Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].C(OC([C:12]1[CH:22]=[CH:21][CH:20]=[C:14]2[C:15]([NH:17][C:18](=[O:19])[C:13]=12)=[O:16])=O)C.Cl.N[CH2:25][CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]1[OH:32]>O>[OH:32][C@H:27]1[CH2:28][CH2:29][CH2:30][CH2:31][C@H:26]1[CH2:25][N:17]1[C:18](=[O:19])[C:13]2[C:14](=[CH:20][CH:21]=[CH:22][CH:12]=2)[C:15]1=[O:16]
Reactant: NCC1CCCCC1O
Reactant: CCOC(=O)c1cccc2c1C(=O)NC2=O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: O=C1c2ccccc2C(=O)N1C[C@@H]1CCCC[C@@H]1O
Reaction time: 3 h
Yield: 74.5 %

Procedure:
Under a nitrogen atmosphere, potassium carbonate (375 mg, 2.72 mmol) and ethoxycarbonylphthalimide (364 mg, 1.66 mmol) were added to an aqueous solution (4 ml) of 2-aminomethylcyclohexanol hydrochloride (250 mg, 1.51 mmol) at room temperature. After 3 hours, the reaction solution was poured into water and extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. The organic layer dried was concentrated under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate) to obtain cis-2-[(2-hydroxycyclohexyl)methyl]-1H-isoindole-1,3(2H)-dione (291.6 mg, 75%).
Reaction SMILES: [CH3:1][N:2]1[N:6]=[N:5][C:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH2:23][C@H:22]([CH2:24][O:25]S(C)(=O)=O)[O:21][C:20]4=[O:30])=[CH:15][C:14]=3[F:31])=[CH:9][N:8]=2)=[N:3]1.[CH3:32][O-].[Na+]>CO>[CH3:1][N:2]1[N:6]=[N:5][C:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH2:23][C@H:22]([CH2:24][O:25][CH3:32])[O:21][C:20]4=[O:30])=[CH:15][C:14]=3[F:31])=[CH:9][N:8]=2)=[N:3]1
Reactant: Cn1nnc(-c2ccc(-c3ccc(N4C[C@H](COS(C)(=O)=O)OC4=O)cc3F)cn2)n1
Reactant: C[O-]
Agent: [Na+]
Solvent: CO
Product: COC[C@H]1CN(c2ccc(-c3ccc(-c4nnn(C)n4)nc3)c(F)c2)C(=O)O1
Temperature: 25 °C
Reaction time: 24 h
Yield: 58.3 %

Procedure:
In 10 ml of methanol was dissolved 400 mg of (R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-methansulfonyloxymethyl oxazolidin-2-on prepared in the secondary step of the Example 24. The solution was added with 90 mg of sodium methoxide at room temperature and then stirred for one day at room temperature. The solution was extracted with ethyl acetate and the organic layer, thus separated, was washed with water and brine. The organic layer was dehydrated, filtered, concentrated in vacuo and purified by column chromatography to provide the title compound 200 mg. Yield 58%.
Reaction SMILES: [CH2:1]([NH:3][C:4](=[O:11])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH3:2].[CH3:12][Si:13](Cl)([CH3:15])[CH3:14]>>[CH2:1]([NH:3][C:4](=[O:11])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[Si:13]([CH3:15])([CH3:14])[CH3:12])[CH3:2]
Reactant: CCNC(=O)c1ccccc1
Reactant: C[Si](C)(C)Cl
Product: CCNC(=O)c1ccccc1[Si](C)(C)C
Yield: 68.3 %

Procedure:
N-Ethylbenzamide (74.5 g, 500 mmol) and TMSCl (135.8 g, 1.25 mol) were combined according to General Method C and purified by HPLC with 1:4 ethyl acetate/hexanes to afford 75.59 g of the title compound, as a white solid, a 68% yield. m.p. 64.0-66.0° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([NH2:9])=[CH:7][C:6]([C:10]#[C:11][C:12]2[C:13]([CH3:24])=[N:14][CH:15]=[N:16][C:17]=2[N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[CH:5][N:4]=1.[Cl:25][C:26]1[S:30][C:29]([S:31](Cl)(=[O:33])=[O:32])=[CH:28][CH:27]=1.N1C=CC=CC=1.O>C(Cl)Cl>[Cl:25][C:26]1[S:30][C:29]([S:31]([NH:9][C:8]2[C:3]([O:2][CH3:1])=[N:4][CH:5]=[C:6]([C:10]#[C:11][C:12]3[C:13]([CH3:24])=[N:14][CH:15]=[N:16][C:17]=3[N:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)[CH:7]=2)(=[O:33])=[O:32])=[CH:28][CH:27]=1
Reactant: COc1ncc(C#Cc2c(C)ncnc2N2CCOCC2)cc1N
Reactant: O=S(=O)(Cl)c1ccc(Cl)s1
Solvent: ClCCl
Solvent: c1ccncc1
Solvent: O
Product: COc1ncc(C#Cc2c(C)ncnc2N2CCOCC2)cc1NS(=O)(=O)c1ccc(Cl)s1
Temperature: 25 °C

Procedure:
To 100 mg (0.31 mmol) 2-Methoxy-5-(4-methyl-6-morpholin-4-yl-pyrimidin-5-ylethynyl)-pyridin-3-ylamine (E-9) in 5 mL DCM is added 112 mg (0.61 mmol) 5-chloro-thiophen-2-sulfonyl chloride and 72 μL (0.97 mmol) pyridine and the reaction mixture is stirred over night at RT. Water (2 mL) is added, the mixture is shaken for five minutes, the aqueous phase is separated and is extracted three times with 4 mL DCM. The combined organic phases are dried over MgSO4 and concentrated under reduced pressure. The crude product is purified by RP chromatography (C18, 20-80% ACN in water containing 1% formic acid). Yield: 101 mg (65%). HPLC-MS: M+H=506/508; tR=0.91 min.
Reaction SMILES: [CH2:1]([CH2:4][CH:5]([OH:14])[C:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:7])[CH:2]=[CH2:3].[OH-].[K+].CO.Cl>C(O)CCC>[OH:14][CH:5]([CH2:4][CH:1]=[CH:2][CH3:3])[C:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:7]
Reactant: C=CCCC(O)C(=O)c1ccccc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCCCO
Solvent: CO
Product: CC=CCC(O)C(=O)c1ccccc1
Temperature: 0 °C
Yield: 45.1 %

Procedure:
Then to 233 grams of 3-allyl-2-hydroxypropiophenone are added 212 grams of potassium hydroxide, 200 ml of methanol and 1100 ml of n-butanol and the mixture is heated to reflux for twenty four hours. It is then poured into ice water, acidified with concentrated hydrochloric acid, crystals separated out therefrom are collected by filtration, washed with water and recrystallized from methanol to give 105 grams of 2-hydroxy-3-propenylpropiophenone, yellow needles, melting point 83° to 85° C.
Reaction SMILES: [ClH:1].Cl.[Br:3][C:4]1[CH:5]=[C:6]([O:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:7]([NH:10][C:11]2[S:12][CH:13]=[C:14]([CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[N:15]=2)=[N:8][CH:9]=1.C(N(CC)CC)C.[C:36](OC(=O)C)(=[O:38])[CH3:37].C([O-])(O)=O.[Na+].Cl>C1COCC1>[ClH:1].[Br:3][C:4]1[CH:5]=[C:6]([O:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:7]([NH:10][C:11]2[S:12][CH:13]=[C:14]([CH:16]3[CH2:21][CH2:20][N:19]([C:36](=[O:38])[CH3:37])[CH2:18][CH2:17]3)[N:15]=2)=[N:8][CH:9]=1
Reactant: Brc1cnc(Nc2nc(C3CCNCC3)cs2)c(Oc2ccccc2)c1
Reactant: CC(=O)OC(C)=O
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(=O)N1CCC(c2csc(Nc3ncc(Br)cc3Oc3ccccc3)n2)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 58.7 %

Procedure:
A 20 mL vial was charged with 5-bromo-3-phenoxy-N-(4-(piperidin-4-yl)thiazol-2-yl)pyridin-2-amine dihydrochloride (80 mg, 0.159 mmol), triethylamine (0.088 mL, 0.64 mmol) and THF (2 mL). Acetic anhydride (0.015 mL, 0.16 mmol) was added and stirred at ambient temperature for 30 minutes. The reaction was poured into saturated aqueous NaHCO3 and extract with EtOAc (2×20 mL). The organic layer was dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel (5% methanol in EtOAc) to afford the title compound (47.6 mg, 58.8% yield) as a white solid after HCl salt formation. 1H NMR (d6-DMSO) δ 11.00 (bs, 1H), 8.23 (d, 1H), 7.44 (m, 2H), 7.40 (d, 1H), 7.21 (t, 1H), 7.11 (d, 2H), 6.70 (s, 1H), 4.41 (d, 1H), 3.12 (m, 1H), 2.83 (tt, 1H), 2.62 (td, 1H), 2.50 (m, 1H), 2.00 (s, 3H), 1.93 (m, 2H), 1.55 (qd, 1H), 1.42 (qd, 1H). Mass spectrum (apci) m/z=475.2 (M+H—HCl).
Reaction SMILES: Cl[C:2]1[N:3]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[C:4](=[O:11])[C:5]2[N:10]=[CH:9][S:8][C:6]=2[N:7]=1.[F:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[OH:27].CO>C(Cl)Cl>[F:19][C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[O:27][C:2]1[N:3]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[C:4](=[O:11])[C:5]2[N:10]=[CH:9][S:8][C:6]=2[N:7]=1
Reactant: O=c1c2ncsc2nc(Cl)n1-c1ccc(F)cc1
Reactant: Oc1ccc(F)cc1F
Solvent: ClCCl
Solvent: CO
Product: O=c1c2ncsc2nc(Oc2ccc(F)cc2F)n1-c1ccc(F)cc1
Temperature: 140 °C
Reaction time: 48 h

Procedure:
5-Chloro-6-(4-fluorophenyl)[1,3]thiazolo[5,4-d]pyrimidin-7(6H)-one (0.2 mmol) and 2.4-difluorophenol (0.4 mmol) are added to a vial, and the sealed mixture is heated with stirring at 140° C. for 48 h. Silica gel column chromatography (MeOH:CH2Cl2=0.5:99.5) gives the title compound as a slightly yellow solid. 1H NMR (400 MHz, CDCl3) 8.70 (1H, s), 7.36 (2H, m), 7.26 (2H, m), 7.14 (1H, m), 6.94 (2H, m). MS (M+1): 376.03; RT=1.33 min.
Reaction SMILES: COC(=O)[C:4]1[C:9]([NH:10][NH:11][C:12](OC(C)(C)C)=[O:13])=[CH:8][C:7]([F:19])=[C:6]([F:20])[C:5]=1[NH:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[Cl:28].C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:28][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[NH:21][C:5]1[C:6]([F:20])=[C:7]([F:19])[CH:8]=[C:9]2[C:4]=1[C:12](=[O:13])[NH:11][NH:10]2
Reactant: COC(=O)c1c(NNC(=O)OC(C)(C)C)cc(F)c(F)c1Nc1ccccc1Cl
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=c1[nH][nH]c2cc(F)c(F)c(Nc3ccccc3Cl)c12
Reaction time: 2 h

Procedure:
6-(N′-tert-Butoxycarbonylhydrazino)-2-(2-chlorophenylamino)-3,4-difluorobenzoic acid methyl ester (1.00 equivalent) is treated with a 1:1 mixture of methylene chloride and TFA and stirred for 2 hours The reaction mixture is concentrated under reduced pressure and the product is purified by trituration or flash column chromatography if needed.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:33]=[CH:34][C:35]=1[Cl:36])[CH2:5][CH:6]1[CH2:11][CH2:10][N:9]([CH2:12][C@H:13]([NH:17][C:18]([NH:20][C:21]2[CH:26]=[C:25]([O:27][CH3:28])[C:24]([O:29][CH3:30])=[C:23]([O:31][CH3:32])[CH:22]=2)=[O:19])[CH:14]([CH3:16])[CH3:15])[CH2:8][CH2:7]1.[I:37][CH2:38][CH3:39]>>[I-:37].[Cl:1][C:2]1[CH:3]=[C:4]([CH:33]=[CH:34][C:35]=1[Cl:36])[CH2:5][CH:6]1[CH2:7][CH2:8][N+:9]([CH2:38][CH3:39])([CH2:12][CH:13]([NH:17][C:18]([NH:20][C:21]2[CH:26]=[C:25]([O:27][CH3:28])[C:24]([O:29][CH3:30])=[C:23]([O:31][CH3:32])[CH:22]=2)=[O:19])[CH:14]([CH3:16])[CH3:15])[CH2:10][CH2:11]1
Reactant: CCI
Reactant: COc1cc(NC(=O)N[C@@H](CN2CCC(Cc3ccc(Cl)c(Cl)c3)CC2)C(C)C)cc(OC)c1OC
Product: CC[N+]1(CC(NC(=O)Nc2cc(OC)c(OC)c(OC)c2)C(C)C)CCC(Cc2ccc(Cl)c(Cl)c2)CC1
Product: [I-]

Procedure:
A solution of 1-{1-(R)-[4-(3,4-dichlorobenzyl)piperidin-1-ylmethyl]-2-methylpropyl}-3-(3,4,5-trimethoxyphenyl)urea (0.19 g, 0.353 mmoles) in iodoethane (4 ml) was stirred overnight at 68° C. degrees under argon. The yellow mixture was concentrated in vacuo and the crude product was flash chromatographed, eluting with 3%-4% methanol/methylene chloride to give 4-(3,4-dichlorobenzyl)-1-ethyl-1-{3-methyl-2-[3-(3,4,5-trimethoxyphenyl)ureido]butyl}piperidinium iodide (0.18 g) as a yellow solid.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[CH:13]=[CH:14][CH:15]=[C:16]3[C:20]=2[NH:19][C:18]([C:21]([O:23]CC)=[O:22])=[CH:17]3)(=[O:10])=[O:9])=[CH:4][CH:3]=1.CO.[OH-].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[CH:13]=[CH:14][CH:15]=[C:16]3[C:20]=2[NH:19][C:18]([C:21]([OH:23])=[O:22])=[CH:17]3)(=[O:9])=[O:10])=[CH:4][CH:3]=1
Reactant: CCOC(=O)c1cc2cccc(NS(=O)(=O)c3ccc(C)cc3)c2[nH]1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: Cc1ccc(S(=O)(=O)Nc2cccc3cc(C(=O)O)[nH]c23)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 95.1 %

Procedure:
To a mixed solution of ethyl 7-{[(4-methylphenyl)sulfonyl]amino}-1H-indole-2-carboxylate (356 mg) in tetrahydrofuran (6 mL)-methanol (6 mL) was added aqueous solution (3 mL) of 85% potassium hydroxide (450 mg), and the mixture was stirred at room temperature for 18 hr. Aqueous citric acid solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained crystals were washed with ethyl acetate-hexane to give the title compound (312 mg, yield 95%) as pale-yellow crystals. melting point 268-269° C.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].C(N(CC)CC)C.[C:13]([O:21][CH:22]([CH3:50])[CH2:23][CH:24]([CH2:27][O:28][C:29](=[O:49])[NH:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])[CH2:25][OH:26])(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>ClCCl>[CH3:1][S:2]([O:26][CH2:25][CH:24]([CH2:23][CH:22]([O:21][C:13](=[O:20])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[CH3:50])[CH2:27][O:28][C:29](=[O:49])[NH:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])(=[O:4])=[O:3]
Reactant: CCCCCCCCCCCCCCCCCCNC(=O)OCC(CO)CC(C)OC(=O)c1ccccc1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCCCCCCCCCCCCCCCNC(=O)OCC(COS(C)(=O)=O)CC(C)OC(=O)c1ccccc1

Procedure:
Using 0.358 ml (4.63 mM) of methanesulfonyl chloride and 0.814 ml (5.79 mM) of triethylamine, 2.059 g (3.86 mM) of 2-(2-benzoyloxypropan-1-yl)-3-octadecylcarbamoyloxypropanol m7 in dichloromethane is converted to the crude titled compound m7a by the same procedure as described in (50).
Reaction SMILES: [CH:1]([C:4]1[CH:11]=[C:10]([CH:12]([CH3:14])[CH3:13])[CH:9]=[C:8]([CH:15]([CH3:17])[CH3:16])[C:5]=1[CH2:6]Br)([CH3:3])[CH3:2].[C:18]1(=[O:28])[NH:22][C:21](=[O:23])[C:20]2=[CH:24][CH:25]=[CH:26][CH:27]=[C:19]12.[K]>CN(C)C=O>[CH:1]([C:4]1[CH:11]=[C:10]([CH:12]([CH3:14])[CH3:13])[CH:9]=[C:8]([CH:15]([CH3:17])[CH3:16])[C:5]=1[CH2:6][N:22]1[C:21](=[O:23])[C:20]2=[CH:24][CH:25]=[CH:26][CH:27]=[C:19]2[C:18]1=[O:28])([CH3:3])[CH3:2]
Reactant: CC(C)c1cc(C(C)C)c(CBr)c(C(C)C)c1
Reactant: O=C1NC(=O)c2ccccc21
Agent: [K]
Solvent: CN(C)C=O
Product: CC(C)c1cc(C(C)C)c(CN2C(=O)c3ccccc3C2=O)c(C(C)C)c1
Temperature: 70 °C
Reaction time: 8 h

Procedure:
A mixture of 2,4,6-triisopropylbenzyl bromide (5.00 g, 16.8 mmol), potassium phthalimide (3.71 g, 19.9 mmol), and dimethylformamide were heated for 3 hours at 70° C. The reaction mixture was allowed to stand overnight at room temperature and was then heated at 90° C. for 1 hour. The solvent was removed on the rotary evaporator, ethyl acetate (250 mL) was added, the organic layer was washed with brine, dried over magnesium sulfate, filtered, and concentrated to a white solid. Hexanes (50 mL) and ethyl acetate (5 mL) was added and the solid collected by filtration, 4.18 g (68%). An analytical sample was obtained by silica gel filtration using 9:1, hexanes/ethyl acetate as eluant. Analysis calculated for (C24H29NO2).
Reaction SMILES: C([O:8][C:9]1[CH:26]=[CH:25][C:12]([O:13][C:14]2[C:23]([CH3:24])=[N:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=2)=[CH:11][CH:10]=1)C1C=CC=CC=1.O>C(Cl)Cl>[OH:8][C:9]1[CH:10]=[CH:11][C:12]([O:13][C:14]2[C:23]([CH3:24])=[N:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=2)=[CH:25][CH:26]=1
Reactant: Cc1nc2ccccc2nc1Oc1ccc(OCc2ccccc2)cc1
Solvent: ClCCl
Solvent: O
Product: Cc1nc2ccccc2nc1Oc1ccc(O)cc1
Yield: 50.7 %

Procedure:
A solution of 12.5 g (0.05 mole) borontribromide in 100 cc methylene chloride was added, over a period of 40 minutes, to a well stirred, cold (-62° C.) solution of 17.1 g 2-(4-benzyloxyphenoxy)-3-methylquinoxaline (0.05 mole) in 400 cc methylene chloride. When the addition was complete, the temperature of the reaction was allowed to rise slowly (2 hours) to room temperature. The reaction mixture was then poured into 1 liter of water and an additional 500 cc of methylene chloride was added. The mixture was stirred vigorously for 40 minutes and the insoluble solid was filtered. Crystallization from an ethanol-water mixture (1:1) gave 6.4 g of product, m.p. 175°-178° C.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[N:11]=[C:12]=[S:13].[NH2:14][C@@H:15]([CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)[CH3:16].Cl[CH:24]([CH3:28])[C:25](O)=[O:26]>>[CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[N:11]=[C:12]1[N:14]([C@@H:15]([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[CH3:16])[C:25](=[O:26])[CH:24]([CH3:28])[S:13]1
Reactant: CC(Cl)C(=O)O
Reactant: Cc1cc([N+](=O)[O-])ccc1N=C=S
Reactant: C[C@@H](N)C1CCCCC1
Product: Cc1cc([N+](=O)[O-])ccc1N=C1SC(C)C(=O)N1[C@H](C)C1CCCCC1

Procedure:
2-Methyl-4-nitrophenyl isothiocyanate was reacted with (1R)-1-amino-1-cyclohexylethane followed by α-chloropropionic acid according to Method C8a to afford 2-(2-methyl-4-nitrophenylimino)-3-((1R)-1-cyclohexylethyl)-5-methyl-1,3-thiazolidin4-one.
Reaction SMILES: [C:1]1([CH2:7][C:8]([OH:10])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH:11]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:13]=[C:12]1[C:20]1[C:24]([NH2:25])=[CH:23][NH:22][N:21]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CS(C)=O>[NH:13]1[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[N:11]=[C:12]1[C:20]1[C:24]([NH:25][C:8](=[O:10])[CH2:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[CH:23][NH:22][N:21]=1
Reactant: Nc1c[nH]nc1-c1nc2ccccc2[nH]1
Reactant: O=C(O)Cc1ccccc1
Agent: On1nnc2ccccc21
Solvent: CS(C)=O
Solvent: ClCCCl
Product: O=C(Cc1ccccc1)Nc1c[nH]nc1-c1nc2ccccc2[nH]1
Temperature: 25 °C
Reaction time: 24 h
Yield: 18.9 %

Procedure:
A mixture of phenylacetic acid (38 mg, 0.28 mmol), 3-(1H-benzimidazol-2-yl)-1H-pyrazol-4-ylamine (50 mg, 0.25 mmol), EDC (58 mg, 0.30 mmol) and HOBt (41 mg, 0.30 mmol) in DMSO (2 ml) was stirred at ambient temperature for 24 h. The reaction mixture was partitioned between EtOAc (40 ml) and water (40 ml) and the organic portion dried (MgSO4), filtered and reduced in vacuo. The residue was purified by flash column chromatography [SiO2, EtOAc-petrol (1:2, 1:1, 2:1)] to give N-[3-(1H-benzimidazol-2-yl)-1H-pyrazol-4-yl]-2-phenyl-acetamide as a brown solid (15 mg, 19%). (LC/MS: Rt 3.26, [M+H]+ 318.13).
Reaction SMILES: N1C=CC=CC=1.[C:7]([CH:15]([OH:29])[C@H:16]1[O:20][C@@H:19]([N:21]2[CH:28]=[CH:27][C:25](=O)[NH:24][C:22]2=[O:23])[CH2:18][CH2:17]1)(=[O:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:31]>O>[C:7]([CH:15]([OH:29])[C@H:16]1[O:20][C@@H:19]([N:21]2[CH:28]=[CH:27][C:25](=[S:31])[NH:24][C:22]2=[O:23])[CH2:18][CH2:17]1)(=[O:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: O=C(c1ccccc1)C(O)[C@@H]1CC[C@H](n2ccc(=O)[nH]c2=O)O1
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Solvent: O
Solvent: c1ccncc1
Product: O=C(c1ccccc1)C(O)[C@@H]1CC[C@H](n2ccc(=S)[nH]c2=O)O1
Yield: 157.8 %

Procedure:
Into 50 ml of pyridine were dissolved 3.16 g of 5'-benzoyl-2',3'-dideoxy-uridine and 0.22 g of distilled water. Then, after added 2.67 g of phosphorus pentasulfide at room temperature under stirring, the mixture was refluxed for 3 hours. After the completion of reaction, the solids deposited by allowing to cool were collected by filtration, which were washed with small amount of pyridine. The pyridine filtrate obtained was concentrated to dryness and the residue was extracted with chloroform to separate 3.15 g of 5'-benzoyl-2',3'-dideoxy-4-thio-uridine(yield: 95%).
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8](Cl)=[N:9]2)([O-])=O.[F:15][C:16]1[CH:17]=[C:18]([S:24](Cl)(=[O:26])=[O:25])[CH:19]=[C:20]([F:23])[C:21]=1[F:22].[NH2:28][CH:29]1[CH2:37][C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:30]1>>[F:15][C:16]1[CH:17]=[C:18]([S:24]([NH:1][C:4]2[CH:13]=[CH:12][CH:11]=[C:10]3[C:5]=2[CH:6]=[CH:7][C:8]([NH:28][CH:29]2[CH2:37][C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[CH2:30]2)=[N:9]3)(=[O:26])=[O:25])[CH:19]=[C:20]([F:23])[C:21]=1[F:22]
Reactant: O=S(=O)(Cl)c1cc(F)c(F)c(F)c1
Reactant: NC1Cc2ccccc2C1
Reactant: O=[N+]([O-])c1cccc2nc(Cl)ccc12
Product: O=S(=O)(Nc1cccc2nc(NC3Cc4ccccc4C3)ccc12)c1cc(F)c(F)c(F)c1

Procedure:
The title compound, MS: m/e=470.5 (M+H+), was prepared in accordance with the general method of example 13 from 5-nitro-2-chloroquinoline, 3,4,5-trifluorobenzenesulfonyl chloride and 2-aminoindane.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([NH:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)[CH:4]=1.Cl[CH2:24][C:25]1[CH:30]=[CH:29][N:28]=[C:27]([C:31]2[CH:36]=[C:35]([O:37][CH3:38])[C:34]([O:39][CH3:40])=[C:33]([O:41][CH3:42])[CH:32]=2)[CH:26]=1>>[C:19]([O:18][C:16]([N:13]1[CH2:14][CH2:15][CH:10]([N:9]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=2)[CH2:24][C:25]2[CH:30]=[CH:29][N:28]=[C:27]([C:31]3[CH:36]=[C:35]([O:37][CH3:38])[C:34]([O:39][CH3:40])=[C:33]([O:41][CH3:42])[CH:32]=3)[CH:26]=2)[CH2:11][CH2:12]1)=[O:17])([CH3:22])([CH3:21])[CH3:20]
Reactant: COc1cc(-c2cc(CCl)ccn2)cc(OC)c1OC
Reactant: COc1cccc(NC2CCN(C(=O)OC(C)(C)C)CC2)c1
Product: COc1cccc(N(Cc2ccnc(-c3cc(OC)c(OC)c(OC)c3)c2)C2CCN(C(=O)OC(C)(C)C)CC2)c1

Procedure:
4-(m-Anisidino)-1-(tert-butoxycarbonyl)piperidine (613 mg) and 4-chloromethyl-2-(3,4,5-trimethoxyphenyl)pyridine (588 mg) was treated in the same manner as described in Example 9 to give light yellow amorphous of the title compound.
Reaction SMILES: CCN(CCCC([NH:11][C:12]1[CH:13]=CN=[C:16]2[CH:21]=[C:20](Cl)[CH:19]=[CH:18][C:17]=12)C)CC.CC1N(/N=C/C2OC([N+]([O-])=O)=CC=2)CCS(=O)(=O)C1.C[C@@H]1[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)[CH2:68][C@H:67](O)[CH2:66][C@@:64]2(O)[O:65][C@H:60]([C@H:61]([C:93](O)=O)[C@@H:62](O)[CH2:63]2)C[C@@H](O[C@@H]2O[C@H](C)[C@@H](O)[C@H](N)[C@@H]2O)C=CC=CC=CC=CC=CC=CC=C1>>[CH3:93][C@@H:61]([CH2:62][CH2:63][CH2:64][CH2:66][CH2:67][CH3:68])[C:60]([NH:11][C@H:12]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:16]=1)[CH3:13])=[O:65]
Reactant: CCN(CC)CCCC(C)Nc1ccnc2cc(Cl)ccc12
Reactant: C[C@@H]1[C@H](O)[C@@H](C)C=CC=CC=CC=CC=CC=CC=C[C@H](O[C@@H]2O[C@H](C)[C@@H](O)[C@H](N)[C@@H]2O)C[C@@H]2O[C@](O)(C[C@@H](O)C[C@@H](O)[C@H](O)CC[C@@H](O)C[C@@H](O)CC(=O)O[C@H]1C)C[C@H](O)[C@H]2C(=O)O
Agent: CC1CS(=O)(=O)CCN1/N=C/c1ccc([N+](=O)[O-])o1
Agent: C[C@@H]1[C@H](O)[C@@H](C)/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](O[C@@H]2O[C@H](C)[C@@H](O)[C@H](N)[C@@H]2O)C[C@@H]2O[C@](O)(C[C@@H](O)C[C@@H](O)[C@H](O)CC[C@@H](O)C[C@@H](O)CC(=O)O[C@H]1C)C[C@H](O)[C@H]2C(=O)O
Product: CCCCCC[C@H](C)C(=O)N[C@@H](C)c1ccccc1

Procedure:
Bioassays. All bioassays were performed in duplicate, testing at 10, 2, 0.4, 0.08 and 0.016 μg/mL. Malaria bioassays were performed as previously reported by our program, using chloroquine as a positive control (IC50=80-100 nM). Chagas bioassays were performed following the protocol of Buckner et al, and using nifurtimox as a positive control (IC50 3-5 μg/mL). Leishmaniasis bioassays were performed using a method previously employed in our laboratory, based on parasite DNA fluorescence. In this latter assay, amphotericin-B was used as the positive control and had an IC50 value of 80 ng/mL. Cytotoxicity bioassays were performed following an MTT cell proliferation assay protocol with green monkey Vero kidney cells.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=3)=[CH:9][C:8]([O:17][S:18]([C:21]([F:24])([F:23])[F:22])(=[O:20])=[O:19])=[CH:7][C:5]=2[N:6]=1.[CH:25]1N=C[N:27]([C:30](N2C=NC=C2)=[O:31])[CH:26]=1.C(CN)[OH:38]>CN(C=O)C.CCOC(C)=O>[OH:38][CH2:25][CH2:26][NH:27][C:30]([NH:1][C:2]1[S:3][C:4]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=3)=[CH:9][C:8]([O:17][S:18]([C:21]([F:23])([F:22])[F:24])(=[O:20])=[O:19])=[CH:7][C:5]=2[N:6]=1)=[O:31]
Reactant: NCCO
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: Nc1nc2cc(OS(=O)(=O)C(F)(F)F)cc(-c3ccccn3)c2s1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=C(NCCO)Nc1nc2cc(OS(=O)(=O)C(F)(F)F)cc(-c3ccccn3)c2s1
Temperature: 25 °C
Yield: 46.4 %

Procedure:
Compound i (445 mg, 1.18 mmol) was dissolved in DMF (7 mL) and solution of CDI (577 mg, 3.56 mmol) in DMF (3 mL) was added drop-wise at 0° C. with stirring under argon. The mixture was warmed to RT and stirred for 16 h. A solution of ethanolamine (710 μL, 11.85 mmol) in DMF (2 mL) was then added and the mixture stirred at RT for 4 h. The mixture was diluted with EtOAc, washed with H2O, brine. The organic fraction was dried (Na2SO4) and concentrated in vacuo. The residue was washed with MeOH and Et2O to afford ii (253 mg, 46%). MS: 463.00 [M+H]+.