Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.CCCCCC.[C:19]([OH:36])(=[O:35])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34].[CH:37](=[O:55])[CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH:45]=[CH:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54].Cl>O1CCCC1>[OH:55][CH:37]([CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH:45]=[CH:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54])[CH:20]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[C:19]([OH:36])=[O:35]
Reactant: CCCCCCCCC=CCCCCCCCC=O
Reactant: CCCCCCCCCCCCCCCC(=O)O
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: CC(C)NC(C)C
Product: CCCCCCCCC=CCCCCCCCC(O)C(CCCCCCCCCCCCCC)C(=O)O
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 47.5 %

Procedure:
Diisopropyl amine (5.04 ml, 36.02 millimole) and dry tetrahydrofuran (30 ml) were introduced into a reaction vessel sufficiently substituted by argon gas. The reaction mixture was cooled to -78° C., and then 1.6M butyl lithium/hexane solution (23.64 ml, 37.82 millimole) was added dropwise thereto. The cooling bath was removed and the solution was allowed to warm to 0° C. and stirred for 30 minutes at the same temperature. The lithium diisopropylamide/tetrahydrofuran solution was again cooled to -78° C., and palmitic acid (4.62 g, 18.02 millimole) in dry tetrahydrofuran (60 ml) was added thereto, and the reaction mixture was stirred for 15 minutes at the same temperature (-78° C.). Then, the reaction temperature was raised to room temperature, and the reaction was continued for 1 hour. The reaction mixture was again cooled to -78° C., and 9-octadecenal (4 g, 15.02 millimole) in dry tetrahydrofuran (60 ml) was added dropwise thereto. The obtained mixture was reacted for 4 hours under the same conditions, and allowed to warm to 0° C., and the reaction was stopped by adding 1N hydrochloric acid (200 ml). The reaction mixture was extracted thrice with chloroform. The organic phase was washed twice with water and then dried over anhydrous sodium sulfate. The inorganic salt was filtered off and the solvent was distilled off from the filtrate. The obtained residue was dissolved in a developing solvent and fractionated through silicagel chromatography (n-hexane:ethyl acetate=8:2→chloroform:methanol=95:5) to give 3-hydroxy-2-n-tetradecyl-11-icosenoic acid (II)(3.73 g, yield 47.5%) in the form of white viscous solid.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C@@H:3]([OH:32])[CH2:4][C@H:5]([NH:19][C:20]([C@@H:22]([NH:27][C:28](=[O:31])[O:29][CH3:30])[C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:9][CH:8]=1.[CH3:40][C:41]([CH3:64])([CH3:63])[C@H:42]([N:46]1[CH2:50][CH2:49][N:48]([CH2:51][C:52]2[N:56]([CH3:57])[C:55]3[CH:58]=[CH:59][CH:60]=[CH:61][C:54]=3[N:53]=2)[C:47]1=[O:62])[C:43](O)=[O:44].CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O.C(N(CC)C(C)C)(C)C>C1COCC1>[CH3:40][C:41]([CH3:64])([CH3:63])[C@H:42]([N:46]1[CH2:50][CH2:49][N:48]([CH2:51][C:52]2[N:56]([CH3:57])[C:55]3[CH:58]=[CH:59][CH:60]=[CH:61][C:54]=3[N:53]=2)[C:47]1=[O:62])[C:43]([NH:1][C@@H:2]([CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[C@@H:3]([OH:32])[CH2:4][C@H:5]([NH:19][C:20]([C@@H:22]([NH:27][C:28](=[O:31])[O:29][CH3:30])[C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:9][CH:8]=1)=[O:44]
Reactant: Cn1c(CN2CCN([C@H](C(=O)O)C(C)(C)C)C2=O)nc2ccccc21
Reactant: COC(=O)N[C@H](C(=O)N[C@H](Cc1ccc(-c2ccccn2)cc1)C[C@H](O)[C@@H](N)Cc1ccccc1)C(C)(C)C
Agent: CCOP(=O)(OCC)On1nnc2ccccc2c1=O
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: COC(=O)N[C@H](C(=O)N[C@H](Cc1ccc(-c2ccccn2)cc1)C[C@H](O)[C@H](Cc1ccccc1)NC(=O)[C@@H](N1CCN(Cc2nc3ccccc3n2C)C1=O)C(C)(C)C)C(C)(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 52 %

Procedure:
A solution containing the product from Example 1H (0.025 g, 0.047 mmol) in THF (0.5 mL) was treated with the product from Example 59F(0.070 mmol), DEPBT (0.021 g, 0.070 mmol), and N,N-diisopropylethylamine (0.041 mL, 0.240 mmol) and the mixture was stirred at 25° C. for 2 hours. The mixture was partitioned between ethyl acetate and 10% Na2CO3 solution. The organic phase was washed with additional 10% Na2CO3 solution and brine, dried over MgSO4, filtered and concentrated. The product was purified by reversed phase chromatography on a C18 column eluting with 5-100% acetonitrile in water (0.1% TFA). The reaction was partitioned between ethyl acetate and saturated NaHCO3, and the organic phase was washed with brine and dried over MgSO4, filtered and concentrated, to give the title compound (0.021 g, 50% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.81 (s, 9 H), 0.88 (s, 9 H), 1.38 (m, 1 H), 1.53 (m, 1 H), 2.40 (m, 1 H), 2.64 (m, 3 H), 2.83 (m, 1 H), 3.12 (m, 4 H), 3.54 (m, 4 H), 3.82 (m, 3 H), 3.95 (m, 1 H), 4.03 (s, 1 H), 4.18 (m, 1 H), 4.43 (d, J=6.99 Hz, 1 H), 4.60 (m, 2 H), 6.92 (m, 4 H), 7.04 (m, 2 H), 7.21 (m, 4 H), 7.32 (m, 1 H), 7.58 (m, 3 H), 7.89 (m, 5 H), 8.65 (d, J=4.41 Hz, 1 H).
Reaction SMILES: [NH2:1][C:2]1[C:10]([O:11]C)=[CH:9][C:8]([Cl:13])=[CH:7][C:3]=1[C:4]([O-:6])=[O:5].Br.C([O-])([O-])=O.[Na+].[Na+]>C(O)(=O)C>[NH2:1][C:2]1[C:10]([OH:11])=[CH:9][C:8]([Cl:13])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5]
Reactant: COc1cc(Cl)cc(C(=O)[O-])c1N
Agent: Br
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: Nc1c(O)cc(Cl)cc1C(=O)O
Temperature: 25 °C
Yield: 35 %

Procedure:
A mixture of 2-amino-5-chloro-3-methoxybenzoate (2.76 g, 12.8 mmol), 48% aqueous solution of hydrobromic acid (25 mL) and glacial acetic acid (1 mL) was heated to reflux for 48 h. The reaction mixture was cooled down to room temperature, treated with saturated solution of Na2CO3 to pH˜6, concentrated and purified by column chromatography (silica gel, 90:10 dichloromethane/methanol) to afford 2-amino-5-chloro-3-hydroxybenzoic acid (0.84 g, 35%) as a light brown solid: MS (ESI+) m/z 188 (M+H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:16])[C:7]1[CH:12]=[CH:11][C:10]([CH:13]=O)=[CH:9][C:8]=1[CH3:15])([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:18][OH:19].C(=O)([O-])O.[Na+]>C(O)C.O>[C:1]([O:5][C:6](=[O:16])[C:7]1[CH:12]=[CH:11][C:10]([CH:13]=[N:18][OH:19])=[CH:9][C:8]=1[CH3:15])([CH3:4])([CH3:3])[CH3:2]
Reactant: NO
Reactant: Cc1cc(C=O)ccc1C(=O)OC(C)(C)C
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: Cc1cc(C=NO)ccc1C(=O)OC(C)(C)C
Temperature: 50 °C
Reaction time: 3.5 h
Yield: 55.5 %

Procedure:
To a suspension of 4-formyl-2-methyl-benzoic acid tert-butyl ester (Example I17) (60.3 g) and hydroxylamine hydrochloride (38.05 g) in ethanol (580 ml) was added a solution of sodium hydrogen carbonate (46 g) in water (60 ml). The reaction mixture was stirred at 50° C. for 3.5 hours. The solvent was removed and the residue diluted with ethyl acetate and water. The phases were separated and the organic layer was washed with water, dried over sodium sulfate and concentrated. The residue was crystallized from ethyl acetate and heptane to give 4-(hydroxyimino-methyl)-2-methyl-benzoic acid tert-butyl ester (35.72 g) as a white crystalline powder. 1H-NMR (CDCl3, 400 MHz): 7.86 (s, 1H), 7.70 (s, 1H), 7.45 (m, 2H), 2.60 (s, 3H), 1.60 (s, 9H).
Reaction SMILES: Cl[C:2]1[N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[CH:5]=[C:4]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=2[Cl:18])[N:3]=1.[F:19][C:20]([F:32])([F:31])[C:21]1[CH:22]=[CH:23][C:24]([NH:27][CH2:28][CH2:29][OH:30])=[N:25][CH:26]=1.ClC1C=CC(C(F)(F)F)=CN=1.NC(O)C>>[Cl:18][C:12]1[CH:13]=[C:14]([Cl:17])[CH:15]=[CH:16][C:11]=1[C:4]1[N:3]=[C:2]([O:30][CH2:29][CH2:28][NH:27][C:24]2[CH:23]=[CH:22][C:21]([C:20]([F:32])([F:19])[F:31])=[CH:26][N:25]=2)[N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[CH:5]=1
Reactant: Clc1ccc(-c2cc3nccn3c(Cl)n2)c(Cl)c1
Reactant: OCCNc1ccc(C(F)(F)F)cn1
Agent: CC(N)O
Agent: FC(F)(F)c1ccc(Cl)nc1
Product: FC(F)(F)c1ccc(NCCOc2nc(-c3ccc(Cl)cc3Cl)cc3nccn23)nc1

Procedure:
In analogy to the procedure described for Example 90, 46 mg (59% of theory) of the product are obtained starting from 50 mg (0.17 mmol) of 5-chloro-7-(2,4-dichlorophenyl)imidazo-[1,2-c]pyrimidine (Example 6A) by reaction with 48 mg (0.23 mmol) of 2-{[5-(trifluoromethyl)pyridin-2-yl]amino}ethanol, which can be prepared in analogy to the synthesis of Example 48A from 2-chloro-5-(trifluoromethyl)pyridine and aminoethanol, after subsequent purification by preparative HPLC.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH2:9][C:10]([CH3:12])=[CH2:11])[CH:3]=1.BrC1C=CC=C(O)C=1.[Cl:21]CC(C)=C.[CH2:26]([O:33][CH:34]1[CH2:39][CH2:38][C:37](=[O:40])[CH:36]([CH2:41][N:42]([CH3:44])[CH3:43])[CH2:35]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>>[ClH:21].[CH2:26]([O:33][CH:34]1[CH2:39][CH2:38][C:37]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH2:9][C:10]([CH3:12])=[CH2:11])[CH:3]=2)([OH:40])[CH:36]([CH2:41][N:42]([CH3:44])[CH3:43])[CH2:35]1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: CN(C)CC1CC(OCc2ccccc2)CCC1=O
Reactant: C=C(C)COc1cccc(Br)c1
Reactant: C=C(C)CCl
Agent: Oc1cccc(Br)c1
Product: C=C(C)COc1cccc(C2(O)CCC(OCc3ccccc3)CC2CN(C)C)c1
Product: Cl
Yield: 33 %

Procedure:
1-bromo-3-(2-methyl-allyloxy)-benzene, prepared by the alkylation of 1-bromo-3-hydroxy-benzene with 3-chloro-2-methyl-1-propene, was reacted with 4-benzyloxy-2-dimethylaminomethyl-cyclohexanone corresponding to the conditions described in Example 1. The base obtained was purified with 9:1 ether/methanol via a silica gel column, taken up in ether and treated with trimethylchlorosilane/water. Compound (4) was obtained.
Reaction SMILES: [CH2:1]([N:3]([CH2:16][CH2:17][N:18]1C(=O)C2=CC=CC=C2C1=O)[CH2:4][CH2:5][O:6][C:7]1[C:8]([N+:13]([O-:15])=[O:14])=[N:9][CH:10]=[CH:11][CH:12]=1)[CH3:2].NCCN(CC)CCF>>[NH2:18][CH2:17][CH2:16][N:3]([CH2:1][CH3:2])[CH2:4][CH2:5][O:6][C:7]1[C:8]([N+:13]([O-:15])=[O:14])=[N:9][CH:10]=[CH:11][CH:12]=1
Reactant: CCN(CCOc1cccnc1[N+](=O)[O-])CCN1C(=O)c2ccccc2C1=O
Agent: CCN(CCN)CCF
Product: CCN(CCN)CCOc1cccnc1[N+](=O)[O-]
Yield: 76.3 %

Procedure:
This compound was prepared, starting from compound 58 (2.00 g, 5.20 mmol), according to the procedure developed for compound 22. Reaction time under reflux: 12 h; the purification was performed using column chromatography (Al2O3, CH2Cl2/EtOH, 95/5, v/v) to give compound 59 (1.01 g, 3.97 mmol) as a yellow oil. Yield 77%; Rf (Al2O3, CH2Cl2/EtOH, 95/5, v/v) 0.36; 1H NMR (200 MHz, CDCl3) δ 1.11 (t, 3H, J=7.1 Hz), 2.72 (m, 8H), 2.99 (t, 2H, J=5.6 Hz), 4.28 (t, 2H, J=5.6 Hz), 7.63 (dd, 1H, J=4.3, 8.4 Hz), 7.71 (dd, 1H, J=1.5, 8.4 Hz), 8.13 (dd, 1H, J=1.5, 4.3 Hz); ESI-MS m/z 255.0 [M+H]+.
Reaction SMILES: N12CCCC1=NCCC2.[Br-].[C:11]([C:15]1[CH:40]=[CH:39][CH:38]=[CH:37][C:16]=1[CH2:17][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:13]C)=[O:12].[C:41]1([CH3:49])[CH:46]=[CH:45][C:44]([CH:47]=O)=[CH:43][CH:42]=1>C(#N)C>[C:11]([C:15]1[CH:40]=[CH:39][CH:38]=[CH:37][C:16]=1[CH:17]=[CH:49][C:41]1[CH:46]=[CH:45][C:44]([CH3:47])=[CH:43][CH:42]=1)([OH:13])=[O:12]
Reactant: Cc1ccc(C=O)cc1
Reactant: COC(=O)c1ccccc1C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: C1CN=C2CCCN2C1
Agent: [Br-]
Solvent: CC#N
Product: Cc1ccc(C=Cc2ccccc2C(=O)O)cc1
Yield: 91.1 %

Procedure:
1,5-Diazabicyclo[4.3.0]non-5-ene (29.1 g) was added to a solution of 2-(carbomethoxy)benzyl triphenylphosphonium bromide (100 g) and p-tolualdehyde (26.7 g) in acetonitrile (250 ml). The mixture was refluxed for 10 minutes, the solvents removed in vacuo and the residue dissolved in chloroform (200 ml). Washed with lN aqueous hydrochloric acid (100ml) and water (100 ml), then dried over sodium sulphate filtered and evaporated. The residue was refluxed overniqht in water (250 ml) and methanol (100 ml) containing potassium hydroxide (56 g). then cooled diluted with water (250 ml) and washed with chloroform (3×250 ml). The aqueous solution was acidified to pH 2 with conc. hydrochloric acid, and extracted with chloroform (3×200 ml). The extract was washed dried and evaporated to afford 2-carboxy-4'-methyl stilbene (44.2 g) as a cis- trans mixture. This mixture was hydrogenated in dimethylformamide (50 ml) at 50 psi in the presence of 10% palladium on charcoal catalyst (2 g). The catalyst was removed by filtration and solvent evaporated. The residue Was dissolVed in ether, ,washed with water, dried and filtered to afford after evaporation and hexane trituration. 2-(2-(4-methylphenyl)ethyl)benzoic acid (40.0 g). m.p. 80°-82° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([C:10]#[CH:11])=[CH:6][CH:5]=1.I[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[OH:20]>>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:20][C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=3[CH:11]=2)=[CH:6][CH:5]=1)=[O:12]
Reactant: Oc1ccccc1I
Reactant: C#Cc1ccc(C(=O)OC)cc1
Product: COC(=O)c1ccc(-c2cc3ccccc3o2)cc1

Procedure:
The general procedure was used to convert 4-Ethynyl-benzoic acid methyl ester and 2-iodophenol to the title product. Purification by flash chromatography (10% ethyl acetate in hexanes) gave the analytically pure product as a white solid (300 mg, 67% yield). 1H NMR δ 8.09 (dd, J=8.70, 2H), 7.90 (d, J=8.70, 2H), 7.52-7.62 (dd, J=8.10, 2H), 7.24-7.33 (m, 2H), 7.13 (s, 1H), 3.93 (s, 3H). 13C NMR δ 167.00, 155.50, 155.00, 134.80, 130.50, 130.00, 129.30, 125.40, 125.0, 123.60, 121.60, 111.70, 103.80, 52.60. Anal. Calcd. for C16H12O3: C, 76.18; H, 4.79. Found C, 75.97; H, 4.75. m.p. 176-178° C. (lit., 5176-177° C.).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10](/[CH:12]=[CH:13]/[C:14]([OH:16])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:39][N:40]([CH:57]([C:65](=[O:68])[NH:66][CH3:67])[CH2:58][C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)[C:41](=[O:56])[CH:42]([NH:54][CH3:55])[CH2:43][C:44]1[CH:53]=[CH:52][C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[CH:45]=1.C(N(C(C)C)C(C)C)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10](/[CH:12]=[CH:13]/[C:14](=[O:16])[N:54]([CH3:55])[C@@H:42]([C:41](=[O:56])[N:40]([CH3:39])[C@@H:57]([C:65](=[O:68])[NH:66][CH3:67])[CH2:58][C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[CH2:43][C:44]2[CH:53]=[CH:52][C:51]3[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=3)[CH:45]=2)[CH2:11]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)N1CC(/C=C/C(=O)O)C1
Reactant: CNC(=O)C(Cc1ccccc1)N(C)C(=O)C(Cc1ccc2ccccc2c1)NC
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2cccnc21
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CNC(=O)[C@@H](Cc1ccccc1)N(C)C(=O)[C@@H](Cc1ccc2ccccc2c1)N(C)C(=O)/C=C/C1CN(C(=O)OC(C)(C)C)C1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 64.5 %

Procedure:
3-((E)-2-Carboxyvinyl)azetidine-1-carboxylic acid tert-butyl ester (0.28 g; 1.24 mmol) was dissolved in methylene chloride (3 mL). 1-Hydroxy-7-azabenzotriazole (0.17 g; 1.24 mmol) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (0.26 g; 1.36 mmol) were added and the reaction mixture was stirred for 15 min at room temperature. N-Methyl-2-methylamino-N-(1-(methyl-carbamoyl)-2-phenylethyl)-3-(2-naphthyl)propionamide (0.50 g; 1.24 mmol) (prepared as in example 1) was dissolved in methylene chloride (3 mL) and added to the reaction mixture. Ethyidiisopropylamine (0.21 mL; 1.24 mmol) was added and the reaction mixture was stirred for 12 hours at room temperature. Methylene chloride (20 mL) was added and the reaction mixture was washed with water (10 mL), an aqueous solution of sodium hydrogen sulfate (10 mL; 10%), an aqueous solution of sodium hydrogen carbonate (10 mL; sat.) and water (10 mL). The organic phase was dried (magnesium sulfate) and evaporated in vacuo. The residue was chromatographed on silica (2,5×20 cm) using 2.5%(7% ammonia in ethanol) in methylene chloride as eluent to afford 0.49 g of 3-((E)-2-(methyl((1R)-1-(methyl((1R)-1-(methylcarbamoyl)-2-phenylethyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)vinyl)azetidine-1-carboxylic acid tert-butyl ester.
Reaction SMILES: [CH2:1]([N:3]([CH2:9][CH3:10])[CH2:4][C:5]#[C:6][CH2:7][NH2:8])[CH3:2].[Cl:11][C:12]([CH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1)([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:13](Cl)=[O:14]>C1C=CC=CC=1>[ClH:11].[CH2:1]([N:3]([CH2:9][CH3:10])[CH2:4][C:5]#[C:6][CH2:7][NH:8][C:13](=[O:14])[C:12]([Cl:11])([CH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:2]
Reactant: O=C(Cl)C(Cl)(c1ccccc1)C1CCCCC1
Reactant: CCN(CC)CC#CCN
Solvent: c1ccccc1
Product: CCN(CC)CC#CCNC(=O)C(Cl)(c1ccccc1)C1CCCCC1
Product: Cl
Temperature: 25 °C
Reaction time: 19.5 h
Yield: 92.8 %

Procedure:
A solution of 4-diethylamino-2-butynylamine (0.14 g) in benzene (2.5 ml) was added dropwise to a solution of 2-chloro-2-cyclohexyl-2-phenylacetyl chloride (0.27 g) in benzene (2.5 ml below 25° C. After being stirred at room temperature for 19.5 hours, the resulting precipitates were collected by filtration and recrystallized from a mixture of acetone and diethyl ether to give N-(4-diethylamino-2-butynyl)-2-chloro-2-cyclohexyl-2-phenylacetamide hydrochloride (0.19 g).
Reaction SMILES: [CH:1]1([CH:7]=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.Cl.[OH-].[Na+]>C(OCC)(=O)C>[CH:1]1([CH:7]([C:13]2[CH:14]=[CH:15][C:10]([NH2:9])=[CH:11][CH:12]=2)[C:13]2[CH:14]=[CH:15][C:10]([NH2:9])=[CH:11][CH:12]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=CC1CCCCC1
Reactant: Nc1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Product: Nc1ccc(C(c2ccc(N)cc2)C2CCCCC2)cc1
Temperature: 110 °C

Procedure:
The synthesis of an amine hardener composition was carried out as follows: Cyclohexane carboxaldehyde (5 g, 44.6 mmol, 1 equiv) and aniline (12.5 g, 134.3 mmol, 3 equiv) were added to a 100 mL two-necked round bottom flask equipped with a condenser and thermocouple. The flask was placed under nitrogen and 0.25 mL concentrated HCl was added. After refluxing at 110° C. for 5 hours, the reaction was allowed to cool to 50° C. and 0.75 mL of 50 wt % aqueous NaOH was added. Ethyl acetate (EtOAc) was added and the solution was washed with water (3×30 mL). The organic layer was dried over MgSO4, filtered, and the solvent removed in vacuo. The resulting mixture contained residual aniline. Purification of the material was performed via column chromatography (66:33 hexane:EtOAc) to yield a tacky yellow solid, 4,4′-(cyclohexylmethylene)dianiline [Structure (XI)], Rf=0.25.
Reaction SMILES: [CH:1]([N:4]1[CH:8]=[CH:7][C:6]([C:9]([OH:11])=[O:10])=[N:5]1)([CH3:3])[CH3:2].S(=O)(=O)(O)O.[CH3:17]O>>[CH:1]([N:4]1[CH:8]=[CH:7][C:6]([C:9]([O:11][CH3:17])=[O:10])=[N:5]1)([CH3:3])[CH3:2]
Reactant: CC(C)n1ccc(C(=O)O)n1
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)c1ccn(C(C)C)n1
Reaction time: 5 h
Yield: 76 %

Procedure:
To a solution of 1-isopropyl-1 h-pyrazole-3-caboxylic acid (0.9757 g, 6.33 mmol, Matrix Scientific) in MeOH (31.6 ml) in a glass pressure vessel was added sulfuric acid (0.355 ml, 6.33 mmol Sigma Aldrich). The vessel was sealed and the rxn was brought to reflux to stir. (NOTE: A portable blast shield was used.) Rxn was allowed to stir for 5 hours. The rxn was concentrated in vacuo. The residue was diluted with water and extracted with EtOAc. The organic extract was washed with water, dried over MgSO4, filtered and concentrated in vacuo to give methyl 1-isopropyl-1H-pyrazole-3-carboxylate (0.8073 g, 4.80 mmol, 76% yield) as a clear oil. MS m/z=168.9 [M+H]+. Calculated for C8H12N2O2: 168.09. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.55 (d, J=6.85 Hz, 6H) 3.93 (s, 3H) 4.63 (dt, J=13.50, 6.75 Hz, 1H) 6.83 (d, J=2.35 Hz, 1H) 7.46 (d, J=2.35 Hz, 1H)
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]([OH:13])=O.[NH2:14][C:15]1[N:19]=[C:18]([NH2:20])[NH:17][N:16]=1>O1CCCC1>[NH2:20][C:18]1[N:19]=[C:15]([NH:14][C:11]([C:2]2[CH:3]=[CH:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:1]=2)=[O:13])[NH:16][N:17]=1
Reactant: Nc1n[nH]c(N)n1
Reactant: O=C(O)c1ccc2ccccc2c1
Solvent: C1CCOC1
Product: Nc1n[nH]c(NC(=O)c2ccc3ccccc3c2)n1
Yield: 32.3 %

Procedure:
A mixture of 2-naphthyl carboxylic acid (2.0 g, 11.6 mmol) and N,N'-carbonyldiimidazole (2.07 g, 12.8 mmol) in dry tetrahydrofuran (50 ml) was stirred at reflux temperature for 1 h. To the cooled reaction mixture was added 3,5-diamino-1,2,4-triazole (1.15 g, 11.6 mmol) and the resulting mixture was refluxed for 3 h. The cooled reaction mixture was quenched with water (75 ml) and extracted with diethyl ether (2×75 ml). The combined organic extracts were washed with saturated aqueous sodium chloride (2×50 ml), dried (MgSO4), filtered and evaporated in vacuo. The residue was crystallised from diethyl ether (20 ml), filtered off and washed with diethyl ether (2×10 ml), dried in vacuo afforded 0.95 g (32%) of the title compound as a solid.
Reaction SMILES: [CH2:1]([N:3]1[C:15]2[CH:14]3[CH2:16][CH2:17][CH:11]([CH2:12][CH:13]3[C:18](O)=[O:19])[C:10]=2[C:9]2[C:4]1=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH3:2].ClC(OCC)=O.[N-:27]=[N+:28]=[N-:29].[Na+].[Cl-].[Na+]>O1CCCC1.O.C(N(CC)CC)C>[CH2:1]([N:3]1[C:15]2[CH:14]3[CH2:16][CH2:17][CH:11]([CH2:12][CH:13]3[C:18]([N:27]=[N+:28]=[N-:29])=[O:19])[C:10]=2[C:9]2[C:4]1=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH3:2]
Reactant: CCn1c2c(c3ccccc31)C1CCC2C(C(=O)O)C1
Reactant: [N-]=[N+]=[N-]
Agent: CCOC(=O)Cl
Agent: [Cl-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: O
Product: CCn1c2c(c3ccccc31)C1CCC2C(C(=O)N=[N+]=[N-])C1
Temperature: 25 °C
Reaction time: 3 h
Yield: 91.3 %

Procedure:
To a stirred solution of 9-ethyl-1,2,3,4-tetrahydro-1,4-ethanocarbazole-2-carboxylic acid (5.0 g, 0.0186 mole, described in Example 3) in dry tetrahydrofuran (50 ml), under nitrogen at 20°-22° C., triethylamine (11.5 ml) was added, followed by ethyl chloroformate (2.8 ml) at 20° C. After stirring at room temperature for 3 hr, the suspension of mixed anhydride was cooled to -10° C. and treated dropwise with a solution of sodium azide (2.94 g in 10 ml of water). The slurries were stirred for 1 hr at -10° C. Water was added and saturated with sodium chloride, then extracted with diethyl ether. The organic layer was washed with water, dried, evaporated to give a yellow oil (ca. 5 g) of 9-ethyl-2,3,4,9-tetrahydro-1,4-ethano-1H-carbazole-2-carbonyl azide: IR (CHCl3) 2135 cm-1.
Reaction SMILES: [C:1]([O:4][CH2:5][CH3:6])(=[O:3])[CH3:2].C(N([CH2:12][CH3:13])CC)C.FC(F)(F)S(O[Si:20](OS(C(F)(F)F)(=O)=O)([CH3:22])[CH3:21])(=O)=O>>[CH3:21][Si:20]([CH3:22])([CH2:2][C:1]([O:4][CH2:12][CH3:13])=[O:3])[CH2:2][C:1]([O:4][CH2:5][CH3:6])=[O:3]
Reactant: CCOC(C)=O
Reactant: CCN(CC)CC
Reactant: C[Si](C)(OS(=O)(=O)C(F)(F)F)OS(=O)(=O)C(F)(F)F
Product: CCOC(=O)C[Si](C)(C)CC(=O)OCC
Temperature: 0 °C
Reaction time: 1 h
Yield: 23 %

Procedure:
An oven-dried 100 mL-RB flask is charged with ethyl acetate (5.3 g, 0.06 mol), and triethylamine (6.1 g, 0.06 mol). The flask is then cooled in an ice-water bath, and dimethylsilanediyl bis(trifluoromethanesulfonate) (10.7 g, 0.03 mol) is added dropwise. After stirring at 0° C. for 1 h, the mixture is warmed up to room temperature and stirred overnight. The mixture is poured into ice-water and then extracted with diethyl ether. The combined ether extract is washed with brine and dried over sodium sulfate. After filtration, the filtrate is concentrated and the residue is distilled in a Kugelrohr to yield 1.6 g (23%) of the product as a light-yellowish oil. 1H NMR (500 MHz, CDCl3, in ppm) δ 4.10 (q, 4H, J=7.5 Hz), 1.99 (s, 4H), 1.24 (t, 6H, J=7.5 Hz), 0.22 (s, 6H).