Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]([CH2:25]O)=[C:5]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[Cl:19])[C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)(Cl)[Cl:47]>>[CH3:1][C:2]1[NH:3][C:4]([CH2:25][Cl:47])=[C:5]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[Cl:19])[C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9]
Reactant: ClC(Cl)(Cl)Cl
Reactant: CCOC(=O)C1=C(C)NC(CO)=C(C(=O)OCC)C1c1ccccc1Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: CCOC(=O)C1=C(C)NC(CCl)=C(C(=O)OCC)C1c1ccccc1Cl

Procedure:
A mixture of diethyl 2-methyl-4-(2-chlorophenyl)-6-hydroxymethyl-1,4-dihydropyridine-3,5-dicarboxylate (379.8 mg) and triphenylphosphine (314.7 mg) in carbon tetrachloride (5 ml) was refluxed for 3.5 hours. After the solvent was removed, the residue was dried under reduced pressure to give diethyl 2-methyl-4-(2-chlorophenyl)-6-chloromethyl-1,4-dihydropyridine-3,5-dicarboxylate. To this residue in 99% ethanol (10 ml) was added N-methylpiperazine (200 mg) and the solution was stirred at room temperature for 50 hours. Ethanol was removed from the reaction mixture and to the residue was added water. The mixture was extracted with ethyl acetate. After washing the extract with water, the extract was back-extracted with dilute hydrochloric acid. The aqueous layer was washed with diethyl ether, basified with an aqueous solution of sodium bicarbonate, and then extracted with ethyl acetate. The extract was washed with water, dried and then concentrated to give crude crystals (115.2 mg) of diethyl 2-methyl-4-(2-chlorophenyl)-6-(N-methylpiperazin-1-yl-methyl)-1,4-dihydropyridine-3,5-dicarboxylate. The crude crystals were recrystallized from a mixture of ethanol and diethyl ether to give colorless needles, m.p. 179° to 180° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[CH:18]=[N:17][CH:16]=[CH:15][C:11]=1[C:12]([OH:14])=O.[C:19]1([NH:25][NH2:26])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>>[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[CH:18]=[N:17][CH:16]=[CH:15][C:11]=1[C:12]([NH:26][NH:25][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:14]
Reactant: NNc1ccccc1
Reactant: O=C(O)c1ccncc1Nc1ccc(I)cc1F
Product: O=C(NNc1ccccc1)c1ccncc1Nc1ccc(I)cc1F

Procedure:
3-[(2-fluoro-4-iodophenyl)amino]-N′-phenylisonicotinohydrazide was synthesized according to the procedure for General Method 1, outlined above, starting with 0.45 mmol of 3-[(2-fluoro-4-iodophenyl)amino]isonicotinic acid (intermediate 1) and 0.7 mmol of phenylhydrazine. LC/MS [9.52 min; 449 (M+1)]
Reaction SMILES: [Cl-].[Ca+2].[Cl-].[NH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[C:11]1([CH3:20])[C:12]([C:17](Cl)=[O:18])=[CH:13][CH:14]=[CH:15][CH:16]=1>N1C=CC=CC=1>[CH3:20][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]([NH:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:18]
Reactant: Cc1ccccc1C(=O)Cl
Reactant: Nc1ccccc1
Agent: [Ca+2]
Agent: [Cl-]
Solvent: c1ccncc1
Product: Cc1ccccc1C(=O)Nc1ccccc1
Reaction time: 2 h

Procedure:
A three necked flack having a capacity of 100 ml, and equipped with a dropping funnel, a thermometer and a drying tube packed with calcium chloride, was charged with 11.2 g of aniline and 30 ml of pyridine. While stirring the solution in the flack by using a magnetic stirrer, 18.5 g of o-toluoyl chloride was added dropwise from the dropping funnel to the solution in such a manner that the temperature of the resultant reaction mixture did not exceed a level of 40° C. Simultaneously with the start of the dropwise addition, an exothermic reaction occurred, and a solid substance was gradually precipitated. Finally, the entire reaction system was solidified so that the stirring became impossible. The reactionwas completed after 2 hours from the start thereof. To the reaction system,an acid water containing hydrochloric acid was added, and then the solid product was pulverized and filtered to collect the reaction product. The reaction product was recrystallized by using a mixed solvent consisting ofethyl alcohol and water. White crystals were obtained in an amount of 24.1 g, and had a melting temperature of 127° C. to 129° C. An NMR measurement, a mass spectrometric analysis and an IR measurement identified that the resultant crystals consisted of the aimed compound.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)[C:5]([C:14]#[C:15][CH:16]([O:20][CH2:21][CH3:22])[O:17][CH2:18][CH3:19])=[CH:4][N:3]=1>C1COCC1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[CH:14]=[C:15]([CH:16]([O:20][CH2:21][CH3:22])[O:17][CH2:18][CH3:19])[N:8]([CH:9]3[CH2:13][CH2:12][CH2:11][CH2:10]3)[C:6]=2[N:7]=1
Reactant: CCOC(C#Cc1cnc(Cl)nc1NC1CCCC1)OCC
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: CCOC(OCC)c1cc2cnc(Cl)nc2n1C1CCCC1
Yield: 75.3 %

Procedure:
To a stirred solution of [2-chloro-5-(3,3-diethoxy-prop-1-ynyl)-pyrimidin-4-yl]-cyclopentyl-amine (7.50 g, 23.3 mmol) in THF (45 mL) is added IN TBAF in THF (100 mL, 116 mmol) at room temperature. The reaction mixture is heated under reflux overnight. After cooling the mixture is partitioned between H2O and dichloromethane. The phases are separated and the aqueous layer is extracted with dichloromethane (×2). The combined organic extracts are dried (MgSO4), filtered and concentrated. The residue is purified by SiO2 chromatography eluting with a gradient of 10% EtOAc/petrol to 30% EtOAc/petrol to give 2-chloro-7-cyclopentyl-6-diethoxymethyl-7H-pyrrolo[2,3-d]pyrimidine, (5.68 g, 76%). MS (ESI) m/z 324.1 (M+H)+
Reaction SMILES: Cl.[Cl:2]C1C=CC([C:9]2[CH:13]=[C:12]([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([C@H:23]4[O:28][CH2:27][CH2:26][NH:25][CH2:24]4)=[CH:19][CH:18]=3)=[O:15])[NH:11][N:10]=2)=CC=1.[Cl:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1C1C=C(C(O)=O)NN=1>>[ClH:2].[Cl:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[C:9]1[CH:13]=[C:12]([C:14]([NH:16][C:17]2[CH:18]=[CH:19][C:20]([C@H:23]3[O:28][CH2:27][CH2:26][NH:25][CH2:24]3)=[CH:21][CH:22]=2)=[O:15])[NH:11][N:10]=1
Reactant: O=C(Nc1ccc([C@@H]2CNCCO2)cc1)c1cc(-c2ccc(Cl)cc2)n[nH]1
Reactant: O=C(O)c1cc(-c2ccccc2Cl)n[nH]1
Agent: Cl
Product: O=C(Nc1ccc([C@@H]2CNCCO2)cc1)c1cc(-c2ccccc2Cl)n[nH]1

Procedure:
The title compound was prepared in analogy to Example 1 using (R)-tert-butyl 2-(4-aminophenyl)morpholine-4-carboxylate (prepared in Example 12) instead of (S)-tert-butyl 2-(4-aminophenyl)morpholine-4-carboxylate and 3-(2-chlorophenyl)-1H-pyrazole-5-carboxylic acid (CAS-890621-13-3) instead of 3-phenyl-1H-pyrazole-5-carboxylic acid. Light brown solid. MS (ISP): 383.1 ([M+H]+).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][CH:5]2[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([N+:20]([O-])=O)[CH:15]=1.Cl.C(O)C>[Fe].O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][CH:5]2[C:14]1[CH:15]=[C:16]([NH2:20])[CH:17]=[CH:18][CH:19]=1
Reactant: CN1Cc2c(Cl)cc(Cl)cc2C(c2cccc([N+](=O)[O-])c2)C1
Agent: [Fe]
Agent: Cl
Solvent: CCO
Solvent: O
Product: CN1Cc2c(Cl)cc(Cl)cc2C(c2cccc(N)c2)C1
Temperature: 80 °C
Reaction time: 0.5 h

Procedure:
Into a 100-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 6,8-dichloro-2-methyl-4-(3-nitrophenyl)-1,2,3,4-tetrahydroisoquinoline (200 mg, 0.59 mmol, 1.00 equiv), Fe (360 mg, 6.43 mmol, 8.60 equiv), hydrogen chloride (0.02 mL), ethanol (0.6 mL), water (0.2 mL). The resulting solution was stirred for 0.5 h at 80° C. in an oil bath. The solids were filtered out. The resulting mixture was concentrated under vacuum. This resulted in 0.2 g (crude) of 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenamine as yellow oil.
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.[N+:15]([C:18]1[CH:19]=[C:20]2[C:25](=O)[O:24][C:22](=[O:23])[C:21]2=[CH:27][CH:28]=1)([O-:17])=[O:16].Cl>>[CH2:8]([N:5]1[CH2:6][CH2:7][CH:2]([N:1]2[C:25](=[O:24])[C:20]3=[CH:19][C:18]([N+:15]([O-:17])=[O:16])=[CH:28][CH:27]=[C:21]3[C:22]2=[O:23])[CH2:3][CH2:4]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: NC1CCN(Cc2ccccc2)CC1
Reactant: O=C1OC(=O)c2cc([N+](=O)[O-])ccc21
Agent: Cl
Product: O=C1c2ccc([N+](=O)[O-])cc2C(=O)N1C1CCN(Cc2ccccc2)CC1

Procedure:
9.51 Grams of 4-amino-1-benzylpiperidine and 9.66 grams of 4-nitrophthalic anhydride were reacted in a similar manner to that described in Example 14 to give 9.19 grams of the title compound as the monohydrochloride quarterhydrate. Melting Point: 240°-2° C.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]([Cl:24])(Cl)(Cl)Cl.[CH3:25][C:26]1[CH:35]=[CH:34][C:29]2C(=O)[CH2:31][O:32][C:28]=2[CH:27]=1>C1(C)C=CC=CC=1>[Cl:24][C:20]1[C:29]2[CH:34]=[CH:35][C:26]([CH3:25])=[CH:27][C:28]=2[O:32][CH:31]=1
Reactant: ClC(Cl)(Cl)Cl
Reactant: Cc1ccc2c(c1)OCC2=O
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: Cc1ccc2c(Cl)coc2c1
Temperature: 60 °C
Reaction time: 2 h
Yield: 40 %

Procedure:
A mixture of triphenylphosphine (8.8 g, 0.033 mol) and carbon tetrachloride (19.5 cm3) was stirred at 60° C. for 2 hr. A solution of 6-methylbenzofuran-3(2H)-one (5.0 g, 0.034 mol) in toluene (50 cm3) was added dropwise and the mixture was stirred at 115° C. for 18 hr. The cooled mixture was filtered and the solvent was removed from the filtrate. The residue was extracted with hot petroleum ether (b.p. 60°-80° C.). The extract was chromatographed on silica using petroleum ether (b.p. 60°-80° C.) as the eluant to give 3-chloro-6-methylbenzofuran (2.3 g, 0.014 mol, 40.0%) RF 0.51.
Reaction SMILES: [ClH:1].Cl.[NH2:3][C:4]1[CH:5]=[C:6]([NH:10][C:11]([N:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[NH:12])[CH:7]=[CH:8][CH:9]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:24](OC(=O)C)(=[O:26])[CH3:25]>O.O1CCCC1>[ClH:1].[CH3:25][C:24]([NH:3][C:4]1[CH:5]=[C:6]([NH:10][C:11]([N:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[NH:12])[CH:7]=[CH:8][CH:9]=1)=[O:26]
Reactant: CC(=O)OC(C)=O
Reactant: N=C(Nc1cccc(N)c1)N1CCCC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CC(=O)Nc1cccc(NC(=N)N2CCCC2)c1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
A solution of the product of step (b), 1.38 g, 0.0050 moles, was dissolved in 20 ml of water. The solution was gradually treated with sodium carbonate, 0.84 g, 0.0100 moles, and cooled to 0° C. Next a solution of 0.5 ml of acetic anhydride in 10 ml of tetrahydrofuran was added. This was stirred overnight under nitrogen. The mixture was diluted with enough water to bring the volume to 100 ml, and washed with 20 ml of chloroform. The aqueous layer was made basic with 50% sodium hydroxide and extracted with 20 ml of chloroform (twice). The chloroform was dried with potassium carbonate, filtered and evaporated. The oil was dissolved in 20 ml of isopropanol and treated with 1 ml of concentrated hydrochloric acid. This mix was then diluted to 250 ml with ether. The solids were filtered and washed with 10 ml of ether (twice). The sample was allowed to dry overnight to yield N-(3-((methylcarbonyl)amino)phenyl)-1-pyrrolidinecarboximidamide monohydrochloride.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([CH3:10])=[CH:5][C:6]=1[C:7]([NH2:9])=[O:8].Cl[C:12](Cl)([O:14]C(=O)OC(Cl)(Cl)Cl)Cl>C1COCC1.O>[CH3:10][C:4]1[S:3][C:2]2[NH:1][C:12](=[O:14])[NH:9][C:7](=[O:8])[C:6]=2[CH:5]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: Cc1cc(C(N)=O)c(N)s1
Solvent: O
Solvent: C1CCOC1
Product: Cc1cc2c(=O)[nH]c(=O)[nH]c2s1
Temperature: 25 °C

Procedure:
To a stirred solution of Step 2 intermediate (16.5 g, 94.82 mmol) in dry THF (316 ml) was added triphosgene (14.07 g, 47.41 mmol) and the mixture was refluxed for overnight under nitrogen atmosphere. The mixture was cooled to room temperature and diluted with water (200 ml) under stirring. The solid precipitated out was collected by filtration and dried to give 13.8 g of the desired product; 1H NMR (300 MHz, DMSO-d6) δ 2.36 (s, 3H), 6.82 (s, 1H), 11.07 (br. s, 1H), 11.79 (br. s, 1H).
Reaction SMILES: [N:1]1([C:7]2[N:8]=[C:9]([CH2:14][C:15]([O-:17])=O)[NH:10][C:11](=[O:13])[CH:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Na+].[OH:19][C:20]1[CH:28]=[CH:27][CH:26]=[C:25]2[C:21]=1[CH:22]([CH3:29])[CH2:23][NH:24]2.Cl.CN(C)CCCN=C=NCC>N1C=CC=CC=1.CN(C)C=O>[OH:19][C:20]1[CH:28]=[CH:27][CH:26]=[C:25]2[C:21]=1[CH:22]([CH3:29])[CH2:23][N:24]2[C:15](=[O:17])[CH2:14][C:9]1[NH:10][C:11](=[O:13])[CH:12]=[C:7]([N:1]2[CH2:2][CH2:3][O:4][CH2:5][CH2:6]2)[N:8]=1
Reactant: O=C([O-])Cc1nc(N2CCOCC2)cc(=O)[nH]1
Reactant: CC1CNc2cccc(O)c21
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: CC1CN(C(=O)Cc2nc(N3CCOCC3)cc(=O)[nH]2)c2cccc(O)c21
Yield: 55.4 %

Procedure:
(±)-2-{2-[4-Hydroxy-3-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one is prepared by following the procedure described in example 1c using 0.70 g of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate, 0.44 g of 4-hydroxy-3-methylindoline (reference example 3c), and 0.68 g of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride in a mixture of 0.65 ml of pyridine and 15 ml of N,N-dimethylformamide. 0.55 g of (±)-2-{2-[4-hydroxy-3-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one is thus obtained in the form of a bright pink powder, the characteristics of which are the following:
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][OH:12].[O:13]1[CH:18]=[CH:17][CH2:16][CH2:15][CH2:14]1>Cl>[Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][O:12][CH:14]1[CH2:15][CH2:16][CH2:17][CH2:18][O:13]1
Reactant: OCCCCCCCCCCCl
Reactant: C1=COCCC1
Agent: Cl
Product: ClCCCCCCCCCCOC1CCCCO1

Procedure:
The compounds in the composition are available commercially or can be prepared synthetically in accordance with the procedure described by S. Voerman in Agric. Ecosystems Environ. 21 31-41 (1988). The synthesis of I is shown in FIG. 1. In brief, 1,10-decanediol (III) is reacted with concentrated hydrochloric acid. Continuous extraction of the reaction mixture with petroleum ether (b.p. 100°-140° C.) gives 10-chlorodecan-1-ol (IV) free of dichloride. IV is reacted with an equimolar quantity of dihydropyran, catalysed by 1 drop of concentrated hydrochloric acid to produce 1-chloro-10-[(tetrahydro-2H-pyran-2-yl)oxy]decane (V). Butyne gas is bubbled into a solution of n-butyl lithium under nitrogen and then V is added dropwise to produce 14-[(tetrahydro-2H-pyran-2-yl)oxy]-3-tetradecyne (VI). VI is hydrogenated with a P2-nickel catalyst (H. C. Brown and V. K. Ahiya, J. Chem. Soc. Chem. Comm., pp. 553-554 (1973)) to produce the Z olefin, 14-[(tetrahydro-2H-pyran-2-yl)oxy]-(Z)-3-tetradecene (VII), with less than 1% of the E isomer. The pheromone component, I, is generated by heating VII for 15 minutes in methanol containing a few drops of hydrochloric acid. II is prepared according to the scheme shown in FIG. 2. The conversions of 1,8-octanediol (VIII) to (Z)-9-dodecen-1-ol (XIII) is carried out the same as III to I except that VIII is substituted for III. XIII is converted to the pheromone component, II, by reaction with acetic anhydride in pyridine.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([NH2:9])[CH:5]=[CH:6][C:7]=1[CH3:8].[Cl:10][C:11]1[CH:19]=[CH:18][C:14]([C:15](Cl)=[O:16])=[CH:13][C:12]=1[N+:20]([O-:22])=[O:21]>>[Cl:10][C:11]1[CH:19]=[CH:18][C:14]([C:15]([NH:9][C:4]2[CH:5]=[CH:6][C:7]([CH3:8])=[C:2]([F:1])[CH:3]=2)=[O:16])=[CH:13][C:12]=1[N+:20]([O-:22])=[O:21]
Reactant: O=C(Cl)c1ccc(Cl)c([N+](=O)[O-])c1
Reactant: Cc1ccc(N)cc1F
Product: Cc1ccc(NC(=O)c2ccc(Cl)c([N+](=O)[O-])c2)cc1F

Procedure:
A mixture of 3-Fluoro-4-methyl-phenylamine was reacted with 4-chloro-3-nitrobenzoyl chloride using the procedure of Example 10A to provide 4-Chloro-N-(3-fluoro-4-methyl-phenyl)-3-nitro-benzamide which was reacted according to the conditions described in Examples 100A, 100B, and 100C to provide the title product.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH:4]1[CH2:9][CH2:8][CH2:7][CH2:6][N:5]1[C:10]([O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])=[O:11].[C:31]1([CH3:41])[CH:36]=[CH:35][C:34]([S:37](Cl)(=[O:39])=[O:38])=[CH:33][CH:32]=1.[OH-].[Na+]>O1CCOCC1>[S:37]([O:1][CH2:2][CH2:3][CH:4]1[CH2:9][CH2:8][CH2:7][CH2:6][N:5]1[C:10]([O:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])=[O:11])([C:34]1[CH:35]=[CH:36][C:31]([CH3:41])=[CH:32][CH:33]=1)(=[O:39])=[O:38]
Reactant: CCCCCCCCCCCCCCCCCCOC(=O)N1CCCCC1CCO
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: CCCCCCCCCCCCCCCCCCOC(=O)N1CCCCC1CCOS(=O)(=O)c1ccc(C)cc1

Procedure:
1,4-Dioxane solution of octadecyl 2-(2-hydroxyethyl)piperidinecarboxylate and p-toluenesulfonyl chloride is added to sodium hydroxide solution and the mixture is reacted at room temperature to obtain octadecyl 2-[2-(tosyloxy)ethyl]piperidinecarboxylate.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][N:3]=1.C(N(CC)C(C)C)(C)C.[C:18]([O:22][CH2:23][CH3:24])(=[O:21])[CH:19]=[CH2:20].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([CH:20]=[CH:19][C:18]([O:22][CH2:23][CH3:24])=[O:21])=[CH:6][CH:7]=1
Reactant: C=CC(=O)OCC
Reactant: Nc1ccc(Br)cn1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)C=Cc1ccc(N)nc1
Temperature: 100 °C
Reaction time: 12 h
Yield: 89 %

Procedure:
2-Amino-5-bromopyridine (15 g) was dissolved in a mixed solvent of N,N-dimethylformamide (hereinafter referred to as “DMF”; 60 ml) and N,N-diisopropylethylamine (60 ml). Ethyl acrylate (12 ml), palladium acetate (980 mg), and tris(2-methylphenyl)phosphine (10.5 g) were added thereto in a nitrogen atmosphere, and the mixture was stirred at 100° C. for 12 hours. The reaction mixture was filtered through Celite and separated with ethyl acetate and water. The organic layer was washed with a saturated sodium chloride solution, and then dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was crystallized with N-hexane to obtain Compound 1a (15.5 g, 89%) as a yellow solid.
Reaction SMILES: [N+:1]([C:4]1[N:5]([CH2:9][C:10]2[N:11]=[N:12][N:13]([CH2:15][CH2:16][OH:17])[CH:14]=2)[CH:6]=[CH:7][N:8]=1)([O-:3])=[O:2].[O:18](S(C1C=CC(C)=CC=1)(=O)=O)[S:19]([C:22]1[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=1)(=O)=[O:20]>C(Cl)Cl>[CH3:26][C:25]1[CH:27]=[CH:28][C:22]([S:19]([O:17][CH2:16][CH2:15][N:13]2[CH:14]=[C:10]([CH2:9][N:5]3[CH:6]=[CH:7][N:8]=[C:4]3[N+:1]([O-:3])=[O:2])[N:11]=[N:12]2)(=[O:20])=[O:18])=[CH:23][CH:24]=1
Reactant: Cc1ccc(S(=O)(=O)OS(=O)(=O)c2ccc(C)cc2)cc1
Reactant: O=[N+]([O-])c1nccn1Cc1cn(CCO)nn1
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)OCCn2cc(Cn3ccnc3[N+](=O)[O-])nn2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 53.1 %

Procedure:
To a round bottom flask containing alcohol 11 (160 mg, 0.672 mmol), TEA (136 mg, 1.34 mmol) and DCM (5 mL) was added Ts2O (263 mg, 0.806 mmol). The reaction was stirred at RT for 4 hrs. TLC indicated that the reaction was complete. The reaction was concentrated in vacuo and purified on a silica gel cartridge using EtOAc:Hex as the eluent to afford 140 mg (53% yield) of 12 as a pale orange oil. Mass Spec (lo-res): Calc'd for C15H16N6O5S: 392.092. found: 393.10 (M+H).
Reaction SMILES: [F:1][C:2]1[CH:8]=[C:7]([S:9][C:10]([F:15])([F:14])[CH:11]([F:13])[Cl:12])[CH:6]=[CH:5][C:3]=1[NH2:4].[F:16][C:17]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:18]=1[C:19]([N:21]=[C:22]=[O:23])=[O:20]>C1(C)C=CC=CC=1>[F:16][C:17]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:18]=1[C:19]([NH:21][C:22]([NH:4][C:3]1[CH:5]=[CH:6][C:7]([S:9][C:10]([F:15])([F:14])[CH:11]([F:13])[Cl:12])=[CH:8][C:2]=1[F:1])=[O:23])=[O:20]
Reactant: Nc1ccc(SC(F)(F)C(F)Cl)cc1F
Reactant: O=C=NC(=O)c1c(F)cccc1F
Solvent: Cc1ccccc1
Product: O=C(NC(=O)c1c(F)cccc1F)Nc1ccc(SC(F)(F)C(F)Cl)cc1F
Reaction time: 1 h
Yield: 82.7 %

Procedure:
In 15 ml of toluene was dissolved 2.6 g of 2-fluoro-4-(1,1,2-trifluoro-2-chloroethylthio)aniline, and 1.8 g of 2,6-difluorobenzoylisocyanate was added dropwise to the solution at room temperature (20° to 25° C.). After the reaction was allowed to proceed at the same temperature for 1 hour, the crystals, which separated out, were recovered by filtration and washed wiht toluene to give 3.6 g of N-(2,6-difluorobenzoyl)-N'-[2-fluoro-4-(1,1,2-trifluoro-2-chloroethylthio)phenyl]urea (Compound No. 39), m.p. of 172°-173° C.
Reaction SMILES: [CH3:1][N:2]([CH3:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[CH:5][CH:4]=1.C1CCC(N=C=NC2CCCCC2)CC1.CS(O[C:33]1[CH:42]=[CH:41][C:40]2[C:35](=[CH:36][CH:37]=[C:38]([C:43](=[NH:45])[NH2:44])[CH:39]=2)[CH:34]=1)(=O)=O>N1C=CC=CC=1>[CH3:1][N:2]([CH3:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7]([O:9][C:33]2[CH:42]=[CH:41][C:40]3[C:35](=[CH:36][CH:37]=[C:38]([C:43](=[NH:44])[NH2:45])[CH:39]=3)[CH:34]=2)=[O:8])=[CH:5][CH:4]=1
Reactant: CN(C)c1ccc(C(=O)O)cc1
Reactant: CS(=O)(=O)Oc1ccc2cc(C(=N)N)ccc2c1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: c1ccncc1
Product: CN(C)c1ccc(C(=O)Oc2ccc3cc(C(=N)N)ccc3c2)cc1
Reaction time: 0.5 h
Yield: 20.5 %

Procedure:
To 50 ml of dried pyridine, were added 2.9 g of 4-dimethylaminobenzoic acid and 4.4 g of DCC. The mixture was stirred for 30 minutes while being cooled in ice. After adding 5.0 g of 6-amidino-2-naphthol methanesulfonate, the mixture was further stirred for one hour under cooling in ice, then overnight at room temperature. The reaction mixture was filtered, the collected precipitate was washed with pyridine and ethyl ether and heated in DMF. The insolubles were filtered off and the filtrate was mixed with ethyl ether. The precipitate which was formed was collected by filtration and recrystallized from a mixture of methanol and ethyl ether to obtain 1.2 g of a white powder of 6-amidino-2-naphthyl 4-dimethylaminobenzoate methanesulfonate.
Reaction SMILES: [CH:1]([N:14]1[CH2:17][CH:16]([OH:18])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CN=C1.[C:24]([Si:28](Cl)([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([CH3:27])([CH3:26])[CH3:25].O>CN(C=O)C>[CH:1]([N:14]1[CH2:17][CH:16]([O:18][Si:28]([C:24]([CH3:27])([CH3:26])[CH3:25])([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: OC1CN(C(c2ccccc2)c2ccccc2)C1
Agent: c1c[nH]cn1
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](OC1CN(C(c2ccccc2)c2ccccc2)C1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A stirred solution of 1-Benzhydrylazetan-3-ol (2.0 g, 8.4 mmol) in DMF (20 ml) at 0° C. is treated with imidazole (0.57 g, 8.4 mmol) and t-butylchlorodiphenyl silane (2.31 g, 8.4 mmol). The reaction mixture is allowed to warm up to room temperature and stirred overnight. The mixture is poured into water (250 ml) and extracted with EtOAc (3×100 ml). The combined organic extracts are washed with water (2×100 ml), brine (100 ml) and dried over MgSO4. The solvent is removed in vacuo to yield the titled compound.