Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([F:12])[CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[C:7]2[CH3:11].[Cl:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[OH:21].Cl.CN(C)CC(O)=O.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.[Cu]I>[Cl:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[O:21][C:2]1[CH:3]=[C:4]([F:12])[CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[C:7]2[CH3:11]
Reactant: Oc1ccc(Cl)cc1Cl
Reactant: Cc1c[nH]c2c(Br)cc(F)cc12
Agent: [Cu]I
Agent: CN(C)CC(=O)O
Agent: Cl
Solvent: C1COCCO1
Product: Cc1c[nH]c2c(Oc3ccc(Cl)cc3Cl)cc(F)cc12
Yield: 34 %

Procedure:
Following general method A-18, 7-Bromo-5-fluoro-3-methyl-1H-indole (1.60 g, 7.02 mmol) was reacted with 2,4-dichlorophenol (1.72 g, 10.5 mmol), CuI (134 mg, 0.702 mmol), N,N-dimethylglycine hydrochloride (293 mg, 2.10 mmol), and Cs2CO3 (4.57 g, 14.0 mmol) in anhydrous dioxane (14 mL). The crude product was purified by silica gel column chromatography utilizing a solvent system of 5% EtOAc/Hexanes to yield 746 mg of I-198B as a yellow oil (34%). 1H NMR (400 MHz, CDCl3)
Reaction SMILES: [CH2:1]([OH:4])[C:2]#[CH:3].[C:5]([O:9][C:10](=[O:21])[CH2:11][O:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15](Br)[C:14]=1[CH3:20])([CH3:8])([CH3:7])[CH3:6].[Cl-].[NH4+]>N1CCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:5]([O:9][C:10](=[O:21])[CH2:11][O:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:3]#[C:2][CH2:1][OH:4])[C:14]=1[CH3:20])([CH3:8])([CH3:7])[CH3:6]
Reactant: Cc1c(Br)cccc1OCC(=O)OC(C)(C)C
Reactant: C#CCO
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCNC1
Product: Cc1c(C#CCO)cccc1OCC(=O)OC(C)(C)C
Temperature: 77.5 °C
Yield: 19.4 %

Procedure:
Tetrakis(triphenylphosphine)palladium(0) (0.41 g, 0.35 mmol) and propargyl alcohol (0.83 mL, 14.3 mmol) were added to a solution of (3-bromo-2-methylphenoxy)acetic acid tert-butyl ester (2.13 g, 7.08 mmol) in pyrrolidine (21 mL) under an argon atmosphere at room temperature. The mixture was heated at 75-80° C. for 2.5 hours. Excess saturated ammonium chloride was added and the mixture was extracted with diethyl ether. The extract was washed with brine, dried over sodium sulfate, and concentrated to dryness. Purification by flash chromatography, eluting with hexane/ethyl acetate, gave [3-(3-hydroxyprop-1-ynyl)-2-methylphenoxy]acetic acid tert-butyl ester as an oil (0.38 g, 19.5%).
Reaction SMILES: C([Li])CCC.BrC1C=CC=CC=1C=O.[CH:15](/[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[Br:33])=[CH:16]\[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26].C(O)C>O1CCCC1.C1(C)C=CC=CC=1.[Rh](Cl)(Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:15]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[Br:33])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]
Reactant: CCCCCCCCCC/C=C/c1ccccc1Br
Agent: Cl[Rh](Cl)Cl
Agent: O=Cc1ccccc1Br
Agent: [Li]CCCC
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CCCCCCCCCCCCc1ccccc1Br
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
To a solution of 1-bromoundecane (0.34 mole) in acetonitrile (800 ml) was added triphenylphosphine (0.37 mole), under argon, and the mixture was refluxed for 24 hours. The reaction mixture was allowed to cool to room temperature and the solvent was removed in vacuo. The resulting oil was redissolved in acetonitrile (100 ml) and then ether (1.2 l) was added. The ether was decanted and the procedure was repeated 4 times, at which point a solid came out of the ether. The solid was collected, washed with ether and air-dried to give the phosphonium salt. The latter (16.2 mmoles) was dissolved in tetrahydrofuran (66 ml), under argon, cooled to 0° C. and n-butyl lithium (7.4 ml, 2.2M in hexane, 16.2 mmoles) was added dropwise over a 10 minute period. This solution was stirred at 0° C. for 15 minutes and then a solution of 2-bromobenzaldehyde (13.5 mmoles) in tetrahydrofuran (15 ml) was added dropwise over 10 minutes. The reaction mixture was stirred for 15 minutes and then the solvent was removed in vacuo. Ether was added to the residue and allowed to sit for 18 hours. The ether layer was filtered away from the gummy residue and the residue treated 3 more times with ether. The combined ether extract was concentrated and flash chromatographed on silica, eluted with hexane, to give a mixture of cis and trans 2-(1-dodecenyl)bromobenzene. The mixture (5.57 mmoles) was dissolved in toluene (75 ml) and ethanol (75 ml) and then tris(triphenylphosphine) rhodium chloride catalyst (0.7 g) was added. The suspension was degassed with argon for 30 minutes and purged with hydrogen under argon for 1 hour. The mixture was hydrogenated at 50 psi for 6 hours and then left standing under hydrogen pressure for 60 hours. The reaction mixture was shaken for 2 hours, argon was bubbled in and the solid filtered. The filtrate was concentrated, the residue triturated with ether and then filtered. This filtrate was treated with charcoal, silica and filtered. The filtrate was concentrated, the residue redissolved in hexane and treated with silica. Concentration of the filtrate gave the product as a solid.
Reaction SMILES: Cl.[NH2:2][C@@H:3]([CH3:8])[C:4]([O:6][CH3:7])=[O:5].C([O-])([O-])=O.[K+].[K+].[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CN(C=O)C>[CH2:15]([N:2]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C@@H:3]([CH3:8])[C:4]([O:6][CH3:7])=[O:5])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: BrCc1ccccc1
Reactant: COC(=O)[C@H](C)N
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)[C@H](C)N(Cc1ccccc1)Cc1ccccc1
Temperature: 25 °C
Reaction time: 38 h

Procedure:
Commercially available (S)-methyl 2-aminopropanoate, hydrochloride (10.0 g, 71.6 mmol) was suspended in DMF (35 mL) and then K2CO3 (31.7 g. 229 mmol) was added followed by benzyl bromide (18.21 mL, 158 mmol). The mixture was left to stir for 38 h at rt. LCMS showed good conversion to the desired product at this time. The reaction was filtered and the solid components were rinsed with EtOAc. The filtrate was then diluted with water and EtOAc and the layers were partitioned. The aqueous portion was extracted with small portions of EtOAc. The combined organic portions were dried over Na2SO4, filtered, and concentrated to a pale yellow, viscous oil. This oil was then chromatographed (ISCO, silica 120 g column, 254 collection, general gradient; hexanes/EtOAc) to afford the desired product (15.76 g, 75%): MS (ESI) m/z 284 (M+H).
Reaction SMILES: [NH2:1][C:2]1[N:6]([CH3:7])[N:5]=[CH:4][C:3]=1[N:8]=O.[S:10](=[O:14])(=[O:13])([OH:12])[OH:11]>O.[Pd]>[S:10](=[O:12])(=[O:11])([OH:14])[OH:13].[NH2:8][C:3]1[CH:4]=[N:5][N:6]([CH3:7])[C:2]=1[NH2:1]
Reactant: Cn1ncc(N=O)c1N
Agent: [Pd]
Agent: O=S(=O)(O)O
Solvent: O
Product: Cn1ncc(N)c1N
Reaction time: 8 h

Procedure:
To a solution of 5-amino-1-methyl-4-nitrosopyrazole (1 g) in water (40 ml) were added concentrated sulfuric acid (0.423 ml) and palladium on carbon (0.3 g) under a hydrogen atmosphere. The mixture was stirred overnight. The reaction mixture was filtered, and the filtrate was evaporated in vacuo. To the residue was added isopropyl alcohol, and the resulting precipitate was collected by filtration to give 4,5-diamino-1-methylpyrazole sulfuric acid salt (1.71 g).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:13]3[CH:14]=[C:15]([C:18]([NH:20][NH2:21])=[O:19])[CH:16]=[CH:17][C:12]=3[O:11][CH:10]=2)=[CH:5][CH:4]=1.C(N(CC)CC)C.[C:29](Cl)(=[O:31])[CH3:30]>O1CCCC1.C(OCC)(=O)C>[C:29]([NH:21][NH:20][C:18]([C:15]1[CH:16]=[CH:17][C:12]2[O:11][CH:10]=[C:9]([C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[C:13]=2[CH:14]=1)=[O:19])(=[O:31])[CH3:30]
Reactant: COc1ccc(-c2coc3ccc(C(=O)NN)cc23)cc1
Reactant: CC(=O)Cl
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COc1ccc(-c2coc3ccc(C(=O)NNC(C)=O)cc23)cc1
Reaction time: 0.5 h
Yield: 94.5 %

Procedure:
To a solution of 3-(4-methoxyphenyl)-1-benzofuran-5-carbohydrazide (565 mg, 2.00 mmol) and triethylamine (0.418 mL, 3.00 mmol) in tetrahydrofuran (30 mL) was added acetyl chloride (0.213 mL, 3.00 mmol) at room temperature, and the resulting mixture was stirred for 30 min. The reaction mixture was diluted with ethyl acetate, washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was washed with hexane/ethyl acetate (1/1) to give the title compound (613 mg, yield 94%) as colorless crystals.
Reaction SMILES: [CH2:1]([N:7]1[CH2:12][CH:11]2[CH:9]([C:10]2([CH3:22])[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([N+:19]([O-])=O)[CH:14]=2)[C:8]1=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[Cl-].[Ca+2].[Cl-].O>C(O)C.[Fe]>[NH2:19][C:15]1[CH:14]=[C:13]([C:10]2([CH3:22])[CH:9]3[CH:11]2[CH2:12][N:7]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[C:8]3=[O:23])[CH:18]=[CH:17][CH:16]=1
Reactant: CCCCCCN1CC2C(C1=O)C2(C)c1cccc([N+](=O)[O-])c1
Agent: [Fe]
Agent: [Ca+2]
Agent: [Cl-]
Solvent: O
Solvent: CCO
Product: CCCCCCN1CC2C(C1=O)C2(C)c1cccc(N)c1
Temperature: 25 °C

Procedure:
3-Hexyl-6-methyl-6-(3-nitrophenyl)-3-azabicyclo[3.1.0]hexan-2-one (Preparation 11, 6.3 g, 19.9 mmol) was dissolved in ethanol (250 ml), and iron powder (8.5 g, 0.15 mol), calcium chloride (0.95 g, 8.6 mmol) and water (50 ml) was added. The reaction mixture was refluxed for 2 h. The reaction mixture was cooled to room temperature and calcium chloride (0.95 g, 8.6 mmol) was added, the reaction mixture was refluxed for a further 16 h. The reaction mixture was cooled and filtered and then concentrated in vacuo, the residue was partitioned between dichloromethane and water and the organic layer separated, the aqueous layer was extracted with dichloromethane (3×) and the combined extracts were dried (Na2SO4) and concentrated in vacuo. The title compound was obtained as an orange solid (5.72 g, 100%).
Reaction SMILES: [CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([C:18]([CH:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)=[O:19])[N:14]3[CH3:17])=[C:10]([N:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)[N:9]=2)[C:6]2[CH:32]=[CH:33][CH:34]=[CH:35][C:5]=2[N:4]=1)[CH3:2].CCN(CC)CC.[CH:43]1([C:46](Cl)=[O:47])[CH2:45][CH2:44]1>C(Cl)Cl>[CH:43]1([C:46]([N:23]2[CH2:22][CH2:21][CH:20]([C:18]([C:13]3[N:14]([CH3:17])[C:15]4[C:11]([N:12]=3)=[C:10]([N:26]3[CH2:27][CH2:28][O:29][CH2:30][CH2:31]3)[N:9]=[C:8]([N:7]3[C:6]5[CH:32]=[CH:33][CH:34]=[CH:35][C:5]=5[N:4]=[C:3]3[CH2:1][CH3:2])[N:16]=4)=[O:19])[CH2:25][CH2:24]2)=[O:47])[CH2:45][CH2:44]1
Reactant: CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(C(=O)C3CCNCC3)n(C)c2n1
Reactant: O=C(Cl)C1CC1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(C(=O)C3CCN(C(=O)C4CC4)CC3)n(C)c2n1
Temperature: 25 °C
Reaction time: 3 h
Yield: 24 %

Procedure:
To a solution of [2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]piperidin-4-ylmethanone (47 mg, 0.10 mmol) and NEt3 (27 μL, 0.20 mmol) in DCM (5 mL) was added cyclopropane carbonyl chloride (10 μL, 0.12 mmol) and the resulting mixture stirred at r.t. for 3 h. The reaction mixture was quenched with H2O and extracted with DCM. The combined organic phases were dried (MgSO4) and concentrated in vacuo and the resulting residue loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% NH4OH in water on a gradient acetonitrile 30-70%) affording 864 (13 mg, 25%). LCMS (method I): RT 4.06 min, [M+H]+ 543.3. 1H NMR (CDCl3, 400 MHz): δ 8.07-8.06 (1 H, m), 7.89-7.82 (1 H, m), 7.40-7.30 (2 H, m), 4.70-4.56 (3 H, m), 4.39-4.28 (1 H, m), 4.13 (3 H, s), 3.93-3.90 (6 H, m), 3.52-3.27 (3 H, m), 2.94-2.80 (1 H, m), 2.08-1.97 (2 H, m), 1.97-1.57 (4 H, m), 1.50 (3 H, t, J=7.40 Hz), 1.04-0.98 (2 H, m), 0.79-0.78 (2 H, m)
Reaction SMILES: [Si:1]([O:18][CH2:19][C@@H:20]1[S:24][C@@:23]([SeH:36])([N:25]2[CH:33]=[N:32][C:31]3[C:26]2=[N:27][C:28](F)=[N:29][C:30]=3[Cl:34])[C@@:22]([F:43])([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:21]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(=O)C>C(Cl)(Cl)Cl>[Si:1]([O:18][CH2:19][C@@H:20]1[S:24][C@@:23]([SeH:36])([N:25]2[CH:33]=[N:32][C:31]3[C:26]2=[N:27][CH:28]=[N:29][C:30]=3[Cl:34])[C@@:22]([F:43])([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:21]1)([C:14]([CH3:15])([CH3:16])[CH3:17])([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: CC(C)(C)[Si](OC[C@H]1C[C@](F)(c2ccccc2)[C@]([SeH])(n2cnc3c(Cl)nc(F)nc32)S1)(c1ccccc1)c1ccccc1
Agent: CC(=O)[O-]
Solvent: ClC(Cl)Cl
Product: CC(C)(C)[Si](OC[C@H]1C[C@](F)(c2ccccc2)[C@]([SeH])(n2cnc3c(Cl)ncnc32)S1)(c1ccccc1)c1ccccc1

Procedure:
(−)-9-[(1S,2S,4R)-5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-2-fluoro-2-phenylselenyl-4-thio-β-L-ribofuranosyl]-6-chloro-2-fluoropurine (L-22, FIG. 4b) was made using the general procedure for condensation reaction of the acetate L-8 with purines. The compound L-22 was obtained on 1.70-mmol scale in 66% yield. [α]24D −86.5° (c 1.44, CHCl3); UV(CHCl3) λmax 266.0 nm; 1H NMR (CDCl3) δ 8.20 (s, 1H), 7.62˜7.06 (m, 15H), 6.37 (d, J=13.9 Hz, 1H), 3.89 (dd, J=9.7, 6.9 Hz, 1H), 3.80 (td, J=7.8, 1.3 Hz, 1H), 3.72˜3.64 (m, 1H), 2.68˜2.57 (m, 1H), 2.52 (td, J=12.9, 7.7 Hz, 1H), 0.98 (s, 9H); 13C NMR (CDCl3) δ 157.03 (d, J=220.8 Hz), 153.55 (d, J=16.7 Hz), 152.44 (d, J=17.3 Hz), 145.53, 136.28, 135.61, 135.54, 132.82, 132.72, 130.05, 129.99, 129.80 (d, J=4.6 Hz), 129.51, 129.03, 127.84, 124.20, 105.00 (d, J=248.3 Hz), 66.56, 65.92 (d, J=21.1 Hz), 47.38, 41.51 (d, J=20.9 Hz), 26.76, 19.19; Anal. Calcd for C32H31ClF2N4OSSeSi: C, 54.89; H, 4.46; N, 8.00; S, 4.58. Found: C, 54.81; H, 4.64; N, 7.81; S, 4.63.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[N:7][C:8](I)=[N:9]2)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(O)=O>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1
Reactant: Brc1ccc2cnc(I)nc2c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: O=CO
Product: Brc1ccc2cncnc2c1
Temperature: 70 °C
Reaction time: 8 h
Yield: 51.1 %

Procedure:
To a mixture of 7-bromo-2-iodoquinazoline (69 mg, 206 μmol), triphenylphosphine (5.4 mg, 21 μmol), and Pd(OAc)2 (3.2 mg, 14 μmol) in DMF (4.0 mL) was added TEA (72 μL, 515 μmol) and formic acid (9.5 μL, 247 μmol). The reaction mixture was stirred at 70° C. overnight. After cooling, the reaction mixture was concentrated, and the crude residue was dissolved in DCM and mixed with SiO2. The solvent was evaporated, and the residue was purified with flash column chromatography (pure DCM→3% MeOH in DCM) to obtain the desired product 7-bromoquinazoline (22 mg, 51%) as a white solid. LCMS (API-ES) m/z (%): 210.0 (100%, M++H).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[NH:5][C:4](=[O:15])[C:3]=1[CH2:16][NH:17]C(=O)OC(C)(C)C.[ClH:25]>>[NH2:17][CH2:16][C:3]1[C:4](=[O:15])[NH:5][C:6]([CH2:8][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[CH:7][C:2]=1[CH3:1].[ClH:25]
Reactant: Cc1cc(Cc2ccccc2)[nH]c(=O)c1CNC(=O)OC(C)(C)C
Agent: Cl
Product: Cc1cc(Cc2ccccc2)[nH]c(=O)c1CN
Temperature: 25 °C

Procedure:
A solution of 1,1-dimethylethyl {[4-methyl-2-oxo-6-(phenylmethyl)-1,2-dihydro-3-pyridinyl]methyl}carbamate (1.2 g, 3.66 mmol) in 4N HCl (in 15 mL 1,4 dioxane) was heated to 60° C. for 1 h. The mixture was cooled to room temperature. The mixture was filtered and dried to give 3-(aminomethyl)-4-methyl-6-(phenylmethyl)-2(1H)-pyridinone as an HCl salt (0.725 g, 87%). LCMS MH+=229.1 1H NMR (400 MHz, DMSO-d6) δ 11.9-12.0 (br s, 1H), 7.99 (br s, 3H), 7.20 (s, 5H), 5.97 (s, 1H), 3.72-3.75 (m, 4H), 2.17 (s, 3H).
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].S(Cl)(Cl)(=O)=O.[CH3:17]O>>[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([O:6][CH3:17])=[O:5]
Reactant: O=C(O)c1ccc(F)cc1F
Reactant: CO
Solvent: O=S(=O)(Cl)Cl
Product: COC(=O)c1ccc(F)cc1F
Yield: 92 %

Procedure:
To a solution of 2,4-difluorobenzoic acid (50.0 g, 316.25 mmol) in methanol (500 mL) was added sulfuryl dichloride (112 g, 949.15 mmol) at 0° C. The resulting solution was heated to reflux overnight and concentrated in vacuo to afford methyl 2,4-difluorobenzoate as a colorless oil (50 g, 92%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C@H:13]([OH:14])[C@@H:12]([OH:15])[C@H:11]([OH:16])[C@@H:10]([CH2:17][O:18][C:19]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[O:9]2)=[CH:4][C:3]=1[CH2:38][C:39]1[CH:44]=[CH:43][C:42]([O:45][CH2:46][CH3:47])=[CH:41][CH:40]=1.[H-].[Na+].[CH2:50](Br)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1>CN(C=O)C.O>[CH2:50]([O:14][C@@H:13]1[C@@H:12]([O:15][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C@H:11]([O:16][CH2:38][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:2]=2)[C@@H:10]([CH2:17][O:18][C:19]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[O:9][C@H:8]1[C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([CH2:38][C:39]2[CH:40]=[CH:41][C:42]([O:45][CH2:46][CH3:47])=[CH:43][CH:44]=2)[CH:4]=1)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1
Reactant: BrCc1ccccc1
Reactant: CCOc1ccc(Cc2cc([C@@H]3O[C@H](COC(c4ccccc4)(c4ccccc4)c4ccccc4)[C@@H](O)[C@H](O)[C@H]3O)ccc2Cl)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOc1ccc(Cc2cc([C@@H]3O[C@H](COC(c4ccccc4)(c4ccccc4)c4ccccc4)[C@@H](OCc4ccccc4)[C@H](OCc4ccccc4)[C@H]3OCc3ccccc3)ccc2Cl)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 178 %

Procedure:
To a solution of (2S,3R,4R,5S,6R)-2-[4-Chloro-3-(4-ethoxy-benzyl)-phenyl]-6-trityloxymethyl-tetrahydro-pyran-3,4,5-triol (9.8 g, 15 mmole) in dry DMF (50 mL), sodium hydride (3.2 g 50% in oil, 67.8 mmole) was added at 0° C. and stirred at room temperature for 2 hours. Benzyl bromide (5.9 mL, 49.7 mmole), tetrabutylammoniuliodide (500 mg) added and the reaction mixture stirred at room temperature for 18 hours. The reaction mixture was diluted with water (500 mL) and extracted with DCM (2×500 mL). The crude product obtained after removal of solvent to furnish 12.3 g of (2S,3S,4R,5R,6R)-3,4,5-tris-benzyloxy-2-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-6-trityloxymethyl-tetrahydro-pyran.
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH3:8])=[C:6]([N+]([O-])=O)[CH:5]=[CH:4][N+:3]=1[O-:12].C(C(C)=O)C.[F:18][C:19]([F:26])([C:22]([F:25])([F:24])[F:23])[CH2:20][OH:21].C(=O)([O-])[O-].[K+].[K+]>CN(C)P(=O)(N(C)C)N(C)C>[CH3:1][C:2]1[C:7]([CH3:8])=[C:6]([O:21][CH2:20][C:19]([F:26])([F:18])[C:22]([F:25])([F:24])[F:23])[CH:5]=[CH:4][N+:3]=1[O-:12]
Reactant: Cc1c([N+](=O)[O-])cc[n+]([O-])c1C
Reactant: OCC(F)(F)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: Cc1c(OCC(F)(F)C(F)(F)F)cc[n+]([O-])c1C
Temperature: 75 °C
Reaction time: 108 h

Procedure:
A mixture of 2,3-dimethyl-4-nitropyridine-1-oxide (2.0 g), methyl ethyl ketone (30 ml), 2,2,3,3,3-pentafluoropropanol (3.05 ml), anhydrous potassium carbonate (3.29 g) and hexamethylphosphoric acid triamide (2.07 g) was heated at 70-80° C. with stirring for 4.5 days. Then, the insoluble matter was filtered off and the filtrate was concentrated. Water was added to the residue and the mixture was extracted with ethyl acetate. The extract layer was dried over magnesium sulfate, then the solvent was distilled off, and the residue was applied to a silica gel column (50 g). Elution with chloroform-methanol (10:1) and recrystallization from ethyl acetate-hexane gave 2.4 g of 2,3-dimethyl-4-(2,2,3,3,3-pentafluoropropoxy)pyridine-1-oxide as colorless needles. Melting point 148-149° C.
Reaction SMILES: Cl[CH2:2][Cl:3].Cl[C:5]1[CH:12]=[CH:11][C:8]([CH:9]=O)=[CH:7][CH:6]=1.[OH-].[Na+]>[Cl-].C([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)C1C=CC=CC=1.O>[Cl:3][C:2]1[CH:11]=[CH:12][CH:5]=[CH:6][C:7]=1[CH:8]=[CH:9][C:8]1[CH:11]=[CH:12][CH:5]=[CH:6][CH:7]=1
Reactant: O=Cc1ccc(Cl)cc1
Reactant: ClCCl
Agent: [Cl-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: Clc1ccccc1C=Cc1ccccc1
Reaction time: 1 h

Procedure:
A 25 ml reaction flask was charged with 12.42 gram (0.03 moles) of polyvinyl benzyl triphenyl phosphonium chloride, 60 ml of dichloromethane, and 14.0 gm (0.10 moles) of p-chlorobenzaldehyde. A magnetic stirr bar was added and a thermometer and a condenser were attached. 20 grams of 50% aqueous NaOH solution was added all at once to the reaction flask. The temperature of the reaction mixture rose to a reflux and was stirred for one hour. 100 ml of H2O was added and the organic layer was separated. The polymer was precipitated from an excess of methanol. 5.55 grams of a white fibrous polymer was obtained. The polymer was continuously extracted with methanol for 24 hours before being dried and submitted for elemental analysis for % Cl and % P. A calculated percent is 14.7% Cland 0.0% P. The analysis indicated 14.55% Cl and 0.3% P.
Reaction SMILES: [Na].[OH:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([OH:17])=[O:16])[CH:10]=2)[CH:6]=[CH:7][CH:8]=1.[C:18]1([C:24]([CH:26](Br)[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C(O)C.S(=O)(=O)(O)O>[OH:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([O:17][CH:26]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:24](=[O:25])[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:16])[CH:10]=2)[CH:6]=[CH:7][CH:8]=1
Reactant: O=C(O)c1cccc(-c2cccc(O)c2)c1
Reactant: O=C(c1ccccc1)C(Br)c1ccccc1
Agent: O=S(=O)(O)O
Agent: [Na]
Solvent: CCO
Product: O=C(OC(C(=O)c1ccccc1)c1ccccc1)c1cccc(-c2cccc(O)c2)c1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 78.1 %

Procedure:
Sodium (64 mg) was dissolved in ethanol (10 ml) and 3'-hydroxy-3-biphenylcarboxylic acid (0.5 g) was added thereto. The mixture was stirred at room temperature for 20 minutes, and then conc. sulfuric acid (1 drop) and desyl bromide (642 mg) was added thereto. The resulting mixture was stirred under reflux for 3 hours, cooled to room temperature, and partitioned between water and ethyl acetate. The organic layer was washed successively with water (twice), 1N hydrochloric acid, sodium bicarbonate aqueous solution, and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was chromatographed (n-hexane--ethyl acetate) over silica gel to afford 2-oxo-1,2-diphenylethyl 3'-hydroxy-3-biphenylcarboxylate (744 mg) as a paste.
Reaction SMILES: O1CCCC1.[NH:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([CH:15]2[CH2:20][CH2:19][N:18]([CH2:21][CH2:22][C:23]3[C:32]4[C:27](=[CH:28][CH:29]=[C:30]([N+:33]([O-])=O)[CH:31]=4)[NH:26][C:25](=[O:36])[CH:24]=3)[CH2:17][CH2:16]2)=[CH:7]1>CO>[NH2:33][C:30]1[CH:31]=[C:32]2[C:27](=[CH:28][CH:29]=1)[NH:26][C:25](=[O:36])[CH:24]=[C:23]2[CH2:22][CH2:21][N:18]1[CH2:17][CH2:16][CH:15]([C:8]2[C:9]3[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=3)[NH:6][CH:7]=2)[CH2:20][CH2:19]1
Reactant: O=c1cc(CCN2CCC(c3c[nH]c4ccccc34)CC2)c2cc([N+](=O)[O-])ccc2[nH]1
Solvent: C1CCOC1
Solvent: CO
Product: Nc1ccc2[nH]c(=O)cc(CCN3CCC(c4c[nH]c5ccccc45)CC3)c2c1
Temperature: 55 °C
Reaction time: 4 h
Yield: 77.3 %

Procedure:
Into a mixed solvent of tetrahydrofuran (800 ml) and methanol (200 ml) was dissolved 4-[2-[4-(1H-indol-3-yl)-1-piperidinyl]ethyl]-6-nitro-2(1H)-quinolinone (III-19) (6 g, 14.4 mmol) under heating. Paladium on carbon (2.5 g) was added thereto and the mixture was stirred under hydrogen atmosphere at 55 ° C. for 4 hours. The reaction mixture was filtered at the same temperature and the solvent was distilled off from the filtrate. The residue was dried and then recrystallized from a mixture of methanol, THF and water to give the desired product (III-20) (4.3 g) as pale yellow crystals (mp 214°-216 ° C. (methanol/tetrahydrofuran water)). Yield 77.3 %.