Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH2:11][CH2:10][C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)=O.[Sn](Cl)(Cl)(Cl)Cl.[C:24](#[N:32])[C:25]1[C:26](=[CH:28][CH:29]=[CH:30][CH:31]=1)[NH2:27].[OH-].[Na+]>O1CCCC1.C(Cl)(Cl)Cl>[CH2:1]([N:8]1[CH2:12][CH2:11][CH2:10][C:9]1=[N:27][C:26]1[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=1[C:24]#[N:32])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: N#Cc1ccccc1N
Reactant: O=C1CCCN1Cc1ccccc1
Agent: Cl[Sn](Cl)(Cl)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClC(Cl)Cl
Solvent: C1CCOC1
Solvent: O=P(Cl)(Cl)Cl
Product: N#Cc1ccccc1N=C1CCCN1Cc1ccccc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 91.1 %

Procedure:
The compound 2-(1-Benzyl-pyrrolidin-2-ylideneamino)benzonitrile (Compound 24) was synthesized by mixing chloroform (25 mL), tetrahydrofuran (25 mL), 1-benzyl-2-pyrrolidinone (5.16 g, 29.4 mmol), phosphorus oxychloride (5.2 mL) and tin(IV) chloride (1.0 mL), stirring at room temperature for 1.5 hours, and adding anthranilonitrile (3.3 g, 27.9 mmol) in portions. The mixture was then stirred at 50° C. for 5 hours under heating and ice-water (15 mL) and 10% aqueous sodium hydroxide solution was added to make weak alkaline. The organic solvent was removed under reduced pressure and the mixture was extracted with chloroform. The extract was dried over anhydrous sodium sulfate and condensed under vacuum. The crude product was purified by flash chromatography (chloroform-methanol, 100:1) to yield 7.0 g (91%) Compound 24 as slightly yellow needles; mp 59-61° C.; IR (KBr): 2217, 1628, 1439, 1279 cm−1; 1H NMR (DMSO-d6): δ 7.06-7.69 (m, 9H), 4.83 (s, 2H), 3.46 (t, 2H), 2.60 (t, 2H), 2.10 (m, 2H); 13C NMR (CDCl3): δ 162.8, 156.3, 137.6, 133.7, 132.9, 128.7, 128.3, 127.4, 122.8, 121.7, 118.8, 105.9, 48.3, 47.3, 27.7, 19.6. Anal. Calcd. for C18H17N3(275.35): C, 78.52; H, 6.22; N, 15.26. Found: C, 78.37; H, 6.20; N, 15.17.
Reaction SMILES: FC(F)(F)C(O)=O.[OH:8][C:9]1[CH:43]=[CH:42][C:12]([O:13][CH2:14][CH2:15][CH:16]2[CH2:21][CH2:20][N:19]([C:22]3[CH:23]=[N:24][CH:25]=[C:26]([O:28][CH2:29][C@@H:30]4[CH2:34][CH2:33][CH2:32][N:31]4C(OC(C)(C)C)=O)[CH:27]=3)[CH2:18][CH2:17]2)=[CH:11][CH:10]=1>C(Cl)Cl.O>[NH:31]1[CH2:32][CH2:33][CH2:34][C@H:30]1[CH2:29][O:28][C:26]1[CH:27]=[C:22]([N:19]2[CH2:18][CH2:17][CH:16]([CH2:15][CH2:14][O:13][C:12]3[CH:42]=[CH:43][C:9]([OH:8])=[CH:10][CH:11]=3)[CH2:21][CH2:20]2)[CH:23]=[N:24][CH:25]=1
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1COc1cncc(N2CCC(CCOc3ccc(O)cc3)CC2)c1
Solvent: O=C(O)C(F)(F)F
Solvent: O
Solvent: ClCCl
Product: Oc1ccc(OCCC2CCN(c3cncc(OC[C@@H]4CCCN4)c3)CC2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 52 %

Procedure:
Trifluoroacetic acid (1.5 mL) was added slowly to a solution of 3-[4-[2-(4-hydroxyphenoxy)ethyl]-1-piperidinyl]-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (260 mg) in CH2Cl2/H2O (7.5/0.15 mL) at room temperature under N2. The solution was stirred overnight at room temperature. After removing the solvent, the residue was purified by preparative HPLC (column: SunFire Prep C18, 100×19 mm, 5 μm particle size; UV detection at 254 nm; flow 18 mL/min; mobile phase: A, water with 0.05% CF3COOH; B, CH3CN; 5% to 30% B in A in 6 min). The eluate was partially evaporated under reduced pressure (bath 30° C.) to remove CH3CN. The residue was basified with saturated aqueous NaHCO3 solution and extracted with EtOAc. The combined organic layers were washed with brine and dried over Na2SO4. After concentration in vacuo, the free base (108 mg, 58%) was obtained as a yellowish solid. LC-MS (ESI) m/z 398 (M+H+).
Reaction SMILES: [N:1]1([C:7]2[CH:8]=[C:9]([CH2:13]O)[CH:10]=[CH:11][CH:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C1C=CC(P([N:29]=[N+:30]=[N-:31])(C2C=CC=CC=2)=O)=CC=1.C1CCN2C(=NCCC2)CC1.CCOC(C)=O>C1COCC1>[N:29]([CH2:13][C:9]1[CH:8]=[C:7]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)[CH:12]=[CH:11][CH:10]=1)=[N+:30]=[N-:31]
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Reactant: OCc1cccc(N2CCOCC2)c1
Solvent: C1CCOC1
Solvent: C1CCC2=NCCCN2CC1
Solvent: CCOC(C)=O
Product: [N-]=[N+]=NCc1cccc(N2CCOCC2)c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 141 %

Procedure:
A solution of (3-morpholin-4-ylphenyl)methanol (0.10 g, 0.52 mmol), in THF (1.0 mL) was cooled to 0° C. and DPPA (0.13 mL, 0.62 mmol) was added, followed by DBU (0.093 mL, 0.62 mmol). The solution was allowed to warm to r.t. and stirred for 12 h. The solution was poured into EtOAc (100 mL) and this was washed with H2O (50 mL) and 5% HCl(aq) (50 mL). The organic layer was dried (Na2SO4), filtered and concentrated in vacuo to give 0.16 g (>100% yield) of 4-[3-(azidomethyl)phenyl]morpholine, (TLC: UV active spot, Rf of 0.7 in 1:1 hexanes/EtOAc), which was used without further purification.
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)C[C:2]1=O.Cl.C1([NH:18]N)C=CC=CC=1>C(O)(=O)C>[NH:18]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH:1]=[CH:2]1
Reactant: O=C1Cc2ccccc2C1
Reactant: NNc1ccccc1
Agent: Cl
Solvent: CC(=O)O
Product: c1ccc2[nH]ccc2c1
Temperature: 0 °C

Procedure:
2-Indanone (5.25 g, 39.7 mmol) and phenylhydrazine hydrochloride (5.74 g, 39.7 mmol), were heated to reflux in glacial acetic acid (60 cm3) for 1 hour, and then cooled. The solution was poured into ice/water, and the solid precipitate collected by filtration. After partial purification by column chromatography, and crystallization (charcoal) from ethyl acetate to yielded colourless needles of the title compound. Yield 0.64 g (80%). M.p. 205° C. 1H NMR (DMSO-d6) δ: 3.65 (2H, s,), 7.0-7.2 (8H,), 10.40 (1H, br,).
Reaction SMILES: Cl[C:2]1[C:3]([NH:12][S:13]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([N+:22]([O-:24])=[O:23])[CH:17]=2)(=[O:15])=[O:14])=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.[Cl:25][C:26]1[CH:31]=[C:30]([NH2:32])[CH:29]=[C:28]([Cl:33])[N:27]=1.CC1C=CC(C)=CC=1>ClCCl>[Cl:25][C:26]1[CH:31]=[C:30]([NH:32][C:2]2[C:3]([NH:12][S:13]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([N+:22]([O-:24])=[O:23])[CH:17]=3)(=[O:14])=[O:15])=[N:4][C:5]3[C:10]([N:11]=2)=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:29]=[C:28]([Cl:33])[N:27]=1
Reactant: Nc1cc(Cl)nc(Cl)c1
Reactant: O=[N+]([O-])c1cccc(S(=O)(=O)Nc2nc3ccccc3nc2Cl)c1
Solvent: ClCCl
Solvent: Cc1ccc(C)cc1
Product: O=[N+]([O-])c1cccc(S(=O)(=O)Nc2nc3ccccc3nc2Nc2cc(Cl)nc(Cl)c2)c1
Temperature: 135 °C
Reaction time: 8 h

Procedure:
A mixture of N-(3-chloroquinoxalin-2-yl)-3-nitrobenzenesulfonamide (1 g), 2,6-dichloropyridin-4-amine (760 mg) and p-xylene (10 mL) was heated at 135° C. with stirring overnight. Upon cooling to room temperature, the mixture was dissolved in dichloromethane, washed with 2 N HCl (2×) and brine, concentrated in vacuo to give a crude product of N-{3-[(2,6-dichloropyridin-4-yl)amino]quinoxalin-2-yl}-3-nitrobenzenesulfonamide. A small portion of this crude product was purified by HPLC to give N-{3-[(2,6-dichloropyridin-4-yl)amino]quinoxalin-2-yl}-3-nitro-benzenesulfonamide. 1H NMR (400 MHz, DMSO) δ 9.71 (s, 1H), 8.90 (s, 1H), 8.50 (d, 2H), 8.8.41 (d, 1H), 8.30 (s, 2H), 7.88-7.78 (m, 27.65 (d, 1H), 7.47-7.37 (m, 2H); MS (EI) m/z for C19H12Cl2N6O4S: 491.1, 493.1 (MH+).
Reaction SMILES: Cl[C:2]1[N:20]=[C:5]2[C:6]([NH:10][CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=3)=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[NH2:21][C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1>>[CH3:19][O:18][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][CH:15]=1)[CH2:11][NH:10][C:6]1[C:5]2[N:4]([N:3]=[C:2]([NH:21][C:22]3[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=3)[N:20]=2)[CH:9]=[CH:8][CH:7]=1
Reactant: COc1cccc(CNc2cccn3nc(Cl)nc23)c1
Reactant: Nc1ccncc1
Product: COc1cccc(CNc2cccn3nc(Nc4ccncc4)nc23)c1

Procedure:
N(8)-(3-Methoxy-benzyl)-N(2)-pyridin-4-yl-[1,2,4]triazolo[1,5-a]pyridine-2,8-diamine was prepared from (2-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-(3-methoxy-benzyl)-amine (99.9 mg, 0.346 mmol) and 4-aminopyridine (36.47 mg, 0.3875 mmol) in a manner analogous to Example 2d. Product was isolated as an off-white foam (3.63 mg, 3%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 10.02 (s, 1H), 8.32 (m, 2H), 8.00 (d, J=6.7 Hz, 1H), 7.69 (m, 2H), 7.23 (t, J=16.4, 8.2 Hz, 1H), 6.97 (s, 2H), 6.79 (m, 2H), 6.67 (m, 1H), 6.34 (d, J=8.0 Hz, 1H), 4.50 (d, J=6.1 Hz, 2H), 3.72 (s, 3H). MS=347 (MH)+.
Reaction SMILES: [CH2:1]1[CH:5]2[CH2:6][NH:7][CH2:8][CH:4]2[CH2:3][N:2]1[C:9]1[CH:18]=[N:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]=1.[N:19]1[N:20]=[C:21]([C:24]2[CH:32]=[CH:31][CH:30]=[CH:29][C:25]=2[C:26](O)=[O:27])[NH:22][CH:23]=1>>[N:19]1[N:20]=[C:21]([C:24]2[CH:32]=[CH:31][CH:30]=[CH:29][C:25]=2[C:26]([N:7]2[CH2:6][CH:5]3[CH2:1][N:2]([C:9]4[CH:18]=[N:17][C:16]5[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=5)[N:10]=4)[CH2:3][CH:4]3[CH2:8]2)=[O:27])[NH:22][CH:23]=1
Reactant: O=C(O)c1ccccc1-c1nnc[nH]1
Reactant: c1ccc2nc(N3CC4CNCC4C3)cnc2c1
Product: O=C(c1ccccc1-c1nnc[nH]1)N1CC2CN(c3cnc4ccccc4n3)CC2C1

Procedure:
The title compound was prepared in a manner analogous to Example 15 utilizing Intermediate 35 and 2-(4H-[1,2,4]triazol-3-yl)benzoic acid. MS (ESI) mass calcd. for C23H21N7O, 411.47; m/z found, 412.2 [M+H]+. 1H NMR (CDCl3): 8.28 (s, 1H), 8.11 (d, J=8.1 Hz, 1H), 8.01 (br s, 1H), 7.89 (dd, J=8.2, 1.2 Hz, 1H), 7.69 (dd, J=8.4, 1.0 Hz, 1H), 7.59 (ddd, J=8.4, 7.0, 1.4 Hz, 1H), 7.55-7.43 (m, 2H), 7.42-7.33 (m, 2H), 3.89-4.00 (m, 2H), 3.82-3.72 (m, 2H), 3.71-3.64 (m, 1H), 3.55-3.42 (m, 2H), 3.20-2.98 (m, 3H).
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:29]([OH:31])=O)[CH2:13][C:14]1[N:18]=[CH:17][N:16](C(OCC2C=CC=CC=2)=O)[CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:32]1([N:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:29]([N:41]1[CH2:42][CH2:43][N:38]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:39][CH2:40]1)=[O:31])[CH2:13][C:14]1[N:18]=[CH:17][NH:16][CH:15]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: c1ccc(N2CCNCC2)cc1
Reactant: O=C(N[C@@H](Cc1cn(C(=O)OCc2ccccc2)cn1)C(=O)O)OCc1ccccc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Solvent: C1CCOC1
Product: O=C(N[C@@H](Cc1c[nH]cn1)C(=O)N1CCN(c2ccccc2)CC1)OCc1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 90.6 %

Procedure:
7.13 g of N,N'-dibenzyloxycarbonyl histidine, 3.00 g of 4-phenylpiperazine and 16.1 g of N-hydroxybenzotriazole were dissolved in 100 ml of tetrahydrofuran, and to the mixture was added 3.84 g of DCC (dicyclohexylcarbodiimide), and the whole was stirred a& a room temperature for three hours. An insoluble matter was filtered off, the filtrate was concentrated under a reduced pressure, and to the concentrate was added 200 ml of ethyl acetate to reform crystals, which were then filtered off. The filtrate was sequentially washed with 20% potassium carbonate aqueous solution and saturated sodium chloride aqueous solution, dried over magnesium sulfate, and concentrated under a reduced pressure. The resulting residue was dissolved in 60 ml of methanol, and after an addition of a 10% ammonium-methanol solution and stirring at a room temperature for 30 minutes, the solution was concentrated under a reduced pressure to obtain a residue, which was then subjected to silica gel chromatography and eluted with chloroform/methanol (50:1 to 10:1) to obtain 6.61 g of the title compound in a colorless amorphous form.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:9]O)=[CH:7][CH:8]=1.S(Cl)([Cl:13])=O>C(Cl)(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:9][Cl:13])=[CH:7][CH:8]=1
Reactant: O=S(Cl)Cl
Reactant: COc1ccc(CO)cc1
Solvent: ClC(Cl)Cl
Product: COc1ccc(CCl)cc1

Procedure:
To 138.0 g of p-methoxybenzyl alcohol in 500 ml of dry chloroform is added, dropwise, 119 g of thionyl chloride. Subsequently, the mixture is stirred and heated under reflux for 2 hours, concentrated from the steam bath and the residue fractionated to give p-methoxybenzyl chloride.
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.C([Si](C1C=CC=CC=1)(C1C=CC=CC=1)[O:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH:36]([S:57]([C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)(=[O:59])=[O:58])[CH2:37][CH2:38][CH2:39][CH2:40]/[CH:41]=[CH:42]\[CH2:43]/[CH:44]=[CH:45]\[CH2:46]/[CH:47]=[CH:48]\[CH2:49]/[CH:50]=[CH:51]\[CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])(C)(C)C.O>C1COCC1>[C:60]1([S:57]([CH:36]([CH2:37][CH2:38][CH2:39][CH2:40]/[CH:41]=[CH:42]\[CH2:43]/[CH:44]=[CH:45]\[CH2:46]/[CH:47]=[CH:48]\[CH2:49]/[CH:50]=[CH:51]\[CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][OH:24])(=[O:58])=[O:59])[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=1
Reactant: CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCCCC(CCCCCCCCCCCO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)S(=O)(=O)c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Solvent: C1CCOC1
Product: CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCCCC(CCCCCCCCCCCO)S(=O)(=O)c1ccccc1
Reaction time: 1 h
Yield: 65.6 %

Procedure:
Tetrabutylammonium fluoride (1 M solution in THF, 0.764 mL, 0.764 mmol) was added drop wise to a stirred solution of tert-butyldiphenyl((17Z,20Z,23Z,26Z)-12-(phenylsulfonyl)dotriaconta-17,20,23,26-tetra-enyloxy)silane (0.16 g, 0.191 mmol) in dry THF (2 mL) and stirring was continued for 1 h. Upon completion of reaction as judged y TLC, water (3 mL) was added and the reaction mixture was extracted with ethyl acetate (3×15 mL). The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated. The crude was purified by silica gel column chromatography using 30% ethyl acetate/hexane to afford the title product as a clear oil (0.075 g, 66%). 1H NMR (CDCl3): δ7.88 (d, 2H, J=7.2 Hz), 7.57 (m, 3H), 5.38 (m, 8H), 3.65 (br s, 2H), 2.81 (m, 7H), 2.05 (m, 4H), 1.81 (m, 2H), 1.37-1.20 (m, 30H), 1.04 (t, 3H, J=6.9 Hz). m/z (APCI) 599.45 (M++1).
Reaction SMILES: C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]#[N:11])[CH:5]=1.O.[NH2:14][NH2:15]>C(O)C>[C:10]([C:6]1[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=1)[C:3]([NH:14][NH2:15])=[O:2])#[N:11]
Reactant: COC(=O)c1cccc(C#N)c1
Reactant: NN
Solvent: CCO
Solvent: O
Product: N#Cc1cccc(C(=O)NN)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 52.7 %

Procedure:
A mixture of 3-cyano-benzoic acid methyl ester (2 g, 12 mmol) and hydrazine monohydrate (0.60 mL, 12 mmol) in ethanol (10 mL) was stirred at room temperature overnight. The reaction mixture was concentrated and then the residue was triturated with diethyl ether to afford 3-cyano-benzoic acid hydrazide (1.02 g, 51%, pink solid). 1H NMR (DMSO) □ (ppm): 10.31 (s, 1H), 8.21 (m, 1H), 8.11 (m, 1H), 7.99 (m, 1H), 7.70 (m, 1H), 4.50 (s, 1H).
Reaction SMILES: [NH:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:2]([C:4]([OH:6])=O)[CH3:3].[NH2:14][C@H:15]([C:17]([O:19][CH3:20])=[O:18])[CH3:16].C1(N=C=NC2CCCCC2)CCCCC1.C(N(CC)CC)C>ClCCl>[NH:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:2]([C:4]([NH:14][C@H:15]([C:17]([O:19][CH3:20])=[O:18])[CH3:16])=[O:6])[CH3:3]
Reactant: C[C@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: COC(=O)[C@H](C)N
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)OC(C)(C)C

Procedure:
Boc-(L)-Ala-(L)-Ala-OMe was prepared as follows. Boc-(L)-Ala-OH (2.06 g, 10.63 mmol) was dissolved in distilled dichloromethane (5 mL). To the resulting solution was added H2N-(L)-Ala-OMe (0.996 g, 9.67 mmol) in 5 mL of distilled dichloromethane. Dicyclohexylcarbodiimide (abbr. DCC; 2.19 g, 10.63 mmol) was dissolved in 3 mL distilled dichloromethane and added to the solution. Dicyclohexylurea (abbr. DCU) precipitation was noted immediately after DCC addition. Triethylamine (3 mL, 21.52 mmol) and additional distilled dichloromethane (4 mL) were added to the reaction mixture. The reaction proceeded for a total of three hours, when TLC analysis indicated consumption of H2N-(L)-Ala-OMe starting material and formation of a new component. DCU precipitation was promoted by storing the reaction at −20° C. The precipitate was filtered through a Buchner funnel and rinsed with cold dichloromethane. The combined filtrate and rinses were dried under vacuum and purified by Silica chromatography to yield dipeptide Boc-(L)-Ala-(L)-Ala-OMe (2.03 g, 7.14 mmol, 74%). 1H-NMR (chloroform-d) δ (ppm): 1.34 (d, J=14.1 Hz, 3H); 1.38 (d, J=14.3 Hz, 3H); 1.40 (s, 9H); 3.73 (s, 3H); 4.14 (s-broad, 1H); 4.55 (quintet, J=14.5 Hz, 1H); 4.97 (s-broad, 1H); 6.59 (s-broad, 1H).
Reaction SMILES: O.[Cl-:2].[CH3:3][N:4]1[CH:8]=[CH:7][N+:6]([CH2:9][CH2:10][N:11]([CH3:23])[C:12]2[CH:17]=[CH:16][C:15]([NH:18][CH3:19])=[C:14]([N+:20]([O-:22])=[O:21])[CH:13]=2)=[CH:5]1>C1(C)C=CC=CC=1>[Cl:2][CH2:9][CH2:10][N:11]([CH3:23])[C:12]1[CH:17]=[CH:16][C:15]([NH:18][CH3:19])=[C:14]([N+:20]([O-:22])=[O:21])[CH:13]=1.[CH3:3][N:4]1[CH:8]=[CH:7][N:6]=[CH:5]1
Reactant: CNc1ccc(N(C)CC[n+]2ccn(C)c2)cc1[N+](=O)[O-]
Reactant: [Cl-]
Solvent: Cc1ccccc1
Solvent: O
Product: CNc1ccc(N(C)CCCl)cc1[N+](=O)[O-]
Product: Cn1ccnc1

Procedure:
From 41.4 g (0.17 mol) of N4-(2-chloroethyl)-N1,N4-dimethyl-2-nitrobenzene-1,4-diamine (RN 14607-54-6) and from 41.8 g (0.51 mol) of 1-methyl-1H-imidazole (RN 616-47-7) in 100 ml of toluene, 37.8 g of purple crystals of 3-methyl-1-{2-(methyl(4-methylamino-3-nitrophenyl)amino)ethyl}-3H-imidazol-1-ium chloride monohydrate were obtained after recrystallization from refluxing ethanol, which crystals melted at 135° C. (Kofler) and had an elemental analysis, calculated for C14H20N5O2Cl+H2O, of:
Reaction SMILES: [CH2:1]([CH:3]([CH2:18][CH2:19][CH2:20][CH3:21])[CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]=[C:6]1[C:14](Cl)(Cl)Cl)[CH3:2].[NH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[OH:29].C(N(CC)CC)C>C(O)C>[CH2:1]([CH:3]([CH2:18][CH2:19][CH2:20][CH3:21])[CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]=[C:6]1[C:14]1[O:29][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[N:22]=1)[CH3:2]
Reactant: Nc1ccccc1O
Reactant: CCCCC(CC)Cn1c(C(Cl)(Cl)Cl)nc2ccccc21
Solvent: CCO
Solvent: CCN(CC)CC
Product: CCCCC(CC)Cn1c(-c2nc3ccccc3o2)nc2ccccc21

Procedure:
28.2 g (0.12 mol) of 1-(2-ethylhexyl)-2-trichloromethylbenzimidazole (prepared by reacting N-2-ethylhexyl-o-phenylenediamine with trichloroacetamido methyl ester), 13.1 g (0.12 mot) of o-aminophenol and 39.4 g (0.38 mot) of triethylamine in 150 ml of ethanol are stirred at room temperature for 15 hours. The ethanol is subsequently removed on a rotary evaporator, ethyl acetate is added to the residue which remains, and the mixture is washed with water and dried over sodium sulfate. 35% of product is identified by BPLC in the product mixture thus ob-5 tained; isolation can be carried out, for example, by column chromatography.
Reaction SMILES: B(Br)(Br)Br.C[O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[CH:12][C:13]([C:17]#[N:18])=[CH:14]2)=[CH:9][CH:8]=1.O.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[OH:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[CH:12][C:13]([C:17]#[N:18])=[CH:14]2)=[CH:9][CH:8]=1
Reactant: COc1ccc2ccc(C#N)cc2c1
Agent: BrB(Br)Br
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: N#Cc1ccc2ccc(O)cc2c1
Reaction time: 30 h
Yield: 79.9 %

Procedure:
A solution of BBr3 (840 μL, 8.8 mmol) in CH2Cl2 (4 mL) is added to a solution of 7-methoxy-2-naphthonitrile (646 mg, 3.53 mmol) in CH2Cl2 (6 mL). The reaction is allowed to stir for 30 hours. Water (about 5 mL) is slowly added. The pH is adjusted to 7 with saturated Na2CO3 then the mixture is extracted with CH2Cl2. The combined organic layers are dried (Na2SO4), filtered and concentrated to dryness. The crude material is purified by column chromatography (step gradient of 1% MeOH in CH2Cl2 to 5% MeOH in CH2Cl12) to give 7-hydroxy-2-naphthonitrile as a white solid (477 mg, 80%). HRMS (EI) calculated for C11H7NO: 169.0528, found 169.0527.
Reaction SMILES: [C:1]([OH:20])(=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].[CH:21]1[C:26]([NH2:27])=[CH:25][CH:24]=[C:23]([NH2:28])[CH:22]=1>>[C:1]([NH:27][C:26]1[CH:21]=[CH:22][C:23]([NH2:28])=[CH:24][CH:25]=1)(=[O:20])[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)O
Reactant: Nc1ccc(N)cc1
Product: CCCCCCCC/C=C\CCCCCCCC(=O)Nc1ccc(N)cc1
Yield: 76.6 %

Procedure:
Oleic acid (2.82 g) and p-phenylenediamine (1.62 g) were reacted in the same manner as in Reference Example 11 to obtain 2.85 g of the objective compound (yield: 77%).
Reaction SMILES: Br[CH2:2][CH2:3][O:4][C:5]1[CH:12]=[CH:11][C:8]([CH:9]=[O:10])=[CH:7][CH:6]=1.[OH:13][C:14]1[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:15]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH:9]([C:8]1[CH:11]=[CH:12][C:5]([O:4][CH2:3][CH2:2][O:13][C:14]2[CH:15]=[CH:16][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:22][CH:23]=2)=[CH:6][CH:7]=1)=[O:10]
Reactant: O=Cc1ccc(OCCBr)cc1
Reactant: COC(=O)c1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(OCCOc2ccc(C=O)cc2)cc1
Yield: 52.4 %

Procedure:
To a solution of 354 (1.21 g, 5.27 mmol) in DMF (10 mL) was added methyl 4-hydroxybenzoate (0.80 g, 5.27 mmol) and K2CO3 (2.91 g, 21.1 mmol). The resultant mixture was stirred at 60° C. for 6 h, filtered, and evaporated. The residue was purified by silica gel column chromatography, eluent EtOAc-hexane (1:2) to afford title compound (0.83 g, 53%). LRMS (ESI): (calc.) 300.3; (found) 301.4 (MH)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([O:17][CH2:18][CH2:19][O:20][CH3:21])=[N:10][CH:11]=[C:12]([CH:16]=2)[C:13]([OH:15])=O)=[CH:4][C:3]=1[F:22].[F:23][C:24]([F:33])([F:32])[C:25]1[N:29]=[C:28]([CH2:30][NH2:31])[O:27][N:26]=1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([O:17][CH2:18][CH2:19][O:20][CH3:21])=[N:10][CH:11]=[C:12]([CH:16]=2)[C:13]([NH:31][CH2:30][C:28]2[O:27][N:26]=[C:25]([C:24]([F:33])([F:32])[F:23])[N:29]=2)=[O:15])=[CH:4][C:3]=1[F:22]
Reactant: NCc1nc(C(F)(F)F)no1
Reactant: COCCOc1ncc(C(=O)O)cc1-c1ccc(Cl)c(F)c1
Product: COCCOc1ncc(C(=O)NCc2nc(C(F)(F)F)no2)cc1-c1ccc(Cl)c(F)c1

Procedure:
The title compound was synthesized in analogy to Example 1 using 5-(4-chloro-3-fluorophenyl)-6-(2-methoxyethoxy)-nicotinic acid (example CF) and 3-trifluoromethyl-[1,2,4]oxadiazol-5-methanamine (example AK) as starting materials; LC-MS (UV peak area/ESI) 100%, 473.0662 (M−H)−.
Reaction SMILES: N(C(OCC)=O)=N[C:3](OCC)=O.C1(C)C=CC=CC=1.O[CH2:21][C@H:22]([NH:30][S:31]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[N+:40]([O-:42])=[O:41])(=[O:33])=[O:32])[C@@H:23]1[CH2:27][C@@H:26]([CH3:28])[C:25](=[O:29])[O:24]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[CH2:28]([C@@H:26]1[CH2:27][C@@H:23]([CH:22]2[CH2:21][N@@:30]2[S:31]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[N+:40]([O-:42])=[O:41])(=[O:33])=[O:32])[O:24][C:25]1=[O:29])[CH3:3]
Reactant: CCOC(=O)N=NC(=O)OCC
Reactant: C[C@@H]1C[C@@H]([C@H](CO)NS(=O)(=O)c2ccccc2[N+](=O)[O-])OC1=O
Agent: CC[C@@H]1C[C@@H](C2C[N@]2S(=O)(=O)c2ccccc2[N+](=O)[O-])OC1=O
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CC[C@@H]1C[C@@H](C2C[N@@]2S(=O)(=O)c2ccccc2[N+](=O)[O-])OC1=O
Reaction time: 0.08 h

Procedure:
1.60 ml of a solution of diethyl azodicarboxylate in toluene (40%) (3.52 mmol) was added to a solution of 1.05 g of N-{(S)-2-hydroxy-1-[(2S,4R)-4-methyl-5-oxotetrahydrofuran-2-yl]ethyl}-2-nitrobenzenesulfonamide obtained in Example (106f) (2.93 mmol) and 923 mg of triphenylphosphine (3.52 mmol) in tetrahydrofuran (30 ml) under ice-cooling over five minutes, and the mixture was stirred at the same temperature for five minutes. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent: toluene/acetone=5/1) to obtain 916 mg of the title compound (yield: 92%).