Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:13][CH2:14][CH:15]([CH3:17])[CH3:16])=[C:7]([NH2:12])[CH:8]=[N:9]2)=[CH:4][CH:3]=1.[C:18](OC)(OC)(OC)[CH2:19][CH2:20][CH2:21][CH3:22]>Cl.N1C=CC=CC=1.C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:13]([CH2:14][CH:15]([CH3:17])[CH3:16])[C:18]([CH2:19][CH2:20][CH2:21][CH3:22])=[N:12][C:7]=3[CH:8]=[N:9][C:10]=2[CH:11]=1
Reactant: CC(C)CNc1c(N)cnc2cc(Br)ccc12
Reactant: CCCCC(OC)(OC)OC
Agent: Cl
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: CCCCc1nc2cnc3cc(Br)ccc3c2n1CC(C)C
Temperature: 25 °C
Yield: 43.9 %

Procedure:
7-Bromo-N4-isobutylquinoline-3,4-diamine (39.4 g of crude material), trimethyl orthovalerate (32 g, 0.20 mol), and pyridine hydrochloride (0.31 g, 2.7 mmol) were combined with anhydrous toluene (500 mL) and heated to reflux for 30 min. The reaction was cooled to room temperature, concentrated, and the residue was purified by chromatography on silica gel (75% ethyl acetate in hexane to 100% ethyl acetate gradient) to afford 21.2 g of 7-bromo-2-butyl-1-isobutyl-1H-imidazo[4,5-c]quinoline as a yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([S:9]([CH2:11][CH:12]([C:19](=[O:31])[N:20]([CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])=[O:10])[CH:5]=[CH:6][C:7]=1[Cl:8].ClC1C=CC=C(C(OO)=[O:40])C=1.S([O-])([O-])=O.[Na+].[Na+]>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([S:9]([CH2:11][CH:12]([C:19](=[O:31])[N:20]([CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])(=[O:40])=[O:10])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCCCCN(CCCCC)C(=O)C(CCC(=O)OC)CS(=O)c1ccc(Cl)c(Cl)c1
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: CCCCCN(CCCCC)C(=O)C(CCC(=O)OC)CS(=O)(=O)c1ccc(Cl)c(Cl)c1
Temperature: 0 °C
Yield: 102 %

Procedure:
Into a solution of methyl 5-(3,4-dichlorophenylsulfinyl)-4-(N,N-dipentylcarbamoyl)pentanoate (95 mg) in dry dichloromethane (10 ml) were added portions of m-chloroperbenzoic acid (80%, 51 mg) with stirring at 0° C. After stirring at room temperature for 2 hours, sodium sulfite was added. The reaction mixture was washed with a saturated sodium bicarbonate solution and water, dried over MgSO4, and concentrated in vacuo. The residue was recrystallized from hexane to give 100 mg of methyl 5-(3,4-dichlorophenylsulfonyl)-4-(N,N-dipentylcarbamoyl)pentanoate. The physical properties of this compound were identical to that of the compound which was prepared in example 1.
Reaction SMILES: S(Cl)(Cl)=O.[NH2:5][CH:6]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=1)[CH2:7][C:8]([OH:10])=[O:9].[CH3:18]O>>[NH2:5][CH:6]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=1)[CH2:7][C:8]([O:10][CH3:18])=[O:9]
Reactant: CO
Reactant: NC(CC(=O)O)c1cccc(Cl)c1
Solvent: O=S(Cl)Cl
Product: COC(=O)CC(N)c1cccc(Cl)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Methanol (110 ml) is cooled to −10° C. and slowly admixed with thionyl chloride (12.0 g, 101.2 mmol). 3-Amino-3-(3-chlorophenyl)propionic acid (10.1 g, 50.6 mmol) is added and the mixture is stirred at room temperature overnight. The solution is concentrated to a high extent, under reduced pressure, and partitioned between ethyl acetate (100 ml) and saturated sodium hydrogen carbonate solution (200 ml). The pH of the aqueous phase is above 7. The aqueous phase is again extracted twice with ethyl acetate (100 ml). The combined ethyl acetate phases are dried over sodium sulfate, filtered and concentrated.
Reaction SMILES: [C:1]([C:4]1[CH:17]=[CH:16][C:7]([O:8][CH2:9][CH:10]([CH3:15])[CH2:11][C:12]([OH:14])=O)=[C:6]([CH2:18][CH2:19][CH3:20])[C:5]=1[OH:21])(=[O:3])[CH3:2].[N:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][CH2:29][CH2:30][CH2:31][NH2:32])[CH:23]=1>>[C:1]([C:4]1[CH:17]=[CH:16][C:7]([O:8][CH2:9][CH:10]([CH3:15])[CH2:11][C:12]([NH:32][CH2:31][CH2:30][CH2:29][CH2:28][C:24]2[CH:23]=[N:22][CH:27]=[CH:26][CH:25]=2)=[O:14])=[C:6]([CH2:18][CH2:19][CH3:20])[C:5]=1[OH:21])(=[O:3])[CH3:2]
Reactant: NCCCCc1cccnc1
Reactant: CCCc1c(OCC(C)CC(=O)O)ccc(C(C)=O)c1O
Product: CCCc1c(OCC(C)CC(=O)NCCCCc2cccnc2)ccc(C(C)=O)c1O

Procedure:
4-(4-Acetyl-3-hydroxy-2-propylphenoxy)-3-methyl butanoic acid was allowed to react with 3-pyridinebutanamine according to procedure A and the product was purified by HPLC to give 4-(4-acetyl-3-hydroxy-2-propylphenoxy)-3-methyl-N-[4-(3-pyridinyl)butyl]-butanamide, the title compound, mp 58°-60° (from ethyl acetate-hexane) in 84% yield.
Reaction SMILES: [C@H:1]12[CH2:7][C@H:4]([NH:5][CH2:6]1)[CH2:3][N:2]2[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[NH:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[N:17]=[C:16]1[C:24](O)=[O:25].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>C(Cl)Cl.O>[NH:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[N:17]=[C:16]1[C:24]([N:5]1[CH2:6][C@@H:1]2[CH2:7][C@H:4]1[CH2:3][N:2]2[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[O:25]
Reactant: O=C(O)c1nc2ccccc2[nH]1
Reactant: CC(C)(C)OC(=O)N1C[C@@H]2C[C@H]1CN2
Agent: On1nnc2ccccc21
Solvent: O
Solvent: ClCCCl
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1C[C@@H]2C[C@H]1CN2C(=O)c1nc2ccccc2[nH]1
Temperature: 25 °C
Reaction time: 18 h
Yield: 63.1 %

Procedure:
A mixture of 1,1-dimethylethyl (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (18.3 g, 92.5 mmol), 1H-benzimidazole-2-carboxylic acid, (15.0 g, 92.5 mmol), EDC (21.3 g, 111 mmol), HOBt (2.5 g, 18.5 mmol), NMM (28 g, 277.5 mmol) in CH2Cl2 (250 mL) was stirred at room temperature for 18 h. The reaction was diluted with water and CH2Cl2 then washed with sat. NaHCO3 (200 mL) and brine (200 mL). The solution was dried over anhydrous Na2SO4 and concentrated to give a crude product which was purified by column chromatography on silica gel (petroleum ether/ethyl acetate: 2/1) to give the title compound (20 g) as a white solid. LCMS (m/z): 343.2 (M+H).
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[Br:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]=[CH:14][C:13]([N+:19]([O-:21])=[O:20])=[C:12]2[NH:22][C:23]1[CH:28]=[CH:27][C:26](F)=[CH:25][C:24]=1[Cl:30]>CS(C)=O>[Br:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]=[CH:14][C:13]([N+:19]([O-:21])=[O:20])=[C:12]2[NH:22][C:23]1[CH:28]=[CH:27][C:26]([N:5]2[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)=[CH:25][C:24]=1[Cl:30]
Reactant: O=[N+]([O-])c1cnc2ccc(Br)cc2c1Nc1ccc(F)cc1Cl
Reactant: CN1CCNCC1
Solvent: CS(C)=O
Product: CN1CCN(c2ccc(Nc3c([N+](=O)[O-])cnc4ccc(Br)cc34)c(Cl)c2)CC1
Temperature: 180 °C

Procedure:
5 ml of N-methylpiperazine are added to a solution of 600 mg (1.5 mmol) of (6-bromo-3-nitro-quinolin-4-yl)-(2-chloro-4-fluoro-phenyl)-amine (Example 63b) in 2 ml of DMSO. The reaction is heated at 180° C. for 1 h in a microwave oven (Emrys Optimizer, Personal Chemistry). After this time, the solution is concentrated to dryness and the crude compound is purified by preparative MPLC. Title compound: ES-MS: 476.3, 478.3, 480.3 (M+H)+; analytical HPLC: tret=4.28 minutes (Grad 2).
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1)[CH3:2].[CH2:10]1[O:12][CH2:11]1>[OH-].[Na+]>[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([O:9][CH2:10][CH2:11][OH:12])=[CH:5][CH:4]=1)[CH3:2]
Reactant: C1CO1
Reactant: CCc1ccc(O)cc1
Agent: [Na+]
Agent: [OH-]
Product: CCc1ccc(OCCO)cc1

Procedure:
p-Ethylphenol (854 parts) is ethoxylated with ethylene oxide (348 parts) using sodium hydroxide (7 parts) as catalyst at 145° C. in a method similar to that used in Example 12 to give 2-(p-ethylphenoxy)ethanol m.p. 48°-49° C. (987 parts).
Reaction SMILES: [OH:1][C@@H:2]1[CH2:7][C@H:6]2[C@H:8]3[C@H:18]([CH2:19][CH2:20][C@:4]2([CH3:5])[C@H:3]1[NH:22][CH3:23])[C@:16]1([CH3:17])[C@H:11]([CH2:12][C:13](=[O:21])[CH2:14][CH2:15]1)[CH2:10][CH2:9]3.[C:24]([O-:31])(=[O:30])/[CH:25]=[CH:26]\[C:27]([O-:29])=[O:28]>>[C:24]([OH:31])(=[O:30])/[CH:25]=[CH:26]\[C:27]([OH:29])=[O:28].[OH:1][C@@H:2]1[CH2:7][C@H:6]2[C@H:8]3[C@H:18]([CH2:19][CH2:20][C@:4]2([CH3:5])[C@H:3]1[NH:22][CH3:23])[C@:16]1([CH3:17])[C@H:11]([CH2:12][C:13](=[O:21])[CH2:14][CH2:15]1)[CH2:10][CH2:9]3
Reactant: O=C([O-])/C=C\C(=O)[O-]
Agent: CN[C@H]1[C@H](O)C[C@H]2[C@@H]3CC[C@H]4CC(=O)CC[C@]4(C)[C@H]3CC[C@@]21C
Product: O=C(O)/C=C\C(=O)O

Procedure:
A sample of 16α-hydroxy-17β-methylamino-5α-androstan-3-one was converted to the maleate, which was crystallised from methylene dichloride-acetone to give pure 16α-hydroxy-17β-methylamino-5α-androstan-3-one maleate as prisms, m.p. 204°-207° C., [α]DDMSO +8° (C 1.0).
Reaction SMILES: [O:1]=[C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:5][CH:4]([C:14]([O:16]C)=O)[CH2:3]1.[CH2:18]([NH2:20])[CH3:19]>CO>[CH2:18]([NH:20][C:14]([CH:4]1[CH2:3][C:2](=[O:1])[N:6]([CH2:7][C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:5]1)=[O:16])[CH3:19]
Reactant: COC(=O)C1CC(=O)N(Cc2ccccc2)C1
Reactant: CCN
Solvent: CO
Product: CCNC(=O)C1CC(=O)N(Cc2ccccc2)C1
Temperature: 100 °C
Yield: 49.4 %

Procedure:
A mixture of 200 g (0.86 mole) of methyl 5-oxo-1-(phenylmethyl)-3-pyrrolidinecarboxylate [J. Org. Chem., 26, 1519 (1961)], 1000 ml methanol and 200 g (4.4 mole) of ethylamine was heated at 100° C. in a pressure reactor for 17.2 hours. The reaction mixture was cooled and the excess ethylamine and methanol were removed under reduced pressure. The residue was taken up in dichloromethane and washed with 3×150 ml 1N sodium hydroxide. The organic layer was dried over magnesium sulfate and the solvent removed at reduced pressure to give 104.6 g of N-ethyl-5-oxo-1-(phenylmethyl)- 3-pyrrolidinecarboxamide as a white solid, mp 97°-99° C.
Reaction SMILES: [CH2:1]([C:5]1[N:6]=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)[S:8][C:9]=1[CH2:10]O)[CH2:2][CH2:3][CH3:4].C(N(CC)CC)C.CS([Cl:33])(=O)=O>ClCCl>[CH2:1]([C:5]1[N:6]=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)[S:8][C:9]=1[CH2:10][Cl:33])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc(-c2ccc(C(F)(F)F)cc2)sc1CO
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCc1nc(-c2ccc(C(F)(F)F)cc2)sc1CCl
Temperature: 25 °C
Reaction time: 3 h

Procedure:
1.0 g [4-Butyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-yl]-methanol were dissolved in 50 ml dichloromethane, 0.88 ml triethylamine and 0.39 ml methanesulfonyl chloride were added. The reaction mixture was stirred at room temperature for a period of three hours then 100 ml of dichloromethane were added and the reaction mixture washed with 50 ml of saturated NaHCO3 solution , water and brine. The organic layer was dried over MgSO4 and the solvent removed under reduced pressure. This provided 1.0 g 4-Butyl-5-chloromethyl-2-(4-trifluoromethyl-phenyl)-thiazole as yellow oil.
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]1[CH:7]=[CH:8][C:9]2[O:14][CH2:13][C:12](=[O:15])[NH:11][C:10]=2[CH:16]=1)=[O:4].[CH2:17]([CH:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C(OCC)C>[CH2:17]([CH:24]1[CH2:29][CH2:28][N:27]([CH2:2][C:3]([NH:5][C:6]2[CH:7]=[CH:8][C:9]3[O:14][CH2:13][C:12](=[O:15])[NH:11][C:10]=3[CH:16]=2)=[O:4])[CH2:26][CH2:25]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: O=C(CCl)Nc1ccc2c(c1)NC(=O)CO2
Reactant: c1ccc(CC2CCNCC2)cc1
Solvent: CCOCC
Product: O=C(CN1CCC(Cc2ccccc2)CC1)Nc1ccc2c(c1)NC(=O)CO2

Procedure:
The title compound is prepared from 2-chloro-N-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-acetamide and 4-benzyl-piperidine according to the method described in Example 142b. Melting Point: 220-222° C. (diethylether)
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][CH3:21])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[N:4][CH:3]=1.[F:22][C:23]1[CH:29]=[C:28]([CH3:30])[C:27]([OH:31])=[CH:26][C:24]=1[NH2:25].Cl>CC(O)CCC.C(O)(C)C>[F:22][C:23]1[CH:29]=[C:28]([CH3:30])[C:27]([OH:31])=[CH:26][C:24]=1[NH:25][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][CH3:21])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[N:4][CH:3]=1
Reactant: Cc1cc(F)c(N)cc1O
Reactant: COCCOCCOc1cc2nncc(Cl)c2cc1OC
Agent: Cl
Solvent: CC(C)O
Solvent: CCCC(C)O
Product: COCCOCCOc1cc2nncc(Nc3cc(O)c(C)cc3F)c2cc1OC

Procedure:
A solution of 4-chloro-6-methoxy-7-[2-(2-methoxyethoxy)ethoxy]cinnoline (130 mg, 0.41 mmol) and 2-fluoro-5-hydroxy-4-methylaniline (70 mg, 0.5 mmol), (prepared as described for the starting material in Example 11), in 2-pentanol (3 ml) containing 5M hydrogen chloride in isopropanol (2drops) was heated at reflux for 45 minutes. After cooling the solid was filtered off, washed with isopropanol followed by ether to give 4-(2-fluoro-5-hydroxy-4-methylanilino)-6-methoxy-7-[2-(2-methoxyethoxy)ethoxy]cinnoline as an hydrochloride salt (159 mg, 88%).
Reaction SMILES: [C:1]([N:4]=[C:5]=[S:6])(=[O:3])[CH3:2].[CH2:7]([N:11]1[C:16]([NH:17][NH2:18])=[CH:15][C:14](=[O:19])[N:13]([CH2:20][CH2:21][CH3:22])[C:12]1=[O:23])[CH2:8][CH2:9][CH3:10]>O1CCOCC1>[C:1]([NH:4][C:5](=[S:6])[NH:18][NH:17][C:16]1[N:11]([CH2:7][CH2:8][CH2:9][CH3:10])[C:12](=[O:23])[N:13]([CH2:20][CH2:21][CH3:22])[C:14](=[O:19])[CH:15]=1)(=[O:3])[CH3:2]
Reactant: CCCCn1c(NN)cc(=O)n(CCC)c1=O
Reactant: CC(=O)N=C=S
Solvent: C1COCCO1
Product: CCCCn1c(NNC(=S)NC(C)=O)cc(=O)n(CCC)c1=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 123.2 %

Procedure:
Acetylisothiocyanate(4.8 g) was added dropwise to a stirred solution of 1-butyl-6-hydrazino-3-propylpyrimidine-2,4(1H,3H)-dione(8.0 g) in dioxane(100 ml). The mixture was stirred for 3 hours at room temperature, then precipitating crystals were collected by filtration. Recrystallization from aqueous alcohol gave colorless crystals (14 g, 94%), m.p. 149°-152° C.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][OH:8])[CH2:3][CH2:2]1.Cl[C:10]([O:12][CH2:13][CH3:14])=[O:11].C(N(CC)CC)C>ClCCl>[OH:8][CH2:7][CH:4]1[CH2:5][CH2:6][N:1]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:2][CH2:3]1
Reactant: CCOC(=O)Cl
Reactant: OCC1CCNCC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)N1CCC(CO)CC1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 96 %

Procedure:
1.0 eq 4-piperidinemethanol (10.00 g, 86.8 mmol) was dissolved in dichloromethane (350 mL), cooled in an ice-H2O bath and treated dropwise with a solution of 1.05 eq ethyl chloroformate (9.89 g, 91.1 mmol) in dichloromethane (50 mL), followed by the dropwise addition of a solution of 1.0 eq triethylamine (8.78 g) in dichloromethane (50 mL). The reaction was stirred at ≈0° C. for 15 minutes, then at room temperature for 10 minutes. The reaction was diluted with dichloromethane (250 mL) and washed successively with (150 mL each) H2O, 0.1 N HCl (aq) (×2), saturated brine, then dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo to afford 15.60 g ethyl 4-(hydroxymethyl)-piperidine-1-carboxylate as a viscous, pale bluish-green oil. 1H-NMR (400 MHz, CDCl3) δ 4.15 (br m, 2H), 4.09 (q, J=7.1 Hz, 2H), 3.46 (d, J=6.4 Hz, 2H), 2.72 (br t, J=12.4 Hz, 2H), 2.07 (s, 1H), 1.70 (m, 2H), 1.63 (m, 1H), 1.23 (t, J=7.2 Hz, 3H), 1.12 (m, 2H); LC/MS [M+H]+ m/z 188.0, retention time 1.56 min (10-99% CH3CN—H2O gradient, with 0.1% TFA, 5 min).
Reaction SMILES: [N:1]1([CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([NH2:16])=[C:12]([N+:17]([O-])=O)[CH:11]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1>CCO.[Pd]>[N:1]1([CH2:7][CH2:8][O:9][C:10]2[CH:11]=[C:12]([NH2:17])[C:13]([NH2:16])=[CH:14][CH:15]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1
Reactant: Nc1ccc(OCCN2CCOCC2)cc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCO
Product: Nc1ccc(OCCN2CCOCC2)cc1N
Reaction time: 18 h

Procedure:
To a solution 4-(2-morpholin-4-ylethoxy)-2-nitrophenylamine (1.0 eq) in EtOH was added Pd/C (0.1 eq). The reaction vessel was repeatedly purged with nitrogen, then stirred under a hydrogen atmosphere (1 atm) for 18 hours. The product was filtered through a Celite plug, and the plug washed with EtOH. The diamine was used without purification. LC/MS m/z 238.3 (MH+), Rt 0.295 minutes.
Reaction SMILES: C([O:8][C:9](=[O:22])[C:10]1[CH:15]=[CH:14][C:13]([N:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)=[CH:12][CH:11]=1)C1C=CC=CC=1.Cl[C:24]1[CH:40]=[CH:39][C:27]([C:28]([NH:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)=[O:29])=[CH:26][N:25]=1.C1(NC(C2C=CC(N3CCN(C4C=CC(C(O)=O)=CC=4)CC3)=NC=2)=O)C=CC=CC=1>>[CH3:38][O:37][C:34]1[CH:33]=[CH:32][C:31]([NH:30][C:28]([C:27]2[CH:39]=[CH:40][C:24]([N:19]3[CH2:18][CH2:17][N:16]([C:13]4[CH:12]=[CH:11][C:10]([C:9]([OH:8])=[O:22])=[CH:15][CH:14]=4)[CH2:21][CH2:20]3)=[N:25][CH:26]=2)=[O:29])=[CH:36][CH:35]=1
Reactant: COc1ccc(NC(=O)c2ccc(Cl)nc2)cc1
Reactant: O=C(OCc1ccccc1)c1ccc(N2CCNCC2)cc1
Agent: O=C(O)c1ccc(N2CCN(c3ccc(C(=O)Nc4ccccc4)cn3)CC2)cc1
Product: COc1ccc(NC(=O)c2ccc(N3CCN(c4ccc(C(=O)O)cc4)CC3)nc2)cc1

Procedure:
4-{4-[5-(4-Methoxy-phenylcarbamoyl)-pyridin-2-yl]-piperazin-1-yl}-benzoic acid was prepared from 4-piperazin-1-yl-benzoic acid benzyl ester and 6-chloro-N-(4-methoxy-phenyl)-nicotinamide with a method similar to the one described in the synthesis of 4-[4-(5-phenylcarbamoyl-pyridin-2-yl)-piperazin-1-yl]-benzoic acid above. HRMS m/z calcd for C24H24N4O4 [M+H]+: 433.1871. Found: 433.1870.
Reaction SMILES: [OH2:1].C([C:14]1[CH:19]=[CH:18][CH:17]=CC=1S(O)(=O)=O)CCCCCCCCCCC.[CH3:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][N:32]1[S:37][C:36]([Cl:38])=[C:35]([Cl:39])[C:33]1=[O:34]>O.C1(OCC(O)C)C=CC=CC=1>[CH3:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][N:32]1[S:37][C:36]([Cl:38])=[C:35]([Cl:39])[C:33]1=[O:34].[CH3:14][CH2:19][CH2:18][CH2:17][O:34][CH2:33][CH2:35][OH:1]
Reactant: CCCCCCCCCCCCc1ccccc1S(=O)(=O)O
Reactant: O
Agent: CCCCCCCCn1sc(Cl)c(Cl)c1=O
Solvent: CC(O)COc1ccccc1
Product: CCCCOCCO
Reaction time: 0.33 h

Procedure:
3000 g of treatment solution was prepared by diluting 90 g (50% solids) of polymer with 2000 g of tap water containing 3 drops of Tego Foamex 805 defoamer with stirring for 20 minutes. (Tap water optionally containing additional surfactant, such as a metal salt of dodecylbenzene sulfonic acid or an alkyl ethoxylate) (0.06%) To the well stirred solution was slowly added 22.5 g (20% DCOIT dissolved in propylene glycol phenyl ether with 0.04% PG, for a final concentration of 1500 ppm DCOIT). Tap water was added to make 3000 g of total solution and the solution was stirred for 60 minutes, and used as is to treat wood.
Reaction SMILES: [O:1]=[C:2]1[C:11]([CH:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C@@H:21]([C:32]([OH:34])=O)[CH2:22][C:23]3[CH:28]=[C:27]([CH3:29])[C:26]([OH:30])=[C:25]([CH3:31])[CH:24]=3)=[O:19])[CH2:14][CH2:13]2)=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[NH:3]1.[O:35]1[CH2:40][CH2:39][CH:38]([N:41]2[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]2)[CH2:37][CH2:36]1>>[O:1]=[C:2]1[C:11]([CH:12]2[CH2:13][CH2:14][N:15]([C:18]([O:20][C@H:21]([CH2:22][C:23]3[CH:28]=[C:27]([CH3:29])[C:26]([OH:30])=[C:25]([CH3:31])[CH:24]=3)[C:32](=[O:34])[N:44]3[CH2:43][CH2:42][N:41]([CH:38]4[CH2:39][CH2:40][O:35][CH2:36][CH2:37]4)[CH2:46][CH2:45]3)=[O:19])[CH2:16][CH2:17]2)=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[NH:3]1
Reactant: C1CN(C2CCOCC2)CCN1
Reactant: Cc1cc(C[C@@H](OC(=O)N2CCC(c3cc4ccccc4[nH]c3=O)CC2)C(=O)O)cc(C)c1O
Product: Cc1cc(C[C@@H](OC(=O)N2CCC(c3cc4ccccc4[nH]c3=O)CC2)C(=O)N2CCN(C3CCOCC3)CC2)cc(C)c1O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Prepared analogously to Example 8i from 80.0 mg (0.17 mmol) (R)-2-(4-hydroxy-3,5-dimethyl-phenyl)-1-carboxy-ethyl 4-(2-oxo-1,2-dihydro-quinolin-3-yl)-piperidine-1-carboxylate and 29.2 mg (0.17 mmol) 1-(tetrahydropyran-4-yl)-piperazine, the reaction mixture being stirred overnight at RT.
Reaction SMILES: COC1C=C2C(C(OC3CC4N(C(=O)CCCCCCC=CC5C(C(O)=O)(NC4=O)C5)C3)=CC(C3SC=CN=3)=N2)=CC=1.C([C:46]1[N:47]=[C:48]([C:51]2[CH:60]=[C:59]([O:61][CH:62]3[CH2:80][CH:79]4[N:64]([C:65](=[O:91])[CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH:72]=[CH:73][CH:74]5[C:76]([C:82]([NH:84][S:85]([CH:88]6[CH2:90][CH2:89]6)(=[O:87])=[O:86])=[O:83])([NH:77][C:78]4=[O:81])[CH2:75]5)[CH2:63]3)[C:58]3[C:53](=[CH:54][C:55]([O:92][CH3:93])=[CH:56][CH:57]=3)[N:52]=2)[S:49][CH:50]=1)(C)C>>[CH3:93][O:92][C:55]1[CH:54]=[C:53]2[C:58]([C:59]([O:61][CH:62]3[CH2:80][CH:79]4[N:64]([C:65](=[O:91])[CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH:72]=[CH:73][CH:74]5[C:76]([C:82]([NH:84][S:85]([CH:88]6[CH2:90][CH2:89]6)(=[O:86])=[O:87])=[O:83])([NH:77][C:78]4=[O:81])[CH2:75]5)[CH2:63]3)=[CH:60][C:51]([C:48]3[S:49][CH:50]=[CH:46][N:47]=3)=[N:52]2)=[CH:57][CH:56]=1
Reactant: COc1ccc2c(OC3CC4C(=O)NC5(C(=O)NS(=O)(=O)C6CC6)CC5C=CCCCCCCC(=O)N4C3)cc(-c3nc(C(C)C)cs3)nc2c1
Agent: COc1ccc2c(OC3CC4C(=O)NC5(C(=O)O)CC5C=CCCCCCCC(=O)N4C3)cc(-c3nccs3)nc2c1
Product: COc1ccc2c(OC3CC4C(=O)NC5(C(=O)NS(=O)(=O)C6CC6)CC5C=CCCCCCCC(=O)N4C3)cc(-c3nccs3)nc2c1

Procedure:
The title compound was prepared from 18-[7-methoxy-2-(thiazol-2-yl)quinolin-4-yloxy]-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid (31) following the procedure reported for synthesis of N-[[18-[2-[4-(isopropyl)thiazol-2-yl]-7-methoxyquinolin-4-yloxy]-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-en-4-yl]carbonyl](cyclopropyl)sulfonamide 11: m/z=694 (M+H)+. 1H NMR (CDCl3): 0.90-1.5 (m, 9H), 1.6-1.8 (m, 8H), 2.1-2.4 (m, 2H), 2.45-2.55 (m, 2H), 2.6-2.7 (m, 1H), 2.9-3 (m, 1H), 3.9 (s, 3H), 4.12 (dd, J=11.6 Hz, J=3.7 Hz, 1H), 5.1 (t, J=7.9 Hz, 1H), 5.00 (t, J=9 Hz, 1H), 5.48 (t, J=2.9 Hz, 1H), 5.7 (dd, J=18.2 Hz, J=8.8 Hz, 1H), 7 (br s, 1H), 7.15 (dd, J=9.1 Hz, J=2.4 Hz, 1H), 7.4 (d, J=2.4 Hz, 1H), 7.5 (d, J=3.2 Hz, 1H), 7.59 (s, 1H), 7.9 (d, J=3.2 Hz, 1H), 7.9 (d, J=9.1 Hz, 1H), 10.3 (br s, 1H).
Reaction SMILES: Cl.[NH2:2][C:3](=NO)[C:4]1[CH:5]=[C:6]([CH:19]=[C:20]([N:22]([CH3:27])[S:23]([CH3:26])(=[O:25])=[O:24])[CH:21]=1)[C:7]([NH:9][C@@H:10]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)[CH3:11])=[O:8].[CH3:30][CH2:31][OH:32]>C(Cl)Cl>[CH2:31]([O:32][C:3]([C:4]1[CH:21]=[C:20]([N:22]([CH3:27])[S:23]([CH3:26])(=[O:25])=[O:24])[CH:19]=[C:6]([C:7]([NH:9][C@@H:10]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH3:11])=[O:8])[CH:5]=1)=[NH:2])[CH3:30]
Reactant: CCO
Reactant: C[C@@H](NC(=O)c1cc(C(N)=NO)cc(N(C)S(C)(=O)=O)c1)c1ccc(F)cc1
Agent: Cl
Solvent: ClCCl
Product: CCOC(=N)c1cc(C(=O)N[C@H](C)c2ccc(F)cc2)cc(N(C)S(C)(=O)=O)c1
Temperature: 0 °C
Reaction time: 2.5 h

Procedure:
Gaseous HCl was bubbled through a solution of 3-[-amino(hydroxyimino)methyl]-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzamide (0.038 g, 0.090 mmol) (Intermediate XI) in 1 mL CH2Cl2 and 1 mL EtOH at 0° C. for 2 min. After stirring at 0° C. for 2.5 h, the reaction was warmed to rt for 18 h. Concentrated, redissolved residue in 4 mL Et2O, cooled to 0° C. and bubbled ammonia through reaction for 1 min. Concentrated and used without further purification for next step.
Reaction SMILES: [NH2:1][C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:9])[NH2:8].[C:13](Cl)(=[O:25])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24].[OH-].[Na+].S(=O)(=O)(O)O>O.C(O)(C)(C)C>[C:13]([NH:1][C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:8])[NH2:9])(=[O:25])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]
Reactant: CCCCCCCCCCCC(=O)Cl
Reactant: N=C(N)NCCC[C@H](N)C(=O)O
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)(C)O
Solvent: O
Product: CCCCCCCCCCCC(=O)N[C@@H](CCCNC(=N)N)C(=O)O
Temperature: 12.5 °C
Yield: 89.9 %

Procedure:
L-Arginine (50 g) was added with t-butyl alcohol (315 g) and water (125 g). The reaction mixture was added dropwise with lauroyl chloride (69 g) and 27 wt % aqueous sodium hydroxide (50 g) over 1 hour and 20 minutes, while the system was maintained at 10 to 15° C. and pH 10 to 11. After the addition, the reaction mixture was warmed to 45° C., added with sulfuric acid (17 g) and uniformly dissolved. Then, the system was adjusted to pH 4.9 with further addition of 27 wt % aqueous sodium hydroxide. The deposited crystals were collected by filtration and washed with water to obtain white crystals (92 g, yield: 90%).