Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[C:6]([S:14][C:15]([S:18][C:19]2[CH:24]=[C:23]([CH:25]([CH3:27])[CH3:26])[C:22]([OH:28])=[C:21]([CH:29]([CH3:31])[CH3:30])[CH:20]=2)([CH3:17])[CH3:16])[CH:7]=[C:8]([CH:11]([CH3:13])[CH3:12])[C:9]=1[OH:10])([CH3:3])[CH3:2]>ClCCl.CCCCCC.[O-2].[O-2].[Mn+4]>[CH3:17][C:15]1([CH3:16])[S:14][C:6]2([CH:5]=[C:4]([CH:1]([CH3:3])[CH3:2])[C:9](=[O:10])[C:8]([CH:11]([CH3:12])[CH3:13])=[CH:7]2)[C:19]2([CH:24]=[C:23]([CH:25]([CH3:27])[CH3:26])[C:22](=[O:28])[C:21]([CH:29]([CH3:31])[CH3:30])=[CH:20]2)[S:18]1
Reactant: CC(C)c1cc(SC(C)(C)Sc2cc(C(C)C)c(O)c(C(C)C)c2)cc(C(C)C)c1O
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCl
Solvent: CCCCCC
Product: CC(C)C1=CC2(C=C(C(C)C)C1=O)SC(C)(C)SC21C=C(C(C)C)C(=O)C(C(C)C)=C1
Reaction time: 4 h

Procedure:
To a mixed solution of 2,2-bis(3,5-diisopropyl-4-hydroxyphenylthio)propane (500 mg, 1.09 mmol) in dichloromethane (5 mL) and hexane (5 mL) was added manganese dioxide (500 mg). The mixture was stirred for 4 hours and then filtered by using a celite, and the resulting filtrate was concentrated. Hexane was added to the residue, and the mixture was stored in a refrigerator. The generated solid was separated by a filtration, washed with hexane, and then dried to synthesize an, objective compound.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([CH3:15])[N:12]=[C:11]([NH2:16])[N:10]=2)=[N:6][CH:7]=1.C(N(CC)C1C=CC=CC=1)C.[N+:28]([C:31]1[CH:39]=[CH:38][C:34]([C:35](Cl)=[O:36])=[CH:33][CH:32]=1)([O-:30])=[O:29]>O1CCOCC1>[NH2:16][C:11]1[N:10]=[C:9]([NH:8][C:5]2[N:6]=[CH:7][C:2]([NH:1][C:35](=[O:36])[C:34]3[CH:33]=[CH:32][C:31]([N+:28]([O-:30])=[O:29])=[CH:39][CH:38]=3)=[CH:3][CH:4]=2)[CH:14]=[C:13]([CH3:15])[N:12]=1
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Reactant: Cc1cc(Nc2ccc(N)cn2)nc(N)n1
Solvent: C1COCCO1
Solvent: CCN(CC)c1ccccc1
Product: Cc1cc(Nc2ccc(NC(=O)c3ccc([N+](=O)[O-])cc3)cn2)nc(N)n1
Temperature: 20 °C
Reaction time: 2 h
Yield: 97.3 %

Procedure:
To a suspension of 10 (500 mg, 2.31 mmol) and N,N-diethylaniline (1 ml, 1.5 eq) in 1,4-dioxane (20 ml) at 0° C. was added dropwise a solution of p-nitrobenzoylchloride (429 mg, 12.31 mmol). The reaction mixture was stirred at 20° C. for 2 h. TLC and mass spectrum showed still presence of 10. Therefore more p-nitrobenzoylchloride (43 mg, 0.1 eq) was added and stirred for 20 h. The resulting precipitate was filtered and washed with more 1,4-dioxane. The collected solid was stirred in aqueous NH3, filtered washed with water and dried to give essentially pure 11 (821 mg, 97%); mp (MeOH)>300° C.; 1H NMR [(CD3)2SO] δ 10.58 (s, 1H, NH), 9.56 (s, 1H, NH), 8.65 (d, J=2.5 Hz, 1 H, H-2′), 8.38 (d, J=8.9 Hz, 2H, H-3, 5), 8.20 (d, J=9.2 Hz, 2H, H-2, 6), 8.17 (d, J=9.1 Hz, 1H, H-5′), 8.02 (dd, J=9.0, 2.6 Hz, 1H, H-4′), 6.45 (s, 1H, H-5″), 6.15 (s, 2H, NH2), 2.12 (s, 3H, CH3); HRMS (FAB+) (M+1) m/z calc. for C17H16N7O3 (M+1) m/z 366.1315, found 366.1314; Anal. calc. for C17H15N7O3: C, 55.9; H, 4.1, N, 26.8, found C, 55.6; H, 4.2; N, 26.8%.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[CH:9]1[CH2:14][C:13]([NH:15][NH:16]S(C2C=CC(C)=CC=2)(=O)=O)=[CH:12][C:11](=O)[CH2:10]1.C(=O)([O-])[O-].[K+].[K+].CO.Br[CH2:37][C:38](=O)[CH3:39]>COCCOC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[CH:9]1[CH2:14][C:13]2[N:15]=[N:16][CH:37]=[C:38]([CH3:39])[C:12]=2[CH2:11][CH2:10]1
Reactant: Cc1ccc(S(=O)(=O)NNC2=CC(=O)CC(c3cc(C)ccc3Cl)C2)cc1
Reactant: CC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: COCCOC
Product: Cc1ccc(Cl)c(C2CCc3c(C)cnnc3C2)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A mixture of 5-(2-chloro-5-methylphenyl)-1-[2-(4-methylphenylsulfonyl)hydrazino]cyclohexen-3-one (2.03 g), anhydrous potassium carbonate (1.73 g) and methanol (20 ml) was stirred at room temperature for 30 minutes, and to the mixture were added 1,2-dimethoxyethane (10 ml) and bromoacetone (0.891 g). The mixture was stirred at 80° C. for 4.5 hours. Under reduced pressure, the solvent was evaporated, and to the residue were added ethyl acetate (200 ml) and water (30 ml). The mixture was shaken, and the separated upper layer was washed with water and concentrated under reduced pressure. The residue was purified with silica gel column chromatography to give 7-(2-chloro-5-methylphenyl)-4-methyl-5,6,7,8-tetrahydrocinnolin,-5-one (0.804 g) as brown crystals.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1)[N:9]=[CH:8][NH:7][C:6]2=O.S(Cl)([Cl:25])=O>CN(C=O)C>[Cl:25][C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH2:14][CH2:15][N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=[CH:8][N:7]=1
Reactant: COc1cc2c(=O)[nH]cnc2cc1OCCN1CCOCC1
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: COc1cc2c(Cl)ncnc2cc1OCCN1CCOCC1
Yield: 68 %

Procedure:
A mixture of 6-methoxy-7-(2-morpholinoethoxy)-3,4-dihydroquinazolin-4-one (310 mg, 1.02 mmol), thionyl chloride (10 ml) and DMF (2 drops) was heated at reflux for 4 hours and allowed to cool. Excess thionyl chloride was removed by evaporation and the residue was azeotroped with toluene. The residue was partitioned between aqueous sodium hydrogen carbonate and methylene chloride. The organic layer was separated, washed with brine and filtered through phase separating paper. The volatiles were removed by evaporation and the residue purified by column chromatography eluting with methylene chloridelinethanol (96/4) to give 4-chloro-6-methoxy-7-(2-morpholinoethoxy)quinazoline (225 mg, 68%).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1C(O)=O.S(=O)(=O)(O)O.[N-:17]=[N+]=[N-].[Na+].[OH-].[Na+]>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[NH2:17]
Reactant: O=C(O)c1c(F)cccc1Cl
Reactant: [N-]=[N+]=[N-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: ClC(Cl)Cl
Product: Nc1c(F)cccc1Cl
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a stirred mixture of 20 g. of 2-chloro-6-fluorobenzoic acid, 100 ml. of chloroform and 50 ml. of concentrated sulfuric acid is added slowly 10.2 g. of sodium azide while the temperature is kept at 40°-55°. Stirring is continued for 2 hours at 40°-55° then the mixture is poured into 500 ml. of ice water containing 80 g. of sodium hydroxide. The mixture is extracted with ether and the other extracts are dried over magnesium sulfate. The dry extracts are then treated with hydrogen chloride, and the resultant product as the hydrochloride salt is collected by filtration yielding 12.6 g. of white solid which sublimes at 160°-170°.
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[NH:11][CH:12]=[CH:13][N:14]=2)[N:5]=1.[CH2:15]([N:18]1[C:22]2[CH:23]=[CH:24][C:25]([C:27]#[N:28])=[CH:26][C:21]=2[N:20]=[C:19]1[CH2:29]Cl)[CH2:16][CH3:17].[I-].[Na+]>CN(C=O)C.O>[CH2:15]([N:18]1[C:22]2[CH:23]=[CH:24][C:25]([C:27]#[N:28])=[CH:26][C:21]=2[N:20]=[C:19]1[CH2:29][N:11]1[CH:12]=[CH:13][N:14]=[C:10]1[C:6]1[N:5]=[C:4]([F:3])[CH:9]=[CH:8][CH:7]=1)[CH2:16][CH3:17]
Reactant: Fc1cccc(-c2ncc[nH]2)n1
Reactant: CCCn1c(CCl)nc2cc(C#N)ccc21
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCn1c(Cn2ccnc2-c2cccc(F)n2)nc2cc(C#N)ccc21
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
To a stirring suspension of sodium hydride (2.25 g of 60% in oil) in DMF (10 mL) at 0° a solution of 2-Fluoro-6-(1H-imidazol-2-yl)-pyridine (7.7 9, 47.2 mmol) in DMF (20 mL) is added. After stirring for 5 minutes, a solution of 1-n-Propyl-2-chloromethyl-5-cyanobenzimidazole (11 g, 47.2 mmol) and sodium iodide (20 mg) in DMF (80 mL) is added. The reaction mixture is stirred for 6 h, gradually warmed to room temperature. The reaction mixture is cooled, water added, the solid collected, rinsed with water and dried to afford the title compound, 1-Propyl-2-{[2-(2-fluoropyrid-6-yl)-1H-imidazol-1-yl]methyl}-5-cyano-1H-benzimidazole.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:39])[NH:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([N:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C@H:20]([N:27]([C:35](=[O:37])[CH3:36])[C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)[CH2:19][C@@H:18]2[CH3:38])=[O:16])=[CH:11][CH:10]=1.[H-].[Na+].[CH2:42](I)[CH3:43]>C1COCC1.CN(C=O)C>[CH3:1][O:2][C:3](=[O:39])[N:4]([CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]([N:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C@H:20]([N:27]([C:35](=[O:37])[CH3:36])[C:28]3[CH:29]=[CH:30][C:31]([Cl:34])=[CH:32][CH:33]=3)[CH2:19][C@@H:18]2[CH3:38])=[O:16])=[CH:13][CH:14]=1)[CH2:42][CH3:43]
Reactant: COC(=O)NCCCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1
Reactant: CCI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CCN(CCCOc1ccc(C(=O)N2c3ccccc3[C@H](N(C(C)=O)c3ccc(Cl)cc3)C[C@@H]2C)cc1)C(=O)OC
Temperature: 25 °C
Reaction time: 7 h
Yield: 35.1 %

Procedure:
(2S,4R)-[3-(4-{4-[Acetyl-(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-propyl]-carbamic acid methyl ester (41 mg, 0.074 mmol) was dissolved in THF/DMF (10:1, 3 mL). To this solution was added Sodium Hydride (2 mg, 0.089 mmol), followed by ethyl iodide (14 mg, 0.089 mmol). The reaction was stirred at room temperature for 7 hours and was quenched by adding 1 mL of water. The mixture was concentrated under reduced pressure and dissolved in DCM (15 mL). The reaction mixture was washed with sat. aq. NaHCO3 (15 mL), water (15 mL) and brine (15 mL). The organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (5/95 ethyl acetate/hexane—50/50 ethyl acetate/hexane gradient) to afford slightly yellow solid product (15 mg, 35%).
Reaction SMILES: [CH3:1][CH:2]([CH3:27])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14](=[O:26])[CH2:15][C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17].[BH4-].[Na+].C(OCC)(=O)C.Cl>CC(O)C>[OH:26][CH:14]([CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH:2]([CH3:27])[CH3:1])[CH2:15][C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17]
Reactant: CC(C)CCCCCCCCCCCC(=O)CC(=O)OCc1ccccc1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(C)O
Solvent: CCOC(C)=O
Product: CC(C)CCCCCCCCCCCC(O)CC(=O)OCc1ccccc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 55.8 %

Procedure:
To a solution of benzyl 15-methyl-3-oxohexadecanoate (3.74 g) in 2-propanol (50 ml) was added sodium borohydride (0.38 g) at 0° C. The mixture was stirred at 0° C. for 2 hours and poured into a mixture of ethyl acetate and diluted hydrochloric acid. The organic layer was washed with water, dried over magnesium sulfate and evaporated. The residue was chromatographed on a silica gel column eluting with a mixture of n-hexane and ethyl acetate (10:1) to give benzyl 3-hydroxy-15-methylhexadecanoate as a colorless oil (2.10 g).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([N+:12]([O-:14])=[O:13])=[CH:4][CH:3]=1.[CH:15]([N:18]([CH:22]([CH3:24])[CH3:23])[CH2:19][CH2:20][NH2:21])([CH3:17])[CH3:16]>>[CH:15]([N:18]([CH:22]([CH3:24])[CH3:23])[CH2:19][CH2:20][NH:21][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([N+:12]([O-:14])=[O:13])=[CH:4][CH:3]=1)([CH3:17])[CH3:16]
Reactant: CC(C)N(CCN)C(C)C
Reactant: O=[N+]([O-])c1ccc(Cl)c2ccccc12
Product: CC(C)N(CCNc1ccc([N+](=O)[O-])c2ccccc12)C(C)C
Yield: 75.7 %

Procedure:
1-Chloro-4-nitronaphthalene and N, N-diisopropylethylenediamine were reacted in the same manner as in Example 1 to obtain the titled compound in a yield of 75.7%.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([O:14][CH2:15][CH:16]=[C:17]([Cl:19])[Cl:18])[CH:5]=[C:6]([Cl:13])[C:7]=1[O:8][CH2:9][CH2:10][CH2:11][OH:12].[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]=[C:28]=[O:29])=[CH:23][CH:22]=1.N1C=CC=CC=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([O:14][CH2:15][CH:16]=[C:17]([Cl:19])[Cl:18])[CH:5]=[C:6]([Cl:13])[C:7]=1[O:8][CH2:9][CH2:10][CH2:11][O:12][C:28](=[O:29])[NH:27][C:24]1[CH:25]=[CH:26][C:21]([Cl:20])=[CH:22][CH:23]=1
Reactant: O=C=Nc1ccc(Cl)cc1
Reactant: OCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Solvent: c1ccncc1
Solvent: Cc1ccccc1
Product: O=C(Nc1ccc(Cl)cc1)OCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Reaction time: 3 h
Yield: 77.4 %

Procedure:
A solution of 0.17 g of 3,5-dichloro-4-(3-hydroxypropyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene, 0.09 g of 4-chlorophenyl isocyanate and a catalytic amount of pyridine dissolved in 10 ml of toluene was heated at 60° to 70° C., while stirring, for 3 hours, and the reaction mixture was then concentrated to give a residue. The residue was subjected to silica gel chromatography, which afforded 0.19 g of 3,5-dichloro-4-(3-(N-(4-chlorophenyl)carbamoyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene (77% yield), m.p., 54.3° C.
Reaction SMILES: [CH3:1][CH:2]([CH2:4][CH2:5][CH2:6][C@H:7]([C@@H:9]1[C@:27]2([CH3:28])[C@H:12]([C@H:13]3[C@H:24]([CH2:25][CH2:26]2)[C@:22]2([CH3:23])[C:16]([CH2:17][C@H:18]([CH2:20][CH2:21]2)[OH:19])=[CH:15][CH2:14]3)[CH2:11][CH2:10]1)[CH3:8])[CH3:3].[C:29](O)(=[O:35])[CH2:30][CH2:31][CH2:32][CH:33]=[CH2:34].C1CCC(N=C=NC2CCCCC2)CC1.C(OC)(C)(C)C>C(Cl)Cl>[C:29]([C@:18]1([OH:19])[CH2:20][CH2:21][C@@:22]2([CH3:23])[C:16](=[CH:15][CH2:14][C@@H:13]3[C@@H:24]2[CH2:25][CH2:26][C@@:27]2([CH3:28])[C@H:12]3[CH2:11][CH2:10][C@@H:9]2[C@H:7]([CH3:8])[CH2:6][CH2:5][CH2:4][CH:2]([CH3:1])[CH3:3])[CH2:17]1)(=[O:35])[CH:30]=[CH:31][CH2:32][CH2:33][CH3:34]
Reactant: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
Reactant: C=CCCCC(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: COC(C)(C)C
Solvent: ClCCl
Product: CCCC=CC(=O)[C@]1(O)CC[C@@]2(C)C(=CC[C@H]3[C@@H]4CC[C@H]([C@H](C)CCCC(C)C)[C@@]4(C)CC[C@@H]32)C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 95 %

Procedure:
To a solution of cholesterol (2.0 g, 5.17 mM) in methylene chloride (20 mL) was added 5-hexenoic acid (0.68 mL, 5.69 mM) followed by the addition of DCC (1.60 g, 7.76 mM) and 4-PP (0.115 g, 0.78 mM) under nitrogen atmosphere. The resulting reaction mixture was stirred at ambient temperature for 1 h and worked up with the addition of methyl t-butyl ether (60 mL). The urea was filtered off, and the product was transferred to a separatory funnel, washed with 1N HCl (10 mL), water (30 mL) and brine (30 mL). The product was filtered after drying over MgSO4 and the solvent was evaporated to leave a residue. The product obtained in >95% yield was characterized by 1H NMR.
Reaction SMILES: [Si]([O:18][CH2:19][C@@H:20]1[O:24][C@@H:23]([P:25]([O:30][CH2:31][CH3:32])([O:27][CH2:28][CH3:29])=[O:26])[S:22][CH2:21]1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>CO.C(Cl)(=O)C.[Cl-].[NH4+]>[CH2:28]([O:27][P:25]([O:30][CH2:31][CH3:32])([C@H:23]1[S:22][CH2:21][C@H:20]([CH2:19][OH:18])[O:24]1)=[O:26])[CH3:29]
Reactant: CCOP(=O)(OCC)[C@@H]1O[C@@H](CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)CS1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CC(=O)Cl
Solvent: CO
Product: CCOP(=O)(OCC)[C@@H]1O[C@@H](CO)CS1
Temperature: 0 °C
Reaction time: 1 h
Yield: 12 %

Procedure:
To a solution of cis and trans-5-t-butyldimethylsilyloxymethyl-2-(diethyloxyphosphinoyl)-1,3-oxathiolane (example 25) (4.00 g, 10.8 mmol) in MeOH (30 mL) was added a few drops of acetyl chloride (200 μL) at 0° C. The mixture was stirred at 0° C. for 1 hr. and at room temperature for 18 hr. A few drops of ammonium chloride was added and the solvent was evaporated under reduced pressure. The crude material was purified by several flash chromatography with a mixture of dichloromethane and methanol (96:4) to give 382 mg of the cis isomer , 1.19 g of the trans isomer and 332 mg of the mixture in a total yield of 80% after the first purification.
Reaction SMILES: C[O:2][C:3]([C:5]1[C:6]([CH3:32])=[C:7]2[C:12]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[O:27][CH3:28])=[CH:16][CH:15]=3)=[C:11]([C:29]#[N:30])[CH:10]=[N:9][N:8]2[CH:31]=1)=[O:4].[OH-].[Na+]>CO.C1COCC1>[C:29]([C:11]1[CH:10]=[N:9][N:8]2[CH:31]=[C:5]([C:3]([OH:4])=[O:2])[C:6]([CH3:32])=[C:7]2[C:12]=1[NH:13][C:14]1[CH:15]=[CH:16][C:17]([O:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[O:27][CH3:28])=[CH:18][CH:19]=1)#[N:30]
Reactant: COC(=O)c1cn2ncc(C#N)c(Nc3ccc(Oc4ccccc4OC)cc3)c2c1C
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: COc1ccccc1Oc1ccc(Nc2c(C#N)cnn3cc(C(=O)O)c(C)c23)cc1
Temperature: 25 °C
Yield: 95.1 %

Procedure:
A mixture of 430C (1.60 g, 3.73 mmol) and 6N NaOH (5 ml, 30 mmol) in a mixed solvent of MeOH/THF (20 ml, 1/1) was heated at reflux for 2 h, cooled to rt. Removed half of the solvent in vacuo. The residue was treated with H2O (30 ml), washed with CH2Cl2 (3×50 ml). The aqueous layer was acidified to PH=5 and extracted with EtOAc (3×50 ml). The combined organic layers were washed with H2O (2×30 ml) and brine (30 ml), dried with Na2SO4. Removal of the solvent under reduced pressure gave 430D (1.47 g, 95%) as a yellow powder. It has retention time of 5.88 min (∠Cl, 8 min. run). MS Found: (M+H)+=415.2.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[Cl-].ClC1N(C)CC[NH+]1C.[CH3:24][O:25][C:26]1[C:27](=[O:50])[C:28]([CH3:49])=[C:29]([CH2:35][C:36]2[CH:37]=[CH:38][C:39]([O:45][C:46](=[O:48])[CH3:47])=[C:40]([CH:44]=2)[C:41](O)=[O:42])[C:30](=[O:34])[C:31]=1[O:32][CH3:33]>C(Cl)Cl>[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:41](=[O:42])[C:40]2[CH:44]=[C:36]([CH2:35][C:29]3[C:30](=[O:34])[C:31]([O:32][CH3:33])=[C:26]([O:25][CH3:24])[C:27](=[O:50])[C:28]=3[CH3:49])[CH:37]=[CH:38][C:39]=2[O:45][C:46](=[O:48])[CH3:47])[CH:3]=1
Reactant: COC1=C(OC)C(=O)C(Cc2ccc(OC(C)=O)c(C(=O)O)c2)=C(C)C1=O
Reactant: Nc1cccnc1
Agent: CN1CC[NH+](C)C1Cl
Agent: [Cl-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC1=C(OC)C(=O)C(Cc2ccc(OC(C)=O)c(C(=O)Nc3cccnc3)c2)=C(C)C1=O
Temperature: 25 °C
Reaction time: 6 h
Yield: 52.6 %

Procedure:
3-Aminopyridine (0.424 g, 4.492 mmol), triethylamine (0.440 g, 4.342 mmol) and 2-chloro-1,3-dimethylimidazolinium chloride (0.735 g, 4.342 mmol) were added to a methylene chloride solution (200 ml) of 5-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-acetoxybenzoic acid (1.120 g, 2.995 mmol) and the resulting solution was stirred at room temperature for 6 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 (0.710 g, 1.576 mmol, 53%).
Reaction SMILES: [CH3:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]([C@@H:11]2[CH2:13][C@H:12]2[CH2:14][OH:15])=[O:10])[CH2:4][CH2:3]1.C(N(CC)CC)C.[CH3:23][S:24](O)(=[O:26])=[O:25]>CN(C)C1C=CN=CC=1.ClCCl>[CH3:1][C@H:2]1[CH2:3][CH2:4][C@H:5]([NH:8][C:9]([C@@H:11]2[CH2:13][C@H:12]2[CH2:14][O:15][S:24]([CH3:23])(=[O:26])=[O:25])=[O:10])[CH2:6][CH2:7]1
Reactant: CS(=O)(=O)O
Reactant: C[C@H]1CC[C@H](NC(=O)[C@@H]2C[C@H]2CO)CC1
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)OC[C@@H]1C[C@H]1C(=O)N[C@H]1CC[C@H](C)CC1
Temperature: 0 °C

Procedure:
Add, dropwise, to a stirring suspension at −20° C. of trans-2-hydroxymethyl-cyclopropanecarboxylic acid trans-(4-methylcyclohexyl)-amide (Example 11c) (2.85 g, 13.5 mmol), triethylamine (3.74 mL, 27.0 mmol) and 4-(dimethylamino)pyridine (0.1 g, 0.82 mmol) in dichloromethane (100 ml) a solution of methanesulfonic acid (1.59 mL, 20.3 mmol) in DCM (10 mL). When the reaction is complete, pour the mixture into ice water and extract the mixture with DCM. Combine the extracts, wash with 0.1N KHSO4, brine, dry over MgSO4 and concentrate under vacuum. Treat the residue with a mixture of isopropanol/heptane and collect the precipitate by filtration to obtain 2.91 g (74%) of solid, MS m/z=290 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([Cl:9])=[C:4]([Cl:10])[N:3]=1.[CH:11]([C:13]1[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][CH:14]=1)=[CH2:12].C(N(CC)C(C)C)(C)C>CC(C)=O>[CH:11]([C:13]1[CH:19]=[CH:18][C:16]([NH:17][C:6]2[C:5]([Cl:9])=[C:4]([Cl:10])[N:3]=[C:2]([Cl:1])[N:7]=2)=[CH:15][CH:14]=1)=[CH2:12]
Reactant: C=Cc1ccc(N)cc1
Reactant: Clc1nc(Cl)c(Cl)c(Cl)n1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)=O
Product: C=Cc1ccc(Nc2nc(Cl)nc(Cl)c2Cl)cc1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a solution of 21.8 g (0.1 moles) of 2,4,5,6-tetrachloropyrimidine in 150 ml of acetone being stirred at 0°-5° C. was added dropwise over a 1/2 hr. period a solution of 11.9 g (0.1 mole) of 4-vinylaniline and 12.9 g (0.1 mole) of N,N-di-iso-propylethylamine. After stirring for 2 hr. at room temperature, the product was isolated by pouring the reaction mixture into 1 of ice water. The solid was collected by filtration and dried in vacuo at room temperature to give 28 g. Recrystallization from a solution of 120 ml of benzene and 200 ml of ligroin gave 17.5 g (58%) (mp 112°-114°).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][OH:16])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[C:17]12[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=1)[NH:22]C(=O)O[C:18]2=[O:19].C1(C)C=CC=CC=1>CCOCC>[C:18]([O:16][CH2:15][CH2:14][N:11]1[CH2:10][CH2:9][N:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[CH2:13][CH2:12]1)(=[O:19])[C:17]1[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=1)[NH2:22]
Reactant: OCCN1CCN(c2cccc(Cl)c2)CC1
Reactant: O=c1[nH]c2ccccc2c(=O)o1
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: Nc1ccccc1C(=O)OCCN1CCN(c2cccc(Cl)c2)CC1
Yield: 70 %

Procedure:
7.2 G. (0.03 mol) of 2-(4-m-chlorophenyl-piperazino)-ethanol and 6.55 g. (0.04 mol) of isatoic anhydride in 125 ml. of toluene are refluxed for 3 hours. The hot toluene solution is filtered and the toluene is evaporated from the filtrate to give a residue which is taken up in ether in order to remove a small amount of unreacted isatoic anhydride, the solution is filtered and the ether is driven off. The remaining product is triturated in petroleum ether, filtered off and recrystallised twice from isopropyl alcohol to give 7.6 g. (yield = 70%) of 2-(4-m-chlorophenylpiperazino)-ethyl anthranilate, which melts at 76°C.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([O:11][CH2:12][CH2:13][O:14][CH3:15])[C:5]([N+:8]([O-:10])=[O:9])=[N:6][CH:7]=1.[CH3:16][S:17]([C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=1)(=[O:19])=[O:18].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH3:16][S:17]([C:20]1[CH:25]=[CH:24][C:23]([O:26][C:2]2[CH:3]=[C:4]([O:11][CH2:12][CH2:13][O:14][CH3:15])[C:5]([N+:8]([O-:10])=[O:9])=[N:6][CH:7]=2)=[CH:22][CH:21]=1)(=[O:18])=[O:19]
Reactant: CS(=O)(=O)c1ccc(O)cc1
Reactant: COCCOc1cc(Cl)cnc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COCCOc1cc(Oc2ccc(S(C)(=O)=O)cc2)cnc1[N+](=O)[O-]
Temperature: 120 °C
Yield: 15 %

Procedure:
5-Chloro-3-(2-methoxy-ethoxy)-2-nitro-pyridine (2.6 mmol) is dissolved in DMF (12 ml), 4-(methylsulfonyl)phenol (3 eq.) and K2CO3 (4 eq.) is added. The reaction is heated to 120° C. in the microwave for 45 min. The reaction solution is pored into water and extracted with Methyltert.-butyl ether. The combined organic layers are washed with brine, dried over MgSO4 and the solvent is removed in vacuo. 5-(4-Methanesulfonyl-phenoxy)-3-(2-methoxy-ethoxy)-2-nitro-pyridine is obtained after column chromatography (heptane/ethyl acetate) as yellow oil in a yield of 15%. HPLC (method C): 1.65 min; LC-MS (method A): 1.534 min, 369.1 (MH+).