Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:11][CH3:12])(=[O:10])[CH:2]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[OH:3]>CO>[C:4]1([C:2](=[O:3])[C:1]([O:11][CH3:12])=[O:10])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: COC(=O)C(O)c1ccccc1
Solvent: CO
Product: COC(=O)C(=O)c1ccccc1

Procedure:
The procedures of Example 1 were repeated except for employing the above-obtained catalyst (8 ml), feeding air and nitrogen at feed rates of 35 ml/min. and 70 ml/min., respectively, and feeding a methyl mandelate solution comprising methanol and methyl mandelate (6:1, by weight) at a feed rate of 17.0 g/hr., to carry out the gaseous catalytic reaction. There was obtained methyl phenylglyoxylate as α-keto acid ester. The results are set forth in Table 5.
Reaction SMILES: [NH2:1][CH:2]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([O:28][C:29]([F:34])([F:33])[CH:30]([F:32])[F:31])[CH:23]=1)[CH:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([CH2:19][CH3:20])[CH:13]=2)=[CH:7][CH:6]=1)[OH:4].[C:35]1([C:46](O)=[O:47])[CH:36]=[CH:37][CH:38]=[C:39]2[CH2:45][CH2:44][CH2:43][CH:42]=[CH:41][C:40]=12.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1>C(#N)C.O>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([O:11][C:8]2[CH:9]=[CH:10][C:5]([CH:3]([OH:4])[CH:2]([NH:1][C:46]([C:35]3[CH:36]=[CH:37][CH:38]=[C:39]4[CH2:45][CH2:44][CH2:43][CH:42]=[CH:41][C:40]=34)=[O:47])[CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([O:28][C:29]([F:34])([F:33])[CH:30]([F:32])[F:31])[CH:23]=3)=[CH:6][CH:7]=2)=[CH:13][C:14]=1[CH2:19][CH3:20]
Reactant: O=C(O)c1cccc2c1C=CCCC2
Reactant: CCc1cc(Oc2ccc(C(O)C(N)Cc3cccc(OC(F)(F)C(F)F)c3)cc2)ccc1Cl
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CC#N
Product: CCc1cc(Oc2ccc(C(O)C(Cc3cccc(OC(F)(F)C(F)F)c3)NC(=O)c3cccc4c3C=CCCC4)cc2)ccc1Cl
Temperature: 25 °C
Reaction time: 8 h
Yield: 79.3 %

Procedure:
To a solution of (1RS,2SR)-2-amino-1-(4-((4-chloro-3-ethylphenyl)oxy)phenyl)-3-(3-((1,1,2,2-tetrafluoroethyl)oxy)phenyl)-1-propanol (300 mg, 0.60 mmol) in acetonitrile (16 ml) were added 6,7-dihydro-5H-benzo[a]cycloheptene-1-carboxylic acid (114 mg, 0.60 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (174 mg, 0.91 mmol) and 1-hydroxy-1H-benzotriazole (92 mg, 0.60 mmol), and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (100 ml) and extracted with ethyl acetate (100 ml×2). The extract was washed successively with 1N hydrochloric acid, 1N aqueous sodium hydroxide solution and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. Recrystallization of the residue from ethyl acetate-hexane gave the title compound (318 mg, 79%).
Reaction SMILES: [CH3:1][C:2]1[CH:19]=[CH:18][CH:17]=[CH:16][C:3]=1[C:4]([NH:6][C:7]1[CH:15]=[CH:14][C:10]([C:11](Cl)=[O:12])=[CH:9][CH:8]=1)=[O:5].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH:32]1[N:36]2[C:37]3[C:42]([NH:43][CH2:44][C:35]2=[CH:34][CH:33]=1)=[CH:41][CH:40]=[CH:39][CH:38]=3>O1CCCC1>[CH3:1][C:2]1[CH:19]=[CH:18][CH:17]=[CH:16][C:3]=1[C:4]([NH:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]([N:43]2[C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[N:36]3[CH:32]=[CH:33][CH:34]=[C:35]3[CH2:44]2)=[O:12])=[CH:9][CH:8]=1)=[O:5]
Reactant: c1ccc2c(c1)NCc1cccn1-2
Reactant: Cc1ccccc1C(=O)Nc1ccc(C(=O)Cl)cc1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: Cc1ccccc1C(=O)Nc1ccc(C(=O)N2Cc3cccn3-c3ccccc32)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 34.4 %

Procedure:
A mixture of 0.51 g of 4-[(2-methylbenzoyl)amino]benzoyl chloride and 0.36 g of 1,1'-carbonyldiimidazole in 6 ml of tetrahydrofuran is stirred at room temperature for 1 hour. To the reaction mixture is added 0.17 g of 4,5-dihydropyrrolo-[1,2-a]-quinoxaline followed by heating at reflux for 60 hours. The volatiles are concentrated in vacuo to a residue which is dissolved in ethyl acetate. The organic layer is washed with 1N HCl, 1M NaHCO3, brine, dried with Na2SO4 and filtered through hydrous magnesium silicate. The volatiles are concentrated in vacuo to a residue which is chromatographed by elution with 1:2 ethyl acetate-hexanes to give 0.14 g of the desired product as a white solid, m.p. 206-207° C.; MASS SPEC (CI) 408(MH+).
Reaction SMILES: B(F)(F)F.CCOCC.[Cl:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][CH:15]=[C:14]2[C:20](=O)[CH2:21][CH2:22][C:23]([O:25][CH3:26])=[O:24].[BH4-].[Na+].Cl>O1CCCC1.C(OCC)(=O)C.CC(C)=O>[Cl:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][CH:15]=[C:14]2[CH2:20][CH2:21][CH2:22][C:23]([O:25][CH3:26])=[O:24]
Reactant: COC(=O)CCC(=O)c1c[nH]c2ccc(Cl)cc12
Agent: Cl
Agent: FB(F)F
Agent: [BH4-]
Solvent: CC(C)=O
Solvent: C1CCOC1
Solvent: CCOCC
Product: COC(=O)CCCc1c[nH]c2ccc(Cl)cc12
Temperature: 25 °C
Reaction time: 3 h
Yield: 34.8 %

Procedure:
Boron trifluoride etherate (4.2 ml) was added to a mixture of methyl 4-(5-chloroindol-3-yl)-4-oxobutyrate (3.00 g) and sodium borohydride (0.855 g) in tetrahydrofuran (100 ml) at 25° C. over 20 minutes. After the mixture was stirred at 25° C. for 3 hours, acetone (5 ml) was added. The reaction mixture was poured into a mixture of ethyl acetate and 1N hydrochloric acid. The organic layer was separated, washed with water and brine, and dried over magnesium sulfate. After evaporation of solvent, the residue was purified by column chromatography on silica gel (200 ml) eluting with chloroform and by recrystallization from a mixture of ethyl acetate and hexane to give methyl 4-(5-chloroindol-3-yl)butyrate (989 mg) as colorless crystals.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1.[CH:20]1[C:33]2[C:32]3([CH2:35][N:36]4[CH2:41][CH2:40][C:39](=[O:42])[CH2:38][CH2:37]4)[CH2:34][CH:25]([C:26]4[C:31]3=[CH:30][CH:29]=[CH:28][CH:27]=4)[C:24]=2[CH:23]=[CH:22][CH:21]=1.[Br-].[Li+]>C1COCC1.CCCCCC.C1COCC1>[CH:30]1[C:31]2[C:32]3([CH2:35][N:36]4[CH2:41][CH2:40][C:39]([C:19]5[C:14]([F:13])=[N:15][CH:16]=[CH:17][CH:18]=5)([OH:42])[CH2:38][CH2:37]4)[CH2:34][CH:25]([C:24]4[C:33]3=[CH:20][CH:21]=[CH:22][CH:23]=4)[C:26]=2[CH:27]=[CH:28][CH:29]=1
Reactant: O=C1CCN(CC23CC(c4ccccc42)c2ccccc23)CC1
Reactant: Fc1ccccn1
Agent: [Br-]
Agent: [Li+]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Solvent: CCCCCC
Product: OC1(c2cccnc2F)CCN(CC23CC(c4ccccc42)c2ccccc23)CC1
Temperature: -20 °C
Yield: 77.4 %

Procedure:
To a cooled solution (-72° C.) of distilled diisopropylamine (7.86 mL, 56.1 mmol, 1.3 eq) in THF/hexane (57 mL/37 mL) under nitrogen was added n-butyllithium (2.5M in hexane, 23.8 mL, 59.4 mmol, 1.4 eq). The resulting solution was warmed to -20° C. to assure deprotonation and then recooled to -72° C. A THF solution (13 mL) of 2-fluoropyridine (4.50 mL, 53.5 mmol, 1.25 eq) was then added dropwise resulting in a yellow precipitate. The deprotonation reaction was warmed to -50° C. for 45 min and briefly allowed to reach -30° C. before being recooled to -72° C. To this solution was added a mixture of 1-(9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)-4-piperidone (described in 1d above) (13.0 g, 42.9 mmol) and lithium bromide (7.45 g, 85.8 mmol, 2 eq) in THF (48 mL) in a dropwise fashion. In the course of the addition, the yellow precipitate dissolved. The reaction was warmed to -20° C. over 1.5 h and quenched with acetic acid (10 mL). The solution was diluted with water (400 mL), basified with 2.5N NaOH and extracted with ethyl acetate (3×300 mL). The combined organic extracts were dried over anhydrous sodium sulfate, filtered and reduced to a solid. The product was purified by recrystallization from ethyl acetate (3 crops) to yield 13.3 g (77%) of the title compound as a white solid. TLC analysis (Rf 0.22, 30% ethyl acetate in hexane). 1H NMR (CDCl3, 300 mHz) 8.09 (d, J=8.2 Hz, 1H), 7.91 (dd, J=8.2, 9.4 Hz, 1H), 7.21 (m, 5H), 6.94 (m, 4H), 4.27 (s, 1H), 3.48 (s, 2H), 2.91 (m, 2H), 2.74 (m, 2H), 2.62 (s, 2H), 2.26 (m, 2H), 1.78 (m, 2H) MS (Cl, CH4) m/z 401 (M+1, 100), 429 (M+29,15), 383 (21) The free base was dissolved in ether and acidified with ethereal HCl. The hydrochloride salt was filtered, washed with fresh ether and dried in vacuo (room temperature, 10 pascal, 18 h) to yield a white solid, mp 188°-191° C. (dec).
Reaction SMILES: [N+](C1C=CC(C(OO)=O)=CC=1)([O-])=O.[C:14]([OH:18])([CH3:17])([CH3:16])C.[OH:19][C:20]1[CH:38]=[CH:37][C:36]2[C@@H:35]3[C@H:25]([C@H:26]4[C@@:30]([CH2:33][CH2:34]3)(CC)[CH:29]=[CH:28]C4)[CH2:24][CH2:23][C:22]=2[CH:21]=1>C(Cl)CCl>[O:18]1[C@H:16]2[C@:30]3([CH2:33][CH2:34][C@H:35]4[C@@H:25]([CH2:24][CH2:23][C:22]5[CH:21]=[C:20]([OH:19])[CH:38]=[CH:37][C:36]=54)[C@@H:26]3[CH2:17][C@@H:14]12)[CH2:29][CH3:28]
Reactant: CC[C@@]12C=CC[C@H]1[C@@H]1CCc3cc(O)ccc3[C@H]1CC2
Reactant: CC(C)(C)O
Agent: O=C(OO)c1ccc([N+](=O)[O-])cc1
Solvent: ClCCCl
Product: CC[C@]12CC[C@@H]3c4ccc(O)cc4CC[C@H]3[C@@H]1C[C@H]1O[C@H]12
Reaction time: 18 h

Procedure:
At room temperature, a solution of 360 mg. of p-nitroperbenzoic acid in 2.5 ml. of tert.-butanol and 0.5 ml. of ethylene chloride is gradually added to 450 mg. of 3-hydroxy-18-methyl-1,3,5(10),16-estratetraene in 15 ml. of ethylene chloride. After 18 hours, the crude product is worked up as described in (A) and purified by preparative layer chromatography (eluent: hexane/ethyl acetate = 7 : 3). In this way, 310 mg. of 16α,17α-epoxy-3-hydroxy-18-methyl-1,3,5(10)-estratriene is isolated as an oily product.
Reaction SMILES: [Si:1]([O:8][C@H:9]([CH2:14][C:15](=[O:23])[CH2:16][P:17]([O:21][CH3:22])([O:19][CH3:20])=[O:18])[CH2:10][C:11]([OH:13])=[O:12])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:24]C(C)=O.CI.C(=O)([O-])[O-].[K+].[K+]>O>[Si:1]([O:8][C@H:9]([CH2:14][C:15](=[O:23])[CH2:16][P:17]([O:19][CH3:20])([O:21][CH3:22])=[O:18])[CH2:10][C:11]([O:13][CH3:24])=[O:12])([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2]
Reactant: CC(C)=O
Reactant: COP(=O)(CC(=O)C[C@H](CC(=O)O)O[Si](C)(C)C(C)(C)C)OC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CI
Product: COC(=O)C[C@@H](CC(=O)CP(=O)(OC)OC)O[Si](C)(C)C(C)(C)C

Procedure:
The concentrated solution (1.88 g) containing (R)-3-t-butyldimethylsilyloxy-6-dimethoxyphosphinyl-5-oxohexanoic acid, which was prepared by concentrating the ethyl acetate portion, was obtained in the same manner as Example 1. To the solution, 24 ml of acetone were added to prepare an acetone solution. 3.1 g of methyl iodide and 0.60 g of potassium carbonate were added to the solution with stirring, and then the mixture was further stirred for 5 hours at room temperature. After 24 ml of water was added to the solution, the solution was extracted with two portios of 30 ml of ethyl acetate. The ethyl acetate portions were combined and dried over anhydrous magnesium sulfate. Then, the solvent was removed by distillation in vacuo to give 1.2 g of methyl (R)-3-t-butyldimethylsilyloxy-6-dimethoxyphosphinyl-5-oxohexanoate as an oil (optical purity: 98% ee; purity: 79%).
Reaction SMILES: [OH:1][CH2:2][C:3]([CH2:8][OH:9])([CH2:6][OH:7])[CH2:4]O.[BrH:10]>C(O)(=O)C>[OH:1][CH2:2][C:3]([CH2:8][OH:9])([CH2:6][OH:7])[CH2:4][Br:10]
Reactant: Br
Reactant: OCC(CO)(CO)CO
Solvent: CC(=O)O
Product: OCC(CO)(CO)CBr
Reaction time: 3 h
Yield: 50 %

Procedure:
200 g (1.47 mol) of pentaerythritol (PE), 1.51 of glacial acetic acid and 17 ml of 48% HBr are refluxed for 1.5 h. A further 170 ml of 48% HBr are added and the reaction mixture is then boiled for another 3 h. The same procedure is repeated with the addition of 96 ml of HBr. The glacial acetic acid and water are then distilled off completely, 750 ml of 98% ethanol and 50 ml of 48% HBr are added to the viscous residue and approx. 500 ml of ethanol are removed by slow distillation. A further 750 ml of ethanol are subsequently added and then distilled off completely. After the addition of 500 ml of toluene, the solvent is distilled off and the same procedure is repeated. The viscous residue is boiled for several hours with 500 ml of dry ether, with stirring, until a white solid deposits. The solid is filtered off with suction, washed with dry ether, dried and recrystallized from chloroform/ethyl acetate=3:2. Yield: 50%. M.p.=75-76° C.
Reaction SMILES: [CH3:1][NH:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([C:9]#[C:10][CH2:11][OH:12])[CH2:5][CH2:4]1.[Br:13][C:14]1[CH:15]=[CH:16][C:17](F)=[N:18][CH:19]=1.C(N(C(C)C)C(C)C)C.[Na+].[I-]>CN(C=O)C>[Br:13][C:14]1[CH:15]=[CH:16][C:17]([N:2]([CH3:1])[C@H:3]2[CH2:4][CH2:5][C@H:6]([C:9]#[C:10][CH2:11][OH:12])[CH2:7][CH2:8]2)=[N:18][CH:19]=1
Reactant: Fc1ccc(Br)cn1
Reactant: CN[C@H]1CC[C@H](C#CCO)CC1
Agent: [I-]
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CN(c1ccc(Br)cn1)[C@H]1CC[C@H](C#CCO)CC1
Temperature: 120 °C

Procedure:
A mixture of 0.67 g (4 mmol) trans-3-(4-Methylamino-cyclohexyl)-prop-2-yn-1-ol, 1.24 ml (12 mmol) of 5-bromo-2-fluoropyridine and 1.76 ml (13.6 mmol) N-ethyldiisopropylamine was heated for 3 h at 80° C. and 24 h at 120° C. The mixture was diluted with 1 ml DMF, treated with a catalytic amount of NaI and heated for 2 days at 120° C. The reaction was cooled, evaporated and partitioned between aqueous saturated NaHCO3/Et2O (3×). The organic phases were washed with aqueous 10% NaCl, dried (NaSO4) and evaporated. Flash chromatography on silica gel (MeCl2/Et2O 97.5:2.5 to 92.5:7.5) gave 0.57 g (44%) of trans-3-{4-[(5-Bromo-pyridin-2-yl)-methyl-amino]-cyclohexyl}-prop-2-yn-1-ol, MS: 323 (MH+, 1Br).
Reaction SMILES: [BrH:1].[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[CH:6]=[CH:5][C:4]=1[CH:10](O)[CH3:11].O>CC(O)=O>[Br:1][CH:10]([C:4]1[CH:5]=[CH:6][C:7]([Cl:9])=[CH:8][C:3]=1[Cl:2])[CH3:11]
Reactant: Br
Reactant: CC(O)c1ccc(Cl)cc1Cl
Solvent: O
Solvent: CC(=O)O
Product: CC(Br)c1ccc(Cl)cc1Cl
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
15 ml of a 33% solution of HBr in AcOH are cooled to 0° C., 2 ml of 2,4-dichloro-1-(1-hydroxyethyl)benzene are added dropwise and the reaction mixture is stirred for 30 minutes at 0° C. and then for 3 hours at RT. It is poured into iced water and extracted with AcOEt, the organic phase is washed with saturated aqueous NaHCO3 solution, with water and with saturated NaCl solution and dried over MgSO4 and the solvent is evaporated off under vacuum to give 3.4 g of the expected product.
Reaction SMILES: C(C1C=CC=CC=1)(CC)C.[Na].[CH3:12][CH:13](O)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C=CC1C=CC=CC=1.[C:29]1([CH2:35][CH2:36][C:37]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)(C)[CH2:38]C)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>CO>[C:14]1([CH2:13][CH2:12][CH:35]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:36][CH:37]([C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH3:38])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: CCC(C)(CCc1ccccc1)c1ccccc1
Reactant: CC(O)c1ccccc1
Agent: CCC(C)c1ccccc1
Agent: [Na]
Solvent: CO
Solvent: C=Cc1ccccc1
Product: CC(CC(CCc1ccccc1)c1ccccc1)c1ccccc1
Temperature: 135 °C
Yield: 460 %

Procedure:
A one-liter glass flask equipped with a stirrer, a dropping funnel with a gas introduction conduit, a reflux condenser with a calcium chloride tube, and a thermometer was charged with 268 grams (2.0 moles) of purified secondary butylbenzene, 4.0 grams (0.17 mole) of metallic sodium and 2.4 grams (0.02 moles) of α-phenethyl alcohol while introducing argon gas through the gas introduction conduit, and the resulting mixture was heated to 135° C. Then 69 grams (0.66 mole) of purified styrene and 20 grams (0.15 mole) of secondary butylbenzene were dropped thereto over 2 hours while maintaining the temperature of the reaction system at 135° C. After dropwise addition was completed, the reaction mixture was stirred while heating for 1 hour and then cooled to room temperature. An excess of metallic sodium was decomposed by dropping methanol in small portions while stirring. Introduction of argon gas was stopped, and the contents were transferred to a separating funnel and then washed with water. The aqueous laer was removed, and the remaining oily layer was analyzed by gas chromatography. This gas chromatographic analysis showed that 40.7 grams (0.17 mole) of 1,3-dipenyl-3-methylpentane and 31.4 grams (0.092 mole) of 1,3,5-triphenyl-5-methylpentane were formed. The total yield (per styrene) was 54 mole %.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10]1[NH:11][C:12]2[C:18]3[CH2:19][C:20]([CH3:23])([CH3:22])[O:21][C:17]=3[C:16]([C:24]([OH:26])=O)=[CH:15][C:13]=2[N:14]=1.S(Cl)(Cl)=O.[F:31][C:32]1[CH:38]=[CH:37][C:35]([NH2:36])=[C:34]([C:39]([F:42])([F:41])[F:40])[CH:33]=1.CCN(C(C)C)C(C)C>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10]1[NH:11][C:12]2[C:18]3[CH2:19][C:20]([CH3:23])([CH3:22])[O:21][C:17]=3[C:16]([C:24]([NH:36][C:35]3[CH:37]=[CH:38][C:32]([F:31])=[CH:33][C:34]=3[C:39]([F:42])([F:40])[F:41])=[O:26])=[CH:15][C:13]=2[N:14]=1
Reactant: Nc1ccc(F)cc1C(F)(F)F
Reactant: CC1(C)Cc2c(c(C(=O)O)cc3nc(Nc4c(F)cccc4Cl)[nH]c23)O1
Solvent: O=S(Cl)Cl
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CC1(C)Cc2c(c(C(=O)Nc3ccc(F)cc3C(F)(F)F)cc3nc(Nc4c(F)cccc4Cl)[nH]c23)O1
Yield: 28 %

Procedure:
The title compound was prepared by following the procedure described for Example-108 using 2-[(2-chloro-6-fluorophenyl)amino]-7,7-dimethyl-7,8-dihydro-1H-furo[3,2-e]benzimidazole-5-carboxylic acid (Intermediate-15, 0.100 g, 0.266 mmol), thionyl chloride (2.0 mL), 4-fluoro-2-(trifluoromethyl)aniline (0.095 g, 0.530 mmol), THF (10.0 mL) and DIPEA (2 mL). The obtained crude product was purified by column chromatography on neutral alumina eluting with 0.7-1.0% MeOH:DCM to afford 0.040 g of the desired product. 1HNMR (DMSO-d6): δ 1.53 (s, 6H), 3.12 (s, 2H), 7.34-7.41 (m, 4H), 7.60-7.67 (m, 2H), 8.40 (m, 1H), 10.02 (s, 1H), 11.20 (s, 2H); MS [M+H]+: 537.17.
Reaction SMILES: [N:1]1[N:2]=[C:3]([N:6]2C(=O)C3C(=CC=CC=3)C2=O)[NH:4][CH:5]=1.[H-].[Na+].[CH3:19][Si:20]([CH2:23][CH2:24][O:25][CH2:26]Cl)([CH3:22])[CH3:21].Cl.O.NN>CN(C=O)C.CCOC(C)=O.CO>[NH2:6][C:3]1[N:4]=[CH:5][N:1]([CH2:26][O:25][CH2:24][CH2:23][Si:20]([CH3:22])([CH3:21])[CH3:19])[N:2]=1
Reactant: O=C1c2ccccc2C(=O)N1c1nnc[nH]1
Reactant: C[Si](C)(C)CCOCCl
Agent: Cl
Agent: NN
Agent: [H-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CO
Product: C[Si](C)(C)CCOCn1cnc(N)n1
Temperature: 50 °C
Reaction time: 5 h

Procedure:
2-(4H-[1,2,4]Triazol-3-yl)-isoindole-1,3-dione (1.60 g, 7.48 mmol) was dissolved in DMF (16 ml) and NaH (55% in oil, 500 mg, 11.5 mmol) and SEMCl (2.00 g, 12.0 mmol) was added thereto at room temperature. After stirring at 50° C. for 5 h, the reaction mixture was diluted with EtOAc. The mixture was poured into diluted HCl aq. and the organic layer was washed with brine, dried over MgSO4. The desiccant was removed through filtration and the filtrate was concentrated under reduced pressure. The residue was dissolved in THF (16 ml) and MeOH (16 ml), and hydrazine hydrate (561 mg, 11.2 mmol) was added thereto. After stirred at room temperature for 15 h, the mixture was concentrated in vacuo. The residue was suspended in EtOAc and the desiccant was removed through filtration and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/EtOAc=5/5 to 0/10) to obtain the intended compound as a colorless solid.
Reaction SMILES: [C:1]([C:4]1[N:9]=[C:8]([C:10]([O:12][CH3:13])=[O:11])[CH:7]=[C:6]([Cl:14])[CH:5]=1)(=[O:3])[CH3:2].[Cl-:15]>C(O)(=O)C>[Cl:14][C:6]1[CH:5]=[C:4]([C:1](=[O:3])[CH2:2][Cl:15])[N:9]=[C:8]([C:10]([O:12][CH3:13])=[O:11])[CH:7]=1
Reactant: COC(=O)c1cc(Cl)cc(C(C)=O)n1
Reactant: [Cl-]
Solvent: CC(=O)O
Product: COC(=O)c1cc(Cl)cc(C(=O)CCl)n1

Procedure:
A solution of methyl 6-acetyl-4-chloro-2-pyridinecarboxylate (6.55 g) and surfuryl chloride (2.73 ml) in acetic acid (33 ml) was stirred at ambient temperature for 14 hours and further at 50° C. for three hours. The solvent was evaporated in vacuo and the residue was mixed with water. The resulting precipitate was collected by filtration and washed with water to give methyl 4-chloro-6-chloroacetyl-2-pyridinecarboxylate (6.75 g).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[NH:7][CH:6]=[C:5]2[CH:12]=[O:13].CC1(C)COB([C:21]2[CH:26]=[CH:25][C:24]([C:27]3([OH:31])[CH2:30][CH2:29][CH2:28]3)=[CH:23][C:22]=2[F:32])OC1.C(=O)([O-])[O-].[K+].[K+]>C(O)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:11][C:10]1[CH:9]=[C:8]2[C:4]([C:5]([CH:12]=[O:13])=[CH:6][NH:7]2)=[CH:3][C:2]=1[C:21]1[CH:26]=[CH:25][C:24]([C:27]2([OH:31])[CH2:28][CH2:29][CH2:30]2)=[CH:23][C:22]=1[F:32]
Reactant: CC1(C)COB(c2ccc(C3(O)CCC3)cc2F)OC1
Reactant: O=Cc1c[nH]c2cc(Cl)c(Br)cc12
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: CCO
Product: O=Cc1c[nH]c2cc(Cl)c(-c3ccc(C4(O)CCC4)cc3F)cc12
Temperature: 130 °C
Yield: 37.7 %

Procedure:
A suspension of 5-bromo-6-chloro-1H-indole-3-carbaldehyde (150 mg, 0.44 mmol), 1-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-3-fluorophenyl]cyclobutanol (181 mg, 0.652 mmol), 2 M aqueous potassium carbonate (0.87 mL, 1.74 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (18 mg, 0.022 mmol) in ethanol (4 mL) was sealed in a reaction vessel and heated thermally to 130° C. for 3 hours. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with brine and dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified using flash chromatography eluting with heptanes/ethyl acetate (0:100 to 60:40) to give the title compound (57 mg, 58%). 1H NMR (500 MHz, DMSO-d6) δ 12.18-12.38 (m, 1 H), 9.95 (s, 1 H), 8.40 (s, 1H), 8.04 (s, 1H), 7.73 (s, 1H), 7.34-7.50 (m, 3H), 5.68 (s, 1H), 2.40-2.47 (m, 2H), 2.21-2.38 (m, 2H), 1.90-1.99 (m, 1H), 1.68-1.81 (m, 1H).
Reaction SMILES: C(C1C=CC=CC=1)(=O)C.C(C1C=CC=CC=1)(=O)C1C=CC=CC=1.[OH:24][C:25]1[CH:38]=[CH:37][C:28]([C:29]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[O:30])=[CH:27][CH:26]=1.Br[CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42].C(=O)([O-])[O-].[K+].[K+]>CC(=O)CC>[CH2:44]([O:43][C:41](=[O:42])[CH2:40][O:24][C:25]1[CH:26]=[CH:27][C:28]([C:29](=[O:30])[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[CH:37][CH:38]=1)[CH3:45]
Reactant: CCOC(=O)CBr
Reactant: O=C(c1ccccc1)c1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: O=C(c1ccccc1)c1ccccc1
Agent: [K+]
Solvent: CCC(C)=O
Solvent: CC(=O)c1ccccc1
Product: CCOC(=O)COc1ccc(C(=O)c2ccccc2)cc1
Reaction time: 3 h

Procedure:
This molecule is an important precursor for the synthesis of the multifunctional acetophenone and benzophenone crosslinking agents disclosed in this application. The ethyl-(4-benzoyl-phenoxy)acetate was prepared by refluxing a mixture of 100.0 grams (0.51 moles) 4-hydroxybenzophenone, 85.2 grams (0.51 moles) ethyl bromoacetate and 800 ml of 2-butanone (MEK) in the presence of an excess of potassium carbonate (209 grams or 1.5 moles). After three hours, the carbonate was filtered off and the MEK removed on a rotovapor. The residue was crystallized from isopropyl alcohol to yield a white, flaky product with a sharp melting point of 82° C. The structure was confirmed by NMR.
Reaction SMILES: Cl[CH:2]([C:7](=O)[C:8]([O:12]C)(OC)[CH3:9])[C:3]([O:5][CH3:6])=[O:4].[NH2:15][C:16]([NH2:18])=[S:17]>CCO>[C:8]([C:7]1[N:15]=[C:16]([NH2:18])[S:17][C:2]=1[C:3]([O:5][CH3:6])=[O:4])(=[O:12])[CH3:9]
Reactant: NC(N)=S
Reactant: COC(=O)C(Cl)C(=O)C(C)(OC)OC
Solvent: CCO
Product: COC(=O)c1sc(N)nc1C(C)=O

Procedure:
A solution of 4.37 g (19 mmol) methyl 2-chloro-4,4-dimethoxy-3-oxopentanoate (Intermediate 17) and 1.8 g (24 mmol) thiourea in 50 ml EtOH was heated at reflux for 3 h. Solvent was removed and the residue was dissolved in 1:1 acetone-5N HCl and the solution was heated at reflux for 4 h. Acetone was removed and the aqueous residue was neutralized with 50% NaOH and then basified with aqueous Na2CO3. Precipitated solids were filtered, washed with water and dried in vacuum. NMR: 2.4 (s, 3H), 3.7 (s, 3H), 8.0 (s, 2H).