Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:14]=[CH:13][C:6]([CH2:7][N:8]2[CH:12]=[N:11][CH:10]=[N:9]2)=[CH:5][CH:4]=1)#[N:2].[Li]CCCC.[F:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][CH2:29]Br)=[CH:23][CH:22]=1>>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([CH:7]([N:8]2[CH:12]=[N:11][CH:10]=[N:9]2)[CH2:29][CH2:28][CH2:27][C:24]2[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=2)=[CH:13][CH:14]=1)#[N:2]
Reactant: Fc1ccc(CCCBr)cc1
Reactant: N#Cc1ccc(Cn2cncn2)cc1
Agent: [Li]CCCC
Product: N#Cc1ccc(C(CCCc2ccc(F)cc2)n2cncn2)cc1

Procedure:
The compound is prepared by the method described in Example 1 starting from 1-(4-cyanobenzyl)-1,2,4-triazole (6.0 g, 0.0272 mol), n-BuLi (0.0272 mol) and 3-(4-fluorophenyl)propylbromide (7.6 g, 0.035 mol). The product is purified first by suspending the residue with 2 M aqueous hydrogen chloride and petrol ether. Petrol ether phase is separated and the aqueous layer and the separated oil are extracted with diethyl ether. Diethyl ether phase is evaporated and the residue is purified by flash chromatography.
Reaction SMILES: C1(C(C2C=CC=CC=2)=[N:8][C:9]2[CH:10]=[N:11][CH:12]=[C:13]([NH:15][C:16]3[CH:25]=[CH:24][CH:23]=[C:22]4[C:17]=3[CH:18]=[CH:19][N:20]=[CH:21]4)[CH:14]=2)C=CC=CC=1>C1COCC1.O.Cl>[CH:21]1[C:22]2[C:17](=[C:16]([NH:15][C:13]3[CH:12]=[N:11][CH:10]=[C:9]([NH2:8])[CH:14]=3)[CH:25]=[CH:24][CH:23]=2)[CH:18]=[CH:19][N:20]=1
Reactant: c1ccc(C(=Nc2cncc(Nc3cccc4cnccc34)c2)c2ccccc2)cc1
Agent: Cl
Solvent: O
Solvent: C1CCOC1
Product: Nc1cncc(Nc2cccc3cnccc23)c1
Reaction time: 2 h
Yield: 69.4 %

Procedure:
A mixture of Example 23D (145 mg; 0.36 mmol) in 3 mL THF at room temperature was treated with 10 drops of water and 3 drops of conc. HCl, stirred for 2 hours, and concentrated. The residue was partitioned between ethyl acetate and concentrated NaHCO3 (aq). The aqueous layer was extracted three times with ethyl acetate. The combined extracts were washed with brine, dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 10% methanol/dichloromethane to provide the desired product (59 mg, 68%).
Reaction SMILES: C(OC([NH:8][CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)=O)(C)(C)C.[C:18]1([C:24]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:25][CH2:26]O)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C(O)(C)C>[C:18]1([C:24]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:25][CH2:26][O:17][C:14]2[CH:13]=[CH:12][C:11]([CH2:10][CH2:9][NH2:8])=[CH:16][CH:15]=2)[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: CC(C)(C)OC(=O)NCCc1ccc(O)cc1
Reactant: OCCC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CC(C)O
Product: NCCc1ccc(OCCC(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 66 %

Procedure:
N-(t-butoxycarbonyl)-2-(4-hydroxyphenyl)ethylamine (1.3 g) and 3,3,3-triphenylpropanol (1.4 g) were coupled by the method of example 5. The product (1.4 g) was dissolved in 15 mL isopropanol containing 1.0 g HCl, and stirred 3 hr at room temperature. A precipitate formed, which was collected and recrystallized from ethanol-ether to provide the hydrochloride salt of the title compound as a white solid, mp 163°-165° C., in 66% yield. Anal. calcd. for C29H29NO.HCl.0.75 H2O: C, 76.13; H, 6.94; N, 3.06. Found: C, 75.99; H, 6.81; N, 3.02.
Reaction SMILES: [C:1]1([C:7]2[N:16]=[CH:15][C:14]3[CH2:13][CH2:12][C:11]4[N:17]=[C:18]([NH2:20])[S:19][C:10]=4[C:9]=3[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[C:28](Cl)(=[O:31])[CH2:29][CH3:30]>ClCCl>[C:1]1([C:7]2[N:16]=[CH:15][C:14]3[CH2:13][CH2:12][C:11]4[N:17]=[C:18]([NH:20][C:28](=[O:31])[CH2:29][CH3:30])[S:19][C:10]=4[C:9]=3[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCC(=O)Cl
Reactant: Nc1nc2c(s1)-c1nc(-c3ccccc3)ncc1CC2
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCC(=O)Nc1nc2c(s1)-c1nc(-c3ccccc3)ncc1CC2
Temperature: 25 °C

Procedure:
0.3 g (1.1 mmol) of the compound obtained in Example 71 are suspended in 15 ml dichloromethane, combined with 0.4 ml (2.5 mmol) triethylamine and gently refluxed. 0.2 ml (2.3 mmol) propionic acid chloride are added and the mixture is refluxed for 5 hours with stirring. After cooling to ambient temperature the reaction solution is washed with sodium hydrogen carbonate and water, dried and evaporated to dryness. The residue is stirred with diethyl ether and suction filtered. Yield: 0.2 g (m.p.: 274-275° C.)
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]([N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)=[O:12])[S:10][C:3]=12.[NH:18]1[CH2:22]CC[CH2:19]1.CN(C)[C@@H]1CCNC1>>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]([N:13]3[CH2:17][CH2:16][C@@H:15]([N:18]([CH3:22])[CH3:19])[CH2:14]3)=[O:12])[S:10][C:3]=12
Reactant: O=C(c1cc2nccc(Cl)c2s1)N1CCCC1
Reactant: C1CCNC1
Agent: CN(C)[C@@H]1CCNC1
Product: CN(C)[C@@H]1CCN(C(=O)c2cc3nccc(Cl)c3s2)C1

Procedure:
Following the procedures described above for the compound 21 (example 5f, steps 1-3) but substituting pyrrolidine in the step 3 for (R)—N,N-dimethylpyrrolidin-3-amine, title compound 24 was obtained as a white solid (58% yield). MS (m/z): 310.0 (M+H).
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=1)[C:11](O)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[NH4+:23].[OH-]>CN(C=O)C.C(Cl)Cl>[CH2:1]([C:8]1[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=1)[C:11]([NH2:23])=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: [NH4+]
Reactant: O=C(O)c1cccc(Cc2ccccc2)c1
Agent: O=C(Cl)C(=O)Cl
Agent: [OH-]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: NC(=O)c1cccc(Cc2ccccc2)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To the product from Step A (0.0119 moles) was added 150 mL of CH2Cl2, one drop of DMF, 10 mL of oxalyl chloride, and the mixture was stirred at room temperature for 3 hours. After cooling to 10° C., 30 mL of NH4OH (exothermic) was added and the mixture was stirred for 30 min. The reaction mixture was then concentrated and the resulting residue diluted with ethyl acetate. The organic layer was washed with 1N NaOH, brine, dried over Na2SO4, and concentrated to give the 3-(benzyl)benzamide as a white solid, which was used without further purification.
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[S:3]([O:6]S(C(F)(F)F)(=O)=O)(=[O:5])=[O:4].O[C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][CH:26]=1)[CH:23]=[C:22]([C@:27]1([CH3:33])[CH2:31][O:30][C:29](=[O:32])[NH:28]1)[CH:21]=[CH:20]2.N1C=CC=CC=1.C(Cl)Cl>>[F:1][C:2]([F:15])([F:14])[S:3]([O:6][C:17]1[CH:26]=[CH:25][C:24]2[C:19](=[CH:20][CH:21]=[C:22]([C@:27]3([CH3:33])[CH2:31][O:30][C:29](=[O:32])[NH:28]3)[CH:23]=2)[CH:18]=1)(=[O:5])=[O:4]
Reactant: C[C@@]1(c2ccc3cc(O)ccc3c2)COC(=O)N1
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: c1ccncc1
Solvent: ClCCl
Product: C[C@@]1(c2ccc3cc(OS(=O)(=O)C(F)(F)F)ccc3c2)COC(=O)N1
Reaction time: 8 h
Yield: 88.5 %

Procedure:
Trifluoromethanesulfonic anhydride (0.144 mL, 0.000859 mol) was slowly added to a solution containing (R)-4-(6-hydroxynaphthalen-2-yl)-4-methyloxazolidin-2-one (190 mg, 0.00078 mol), pyridine (2 mL, 0.02 mol), and methylene chloride (2 mL, 0.03 mol) at 0° C. After stirring overnight TLC showed complete reaction. After concentration, the crude was purified by chromatography using a 0-100% EtOAc/hexane gradient to give (R)-6-(4-methyl-2-oxooxazolidin-4-yl)naphthalen-2-yl trifluoromethanesulfonate as a yellow gel (259 mg, 88%). 1H NMR (400 MHz, CDCl3-d) δ=7.95 (s, 1H), 7.94-7.89 (m, 2H), 7.77 (d, J=1.9 Hz, 1H), 7.59 (dd, J=1.6, 8.6 Hz, 1H), 7.42 (d, J=9.0 Hz, 1H), 4.48 (d, J=8.4 Hz, 1H), 4.43 (d, J=8.4 Hz, 1H), 1.88 (s, 3H).
Reaction SMILES: [C:1]([S:5][S:6][CH2:7][CH2:8][NH2:9])([CH3:4])([CH3:3])[CH3:2].[C:10]([O:14][CH3:15])(=[O:13])[CH:11]=[CH2:12].CCN(C(C)C)C(C)C.[C:25](OC([O-])=O)([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26].[Cl-].[NH4+]>ClC(Cl)C>[C:28]([O:27][C:25]([N:9]([CH2:8][CH2:7][S:6][S:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:12][CH2:11][C:10]([O:14][CH3:15])=[O:13])=[O:26])([CH3:31])([CH3:30])[CH3:29]
Reactant: CC(C)(C)SSCCN
Reactant: CC(C)(C)OC(=O)OC(=O)[O-]
Reactant: C=CC(=O)OC
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(Cl)Cl
Product: COC(=O)CCN(CCSSC(C)(C)C)C(=O)OC(C)(C)C
Temperature: 85 °C
Reaction time: 2 h
Yield: 386.1 %

Procedure:
2-(tert-Butyldisulfanyl)ethanamine (Compound 6c-A, 0.80 g, 0.84 mmol) and methyl acrylate (1.74 ml, 19.36 mmol) were dissolved in dichloroethane (14.0 ml), DIPEA (4.23 ml, 24.20 mmol) was added and the mixture was stirred at 85° C. for 2 hours. The reaction mixture was left to cool and tert-butyl dicarbonate (1.37 g, 6.29 mmol) was added. After stirring at room temperature for 45 minutes, a saturated aqueous ammonium chloride solution was added, followed by extraction with DCM. The resulting organic layer was washed with a saturated aqueous sodium chloride solution, and then dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography (hexane:ethyl acetate=3:1) to afford the title compound (1.14 g, 67%).
Reaction SMILES: [CH3:1][N:2]([C@@H:4]1[C:27](=[O:28])[C:26]([C:29]([NH2:31])=[O:30])=[C:25]([OH:32])[C@:24]2([OH:33])[C@H:5]1[CH2:6][C@H:7]1[C:21]([C:22]2=[O:23])=[C:20]([OH:34])[C:10]2[C:11]([OH:19])=[C:12]([NH2:18])[CH:13]=[C:14]([N:15]([CH3:17])[CH3:16])[C:9]=2[CH2:8]1)[CH3:3].ClCC(OC)(OC)OC.Cl[CH2:45][C:46]1O[C:48]2[CH:54]=CC=C[C:49]=2[N:50]=1.C(N)CC.C(NCC1OC2C=CC=CC=2N=1)CC.N>CN(C=O)C>[CH3:17][N:15]([CH3:16])[C:14]1[C:9]2[CH2:8][C@@H:7]3[C:21](=[C:22]([OH:23])[C@@:24]4([OH:33])[C@@H:5]([CH2:6]3)[C@H:4]([N:2]([CH3:1])[CH3:3])[C:27]([OH:28])=[C:26]([C:29]([NH2:31])=[O:30])[C:25]4=[O:32])[C:20](=[O:34])[C:10]=2[C:11]2[O:19][C:45]([CH2:46][NH:50][CH2:49][CH2:48][CH3:54])=[N:18][C:12]=2[CH:13]=1
Reactant: CN(C)c1cc(N)c(O)c2c1C[C@H]1C[C@H]3[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]3(O)C(=O)C1=C2O
Reactant: ClCc1nc2ccccc2o1
Agent: CCCNCc1nc2ccccc2o1
Agent: COC(CCl)(OC)OC
Agent: N
Solvent: CN(C)C=O
Solvent: CCCN
Product: CCCNCc1nc2cc(N(C)C)c3c(c2o1)C(=O)C1=C(O)[C@]2(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]2C[C@@H]1C3
Temperature: 25 °C

Procedure:
9-aminominocycline sulfate salt (1.0 g, 1.50 mmol) is dissolved in DMF (50 mL) and treated with a solution of 2-chloro-1,1,1-trimethoxyethane (0.463 g, 3.00 mmol, 2 equivalents). The reaction is stirred at room temperature until mass spectrometry shows conversion to the chloromethylbenzoxazole derivative. The solution is then treated with n-propylamine (10 mL, excess) and stirred until mass spectrometry shows conversion to the n-propylaminomethyl benzoxazole. The mixture is concentrated under reduced pressure to remove excess n-propylamine, and then poured slowly into ether (1 L) and HCl/ether is added to precipate the salt. The solid is rinsed with fresh ether and dried under vacuum. The crude solid is dissolved in water (100 mL) giving a solution at pH 2. The pH is raised successively by 0.5 units with aqueous ammonia, and extracted with dichloromethane. The fractions extracted at pH 4–4.5 are combined, dried (Na2SO4), filtered and concentrated nearly to dryness. A small volume of methanol is added and the solution is treated with 1M HCl in ether. The precipitated solid is collected by filtration, washed with fresh ether and dried under vacuum to yield 0.067 g of the product as its HCl salt.
Reaction SMILES: [NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[CH:5]=[CH:4][C:3]=1[NH2:18].[S:19](Cl)(Cl)=O.C(N(CC)CC)C>C1COCC1>[CH:10]1[CH:11]=[CH:12][C:13]2[C:14](=[O:16])[C:15]3[C:2]4=[N:1][S:19][N:18]=[C:3]4[CH:4]=[CH:5][C:6]=3[C:7](=[O:17])[C:8]=2[CH:9]=1
Reactant: Nc1ccc2c(c1N)C(=O)c1ccccc1C2=O
Reactant: O=S(Cl)Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=C1c2ccccc2C(=O)c2c1ccc1nsnc21

Procedure:
The compound 1,2-Diaminoanthraquinone (1.19 g, 5 mmol) is dissolved in THF (30 mL), and thionyl chloride (0.15 g, 20 mmol) is then dripped thereinto; triethylamine (TEA, 3 mL) is lastly added thereinto for catalyzation. After being mixed at room temperature for one hour, the mixture is transferred into a container with 200 mL of icy water for crystallization. After filtration, a precipitate is collected and re-crystallized with hot alcohol, so as to obtain the yellow compound NSC745885 with a melting point of 227-228° C., and the production rate is about 74%.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Cl.C(N=C=NCCCN(C)C)C.[CH3:19][O:20][C:21]1[C:22](=[O:48])[C:23]([CH3:47])=[C:24]([CH2:30][C:31]2[CH:32]=[CH:33][C:34]([O:40][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)=[C:35]([CH:39]=2)[C:36](O)=[O:37])[C:25](=[O:29])[C:26]=1[O:27][CH3:28]>C(Cl)Cl>[CH3:19][O:20][C:21]1[C:22](=[O:48])[C:23]([CH3:47])=[C:24]([CH2:30][C:31]2[CH:32]=[CH:33][C:34]([O:40][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)=[C:35]([CH:39]=2)[C:36]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)=[O:37])[C:25](=[O:29])[C:26]=1[O:27][CH3:28]
Reactant: C1COCCN1
Reactant: COC1=C(OC)C(=O)C(Cc2ccc(Oc3ccccc3)c(C(=O)O)c2)=C(C)C1=O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Product: COC1=C(OC)C(=O)C(Cc2ccc(Oc3ccccc3)c(C(=O)N3CCOCC3)c2)=C(C)C1=O
Temperature: 25 °C
Reaction time: 12 h
Yield: 48.8 %

Procedure:
Morpholine (0.030 g, 0.343 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.099 g, 0.515 mmol) were added to a methylene chloride solution (5 ml) of 5-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-phenoxybenzoic acid (0.070 g, 0.172 mmol) and the resulting solution was stirred at room temperature for 12 hours. The reaction solution was poured into ice water and then extracted with methylene chloride. The extract was washed with water and then dried, and the solvent was removed by distillation. The obtained residue was purified by preparative thin-layer chromatography (chloroform:methanol=10:1) to obtain the titled compound (0.040 g, 0.0839 mmol, 49%).
Reaction SMILES: [CH2:1]([N:3](CC)CC)[CH3:2].CS(Cl)(=O)=O.O[CH:14]([C:20]1[CH:25]=[CH:24][C:23]([NH:26][C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=2)=[O:28])=[CH:22][C:21]=1[F:35])[CH:15]([CH3:19])[CH2:16][CH2:17]O.C(=O)(O)[O-:37].[Na+]>O.C(Cl)(Cl)Cl>[C:1]([N:3]1[CH2:17][CH2:16][CH:15]([CH3:19])[CH:14]1[C:20]1[CH:25]=[CH:24][C:23]([NH:26][C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=2)=[O:28])=[CH:22][C:21]=1[F:35])(=[O:37])[CH3:2]
Reactant: CC(CCO)C(O)c1ccc(NC(=O)c2ccccn2)cc1F
Reactant: O=C([O-])O
Reactant: CCN(CC)CC
Agent: CS(=O)(=O)Cl
Agent: [Na+]
Solvent: O
Solvent: ClC(Cl)Cl
Product: CC(=O)N1CCC(C)C1c1ccc(NC(=O)c2ccccn2)cc1F
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
0.18 ml of triethylamine and 0.07 ml of methanesulfonyl chloride were added in order to a chloroform (5 ml) solution of 100 mg of N-(4-(1,4-dihydroxy-2-methylbutyl)-3-fluorophenyl)pyridine-2-carboxamide, and the reaction liquid was stirred at room temperature for 30 minutes. Aqueous saturated sodium bicarbonate was added to the reaction liquid, extracted with chloroform, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 23 mg of sodium azide was added to a dimethylformamide (4 ml) solution of the resulting residue, and the reaction liquid was stirred at 40° C. for 2 hours. The reaction liquid was cooled to room temperature, water was added to it, extracted with ethyl acetate, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 50 mg of sodium borohydride and 5 mg of copper sulfate pentahydrate were added in order to a methanol (5 ml) solution of the resulting residue, and the reaction liquid was stirred at 40° C. for 15 minutes. The reaction liquid was cooled to room temperature, and then aqueous saturated sodium bicarbonate was added to it, extracted with chloroform and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and 0.08 ml of triethylamine, 0.07 ml of acetic anhydride and 5 mg of N,N-4-dimethylaminopyridine were added in order to a chloroform (4 ml) solution of the resulting residue, and the reaction liquid was stirred at room temperature for 30 minutes. Aqueous saturated sodium bicarbonate was added to the reaction liquid, extracted with chloroform, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through silica gel column chromatography (developing solvent: chloroform/methanol=100/1) to obtain the entitled compound as a colorless oily substance.
Reaction SMILES: [N:1]1([CH:6]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14](=O)[CH3:15])=[C:9]([N+:17]([O-:19])=O)[CH:8]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.CC(O)C.Cl.[H][H]>CO>[N:1]1([CH:6]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:7]2[CH:12]=[CH:11][C:10]3[N:13]=[C:14]([CH3:15])[N:17]([OH:19])[C:9]=3[CH:8]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: CC(=O)Nc1ccc(C(c2ccccc2)n2ccnc2)cc1[N+](=O)[O-]
Reactant: [H][H]
Agent: Cl
Solvent: CO
Solvent: CC(C)O
Product: Cc1nc2ccc(C(c3ccccc3)n3ccnc3)cc2n1O
Yield: 40.6 %

Procedure:
A mixture of 4.9 parts of N-[4-[(1H-imidazol-1-yl)phenylmethyl]-2-nitrophenyl]acetamide, 12 parts of 2-propanol, saturated with hydrogen chloride and 200 parts of methanol was hydrogenated at normal pressure and at room temperature with 2 parts of platinium-on-charcoal catalyst 5%. After the calculated amount of hydrogen was taken up, the catalyst was filtered off and the filtrate was evaporated. The residue was dissolved in dichloromethane and water and then the solution was neutralized with an ammonium hydroxide solution. The dichloromethane layer was separated, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (85:15 by volume) as eluent. The pure fractions were collected and the eluent was evaporated, yielding 2.2 parts (40.6%) of 6-[(1H-imidazol-1-yl)phenylmethyl]-2-methyl-1H-benzimidazol-1-ol as a residue (compound 219).
Reaction SMILES: [N:1]1[C:8]([Cl:9])=[N:7][C:5]([Cl:6])=[N:4][C:2]=1Cl.O.[CH2:11]([NH2:14])[CH:12]=[CH2:13].C(=O)([O-])[O-].[Na+].[Na+]>CC(C)=O>[CH2:11]([NH:14][C:2]1[N:1]=[C:8]([Cl:9])[N:7]=[C:5]([Cl:6])[N:4]=1)[CH:12]=[CH2:13]
Reactant: Clc1nc(Cl)nc(Cl)n1
Reactant: C=CCN
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Product: C=CCNc1nc(Cl)nc(Cl)n1

Procedure:
18.5 parts of cyanuric chloride were dissolved in 100 parts of acetone and added, while stirring, to a mixture of 300 parts of water and 400 parts of crushed ice. The suspension thus obtained was added to 5.7 parts of allylamine over a period of 30 minutes and subsequently to an aqueous solution of 5.3 parts of sodium carbonate. The white crystalline reaction product was suction-filtered, washed several times with iced water, and dried over phosphorus pentoxide.
Reaction SMILES: [O:1]1[CH2:5][CH2:4][C:3]([C:6]2[C:7]([CH3:25])=[C:8]([C:16]([C:18]3[CH:19]=[N:20][N:21]([CH3:24])[C:22]=3[OH:23])=[O:17])[CH:9]=[CH:10][C:11]=2[S:12]([CH3:15])(=[O:14])=[O:13])=[N:2]1.C(N(CC)CC)C.[CH3:33][CH2:34][S:35][C:36](Cl)=[O:37].C(OCC)(=O)C>O1CCCC1>[CH3:25][C:7]1[C:6]([C:3]2[CH2:4][CH2:5][O:1][N:2]=2)=[C:11]([S:12]([CH3:15])(=[O:14])=[O:13])[CH:10]=[CH:9][C:8]=1[C:16]([C:18]1[CH:19]=[N:20][N:21]([CH3:24])[C:22]=1[O:23][C:36]([S:35][CH2:34][CH3:33])=[O:37])=[O:17]
Reactant: Cc1c(C(=O)c2cnn(C)c2O)ccc(S(C)(=O)=O)c1C1=NOCC1
Reactant: CCSC(=O)Cl
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CCSC(=O)Oc1c(C(=O)c2ccc(S(C)(=O)=O)c(C3=NOCC3)c2C)cnn1C
Reaction time: 1 h
Yield: 66 %

Procedure:
To a solution of 5-hydroxy-1-methylpyrazol-4-yl 3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-(methylsulfonyl)phenyl ketone (100 mg, 2.75×10−4 mol) in anhydrous tetrahydrofuran (5 mL) were added triethylamine (55 mg) and 96% S-ethyl chlorothiolformate (45 mg) at room temperature. After the reaction solution was stirred for 1 hour, 150 mL of ethyl acetate was added, and the solution was washed twice with a saturated brine. The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=6:4) to obtain the desired product (82 mg) as an oil.
Reaction SMILES: [CH3:1][NH:2][C:3]([C:5]1[C:6]([I:20])=[C:7]([C:11]([I:19])=[C:12]([C:15](=[O:18])[NH:16][CH3:17])[C:13]=1[I:14])[C:8](N)=[O:9])=[O:4].N([O-])=[O:22].[Na+].O>C(O)(=O)C.S(=O)(=O)(O)O>[CH3:1][NH:2][C:3]([C:5]1[C:6]([I:20])=[C:7]([C:11]([I:19])=[C:12]([C:15](=[O:18])[NH:16][CH3:17])[C:13]=1[I:14])[C:8]([OH:22])=[O:9])=[O:4]
Reactant: O=N[O-]
Reactant: CNC(=O)c1c(I)c(C(N)=O)c(I)c(C(=O)NC)c1I
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: CNC(=O)c1c(I)c(C(=O)O)c(I)c(C(=O)NC)c1I
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 86.9 %

Procedure:
12.3 g of 3,5-bis(N-methylcarbamoyl)-2,4,6-triiodobenzoic acid amide is suspended in 80 ml of glacial acetic acid. Under agitation, a mixture of 1.66 g of sodium nitrite in 12 ml of concentrated sulfuric acid (prepared under ice cooling) is added in small portions at room temperature; during this step the temperature rises from 24° C. to 42° C. The mixture is then stirred for 3 hours at room temperature, 30 minutes at 50° C., and 90 minutes at 70° C. After agitating overnight at room temperature, the reaction mixture is stirred into 400 ml of water. The precipitate is vacuum-filtered after 4 hours, washed with water, and dried at 50° C. under vacuum. The crude product (11.9 g) is dissolved in 110 ml of water and 12 ml of 2 N sodium hydroxide solution, adjusted to pH 6.5 with 2 N acetic acid, and stirred for 30 minutes with 1 g of carbon. After the carbon has been removed by vacuum-filtering, the solution is precipitated with 16 ml of 2 N hydrochloric acid. After vacuum-filtering and drying at 50° C. under vacuum, 10.7 g (87% of theory) of 3,5-bis(N-methylcarbamoyl)-2,4,6-triiodobenzoic acid is obtained, mp>300° C.
Reaction SMILES: C12(COC3C(I)=CC(C(O)=O)=C(F)C=3)CC3CC(CC(C3)C1)C2.[CH:24]1([CH2:29][O:30][C:31]2[C:39]([CH:40]3[CH2:42][CH2:41]3)=[CH:38][C:34]([C:35]([OH:37])=O)=[C:33]([F:43])[CH:32]=2)[CH2:28][CH2:27][CH2:26][CH2:25]1.N1(S(N)(=O)=O)CCC1.[CH3:52][O:53][CH:54]1[CH2:57][N:56]([S:58]([NH2:61])(=[O:60])=[O:59])[CH2:55]1>CO>[CH:24]1([CH2:29][O:30][C:31]2[C:39]([CH:40]3[CH2:42][CH2:41]3)=[CH:38][C:34]([C:35]([NH:61][S:58]([N:56]3[CH2:57][CH:54]([O:53][CH3:52])[CH2:55]3)(=[O:60])=[O:59])=[O:37])=[C:33]([F:43])[CH:32]=2)[CH2:25][CH2:26][CH2:27][CH2:28]1
Reactant: COC1CN(S(N)(=O)=O)C1
Reactant: O=C(O)c1cc(C2CC2)c(OCC2CCCC2)cc1F
Agent: NS(=O)(=O)N1CCC1
Agent: O=C(O)c1cc(I)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
Solvent: CO
Product: COC1CN(S(=O)(=O)NC(=O)c2cc(C3CC3)c(OCC3CCCC3)cc2F)C1

Procedure:
Following the procedure as described in Example 299 Step 2 and making variations as required to replace 4-(adamantan-1-ylmethoxy)-2-fluoro-5-iodobenzoic acid with 4-(cyclopentylmethoxy)-5-cyclopropyl-2-fluorobenzoic acid and azetidine-1-sulfonamide with 3-methoxyazetidine-1-sulfonamide, the title compound was obtained as a colorless solid (0.04 g, 11%) after trituration in methanol: 1H NMR (300 MHz, DMSO-d6) δ 11.70 (br s, 1H), 7.12 (d, J=8.3 Hz, 1H), 6.96 (d, J=13.0 Hz, 1H), 4.24-4.11 (m, 3H), 3.99-3.91 (m, 4H), 3.17 (s, 3H), 2.43-2.26 (m, 1H), 2.08-1.95 (m, 1H), 1.86-1.73 (m, 2H), 1.69-1.50 (m, 4H), 1.45-1.31 (m, 2H), 0.93-0.85 (m, 2H), 0.71-0.64 (m, 2H); MS (ES−) m/z 425.2 (M−1).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](/[CH:11]=[CH:12]/[CH2:13][CH2:14][NH2:15])=[CH:3][N:2]=1>C(O)C.[Pd]>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([CH2:11][CH2:12][CH2:13][CH2:14][NH2:15])=[CH:3][N:2]=1
Reactant: NCC/C=C/c1cncc2ccccc12
Agent: [Pd]
Solvent: CCO
Product: NCCCCc1cncc2ccccc12
Reaction time: 8 h
Yield: 88.4 %

Procedure:
A solution of 1 g of (E)-4-(4-isoquinolinyl)-3-buten-1-amine in 20 mL of ethanol was hydrogenated over 0.12 g of 10% Pd/C at room temperature and atmospheric pressure. After 8 hours. the catalyst was removed by filtration and the filtrate was concentrated to yield 0.893 g of 4-isoquinolinebutanamine.