Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[I:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9]N)=[CH:5][CH:4]=1.[F:11][C:12]1[CH:20]=[CH:19][CH:18]=[CH:17][C:13]=1[CH2:14][CH2:15]Br.C(NCC)C.Cl.[CH3:27][N:28]1[CH2:33][CH2:32][C:31](=O)[CH2:30][CH2:29]1.FC(F)(F)C([O-])=O>C(O)C>[F:11][C:12]1[CH:20]=[CH:19][CH:18]=[CH:17][C:13]=1[CH2:14][CH2:15][N:9]1[C:6]2[CH:7]=[CH:8][C:3]([I:2])=[CH:4][C:5]=2[C:30]2[CH2:29][N:28]([CH3:27])[CH2:33][CH2:32][C:31]1=2
Reactant: NNc1ccc(I)cc1
Reactant: Fc1ccccc1CCBr
Reactant: CN1CCC(=O)CC1
Agent: Cl
Agent: O=C([O-])C(F)(F)F
Solvent: CCO
Solvent: CCNCC
Product: CN1CCc2c(c3cc(I)ccc3n2CCc2ccccc2F)C1
Yield: 0.5 %

Procedure:
Preparation of the title compound was carried out according to General Method 8. 4-Iodophenylhydrazine hydrochloride (500 mg, 2.1 mmol), 2-fluorophenethylbromide (0.3 ml, 2.1 mmol), diethyl amine (0.8 ml, 6.3 mmol) and N-methyl-4-piperidone hydrochloride (312 mg, 2.1 mmol) were taken in ethanol (10 ml) to obtain 5 mg of 5-(2-fluorophenethyl)-2,3,4,5-tetrahydro-8-iodo-2-methyl-1H-pyrido[4,3-b]indole as a trifluoroacetate salt after purification by reverse-phase chromatography (C-18, 500 mm×50 mm, Mobile Phase A=0.05% TFA in water, B=0.05% TFA in acetonitrile, Gradient: 10% B to 80% B in 30 min, injection vol. 5 mL).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[S:9][CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13].[O:16]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[CH:18]=[C:17]1[S:25](Cl)(=[O:27])=[O:26]>N1C=CC=CC=1.CCOC(C)=O>[O:16]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[CH:18]=[C:17]1[S:25]([NH:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[S:9][CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])(=[O:27])=[O:26]
Reactant: O=S(=O)(Cl)c1cc2ccccc2o1
Reactant: COC(=O)CCSc1ccc(Cl)cc1N
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: COC(=O)CCSc1ccc(Cl)cc1NS(=O)(=O)c1cc2ccccc2o1
Temperature: 25 °C
Reaction time: 72 h
Yield: 52.4 %

Procedure:
To a solution of methyl 3-((2-amino-4-chlorophenyl)thio)propanoate (412 mg, 1.67 mmol) in pyridine (2 ml) was added 1-benzofuran-2-sulfonyl chloride (363 mg, 1.67 mmol). The reaction was stirred at room temperature for 72 hours, diluted with EtOAc and extracted with HCl, brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (10-20% EtOAc in hexane) to yield the title compound (373 mg, 52%).
Reaction SMILES: [CH2:1]([O:9][C:10]1[CH:18]=[CH:17][C:13]([C:14](O)=[O:15])=[CH:12][CH:11]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].S(Cl)([Cl:21])=O>C1C=CC=CC=1>[CH2:1]([O:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]([Cl:21])=[O:15])=[CH:12][CH:11]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: O=S(Cl)Cl
Reactant: CCCCCCCCOc1ccc(C(=O)O)cc1
Solvent: c1ccccc1
Product: CCCCCCCCOc1ccc(C(=O)Cl)cc1

Procedure:
4-n-Octyloxybenzoic acid in the amount of 2.0 g was reacted with 1 g of thionyl chloride in 10 ml of benzene at a temperature of 100°-110° C. for 6 hours to obtain 4-n-octyloxybenzoic chloride in the amount of 2.2 g.
Reaction SMILES: Cl.[CH3:2][C:3]1[N:7]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[C:6]2[CH:14]=[CH:15][C:16]([C:18]([OH:20])=O)=[CH:17][C:5]=2[N:4]=1.[NH2:21][C:22]1[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][C:23]=1O.CCN=C=NCCCN(C)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.O.CN(C=O)C>[CH3:28][C:25]1[CH:26]=[CH:27][C:22]2[N:21]=[C:18]([C:16]3[CH:15]=[CH:14][C:6]4[N:7]([CH:8]5[CH2:9][CH2:10][O:11][CH2:12][CH2:13]5)[C:3]([CH3:2])=[N:4][C:5]=4[CH:17]=3)[O:20][C:23]=2[CH:24]=1
Reactant: Cc1ccc(N)c(O)c1
Reactant: Cc1nc2cc(C(=O)O)ccc2n1C1CCOCC1
Agent: CCN=C=NCCCN(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: Cl
Solvent: Cc1ccccc1
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccc2nc(-c3ccc4c(c3)nc(C)n4C3CCOCC3)oc2c1
Yield: 4.8 %

Procedure:
2-methyl-1-(tetrahydropyran-4-yl)benzimidazole-5-carboxylic acid HCl salt (see Working Example 4-3) (0.25 g, 0.96 mmol), 2-amino-5-methylphenol (0.13 g, 1.05 mmol), anhydrous DMF (10 mL) and WSC (0.22 g, 1.14 mmol) were stirred overnight at room temperature. After the reaction was complete, water (50 mL) was added, the precipitated crystals were filtered off, and the filter residue was extracted with water/chloroform. After the organic layer was dried over anhydrous sodium sulfate, filtration and concentration gave crystals that were dissolved in toluene (5 mL), to which p-toluenesulfonic acid hydrate (0.45 g, 2.37 mmol) was added and this was stirred at reflux for 2 hours. After the solvent was concentrated at reduced pressure, water (5 mL) was added and the solid obtained was filtered off, and after washing with water, drying at reduced pressure at 50° C. yielded the title compound (16 mg, 4.8% yield) as an orange solid.
Reaction SMILES: [CH3:1][OH:2].C(N(CC)CC)C.[C:10]1([P:16](Cl)Cl)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CC[O:21][CH2:22]C>>[CH3:1][O:2][P:16]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[O:21][CH3:22]
Reactant: CCOCC
Reactant: CO
Reactant: ClP(Cl)c1ccccc1
Solvent: CCN(CC)CC
Product: COP(OC)c1ccccc1
Reaction time: 8 h

Procedure:
Methanol (12.8 gm., 0.4 mol.) and triethylamine (40.4 gm., 0.4 mol.) are dissolved in 750 ml. ether and chilled in an ice bath. Phenyl dichlorophosphine (35.8 gm., 0.2 mol.) is added dropwise and the reaction mixture is stirred overnight. The resulting suspension is filtered and the filtrate concentrated to an oil which is distilled in vacuo to give the product, phenylphosphonous acid dimethyl ester, b.p. 100°-105° /10 mm; yield 20 gm. (59%).
Reaction SMILES: [CH2:1]([N:8]1[C:14](=[O:15])[C@H:13]2[CH2:16][CH2:17][CH2:18][C@H:12]2[NH:11][C:10]2[CH:19]=[CH:20][CH:21]=[CH:22][C:9]1=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:23][CH2:24][C:25](Cl)=[O:26]>ClCCCl>[CH2:1]([N:8]1[C:14](=[O:15])[C@H:13]2[CH2:16][CH2:17][CH2:18][C@H:12]2[N:11]([C:25](=[O:26])[CH2:24][Cl:23])[C:10]2[CH:19]=[CH:20][CH:21]=[CH:22][C:9]1=2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1[C@H]2CCC[C@H]2Nc2ccccc2N1Cc1ccccc1
Reactant: O=C(Cl)CCl
Solvent: ClCCCl
Product: O=C1[C@H]2CCC[C@H]2N(C(=O)CCl)c2ccccc2N1Cc1ccccc1
Reaction time: 0.17 h
Yield: 88 %

Procedure:
On a water-bath kept at 14° C., to a solution of (3aR*,10aS*)-9-benzyl-2,3,3a,4,9,10a-hexahydrobenzo[b]cyclopenta[e][1,4]diazepin-10(1H)-one (5.85 g, 20 mmol) in 1,2-dichloroethane (20 mL) was added dropwise a solution of chloroacetyl chloride (2.5 g, 22 mmol) in 1,2-dichloroethane (15 mL), and the mixture was stirred for 10 minutes. The aqueous layer of this mixture was separated, and the organic layer was washed with water and a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, which was subjected to filtration, and the filtrate was concentrated under reduced pressure. The concentrate was recrystallized from dichloromethane-hexane to give 6.49 g (yield 88%) of the titled compound, m.p. 154°-156° C.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][N:20]([C:23]1[S:24][CH:25]=[C:26]([C:28]([O:30]C)=[O:29])[N:27]=1)[CH2:19][CH2:18]2)=[O:12].[OH-].[Na+].Cl>C1COCC1.CO>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][N:20]([C:23]1[S:24][CH:25]=[C:26]([C:28]([OH:30])=[O:29])[N:27]=1)[CH2:19][CH2:18]2)=[O:12]
Reactant: COC(=O)c1csc(N2CCc3cccc(C(=O)Nc4nc5ccccc5s4)c3C2)n1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)c1csc(N2CCc3cccc(C(=O)Nc4nc5ccccc5s4)c3C2)n1
Temperature: 50 °C
Reaction time: 4 h

Procedure:
The title compound 2-(8-(Benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)thiazole-4-carboxylic acid (1) was prepared by following procedure: To a solution of methyl 2-(8-(benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)thiazole-4-carboxylate (1C) (180 mg, 4 mmol) in THF (4 mL) and MeOH (2 mL) was added 2N NaOH (2 mL). The reaction mixture was stirred at 50° C. for 4 hours and neutralized by slowly adding 5% aq. HCl. The precipitate was then filtered, dried, dissolved in DMSO/MeOH (1:1) and purified by column chromatography on silica gel to provide the desired product 2-(8-(Benzo[d]thiazol-2-ylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)thiazole-4-carboxylic acid (1): 1H NMR (300 MHz, DMSO-D6) δ ppm 7.99 (1H, d), 7.76 (1H, d), 7.69 (1H, dd), 7.52 (1H, s), 7.38 (4H, m), 4.91 (2H, s), 3.75 (2H, t), 3.05 (2H, t). MS (ESI(+)): m/z 437 (M+H).
Reaction SMILES: CN([CH2:4][C:5]1[CH:10]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[C:8]([OH:15])=[C:7]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH:6]=1)C.[CH2:20]=[CH:21][CH:22]=[CH2:23]>CN(C)C=O>[C:16]([C:7]1[C:8](=[O:15])[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:10][C:5]2([CH2:23][CH2:22][CH:21]=[CH:20][CH2:4]2)[CH:6]=1)([CH3:19])([CH3:18])[CH3:17]
Reactant: C=CC=C
Reactant: CN(C)Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Solvent: CN(C)C=O
Product: CC(C)(C)C1=CC2(C=C(C(C)(C)C)C1=O)CC=CCC2
Temperature: 110 °C
Yield: 4 %

Procedure:
To a 250 mL glass reaction vessel there was added a dimethylformamide (10 mLs) solution of N,N-dimethyl,2,6-di-t-butyl-4-aminomethylphenol (2.63 g; 10 mmols). The vessel was sealed and 1,3-butadiene (40 mmols) was introduced into the system. The reaction mixture was then heated to 110° C. and the pressure was increased from atmospheric up to approximately 50 psig. The reaction was maintained at these conditions for approximately 48 hours. The reaction vessel was then cooled to room temperature. After cooling, the reaction mixture was filtered to remove ammonium iodide salt by-product. The filtrate was concentrated to afford a viscous oil crystallized with ethanol:water (60:40) to give 0.11 g of 2,4-di-t-butylspiro[5.5]undeca-1,4,8-trien-3-one (49% yield based on N,N-dimethyl,2,6-di-t-butyl-4-aminomethylphenol starting reactant).
Reaction SMILES: C([Al:5](CC(C)C)CC(C)C)C(C)C.[C:14]([OH:23])(=[O:22])[C:15]1[C:16](=[CH:18][CH:19]=[CH:20][CH:21]=1)[OH:17]>C1C=CC=CC=1.O1CCCC1>[OH:17][C:16]1[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=1[C:14]([O-:23])=[O:22].[OH:17][C:16]1[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=1[C:14]([O-:23])=[O:22].[OH:17][C:16]1[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=1[C:14]([O-:23])=[O:22].[Al+3:5]
Reactant: CC(C)C[Al](CC(C)C)CC(C)C
Reactant: O=C(O)c1ccccc1O
Solvent: C1CCOC1
Solvent: c1ccccc1
Product: O=C([O-])c1ccccc1O
Product: [Al+3]
Temperature: 15 °C
Reaction time: 2 h
Yield: 85.7 %

Procedure:
3.96 g of tri-isobutyl aluminum were dissolved in 100 ml of benzene, and the solution was maintained at 15° C. under nitrogen gas current by ice cooling. A solution of 8.28 g of salicylic acid dissolved in 100 ml of tetrahydrofuran was added dropwise little by little to the above benzene solution. After completion of the dropwise addition, the reaction was further carried out for 2 hours at room temperature under agitation. After completion of the reaction, the solvent was distilled off under reduced pressure to yield 7.5 g of aluminum tris-(o-hydroxybenzoate) in the form of a white powder having a melting point above 300° C. The resulting aluminum salt had a molecular weight of about 530, and the average degree of polymerization was found to be about 1.2. The infrared absorption spectrum of the salt is as follows:
Reaction SMILES: [C:1]1([C:7]2[CH:12]=[C:11]([CH3:13])[CH:10]=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[Na+].[Na+].[Br:20]Br>C(Cl)(Cl)(Cl)Cl>[C:1]1([C:7]2[CH:12]=[C:11]([CH2:13][Br:20])[CH:10]=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: BrBr
Reactant: Cc1ccnc(-c2ccccc2)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClC(Cl)(Cl)Cl
Product: BrCc1ccnc(-c2ccccc2)c1

Procedure:
To a solution of 100 mg of 2-phenyl-4-methylpyridine in 2 mL of carbon tetrachloride was added 300 mg of sodium carbonate and 100 mg of bromine. The reaction mixture was stirred and irradiated with a 500 W lamp for 1 h, filtered and the solvent removed by evaporation under reduced pressure to yield 2-phenyl-4-bromomethylpyridine which was used in the next step without further purification or characterization
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][N:4]=1.Cl[C:13]1[N:18]=[N:17][C:16]([N:19]2[CH2:24][CH2:23][CH:22]([N:25]3[C:33]4[C:28](=[CH:29][CH:30]=[C:31]([F:34])[CH:32]=4)[CH2:27][CH2:26]3)[CH2:21][CH2:20]2)=[CH:15][CH:14]=1>>[F:34][C:31]1[CH:32]=[C:33]2[C:28]([CH2:27][CH2:26][N:25]2[CH:22]2[CH2:23][CH2:24][N:19]([C:16]3[N:17]=[N:18][C:13]([C:6]4[CH:5]=[N:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=4)=[CH:14][CH:15]=3)[CH2:20][CH2:21]2)=[CH:29][CH:30]=1
Reactant: Fc1ccc2c(c1)N(C1CCN(c3ccc(Cl)nn3)CC1)CC2
Reactant: COc1ccc(B(O)O)cn1
Product: COc1ccc(-c2ccc(N3CCC(N4CCc5ccc(F)cc54)CC3)nn2)cn1

Procedure:
The title compound was prepared following the procedure as described in Example 1, Method A, STEP 4, reacting 2-methoxypyridine-5-boronic acid and 1-(1-(6-chloropyridazin-3-yl)piperidin-4-yl)-6-fluoroindoline.
Reaction SMILES: [Si]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[S:15]([C:18]1[CH:31]=[CH:30][C:21]2[O:22][C:23]([CH3:29])([CH3:28])[C@@:24]3([CH3:27])[O:26][C@H:25]3[C:20]=2[CH:19]=1)(=[O:17])=[O:16])(C(C)(C)C)(C)C.[CH3:32][N:33]1[C:38](=[O:39])[CH:37]=[CH:36][C:35]([OH:40])=[N:34]1.N1C=CC=CC=1>O1CCOCC1>[CH3:32][N:33]1[C:38](=[O:39])[CH:37]=[CH:36][C:35]([O:40][C@H:25]2[C@@:24]([OH:26])([CH3:27])[C:23]([CH3:29])([CH3:28])[O:22][C:21]3[CH:30]=[CH:31][C:18]([S:15]([C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=4[OH:8])(=[O:17])=[O:16])=[CH:19][C:20]2=3)=[N:34]1
Reactant: CC1(C)Oc2ccc(S(=O)(=O)c3ccccc3O[Si](C)(C)C(C)(C)C)cc2[C@@H]2O[C@@]21C
Reactant: Cn1nc(O)ccc1=O
Solvent: c1ccncc1
Solvent: C1COCCO1
Product: Cn1nc(O[C@@H]2c3cc(S(=O)(=O)c4ccccc4O)ccc3OC(C)(C)[C@@]2(C)O)ccc1=O

Procedure:
(3S,4S)-6-(2-tert-Butyldimethylsilyloxyphenyl)sulphonyl-3,4-dihydro-3,4-epoxy-2,2,3-trimethyl-2H-benzo[b]pyran (0.5 g) (see Preparation 16) and 2,3-dihydro-2-methyl-3-oxo-6-hydroxypyridazin (0.41 g) (see J.Org.Chem., 1971, 36, 3372) were suspended in dry 1,4-dioxane (8 ml), pyridine (0.085 g) was added and the mixture was heated under reflux (a calcium chloride drying tube was attached to the flask) for 20 hours. The solvent was removed under reduced pressure, the residue was stirred with dichloromethane (30 ml) and filtered. The filtrate was evaporated and the residue was chromatographed on silica using 1:1 hexane:ethyl acetate as the eluent to yield a mixture of the required product and the epoxide starting material. This mixture was redissolved in dry 1,4-dioxane (7 ml), 2,3-dihydro-2-methyl-3-oxo-6-hydroxypyridazin (0.2 g) and pyridine (0.08 g) were added and the reaction was heated under reflux for a further 18 hours. The solvent was removed under reduced pressure and the residue was dissolved in 5% methanol/dichloromethane and filtered. The filtrate was evaporated and the residue was chromatographed on silica using 2.5:97.5 methanol:dichloromethane as the eluent to yield (3S,4R)-3,4-dihydro-4-(2,3-dihydro-2-methyl-3-oxopyridazin-6-yl)oxy-3-hydroxy-6-(2-hydroxyphenyl)-sulphonyl-2,2,3-trimethyl-2H-benzo[b]pyran (0.17 g) as a yellow foam. Found: C,54.19; H,4.85; N,5.21. C23H24N2O7S, 0.625 CH2Cl2 requires C,54.06; H,4.73; N,5.34%.
Reaction SMILES: CS[C:3]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:10]=1)([CH3:8])[C:4]([O:6][CH3:7])=[O:5].C(OCC)C>C(O)(=O)C.S([O-])([O-])(=O)=O.[Cu+2].[Zn]>[O:15]([C:11]1[CH:10]=[C:9]([CH:3]([CH3:8])[C:4]([O:6][CH3:7])=[O:5])[CH:14]=[CH:13][CH:12]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: COC(=O)C(C)(SC)c1cccc(Oc2ccccc2)c1
Agent: [Cu+2]
Agent: O=S(=O)([O-])[O-]
Agent: [Zn]
Solvent: CCOCC
Solvent: CC(=O)O
Product: COC(=O)C(C)c1cccc(Oc2ccccc2)c1
Yield: 97.3 %

Procedure:
Methyl α-methylthio-α-(m-phenoxyphenyl)propionate (302 mg) was dissolved in 2 ml of acetic acid, and 16 mg of anhydrous copper sulfate and 150 mg of zinc powder were added. With stirring, the mixture was heated under reflux for 9 hours. Furthermore, 50 mg of zinc powder was added, and the mixture was heated under reflux for 2 hours. Diethyl ether (60 mg) was added, and the insoluble matter was separated by filtration. The filtrate was washed twice with 10 ml of water and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was subjected to short-path distillation (bath temperature 140°-160° C./0.02 mmHg) to afford 249 mg of methyl α-(m-phenoxyphenyl)propionate as a colorless oil in a yield of 97%.
Reaction SMILES: [C:1]([O:4][C@H:5]1[C@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:10]([O:16][C:17](=[O:19])[CH3:18])[C@H:9]([CH3:20])[O:8][CH:6]1[OH:7])(=[O:3])[CH3:2].[Cl:21][C:22]([Cl:26])([Cl:25])[C:23]#[N:24].C(=O)([O-])[O-].[K+].[K+]>ClCCl>[Cl:21][C:22]([Cl:26])([Cl:25])[C:23](=[NH:24])[O:7][C@H:6]1[O:8][C@@H:9]([CH3:20])[C@@H:10]([O:16][C:17](=[O:19])[CH3:18])[C@@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@@H:5]1[O:4][C:1](=[O:3])[CH3:2]
Reactant: CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@H](C)OC(O)[C@H]1OC(C)=O
Reactant: N#CC(Cl)(Cl)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: CC(=O)O[C@H]1[C@H](OC(C)=O)[C@@H](OC(=N)C(Cl)(Cl)Cl)O[C@@H](C)[C@H]1OC(C)=O
Temperature: 25 °C
Reaction time: 4 h
Yield: 76 %

Procedure:
A mixture of 2,3,4-tri-O-acetyl-L-fucopyranose (anomer mixture) (0.85 g, 2.93 mmol), trichloroacetonitrile (3 ml, 30 mmol) and potassium carbonate (2.73 g, 19.7 mmol) in dry dichloromethane (12 ml) is stirred under nitrogen at room temperature for about 4 h. After filtration through kieselguhr, the solvent is removed. After chromatographic purification (petroleum ether/diethyl ether 2:5), a mixture of O-(2,3,4-tri-O-acetyl-α-L-fucopyranosyl) trichloroacetimidate (3) and O-(2,3,4-tri-O-acetyl-β-L-fucopyranosyl) trichloroacetimidate (2) is obtained in a yield of 76% (α:β=1:1.3). α-Anomer: [α]D =-116.0 (c=1, chloroform), Rf =0.54 (petroleum ether/ethyl acetate 2:1), m.p. 107°-109° C. β-Anomer: [α]D =-24.5 (c=1, chloroform), Rf =0.34 (petroleum ether/ethyl acetate 2:1), m.p. 60°-63° C.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][NH2:12])=[C:7]([N+:13]([O-:15])=[O:14])[CH:6]=1)=[O:4].[C:16](O)(=[O:18])[CH3:17]>>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([N:11]([C:16](=[O:18])[CH3:17])[NH2:12])=[C:7]([N+:13]([O-:15])=[O:14])[CH:6]=1)=[O:4]
Reactant: CC(=O)O
Reactant: COC(=O)c1ccc(NN)c([N+](=O)[O-])c1
Product: COC(=O)c1ccc(N(N)C(C)=O)c([N+](=O)[O-])c1
Yield: 97 %

Procedure:
After boiling 105.6 g of 4-methoxycarbonyl-2-nitrophenylhydrazine with 1 liter of glacial acetic acid for 1 hour, the clear orange-red solution was evaporated under reduced pressure. The residue was stirred with 1500 ml of water, the crystalline precipitate was filtered by suction, washed with water and dried at 80° C. to give 123 g (97%) of 4-methoxycarbonyl-2-nitro-N-acetylphenylhydrazine, in the form of yellow powder-like crystals, m.p.: 182°-185° C., which melted at 190°-192° C. after recrystallization from aqueous ethanol.
Reaction SMILES: Br[C:2]1[C:3]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:7][CH:6]=2.[C:22]1([CH:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.CCN(C(C)C)C(C)C>CN(C)C=O>[C:16]1([C:3]2[C:2]([N:31]3[CH2:32][CH2:33][CH:28]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH2:29][CH2:30]3)=[N:11][C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:12]([O:14][CH3:15])=[O:13])[CH:9]=3)[N:4]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: COC(=O)c1ccc2nc(-c3ccccc3)c(Br)nc2c1
Reactant: c1ccc(C2CCNCC2)cc1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1ccc2nc(-c3ccccc3)c(N3CCC(c4ccccc4)CC3)nc2c1
Temperature: 100 °C
Reaction time: 8 h

Procedure:
Into a 8-mL sealed tube, was placed methyl 3-bromo-2-phenylquinoxaline-6-carboxylate (150 mg, 0.44 mmol, 1.00 equiv), 4-phenylpiperidine (141.68 mg, 0.88 mmol, 2.00 equiv), DIEA (170.3 mg, 1.32 mmol, 3.00 equiv), N,N-dimethylformamide (4 mL). The resulting solution was stirred overnight at 100° C. in an oil bath. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with PE/EA (100:1). This resulted in 92.9 mg (49%) of methyl 2-phenyl-3-(4-phenylpiperidin-1-yl)quinoxaline-6-carboxylate as a yellow solid.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([O:19]C)=[CH:15][CH:14]=2)[C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.Br.C(O)(=O)C>O>[Cl:1][C:2]1[N:3]=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=2)[C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2
Reactant: COc1ccc(Nc2nc(Cl)cc3ccccc23)cc1
Agent: Br
Solvent: O
Solvent: CC(=O)O
Product: Oc1ccc(Nc2nc(Cl)cc3ccccc23)cc1
Yield: 101.9 %

Procedure:
A mixture of 3-chloro-1-[N-(4-methoxyphenyl)amino]isoquinoline (1.90 g), hydrogen bromide (10 ml of 48%) and glacial acetic acid was heated under reflux for a period of 9.5 hours. The reaction mixture was poured into water, and the aqueous mixture was extracted with ethyl acetate. The organic phase was dried over anhydrous magnesium sulfate and the solvent was removed by distillation under reduced pressure to give 4-[N-(3-chloroisoquinolin-1-yl)amino]phenol (1.84 g) as pale yellow crystals mp 170° C.
Reaction SMILES: Cl.[N:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]([CH2:32][CH2:33][C:34]([O:36][CH3:37])=[O:35])[C:9]([C:11]1[CH:31]=[CH:30][C:14]2[N:15]([CH3:29])[C:16]([CH2:18][NH:19][C:20]3[CH:25]=[CH:24][C:23]([C:26](=[NH:28])[NH2:27])=[CH:22][CH:21]=3)=[N:17][C:13]=2[CH:12]=1)=[O:10].Cl[C:39]([O:41][CH2:42][CH3:43])=[O:40]>ClCCl.CO>[N:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]([CH2:32][CH2:33][C:34]([O:36][CH3:37])=[O:35])[C:9]([C:11]1[CH:31]=[CH:30][C:14]2[N:15]([CH3:29])[C:16]([CH2:18][NH:19][C:20]3[CH:25]=[CH:24][C:23]([C:26](=[NH:27])[NH:28][C:39]([O:41][CH2:42][CH3:43])=[O:40])=[CH:22][CH:21]=3)=[N:17][C:13]=2[CH:12]=1)=[O:10]
Reactant: COC(=O)CCN(C(=O)c1ccc2c(c1)nc(CNc1ccc(C(=N)N)cc1)n2C)c1ccccn1
Reactant: CCOC(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CO
Product: CCOC(=O)NC(=N)c1ccc(NCc2nc3cc(C(=O)N(CCC(=O)OC)c4ccccn4)ccc3n2C)cc1
Yield: 72 %

Procedure:
Prepared analogously to Example 90 from 1-methyl-2-[N-(4-amidinophenyl)aminomethyl]benzimidazol-5-yl-carboxylic acid-N-(2-pyridyl)-N-(2-methoxycarbonylethyl)amide hydrochloride and ethyl chloroformate. Yield: 72% of theory, C29H31N7O5 (557.6); Rf value: 0.58 (silica gel; dichloromethane/methanol=9:1); EKA mass spectrum: (M+H)+=558; (M+H+Na)++=290.8; (M+Na)+=580.