Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:7][C:8](=[O:21])[C:9]([CH2:11][C:12]([O:14]CCCCCC)=O)=[CH2:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[CH2:22]([CH:24]([CH2:27][CH2:28][CH2:29][CH3:30])[CH2:25][NH2:26])[CH3:23]>>[CH2:1]([O:7][C:8]([CH:9]1[CH2:11][C:12](=[O:14])[N:26]([CH2:25][CH:24]([CH2:22][CH3:23])[CH2:27][CH2:28][CH2:29][CH3:30])[CH2:10]1)=[O:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCC(CC)CN
Reactant: C=C(CC(=O)OCCCCCC)C(=O)OCCCCCC
Product: CCCCCCOC(=O)C1CC(=O)N(CC(CC)CCCC)C1
Temperature: 45 °C
Reaction time: 1 h

Procedure:
Bis(hexyl)itaconate (400 g; 1.34 Mol) was charged to a 1 L reaction vessel and the material stirred mechanically under nitrogen while heating to 45° C. 2-Ethylhexylamine (1.05 equiv.; 1.41 Mol; 182 g) was charged to a pressure-equalizing addition funnel and the amine added dropwise to the stirred diester over the course of one hour. During the addition, a moderate exotherm was observed. When the addition was complete, the mixture was heated to 75° C. and held for one hour before cooling to room temperature overnight. The following day, the vessel was equipped with a distillation sidearm/condenser and heated to 90° C. under reduced pressure (−25″ Hg) (−635 mm) in order to remove hexanol and excess amine. When stripping was complete, H-NMR analysis of the product was consistent with the expected lactam structure. 136.6 g was recovered of yellow moderately viscous liquid. Sample materials were collected from this preparation and designated 1-(2-ethylhexyl)-5-oxo-3-pyrrolidinecarboxylic acid hexyl ester for comparison testing described in the Examples below.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:3]=1[C:4](Cl)=O.[C:14](#[N:17])[CH:15]=C.C(N(CCCC)CCCC)CCC>CC1C=CC(C)=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:3]=1[CH:4]=[CH:15][C:14]#[N:17]
Reactant: C=CC#N
Reactant: Cc1ccc([N+](=O)[O-])cc1C(=O)Cl
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: CCCCN(CCCC)CCCC
Solvent: Cc1ccc(C)cc1
Product: Cc1ccc([N+](=O)[O-])cc1C=CC#N

Procedure:
0.336 g (1.5 millimols) of palladium acetate, 29.93 g (150 millimols) of 2-methyl-5-nitrobenzoyl chloride, 9.94 g (187.5 millimols) of acrylonitrile and 27.80 g (150 millimols) of tri-n-butylamine, in 150 ml of p-xylene, are stirred for 80 minutes at 130°. The mixture is then extracted, and dried, as described in Example 68. The crude product is chromatographed on silica gel in toluene and is then recrystallised from carbon tetrachloride/cyclohexane. 6.3 g (22% of theory) of white crystals, of melting point 115.6° C., are obtained. Analysis for C10H8N2O2 : calculated C 63.83%, H 4.29%, N 14.89%; found C 63.8%, H 4.2%, N 15.1%.
Reaction SMILES: [C:1]1([NH2:11])[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.N1C2C(=CC=C3CCCC3=2)[C:14](=[O:24])[C:13]1=[O:25]>>[CH:7]1[CH:6]=[C:5]2[CH:4]=[CH:3][C:2]3[C:13](=[O:25])[C:14](=[O:24])[NH:11][C:1]=3[C:10]2=[CH:9][CH:8]=1
Reactant: O=C1Nc2c(ccc3c2CCC3)C1=O
Reactant: Nc1cccc2c1CCCC2
Product: O=C1Nc2c(ccc3ccccc23)C1=O
Yield: 54 %

Procedure:
The benz[g]isatin was prepared in two steps from 5,6,7,8-tetrahydro-1-naphthylamine using the methods described for 1,6,7,8-tetrahydrocyclopenta[g]indole-2,3-dione (G. W. Rewcastle et. al., J. Med. Chem., 1991, 34, 217). The product (54% yield from N-[1-(5,6,7,8-tetrahydronaphthalenyl)]-2-(hydroximino)acetamide) was obtained as an orange solid: mp. 234–235° C. (lit. [U.S. Pat. No. 1,856,210, 1929] 232° C.); NMR δH (400 MHz, DMSO-d6) 1.73 (4H, m), 2.49 (2H, m), 2.73 (2H, m), 6.78 (1H, d, J 7.7 Hz), 7.21 (1H, d, J 7.7 Hz) and 10.92 (1H, s).
Reaction SMILES: Cl.[F:2][C:3]1[CH:20]=[CH:19][C:6]([C:7]([N:9]2[CH2:14][CH2:13][CH2:12][C@H:11]([C:15]([NH:17][NH2:18])=[O:16])[CH2:10]2)=[O:8])=[CH:5][CH:4]=1.[F:21][C:22]1[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.C(N(CC)CC)C.Cl>ClCCl>[F:2][C:3]1[CH:20]=[CH:19][C:6]([C:7]([N:9]2[CH2:14][CH2:13][CH2:12][C@H:11]([C:15]([NH:17][NH:18][C:26](=[O:27])[C:25]3[CH:29]=[CH:30][C:22]([F:21])=[CH:23][CH:24]=3)=[O:16])[CH2:10]2)=[O:8])=[CH:5][CH:4]=1
Reactant: NNC(=O)[C@H]1CCCN(C(=O)c2ccc(F)cc2)C1
Reactant: O=C(O)c1ccc(F)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(NNC(=O)[C@H]1CCCN(C(=O)c2ccc(F)cc2)C1)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 6 %

Procedure:
A mixture of 1-(4-fluoro-benzoyl)-(S)-piperidine-3-carboxylic acid hydrazide hydrochloride, already prepared as described in Example 57 (C) (2.97 g, 11.2 mmol), 4-fluorobenzoic acid (1.68 g, 11.2 mmol), HOBT (1.5 g, 11.2 mmol), EDCI.HCl (3.2 g, 16.8 mmol) and dry triethylamine (5.43 mL, 39.5 mmol) in dry dichloromethane (80 mL) was kept under stirring overnight at ambient temperature, under nitrogen atmosphere. HCl 1N (80 mL) was then added and the phases separated. The organic layer was washed with HCl 1N (80 mL), with NaOH 1N (80 mL×2 times), then with water (80 mL). Evaporation of the organic solvent afforded a crude oil which was purified by flash chromatography (silica gel, eluent: DCM/MeOH/NH4OH 98/2/0.2). The compound obtained after column chromatography was purified again by flash chromatography (silica gel, eluent: DCM/MeOH/NH4OH 98/2/0.2) to provide the pure 4-fluoro-benzoic acid N′-[(S)-1-(4-fluoro-benzoyl)-piperidine-3-carbonyl]-hydrazide as a white solid (250 mg).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([O:13][CH3:14])[C:10]=1[O:11][CH3:12])[CH:6]=[O:7].[CH2:15]([Mg]Br)[CH2:16][CH3:17]>>[CH3:14][O:13][C:9]1[CH:8]=[C:5]([C:6](=[O:7])[CH2:15][CH2:16][CH3:17])[CH:4]=[C:3]([O:2][CH3:1])[C:10]=1[O:11][CH3:12]
Reactant: COc1cc(C=O)cc(OC)c1OC
Reactant: CCC[Mg]Br
Product: CCCC(=O)c1cc(OC)c(OC)c(OC)c1

Procedure:
Substantially the same procedure as in Process 1 of Example 48 was repeated using 3,4,5-trimethoxybenzaldehyde (43.12 g) and propylmagnesium bromide (1.0 M tetrahydrofuran solution, 330 ml) to give 1-(3,4,5-trimethoxyphenyl)-1-butanone (17.43 g).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:10][C:11]3[C:16]([N:17]=2)=[CH:15][CH:14]=[CH:13][N:12]=3)=[CH:5][CH:4]=1)#[N:2].S(=O)(=O)(O)[OH:19]>>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]2[O:10][C:11]3[C:16]([N:17]=2)=[CH:15][CH:14]=[CH:13][N:12]=3)=[CH:7][CH:8]=1)(=[O:19])[NH2:2]
Reactant: O=S(=O)(O)O
Reactant: N#Cc1ccc(-c2nc3cccnc3o2)cc1
Product: NC(=O)c1ccc(-c2nc3cccnc3o2)cc1
Reaction time: 16 h

Procedure:
A solution of 600 mg. of 2-(4-cyanophenyl)oxazolo[5,4-b]pyridine in 8 ml. of concentrated sulfuric acid was allowed to stand at room temperature for 16 hours. The solution was poured onto ice and the white precipitate was collected on a filter to give 2-(4-carbamylphenyl)oxazolo[5,4-b]pyridine, m.p. 315° C. (dec.).
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:32][C:33]1[CH:38]=[C:37]([OH:39])[CH:36]=[CH:35][C:34]=1[C:40](=[O:42])[CH3:41].[C:43]([O:47][C:48]([N:50]1[CH2:55][CH2:54][CH:53](O)[CH2:52][CH2:51]1)=[O:49])([CH3:46])([CH3:45])[CH3:44]>O1CCCC1>[C:43]([O:47][C:48]([N:50]1[CH2:55][CH2:54][CH:53]([O:39][C:37]2[CH:36]=[CH:35][C:34]([C:40](=[O:42])[CH3:41])=[C:33]([F:32])[CH:38]=2)[CH2:52][CH2:51]1)=[O:49])([CH3:46])([CH3:44])[CH3:45]
Reactant: CC(C)(C)OC(=O)N1CCC(O)CC1
Reactant: CC(=O)c1ccc(O)cc1F
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(=O)c1ccc(OC2CCN(C(=O)OC(C)(C)C)CC2)cc1F
Temperature: 25 °C

Procedure:
In a 500 mL round bottom flask, diethyl azodicarboxylate (16.9 g, 97.3 mmol) and triphenylphosphine (25.5 g, 97.3 mmol) in tetrahydrofuran (200 mL) were cooled to 0° C. 1-(2-Fluoro-4-hydroxy-phenyl)-ethanone (10.0 g, 64.9 mmol) and 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (15.67 g, 77.9 mmol) in tetrahydrofuran (100 mL) were added. The reaction was warmed to ambient temperature 14 h. The solvents were concentrated under vacuum and methylene chloride (100 mL) and hexanes (500 mL) were added. The solids were filtered off. The mother liquor was concentrated under vacuum and chromatographed through silica gel with hexanes/ethyl acetate (7:3) as eluent to produce 17.5 g (80%). Mp 72-73° C.
Reaction SMILES: [CH2:1]([N:8]1[CH:15](O)[C@H:14]2[N:10]([C@H:11]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[S:12][CH2:13]2)[C:9]1=[O:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:24][Si:25]([CH3:39])([CH3:38])[O:26][C:27]1[CH2:32][CH2:31][CH2:30][CH2:29][C:28]=1[O:33][Si](C)(C)C.B(F)(F)F.CCOCC>ClCCl.CCOCC>[CH2:1]([N:8]1[C@@H:15]([C:27]2([O:26][Si:25]([CH3:39])([CH3:38])[CH3:24])[CH2:32][CH2:31][CH2:30][CH2:29][C:28]2=[O:33])[C@H:14]2[N:10]([C@H:11]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[S:12][CH2:13]2)[C:9]1=[O:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C[Si](C)(C)OC1=C(O[Si](C)(C)C)CCCC1
Reactant: O=C1N(Cc2ccccc2)C(O)[C@@H]2CS[C@@H](c3ccccc3)N12
Agent: FB(F)F
Solvent: CCOCC
Solvent: ClCCl
Product: C[Si](C)(C)OC1([C@H]2[C@@H]3CS[C@@H](c4ccccc4)N3C(=O)N2Cc2ccccc2)CCCCC1=O
Temperature: 10 °C
Yield: 98 %

Procedure:
To a solution of compound 6-benzyl-7-hydroxy-3-phenyl-(3S, 7aR)-perhydroimidazo[1,5-C][1,3]thiazol-5-one of formula (6) (0.340 parts, 1 mmol) in dichloromethane (10 parts) was added 1,2-bistrimethylsilyloxy cyclohexene (0.516 parts, 2 mmol). Then the solution was cooled to 10° C., and Lewis acid for example BF3.Et2O (0.142 parts, 1 mmol) was added drop wise. The reaction mixture was stirred at 10° C. for 10 mints, and the reaction mixture was quenched with saturated ammonium chloride (10 parts). Then the organic layer was separated, concentrated and column purification with ethylacetate:pet.ether (15:85) as eluent provided compound 6-benzyl-7-(1-trimethylsilyloxy-2-oxocyclohexyl)-3-phenyl-(3S, 7R, 7aR)-perhydroimidazo[1,5-C][1,3]thiazole-5-one of formula (7e) (viscous liquid, 0.490 parts, 0.98 mmol) in 98% yield.
Reaction SMILES: [NH2:1][C@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.[C:14](OC(=O)C)(=[O:16])C>C(O)=O.O>[CH:14]([NH:1][C@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([OH:10])=[CH:8][CH:9]=1)=[O:16]
Reactant: CC(=O)OC(C)=O
Reactant: N[C@@H](Cc1ccc(O)cc1)C(=O)O
Solvent: O
Solvent: O=CO
Product: O=CN[C@@H](Cc1ccc(O)cc1)C(=O)O
Temperature: 10 °C
Reaction time: 1 h
Yield: 88 %

Procedure:
L-Tyrosine (60 g; 0.33 mol) was dissolved in 98% formic acid (400 ml) and cooled to 10° C. Acetic anhydride, (192 ml; 1.73 mol) was added in four stages for five minutes, while at the same time maintaining a temperature of 10° C. The mixture was then stirred for 60 min at 10° C. and then kept at room temperature for 30 min. Water (192 ml) was added with stirring at 10 to 15° C. for 30 min, and then the mixture was subjected to evaporation under reduced pressure at 70° C., until a dry residue was obtained. The residual oily solid was dissolved in a minimal volume of boiling water, and then cooled to produce fine white crystals of N-formyl-L-tyrosine (60.6 g; 88%).
Reaction SMILES: S(=O)(=O)(O)O.C([O:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17](=[O:19])[CH3:18])=[CH:12][C:11]=1[O:20]C(=O)C)(=O)C.[C:24](OCC)(=O)[CH3:25]>>[CH3:24][C:25]1[C:14]2[C:13](=[CH:12][C:11]([OH:20])=[C:10]([OH:9])[CH:15]=2)[O:16][C:17](=[O:19])[CH:18]=1
Reactant: CCOC(C)=O
Reactant: CC(=O)Oc1ccc(OC(C)=O)c(OC(C)=O)c1
Agent: O=S(=O)(O)O
Product: Cc1cc(=O)oc2cc(O)c(O)cc12
Yield: 95 %

Procedure:
45 ml 75% sulphuric acid is added dropwise to a mixture of 5.8 ml ethyl acetate and 11.4 g 1,2,4-triacetoxy- benzene, heated for 30 min to 80° C., poured onto ice, filtered, the precipitate is washed neutral and dried in a vacuum. 8.2 g of the title compound (95 % of theory) is obtained with a melting point of 270° to 272° C.
Reaction SMILES: [OH:1][CH2:2][CH:3]1[CH2:8][CH2:7][CH:6]=[CH:5][O:4]1.[S:9](Cl)([C:12]1[CH:18]=[CH:17][C:15]([CH3:16])=[CH:14][CH:13]=1)(=[O:11])=[O:10]>N1C=CC=CC=1>[S:9]([O:1][CH2:2][CH:3]1[CH2:8][CH2:7][CH:6]=[CH:5][O:4]1)([C:12]1[CH:18]=[CH:17][C:15]([CH3:16])=[CH:14][CH:13]=1)(=[O:11])=[O:10]
Reactant: OCC1CCC=CO1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OCC2CCC=CO2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Whilst cooling a solution of 14.2 g of 2-hydroxymethyl-3,4-dihydro-2H-pyran in 120 ml of pyridine on an ice-water bath at 0°-5° C., 28.4 g of crystals of tosyl chloride were added and the mixture was then stirred at room temperature overnight. The salt which precipitated with the aid of a Celite (Trademark) filter aid was separated by filtration and the filtrate was concentrated under reduced pressure. Water was added to the residue and the resulting mixture was extracted with diethyl ether. The ethereal extract was washed with a saturated aqueous solution of sodium bicarbonate and then with aqueous sodium chloride, after which the solvent was evaporated off under reduced pressure. The residue was purified by column chromatography through silica gel eluted with a 7:1 by volume mixture of hexane and ethyl acetate, to give 31.5 g of the title compound, in the form of colourless crystals melting at 47°-48° C.
Reaction SMILES: [Br:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][C:5]([NH:11][C:12]2[N:17]=[C:16]([C:18]3[CH:19]=[N:20][N:21]4[CH2:26][CH2:25][CH2:24][CH2:23][C:22]=34)[CH:15]=[CH:14][N:13]=2)=[C:4]([O:27][CH3:28])[CH:3]=1.[NH4+].[Cl-].O>C(O)C.[Fe]>[Br:1][C:2]1[CH:3]=[C:4]([O:27][CH3:28])[C:5]([NH:11][C:12]2[N:17]=[C:16]([C:18]3[CH:19]=[N:20][N:21]4[CH2:26][CH2:25][CH2:24][CH2:23][C:22]=34)[CH:15]=[CH:14][N:13]=2)=[CH:6][C:7]=1[NH2:8]
Reactant: COc1cc(Br)c([N+](=O)[O-])cc1Nc1nccc(-c2cnn3c2CCCC3)n1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: COc1cc(Br)c(N)cc1Nc1nccc(-c2cnn3c2CCCC3)n1
Yield: 92.5 %

Procedure:
N-(4-Bromo-2-methoxy-5-nitrophenyl)-4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-amine (Intermediate 138, 944 mg, 2.12 mmol), iron (710 mg, 12.7 mmol) and NH4Cl (85 mg, 1.59 mmol) were heated in ethanol (40 mL) and water (13 mL) at reflux for 1.5 h. The mixture was then cooled and filtered. The residue was triturated in 10% CH3OH in CH2Cl2 (30 mL) for 15 minutes and then filtered. The residues were triturated again with 10% CH3OH in CH2Cl2 (30 mL) and filtered. The combined filtrates were washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 0-5% CH3OH in CH2Cl2 gave the title compound (814 mg, 92%) as a brown solid after trituration with diethyl ether; 1H NMR: 1.80-1.87 (2H, m), 1.96-2.03 (2H, m), 3.13 (2H, t), 3.77 (3H, s), 4.12 (2H, t), 4.82 (2H, s), 7.02 (1H, s), 7.05 (1H, d), 7.75 (1H, s), 7.77 (1H, s), 8.10 (1H, s), 8.34 (1H, d); m/z: ES+ MH+ 415/417.
Reaction SMILES: [NH2:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:12][CH:11]=2)[CH2:4][CH2:3]1.[C:19]1([N:25]=[C:26]=[O:27])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C1C=CC=CC=1>CCOCC>[NH:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]([CH2:9][CH2:8][N:5]2[CH2:6][CH2:7][N:2]([NH:1][C:26]([NH:25][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:27])[CH2:3][CH2:4]2)=[CH:11]1
Reactant: O=C=Nc1ccccc1
Reactant: NN1CCN(CCc2c[nH]c3ccccc23)CC1
Solvent: CCOCC
Solvent: c1ccccc1
Product: O=C(Nc1ccccc1)NN1CCN(CCc2c[nH]c3ccccc23)CC1
Reaction time: 8 h

Procedure:
A stirred solution of 6.13 g of 3-[2-(4-aminopiperazin-1-yl)ethyl]indole and 3.53 g of phenylisocyanate in 100 ml. of dry benzene is refluxed for 6 hours and then allowed to stand at ambient temperature overnight. Ether is added slowly to promote crystallization. The solid product is filtered, washed with ether and dried. The solid is recrystallized twice from a dimethylformamide water mixture to give crystals m.p. 168°-171° C. of 1-[1-(indol-3-ylethyl)piperazin-4-yl]-3-phenylurea.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH:4]1[CH2:9][CH2:8][CH:7]([P:10]([CH2:17][O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)(=[O:16])[O:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH2:6][CH2:5]1.[CH2:25]([O:32][C:33]1[CH:43]=[CH:42][C:36]([O:37][CH2:38][C@@H:39]2[CH2:41][O:40]2)=[CH:35][CH:34]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>>[CH2:25]([O:32][C:33]1[CH:34]=[CH:35][C:36]([O:37][CH2:38][CH:39]([OH:40])[CH2:41][NH:1][CH2:2][CH2:3][CH:4]2[CH2:9][CH2:8][CH:7]([P@:10]([CH2:17][O:18][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)(=[O:16])[O:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH2:6][CH2:5]2)=[CH:42][CH:43]=1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1
Reactant: c1ccc(COc2ccc(OC[C@@H]3CO3)cc2)cc1
Reactant: CCCCOP(=O)(COc1ccccc1)C1CCC(CCN)CC1
Product: CCCCO[P@](=O)(COc1ccccc1)C1CCC(CCNCC(O)COc2ccc(OCc3ccccc3)cc2)CC1

Procedure:
The title compound was prepared from 4-(2-aminoethyl)phenoxy methylcyclohexylphosphinic acid, n-butyl ester and (S)-2-(4-benzyloxyphenoxymethyl)oxirane according to the method described in Procedure 13.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[NH2:5][C:6]1[N:10]=[C:9]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[NH:8][N:7]=1>C1COCC1>[C:1]([N:7]1[C:6]([NH2:5])=[N:10][C:9]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])=[N:8]1)(=[O:3])[CH3:2]
Reactant: CCCCCCCCCCCc1nc(N)n[nH]1
Reactant: CC(=O)Cl
Solvent: C1CCOC1
Product: CCCCCCCCCCCc1nc(N)n(C(C)=O)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 88.8 %

Procedure:
Acetyl chloride (1.04 mL, 14.7 mmol) was added in one portion to a slurry of 3-amino-5-undecyl-1H-1,2,4-triazole (3.50 g, 14.7 mmol) in THF (100 mL). The resulting slurry was stirred (1 hour, 25° C.), then concentrated in vacuo. The residue was suspended in ethyl acetate (300 mL), washed with ice cold water (2×100 mL), washed with ice cold brine (1×100 mL), then dried (MgSO4) and concentrated to yield 3.66 g (89.3%) of 2-acetyl-3-amino-5-undecyl-2H-1,2,4-triazole as a waxy solid.
Reaction SMILES: C([O:3][C:4](=O)[CH:5]([N:7]1[C:12]2[CH:13]=[C:14]([Br:18])[C:15]([CH3:17])=[CH:16][C:11]=2[O:10][CH2:9][C:8]1=S)[CH3:6])C.O.[NH2:22][NH2:23]>CCO>[Br:18][C:14]1[CH:13]=[C:12]2[C:11](=[CH:16][C:15]=1[CH3:17])[O:10][CH2:9][C:8]1[N:7]2[CH:5]([CH3:6])[C:4](=[O:3])[NH:22][N:23]=1
Reactant: CCOC(=O)C(C)N1C(=S)COc2cc(C)c(Br)cc21
Reactant: NN
Solvent: CCO
Solvent: O
Product: Cc1cc2c(cc1Br)N1C(=NNC(=O)C1C)CO2
Temperature: 25 °C
Yield: 90.2 %

Procedure:
To a solution of 2-(6-bromo-7-methyl-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester (0.192 g, 0.536 mmol) in EtOH (3 mL) was added anhydrous hydrazine hydrate (0.107 g, 2.144 mmol) and the mixture was heated at reflux for 4 h. The reaction mixture was cooled to ambient temperature and evaporated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 25% EtOAc in petroleum ether) to give 6-bromo-4,7-dimethyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one as white solid (0.15 g, 90%). 1H NMR (DMSO-d6, 400 MHz): δ 10.80 (s, 1H), 7.46 (s, 1H), 7.02 (s, 1H), 4.86 (q, J=6.8 Hz, 1H), 4.60 (dd, J=12.8 Hz, 2H), 2.26 (s, 3H), 1.27 (d, J=6.8 Hz, 3H).
Reaction SMILES: [F:1][C:2]1[C:15]([F:16])=[C:14]([F:17])[C:13]([F:18])=[C:12]2[C:3]=1[C:4]([OH:22])=[C:5]1[C:10](=[C:11]2[OH:19])[C:9](=[O:20])[CH2:8][CH2:7][C:6]1=[O:21].[F:23][C:24]1[C:32]([F:33])=[C:31]([F:34])[C:30]([F:35])=[C:29]2[C:25]=1[C:26](=[O:37])[O:27][C:28]2=O>>[F:1][C:2]1[C:3]2[C:12](=[C:11]([OH:19])[C:10]3[C:9](=[O:20])[C:8]4[C:7]([C:6](=[O:21])[C:5]=3[C:4]=2[OH:22])=[C:28]([OH:27])[C:29]2[C:25](=[C:24]([F:23])[C:32]([F:33])=[C:31]([F:34])[C:30]=2[F:35])[C:26]=4[OH:37])[C:13]([F:18])=[C:14]([F:17])[C:15]=1[F:16]
Reactant: O=C1OC(=O)c2c(F)c(F)c(F)c(F)c21
Reactant: O=C1CCC(=O)c2c1c(O)c1c(F)c(F)c(F)c(F)c1c2O
Product: O=C1c2c(c(O)c3c(F)c(F)c(F)c(F)c3c2O)C(=O)c2c1c(O)c1c(F)c(F)c(F)c(F)c1c2O

Procedure:
{1-1} First, 1,2,3,4,8,9,10,11-octafluoro-5,7,12,14-tetrahydroxypentacene-6,13-dione (3) was synthesized from 5,6,7,8-tetrafluoro-9,10-dihydroxy-2,3-dihydroanthracene-1,4-dione (1) and 4,5,6,7-tetrafluoroisobenzofuran-1,3-dione (2).
Reaction SMILES: [CH2:1]([O:5][CH:6]([C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=1)[CH3:7])[CH:2]([CH3:4])[CH3:3].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)CC)C.[NH2:48][CH2:49][C:50]1[C:51]([OH:58])=[N:52][C:53]([CH3:57])=[CH:54][C:55]=1[CH3:56]>ClCCl>[OH:58][C:51]1[C:50]([CH2:49][NH:48][C:12](=[O:14])[C:11]2[CH:10]=[CH:9][C:8]([CH:6]([O:5][CH2:1][CH:2]([CH3:3])[CH3:4])[CH3:7])=[CH:16][CH:15]=2)=[C:55]([CH3:56])[CH:54]=[C:53]([CH3:57])[N:52]=1
Reactant: CC(C)COC(C)c1ccc(C(=O)O)cc1
Reactant: Cc1cc(C)c(CN)c(O)n1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1cc(C)c(CNC(=O)c2ccc(C(C)OCC(C)C)cc2)c(O)n1
Reaction time: 0.5 h
Yield: 58.2 %

Procedure:
A solution of 4-(1-isobutoxyethyl)benzoic acid (132 mg, 0.59 mmol) in dichloromethane (50 mL) was added 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (35 mg, 0.5 mmol), triethylamine (32 mg, 0.7 mmol), stirred for 30 minutes. Then 3-(aminomethyl)-4,6-dimethylpyridin-2-ol (27 mg, 0.4 mmol) was added and the mixture was stirred at room temperature for 12 hours. The mixture was washed with water (50 mL), dried over sodium sulphate, concentrated. The residue was purified through column chromatography (silica gel, dichloromethane/methanol=20:1) to give the product N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)-4-(1-isobutoxyethyl)benzamide (83 mg, 40%) as white solid. LRMS (M+H+) m/z: calcd 356.13. found 356. HPLC Purity (214 nm): 97%. 1H NMR (300 MHz, CD3OD) δ 7.76 (d, J=8.1 Hz, 2H), 7.38 (d, J=8.1 Hz, 2H), 6.10 (s, 1H), 4.49-4.43 (m, 3H), 3.14-3.00 (m, 2H), 2.37 (s, 3H), 2.24 (s, 3H), 1.84-1.79 (m, 2H), 1.39 (d, J=6.3 Hz, 3H), 0.88 (d, J=6.6 Hz, 6H).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([NH2:11])=[CH:7][N:6]=1)=[O:4].[BrH:12].OO.N>>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([NH2:11])=[C:7]([Br:12])[N:6]=1)=[O:4]
Reactant: COC(=O)c1ccc(N)cn1
Reactant: Br
Agent: N
Agent: OO
Product: COC(=O)c1ccc(N)c(Br)n1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 5.00 g 5-amino-pyridine-2-carboxylic acid methyl ester in 75 mL of a 48% aqueous solution of hydrobromic acid, 3.39 mL of a 32% aqeous solution of hydrogen peroxide were added. The mixture was stirred at room temperature for 2 hours, then additional 0.80 mL hydrogen peroxide solution were added. After stirring for 1 hour the reaction mixture was cooled down and brought to pH 8 by addition of concentrated aqueous ammonia. The mixture was extracted with 300 mL ethyl acetate. The aqueous layer was washed with additional ethyl acetate and then the combined organic phases were dried over sodium sulfate. After filtration the solvent was removed under reduced pressure and the residue was purified by chromatography on silica gel eluting with a n-heptane/ethyl acetate gradient. Yield: 2.83 g MS(ES+): m/e=231.