Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[O:5][C:4](=[O:12])[N:3]=1.Cl.Cl.[NH2:15][CH:16]([CH2:29][CH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1)[C:17]([NH:19][C:20]1([C:27]#[N:28])[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]1)=[O:18]>>[C:27]([C:20]1([NH:19][C:17](=[O:18])[CH:16]([NH:15][C:2]2[C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=3[O:5][C:4](=[O:12])[N:3]=2)[CH2:29][CH:30]2[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]2)[CH2:21][CH2:22][N:23]([CH3:26])[CH2:24][CH2:25]1)#[N:28]
Reactant: CN1CCC(C#N)(NC(=O)C(N)CC2CCCCC2)CC1
Reactant: O=c1nc(Cl)c2ccccc2o1
Agent: Cl
Product: CN1CCC(C#N)(NC(=O)C(CC2CCCCC2)Nc2nc(=O)oc3ccccc23)CC1

Procedure:
The title compound was prepared starting from 4-chloro-benzo[e][1,3] oxazin-2-one (prepared from benzo [e][1,3] oxazin-2,4-dione and PCl5 in refluxing toluene) and 2-amino-N-(4-cyano-1-methyl-piperidin-4-yl)-3-cyclohexyl-propionamide bis hydrochloride salt according to the procedure from Example 81. MS, m/z 438=M+1.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.[CH2:7]([CH:11]([C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[C:17]([C:25]([F:28])([F:27])[F:26])[CH:16]=1)[C:12]([OH:14])=O)[CH2:8][CH:9]=[CH2:10].Cl.[O:30]=[C:31]1[CH2:36][CH2:35][C:34]([NH2:43])([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:33][CH2:32]1.N1C=CC=CC=1>ClCCl.CN(C)C=O>[CH2:7]([CH:11]([C:15]1[CH:16]=[C:17]([C:25]([F:27])([F:28])[F:26])[CH:18]=[C:19]([C:21]([F:24])([F:22])[F:23])[CH:20]=1)[C:12]([NH:43][C:34]1([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:33][CH2:32][C:31](=[O:30])[CH2:36][CH2:35]1)=[O:14])[CH2:8][CH:9]=[CH2:10]
Reactant: NC1(c2ccccc2)CCC(=O)CC1
Reactant: C=CCCC(C(=O)O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Agent: Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: c1ccncc1
Product: C=CCCC(C(=O)NC1(c2ccccc2)CCC(=O)CC1)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 51.7 %

Procedure:
Oxalyl chloride (4.22 mL, 48.4 mmol) was added to a solution of (RS)-α-(3-butenyl)-3,5-bis(trifluoromethyl)benzeneacetic acid (Description 8, 24.2 mmol) and dimethylformamide (0.1 mL) in dichloromethane (80 mL) and the mixture was stirred at room temperature for 3 hours. The solvent was evaporated under reduced pressure and toluene was added and evaporated under reduced pressure. The residue was dissolved in dichloromethane (50 mL) and added to a stirred, cooled (0° C.) solution of 4-oxo-1-phenylcyclohexylamine hydrochloride (Description 3, 4.58 g, 24.2 mmol) in dichloromethane (150 mL). Pyridine (4.1 mL, 50.8 mmol) was added and the mixture was stirred at room temperature overnight. The mixture was washed with hydrochloric acid (1M, 2×200 mL), saturated aqueous sodium hydrogen carbonate (2×200 mL) and brine (200 mL), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was triturated with isohexane/diethylether (7:1) and the solid was collected and dried in vacuo. The solid was purified by flash column chromatography on silica gel, eluting with isohexane/EtOAc (2:1), to give the title compound (6.22 g, 52%). 1H NMR (400 MHz, CDCl3) δ 7.80 (1H, s), 7.73 (2H, s), 7.31-7.25 (5H, m), 5.80-5.70 (2H, m), 5.05-4.97 (2H, m), 3.52-3.47 (1H, m), 2.86-2.80 (1H, m), 2.65-2.57 (1H, m), 2.50-2.31 (6H, m), 2.27-2.18 (1H, m), 2.09-1.95 (2H, m), and 1.81-1.72 (1H, m).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)C#N.[C:10]([C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1)([CH3:13])([CH3:12])[CH3:11].[C:21](=[O:24])([O-])[O-:22].[K+].[K+].S([O-])(O)(=O)=O.[K+]>N1C=CC=CC=1>[C:10]([C:14]1[CH:15]=[CH:16][C:17]([O:20][C:2]2[CH:9]=[C:8]([CH:7]=[CH:4][CH:3]=2)[C:21]([OH:22])=[O:24])=[CH:18][CH:19]=1)([CH3:13])([CH3:11])[CH3:12]
Reactant: N#Cc1cccc(Br)c1
Reactant: CC(C)(C)c1ccc(O)cc1
Reactant: O=C([O-])[O-]
Agent: O=S(=O)([O-])O
Agent: [K+]
Solvent: c1ccncc1
Product: CC(C)(C)c1ccc(Oc2cccc(C(=O)O)c2)cc1
Yield: 53.6 %

Procedure:
To a solution of 3-bromobenzonitrile (4.35 g, 23.9 mmol) and p-t-butylphenol (4.30 g, 28.7 mmol) in pyridine (45 ml) were added potassium carbonate (6.61 g, 47.8 mmol) and cupric oxide (3.42 g, 43 mmol), and the resultant mixture was refluxed for 46 hours. The reaction mixture was poured into saturated potassium hydrogensulfate solution and extracted with ethyl acetate. The organic layer was concentrated, and the residue was dissolved in ethylene glycol (20 ml), mixed with 2N potassium hydroxide solution (130 ml) and refluxed for 20 hours. The reaction mixture was poured into chilled water and extracted with diethyl ether under acidic conditions. The organic layer was dried and concentrated. The residue was chromatographed on a silica gel column to give the titled compound (3.46 g, yield 54%).
Reaction SMILES: [Si]([O:8][C:9]([C:12]1[N:17]=[CH:16][C:15]([C:18]2[S:22][C:21]([N+:23]([O-:25])=[O:24])=[C:20]([C:26]([NH2:28])=[O:27])[CH:19]=2)=[CH:14][CH:13]=1)([CH3:11])[CH3:10])(C(C)(C)C)(C)C.CC(O)=O.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.O>[OH:8][C:9]([C:12]1[N:17]=[CH:16][C:15]([C:18]2[S:22][C:21]([N+:23]([O-:25])=[O:24])=[C:20]([C:26]([NH2:28])=[O:27])[CH:19]=2)=[CH:14][CH:13]=1)([CH3:11])[CH3:10]
Reactant: CC(C)(O[Si](C)(C)C(C)(C)C)c1ccc(-c2cc(C(N)=O)c([N+](=O)[O-])s2)cn1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: O
Product: CC(C)(O)c1ccc(-c2cc(C(N)=O)c([N+](=O)[O-])s2)cn1
Temperature: 90 °C
Reaction time: 18 h

Procedure:
To a solution of 5-[6-(1-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyl)pyridin-3-yl]-2-nitrothiophene-3-carboxamide (665 mg, 1.58 mmol) in THF (10 mL) were added AcOH (0.36 ml, 6.13 mmol) and TBAF (1.0 M in THF, 6.31 mL, 6.31 mmol). The sealed reaction was stirred at 90° C. for 18 h. Additional AcOH (0.361 ml, 6.13 mmol) and TBAF (6.31 mL, 6.31 mmol) were added, and the reaction was stirred at 90° C. for another 24 h. The brown solution was cooled to room temperature, diluted with water, and extracted with EtOAc (2×). The combined organic extracts were washed with brine (2×), dried (MgSO4), filtered, and evaporated. Flash chromatography of the crude residue (50-100% EtOAc/hexanes) provided a yellow residue that was triturated with Et2O and filtered to isolate the title compound as a yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.Br[CH2:15][CH2:16][CH2:17][NH:18][C:19]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[CH2:13][CH2:12][N:11]([CH2:15][CH2:16][CH2:17][NH:18][C:19]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: BrCCCNC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: Clc1cccc(N2CCNCC2)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Clc1cccc(N2CCN(CCCNC(c3ccccc3)(c3ccccc3)c3ccccc3)CC2)c1
Temperature: 90 °C
Reaction time: 6.5 h
Yield: 105.5 %

Procedure:
A mixture of 5.9 g (30 mmol) of 1-(3-chlorophenyl)piperazine, 12.55 g (33 mmol) of 3-bromo-N-(triphenylmethyl)propanamine, 6.2 g (45 mmol) of potassium carbonate and 60 ml of dimethylformamide is stirred at 90° C. for 6.5 h under argon. The mixture is then poured into iced water and is extracted with ethyl acetate. The organic phase is separated off, is washed with water, is dried and the solvent is evaporated off. 15.7 g of oily residue are obtained and are purified by chromatography on a column of silica gel by eluting with a 99/1 dichloromethane/methanol mixture, which yields 11.8 g of light yellow oil.
Reaction SMILES: [CH2:1]([CH:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][NH2:17])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:18]([C:20]1[CH:21]=[C:22]([N:26]=[C:27]=[O:28])[CH:23]=[CH:24][CH:25]=1)#[N:19]>C1COCC1>[C:18]([C:20]1[CH:21]=[C:22]([NH:26][C:27]([NH:17][CH2:16][CH2:15][CH2:14][N:11]2[CH2:10][CH2:9][CH:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:13][CH2:12]2)=[O:28])[CH:23]=[CH:24][CH:25]=1)#[N:19]
Reactant: NCCCN1CCC(Cc2ccccc2)CC1
Reactant: N#Cc1cccc(N=C=O)c1
Solvent: C1CCOC1
Product: N#Cc1cccc(NC(=O)NCCCN2CCC(Cc3ccccc3)CC2)c1
Reaction time: 0.5 h
Yield: 90 %

Procedure:
4-benzyl-1-(3-amino-n-prop-1-yl)piperidine (300 mg, 1.29 mmol, 1 eq) was dissoved in THF at 25° C. under N2 then 3-cyanophenyl isocyanate (186 mg, 1.29 mmol, 1 eq) was added. TLC after 30 minutes shows the reaction complete. The solvent was removed in vacuo then the residue was purified over silica gel in 100% EtOAc to 8:2 chloroform/MeOH to yield 437 mg of an amber oil as product. NMR (300 MHz, DMSO-d6) δ 9.90-9.50 (m, 1H); 9.32 (s, 1H); 7.93 (s, 1H); 7.59 (d, 1H, J=7 Hz); 7.43 (t, 1H, J=7 Hz); 7.40-7.24 (m, 3H); 7.24-7.10 (m, 3H); 6.68 (t, 1H, J=7 Hz); 3.50-3.25 (m, 2H); 3.25-3.07 (m, 2H); 3.07-2.90 (m, 2H); 2.90-2.60 (m, 2H); 2.60-2.40 (m, 2H); 2.00-1.60 (m, 5H); 1.60-1.30 (m, 2H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:18](O)=[O:19])[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:21][O:22][NH:23][CH3:24].CN1CCOCC1.O.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>CO>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:18](=[O:19])[N:23]([O:22][CH3:21])[CH3:24])[CH:14]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]
Reactant: CNOC
Reactant: CC(C)(C)OC(=O)N1CCc2cc(C(=O)O)ccc2C1
Agent: COc1nc(OC)nc([N+]2(C)CCOCC2)n1
Agent: [Cl-]
Solvent: CN1CCOCC1
Solvent: CO
Solvent: O
Product: CON(C)C(=O)c1ccc2c(c1)CCN(C(=O)OC(C)(C)C)C2
Temperature: 25 °C

Procedure:
To 2.00 g (7.21 mmol) 3,4-dihydro-1H-isoquinoline-2,6-dicarboxylic acid 2-tert-butyl ester in 70 mL MeOH is added at RT 844 mg (8.65 mmol) O,N-dimethyl-hydroxylamine and 1.59 mL (14.4 mmol) 4-methyl-morpholine. The mixture is stirred at RT and then 2.10 g (7.57 mmol) 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholin-4-ium chloride hydrate is added and the mixture is stirred overnight at RT. The residue is directly purified via reverse HPLC chromatography (Waters XBridge, C18; water (0.3% NH4OH)/acetonitrile (0.3% NH4OH) 90:10 to 10:90).
Reaction SMILES: [C:1]([C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1)#N.[Cl:13][C:14]1[CH:19]=[CH:18][C:17](Br)=[CH:16][CH:15]=1.[Mg].[Br-].[NH4+].S(=O)(=O)(O)[OH:25]>CCOCC>[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C:1]([C:3]2[CH:12]=[CH:11][C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[N:4]=2)=[O:25])=[CH:16][CH:15]=1
Reactant: Clc1ccc(Br)cc1
Reactant: N#Cc1ccc2ccccc2n1
Reactant: O=S(=O)(O)O
Agent: [Br-]
Agent: [Mg]
Agent: [NH4+]
Solvent: CCOCC
Product: O=C(c1ccc(Cl)cc1)c1ccc2ccccc2n1
Reaction time: 8 h
Yield: 89 %

Procedure:
The starting substance is prepared as follows: 15.4 g (0.1 mole) of 2-cyano-quinoline are dissolved in 200 ml of anhydrous ether, and a Grignard reagent prepared from 2.5 g (0.13 moles) of 4-chloro-bromobenzene and 3.16 g (0.13 moles) of magnesium metal are added. The reaction mixture is allowed to stand overnight, thereafter it is poured into a mixture of 15 g of ammonium bromide and ice, acidified with sulfuric acid and the organic phase is separated. After evaporating the ether the product thus-obtained (24 g) is recrystallized from ethanol. The 2-(4-chlorobenzoyl)-quinoline is obtained with a yield of 89%.
Reaction SMILES: [OH:1][C@@H:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C@@H:3]1[NH:11][C:12](=[O:48])[C@H:13]([O:39][CH2:40][C:41]1[CH:46]=[CH:45][C:44](Br)=[CH:43][CH:42]=1)[C@H:14]([OH:38])[C@@H:15]([OH:37])[C@@H:16]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33](Br)=[CH:32][CH:31]=1)[C:17]([NH:19][C@H:20]([C:24](=[O:27])[NH:25][CH3:26])[CH:21]([CH3:23])[CH3:22])=[O:18].C([Sn](CCCC)(CCCC)[C:54]1[S:55][CH:56]=[CH:57][N:58]=1)CCC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C=O)C>[OH:1][C@@H:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C@@H:3]1[NH:11][C:12](=[O:48])[C@H:13]([O:39][CH2:40][C:41]1[CH:46]=[CH:45][C:44]([C:54]2[S:55][CH:56]=[CH:57][N:58]=2)=[CH:43][CH:42]=1)[C@H:14]([OH:38])[C@@H:15]([OH:37])[C@@H:16]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:54]2[S:55][CH:56]=[CH:57][N:58]=2)=[CH:32][CH:31]=1)[C:17]([NH:19][C@H:20]([C:24](=[O:27])[NH:25][CH3:26])[CH:21]([CH3:23])[CH3:22])=[O:18]
Reactant: CNC(=O)[C@@H](NC(=O)[C@H](OCc1ccc(Br)cc1)[C@H](O)[C@@H](O)[C@@H](OCc1ccc(Br)cc1)C(=O)N[C@H]1c2ccccc2C[C@H]1O)C(C)C
Reactant: CCCC[Sn](CCCC)(CCCC)c1nccs1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Product: CNC(=O)[C@@H](NC(=O)[C@H](OCc1ccc(-c2nccs2)cc1)[C@H](O)[C@@H](O)[C@@H](OCc1ccc(-c2nccs2)cc1)C(=O)N[C@H]1c2ccccc2C[C@H]1O)C(C)C
Temperature: 90 °C
Reaction time: 16 h
Yield: 73 %

Procedure:
A mixture of N1-[(1S,2R)-2-hydroxy-2,3-dihydro-1H-1-indenyl]-N6-[(1S)-2-methyl-1-(methylcarbamoyl)propyl]-(2R,3R,4R,5R)-2,5-di(4-bromobenzyloxy)-3,4-dihydroxyhexanediamide, prepared analagously to Example 11 of WO98/45330 using 4-bromobenzyl (130 mg, 0.164 mmol), tributyl-2-thiazolyltin (554 mg, 1.47 mmol), PdCl2(PPh3)2 (120 mg, 0.5 M suspension in DMF), and dry DMF (3 ml) was twice degassed and flushed with argon and then stirred at 90° C./16 h, evaporated to near dryness, washed with a little ether and purified by silica gel column chromatography (chloroform-methanol 20:1) to yield 95.5 mg (73%) of off-white solid.
Reaction SMILES: [CH:1]1[C:6]2[C:7]([C:16]3[CH:23]=[CH:22][C:19]([CH:20]=[O:21])=[CH:18][C:17]=3[F:24])=[N:8][C:9]3[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=3[O:11][C:5]=2[CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[C-]#N.[K+].[OH:35][C:36](C)(C)C#N>CO>[CH:1]1[C:6]2[C:7]([C:16]3[CH:23]=[CH:22][C:19]([C:20]([O:35][CH3:36])=[O:21])=[CH:18][C:17]=3[F:24])=[N:8][C:9]3[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=3[O:11][C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: O=Cc1ccc(C2=Nc3ccccc3Oc3ccccc32)c(F)c1
Reactant: CC(C)(O)C#N
Agent: [C-]#N
Agent: [K+]
Solvent: CO
Solvent: CCN(CC)CC
Product: COC(=O)c1ccc(C2=Nc3ccccc3Oc3ccccc32)c(F)c1
Temperature: 40 °C
Reaction time: 24 h
Yield: 56 %

Procedure:
A mixture of compound 102 (0.59 g, 1.90 mmol), triethylamine (1.6 mL, 11.48 mmol), potassium cyanide (0.061 g, 0.93) and 2-hydroxy-2-methylpropanenitrile (1 mL, 10.93) in methanol (15 mL) was stirred at 40° C. for 24 h then solvent evaporated. The resulting crude residue was purified on ISCO (0-100% EtOAc in Hexanes) to afford title compound 103 (0.364 g, 56%) as a yellow solid. LRMS (ESI): (calc) 347.10. (found) 348.4 (MH)+.
Reaction SMILES: [C:1](Cl)(=[O:11])[C:2]1[C:3](=[CH:7][CH:8]=[CH:9][CH:10]=1)[C:4](Cl)=[O:5].[CH2:13]([O:20][N:21]1[CH:29]=[N:28][C:27]2[C:22]1=[N:23][CH:24]=[N:25][C:26]=2[NH2:30])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(N(CC)CC)C>CN(C)C1C=CN=CC=1.O1CCCC1>[CH2:13]([O:20][N:21]1[CH:29]=[N:28][C:27]2[C:22]1=[N:23][CH:24]=[N:25][C:26]=2[N:30]1[C:4](=[O:5])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]2[C:1]1=[O:11])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: Nc1ncnc2c1ncn2OCc1ccccc1
Reactant: O=C(Cl)c1ccccc1C(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C1c2ccccc2C(=O)N1c1ncnc2c1ncn2OCc1ccccc1
Yield: 49 %

Procedure:
Phthaloyl dichloride (13.35 g; 92.2 mmol) was added to a cooled solution of 9-benzyloxyadenine (14.9 g, 61.5 mmol), 4-dimethylaminopyridine (1.5 g, 12.3 mmol) and triethylamine (25.7 ml, 184.4 mmol) in tetrahydrofuran (200 ml). After 1 hour at room temperature the solvent was removed under reduced pressure and the residue partitioned between chloroform (500 ml) and saturated potassium bicarbonate (300 ml). The organic phase was separated, washed with water (200 ml), brine (200 ml), dried (MgSO4) and evaporated to dryness. Column chromatography on silica gel eluting with chloroformmethanol (100:1) afforded the title compound (11.20 g, 49%). IR: νmax (KBr) 3070, 1800, 1740, 1730, 1605, 1585, 1450 and 1410 cm-1 ; 1H NMR δH [(CD3)2SO] 5.70(2H, s, CH2Ph), 7.55(5H, s, CH2Ph), 8.20(4H, s, Ar), 8.95(1H, s, H-2), 9.25(1H, s, H-8). Found: C, 64.71; H, 3.78; N, 18.85%; m/z 371.1025. C20H13N5O3 requires: C, 64.68; H, 3.54; N, 18.86%; m/e 371.1018.
Reaction SMILES: [CH2:1]1[O:6][CH:2]1[CH2:3][CH2:4][CH3:5].[CH2:7]([NH2:20])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][NH2:19]>>[CH2:18]([NH:19][CH2:1][CH:2]([OH:6])[CH2:3][CH2:4][CH3:5])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][NH:20][CH2:1][CH:2]([OH:6])[CH2:3][CH2:4][CH3:5]
Reactant: CCCC1CO1
Reactant: NCCCCCCCCCCCCN
Product: CCCC(O)CNCCCCCCCCCCCCNCC(O)CCC

Procedure:
Condensation of 1-pentene oxide and 1,12-dodecanediamine affords N,N'-(1,12-dodecylene)-bis[2-hydroxypentylamine] (I: R = CH3 (CH2)2, R' = H, X = (CH2)12, Z = H).
Reaction SMILES: Cl[S:2]([C:5]1[CH:14]=[CH:13][C:12]2[NH:11][C:10](=[O:15])[C:9]3[NH:16][CH:17]=[C:18]([C:19]([OH:21])=[O:20])[C:8]=3[C:7]=2[CH:6]=1)(=[O:4])=[O:3].[CH:22]1([NH2:29])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1>>[CH:22]1([NH:29][S:2]([C:5]2[CH:14]=[CH:13][C:12]3[NH:11][C:10](=[O:15])[C:9]4[NH:16][CH:17]=[CH:18][C:8]=4[C:7]=3[CH:6]=2)(=[O:3])=[O:4])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.[CH2:18]([C:19]([O-:21])=[O:20])[CH3:17]
Reactant: NC1CCCCCC1
Reactant: O=C(O)c1c[nH]c2c(=O)[nH]c3ccc(S(=O)(=O)Cl)cc3c12
Product: CCC(=O)[O-]
Product: O=c1[nH]c2ccc(S(=O)(=O)NC3CCCCCC3)cc2c2cc[nH]c12
Yield: 15.1 %

Procedure:
This compound is prepared according to synthesis 25, from 150 mg (0.46 mmol) of 8-chlorosulfonyl-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-carboxylic acid (synthesis 2) and 70 μL (0.55 mmol) of cycloheptylamine. After purification by chromatography on silica gel (dichloromethane/methanol 96/4) then trituration in diethyl ether, 15 mg (8%) of 8-cycloheptylsulfamoyl-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-ethyl carboxylate is obtained in the form of a white solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[CH:6]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:14]=2[CH:23]=O)[C:8]([O:11][CH3:12])=[CH:9][CH:10]=1.[CH:26]1([NH2:30])[CH2:29][CH2:28][CH2:27]1>>[CH3:1][O:2][C:3](=[O:25])[CH2:4][C:5]1[CH:6]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:14]=2[CH2:23][NH:30][CH:26]2[CH2:29][CH2:28][CH2:27]2)[C:8]([O:11][CH3:12])=[CH:9][CH:10]=1
Reactant: NC1CCC1
Reactant: COC(=O)Cc1ccc(OC)c(-c2ccc(C(F)(F)F)cc2C=O)c1
Product: COC(=O)Cc1ccc(OC)c(-c2ccc(C(F)(F)F)cc2CNC2CCC2)c1

Procedure:
Prepared according to the procedure described in Example 1, Step 5, using the following starting materials: (2′-formyl-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid methyl ester and cyclobutylamine.
Reaction SMILES: [CH:1]([C:5]1[C:6]([CH3:20])=[CH:7][C:8]([I:19])=[C:9]([CH:18]=1)[O:10][C:11](=[CH:14][N:15]([CH3:17])C)[C:12]#[N:13])=[CH:2][CH:3]=[CH2:4].Cl.N[C:23]1[CH:28]=[CH:27]C=[CH:25][CH:24]=1>C(O)C>[CH:1]([C:5]1[C:6]([CH3:20])=[CH:7][C:8]([I:19])=[C:9]([CH:18]=1)[O:10][C:11](=[CH:14][NH:15][C:17]1[CH:27]=[CH:28][CH:23]=[CH:24][CH:25]=1)[C:12]#[N:13])=[CH:2][CH:3]=[CH2:4]
Reactant: C=CC=Cc1cc(OC(C#N)=CN(C)C)c(I)cc1C
Reactant: Nc1ccccc1
Agent: Cl
Solvent: CCO
Product: C=CC=Cc1cc(OC(C#N)=CNc2ccccc2)c(I)cc1C

Procedure:
To the crude crude 2-(5-buta-1,3-dienyl-2-iodo-4-methyl-phenoxy)-3-dimethylamino-acrylonitrile of step 3 was added aniline hydrochloride (2.54 g, 19.59 mmol) and ethanol (25 mL). The mixture was heated to reflux for 16 hours under nitrogen atmosphere. The mixture was cooled and concentrated under reduced pressure to yield crude 2-(5-buta-1,3-dienyl-2-iodo-4-methyl-phenoxy)-3-phenylamino-acrylonitrile, which was used in the same flask directly in the following step.
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][C:6]([S:9][C:10]([CH3:19])([CH3:18])[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:5][CH:4]=1)=O.[CH3:20][O:21][CH2:22][CH2:23][NH2:24].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCCl.C(OCC)(=O)C>[CH3:20][O:21][CH2:22][CH2:23][NH:24][CH2:1][C:3]1[CH:8]=[CH:7][C:6]([S:9][C:10]([CH3:19])([CH3:18])[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:5][CH:4]=1
Reactant: CC(C)(C)OC(=O)C(C)(C)Sc1ccc(C=O)cc1
Reactant: COCCN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: ClCCCl
Product: COCCNCc1ccc(SC(C)(C)C(=O)OC(C)(C)C)cc1

Procedure:
4.00 g (14.27 mmol) of tert-butyl 2-[(4-formylphenyl)sulphanyl]-2-methylpropanoate (Example II-2) and 1.07 g (14.27 mmol) of 2-methoxyethylamine are dissolved in 80 ml of 1,2-dichloroethane and, after 30 min and after 10 hours, admixed with 4.54 g (21.40 mmol) of sodium triacetoxyborohydride. The reaction is checked by TLC, and ethyl acetate and saturated sodium bicarbonate solution are then added and the product is extracted with ethyl acetate. The organic phase is washed with 1 N HCl and dried over magnesium sulphate, and the product is, after distillative removal of the solvent, purified by silica gel chromatography (ethyl acetate/cyclohexane 1:1).
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[Br:6][C:7]1[N:8]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]([CH:27]3[CH2:29][CH2:28]3)=[CH:19][CH:18]=2)[C:9]([S:12][CH2:13][C:14]([OH:16])=[O:15])=[N:10][N:11]=1.[C:30]([O:49][CH2:50][CH:51]([CH2:53]O)[OH:52])(=[O:48])[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37]/[CH:38]=[CH:39]\[CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47]>N1C=CC=CC=1>[C:30]([O:49][CH2:50][CH:51]([OH:52])[CH2:53][O:15][C:14](=[O:16])[CH2:13][S:12][C:9]1[N:8]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]([CH:27]3[CH2:29][CH2:28]3)=[CH:19][CH:18]=2)[C:7]([Br:6])=[N:11][N:10]=1)(=[O:48])[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37]/[CH:38]=[CH:39]\[CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47]
Reactant: O=C(O)CSc1nnc(Br)n1-c1ccc(C2CC2)c2ccccc12
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)OCC(O)CO
Solvent: c1ccncc1
Solvent: O=P(Cl)(Cl)Cl
Product: CCCCCCCC/C=C\CCCCCCCC(=O)OCC(O)COC(=O)CSc1nnc(Br)n1-c1ccc(C2CC2)c2ccccc12
Temperature: 0 °C
Reaction time: 1 h

Procedure:
Phosphorus oxychloride (2.4 mmol) is added dropwise over 5 mins to a solution of 2-(5-bromo-4-(1-cyclopropylnaphthalen-4-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid (810 mg, 2.0 mmol) in pyridine (20 mL) at 0° C. The mixture is stirred at 0° C. for a further 1 hour and then glyceryl monooleate (715 mg, 2.0 mmol) dissolved in pyridine (5 mL) is added dropwise over 5 mins. The mixture is stirred at 0° C. for a further 3 hours and 1 hour at 20° C. and then quenched by addition of water (1 mL). Volatile solvents are removed in vacuo and DCM (200 mL) added. The organic phase is washed with water (1×50 mL), saturated sodium carbonate solution (1×50 mL) and brine (1×50 mL), dried over Na2SO4, concentrated to dryness and purified by column chromatography (acetone/DCM eluent) to provide 3-(2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetoxy)-2-hydroxypropyl oleate.