Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1.[Li][CH2:13][CH2:14][CH2:15][CH3:16].[Br:17][C:18]1[CH:31]=[CH:30][C:29]2[C:28](=O)[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21](=O)[C:20]=2[CH:19]=1.Cl>C(O)(=O)C.C1COCC1>[Br:17][C:18]1[CH:31]=[CH:30][C:29]2[C:20](=[C:21]([C:13]3[C:11]4[C:2](=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH:16]=[CH:15][CH:14]=3)[C:22]3[C:27]([C:28]=2[C:2]2[C:11]4[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=4)[CH:5]=[CH:4][CH:3]=2)=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH:19]=1
Reactant: O=C1c2ccccc2C(=O)c2cc(Br)ccc21
Reactant: Brc1cccc2ccccc12
Reactant: [Li]CCCC
Agent: Cl
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: Brc1ccc2c(-c3cccc4ccccc34)c3ccccc3c(-c3cccc4ccccc34)c2c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
360 g (1.74 mol) of bromonaphthalene was dissolved with THF in a 5 L flask and the temperature was lowered to −78° C. and 1600 ml (1.6 mol) of 1.6M n-BuLi was slowly added dropwise thereto. The mixture was stirred for one hour, and then 200 g (0.68 mol) of 2-bromoanthraquinone was added thereto in a solid state and then the temperature was slowly raised to room temperature and the resultant mixture was stirred. After 12 hours, 500 ml of 2N HCl(aq) was added thereto. Then, an organic layer was isolated and dried over MgSO4 and condensed under reduced pressure, thereby producing Compound C. The Compound C was used in the subsequent reaction without purification. Compound C, 346 g (2.09 mol) of KI, and 443 g (4.1 mol) of NaH2PO2.H2O were diluted with an acetic acid and then the mixture was refluxed while heating. The temperature was lowered to room temperature and thus a solid was precipitated. The solid was filtered, washed with excess water and MeOH, and re-crystallized with 300 ml of toluene, thereby producing 2-bromo-9,10-di(2-naphthyl)anthracene (230 g, 64%).
Reaction SMILES: Br[C:2]1[N:6]([CH:7]([CH3:9])[CH3:8])[C:5]2[CH:10]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)[N:11]([C:14]3[CH:19]=[C:18]([Cl:20])[C:17](=[O:21])[N:16]([CH3:22])[C:15]=3[F:23])[C:12](=[O:13])[C:4]=2[CH:3]=1.[CH3:31][O:32][C:33]1[N:38]=[C:37]([O:39][CH3:40])[C:36](B(O)O)=[CH:35][N:34]=1.BrC1N(C(C)C)C2C(C3C=CC(Cl)=CC=3)N(C3C=C(Cl)C=CC=3C)C(=O)C=2C=1.COC1C(B2OC(C)(C)C(C)(C)O2)=CN=C(N)N=1>>[Cl:20][C:18]1[C:17](=[O:21])[N:16]([CH3:22])[C:15]([F:23])=[C:14]([N:11]2[C:12](=[O:13])[C:4]3[CH:3]=[C:2]([C:36]4[C:37]([O:39][CH3:40])=[N:38][C:33]([O:32][CH3:31])=[N:34][CH:35]=4)[N:6]([CH:7]([CH3:9])[CH3:8])[C:5]=3[CH:10]2[C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)[CH:19]=1
Reactant: CC(C)n1c(Br)cc2c1C(c1ccc(Cl)cc1)N(c1cc(Cl)c(=O)n(C)c1F)C2=O
Reactant: COc1ncc(B(O)O)c(OC)n1
Agent: COc1nc(N)ncc1B1OC(C)(C)C(C)(C)O1
Agent: Cc1ccc(Cl)cc1N1C(=O)c2cc(Br)n(C(C)C)c2C1c1ccc(Cl)cc1
Product: COc1ncc(-c2cc3c(n2C(C)C)C(c2ccc(Cl)cc2)N(c2cc(Cl)c(=O)n(C)c2F)C3=O)c(OC)n1

Procedure:
The title compound was prepared in analogy to the procedure described for Example 25 but 2-bromo-5-(5-chloro-2-fluoro-1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one (Intermediate AT) and 2,4-dimethoxypyrimidine-5-boronic acid were used instead of 2-bromo-5-(5-chloro-2-methyl-phenyl)-6-(4-chloro-phenyl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-b]pyrrol-4-one and 4-methoxy-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidin-2-ylamine respectively. The title compound was obtained as a light pink foam. ESI-MS: tR=1.08 min, [M+H]+ 572/574/576 (LC-MS 1); TLC: Rf=0.14 (4:1 EtOAc/heptanes).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][NH:8][C:9]([C@H:11]([C@@H:21]([CH2:30][CH:31]([CH3:33])[CH3:32])[C:22]([NH:24][NH:25][CH2:26][CH:27]([CH3:29])[CH3:28])=[O:23])[CH2:12]/[CH:13]=[CH:14]/[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:10].C(N(CC)CC)C.[NH:41]1[CH:45]=[CH:44][CH:43]=[C:42]1[C:46](O)=[O:47].ClCCl.CO>ClCCl>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][NH:8][C:9]([C@H:11]([C@@H:21]([CH2:30][CH:31]([CH3:33])[CH3:32])[C:22]([NH:24][N:25]([CH2:26][CH:27]([CH3:28])[CH3:29])[C:46]([C:42]1[NH:41][CH:45]=[CH:44][CH:43]=1)=[O:47])=[O:23])[CH2:12]/[CH:13]=[CH:14]/[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:10]
Reactant: O=C(O)c1ccc[nH]1
Reactant: CC(C)CNNC(=O)[C@H](CC(C)C)[C@H](C/C=C/c1ccccc1)C(=O)NOC1CCCCO1
Solvent: ClCCl
Solvent: CO
Solvent: CCN(CC)CC
Product: CC(C)C[C@@H](C(=O)NN(CC(C)C)C(=O)c1ccc[nH]1)[C@H](C/C=C/c1ccccc1)C(=O)NOC1CCCCO1
Temperature: 0 °C
Reaction time: 2 h
Yield: 40.8 %

Procedure:
A solution of 0.459 g of (E)-2(R)-[1(S)-[(tetrahydro-2(RS)-pyranyloxy)carbamoyl]-4-phenyl-3-butenyl]-2′-isobutyl-4-methylvalerohydrazide in 5 ml of dichloromethane was treated under nitrogen at 0° C. with 0.28 ml of triethylamine and a solution of the acid chloride prepared from 0.166 g of 2-pyrrolecarboxylic acid in 3 ml of dichloromethane. The mixture was stirred at 0° C. for 2 hours and evaporated. The residue was dissolved in ethyl acetate. The solution was washed with 5% aqueous sodium hydrogen carbonate solution, water, 5% citric acid solution and saturated sodium chloride solution, dried over anhydrous magnesium sulphate and was evaporated to give a solid. Chromatography of this solid on silica gel using dichloromethane/methanol (50:1) for the elution followed by evaporation and trituration with diethyl ether gave 0.225 g of (E)-2(R)-[1(S)-[(tetrahydro-2(RS)-pyranyloxy)carbamoyl]-4-phenyl-3-butenyl]-2′-isobutyl-4-methyl-2′-[(2-pyrrolyl)carbonyl]valerohydrazide in the form of a white solid.
Reaction SMILES: [O-]CC.[K+].[C:5]([O:12][CH2:13][CH3:14])(=[O:11])[C:6]([O:8]CC)=O.[CH3:15][O:16][C:17]1[N:22]=[C:21]([CH3:23])[C:20]([N+:24]([O-:26])=[O:25])=[CH:19][CH:18]=1>C(OCC)C.C(O)C>[CH2:13]([O:12][C:5](=[O:11])[C:6](=[O:8])[CH2:23][C:21]1[C:20]([N+:24]([O-:26])=[O:25])=[CH:19][CH:18]=[C:17]([O:16][CH3:15])[N:22]=1)[CH3:14]
Reactant: CCOC(=O)C(=O)OCC
Reactant: COc1ccc([N+](=O)[O-])c(C)n1
Agent: CC[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: CCO
Product: CCOC(=O)C(=O)Cc1nc(OC)ccc1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a stirred suspension of potassium ethoxide (0.55 g, 6.55 mmol) in diethyl ether (20 mL, anhydrous) and ethanol (4 mL) was added diethyl oxalate (894 μL, 6.55 mmol) and the reaction mixture was stirred for 30 min prior to the addition of 6-methoxy-2-methyl-3-nitropyridine (Preparation 33, 1.0 g, 5.95 mmol) in diethyl ether (8 mL). The resulting red suspension was stirred at rt, under argon, for 20 h. The mixture was filtered, the solid washed thoroughly with diethyl ether then dried. The red solid was then taken up in hot water and the solution cooled to 0° C. The precipitate was filtered, washed with cold water, and dried to give the title compound as a beige solid. δH (CDCl3): 1.40 (3H, t), 4.07 (3H, s), 4.39 (2H, q), 6.74 (1H, d), 7.57 (1H, s), 8.40 (1H, d), 13.82 (1H, s).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[O:9])=[CH:4][CH:3]=1.[Cl:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>C(O)(C)C.O>[ClH:16].[Cl:16][C:17]1[CH:22]=[C:21]([C:2]2[CH:7]=[CH:6][C:5]([C:8]([CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)=[O:9])=[CH:4][CH:3]=2)[CH:20]=[CH:19][CH:18]=1
Reactant: OB(O)c1cccc(Cl)c1
Reactant: O=C(c1ccc(Br)cc1)C1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)O
Solvent: O
Product: Cl
Product: O=C(c1ccc(-c2cccc(Cl)c2)cc1)C1CCNCC1
Temperature: 80 °C
Reaction time: 0.08 h
Yield: 82.2 %

Procedure:
A round bottom flask was charged with (4-bromophenyl)(piperidine-4-yl)methanone (4.00 g, 14.9 mmol), 3-chlorophenyl boronic acid (3.26 g, 20.9 mmol, 1.4 eq), and Fibrecat 1029® (0.70 g, 0.448 mmol, 0.03 eq, Johnson Matthey). These solids were suspended in isopropanol (68 ml) and allowed to stir for five minutes. To this stirring solution was added potassium carbonate (6.18 g, 44.8 mmol, 3 eq.) dissolved in H2O (12 ml). The resulting solution was heated to 80° C. for 16 hours, at which time the reaction was deemed complete by LC/MS. The reaction mixture was filtered through a small bed of Celite® and the filtrate was concentrated to dryness. The resulting solids were dissolved in isopropyl acetate (100 ml) and washed with water (3×50 ml). The organics were cooled to 0° C., and to this stirring mixture was added slowly 6N HCl until solids crashed out of solution. The solids were filtered and dried for 16 hours at 50° C. in a vacuum oven to afford 2.89 g of compound 2 (72%) in >98% HPLC purity. MH+=300, 302 (about 3:1). Palladium: 4 ppm
Reaction SMILES: O.[NH2:2][C:3]1[C:8]2[CH2:9][C:10]([CH3:13])([CH3:12])[O:11][C:7]=2[C:6]([OH:14])=[CH:5][CH:4]=1.[CH:15](=O)[C:16]1[C:17](=[CH:19][CH:20]=[CH:21][CH:22]=1)[OH:18]>C(OCC)(=O)C>[CH3:13][C:10]1([CH3:12])[CH2:9][C:8]2[C:3]([N:2]=[CH:15][C:16]3[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=3[OH:18])=[CH:4][CH:5]=[C:6]([OH:14])[C:7]=2[O:11]1
Reactant: CC1(C)Cc2c(N)ccc(O)c2O1
Reactant: O=Cc1ccccc1O
Solvent: CCOC(C)=O
Solvent: O
Product: CC1(C)Cc2c(N=Cc3ccccc3O)ccc(O)c2O1
Temperature: 25 °C
Yield: 73.3 %

Procedure:
To a 500 milliliter round bottom flask equipped with a water collector, water condenser, magnetic stirrer and drying tube was added 5.38 grams (0.030 moles) of 4-amino-2,3-dihydro-2,2-dimethyl-7-hydroxybenzofuran, 3.91 grams (0.032 moles) of salicylaldehyde and 300 milliliters of ethyl acetate. The resulting reaction mixture was heated to reflux with removal of the first 50 milliliters of distillate, and the remaining mixture allowed to reflux for 1 additional hour with continuous stirring. After the stirring and refluxing period, the reaction mixture was cooled to room temperature, filtered, dried over magnesium sulfate and concentrated under reduced pressure to give 6.15 grams (0.022 moles) of 2,3-dihydro-2,2-dimethyl-4-(2-hydroxybenzylideneamino)benzofuran-7-ol in the form of a dark red oil.
Reaction SMILES: [CH2:1]([C@@H:8]1[O:10][C@@H:9]1[CH2:11][OH:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=[O:14].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>CN(C=O)C.O.Cl>[CH2:1]([C@@H:8]1[O:10][C@@H:9]1[C:11]([OH:14])=[O:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Reactant: CCCCCCC[C@@H]1O[C@@H]1CO
Agent: Cl
Agent: c1cc[nH+]cc1
Solvent: CN(C)C=O
Solvent: O
Product: CCCCCCC[C@@H]1O[C@@H]1C(=O)O
Reaction time: 8 h

Procedure:
To a solution of 500 mg (2.50 mmole) of (2R-cis)-3-heptyloxiranemethanol in 50 ml of DMF was added 3.30 g (8.75 mmole) of pyridinium dichromate. The reaction was allowed to stir overnight under argon. The mixture was then diluted with 150 ml H2O and 20 ml 0.1M HCl and washed three times with 50 ml of Et2O. The combined Et2O layers were dried over MgSO4, filtered and evaporated to afford a white powder. This residue was crystallized from petroleum ether to afford 39 mg of white power, mp 62°-3° C. 1H NMR (CDCl3) δ3.59 (d, 1, J=5 Hz), 3.24 (m, 1), 1.6-1.2 (m, 12), 0.88 (t, 3, J=7 Hz). Mass Spectra: M+(19.1)186.1, M-45(42.3)141.1, M(100)95.1.
Reaction SMILES: Cl[CH2:2][C:3](=[O:9])[CH2:4][C:5]([O:7][CH3:8])=[O:6].[F:10][C:11]1[CH:12]=[C:13]([SH:19])[CH:14]=[C:15]([O:17][CH3:18])[CH:16]=1.CN(C=O)C>O>[F:10][C:11]1[CH:12]=[C:13]([S:19][CH2:2][C:3](=[O:9])[CH2:4][C:5]([O:7][CH3:8])=[O:6])[CH:14]=[C:15]([O:17][CH3:18])[CH:16]=1
Reactant: COC(=O)CC(=O)CCl
Reactant: COc1cc(F)cc(S)c1
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)CC(=O)CSc1cc(F)cc(OC)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of methyl 4-chloroacetoacetate (1.871 mL), K2OC3 (2.210 g), 3-fluoro-5-methoxybenzenethiol (2.3 g) and DMF (30 mL) was stirred at room temperature for 1 h. The mixture was poured into water and extracted with EtOAc. The organic layer was separated, washed successively with water and brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/hexane) to give the title compound (2.87 g).
Reaction SMILES: BrC1C=CC(O)=C(C2C=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:18]4[N:22]([CH:23]5[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]5)[C:21]5[CH:29]=[CH:30][C:31]([C:33]([OH:35])=[O:34])=[CH:32][C:20]=5[N:19]=4)[CH:14]=3)[N:9]=2)C=1.[CH3:37][O:38][C:39]1[CH:40]=[CH:41][C:42]2[O:46][CH:45]=[C:44]([C:47](=O)[CH3:48])[C:43]=2[CH:50]=1.[OH-].[K+]>C(O)C>[CH:23]1([N:22]2[C:21]3[CH:29]=[CH:30][C:31]([C:33]([OH:35])=[O:34])=[CH:32][C:20]=3[N:19]=[C:18]2[C:13]2[CH:14]=[C:15]3[C:10](=[CH:11][CH:12]=2)[N:9]=[C:47]([C:44]2[C:43]4[CH:50]=[C:39]([O:38][CH3:37])[CH:40]=[CH:41][C:42]=4[O:46][CH:45]=2)[CH:48]=[CH:16]3)[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]1
Reactant: O=C(O)c1ccc2c(c1)nc(-c1ccc3nc(-c4cc(Br)ccc4O)ccc3c1)n2C1CCCCC1
Reactant: COc1ccc2occ(C(C)=O)c2c1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: COc1ccc2occ(-c3ccc4cc(-c5nc6cc(C(=O)O)ccc6n5C5CCCCC5)ccc4n3)c2c1
Yield: 8 %

Procedure:
Following the procedure and workup for Compound 354, Compound 354e (100 mg, 0.256 mmol) was reacted with 1-(5-methoxy-benzofuran-3-yl)-ethanone (0.256 mmol) in ethanol (2 mL) using 10% w/v KOH in ethanol (506 μL, 0.64 mmol) to produce the title compound (10 mg, 8% yield). MS: 518.24 (M+H+); HPLC Procedure B, retention time=7.60 min.
Reaction SMILES: [C:1]([C:5]1[N:6]=[C:7]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([CH2:19][C:20]#[N:21])=[CH:15][C:13]=3[CH:14]=2)[S:8][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].C(N)(=[S:24])C.Cl.O1CCOCC1>C(Cl)(Cl)Cl>[C:1]([C:5]1[N:6]=[C:7]([C:10]2[O:11][C:12]3[CH:18]=[CH:17][C:16]([CH2:19][C:20](=[S:24])[NH2:21])=[CH:15][C:13]=3[CH:14]=2)[S:8][CH:9]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1csc(-c2cc3cc(CC#N)ccc3o2)n1
Reactant: CC(N)=S
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: C1COCCO1
Product: CC(C)(C)c1csc(-c2cc3cc(CC(N)=S)ccc3o2)n1

Procedure:
A mixture of 4-tert-butyl-2-[5-(cyanomethyl)benzofuran-2-yl]thiazole (1.31 g) and thioacetamide in a mixture of 4N-hydrogen chloride of 1,4-dioxane (4 ml) and chloroform was stirred under reflux for 30 minutes and removed the solvent at the same temperature. The residue was washed with water to give crude 4-tert-butyl-2-[5-(thiocarbamoylmethyl)-benzofuran-2-yl]thiazole (1.23 g).
Reaction SMILES: [NH3:1].C(O)C.Cl.[CH2:6]([O:8][C:9]([CH2:11][C:12](=[NH:16])OCC)=[O:10])[CH3:7].[N:17]([O-:19])=O.[Na+].O.Cl>>[CH2:6]([O:8][C:9](=[O:10])[CH:11]([C:12](=[NH:16])[NH2:1])[N:17]=[O:19])[CH3:7]
Reactant: CCOC(=N)CC(=O)OCC
Reactant: O=N[O-]
Reactant: N
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CCOC(=O)C(N=O)C(=N)N
Reaction time: 3 h

Procedure:
To a solution of 2M ammonia in Ethanol (152 ml, 0.304 mmol) at 0° C. to 5° C., ethyl ethoxycarbonylacetimidate HCl (25 g, 0.127 mmol) was added over 30 minutes. The reaction was stirred vigorously at this temperature for 3 hours, after which a solution of sodium nitrite in water (9.63 g, 0.139 mmol) was added in a single portion. The pH of the mixture was adjusted to pH6 with the addition of 5N HCl. The reaction mixture was left to stir at RT overnight. The yellow precipitate formed was filtered under vacuum, washed with water and dried to give the title compound;
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[C:8]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:7]=[CH:6][C:5]=1[NH2:17])([O-:3])=[O:2].[Br:18]Br.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(Cl)Cl>[Br:18][C:6]1[CH:7]=[C:8]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[C:5]=1[NH2:17]
Reactant: BrBr
Reactant: Nc1ccc(Oc2ccccc2)cc1[N+](=O)[O-]
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClCCl
Product: Nc1c(Br)cc(Oc2ccccc2)cc1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 2 h
Yield: 92 %

Procedure:
2-Nitro-4-phenoxy-phenylamine (2.3 g, 10 mmol) prepared in Preparation 1 was dissolved in DCM (30 mL), Br2 (720 ul, 35%) was added thereto at 0° C., and the mixture was stirred for 2 h. After completion of the reaction, saturated aqueous sodium thiosulfate solution was added. The resulting mixture was extracted with EtOAc, and dried over MgSO4. The solvent was removed under reduced pressure, and the residue was purified by column chromatography to give the title compound (2.84 g, Yield 92%).
Reaction SMILES: [C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[C:12]([O:14][CH2:15][CH3:16])[C:11]([C:17]([F:20])([F:19])[F:18])=[CH:10][C:9]=1[NH2:21])([CH3:4])([CH3:3])[CH3:2].C([O:27][C:28](=O)[CH2:29][C:30]([C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([C:38]2[CH:43]=[C:42]([CH3:44])[N:41]=[C:40]([CH3:45])[CH:39]=2)[CH:33]=1)=[O:31])(C)(C)C>>[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[C:12]([O:14][CH2:15][CH3:16])[C:11]([C:17]([F:20])([F:19])[F:18])=[CH:10][C:9]=1[NH:21][C:28](=[O:27])[CH2:29][C:30]([C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([C:38]2[CH:39]=[C:40]([CH3:45])[N:41]=[C:42]([CH3:44])[CH:43]=2)[CH:33]=1)=[O:31])([CH3:2])([CH3:3])[CH3:4]
Reactant: Cc1cc(-c2cccc(C(=O)CC(=O)OC(C)(C)C)c2)cc(C)n1
Reactant: CCOc1cc(NC(=O)OC(C)(C)C)c(N)cc1C(F)(F)F
Product: CCOc1cc(NC(=O)OC(C)(C)C)c(NC(=O)CC(=O)c2cccc(-c3cc(C)nc(C)c3)c2)cc1C(F)(F)F

Procedure:
The title compound was prepared from [2-amino-5-ethoxy-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J8) (320 mg, 1.0 mmol) and 3-[3-(2,6-dimethyl-pyridin-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (Example K15) (325 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (530 mg, 93%).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([NH2:12])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].C(N([CH2:18][CH3:19])CC)C.[CH2:20]([CH:30]([CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45])[C:31](Cl)=[O:32])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]>O1CCCC1>[CH2:34]([CH:30]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:18][CH3:19])[C:31]([NH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([NH:12][C:31](=[O:32])[CH:30]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6])=[O:32])[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43]
Reactant: CCCCCCCCCCCCC(CCCCCCCCCC)C(=O)Cl
Reactant: COC(=O)c1cc(N)cc(N)c1
Reactant: CCN(CC)CC
Solvent: C1CCOC1
Product: CCCCCCCCCCCCC(CCCCCCCCCC)C(=O)Nc1cc(NC(=O)C(CCCCCCCCCC)CCCCCCCCCCCC)cc(C(=O)OC)c1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
3,5-Diaminobenzoic acid (Sigma-Aldrich) was esterified using a known procedure (Electrochimica Acta 2001, 46, 3955-3962) with thionyl chloride and anhydrous methanol to give the corresponding methyl ester, methyl 3,5-diaminobenzoate. Methyl 3,5-diaminobenzoate (260.8 mg, 1.9 mmol) was dissolved in dry tetrahydrofuran (5 mL) in a 100 mL vessel under inert atmosphere. Triethylamine (0.7 mL, 4.99 mmol) was then added and the solution was cooled to 0° C. A solution of 2-decyltetradecanoyl chloride from Step 1 in dry tetrahydrofuran (10 mL) was then added slowly, dropwise. The reaction was then allowed to warm slowly to room temperature. After stirring overnight, the reaction was quenched with water and the tetrahydrofuran was removed by rotary evaporation. The crude product residue was then dissolved in diethyl ether (50 mL) and washed with deionized water (20 mL). The ether layer was separated and concentrated to give methyl 3,5-bis(2′-decyltetradecanamido)benzoate as a pale pink solid (1.17 g).
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]2[C:11](=[C:12]([CH2:15][CH2:16][CH3:17])[C:13]=1[OH:14])[N:10]=[C:9]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:8]=[C:7]2[N:23]([CH3:25])[CH3:24])(=[O:3])[CH3:2].[C:26](OCC)(=O)[C:27]([O:29][CH2:30][CH3:31])=[O:28].CCOCC.[H-].[Na+]>CN(C)C=O.Cl.O>[CH3:25][N:23]([CH3:24])[C:7]1[C:6]2[C:11](=[C:12]([CH2:15][CH2:16][CH3:17])[C:13]3[O:14][C:26]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:2][C:1](=[O:3])[C:4]=3[CH:5]=2)[N:10]=[C:9]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:8]=1
Reactant: CCCc1c(O)c(C(C)=O)cc2c(N(C)C)cc(C(=O)OCC)nc12
Reactant: CCOC(=O)C(=O)OCC
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CCOCC
Solvent: CN(C)C=O
Product: CCCc1c2nc(C(=O)OCC)cc(N(C)C)c2cc2c(=O)cc(C(=O)OCC)oc12
Reaction time: 7 h

Procedure:
A mixture of the product of step (b) (1.6 g; 4.8426 mmole) and diethyl oxalate (5.7 g; 39.041 mmole; 5.3 ml) in dry dimethylformamide (60 ml) was added slowly to a stirring suspension of ether washed sodium hydride (0.29 g; 12.0808 mmole) in dry dimethylformamide (10 ml) under nitrogen. After the addition, the mixture was allowed to stir for 7 hours. The reaction mixture was poured onto ice and was then acidified with dilute hydrochloric acid. The pH of the mixture was adjusted to about 6 before being extracted into chloroform. This was washed with water, dried and evaporated to give a yellow solid. The solid was taken up in ethanolic hydrogen chloride (50 ml) and heated to reflux on the steambath for 3 hours. The solution was cooled, treated with water and then concentrated. The pH of the mixture was adjusted to about 7 and then extracted into chloroform. The extract was washed with water, dried and evaporated, to give a brown solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH2:9])[CH:5]=[CH:6][C:7]=1[Cl:8].N1C(C)=CC=CC=1C.Br[CH2:19][CH2:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22]>C1(C)C=CC=CC=1>[C:24]([O:23][C:21](=[O:22])[CH2:20][CH2:19][NH:9][C:4]1[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=1)([CH3:27])([CH3:26])[CH3:25]
Reactant: Nc1ccc(Cl)c(Cl)c1
Reactant: CC(C)(C)OC(=O)CCBr
Solvent: Cc1cccc(C)n1
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)CCNc1ccc(Cl)c(Cl)c1
Reaction time: 30 h
Yield: 52.2 %

Procedure:
A solution of 9.61 g (59.33 mmol) of 3,4-dichloro-phenylamine and 10.21 ml (59.33 mmol) of 2,6-lutidine in 55 ml of toluene was treated slowly with 6.50 ml (59.33 mmol) of tert-butyl 3-bromopropionate and stirred 30 h at reflux temperature. The reaction was then partitioned between 10% aq. KHSO4 solution and EtOAc (3×). The organic phases were washed with 10% aq. NaCl solution, dried over Na2SO4 evaporated and purified by flash silica gel column (n-heptane:EtOAc 9:1) to yield 8.98 g (52%) of the title compound as off-white solid. MS: 290.0 (MH+, 2Cl).
Reaction SMILES: C(OC([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][C@@H:16]([C:25]([OH:27])=O)[NH:17]C(OC(C)(C)C)=O)=O)C1C=CC=CC=1.[CH3:28][S:29](Cl)(=[O:31])=[O:30].[NH:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1>>[NH2:17][C@H:16]([C:25]([N:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1)=[O:27])[CH2:15][CH2:14][CH2:13][CH2:12][NH:11][S:29]([CH3:28])(=[O:31])=[O:30]
Reactant: CC(C)(C)OC(=O)N[C@@H](CCCCNC(=O)OCc1ccccc1)C(=O)O
Reactant: C1CCNC1
Reactant: CS(=O)(=O)Cl
Product: CS(=O)(=O)NCCCC[C@H](N)C(=O)N1CCCC1

Procedure:
Starting from (S)-N6-(benzyloxycarbonyl)-N2-(tert-butyloxycarbonyl)-lysine, methane-sulphonyl chloride and pyrrolidine, the expected product is obtained according to the procedure described in Steps A to C of Example 3.
Reaction SMILES: Cl.[NH:2]1[CH2:6][CH2:5][CH:4]([S:7][C:8]2[CH:9]=[C:10]([OH:14])[CH:11]=[CH:12][CH:13]=2)[CH2:3]1.[C:15]1([CH2:21][CH2:22][CH:23]=O)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>>[C:15]1([CH2:21][CH2:22][CH2:23][N:2]2[CH2:6][CH2:5][CH:4]([S:7][C:8]3[CH:9]=[C:10]([OH:14])[CH:11]=[CH:12][CH:13]=3)[CH2:3]2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: Oc1cccc(SC2CCNC2)c1
Reactant: O=CCCc1ccccc1
Agent: Cl
Product: Oc1cccc(SC2CCN(CCCc3ccccc3)C2)c1

Procedure:
The title compound, MS: m/e=314.3 (M+H+) was prepared from (RS)-3-(pyrrolidin-3-yl-sulfanyl)-phenol hydrochloride and 3-phenylpropionaldehyde.