Ethyl 1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate (1.29 g, 5 mmol; European Patent No. EP 064 317 B1) and methylamine hydrochloride (0.67 g, 10 mmol) were added to a solution of methylamine in THF (2 M, 15 mL) and the suspension was heated to 80° C. in a sealed tube under nitrogen stirring for 72 hours. Solvent was evaporated to give a crude product, which was purified by chromatography on silica gel eluting with MeOH-DCM (1:9 to 1:4) to give the title compound (0.8 g); 1H-NMR (CDCl3): δ 8.46 (1H, br s), 8.24 (1 H, s), 7.48 (1H, d)), 7.30 (1H, d), 7.16 (1H, m), 7.10 (1H, m), 3.70 (1H, d), 3.66 (1H, dd), 3.46 (1H, dd), 3.08 (2H, m), 2.87 (2H, m), 2.73 (3H, d), 1.9 (1H, br s); MS (ES): 244 (MH+).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([CH:8]2[CH2:10][CH2:9]2)[N:5]=[C:4]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=2)[N:3]=1.[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][C:26]([NH2:28])=[O:27])=[CH:21][CH:20]=1>CN1C(=O)CCC1.O>[Cl:17][C:13]1[CH:12]=[C:11]([C:4]2[N:3]=[C:2]([NH:18][C:19]3[CH:20]=[CH:21][C:22]([CH2:25][C:26]([NH2:28])=[O:27])=[CH:23][CH:24]=3)[CH:7]=[C:6]([CH:8]3[CH2:10][CH2:9]3)[N:5]=2)[CH:16]=[CH:15][CH:14]=1
Reactant: Clc1cccc(-c2nc(Cl)cc(C3CC3)n2)c1
Reactant: NC(=O)Cc1ccc(N)cc1
Solvent: CN1CCCC1=O
Solvent: O
Product: NC(=O)Cc1ccc(Nc2cc(C3CC3)nc(-c3cccc(Cl)c3)n2)cc1
Temperature: 120 °C
Yield: 74.3 %

Procedure:
A 10-mL microwave vial was charged with 4-chloro-2-(3-chlorophenyl)-6-cyclopropylpyrimidine (0.100 g, 0.38 mmol) and (4-aminophenyl)acetamide (0.113 g, 0.75 mmol) in NMP (3 mL). The resulting mixture was heated at 120° C. under microwave irradiation for 2 h. The reaction mixture was cooled, diluted with water (50 mL) affording a solid. The solid was isolated by filtration and purified by chromatography on silica using hexanes/ethyl acetate (10:0 to 0:10) as eluent to afford the title compound (0.107 g, 78%) as a white solid. MW=378.85. M.p. 174-176° C. 1H NMR (DMSO-d6, 500 MHz) δ 9.51 (s, 1H), 8.27-8.22 (m, 2H), 7.61 (d, J=8.0 Hz, 2H), 7.57-7.52 (m, 2H), 7.43 (br s, 1H), 7.25 (d, J=8.5 Hz, 2H), 6.85 (br s, 1H), 6.63 (s, 1H), 3.35 (s, 2H), 2.07-2.00 (m, 1H), 1.12-1.06 (m, 2H), 1.03-0.95 (m, 2H); ESI MS m/z 379 [M+H]+.
Reaction SMILES: [OH:1][C:2]1[N:6]([C:7]2[CH:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][N:8]=2)[N:5]=[CH:4][CH:3]=1.[I:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22]O)=[C:18]([O:24][CH3:25])[CH:17]=1>>[I:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][O:1][C:2]2[N:6]([C:7]3[CH:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][N:8]=3)[N:5]=[CH:4][CH:3]=2)=[C:18]([O:24][CH3:25])[CH:17]=1
Reactant: N#Cc1ccnc(-n2nccc2O)c1
Reactant: COc1cc(I)ccc1CO
Product: COc1cc(I)ccc1COc1ccnn1-c1cc(C#N)ccn1

Procedure:
The title compound was prepared from 2-(5-hydroxy-1H-pyrazol-1-yl)pyridine-4-carbonitrile and (4-iodo-2-methoxyphenyl)methanol according to the procedure for the preparation of Example 39, part C. 1H NMR (400 MHz, CDCl3): δ 3.88 (3H, s), 5.20 (2H, s), 5.77 (1H, d, J=2.0 Hz), 7.13 (1H, d, J=8.0 Hz), 7.23 (1H, d, J=1.6 Hz), 7.33 (1H, dd, J=1.6 Hz, 8.0 Hz), 7.39 (1H, dd, J=1.2 Hz, 4.8 Hz), 7.57 (1H, d, J=2.0 Hz), 8.05 (1H, t, J=1.2 Hz), 8.70 (1H, d, J=0.8 Hz, 5.2 Hz). [M+H] Calc'd for C17H131 N4O2, 433. Found, 433.
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[CH2:7][CH:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:5][C:4]([CH3:18])([CH3:17])[NH:3]1.[O:20]1[CH2:44][CH:21]1[CH2:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([C:33]2[CH:38]=[CH:37][C:36]([O:39][CH2:40][CH:41]3[O:43][CH2:42]3)=[CH:35][CH:34]=2)([CH3:32])[CH3:31])=[CH:26][CH:25]=1>CO>[OH:43][CH:41]([CH2:42][N:8]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH:6]1[CH2:7][C:2]([CH3:1])([CH3:19])[NH:3][C:4]([CH3:17])([CH3:18])[CH2:5]1)[CH2:40][O:39][C:36]1[CH:37]=[CH:38][C:33]([C:30]([C:27]2[CH:28]=[CH:29][C:24]([O:23][CH2:22][CH:21]([OH:20])[CH2:44][N:8]([CH:6]3[CH2:5][C:4]([CH3:18])([CH3:17])[NH:3][C:2]([CH3:19])([CH3:1])[CH2:7]3)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])=[CH:25][CH:26]=2)([CH3:32])[CH3:31])=[CH:34][CH:35]=1
Reactant: CCCCCCCCNC1CC(C)(C)NC(C)(C)C1
Reactant: CC(C)(c1ccc(OCC2CO2)cc1)c1ccc(OCC2CO2)cc1
Solvent: CO
Product: CCCCCCCCN(CC(O)COc1ccc(C(C)(C)c2ccc(OCC(O)CN(CCCCCCCC)C3CC(C)(C)NC(C)(C)C3)cc2)cc1)C1CC(C)(C)NC(C)(C)C1
Reaction time: 6 h

Procedure:
A mixture of 13 g of 2,2,6,6-tetramethyl-4-octylaminopiperidine and 8 g of 2,2-bis[p-(2,3-epoxypropoxy)phenyl]propane in 200 ml of methanol was refluxed, with stirring, for 6 hours. At the end of this time, the solvent was removed from the residue by evaporation under reduced pressure, leaving a residue, which was purified by column chromatography through silica gel eluted with a 20:4:2:1 by volume mixture of ethyl acetate, benzene, ethanol and triethylamine. The desired compound was obtained in the form of a colourless, transparent, very viscous liquid having an Rf value of 0.27 on thin layer chromatography on silica gel developed with a 20:4:2:1 by volume mixture of ethyl acetate, benzene, ethanol and triethylamine.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1F)([O-:3])=[O:2].[CH:11]1[CH:12]=[CH:13][C:14]([NH2:22])=[C:15]([C:17]([CH2:19][CH2:20][NH2:21])=[O:18])[CH:16]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[NH2:22][C:14]1[CH:13]=[CH:12][CH:11]=[CH:16][C:15]=1[C:17]([CH:19]([C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[N+:1]([O-:3])=[O:2])[CH2:20][NH2:21])=[O:18]
Reactant: NCCC(=O)c1ccccc1N
Reactant: O=[N+]([O-])c1ccccc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: NCC(C(=O)c1ccccc1N)c1ccccc1[N+](=O)[O-]

Procedure:
2 ml of 2-nitro-fluorobenzene were reacted in 20 ml DMF, at room temperature, with 5 g of kynuramine and 3 g of potassium carbonate, to yield the desired product; reaction time was 2 h. The reaction mixture was placed in 250 ml of water and stirred. It was extracted into ethylacetate (2×100 ml), ethylacetate layer was washed twice with water (50 ml), dried with sodium sulphate and the solvent was distilled off. The crude material was purified by column chromatography run with ethylacetate and hexane mixture (1:9).
Reaction SMILES: [O-]CC.[Na+].Cl.[Cl:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]([NH2:13])=[NH:12])=[CH:9][CH:8]=1.C([O:18][C:19](=O)[CH:20]([CH3:26])[C:21](OCC)=[O:22])C.Cl>C(O)C>[Cl:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]2[N:13]=[C:19]([OH:18])[C:20]([CH3:26])=[C:21]([OH:22])[N:12]=2)=[CH:9][CH:8]=1
Reactant: CCOC(=O)C(C)C(=O)OCC
Reactant: N=C(N)c1ccc(Cl)cc1
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: Cc1c(O)nc(-c2ccc(Cl)cc2)nc1O
Temperature: 40 °C
Reaction time: 44 h

Procedure:
To ethanol (20 ml) was added sodium ethoxide solution (7.76 ml of a 21% wt solution in ethanol), 4-chlorobenzamidine hydrochloride (1.0 g) and diethylmethylmalonate (0.89 ml). The suspension was stirred at 40° C. in an inert atmosphere for 44 hrs after which time it was cooled to 5° C. and treated dropwise with concentrated hydrochloric acid to a pH of 2. The resulting suspension was filtered and washed with excess water, then ethanol (20 ml) and diethyl ether (20 ml) affording the title compound as a solid (1.71 g).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][CH:9]([NH2:11])[CH3:10])[CH:5]=[CH:6][CH:7]=1.[CH:12](OCC)=[O:13]>>[NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][CH:9]([NH:11][CH:12]=[O:13])[CH3:10])[CH:5]=[CH:6][CH:7]=1
Reactant: CCOC=O
Reactant: CC(N)Cc1cccc(N)c1
Product: CC(Cc1cccc(N)c1)NC=O
Reaction time: 10 h

Procedure:
A mixture of 1-(3'-amino-phenyl)-2-amino-propane and 12.5 ml of ethyl formate was boiled for 10 hours, and then the reaction mixture was evaporated, leaving 1-(3'-aminophenyl)-2-(formyl-amino)-propane. 4.45 gm of this amide were dissolved in 25 ml of pyridine, 2.6 ml of chlorothioformic acid-S-ethyl ester were added to the solution at 10°-20° C., and the mixture was allowed to stand for a few hours. Thereafter, the reaction solution was poured into ice water, and the aqueous mixture was extracted with ether. The ethereal extract was washed five times with water and once briefly with 1/10 N hydrochloric acid, and was then evaporated, leaving as a residue 1-[3'-(ethylthiocarbonyl-amino)-phenyl]-2-(formyl-amino)-propane. The residue was added to a mixture of 75 ml of methanol and 5 ml of concentrated hydrochloric acid, and the mixture was allowed to stand for three days at room temperature. Thereafter, the resulting solution was evaporated, the residue was triturated with acetonitrile, and the crystalline product formed thereby was recrystallized from acetonitrile and a little water, yielding the hydrochloride of the formula ##STR21## which had a melting point of 185°-186° C.
Reaction SMILES: [CH3:1][CH:2]([CH3:12])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]([OH:11])=[O:10].[CH2:13](O)[C:14]1[CH:22]=[CH:21][C:19]([OH:20])=[C:16]([O:17][CH3:18])[CH:15]=1.O>CCCCCCC>[CH3:1][CH:2]([CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]([O:11][CH2:13][C:14]1[CH:22]=[CH:21][C:19]([OH:20])=[C:16]([O:17][CH3:18])[CH:15]=1)=[O:10])[CH3:12]
Reactant: COc1cc(CO)ccc1O
Reactant: CC(C)CCCCCCC(=O)O
Solvent: O
Solvent: CCCCCCC
Product: COc1cc(COC(=O)CCCCCCC(C)C)ccc1O
Temperature: 45 °C
Reaction time: 37.5 h
Yield: 93.2 %

Procedure:
8-Methylnonanoic acid (1.65 g, 9.59 mmol), vanillyl alcohol (1.34 g, 8.70 mmol), and lipase PS-C “Amano” I (enzyme immobilized on ceramic: 335 mg) were measured and placed in a flask (25 ml). The mixture in the flask free of a plug was heated with stirring in an oil bath at 45° C. for 37.5 hours. After 2 to 3 hours of stirring with heating, attachment of water on the wall of the upper part of the flask was observed. The flask was returned to room temperature, heptane (10 ml) was added to the reaction mixture, and the mixture was stirred for 10 minutes. The immobilized enzyme and a small amount of precipitated vanillyl alcohol were removed by filtration. The filtrate was concentrated under reduced pressure, and the obtained oil was analyzed by HPLC to find that dihydrocapsiate was contained in 95.7 area %. The mixture was partitioned with heptane (20 ml) and 10% aqueous citric acid solution (20 ml), and the aqueous layer was further extracted with heptane (20 ml). The combined heptane layer was washed with saturated brine (15 ml) and dried over anhydrous magnesium sulfate. Magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure to give a mixture (2.50 g) of dihydrocapsiate and 8-methylnonanoic acid as a colorless oil. As a result of the analysis, the yield of dihydrocapsiate was 73.1%, and the purity was 99.3 area % by HPLC. The mixture contained 27.4 wt % of 8-methylnonanoic acid relative to dihydrocapsiate.
Reaction SMILES: [CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][CH2:5][OH:6].[C:8]([C:12]1[CH:13]=[C:14]([CH:18]=[C:19]([C:22]([CH3:25])([CH3:24])[CH3:23])[C:20]=1[OH:21])[C:15](Cl)=[O:16])([CH3:11])([CH3:10])[CH3:9].[OH-].[Na+]>C(Cl)Cl.O>[C:22]([C:19]1[CH:18]=[C:14]([CH:13]=[C:12]([C:8]([CH3:11])([CH3:10])[CH3:9])[C:20]=1[OH:21])[C:15]([O:6][CH2:5][CH2:4][CH2:3][N:2]([CH3:7])[CH3:1])=[O:16])([CH3:25])([CH3:24])[CH3:23]
Reactant: CC(C)(C)c1cc(C(=O)Cl)cc(C(C)(C)C)c1O
Reactant: CN(C)CCCO
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Product: CN(C)CCCOC(=O)c1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 68.8 %

Procedure:
A solution of 41.3 g (400 mmol) of 3-dimethylaminopropanol in 200 ml of methylene chloride was added to a solution of 107.3 g (400 mmol) of 3,5-di-tert-butyl-4-hydroxybenzoyl chloride prepared as described in Example 1 in 400 ml of methylene chloride over a period of seven minutes. The reaction was exothermic. The reaction mixture was stirred for 90 minutes at room temperature and then washed with a solution of 16.0 g (400 mmol) of NaOH in 600 ml of water and then with water. The solution was dried over magnesium sulfate and concentrated to a residue on a rotary evaporator. The residue was then heated to reflux in 800 ml of heptane and filtered through supercel. The filtrate was cooled and the white solid was collected, washed with heptane and dried to give 92.3 g (68.8% of theory) of 3-dimethylaminopropyl 3,5-di-tert-butyl-4-hydroxybenzoate.