Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(N(C(C)C)CC)(C)C.P(Cl)(OC1C=CC=CC=1)(OC1C=CC=CC=1)=O.[OH:27][C@@H:28]([C@H:30]1[C:50](=[O:51])[N:32]2[CH:33]([C:37]([O:39][CH2:40][C:41]3[CH:46]=[CH:45][C:44]([N+:47]([O-:49])=[O:48])=[CH:43][CH:42]=3)=[O:38])[C:34](=O)[CH2:35][C@H:31]12)[CH3:29].FC(F)(F)S(O)(=O)=O.[SH:60][C@@H:61]1[CH2:65][N:64]([C:66]([O:68][CH2:69][C:70]2[CH:75]=[CH:74][C:73]([N+:76]([O-:78])=[O:77])=[CH:72][CH:71]=2)=[O:67])[C@H:63]([C:79]([N:81]2[CH2:86][CH2:85][N:84]([CH3:87])[CH2:83][CH2:82]2)=[O:80])[CH2:62]1>C(#N)C>[OH:27][C@@H:28]([C@H:30]1[C:50](=[O:51])[N:32]2[C:33]([C:37]([O:39][CH2:40][C:41]3[CH:42]=[CH:43][C:44]([N+:47]([O-:49])=[O:48])=[CH:45][CH:46]=3)=[O:38])=[C:34]([S:60][C@@H:61]3[CH2:65][N:64]([C:66]([O:68][CH2:69][C:70]4[CH:75]=[CH:74][C:73]([N+:76]([O-:78])=[O:77])=[CH:72][CH:71]=4)=[O:67])[C@H:63]([C:79]([N:81]4[CH2:82][CH2:83][N:84]([CH3:87])[CH2:85][CH2:86]4)=[O:80])[CH2:62]3)[CH2:35][C@H:31]12)[CH3:29]
Reactant: CN1CCN(C(=O)[C@@H]2C[C@H](S)CN2C(=O)OCc2ccc([N+](=O)[O-])cc2)CC1
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)C(=O)C[C@H]12
Agent: O=P(Cl)(Oc1ccccc1)Oc1ccccc1
Agent: O=S(=O)(O)C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@H]3C[C@@H](C(=O)N4CCN(C)CC4)N(C(=O)OCc4ccc([N+](=O)[O-])cc4)C3)C[C@H]12
Reaction time: 1 h
Yield: 61.2 %

Procedure:
85 μl of diisopropylethylamine and 86 μl of diphenyl chlorophosphate were simultaneously added, whilst ice-cooling, to a solution of 161 mg of 4-nitrobenzyl (5R,6S)-6-[(1R)-1-hydroxyethyl]-2-oxo-1-carbapenam-3-carboxylate in 2 ml of anhydrous acetonitrile, and the resulting mixture was stirred at the same temperature for 1 hour. At the end of this time, 232 μof diisopropylethylamine and a solution of 310 mg of (2S,4S)-4-mercapto-2-(4-methyl-1-piperazinylcarbonyl)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine trifluoromethanesulfonate [prepared as described in Example 1(1)] in 2 ml of anhydrous acetonitrile were added dropwise to the mixture, whilst ice-cooling, and the resulting mixture was stirred at the same temperature for 2 hours, after which it was allowed to stand overnight, whilst ice-cooling. At the end of this time, the solvent was removed by distillation under reduced pressure, and the resulting residue was worked up and purified in a similar manner to that described in Example 29(1), to afford 209 mg of the title compound as a powder.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:16]=[CH:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH:8]=2)=[N:4][C:3]=1[CH:17]=[CH:18][C:19]1[CH:28]=[CH:27][C:22](/[CH:23]=[CH:24]/[CH:25]=O)=[CH:21][CH:20]=1.[O:29]1[CH2:33][C:32](=[O:34])[NH:31][C:30]1=[O:35].N1CCCCC1.C(O)C>O1CCCC1>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:16]=[CH:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH:8]=2)=[N:4][C:3]=1[CH2:17][CH2:18][C:19]1[CH:28]=[CH:27][C:22]([CH2:23][CH2:24][CH2:25][CH:33]2[O:29][C:30](=[O:35])[NH:31][C:32]2=[O:34])=[CH:21][CH:20]=1
Reactant: O=C1COC(=O)N1
Reactant: Cc1oc(-c2ccc3ccccc3c2)nc1C=Cc1ccc(/C=C/C=O)cc1
Solvent: CCO
Solvent: C1CCNCC1
Solvent: C1CCOC1
Product: Cc1oc(-c2ccc3ccccc3c2)nc1CCc1ccc(CCCC2OC(=O)NC2=O)cc1
Yield: 11.7 %

Procedure:
A mixture of (E)-4-[2-[5-methyl-2-(2-naphthyl)-4-oxazolyl]vinyl]cinnamaldehyde (2.00 g), 2,4-oxazolidinedione (1.11 g), piperidine (0.23 g), ethanol (100 ml) and tetrahydrofuran (50 ml) was refluxed under heating conditions for 8 hours. After the reaction mixture was concentrated, chloroform was added to the residue; the mixture was then washed with 2N HCl and water. The organic layer was washed with water, dried (MgSO4) and then concentrated. The residue was subjected to silica gel column chromatography. The crystal obtained from the fraction eluted with ethyl acetate-chloroform (1:9, v/v) was dissolved in tetrahydrofuran (100 ml), and subjected to catalytic hydrogenation at 1 atm and room temperature in the presence of palladium-carbon (5%, 0.5 g). After the catalyst was filtered off, the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to yield 5-[3-[4-[2-[5-methyl-2-(2-naphthyl)-4-oxazolyl]ethyl]phenyl]propyl]-2,4-oxazolidinedione (0.29 g, 12%) from the fraction eluted with methanol-chloroform (2:98, v/v), which was then recrystallized from dichloromethane-isopropyl ether to yield a colorless prisms having a melting point of 168°-169° C.
Reaction SMILES: Cl[C:2]1[C:3]([N+:13]([O-:15])=[O:14])=[C:4]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2.[CH3:16][NH2:17]>C(O)C>[CH3:16][NH:17][C:2]1[C:3]([N+:13]([O-:15])=[O:14])=[C:4]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2
Reactant: CN
Reactant: Cc1cc(Cl)c([N+](=O)[O-])c2cccnc12
Solvent: CCO
Product: CNc1cc(C)c2ncccc2c1[N+](=O)[O-]
Temperature: 80 °C
Reaction time: 1 h

Procedure:
A mixture of 6-chloro-8-methyl-5-nitroquinoline (420 mg, 1.9 mmol) in methanamine as a solution in ethyl alcohol (30 mL) was heated to 80° C. and stirred for 1 h. After concentration under reduced pressure, the reaction mixture was extracted with DCM (50 mL). The organic layer was washed with water (20 mL×2), dried over Na2SO4, and concentrated under reduced pressure to give 410 mg of N,8-dimethyl-5-nitroquinolin-6-amine as a yellow solid. MS (ESI): m/z 218 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[CH:30]=[CH:29][C:5]2[NH:6][C:7]([C:12]3[C:13](=[O:28])[N:14]([CH2:23][CH2:24][CH:25]([CH3:27])[CH3:26])[C:15]4[C:20]([C:21]=3[OH:22])=[CH:19][CH:18]=[CH:17][N:16]=4)=[N:8][S:9](=[O:11])(=[O:10])[C:4]=2[CH:3]=1.[C:31](OC(=O)C)(=[O:33])[CH3:32].O>N1C=CC=CC=1>[OH:22][C:21]1[C:20]2[C:15](=[N:16][CH:17]=[CH:18][CH:19]=2)[N:14]([CH2:23][CH2:24][CH:25]([CH3:27])[CH3:26])[C:13](=[O:28])[C:12]=1[C:7]1[NH:6][C:5]2[CH:29]=[CH:30][C:2]([NH:1][C:31](=[O:33])[CH3:32])=[CH:3][C:4]=2[S:9](=[O:11])(=[O:10])[N:8]=1
Reactant: CC(C)CCn1c(=O)c(C2=NS(=O)(=O)c3cc(N)ccc3N2)c(O)c2cccnc21
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Solvent: O
Product: CC(=O)Nc1ccc2c(c1)S(=O)(=O)N=C(c1c(O)c3cccnc3n(CCC(C)C)c1=O)N2
Temperature: 100 °C
Yield: 71.6 %

Procedure:
To the product of Example 205 (0.020 g, 0.047 mmol) in pyridine (0.5 mL) was added acetic anhydride (0.057 g, 0.0053 mL, 0.056 mmol). The reaction mixture was heated in a microwave reactor at 100° C. for 30 minutes. The reaction was poured into 30 mL of water. The solid was collected by filtration to give the title compound (15.8 mg, 72%). 1H NMR (300 MHz, DMSO-d6) δ 0.98 (d, J=6.62 Hz, 6 H) 1.57 (m, 2 H) 1.70 (m, 1 H) 2.10 (s, 3 H) 4.48 (m, 2 H) 7.48 (dd, J=8.09, 4.78 Hz, 1 H) 7.66 (d, J=8.82 Hz, 1 H) 7.78 (m, 1 H) 8.30 (d, J=1.84 Hz, 1 H) 8.55 (dd, J=7.72, 1.84 Hz, 1 H) 8.87 (dd, J=4.60, 1.65 Hz, 1 H) 10.39 (s, 1 H) 14.21 (br s, 1 H). MS (ESI−) m/z 468 (M−H)−.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][NH:7][CH3:8])=[CH:4][CH:3]=1.[O-]S(C(F)(F)F)(=O)=O.[N:19]1([S:24](N2C=C[N+](C)=C2)(=[O:26])=[O:25])[CH:23]=[CH:22][N:21]=[CH:20]1>C(#N)C>[F:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][N:7]([CH3:8])[S:24]([N:19]2[CH:23]=[CH:22][N:21]=[CH:20]2)(=[O:26])=[O:25])=[CH:4][CH:3]=1
Reactant: C[n+]1ccn(S(=O)(=O)n2ccnc2)c1
Reactant: CNCc1ccc(F)cc1
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: CC#N
Product: CN(Cc1ccc(F)cc1)S(=O)(=O)n1ccnc1
Temperature: 25 °C
Reaction time: 120 h
Yield: 39.8 %

Procedure:
A solution of 4-fluoro-N-methylbenzylamine (420 μL, 3.19 mmol) in acetonitrile (10 mL) was treated with 3-(imidazole-1-sulfonyl)-1-methyl-3H-imidazol-1-ium triflate (1.50 g, 4.14 mmol) and stirred at ambient temperature for 5 days. The mixture was concentrated under vacuum and purified by silica gel chromatography to afford the title compound (342 mg, 40%) as a pale yellow/orange oil. 1H NMR (400 MHz, DMSO) δ 7.98 (br s, 1H), 7.25 (m, 4H), 7.08 (m, 2H), 4.26 (s, 2H), 2.75 (s, 3H). LCMS (m/z, Method A) ES+ 270.0 [M+1]+.
Reaction SMILES: CCN(C(C)C)C(C)C.[C:10]1([C:16]2[CH:24]=[CH:23][C:19]([C:20](Cl)=[O:21])=[CH:18][CH:17]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(O)(=O)/C=C\C(O)=O.[Cl:33][C:34]1[CH:53]=[CH:52][C:37]2[O:38][C:39]3[CH:51]=[CH:50][CH:49]=[CH:48][C:40]=3[C@@H:41]3[C@H:46]([NH2:47])[CH2:45][CH2:44][CH2:43][N:42]3[C:36]=2[CH:35]=1>C(Cl)Cl>[Cl:33][C:34]1[CH:53]=[CH:52][C:37]2[O:38][C:39]3[CH:51]=[CH:50][CH:49]=[CH:48][C:40]=3[C@@H:41]3[C@H:46]([NH:47][C:20](=[O:21])[C:19]4[CH:23]=[CH:24][C:16]([C:10]5[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=5)=[CH:17][CH:18]=4)[CH2:45][CH2:44][CH2:43][N:42]3[C:36]=2[CH:35]=1
Reactant: N[C@@H]1CCCN2c3cc(Cl)ccc3Oc3ccccc3[C@H]12
Reactant: O=C(Cl)c1ccc(-c2ccccc2)cc1
Agent: O=C(O)/C=C\C(=O)O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C(N[C@@H]1CCCN2c3cc(Cl)ccc3Oc3ccccc3[C@H]12)c1ccc(-c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 47.8 %

Procedure:
DIPEA (18.6 μL, 0.14 mmol) and 4-phenylbenzoyl chloride (15.2 mg, 0.07 mmol) were added to a solution of trans-7-chloro-2,3,4,14b-tetrahydro-1H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepine-1-amine maleate (9.6 mg, 0.02 mmol) in 1 mL of CH2Cl2. The resulting mixture was stirred for 18 h at room temperature. The organic layer was washed with 5% aqueous sodium bicarbonate and H2O, dried (Na2SO4) and evaporated. Additional chromatography on silica (elution with toluene/ethyl acetate 9:1→toluene/ethyl acetate 1:1) gave trans-N-(7-chloro-2,3,4,14b-tetrahydro-1H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepin-1-yl)-4-phenylbenzamide (4.6 mg, 44%). Data: (m/z)=350 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([F:20])=[N:7][N:8]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[C:4]([N+:21]([O-])=O)[CH:3]=1>C(O)(=O)C.C(OCC)(=O)C.[Fe]>[Br:1][C:2]1[CH:3]=[C:4]([NH2:21])[C:5]2[C:6]([F:20])=[N:7][N:8]([S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)(=[O:12])=[O:13])[C:9]=2[CH:10]=1
Reactant: O=[N+]([O-])c1cc(Br)cc2c1c(F)nn2S(=O)(=O)c1ccccc1
Agent: [Fe]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: Nc1cc(Br)cc2c1c(F)nn2S(=O)(=O)c1ccccc1
Reaction time: 0.08 h

Procedure:
6-Bromo-3-fluoro-4-nitro-1-(phenylsulfonyl)-1H-indazole (5.9 g) was suspended in acetic acid (60 ml) and iron powder (4.12 g) was added. The suspension was heated to reflux. After 2 h the reaction mixture was diluted with ethyl acetate (100 ml) and filtered through celite. The filter cake was washed well with ethyl acetate then the filtrate basified to pH 8-9. The biphasic system was then stirred for ˜5 min. The layers were then separated, the aq washed with ethyl acetate and the combined organics washed with brine, dried (magnesium sulphate), filtered and concentrated in vacuum to yield a crude loaded onto a 330 g silica cartridge, purified on a 0-100% ethyl acetate:cyclohexane gradient and the relevant fractions combined and concentrated to yield the title compound, 2.4 g as a yellow solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[C:18]([CH3:23])[C:17]=1[CH3:24].C1(C)C=CC=CC=1.C(N(CC)CC)C.Cl[C:40](Cl)([O:42]C(=O)OC(Cl)(Cl)Cl)Cl.[Br:51][C:52]1[CH:53]=[C:54]([CH:58]=[CH:59][CH:60]=1)[CH:55]([OH:57])[CH3:56]>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:40](=[O:42])[O:57][CH:55]([C:54]2[CH:58]=[CH:59][CH:60]=[C:52]([Br:51])[CH:53]=2)[CH3:56])=[C:18]([CH3:23])[C:17]=1[CH3:24]
Reactant: CC(O)c1cccc(Br)c1
Reactant: COc1cc2nccc(Oc3ccc(N)c(C)c3C)c2cc1OC
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3ccc(NC(=O)OC(C)c4cccc(Br)c4)c(C)c3C)c2cc1OC
Temperature: 25 °C
Yield: 71.8 %

Procedure:
4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (68 mg) was added to toluene/triethylamine=10/1 (7 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 3-bromo-α-methylbenzyl alcohol (75 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (83 mg, yield 67%).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[CH2:4][NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N+:15]([O-:17])=[O:16])(=[O:8])=[O:7].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Cl[CH2:28][C:29]1[CH:34]=[CH:33][N:32]=[C:31]([C:35]2[CH:40]=[C:39]([O:41][CH3:42])[C:38]([O:43][CH3:44])=[C:37]([O:45][CH3:46])[CH:36]=2)[CH:30]=1>C(#N)C>[CH3:1][O:2][C:3](=[O:18])[CH2:4][N:5]([S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[N+:15]([O-:17])=[O:16])(=[O:7])=[O:8])[CH2:28][C:29]1[CH:34]=[CH:33][N:32]=[C:31]([C:35]2[CH:40]=[C:39]([O:41][CH3:42])[C:38]([O:43][CH3:44])=[C:37]([O:45][CH3:46])[CH:36]=2)[CH:30]=1
Reactant: COc1cc(-c2cc(CCl)ccn2)cc(OC)c1OC
Reactant: COC(=O)CNS(=O)(=O)c1ccccc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC#N
Product: COC(=O)CN(Cc1ccnc(-c2cc(OC)c(OC)c(OC)c2)c1)S(=O)(=O)c1ccccc1[N+](=O)[O-]

Procedure:
N-(2-Nitrobenzenesulfonyl)glycine methyl ester (5.60 g) was dissolved in acetonitrile (100 mL), and to the solution potassium carbonate (3.10 g) and potassium iodide (2.29 g) were added. To the mixture, 4-chloromethyl-2-(3,4,5-trimethoxyphenyl)pyridine (6.00 g) was then added, and the resultant mixture was stirred at 80° C. for 1 hour. The reaction mixture was concentrated under reduced pressure, ethyl acetate was added to the residue, and the resultant mixture was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (chloroform:methanol=50:1) to obtain the title compound.
Reaction SMILES: [C:1]([OH:6])(=[O:5])[C:2]([CH3:4])=[CH2:3].[CH2:7]([O:10][CH2:11][CH2:12]O)[CH:8]=[CH2:9].C1(C)C=CC=CC=1>C1(C)C=CC(S(O)(=O)=O)=CC=1.O>[C:1]([O:6][CH2:12][CH2:11][O:10][CH2:7][CH:8]=[CH2:9])(=[O:5])[C:2]([CH3:4])=[CH2:3]
Reactant: C=CCOCCO
Reactant: C=C(C)C(=O)O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: C=CCOCCOC(=O)C(=C)C
Temperature: 120 °C
Yield: 72.5 %

Procedure:
To a three-necked flask equipped with a stirrer, a thermometer, a ref lux condenser and a Dean-Stark apparatus were added methacrylic acid (137.7 g, 1.6 moles), ethyleneglycol monoallylether (80.7 g, 0.8 moles), p-toluenesulfonic acid (0.76 g, 4.0 mmole) and toluene (650 mL). The mixture was heated to 120° C. for 5 hours with exclusion of water. Another portion of p-toluenesulfonic acid (0.12 g) and the mixture was heated to 120° C. for 6 hours. The other portion of p-toluenesulfonic acid (0.1 g) was added and the mixture was heated to 120° C. for 9 hours. During the reaction, the consumption of methacrylic acid and ethyleneglycol monoallylether were monitored by liquid chromatography and the conversion reached 98%. The mixture was neutralized by addition of aq. NaHCO3 and the layers were separated. The aqueous layer was extracted with toluene and the combined organic layers were dried over CaCl2 and concentrated under reduced pressure. Distillation of the crude material (60° C. at 2 mmHg) yielded 2-allyloxyethyl methacrylate (98.7 g, 73%) shown below.
Reaction SMILES: [CH2:1]([N:8]1[C:16]([C:17]2[CH:18]=[C:19]([OH:23])[CH:20]=[CH:21][CH:22]=2)=[C:15]2[C:10]([C:11]([C:24]([F:27])([F:26])[F:25])=[CH:12][CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:28][O:29][C:30](=[O:49])[C:31]([CH3:48])([C:33]1[CH:38]=[CH:37][CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=1)[CH3:32].N1C=CC=CC=1>C(Cl)Cl.Cl.CC([O-])=O.CC([O-])=O.[Cu+2]>[CH3:28][O:29][C:30](=[O:49])[C:31]([C:33]1[CH:34]=[CH:35][CH:36]=[C:37]([O:23][C:19]2[CH:20]=[CH:21][CH:22]=[C:17]([C:16]3[N:8]([CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[N:9]=[C:10]4[C:15]=3[CH:14]=[CH:13][CH:12]=[C:11]4[C:24]([F:27])([F:25])[F:26])[CH:18]=2)[CH:38]=1)([CH3:48])[CH3:32]
Reactant: Oc1cccc(-c2c3cccc(C(F)(F)F)c3nn2Cc2ccccc2)c1
Reactant: COC(=O)C(C)(C)c1cccc(B2OC(C)(C)C(C)(C)O2)c1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: COC(=O)C(C)(C)c1cccc(Oc2cccc(-c3c4cccc(C(F)(F)F)c4nn3Cc3ccccc3)c2)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
3-(2-Benzyl-7-trifluoromethyl-2H-indazol-3-yl)-phenol (96 mg, 0.26 mmol), 2-methyl-2-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propionic acid methyl ester (80 mg, 0.26 mmol), Cu(OAc)2 (47 mg, 0.26 mmol) and pyridine (42 μL, 0.52 mmol) were dissolved in 3 ml anhydrous CH2Cl2 and stirred at room temperature with crushed molsieves (4 Å) overnight. The reaction mixture was diluted with 1 M HCl (aq.) and the product was extracted three times with CH2Cl2. The combined organic phases were dried, evaporated and the crude material was purified by preparative HPLC using a gradient with an acidic mobile phase on an ACE-C8 column to afford 8.4 mg of analytically pure product.
Reaction SMILES: C[O:2][C:3](=[O:42])[CH2:4][CH2:5][NH:6][C:7](=[O:41])[C:8]1[CH:13]=[CH:12][C:11]([CH:14]([NH:26][C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([O:36][C:37]([F:40])([F:39])[F:38])=[CH:32][CH:31]=2)=[O:28])[CH:15]2[CH2:20][CH2:19][N:18]([C:21]([CH:23]3[CH2:25][CH2:24]3)=[O:22])[CH2:17][CH2:16]2)=[CH:10][CH:9]=1.[OH-].[Li+]>C(O)C.O>[CH:23]1([C:21]([N:18]2[CH2:17][CH2:16][CH:15]([CH:14]([NH:26][C:27]([NH:29][C:30]3[CH:31]=[CH:32][C:33]([O:36][C:37]([F:40])([F:38])[F:39])=[CH:34][CH:35]=3)=[O:28])[C:11]3[CH:12]=[CH:13][C:8]([C:7]([NH:6][CH2:5][CH2:4][C:3]([OH:42])=[O:2])=[O:41])=[CH:9][CH:10]=3)[CH2:20][CH2:19]2)=[O:22])[CH2:24][CH2:25]1
Reactant: COC(=O)CCNC(=O)c1ccc(C(NC(=O)Nc2ccc(OC(F)(F)F)cc2)C2CCN(C(=O)C3CC3)CC2)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C(O)CCNC(=O)c1ccc(C(NC(=O)Nc2ccc(OC(F)(F)F)cc2)C2CCN(C(=O)C3CC3)CC2)cc1
Temperature: 50 °C
Reaction time: 2 h

Procedure:
The above 3-{4-[1-(1-cyclopropanecarbonylpiperidin-4-yl)-3-(4-trifluoromethoxyphenyl)ureidomethyl]benzoylamino}propionic acid methyl ester (0.17 g, 0.28 mmol) was dissolved in 10 mL ethanol and hydrolysed by adding lithium hydroxide (14 mg, 0.56 mmol) dissolved in water (1 mL). The mixture was stirred at 50° C. for 2 hours. The solvent was evaporated and water (25 mL) was added to the mixture followed by HCl (1 N) adjusting pH to 3-4 allowing the title compound to be isolated as a precipitate.
Reaction SMILES: [O:1]=[C:2]1[NH:6][C@@H:5]([C@@H:7]([CH3:11])[C:8]([OH:10])=O)[CH2:4][O:3]1.ClC(N(C)C)=C(C)C.[CH3:20][NH:21][O:22][CH3:23].N1C=CC=CC=1>C(Cl)Cl.O.C(=O)(O)[O-].[Na+]>[CH3:23][O:22][N:21]([CH3:20])[C:8](=[O:10])[C@@H:7]([C@H:5]1[CH2:4][O:3][C:2](=[O:1])[NH:6]1)[CH3:11]
Reactant: CNOC
Reactant: C[C@@H](C(=O)O)[C@H]1COC(=O)N1
Agent: CC(C)=C(Cl)N(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Solvent: c1ccncc1
Product: CON(C)C(=O)[C@H](C)[C@H]1COC(=O)N1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 195.4 %

Procedure:
To a mixture of (R)-2-((S)-2-oxooxazolidin-4-yl)propanoic acid (1.1 g, 6.91 mmol) in DCM (20 mL) was added 1-chloro-N,N,2-trimethylprop-1-en-1-amine (1.385 g, 10.37 mmol) at 0° C. The ice bath was removed and the mixture was stirred for 30 min at ambient temperature. A mixture of N,O-dimethylhydroxylamine (1.011 g, 10.37 mmol) and pyridine (1.677 mL, 20.74 mmol) in DCM (20 mL) was added and stirring was continued for ˜1 hr. The mixture was diluted with water (˜2 mL) and saturated sodium bicarbonate solution (˜2 mL) and stirred for ˜15 min. The mixture was diluted with dichloromethane (˜30 mL). The separated aqueous layer was extracted with DCM (1×), the organic layers were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure providing crude (R)—N-methoxy-N-methyl-2-((S)-2-oxooxazolidin-4-yl)propanamide (2.73 g) as an orange oil which was directly used without further purification. MS m/z 203.1 (M+H)+; Rt-0.36 min.
Reaction SMILES: [CH3:1][CH:2]([C:8](=[O:16])[NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:3]([O:5]CC)=[O:4].[OH-].[Na+].O.CO>C1COCC1>[CH3:1][CH:2]([C:8](=[O:16])[NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:3]([OH:5])=[O:4]
Reactant: CCOC(=O)C(C)C(=O)Nc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: CC(C(=O)O)C(=O)Nc1ccccc1

Procedure:
Prepared according to Procedure B using ethyl 2-methyl-3-oxo-3-(phenylamino)-propanoate (8.60 g, 39 mmol) and sodium hydroxide (2.00 g, 50 mmol) in THF (40.00 mL), water (10.00 mL, 555 mmol) and MeOH (10.00 mL) to afford product as a colorless solid, which was used without further purification. Mass Spectrum (ESI) m/e=192.1 [M−1].
Reaction SMILES: COC1C=CC(C[N:8]2[C:12]3[N:13]=[CH:14][C:15]4[CH2:16][N:17]([C:21](=[O:29])[CH2:22][C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)[CH2:18][CH2:19][C:20]=4[C:11]=3[CH:10]=[N:9]2)=CC=1.FC(F)(F)C(O)=O.C1(C)C=CC=CC=1>ClCCl>[CH:10]1[C:11]2[C:20]3[CH2:19][CH2:18][N:17]([C:21](=[O:29])[CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH2:16][C:15]=3[CH:14]=[N:13][C:12]=2[NH:8][N:9]=1
Reactant: COc1ccc(Cn2ncc3c4c(cnc32)CN(C(=O)Cc2ccccc2)CC4)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Solvent: Cc1ccccc1
Product: O=C(Cc1ccccc1)N1CCc2c(cnc3[nH]ncc23)C1
Temperature: 70 °C
Yield: 28.6 %

Procedure:
To 1-(3-(4-methoxybenzyl)-8,9-dihydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-7(6H)-yl)-2-phenylethanone (0.203 g, 0.49 mmol) was added trifluoroacetic acid (2 mL). The reaction was heated at 70° C. for 18 hours. To the crude reaction mixture was added toluene (5 mL) and the resulting mixture was evaporated under reduced pressure to give a crude product. The residue was diluted in dichloromethane (4 mL/mmol) and washed with saturated aqueous sodium carbonate. The combined aqueous layers were washed with dichloromethane. The combined organics extract was dried over Na2SO4 and concentrated under reduced pressure to give a brown oil. The oily residue was triturated with a mixture of dichloromethane and methanol to yield the desired product, 1-(8,9-dihydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-7(6H)-yl)-2-phenylethanone as an off-white solid (0.041 g, 18%). M.p.=164-166° C.; 1H NMR (DMSO-d6), 400 MHz) δ 13.57 (s, 1H), 8.36 (s, 1H), 8.12 (s, 1H), 7.27 (m, 5H), 4.87 (s, 1H), 4.77 (s, 1H), 3.82-3.86 (m, 4H), 3.01 (m, 2H); LCMS [M+H]: 293.
Reaction SMILES: [C:1]([O:9][CH:10]([CH2:22][O:23][C:24](=[O:32])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[CH2:11][O:12][C:13](=[O:21])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])(=[O:8])[CH2:2][CH2:3][CH2:4][C:5]([OH:7])=[O:6].FC(F)(F)C(OC(=O)C(F)(F)F)=O.[CH:46]1[C:51]([Cl:52])=[CH:50][C:49](O)=[C:48]([O:54][C:55]2[CH:56]=[CH:57][C:58]([Cl:62])=[CH:59][C:60]=2[Cl:61])[CH:47]=1>C1(C)C=CC=CC=1>[C:5]([O:7][C:49]1[CH:50]=[C:51]([Cl:52])[CH:46]=[CH:47][C:48]=1[O:54][C:55]1[CH:56]=[CH:57][C:58]([Cl:62])=[CH:59][C:60]=1[Cl:61])(=[O:6])[CH2:4][CH2:3][CH2:2][C:1]([O:9][CH:10]([CH2:22][O:23][C:24](=[O:32])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[CH2:11][O:12][C:13](=[O:21])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])=[O:8]
Reactant: CCCCCCCC(=O)OCC(COC(=O)CCCCCCC)OC(=O)CCCC(=O)O
Reactant: Oc1cc(Cl)ccc1Oc1ccc(Cl)cc1Cl
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Solvent: Cc1ccccc1
Product: CCCCCCCC(=O)OCC(COC(=O)CCCCCCC)OC(=O)CCCC(=O)Oc1cc(Cl)ccc1Oc1ccc(Cl)cc1Cl
Reaction time: 20 h

Procedure:
2-Octanoyloxy-1-(octanoyloxymethyl)ethyl hydrogen glutarate (4.22 g.) was dissolved in dry toluene (40 ml.) and stirred with trifluoroacetic anhydride (5.2 ml.) for 2.5 hours. Triclosan (2.67 g.) was added and the mixture stirred for a further 20 hours. The solution obtained was washed successively with water (2×40 ml.), saturated sodium bicarbonate solution (2×40 ml.) and saturated brine (40 ml.). The organic phase was dried (MgSO4) and evaporated. The oil obtained was chromatographed on silica gel using methylene chloride as eluant to give 5-chloro-2-(2,4-dichlorophenoxy)phenyl 2-octanoyloxy-1-(octanoyloxymethyl)ethyl glutarate as an oil, having the same NMR and mass spectra as described for the ester in Example 1.