Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [BH4-].[Na+].[F:3][C:4]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[C:8](=[O:15])[C:7]2[CH:16]=[CH:17][CH:18]=[CH:19][C:6]=2[C:5]=1[F:20]>O.CO>[F:3][C:4]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[CH:8]([OH:15])[C:7]2[CH:16]=[CH:17][CH:18]=[CH:19][C:6]=2[C:5]=1[F:20]
Reactant: O=c1c2ccccc2c(F)c(F)c2ccccc12
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: OC1c2ccccc2C(F)=C(F)c2ccccc21
Reaction time: 1 h

Procedure:
In a similar manner, a solution of 0.20 gram (52 millimoles) of sodium borohydride in 5 milliliters of water was added dropwise with stirring to a boiling refluxing solution of 0.50 gram (21 millimoles) of 10,11-difluoro-5H-dibenzo[a,d]cyclohepten-5-one in 50 milliliters of methanol; the stirring and refluxing were continued for one hour, and the mixture thereafter allowed to cool. Most of methanol then was vaporized from the mixture, water added and stirred to obtain white crystalline 10,11-difluoro-5H-dibenzo[a,d]cyclohepten-5-ol intermediate. The latter was washed with water and dried under reduced pressure at about 75° C.
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]1[C:7]([N:31]2[CH2:43][CH2:42][N:34]3[C:35]4[CH2:36][CH2:37][CH2:38][CH2:39][C:40]=4[CH:41]=[C:33]3[C:32]2=[O:44])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:28]=[C:22]3[CH2:23][N:24]([CH3:27])[CH2:25][CH2:26][N:21]3[N:20]=2)[C:15](=[O:29])[N:14]([CH3:30])[CH:13]=1)(=[O:3])[CH3:2].[C:45]([O:48][CH2:49]C1C(N2CCN3C4CCCCC=4C=C3C2=O)=NC=CC=1B1OC(C)(C)C(C)(C)O1)(=O)C.BrC1C=C(NC2C=C3CN(C4COC4)CCN3N=2)C(=O)N(C)C=1>>[C:1]([O:4][CH2:5][C:6]1[C:7]([N:31]2[CH2:43][CH2:42][N:34]3[C:35]4[CH2:36][CH2:37][CH2:38][CH2:39][C:40]=4[CH:41]=[C:33]3[C:32]2=[O:44])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:28]=[C:22]3[CH2:23][N:24]([CH:27]4[CH2:49][O:48][CH2:45]4)[CH2:25][CH2:26][N:21]3[N:20]=2)[C:15](=[O:29])[N:14]([CH3:30])[CH:13]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)OCc1c(B2OC(C)(C)C(C)(C)O2)ccnc1N1CCn2c(cc3c2CCCC3)C1=O
Reactant: CC(=O)OCc1c(-c2cc(Nc3cc4n(n3)CCN(C)C4)c(=O)n(C)c2)ccnc1N1CCn2c(cc3c2CCCC3)C1=O
Agent: Cn1cc(Br)cc(Nc2cc3n(n2)CCN(C2COC2)C3)c1=O
Product: CC(=O)OCc1c(-c2cc(Nc3cc4n(n3)CCN(C3COC3)C4)c(=O)n(C)c2)ccnc1N1CCn2c(cc3c2CCCC3)C1=O
Yield: 60 %

Procedure:
Following the procedures as described for compound 113j, 3-(acetoxymethyl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-4-ylboronic acid 113i (200 mg, 0.52 mmol) and 125i (198 mg, 0.52 mmol) were reacted to give 125j as a yellow solid (200 mg, 60%). LCMS: [M+H]+ 639
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4]C(C#N)=[N:6][CH:7]=1.[OH-].[Na+].N.[C:13]([OH:16])(=[O:15])[CH3:14]>C(O)C.O>[Br:1][C:2]1[CH:3]=[CH:4][C:14]([C:13]([OH:16])=[O:15])=[N:6][CH:7]=1
Reactant: CC(=O)O
Reactant: N#Cc1ccc(Br)cn1
Agent: N
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C(O)c1ccc(Br)cn1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 5-bromopyridine-2-carbonitrile (commercially available from Sigma-Aldrich, St. Louis, Mo.) in ethanol (1.4 M) was added 3 equivalents of sodium hydroxide as a 1.5 M aqueous solution and the resulting solution was allowed to reflux at a temperature of about 85° C. until no further evolution of ammonia gas was detected. The resulting solution was then concentrated under reduced pressure to provide a residue. The residue was dissolved in water, acidified with acetic acid, and allowed to stir for about 16 h at a temperature of about 25° C. to provide a solid precipitate. The solid was collected by vacuum filtration and washed with acetone to provide 5-bromopyridine-2-carboxylic acid (Compound B) as a solid. 5-bromopyridine-2-carboxylic acid (Compound B), 0.5 equivalents of HOBT, and 1 equivalent of EDCI were dissolved in DMF and combined with about 1.1 equivalents of 4-tert-butylaniline (Compound C; commercially available from Sigma-Aldrich) dissolved in DMF (0.8 M) and the resulting mixture was allowed to stir for about 2 h at about 25° C. The reaction mixture was then diluted with about 80 mL of 2N aqueous sodium hydroxide and extracted with ethyl acetate (3 extractions, 80 mL/extraction). The ethyl acetate layers were combined and the ethyl acetate was removed under reduced pressure to provide a solid. The resulting solid was suspended in water and filtered using vacuum filtration to provide Compound D as a solid. Compound D was dissolved in DMF (0.04M) and about 3 equivalents of the zinc bromide Compound F (commercially available from Sigma-Aldrich) and about 0.05 equivalents of Pd(PPh3)4 (commercially available from Sigma-Aldrich) were added to the solution under a nitrogen atmosphere, and the resulting reaction mixture was allowed to stir for about 2 h at a temperature of about 100° C. The solvent was then removed under reduced pressure to provide Pyridylene Compound E35(a). Pyridylene Compound E35(a) was purified using preparative thin-layer chromatography with a 1:1 ethyl acetate:hexane mobile phase to provide purified Pyridylene Compound E35(a) as an off-white solid (yield 47%).
Reaction SMILES: [F:1][C:2]1[CH:30]=[CH:29][C:5]([C:6]([NH:8][CH2:9][C:10]2([C:25]([F:28])([F:27])[F:26])[C:15]3[CH:16]=[C:17]([C:20]([NH:22]C)=O)[CH:18]=[CH:19][C:14]=3[NH:13][C:12](=[O:24])[O:11]2)=[O:7])=[CH:4][CH:3]=1.[N-:31]=[N+:32]=[N-:33].[Na+].[Cl-].[NH4+].O>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([NH:8][CH2:9][C:10]2([C:25]([F:26])([F:27])[F:28])[C:15]3[CH:16]=[C:17]([C:20]4[NH:33][N:32]=[N:31][N:22]=4)[CH:18]=[CH:19][C:14]=3[NH:13][C:12](=[O:24])[O:11]2)=[O:7])=[CH:29][CH:30]=1
Reactant: CNC(=O)c1ccc2c(c1)C(CNC(=O)c1ccc(F)cc1)(C(F)(F)F)OC(=O)N2
Reactant: [N-]=[N+]=[N-]
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: O=C1Nc2ccc(-c3nnn[nH]3)cc2C(CNC(=O)c2ccc(F)cc2)(C(F)(F)F)O1
Temperature: 110 °C
Reaction time: 12 h

Procedure:
N-{[6-cyano-2-oxo-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-4-yl]methyl}-4-fluorobenzamide (30 mg, 0.076 mmol) synthesized in Example 159, sodium azide (24.8 mg, 0.38 mmol) and ammonium chloride (20.4 mg, 0.38 mmol) were dissolved in DMF (0.5 mL), and the solution was stirred for 12 hours under heating at 110° C. Water was added to the solution and the solution was extracted twice with ethyl acetate-ethanol, and the resulting organic layer was dried over magnesium sulfate. After the drying agent was removed by filtration, the solvent was evaporated under reduced pressure. The residue was purified by reverse-phase HPLC, whereby the objective compound (3.4 mg, 10%) was obtained as a white solid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[C:11]([CH3:34])[C:12]([CH3:33])=[C:13]([CH2:15][NH:16][C:17]3[C:18]([F:32])=[C:19]([CH:28]=[CH:29][C:30]=3[F:31])[O:20][CH2:21][C:22]([O:24]C(C)C)=[O:23])[CH:14]=2)[CH:5]=[CH:6][C:7]=1[F:8].[Li+].[OH-]>C1COCC1.CO>[F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[C:11]([CH3:34])[C:12]([CH3:33])=[C:13]([CH2:15][NH:16][C:17]3[C:18]([F:32])=[C:19]([CH:28]=[CH:29][C:30]=3[F:31])[O:20][CH2:21][C:22]([OH:24])=[O:23])[CH:14]=2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: Cc1cc(-c2ccc(F)c(F)c2)cc(CNc2c(F)ccc(OCC(=O)OC(C)C)c2F)c1C
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: Cc1cc(-c2ccc(F)c(F)c2)cc(CNc2c(F)ccc(OCC(=O)O)c2F)c1C
Temperature: 25 °C
Reaction time: 1 h
Yield: 96.9 %

Procedure:
To a solution of isopropyl 2-[3-[[5-(3,4-difluorophenyl)-2,3-dimethyl-phenyl]methylamino]-2,4-difluoro-phenoxy]acetate (70 mg, 0.15 mmol, 1.0 eq) in a mixture of THF (1.5 mL) and MeOH (0.5 mL) was added LiOH (2M aqueous solution, 1.5 mL, 3.0 mmol). The reaction was stirred at room temperature for 1 h then the organic solvent was removed under reduced pressure. The remaining aqueous solution was diluted with water and the solution acidified to pH 4-5 with 3M HCl. The mixture was extracted with EtOAc and the combined organic extracts were washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo to give the title compound as a white solid (63 mg, 99%).
Reaction SMILES: [C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[CH2:13]([NH:20][CH2:21][C:22]1[CH:23]=[C:24]([CH2:44][N:45]2[CH2:50][CH2:49][O:48][CH2:47][CH2:46]2)[CH:25]=[C:26]2[C:31]=1[N:30]=[CH:29][C:28]([C:32]([NH:34][CH2:35][C:36]1[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=1)=[O:33])=[C:27]2[OH:43])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>CN1C(=O)CCC1>[CH2:13]([N:20]1[CH2:21][C:22]2[C:31]3=[C:26]([C:27](=[O:43])[C:28]([C:32]([NH:34][CH2:35][C:36]4[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=4)=[O:33])=[CH:29][N:30]3[C:1]1=[O:2])[CH:25]=[C:24]([CH2:44][N:45]1[CH2:46][CH2:47][O:48][CH2:49][CH2:50]1)[CH:23]=2)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: O=C(NCc1ccc(Cl)cc1)c1cnc2c(CNCc3ccccc3)cc(CN3CCOCC3)cc2c1O
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: CN1CCCC1=O
Product: O=C(NCc1ccc(Cl)cc1)c1cn2c3c(cc(CN4CCOCC4)cc3c1=O)CN(Cc1ccccc1)C2=O
Reaction time: 0.25 h
Yield: 83.6 %

Procedure:
A solution of 1,1′-carbonyldiimidazole (82 mg) in NMP (2.0 mL) is added over 15 min to a solution of 8-((benzylamino)methyl)-N-(4-chlorobenzyl)-4-hydroxy-6-(4-morpholinylmethyl)-3-quinolinecarboxamide (Preparation 29, 106 mg) in NMP (6 mL). After an additional 15 min, the solvent is removed under reduced pressure and the residual solid is triturated with methanol to afford 93 mg of the title compound. Physical characteristics: M.p. 201-204° C.; 1H NMR (CDCl3) δ2.44, 3.58, 3.70, 4.67, 4.73, 4.87, 7.3-7.45, 7.51, 8.19, 9.90, 10.1; Anal. Found: C, 66.67; H, 5.31; N, 9.99; Cl, 6.35.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([NH:13][C:14]([C@H:16]2[C:25]3[C:20](=[CH:21][C:22]([CH2:26][O:27][CH3:28])=[CH:23][CH:24]=3)[CH2:19][CH2:18][N:17]2[C:29]([C@@H:31]2[CH2:34][C@H:33]([CH2:35][C:36]([OH:38])=[O:37])[CH2:32]2)=[O:30])=[O:15])[CH:5]=[C:6]2[C:10]=1[C:9]([CH3:12])([CH3:11])[CH2:8][CH2:7]2.[OH-].[K+:40]>C(#N)C>[C:4](#[N:13])[CH3:3].[F:1][C:2]1[CH:3]=[C:4]([NH:13][C:14]([C@H:16]2[C:25]3[C:20](=[CH:21][C:22]([CH2:26][O:27][CH3:28])=[CH:23][CH:24]=3)[CH2:19][CH2:18][N:17]2[C:29]([C@@H:31]2[CH2:34][C@H:33]([CH2:35][C:36]([O-:38])=[O:37])[CH2:32]2)=[O:30])=[O:15])[CH:5]=[C:6]2[C:10]=1[C:9]([CH3:12])([CH3:11])[CH2:8][CH2:7]2.[K+:40]
Reactant: COCc1ccc2c(c1)CCN(C(=O)[C@H]1C[C@@H](CC(=O)O)C1)[C@H]2C(=O)Nc1cc(F)c2c(c1)CCC2(C)C
Agent: [K+]
Agent: [OH-]
Solvent: CC#N
Product: COCc1ccc2c(c1)CCN(C(=O)[C@H]1C[C@@H](CC(=O)[O-])C1)[C@H]2C(=O)Nc1cc(F)c2c(c1)CCC2(C)C
Temperature: 25 °C
Reaction time: 14 h

Procedure:
To a mixture of (cis-3-(((1R)-1-((7-fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)carbamoyl)-6-(methoxymethyl)-3,4-dihydroisoquinolin-2(1H)-yl)carbonyl)cyclobutyl)acetic acid (580 mg, 1.11 mmol) in acetonitrile (40 mL) was added 0.1N aqueous potassium hydroxide solution (11.10 mL, 1.11 mmol) at room temperature, and the solvent was evaporated under reduced pressure. To the obtained residue was added acetonitrile (40 mL), and the mixture was stirred at room temperature for 14 hr. The precipitate was collected by filtration, and washed with acetonitrile to give the title compound (586.6 mg, 1.046 mmol, 94%) as white crystals.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:28]=[CH:27][C:8]2[N:9]([CH3:26])[C:10]([NH:12][C:13]3[S:14][C:15]4[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:16]=4[N:17]=3)=[N:11][C:7]=2[CH:6]=1)=[O:4].[OH-].[Li+]>>[CH3:26][N:9]1[C:8]2[CH:27]=[CH:28][C:5]([C:3]([OH:4])=[O:2])=[CH:6][C:7]=2[N:11]=[C:10]1[NH:12][C:13]1[S:14][C:15]2[CH:21]=[C:20]([C:22]([F:24])([F:23])[F:25])[CH:19]=[CH:18][C:16]=2[N:17]=1
Reactant: COC(=O)c1ccc2c(c1)nc(Nc1nc3ccc(C(F)(F)F)cc3s1)n2C
Agent: [Li+]
Agent: [OH-]
Product: Cn1c(Nc2nc3ccc(C(F)(F)F)cc3s2)nc2cc(C(=O)O)ccc21
Yield: 58.8 %

Procedure:
1-Methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (434 mg) was prepared by following General Procedure E starting from 1-methyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid methyl ester (765 mg) and lithium hydroxide (316 mg). LC/MS: m/z 393.9. 1H NMR (DMSO-d6, 400 MHz): δ 12.77 (bs, 1H), 12.49 (bs, 1H), 8.34-8.14 (m, 2H), 7.93-7.73 (m, 2H), 7.67 (d, 1H), 7.52 (d, 1H), 3.64 (bs, 3H).
Reaction SMILES: [C:1]([N:4]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH:9]=[CH:8][C:7]2[CH:16]=[N:17][C:18](Cl)=[CH:19][C:6]=2[CH2:5]1)(=[O:3])[CH3:2].[C:21]1(B(O)O)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(N1C2C=CC=CC=2C=CC2N=C(C3C=NC(OC)=CC=3)C(F)=CC=2C1)(=O)C>>[C:1]([N:4]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH:9]=[CH:8][C:7]2[CH:16]=[N:17][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:19][C:6]=2[CH2:5]1)(=[O:3])[CH3:2]
Reactant: CC(=O)N1Cc2cc(Cl)ncc2C=Cc2ccccc21
Reactant: OB(O)c1ccccc1
Agent: COc1ccc(-c2nc3c(cc2F)CN(C(C)=O)c2ccccc2C=C3)cn1
Product: CC(=O)N1Cc2cc(-c3ccccc3)ncc2C=Cc2ccccc21
Yield: 69.4 %

Procedure:
The title compound (12.0 mg, 70%) was prepared from 25E (15.0 mg, 0.053 mmol) and phenylboronic acid (9.6 mg, 0.079 mmol) by a route analogous to that used for the preparation of 2B. HPLC Rt=2.356 min; LCMS Found: (M+H)+=327.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[CH2:6].C[N+]1([O-])CC[O:14]CC1.C1C=C(Cl)C=C(C(OO)=O)C=1>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[C@H:5]1[O:14][CH2:6]1
Reactant: C[N+]1([O-])CCOCC1
Reactant: C=Cc1cccc(Cl)c1
Agent: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: Clc1cccc([C@@H]2CO2)c1
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 86.3 %

Procedure:
A round-bottom flask equipped with a overhead stirrer was charged with 3-chlorostyrene (1.00 g, 7.22×10−3 mol), CH2Cl2 (78 mL), (R,R)-4 (0.349 g, 3.61×10−4 mol), and NMO (4.22 g, 3.62×10−2 mol). The solution was cooled to −78° C. before solid m-CPBA (2.51 g, 1.46×10−2 mol) was added in portions over 1.5 minutes. The reaction was monitored by GC. Upon completion (3 h), the reaction was quenched by the addition of a solution of dimethyl sulfide (6 mL) in CH2Cl2 (25 mL) precooled to −78° C. The solution was stirred for an additional 10 minutes at −78° C. before removal of the cold bath and addition of 2N NaOH (20 mL) and CH2Cl2 (20 mL). The phases were separated and the aqueous layer was washed with CH2Cl2 (2×50 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. Removal of the catalyst was effected by elution through a pad of SiO2 (10 g) using pentane and CH2Cl2 (1:1). The eluent was concentrated in vacuo, and subsequent bulb-to-bulb distillation from CaH2 afforded (R)-3-chlorostyrene oxide (0.963 g, 86%) as a colorless liquid in 81% ee.
Reaction SMILES: [CH:1]1[C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[S:6][C:5]=2[C:4]([C:14]2[CH:19]=[C:18]([CH3:20])[CH:17]=[C:16]([C:21]3[C:26]4[S:27][C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=5[C:25]=4[CH:24]=[CH:23][CH:22]=3)[C:15]=2[OH:34])=[CH:3][CH:2]=1.C(Cl)Cl.C(N(CC)CC)C.[C:45](Cl)(=[O:48])[CH:46]=[CH2:47]>O>[C:45]([O:34][C:15]1[C:16]([C:21]2[C:26]3[S:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[C:25]=3[CH:24]=[CH:23][CH:22]=2)=[CH:17][C:18]([CH3:20])=[CH:19][C:14]=1[C:4]1[C:5]2[S:6][C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=3[C:9]=2[CH:1]=[CH:2][CH:3]=1)(=[O:48])[CH:46]=[CH2:47]
Reactant: Cc1cc(-c2cccc3c2sc2ccccc23)c(O)c(-c2cccc3c2sc2ccccc23)c1
Reactant: C=CC(=O)Cl
Solvent: O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=CC(=O)Oc1c(-c2cccc3c2sc2ccccc23)cc(C)cc1-c1cccc2c1sc1ccccc12
Reaction time: 0.5 h
Yield: 57 %

Procedure:
1.35 g of the thus obtained 2,6-bis(4-dibenzothiophenyl)-4-methylphenol is placed in a round bottom flask; 20 mL of methylene chloride is added; after ice cooling the flask, 0.33 g of triethylamine is added; 0.30 g of acryloyl chloride is then added dropwise; after adding the whole, the temperature is returned to room temperature; and the mixture is stirred for 30 minutes. 10 mL of water is added; the mixture is vigorously stirred; an aqueous layer is then removed; the aqueous layer is washed with methylene chloride and then gathered with the original methylene chloride solution; and the mixture is dried upon application of magnesium sulfate. The resulting mixture is concentrated by filtration with a filter paper; and the concentrate is separated by a silica gel column (eluate: hexane/ethyl acetate=80/20 (volume ratio)) to concentrate a component having an Rf of 0.42, thereby obtaining 0.85 g (yield: 57%) of the foregoing white solid. 1H NMR (CDCl3, 400 MHz): δ (ppm) 2.57 (s, 3H), 5.41 (dd=1.2 & 10.4 Hz, 1H), 5.64 (dd=10.4 & 17.2 Hz, 1H), 5.97 (dd=1.2 & 17.2 Hz, 1H), 7.49 to 7.59 (m, 10H), 7.90 (m, 2H), 8.16 to 8.21 (m, 4H)
Reaction SMILES: [CH2:1]([N:3]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][C:12]([N+:18]([O-])=O)=[CH:13][CH:14]=2)[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]1=2)[CH3:2]>C(O)C.[Pd]>[NH2:18][C:12]1[CH:11]=[C:10]2[C:15]([C:16](=[O:17])[N:3]([CH2:1][CH3:2])[C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:9]=32)=[CH:14][CH:13]=1
Reactant: CCn1c(=O)c2ccc([N+](=O)[O-])cc2c2ccccc21
Agent: [Pd]
Solvent: CCO
Product: CCn1c(=O)c2ccc(N)cc2c2ccccc21
Reaction time: 18 h
Yield: 52.5 %

Procedure:
A solution of 5-ethyl-9-nitro-5H-phenanthridin-6-one (5.4 g, 20 mmol) in ethyl alcohol (400 ml) was charged with 10% palladium on activated carbon (500 mg). The resultant suspension was placed on a Parr hydrogenation apparatus and shaken under 50 psi H2 for 18 hours. The catalyst was removed by filtration, and the filtrate was concentrated in vacuo to afford 9-amino-5-ethyl-5H-phenanthridin-6-one (2.5 g, quantitative).
Reaction SMILES: [F:1][C:2]1([F:33])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[N:22]=[C:21]([C:23]5[C:24]([O:30]C)=[N:25][CH:26]=[C:27]([F:29])[CH:28]=5)[C:20]([CH3:32])=[CH:19][CH:18]=4)=[O:15])[CH2:13][CH2:12]3)=[CH:10][C:4]=2[O:3]1.I[Si](C)(C)C>C(Cl)(Cl)Cl>[F:33][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3([C:14]([NH:16][C:17]4[CH:18]=[CH:19][C:20]([CH3:32])=[C:21]([C:23]5[C:24](=[O:30])[NH:25][CH:26]=[C:27]([F:29])[CH:28]=5)[N:22]=4)=[O:15])[CH2:12][CH2:13]3)=[CH:10][C:4]=2[O:3]1
Reactant: COc1ncc(F)cc1-c1nc(NC(=O)C2(c3ccc4c(c3)OC(F)(F)O4)CC2)ccc1C
Agent: C[Si](C)(C)I
Solvent: ClC(Cl)Cl
Product: Cc1ccc(NC(=O)C2(c3ccc4c(c3)OC(F)(F)O4)CC2)nc1-c1cc(F)c[nH]c1=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 47.6 %

Procedure:
To 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(5′-fluoro-2′-methoxy-3-methyl-2,3′-bipyridin-6-yl)cyclopropanecarboxamide (42 mg, 0.09 mmol) in chloroform (1 mL) was added iodotrimethylsilane (55 mg, 0.3 mmol). The reaction mixture was stirred at room temperature for three hours. At this point the reaction mixture was purified directly by silica gel chromatography (eluting with 0-100% ethyl acetate in hexanes) to yield the product (19 mg, 47%). ESI-MS m/z calc. 443.38. found 443.96 (M+1)+. Retention time 1.56 minutes.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[CH:14]=[C:13]([S:18][C:19]2[N:20]([CH3:24])[CH:21]=[CH:22][N:23]=2)[CH:12]=[CH:11]3)=[CH:4][CH:3]=1.ClC1C=CC=C(C(OO)=O)C=1.[OH-:36].[Ca+2].[OH-:38]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[CH:14]=[C:13]([S:18]([C:19]2[N:20]([CH3:24])[CH:21]=[CH:22][N:23]=2)(=[O:38])=[O:36])[CH:12]=[CH:11]3)=[CH:6][CH:7]=1
Reactant: [OH-]
Reactant: Cn1ccnc1Sc1ccc2cc(-c3ccc(F)cc3)ccc2c1
Agent: O=C(OO)c1cccc(Cl)c1
Agent: [Ca+2]
Solvent: ClCCl
Product: Cn1ccnc1S(=O)(=O)c1ccc2cc(-c3ccc(F)cc3)ccc2c1
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 45.7 %

Procedure:
2-{[6-(4-Fluorophenyl)-2-naphthyl]thio}-1-methyl-1H-imidazole (125 mg, 0.4 mmol) was dissolved in CH2Cl2 (1 mL) and was cooled to 0° C. 3-Chloroperbenzoic acid (224 mg, 1.0 mmol) was added and the solution stirred at ambient temperature for 1.5 h. The solution was diluted with CH2Cl2 (1 mL) and calcium hydroxide (277 mg, 0.6 mmol) was added. The suspension was stirred for 30 minutes before filtering through a pad of Hyflo; the liquors were evaporated in vacuo. The residue was purified by flash column chromatography on silica, eluting with 55% ethyl acetate/isohexane, to give the title compound as a white solid (67 mg). 1H NMR (500 MHz, d6-DMSO): δ 8.74 (1H, s), 8.36 (2H, m), 8.22 (1H, d, J=8.7 Hz), 8.04 (1H, d, J=8.6 Hz), 7.93-7.91 (3H, m), 7.50 (1H, s), 7.38 (2H, t, J=8.8 Hz), 7.12 (1H, s), 3.97 (3H, s); m/z (ES+) 367 [MH+].
Reaction SMILES: O.[NH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[OH:9].CO[CH:12]1[CH2:16][CH2:15][CH:14](OC)O1>C(O)(=O)C>[N:2]1([C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[OH:9])[CH:12]=[CH:16][CH:15]=[CH:14]1
Reactant: COC1CCC(OC)O1
Reactant: Nc1ccccc1O
Solvent: O
Solvent: CC(=O)O
Product: Oc1ccccc1-n1cccc1
Temperature: 100 °C
Yield: 74.1 %

Procedure:
A 5 L 3-neck round bottom flask was fitted with a mechanical stirrer, a heating mantle, a water cooled reflux condenser, a temperature probe/controller and a nitrogen inlet/outlet. The vessel was charged with (50 g, 0.46 mol) of 2-aminophenol and acetic acid (750 mL) which provided a very dark solution. Stirring was commenced and the vessel was charged with 2,5-dimethoxytetrahydrofuran (59.4 mL, 0.458 mol) dropwise over 2 minutes. The dark mixture was then heated at 100° C. for 15 min. The mixture was allowed to cool to room temperature and was filtered through a pad of Celite to remove residual solids. The filtrate was concentrated under reduced pressure azeotroping with toluene. The residual oil was dissolved in ethyl acetate (1000 mL) and was partitioned with water (500 mL). The organic layer was separated and was washed with water (500 mL), dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to provide 2-(1H-pyrrol-1-yl)phenol (54 g, 74%) as a dark oil. ESI-MS m/z calc. 159.1, found 160.2 (M+1)+. Retention time: 2.67 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.37-7.23 (m, 2H), 7.13-6.97 (m, 2H), 6.91 (t, J=1.9 Hz, 2H), 6.43 (t, J=1.9 Hz, 2H), 5.35 (s, 1H).
Reaction SMILES: ClCCCS(N[CH2:9][C:10]1([CH2:15][S:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[CH2:14][CH2:13][CH2:12][O:11]1)(=O)=O.C(SCC(OC)CN[S:54]([CH2:57][CH2:58][CH2:59][I:60])(=[O:56])=[O:55])CCCCCCCCCCCCCCC>>[CH2:17]([S:16][CH2:15][C:10]1([CH2:9][S:54]([CH2:57][CH2:58][CH2:59][I:60])(=[O:56])=[O:55])[CH2:14][CH2:13][CH2:12][O:11]1)[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]
Reactant: CCCCCCCCCCCCCCCCSCC1(CNS(=O)(=O)CCCCl)CCCO1
Reactant: CCCCCCCCCCCCCCCCSCC(CNS(=O)(=O)CCCI)OC
Product: CCCCCCCCCCCCCCCCSCC1(CS(=O)(=O)CCCI)CCCO1

Procedure:
2-(3-Chloropropylsulfonylaminomethyl)-2-hexadecylthiomethyltetrahydrofuran IIIb1 is allowed to react and worked by the same procedure as described in (5). m.p. 36° to 37° C. The summary of the experimental condition and the physical data of the prodcut are listed in the Table 8.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([OH:11])[C:5]([N+:8]([O-])=O)=[CH:6][CH:7]=1>[Pd]>[OH:11][C:4]1[CH:3]=[C:2]([F:1])[CH:7]=[CH:6][C:5]=1[NH2:8]
Reactant: O=[N+]([O-])c1ccc(F)cc1O
Agent: [Pd]
Product: Nc1ccc(F)cc1O
Reaction time: 12 h
Yield: 100.1 %

Procedure:
3-fluoro 6-nitro phenol (2 g, 11 mmol) was treated with 10%Pd/C (1 g) at 23° C. The reaction mixture was flushed with hydrogen gas and the reaction was allowed to stir 12 h before it was filtered through celite. The filtrate was concentrated in vacuo to afford the title compound (1.4 g, 77%). EI-MS m/z 169 (M+H)+
Reaction SMILES: [F:1][CH2:2][CH:3]([CH2:22][F:23])[O:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([O:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[CH:13]=1)[C:8]([OH:10])=O.[CH2:24]([O:26][C:27](=[O:36])[CH2:28][S:29][C:30]1[S:34][C:33]([NH2:35])=[N:32][CH:31]=1)[CH3:25]>>[CH2:24]([O:26][C:27](=[O:36])[CH2:28][S:29][C:30]1[S:34][C:33]([NH:35][C:8](=[O:10])[C:7]2[CH:11]=[C:12]([O:14][C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[CH:13]=[C:5]([O:4][CH:3]([CH2:2][F:1])[CH2:22][F:23])[CH:6]=2)=[N:32][CH:31]=1)[CH3:25]
Reactant: O=C(O)c1cc(Oc2ccc(F)cc2)cc(OC(CF)CF)c1
Reactant: CCOC(=O)CSc1cnc(N)s1
Product: CCOC(=O)CSc1cnc(NC(=O)c2cc(Oc3ccc(F)cc3)cc(OC(CF)CF)c2)s1

Procedure:
The title compound was prepared from 3-(2-fluoro-1-fluoromethyl-ethoxy)-5-(4-fluoro-phenoxy)-benzoic acid and (2-amino-thiazol-5-ylsulfanyl)-acetic acid ethyl ester following general procedure A