Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][Br:12].[C:13]1(=[O:23])[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15](=[O:22])[NH:14]1.[K].C>CN(C)C=O>[Br:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N:14]1[C:15](=[O:22])[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:13]1=[O:23]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: BrCCCCCCCCCCBr
Agent: [K]
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1CCCCCCCCCCBr
Yield: 66.4 %

Procedure:
A mixture of 100.0 g of 1,10-dibromodecane and 50.0 g of 1H-isoindole-1,3(2H)-dione, potassium salt in 500 ml of N,N-dimethylformamide was stirred and heated on a steam bath for eight hours. The reaction mixture was clarified while hot with activated charcoal, then filtered. The material on the filter was washed with 100 ml of N,N-dimethylformamide. The filtrate and wash were combined and taken to dryness in vacuo. The residue was triturated with 100 ml of hexane. The insoluble product was collected, washed with 50 ml of hexane, then air dried and gave 81.0 g of 2-(10-bromodecyl)-1H-isoindole-1,3(2H)-dione.
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[C:22]([CH3:23])=[CH:21][C:19]([NH2:20])=[C:18]([CH3:24])[CH:17]=1.Cl[C:26](Cl)([O:28][C:29](=[O:35])OC(Cl)(Cl)Cl)Cl.[CH3:37][N:38]1[CH2:43][CH2:42]C(O)[CH2:40][CH2:39]1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(N(CC)CC)C.C1(C)C=CC=CC=1>[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[C:22]([CH3:23])=[CH:21][C:19]([NH:20][C:29](=[O:35])[O:28][CH:26]2[CH2:42][CH2:43][N:38]([CH3:37])[CH2:39][CH2:40]2)=[C:18]([CH3:24])[CH:17]=1
Reactant: COc1cc2nccc(Oc3cc(C)c(N)cc3C)c2cc1OC
Reactant: CN1CCC(O)CC1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: COc1cc2nccc(Oc3cc(C)c(NC(=O)OC4CCN(C)CC4)cc3C)c2cc1OC
Yield: 57.1 %

Procedure:
4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml) and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 1-methyl-4-piperidinol (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, and the extract was washed with water and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (41 mg, yield 51%).
Reaction SMILES: S(Cl)(Cl)=O.[CH3:5][C:6]1[N:7]=[N:8][S:9][C:10]=1[CH2:11]O.C(=O)([O-])[O-].[K+].[K+].[C:19]1([SH:25])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CC(C)=O>[CH3:5][C:6]1[N:7]=[N:8][S:9][C:10]=1[CH2:11][S:25][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: Sc1ccccc1
Reactant: Cc1nnsc1CO
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: O=S(Cl)Cl
Product: Cc1nnsc1CSc1ccccc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 84.7 %

Procedure:
At an ice-cooled temperature, 3 ml of thionyl chloride was added to 0.50 g (3.8 mmol) of 4-methyl-1,2,3-thiadiazol-5-ylmethanol and stirred for 4 hours. Then, the reaction mixture was concentrated under reduced pressure, and 1.30 g (11.5 mmol) of potassium carbonate, 0.38 g (3.4 mmol) of thiophenol and 10 ml of acetone were added to the concentrate and reacted for 7 hours with heating under reflux. After the reaction was completed, the reaction mixture was cooled to room temperature, the precipitated matter was filtered off, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography using 5:1 mixture of n-hexane and ethyl acetate. Thus, 0.64 g of the objective compound was obtained.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10](Cl)(=[O:12])=[O:11])([O-])=O.[OH-:14].[Na+].Cl>[Zn]>[NH2:1][C:4]1[CH:9]=[CH:8][C:7]([C:7]2[CH:8]=[CH:9][C:4]([NH2:1])=[C:5]([S:10]([OH:12])(=[O:11])=[O:14])[CH:6]=2)=[CH:6][C:5]=1[S:10]([OH:12])(=[O:14])=[O:11]
Reactant: [OH-]
Reactant: O=[N+]([O-])c1ccccc1S(=O)(=O)Cl
Agent: Cl
Agent: [Na+]
Agent: [Zn]
Product: Nc1ccc(-c2ccc(N)c(S(=O)(=O)O)c2)cc1S(=O)(=O)O
Temperature: 80 °C
Reaction time: 1 h
Yield: 25.2 %

Procedure:
A 500 mL flask equipped with mechanical stirrer, condenser, addition funnel, and thermometer was charged with 50.0 g (0.255 mol) of 2-nitrobenzene sulfonyl chloride (Aldrich). Upon dropwise addition of 5M aqueous sodium hydroxide (125 mL, 0.625 mol) the reaction mixture warmed to 80° C. and a dark red/brown solution resulted. The mixture was stirred for 1 hour and the flask allowed to cool to room temperature. Next, 52.5 g of zinc dust (0.803 mol, Mallinckrodt) was added in one portion. The reaction mixture turned green and warmed to 40° C. Sodium hydroxide (50 percent w/w, 113.75 g, 1.42 mol) was then cautiously added dropwise. The temperature of the reaction mixture rose quickly and vigorous reflux ensued. The reaction mixture turned black, then light green, and finally gray. After addition was complete, the reaction mixture was heated to 90° C. and stirred for 30 minutes. The reaction mixture was cooled and filtered through diatomaceous earth. The zinc salts were washed several times with water yielding 850 mL of an orange/brown filtrate. The filtrate was immediately transferred to a 2 L flask equipped with mechanical stirrer, condenser, addition funnel, nitrogen inlet, and thermometer. Concentrated hydrochloric acid (250 mL) was added dropwise. A light yellow precipitate formed, leaving a clear yellow supernatant (pH=7). Further addition of acid caused the solid to dissolve and the solution to turn orange and then brown (pH=4). More acid caused a tan precipitate to form and persist. After HCl addition was complete, the temperature had risen to 45° C. and the pH was 1. The reaction mixture was stirred for an additional hour and then cooled in an ice bath. The precipitate was collected by filtration and dried in a vacuum oven at ambient temperature yielding a cake which weighed 11.69 g. The product was purified by dissolving it in 150 mL of hot water containing 13.5 mL of 5M sodium hydroxide. Concentrated HCl (15 mL) was then slowly added to reprecipitate the product. Vacuum filtration and drying in a vacuum oven at ambient temperature yielded 11.07 g (28.6 percent) of 4,4'-diaminobiphenyl-3,3'-disulfonic acid.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][C:7]([NH:10][CH3:11])=[CH:8][CH:9]=1)([O-])=O.[H][H]>[Pt]=O.C(O)C>[NH2:1][C:4]1[CH:5]=[N:6][C:7]([NH:10][CH3:11])=[CH:8][CH:9]=1
Reactant: [H][H]
Reactant: CNc1ccc([N+](=O)[O-])cn1
Agent: O=[Pt]
Solvent: CCO
Product: CNc1ccc(N)cn1

Procedure:
To 40 ml of an ethanol solution of the methylamino compound (4 g) obtained in (a) described above was added, 400 mg of platinum oxide, followed by reaction in an atmosphere of hydrogen at room temperature for 15 hours. The solvent was thereafter removed by distillation, and the residue was purified by silica gel column chromatography (eluent: chloroform, and subsequently chloroform: methanol=20:1 (v/v)) to obtain 320 mg of the intended product as brown crystals.
Reaction SMILES: [CH2:1]([C@H:6]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:20]=[CH:19][C:15]([C:16](O)=[O:17])=[CH:14][CH:13]=2)[CH2:8][CH2:7]1)[CH2:2][CH2:3][CH2:4][CH3:5].P(Cl)(Cl)(Cl)(Cl)[Cl:22]>C1C=CC=CC=1>[CH2:1]([C@H:6]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:20]=[CH:19][C:15]([C:16]([Cl:22])=[O:17])=[CH:14][CH:13]=2)[CH2:8][CH2:7]1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: CCCCC[C@H]1CC[C@H](c2ccc(C(=O)O)cc2)CC1
Reactant: ClP(Cl)(Cl)(Cl)Cl
Solvent: c1ccccc1
Product: CCCCC[C@H]1CC[C@H](c2ccc(C(=O)Cl)cc2)CC1

Procedure:
In a 30 ml-reaction vessel, 2.0 g (7.3 mM) of p-(trans-4-pentylcyclohexyl)benzoic acid and 10 ml of benzene were placed. To the mixture, 1.55 g (7.4 mM) of PCl5 was added in 25 minutes to room temperature, followed by heat-refluxing for 4 hours and distilling-off of the solvent to obtain p-(trans-4-pentylcyclohexyl)benzoic acid chloride.
Reaction SMILES: [C:1](Cl)(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].C1C=CN=CC=1.[FH:25]>>[C:1]([F:25])(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCCCCCCCCC(=O)Cl
Reactant: F
Solvent: c1ccncc1
Product: CCCCCCCCCCCCCCCC(=O)F
Temperature: 20 °C
Reaction time: 0.33 h
Yield: 76 %

Procedure:
Palmitoyl chloride (651 mg, 2.2 mole) was added to pyridinium poly(hydrogen fluoride) (1 ml) in a teflon reaction vial and the mixture stirred at 20° C. for 20 min. After cooling to 0° C., it was quenched with ice-water (5 ml), extracted with ethyl acetate, and the organic layer washed (water, brine), dried over anhydrous magnesium sulfate, concentrated and evaporatively distilled (120° C./0.025 torr) to give palmitoyl fluoride (76%) (contaminated with 5% of the corresponding acid). Since this concentration of contaminant is not harmful to the biological activity of the compound, no further purification is required.
Reaction SMILES: [C-:1]#[N:2].[Na+].[CH2:4]([O:6][C:7](=[O:34])[C@@H:8]1[CH2:12][C@H:11](OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:10][N:9]1[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25])[CH3:5]>CS(C)=O.[Cl-].[Na+].O.O>[CH2:4]([O:6][C:7](=[O:34])[C@@H:8]1[CH2:12][C@@H:11]([C:1]#[N:2])[CH2:10][N:9]1[C:24]([O:26][CH2:27][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)=[O:25])[CH3:5]
Reactant: CCOC(=O)[C@@H]1C[C@H](OS(=O)(=O)c2ccc(C)cc2)CN1C(=O)OCc1ccccc1
Reactant: [C-]#N
Agent: [Cl-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CCOC(=O)[C@@H]1C[C@@H](C#N)CN1C(=O)OCc1ccccc1
Temperature: 25 °C
Yield: 70.1 %

Procedure:
Finely powdered NaCN (0.49 g, 10 mmol) was suspended in a stirring mixture of 5 (3.0 g, 6.7 mmol) in DMSO (7 mL). The reaction flask was heated in an oil bath at 80° C. for 3 h, during which time the NaCN had completely dissolved and the reaction mixture had turned a deep orange color. After cooling to room temperature, the reaction was diluted with brine (3 mL) and H2O (4 mL), then extracted with Et2O (5×11 mL). The combined organic layers were dried (MgSO4) and concentrated to a yellow syrup which was purified by flash chromatography (silica gel, using 1:1 ethyl ether-petroleum ether) yielding 1.42 g (70%) of the N-CBZ-trans-4-cyano-L-proline ethyl ester as a colorless viscous oil: TLC Rf 0.22 (4:2 ethyl ether-petroleum ether); [α]24D -39° (c 1.05, CHCl3); 1H NMR (250 MHz, CDCl3) δ 7.38-7.27 (m, 5 H), 5.21-5.03 (m 2 H, PhCH2), 4.55-4.45 (m, 1 H, H-2), 4.21 (q, J=7.1 Hz, 1 H, CO2CH2CH3, one of two rotamers), 4.09-3.94 (m, 2 H, CO2CH2CH3 and H-5), 3.80-3.67 (m, 1 H, H-5), 3.35-3.21 (m, 1 H, H-4), 2.62-2.34 (m, 2 H, H-3), 1.28+1.13 (t, J=7.1 Hz, CO2CH2CH3, two rotamers); IR (CHCl3) 2995, 2900, 2250, 1740, 1705, 1420, 1355, 1195, 1125, 1020 cm-1 ; LRMS (CI, 70 eV, isobutane) m/e 303 (MH+, 66), 259 (44), 91 (100); HRMS (EI, 21 eV) m/e 302.1264 (302.1266 calcd for C16H18N2O4).
Reaction SMILES: Cl[C:2]1[C:3]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[C:4]([CH3:9])[NH:5][C:6](=[O:8])[CH:7]=1.[CH3:15][C:16]1[CH:17]=[C:18]([SH:23])[CH:19]=[C:20]([CH3:22])[CH:21]=1>C(O)C.C(N(CC)CC)C>[CH3:15][C:16]1[CH:17]=[C:18]([S:23][C:2]2[C:3]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[C:4]([CH3:9])[NH:5][C:6](=[O:8])[CH:7]=2)[CH:19]=[C:20]([CH3:22])[CH:21]=1
Reactant: Cc1cc(C)cc(S)c1
Reactant: CCOC(=O)c1c(Cl)cc(=O)[nH]c1C
Solvent: CCO
Solvent: CCN(CC)CC
Product: CCOC(=O)c1c(Sc2cc(C)cc(C)c2)cc(=O)[nH]c1C

Procedure:
A mixture of the intermediate 13 (1.2 g; 5.6 mmol) in ethanol (15 ml), triethylamine (1.5 ml) and 3,5-dimethylthiophenol (1.45 ml; 11 mmol) was heated under reflux for 16 hours. After evaporation under reduced pressure, diethylether (50 ml) was added and the precipitate was filtered off. The intermediate 14 was obtained (1.42 g; 80%) as a colorless solid m.p.=233–235° C.
Reaction SMILES: [H-].[Na+].Cl.[NH:4]1[CH2:7][CH:6]([C:8]2[O:12][N:11]=[C:10]([C:13]3[N:18]=[C:17]([N:19]([CH3:26])[C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[N:16]=[C:15]([NH2:27])[N:14]=3)[N:9]=2)[CH2:5]1.[F:28][C:29]([F:40])([F:39])[CH2:30]OS(C(F)(F)F)(=O)=O>CN(C=O)C.CCOC(C)=O>[CH3:26][N:19]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:17]1[N:16]=[C:15]([NH2:27])[N:14]=[C:13]([C:10]2[N:9]=[C:8]([CH:6]3[CH2:5][N:4]([CH2:30][C:29]([F:40])([F:39])[F:28])[CH2:7]3)[O:12][N:11]=2)[N:18]=1
Reactant: CN(c1ccccc1)c1nc(N)nc(-c2noc(C3CNC3)n2)n1
Reactant: O=S(=O)(OCC(F)(F)F)C(F)(F)F
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CN(c1ccccc1)c1nc(N)nc(-c2noc(C3CN(CC(F)(F)F)C3)n2)n1
Temperature: 25 °C
Reaction time: 16 h
Yield: 8.9 %

Procedure:
To a solution of sodium hydride (60% dispersion in mineral oil, 16 mg, 0.41 mmol) in anhydrous DMF (20 mL) at 0 C was added 6-[5-(azetidin-3-yl)-1,2,4-oxadiazol-3-yl]-2-N-methyl-2-N-phenyl-1,3,5-triazine-2,4-diamine hydrochloride (Intermediate 129, 50 mg, 0.138 mmol) and trifluoromethanesulfonic acid 2,2,2-trifluoro-ethyl ester (160 mg, 0.69 mmol) under nitrogen. The reaction mixture was stirred at room temperature for 16 h and then was quenched with saturated ammonium chloride aqueous solution (10 mL) and evaporated to dryness. The solid obtained was dissolved in EtOAc (20 mL), washed with water (2×25 mL), dried over magnesium sulfate and evaporated to dryness. The resulting crude product was purified by silica chromatography (2% MeOH in DCM) and then further by preparative HPLC-MS (Method B) to afford the title compound as white solid (5 mg, 9%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9]3[C:15](=O)[N:14]([CH3:17])[C:13]4[CH:18]=[CH:19][CH:20]=[CH:21][C:12]=4[O:11][C:10]=3[C:5]2=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)(Cl)Cl.[CH3:28][N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6](=[N:8][C:9]3[C:10]=2[O:11][C:12]2[CH:21]=[CH:20][CH:19]=[CH:18][C:13]=2[N:14]([CH3:17])[C:15]=3[N:32]2[CH2:33][CH2:34][N:29]([CH3:28])[CH2:30][CH2:31]2)[CH:7]=1
Reactant: CN1CCNCC1
Reactant: CN1C(=O)c2[nH]c3cc(Cl)ccc3c2Oc2ccccc21
Agent: ClP(Cl)(Cl)(Cl)Cl
Product: CN1CCN(C2=C3N=c4cc(Cl)ccc4=C3Oc3ccccc3N2C)CC1

Procedure:
In the same way as described in example 1, 3-chloro-7-methyl-7H-indolo[3,2-b][1,5]benzoxazepine-6(5H)-one, phosphorous pentachloride and N-methyl piperazine were reacted. The solid product was recrystallized from ethanol for analysis, mp. 187°-8°.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([CH:13]2[C:21]3[C:16](=[CH:17][C:18]([C:22]([NH2:24])=[O:23])=[CH:19][CH:20]=3)[C:15](=[O:25])[N:14]2[CH3:26])[CH2:10][CH:11]=O)[CH:5]=[CH:6][C:7]=1[Cl:8].[O:27]=[C:28]1[NH:33][CH2:32][CH2:31][CH2:30][N:29]1[CH:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1>>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([CH:13]2[C:21]3[C:16](=[CH:17][C:18]([C:22]([NH2:24])=[O:23])=[CH:19][CH:20]=3)[C:15](=[O:25])[N:14]2[CH3:26])[CH2:10][CH2:11][N:37]2[CH2:38][CH2:39][CH:34]([N:29]3[CH2:30][CH2:31][CH2:32][NH:33][C:28]3=[O:27])[CH2:35][CH2:36]2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: CN1C(=O)c2cc(C(N)=O)ccc2C1C(CC=O)c1ccc(Cl)c(Cl)c1
Reactant: O=C1NCCCN1C1CCNCC1
Product: CN1C(=O)c2cc(C(N)=O)ccc2C1C(CCN1CCC(N2CCCNC2=O)CC1)c1ccc(Cl)c(Cl)c1
Product: Cl
Yield: 124.9 %

Procedure:
3-(3,4-Dichlorophenyl)-3-(5-aminocarbonyl-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)propionaldehyde (0.2 g) was coupled to 4-(2-oxoperhydropyrimidine-1-yl)piperidine (0.093 g) by a method similar to that described in Example 8. The reaction product was not purified by chromatography but converted to the corresponding hydrochloride salt as described in the Example 8 to afford the title compound (0.19 g); mp 240°-250° C. (d); MS: m/z=558(M+1); NMR: 2.60-2.77 (m,3), 3.29 (broad,3), 4.67 (m,1), 5.21 (s,1), 6.63 (m,1), 6.85 (s,1), 7.19 (d, J=8, 1), 7.63-7.82 (m,3). Analysis for C27H31Cl2N4 O2Br.1.0H2O.1.3HCl.0.2C4H10O: Calculated: C, 54.16; H, 6.04, N, 10.96; Found: C, 54.21; H, 5.86; N, 10.74.
Reaction SMILES: C1(CCN2C3C(=CC=CC=3)C(=O)C2=O)CC1.[Br:17][C:18]1[CH:26]=[CH:25][CH:24]=[C:23]2[C:19]=1[C:20](=[O:35])[C:21](=[O:34])[N:22]2[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1.O1C2C=CC(O)=CC=2OC1.[O:46]1[C:50]2[CH:51]=[C:52]([OH:55])[CH:53]=[CH:54][C:49]=2[CH2:48][CH2:47]1>>[Br:17][C:18]1[CH:26]=[CH:25][CH:24]=[C:23]2[C:19]=1[C:20]([OH:35])([C:53]1[C:52]([OH:55])=[CH:51][C:50]3[O:46][CH2:47][CH2:48][C:49]=3[CH:54]=1)[C:21](=[O:34])[N:22]2[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1
Reactant: O=C1C(=O)N(Cc2ccccn2)c2cccc(Br)c21
Reactant: Oc1ccc2c(c1)OCC2
Agent: O=C1C(=O)N(CCC2CC2)c2ccccc21
Agent: Oc1ccc2c(c1)OCO2
Product: O=C1N(Cc2ccccn2)c2cccc(Br)c2C1(O)c1cc2c(cc1O)OCC2

Procedure:
Following the procedure as described in PREPARATION 2B, and making non-critical variations to replace 1-(2-cyclopropylethyl)-1H-indole-2,3-dione with 4-bromo-1-(pyridin-2-ylmethyl)-1H-indole-2,3-dione, and 1,3-benzodioxol-5-ol with 2,3-dihydrobenzofuran-6-ol, the title compound was obtained (91%) as a colorless solid: mp>225° C.; 1H NMR (300 MHz, DMSO-d6) δ 9.29 (s, 1H), 8.54 (d, 1H), 7.70 (dt, 1H); 7.61 (br, 1H), 7.32-7.26 (m, 2H), 7.07 (d, 1H), 7.00 (d, 1H), 6.72 (d, 1H), 6.60 (br, 1H), 6.02 (s, 1H), 4.91 (ABq, 2H), 4.47 (t, 2H), 3.06 (d, 2H); 13C NMR (75 MHz, DMSO-d6) δ 176.9, 160.4, 156.3, 153.8, 149.6, 146.1, 137.5, 130.9, 130.8, 126.5, 125.8, 123.1, 121.5, 118.8, 117.3, 116.4, 108.3, 96.7, 76.6, 71.9, 45.7, 29.1; MS (ES+) m/z 455.4 (M+1), 437.4 (M−17).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([OH:8])=[N:6][CH:7]=1.[H-].[Na+].Cl[C:12]1[N:16]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:15]2[CH:25]=[CH:26][CH:27]=[CH:28][C:14]=2[N:13]=1.O>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][C:12]2[N:16]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:23])([CH3:24])[CH3:22])[C:15]3[CH:25]=[CH:26][CH:27]=[CH:28][C:14]=3[N:13]=2)=[N:6][CH:7]=1.[Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:8])[N:6]([C:12]2[N:16]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:23])([CH3:24])[CH3:22])[C:15]3[CH:25]=[CH:26][CH:27]=[CH:28][C:14]=3[N:13]=2)[CH:7]=1
Reactant: Oc1ccc(Br)cn1
Reactant: C[Si](C)(C)CCOCn1c(Cl)nc2ccccc21
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: C[Si](C)(C)CCOCn1c(-n2cc(Br)ccc2=O)nc2ccccc21
Product: C[Si](C)(C)CCOCn1c(Oc2ccc(Br)cn2)nc2ccccc21
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a stirred mixture of 5-bromopyridin-2-ol (500 mg) in DMF (10 mL) was added NaH (60% in oil, 115 mg) at room temperature. The mixture was stirred at room temperature for 30 min and then 2-chloro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzo[d]imidazole (813 mg) was added. The mixture was exposed to microwave irradiation at 200° C. for 1 h, treated with water, and extracted with AcOEt. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (AcOEt/MeOH) and crystallized from AcOEt/hexane to give 2-(5-bromopyridin-2-yloxy)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazole (336 mg) and 5-bromo-1-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one (170 mg).
Reaction SMILES: [C:1]([C:4]1[CH:19]=[CH:18][C:7]([O:8][C:9]2[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=2[C:11]([OH:13])=O)=[CH:6][CH:5]=1)([OH:3])=[O:2].S(=O)(=O)(O)O>O>[O:13]=[C:11]1[C:6]2[CH:5]=[C:4]([C:1]([OH:3])=[O:2])[CH:19]=[CH:18][C:7]=2[O:8][C:9]2[C:10]1=[CH:14][CH:15]=[CH:16][CH:17]=2
Reactant: O=C(O)c1ccc(Oc2ccccc2C(=O)O)cc1
Agent: O=S(=O)(O)O
Solvent: O
Product: O=C(O)c1ccc2oc3ccccc3c(=O)c2c1
Temperature: 80 °C
Reaction time: 0.5 h
Yield: 87.6 %

Procedure:
A mixture of 29.9 g (0.11 mol) of 2-(4-carboxyphenoxy)benzoic acid (Example 10e) and 250 ml of concentrated sulfuric acid is heated at 80° C. for one hour. The resulting solution is then poured onto about 2.5 litres of water and the mixture is stirred vigorously for 30 minutes. The product which has precipitated is filtered off, washed with water and dried under a high vacuum. 23.15 g (85%) of 9-oxo-9H-xanthene-2-carboxylic acid, melting point >280° C., result as a beige powder.
Reaction SMILES: [CH3:1][C@H:2]([NH:11][CH3:12])[C@@H:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:13](OC(=O)CCCCC)(=O)[CH2:14]CCCC.[O:28]1[CH2:32][CH2:31][CH2:30][CH2:29]1>>[OH:10][CH:3]([C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)[CH:2]([N:11]([CH3:12])[C:32](=[O:28])[CH2:31][CH2:30][CH2:29][CH2:13][CH3:14])[CH3:1]
Reactant: CCCCCC(=O)OC(=O)CCCCC
Reactant: CN[C@@H](C)[C@@H](O)c1ccccc1
Reactant: C1CCOC1
Product: CCCCCC(=O)N(C)C(C)C(O)c1ccccc1
Temperature: 23 °C
Reaction time: 0.42 h
Yield: 91 %

Procedure:
In a dry 2 L round-bottomed flask equipped with a magnetic stirrer was added (+)-pseudoephedrine (40.0 g, 242.06 mmol, 1.0 equiv) and tetrahydrofuran (500 mL), and the mixture was stirred in a 23° C. water bath. Hexanoic anhydride (55.51 g, 259 mmol, 1.07 equiv) was added via cannula over a 10 minute interval, and transfer was quantitated with an additional portion of tetrahydrofuran (10 mL). After 25 minutes, the reaction was quenched with saturated sodium bicarbonate (300 mL). Volatile components were removed under reduced pressure, and the residue was extracted from water (500 mL) with ethyl acetate (3×250 mL). The organic extracts were dried over sodium sulfate, and after removal of the solvent under reduced pressure, a white solid was obtained, which was recrystallized from 1:1 ether/hexanes (200 mL) to afford the hexanamide as white crystals (58.2 g, 91% yield): mp 62°-63° C.; 1H NMR (300 MHz, C 6D6) δ7.0-7.4 (m, 5H), 4.9 (br, 1H), 4.52 (d, 1H, J=6.9 Hz), 4.14 (m, 1H), 3.77 (m, 1H), 2.79 (s, 3H), 2.42 (m, 2H), 2.13 (s, 3H), 1.83 (m, 2H), 1.59 (qn, 2H, J=7.6 Hz), 1.1-1.4 (m, 4H), 0.99 (d, 3H, J=7.0 Hz), 0.86 (t, 3H, J=7.0 Hz), 0.59 (d, 3H, J=6.8 Hz); 13C NMR (75.5 MHz, CDCl3) δ175.2, 174.2, 142.3, 141.6, 128.3, 128.0, 127.8, 127.3, 126.7, 126.2, 76.1, 75.1, 58.2, 57.0, 34.1, 33.4, 32.4, 31.5, 31.3, 26.6, 24.9, 24.5, 22.31, 22.29, 15.2, 14.2, 13.82, 13.79; FTIR (neat film) cm-1 3378 (br, m), 2956 (m), 2931 (m), 2871 (m), 1618 (s), 1453 (m), 1406 (m), 1051 (m), 701 (m); HRMS (FAB) Calcd for C16H26N02 (MH+): 264.1965. Found: 264.1966.