Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]([N:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1)=[O:12])[C:5]([OH:7])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(C(C)C)CC)(C)C.[Cl:49][C:50]1[CH:70]=[CH:69][C:53]2[NH:54][C:55]([C@@H:57]([NH2:68])[CH2:58][C:59]3[C:67]4[C:62](=[CH:63][CH:64]=[CH:65][CH:66]=4)[NH:61][CH:60]=3)=[N:56][C:52]=2[CH:51]=1.ClCl>O1CCCC1.ClCCl.C(O)C>[Cl:49][C:50]1[CH:70]=[CH:69][C:53]2[NH:54][C:55]([C@@H:57]([NH:68][C:5](=[O:7])[C:4]3[CH:8]=[CH:9][C:10]([C:11]([N:13]4[CH2:17][CH2:16][CH2:15][CH2:14]4)=[O:12])=[C:2]([CH3:1])[CH:3]=3)[CH2:58][C:59]3[C:67]4[C:62](=[CH:63][CH:64]=[CH:65][CH:66]=4)[NH:61][CH:60]=3)=[N:56][C:52]=2[CH:51]=1
Reactant: N[C@@H](Cc1c[nH]c2ccccc12)c1nc2cc(Cl)ccc2[nH]1
Reactant: Cc1cc(C(=O)O)ccc1C(=O)N1CCCC1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: ClCl
Agent: F[B-](F)(F)F
Solvent: CCO
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cc(C(=O)N[C@@H](Cc2c[nH]c3ccccc23)c2nc3cc(Cl)ccc3[nH]2)ccc1C(=O)N1CCCC1

Procedure:
Prepared analogously to Example 1g from 3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzoic acid, TBTU, diisopropylethylamine, and (1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-(1H-indol-3-yl)ethylamine in tetrahydrofuran. Yield: %; Rf value: 0.48 (silica gel: dichloromethane/ethanol=9:1); C30H28ClN5O2 (526.04); mass spectrum: (M+H)+=526/528(chlorine isotope).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[CH:10]=[CH2:11].[CH2:12]([O:19][C:20]1[CH:25]=[C:24](I)[CH:23]=[CH:22][C:21]=1[N:27]1[S:31](=[O:33])(=[O:32])[NH:30][C:29](=[O:34])[CH2:28]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(N(CC)CC)C>C(#N)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:12]([O:19][C:20]1[CH:25]=[C:24]([CH:10]([C:3]2[C:4]([CH3:9])=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=2[CH3:1])[CH3:11])[CH:23]=[CH:22][C:21]=1[N:27]1[S:31](=[O:33])(=[O:32])[NH:30][C:29](=[O:34])[CH2:28]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: C=Cc1c(C)cc(C)cc1C
Reactant: O=C1CN(c2ccc(I)cc2OCc2ccccc2)S(=O)(=O)N1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: CC#N
Solvent: CCN(CC)CC
Product: Cc1cc(C)c(C(C)c2ccc(N3CC(=O)NS3(=O)=O)c(OCc3ccccc3)c2)c(C)c1
Temperature: 120 °C

Procedure:
A mixture of 1,3,5-trimethyl-2-vinylbenzene (0.058 mL, 0.36 mmol), 5-(2-benzyloxy-4-iodophenyl)-1,1-dioxo-1,2,5-thiadiazolidin-3-one (80 mg, 0.18 mmol), Pd(OAc)2 (5 mg, 0.09 mmol) and triethylamine (0.13 mL, 0.9 mmol) in acetonitrile (1.5 mL) is heated in a microwave apparatus at 120° C. for 1 h. The mixture is filtered over Celite and the filtrate is evaporated to give the title compound which is used directly in the next step.
Reaction SMILES: [CH2:1]([C:3]([CH2:7][OH:8])([CH2:5][OH:6])[CH3:4])[OH:2].O[CH2:10]C(CO)(CO)CO>>[CH2:1]([C:3]([CH2:7][OH:8])([CH2:5][OH:6])[CH2:4][CH3:10])[OH:2]
Reactant: CC(CO)(CO)CO
Reactant: OCC(CO)(CO)CO
Product: CCC(CO)(CO)CO

Procedure:
1,1,1-trimethylolethane; pentaerythritol;
Reaction SMILES: [CH2:1]([C:4]1[CH:5]=[C:6]([CH:11]=[CH:12][C:13]=1OS(C(F)(F)F)(=O)=O)[C:7]([O:9][CH3:10])=[O:8])[CH2:2][CH3:3].[CH:22]([Sn](CCCC)(CCCC)CCCC)=[CH2:23]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([C:4]1[CH:5]=[C:6]([CH:11]=[CH:12][C:13]=1[CH:22]=[CH2:23])[C:7]([O:9][CH3:10])=[O:8])[CH2:2][CH3:3]
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Reactant: CCCc1cc(C(=O)OC)ccc1OS(=O)(=O)C(F)(F)F
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Product: C=Cc1ccc(C(=O)OC)cc1CCC
Temperature: 60 °C
Reaction time: 6 h
Yield: 62.9 %

Procedure:
To a solution of 8.053 g (24.7 mmol) of the product of Step A and 8.136 g (25.7 mmol) of vinyltributyltin in 50 mL of anhydrous DMF was added 0.520 g (0.74 mmol) of bis(triphenylphosphine)palladium(II) chloride, the mixture was freed of air by alternate vacuum and nitrogen flush cycles, and the reaction mixture was magnetically stirred at 60° C. for 6 hours. The reaction mixture was then cooled to room temperature, partitioned between EtOAc and saturated brine, and extracted. The organic layer was washed three times with brine, separated, dried (MgSO4), filtered and evaporated. The residue was purified on a silica gel flash chromatography column eluted with 3% EtOAc in hexane. Evaporation of the purified fractions and drying in vacuo afforded 3.176 g (63%) of the title compound as a clear oil.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:17]([O:23][C:24](=[O:26])[CH3:25])[CH2:16][S:15][C@H:6]1[O:7][C:8]1[CH:9]=[N:10][CH:11]=[C:12](I)[CH:13]=1)(=[O:3])[CH3:2].[F:27][C:28]1[CH:33]=[CH:32][C:31]([S:34]([O-:36])=[O:35])=[CH:30][CH:29]=1>>[C:1]([O:4][C@@H:5]1[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:17]([O:23][C:24](=[O:26])[CH3:25])[CH2:16][S:15][C@H:6]1[O:7][C:8]1[CH:9]=[N:10][CH:11]=[C:12]([S:34]([C:31]2[CH:32]=[CH:33][C:28]([F:27])=[CH:29][CH:30]=2)(=[O:36])=[O:35])[CH:13]=1)(=[O:3])[CH3:2]
Reactant: O=S([O-])c1ccc(F)cc1
Reactant: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cncc(I)c1
Product: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cncc(S(=O)(=O)c2ccc(F)cc2)c1

Procedure:
By following a procedure analogous to Example 139 starting from 5-iodo-3-pyridinyl 2,3,4-tri-O-acetyl-5-thio-β-D-xylopyranoside and 4-fluorophenyl sulfinate, 5-[(4-fluorophenyl)sulfonyl]-3-pyridinyl 2,3,4-tri-O-acetyl-5-thio-β-D-xylopyranoside is obtained in the form of a white solid (yield=24%).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([NH:21][C:22]4[CH:27]=[CH:26][N:25]=[CH:24][N:23]=4)(=[O:20])=[O:19])=[CH:15][CH:16]=3)[CH:11]=[CH:10][N:9]=2)=[C:4]([CH3:28])[CH:3]=1.[F:29][C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>>[F:29][C:30]1[CH:35]=[C:34]([C:2]2[CH:7]=[CH:6][C:5]([C:8]3[C:17]4[C:12](=[CH:13][C:14]([S:18]([NH:21][C:22]5[CH:27]=[CH:26][N:25]=[CH:24][N:23]=5)(=[O:19])=[O:20])=[CH:15][CH:16]=4)[CH:11]=[CH:10][N:9]=3)=[C:4]([CH3:28])[CH:3]=2)[CH:33]=[CH:32][CH:31]=1
Reactant: OB(O)c1cccc(F)c1
Reactant: Cc1cc(Cl)ccc1-c1nccc2cc(S(=O)(=O)Nc3ccncn3)ccc12
Agent: COc1cccc(OC)c1-c1ccccc1P(C1CCCCC1)C1CCCCC1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Product: Cc1cc(-c2cccc(F)c2)ccc1-c1nccc2cc(S(=O)(=O)Nc3ccncn3)ccc12
Temperature: 100 °C
Yield: 42 %

Procedure:
A vial was charged with 1-(4-chloro-2-methylphenyl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (EXAMPLE 357; 61.66 mg, 0.150 mmol) (3-fluorophenyl)boronic acid (42.0 mg, 0.300 mmol), dicyclohexyl(2′,6′-dimethoxy-[1,1′-biphenyl]-2-yl)phosphine (3.08 mg, 7.50 mmol), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(ii) dichloromethane (11.37 mg, 0.015 mmol) and potassium phosphate (96 mg, 0.450 mmol). The vial was flushed with Ar (g), then 1,4-dioxane (682 μl) and water (68.2 μl) were added in sequence. The vial was sealed and heated in a Biotage Initiator microwave reactor for 1 h 45 min at 100° C. The mixture was extracted with EtOAc (3×). The combined organic extracts were concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 3% MeOH/DCM) to give 1-(3′-fluoro-3-methyl-[1,1′-biphenyl]-4-yl)-N-(pyrimidin-4-yl)isoquinoline-6-sulfonamide (29.49 mg, 0.063 mmol, 41.8% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=13.08 (br. s., 1H), 8.77-8.67 (m, 2H), 8.58 (s, 1H), 8.24 (br. s., 1H), 8.15 (d, J=5.6 Hz, 1H), 7.98 (dd, J=1.8, 8.9 Hz, 1H), 7.80-7.72 (m, 2H), 7.71-7.61 (m, 3H), 7.55 (dt, J=6.2, 8.0 Hz, 1H), 7.39 (d, J=7.9 Hz, 1H), 7.28-7.19 (m, 1H), 7.03 (br. s., 1H), 2.06 (s, 3H). m/z (ESI) 471.2 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH:18]=[CH:19][C:20]2[N:29]=[C:28]3[C:23]([C:24]([CH3:32])=[C:25]([CH3:31])[C:26](=[O:30])[NH:27]3)=[CH:22][CH:21]=2)[CH2:11][CH2:10]1>C1COCC1.C(O)C.[Ni]>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20]2[N:29]=[C:28]3[C:23]([C:24]([CH3:32])=[C:25]([CH3:31])[C:26](=[O:30])[NH:27]3)=[CH:22][CH:21]=2)[CH2:11][CH2:10]1
Reactant: Cc1c(C)c2ccc(C=CCCCN3CCN(c4cccc(Cl)c4Cl)CC3)nc2[nH]c1=O
Agent: [Ni]
Solvent: CCO
Solvent: C1CCOC1
Product: Cc1c(C)c2ccc(CCCCCN3CCN(c4cccc(Cl)c4Cl)CC3)nc2[nH]c1=O
Reaction time: 3 h
Yield: 79.5 %

Procedure:
7-{5-[4-(2,3-Dichloro-phenyl)-piperazin-1-yl]-pent-1-enyl}-3,4-dimethyl-1H-[1,8]naphthyridin-2-one (80 mg, 0.17 mmol) was dissolved in a minimal amount of THF (2 mL) and the solution was diluted with ethanol (10 mL). The solution was treated with Raney Nickel (0.5 mL slurry in water) and shaken under 45 psi H2 for 3 h. The mixture was filtered through celite. The celite pad was washed with THF (2×10 mL), and the filtrate was evaporated in vacuo. The crude solid was purified by column chromatography (5% MeOH/CH2Cl2) to yield the title compound as a white solid (64 mg, 80%). mp 202–203° C., 1H NMR (400 MHz, CDCl3) δ 8.98 (br s, 1H) 7.84 (d, 1H), 7.20–7.15 (m, 2H), 7.04 (d, 1H), 6.98–6.95 (m, 1H), 3.15–3.00 (m, 4H), 2.81 (t, 2H), 2.70–2.55 (m, 4H), 2.46–2.36 (m, 5H), 2.22 (s, 3H), 1.82–1.75 (m, 2H), 1.60–1.50 (m, 2H), 1.45–1.36 (m, 2H), MS ES+ 473.00 (M+H)+ (Exact Mass: 472.18).
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1.C([O-])([O-])=O.[Na+].[Na+].[N:18]1[CH:23]=[CH:22][CH:21]=[C:20](B(O)O)[CH:19]=1>CN(C=O)C.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]>[CH3:8][C:6]1[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=[C:2]([C:20]2[CH:19]=[N:18][CH:23]=[CH:22][CH:21]=2)[CH:7]=1
Reactant: OB(O)c1cccnc1
Reactant: Cc1cc(Br)ncc1[N+](=O)[O-]
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CN(C)C=O
Product: Cc1cc(-c2cccnc2)ncc1[N+](=O)[O-]
Reaction time: 6 h
Yield: 79.9 %

Procedure:
To a solution of 2-bromo-4-methyl-5-nitropyridine (217 g, 1 mol) in DMF (2000 mL) was added Pd(dppf)Cl2 (5 g), saturated solution of Na2CO3 (200 mL) and pyridin-3-ylboronic acid (147 g, 1.2 mol). The mixture was stirred under argon for 6 h at 100. After cooling down, the solvent was removed under reduced pressure evaporation and the residue was purified by silica-gel column chromatography (mobile phase: EA:PE=1:1) to afford 4-methyl-5-nitro-2,3′-bipyridine (172 g, 80%).
Reaction SMILES: [C:1]([N:9]1[C:21]2[CH2:20][CH2:19][CH2:18][CH:17]([C:22]([O:24]CC3C=CC=CC=3)=[O:23])[C:16]=2[C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][CH:14]=2)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H][H]>[Pd].C(O)C>[C:1]([N:9]1[C:21]2[CH2:20][CH2:19][CH2:18][CH:17]([C:22]([OH:24])=[O:23])[C:16]=2[C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][CH:14]=2)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: [H][H]
Reactant: O=C(OCc1ccccc1)C1CCCc2c1c1ccccc1n2C(=O)c1ccccc1
Agent: [Pd]
Solvent: CCO
Product: O=C(O)C1CCCc2c1c1ccccc1n2C(=O)c1ccccc1

Procedure:
A solution of 5.6 g. benzyl 9-benzoyl-1,2,3,4-tetrahydrocarbazole-4-carboxylate in 250 ml. ethyl alcohol containing 0.5 g. 10% palladium-on-charcoal was subjected to a hydrogen atmosphere at 40 p.s.i., while being heated with an infrared lamp and agitated, until uptake of hydrogen ceased. The mixture was filtered, the filtrate was evaporated to dryness under reduced pressure, the resulting residue was dissolved in ether, the ether solution was extracted with dilute potassium bicarbonate, the bicarbonate extract was acidified with 3N-hydrochloric acid and extracted with ether and the ether extract was dried and evaporated to dryness. The resulting residue was crystallized from ether-pentane and a solution of the resulting crystals in 5% potassium bicarbonate solution was acidified with 3N hydrochloric acid and the resulting solid was filtered and washed with water to give 1.3 g. of the title compound; m.p. 70°-80°C.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([NH:8][C:9]([C:11]2[C:19]3[O:18][CH2:17][O:16][C:15]=3[C:14]([N+:20]([O-])=O)=[CH:13][CH:12]=2)=[O:10])[CH2:4][CH2:3]1>CO>[NH2:20][C:14]1[C:15]2[O:16][CH2:17][O:18][C:19]=2[C:11]([C:9]([NH:8][CH:5]2[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)=[O:10])=[CH:12][CH:13]=1
Reactant: CN1CCC(NC(=O)c2ccc([N+](=O)[O-])c3c2OCO3)CC1
Solvent: CO
Product: CN1CCC(NC(=O)c2ccc(N)c3c2OCO3)CC1
Reaction time: 2 h
Yield: 95.5 %

Procedure:
N-(1-methyl-4-piperidyl)-7-nitro-benzo[1,3]dioxole-4-carboxamide (Intermediate 224; 290 mg, 0.94 mmol) was suspended in methanol (50 mL) and the system purged with nitrogen. 10% Pd/C (30 mg) was added and the mixture stirred under a hydrogen atmosphere for 2 hours. The catalyst was filtered off and the filtrate evaporated to give the title compound as a white solid (249 mg, 96%).
Reaction SMILES: [H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][C:13](=O)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Cl.COP([CH2:24][C:25]([O:27][CH3:28])=[O:26])(OC)=O>O1CCCC1.C(OCC)(=O)C>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][C:13](=[CH:24][C:25]([O:27][CH3:28])=[O:26])[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: COC(=O)CP(=O)(OC)OC
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COC(=O)C=C1CCN(C(=O)OC(C)(C)C)CC1

Procedure:
In tetrahydrofuran (40 ml), methyl dimethylphosphonoacetate (1.8 ml) was dissolved. To the resulting solution, 60% oily sodium hydride (450 mg) was added under ice cooling, followed by stirring under the same condition. After the addition of a solution of 1-(tert-butoxycarbonyl)-4-piperidone (2.0 g) in tetrahydrofuran (tetrahydrofuran: 10 ml) and stirring at room temperature for 30 minutes, the reaction mixture was diluted with ethyl acetate. To the diluted solution, 2N hydrochloric acid was added. The organic layer was separated, washed with a saturated aqueous solution of sodium bicarbonate and saturated aqueous NaCl solution, and dried over anhydrous sodium sulfate. The solvent was then distilled off under reduced pressure. The residue was purified by chromatography on a silica gel column (hexane:ethyl acetate=6:1), whereby the title compound (2.35 g, 92%) was obtained.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=2[O:20][CH:21]([C:28]([O:30]C)=[O:29])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].OS([O-])(=O)=O.[K+]>CO>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=2[O:20][CH:21]([C:28]([OH:30])=[O:29])[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)C(Oc1ccc(Cl)cc1OC1CN(C(=O)OC(C)(C)C)C1)c1ccccc1
Agent: O=S(=O)([O-])O
Agent: [K+]
Agent: [Na+]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CC(Oc2cc(Cl)ccc2OC(C(=O)O)c2ccccc2)C1
Reaction time: 18 h
Yield: 102.4 %

Procedure:
To the title compound of Example 148 Step A (0.16 g, 0.36 mmol) in MeOH (3 mL) was added 1N NaOH (3 mL). After 18 h, the solution was acidified with 1N KHSO4 and extracted with EtOAc (2×). The combined organics were washed with brine and dried to give 0.16 g (>98%) of the title compound. 1H NMR (CDCl3): 8.56-8.19 (broad s, 1H), 7.55-7.51 (m, 2H), 7.41-7.36 (m, 3H), 6.85-6.84 (m, 2H), 6.54 (s, 1H), 5.55 (s, 1H), 4.88-4.83 (m, 1H), 4.29-4.24 (m, 2H), 4.06-3.97 (m, 2H), 1.44 (s, 9H).
Reaction SMILES: [C:1]([O:4][C:5]1[C:10]([C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:9][C:8]([O:15][CH3:16])=[C:7](CC=C)[C:6]=1[C:20]([CH3:23])([CH3:22])[CH3:21])(=[O:3])[CH3:2].I([O-])(=O)(=O)=O.[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+].[O:37]1CC[CH2:39][CH2:38]1>O.[Os](=O)(=O)(=O)=O>[C:1]([O:4][C:5]1[C:10]([C:11]([CH3:12])([CH3:14])[CH3:13])=[CH:9][C:8]([O:15][CH3:16])=[C:7]([CH2:39][CH:38]=[O:37])[C:6]=1[C:20]([CH3:21])([CH3:22])[CH3:23])(=[O:3])[CH3:2]
Reactant: C1CCOC1
Reactant: C=CCc1c(OC)cc(C(C)(C)C)c(OC(C)=O)c1C(C)(C)C
Agent: O=[Os](=O)(=O)=O
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: O
Product: COc1cc(C(C)(C)C)c(OC(C)=O)c(C(C)(C)C)c1CC=O
Temperature: 25 °C
Reaction time: 48 h
Yield: 83 %

Procedure:
4-Acetoxy-3,5-di-tert-butyl-2-(2-propenyl)anisole (19 g) was dissolved in a 1:1 mixture (200 ml) of tetrahydrofuran and water. After adding osmium tetroxide (0.12 g) and sodium periodate (26.9 g), the mixture was stirred at room temperature for 48 h. After the end of the reaction, a saturated aqueous solution of sodium thiosulfate was added and the mixture was subjected to extraction with ethyl acetate and the organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The concentrate was purified by silica gel chromatography (25% ethyl acetate in n-hexane) to afford 4-acetoxy-3,5-di-tert-butyl-2-formylmethylanisole [16 g (yield, 83%)].
Reaction SMILES: C1(C)C=CC(S(O)(=O)=O)=CC=1.[C:12]([C:15]1[CH:45]=[CH:44][C:18]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([CH:27]([O:37]C3CCCCO3)[C:28]3[CH:29]=[C:30]([CH:34]=[CH:35][CH:36]=3)[C:31]([OH:33])=[O:32])=[CH:23][CH:22]=2)=[C:17]([Cl:46])[C:16]=1[OH:47])(=[O:14])[CH3:13]>CO.C(OCC)(=O)C>[C:12]([C:15]1[CH:45]=[CH:44][C:18]([O:19][CH2:20][C:21]2[CH:22]=[CH:23][C:24]([CH:27]([OH:37])[C:28]3[CH:29]=[C:30]([CH:34]=[CH:35][CH:36]=3)[C:31]([OH:33])=[O:32])=[CH:25][CH:26]=2)=[C:17]([Cl:46])[C:16]=1[OH:47])(=[O:14])[CH3:13]
Reactant: CC(=O)c1ccc(OCc2ccc(C(OC3CCCCO3)c3cccc(C(=O)O)c3)cc2)c(Cl)c1O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCOC(C)=O
Solvent: CO
Product: CC(=O)c1ccc(OCc2ccc(C(O)c3cccc(C(=O)O)c3)cc2)c(Cl)c1O
Reaction time: 8 h
Yield: 93.9 %

Procedure:
Add p-toluenesulfonic acid (16.8 mg, 0.098 mmol) to a solution of 3-[[4-(4-acetyl-2-chloro-3-hydroxy-phenoxymethyl)-phenyl]-(tetrahydro-pyran-2-yloxy)-methyl]-benzoic acid (1.00 g, 1.96 mmol) in methanol (0.20M) and stir overnight. Evaporate solvents, dilute with ethyl acetate and wash with water (1×) and brine (1×). Dry and concentrate to afford the title compound as a white solid (0.786 mg, 1.84 mmol, 94%): MS (m/z): 426 (M−H).
Reaction SMILES: [CH3:1][Si:2]([CH3:18])([CH3:17])[C:3]1[O:7][C:6]([CH3:8])=[C:5]([CH2:9][OH:10])[C:4]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[C:19](Cl)(=[O:31])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]>C(N(CC)CC)C>[CH3:18][Si:2]([CH3:17])([CH3:1])[C:3]1[O:7][C:6]([CH3:8])=[C:5]([CH2:9][O:10][C:19](=[O:31])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[C:4]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: CCCCCCCCCCCC(=O)Cl
Reactant: Cc1oc([Si](C)(C)C)c(-c2ccccc2)c1CO
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCC(=O)OCc1c(C)oc([Si](C)(C)C)c1-c1ccccc1

Procedure:
4-Phenyl-5-trimethylsilyl-3-furancarboxaldehyde (Compound 12) is reduced with lithium aluminum hydride to yield the corresponding alcohol (Compound 13), which is thereafter methylated with methyl iodide in the presence of n butyl lithium and lithium chloride in the 5-position of the furan nucleus to yield 5-trimethylsilyl-4-phenyl-3-hydroxymethyl-2-methylfuran (Compound 14). 5-Trimethylsilyl-4-phenyl-3-hydroxymethyl-2-methylfuran (Compound 14) is esterified by treatment with lauroyl chloride in the presence of triethylamine to yield 5-trimethylsilyl-4-phenyl-3-dodecoyloxymethyl-2-methylfuran (Compound 15). Compound 15 is subjected to singlet oxidation, in a chilled (approximately -5° C.) dry tetrahydrofuran solution, in the presence of Rose Bengal dye under irradiation with light to provide 4-dodecoyloxymethyl-5-hydroxy-5-methyl-3-phenyl-2-furanone (Compound 5).
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:20]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[O:28][CH3:29])=[C:19]([O:30][CH2:31][CH2:32][NH2:33])[N:18]=[C:17]([CH:34]3[CH2:36][CH2:35]3)[N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:37]([S:39](Cl)(=[O:41])=[O:40])[CH3:38]>>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([S:11]([NH:14][C:15]2[C:20]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[O:28][CH3:29])=[C:19]([O:30][CH2:31][CH2:32][NH:33][S:39]([CH2:37][CH3:38])(=[O:41])=[O:40])[N:18]=[C:17]([CH:34]3[CH2:36][CH2:35]3)[N:16]=2)(=[O:12])=[O:13])=[CH:9][CH:10]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CCS(=O)(=O)Cl
Reactant: COc1ccccc1Oc1c(NS(=O)(=O)c2ccc(C(C)(C)C)cc2)nc(C2CC2)nc1OCCN
Product: CCS(=O)(=O)NCCOc1nc(C2CC2)nc(NS(=O)(=O)c2ccc(C(C)(C)C)cc2)c1Oc1ccccc1OC

Procedure:
According to Example 40) 256 mg 4-tert.-butyl-N-[6-(2-aminoethoxy)-5-(o-methoxyphenoxy)-2-cyclopropyl-pyrimidin-4-yl]-benzene-sulfonamide was reacted with ethanesulfonylchloride to give 120 mg 4-tert.-butyl-N-[6-(2-ethanesulfonylamino-ethoxy)-5-(o-methoxyphenoxy)-2-cyclopropyl-pyrimidin-4-yl]-benzene-sulfonamide. LC-MS: tR=5.79 min. [M−1]−=603.90.
Reaction SMILES: O[C:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11](O)([CH3:13])[CH3:12])=[CH:7][CH:6]=1)([CH3:4])[CH3:3].[CH3:15][C:16]1[CH:21]=[C:20]([CH3:22])[CH:19]=[CH:18][C:17]=1[OH:23]>>[OH:23][C:17]1[C:16]([CH3:15])=[CH:21][C:20]([CH3:22])=[CH:19][C:18]=1[C:9]1[CH:10]=[C:5]([CH:2]([CH3:4])[CH3:3])[CH:6]=[CH:7][C:8]=1[CH:11]([CH3:13])[CH3:12]
Reactant: Cc1ccc(O)c(C)c1
Reactant: CC(C)(O)c1ccc(C(C)(C)O)cc1
Product: Cc1cc(C)c(O)c(-c2cc(C(C)C)ccc2C(C)C)c1
Reaction time: 0.25 h
Yield: 80 %

Procedure:
A solution of 1164 g (6 mols) of α,α'-dihydroxy-p-diisopropyl benzene in 5490 g (45 mols) of 2,4-dimethyl phenol is added dropwise with stirring over a period of 9 to 10 hours at 150° C in a nitrogen atmosphere to a solution of 1830 g (15 mols) of 2,4-dimethyl phenol. At the same time, about 200 to 210 g of water distilled over. The reaction mixture is stirred for 15 minutes, the catalyst is neutralised with 6.5 g of soda and freed from 2,4-dimethyl phenol under reduced pressure up to a sump temperature of 140° C/12 Torr. This leaves a light, crystallising residue of 2230 g (93% of the theoretical). The recrystallisation of 100 g from 150 ml of tetrachloroethane gives α,α'-bis-(2-hydroxy-3,5-dimethyl phenyl-p-diisopropyl benzene in a yield of 80% (melting point 179° C).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([CH2:7][S:8][CH:9]([CH3:13])[C:10]([O-:12])=[O:11])=[CH:3][CH:2]=1.[Na+].[CH2:15](O)[CH3:16]>>[N:1]1[CH:6]=[CH:5][C:4]([CH2:7][S:8][CH:9]([CH3:13])[C:10]([O:12][CH2:15][CH3:16])=[O:11])=[CH:3][CH:2]=1
Reactant: CC(SCc1ccncc1)C(=O)[O-]
Reactant: CCO
Agent: [Na+]
Product: CCOC(=O)C(C)SCc1ccncc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
Crude sodium 2-(4-picolylthio)propionate (approximately 7 g.) was taken up in 100 ml. of absolute ethanol and approximately 5 cc. of 3 A molecular sieves were added. Dry hydrogen chloride was bubbled into the reaction mixture, which was refluxed for 75 minutes, while continuing to saturate with hydrogen chloride during the initial 15 minutes. The mixture was cooled to room temperature and allowed to stir overnight (approximately 16 hours). The mixture was filtered through diatomaceous earth and concentrated to a semi-solid mixture. The esterification step was repeated on this mixture, except saturation with hydrogen chloride was continued during 1 hour of reflux and refluxing was continued overnight. The reaction mixture was cooled to room temperature, filtered through diatomaceous earth and evaporated to an oil. The oil was extracted with chloroform, leaving filterable salts behind, and the chloroform stripped to yield ethyl 2-(4-picolylthio)propionate (waxy solid; ir (KBr) 3.0, 3.5, 5.75, 6.15, 6.30, 6.70, 8.6, 12.25μ; m.s.: m/e calcd: 225; found: 225, 152, 124, 102, 92, 45).