Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:34])[C@@H:12]([NH:20][C:21](=[O:33])[CH:22]([NH2:32])[C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([CH3:31])[CH:24]=2)[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[S:8][CH:9]=1)=[O:4].C(N(C(C)C)CC)(C)C.[O:44]=[C:45](Cl)OC(Cl)(Cl)Cl.O>ClCCl>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:34])[C@@H:12]([N:20]2[C:21](=[O:33])[CH:22]([C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25]([CH3:31])[CH:24]=3)[NH:32][C:45]2=[O:44])[CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[S:8][CH:9]=1)=[O:4]
Reactant: O=C(Cl)OC(Cl)(Cl)Cl
Reactant: COC(=O)c1csc(NC(=O)[C@H](Cc2ccccc2)NC(=O)C(N)c2ccc(OC)c(C)c2)n1
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COC(=O)c1csc(NC(=O)[C@H](Cc2ccccc2)N2C(=O)NC(c3ccc(OC)c(C)c3)C2=O)n1
Temperature: -10 °C
Reaction time: 0.5 h

Procedure:
A solution of 2-{(S)-2-[2-amino-2-(4-methoxy-3-methyl-phenyl)-acetylamino]-3-phenyl-propionylamino}-thiazole-4-carboxylic acid methyl ester (0.40 g , 0.83 mmol) and diisopropylethylamine (0.72 mL, 4.14 mmol) in dichloromethane (20 mL) was added to a solution of diphosgene (0.07 mL, 0.58 mmol) in dichloromethane (20 mL) at −10° C. The mixture was stirred at −10° C. for 0.5 hours. Water was added to quench the reaction, then the mixture was extracted with ethyl acetate. The organic layer was separated, washed with water, brine, dried over sodium sulfate and concentrated. The residue was purified by chromatography over silica gel eluted with ethyl acetate to give 2-{(S)-2-[4-(4-methoxy-3-methyl-phenyl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-propionylamino}-thiazole-4-carboxylic acid methyl ester as an off white foam (0.29 g, 69%).
Reaction SMILES: [CH2:1]([C:3]1[N:12]=[C:11]([CH2:13][CH3:14])[CH:10]=[C:9]2[C:4]=1[CH:5]=[C:6]([C:53]([O:55][CH2:56][CH3:57])=[O:54])[C:7](=[O:52])[N:8]2[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[C:28]2[N:29]=[N:30][N:31](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[N:32]=2)=[CH:18][CH:17]=1)[CH3:2].CO.[ClH:60]>ClCCl>[ClH:60].[CH2:1]([C:3]1[N:12]=[C:11]([CH2:13][CH3:14])[CH:10]=[C:9]2[C:4]=1[CH:5]=[C:6]([C:53]([O:55][CH2:56][CH3:57])=[O:54])[C:7](=[O:52])[N:8]2[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[C:28]2[NH:32][N:31]=[N:30][N:29]=2)=[CH:18][CH:17]=1)[CH3:2]
Reactant: CCOC(=O)c1cc2c(CC)nc(CC)cc2n(Cc2ccc(-c3ccccc3-c3nnn(C(c4ccccc4)(c4ccccc4)c4ccccc4)n3)cc2)c1=O
Agent: Cl
Solvent: ClCCl
Solvent: CO
Product: CCOC(=O)c1cc2c(CC)nc(CC)cc2n(Cc2ccc(-c3ccccc3-c3nnn[nH]3)cc2)c1=O
Reaction time: 0.33 h

Procedure:
Ethyl 5,7-diethyl-2-oxo-1-[(2'-(2-triphenylmethyl-2H-tetrazol-5-yl)biphenyl-4-yl)methyl]-1,2-dihydro-1,6-naphthyridin-3-carboxylate (A) (0.42 g) was added to a mixture of methanol (5 ml), dichloromethane (1 ml) and concentrated hydrochloric acid (0.15 ml) and the mixture was stirred for 20 minutes. Volatile material was removed by evaporation and the residue was triturated with ether to give a white solid. The solid was purified by dissolution in hot ethanol and precipitation by adding ether to give ethyl 5,7-diethyl-2-oxo-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-1,2-dihydro-1,6-naphthyridine-3-carboxylate hydrochloride (0.186 g); NMR (d6 -DMSO): 1.25(t, 3H), 1.32(t, 3H), 1.34(t, 3H), 2.95(q, 2H), 3.35(q, 2H), 4.34(q, 2H), 5.55(s, 2H), 7.07(d, 2H), 7.21(d, 2H), 7.4-7.8(complex m, 6H), 8.7(s, 1H); mass spectrum (+ve FAB, DMSO/NBA): 509 (M+H)+ ; microanalysis, found: C, 62.5; H, 5.6; N, 14.8%; C29H28N6O3.HCl.0.14 (CH3CO2C2H5).0.5 H2O requires: C, 62.6; H, 5.5; N, 14.8%.
Reaction SMILES: F[C:2]1[CH:23]=[CH:22][C:5]([C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]#[C:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1.[C:24]1([OH:30])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+]>>[O:30]([C:2]1[CH:23]=[CH:22][C:5]([C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]#[C:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:10][CH:9]=2)=[O:7])=[CH:4][CH:3]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: Oc1ccccc1
Reactant: O=C(c1ccc(F)cc1)c1ccc(C#Cc2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: O=C(c1ccc(C#Cc2ccccc2)cc1)c1ccc(Oc2ccccc2)cc1
Yield: 60 %

Procedure:
The phenylethynyl group has several unexpected advantages over the ethynyl based analog. See the Hergenrother and Delfort references supra. When 4-fluoro-4'-phenylethynylbenzophenone was treated with phenol in the presence of an alkali metal base such as potassium carbonate in a polar aprotic solvent at 160° C., the expected 4-phenoxy-4'-phenylethynylbenzophenone was afforded in nearly quantitativeyield. However, when 4-ethynyl-4'-fluorobenzophenone was used in the same procedure, the result was a mixture of products with a total yield of 60%.Several variations in the procedure were tried, but the resulting product was not exclusively tile expected ethynyl arylene-ether. This indicates that when the phenylethynyl endcapping compound is used to terminate nucleophilic reagents, the reaction proceeds qualitatively to afford the phenylethynyl terminated reactive oligomers exclusively. If the ethynyl adduct is used, a variety of products results.
Reaction SMILES: [F:1][C:2]1[CH:28]=[CH:27][C:26]([C:29]([NH:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[CH:33]=2)=[O:30])=[CH:25][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([C:11]2[NH:15][CH:14]=[C:13]([C:16]([NH:18][CH2:19][CH2:20][C:21]([O:23]C)=[O:22])=[O:17])[CH:12]=2)[CH:6]=1.[OH-].[Na+].O.Cl>C1COCC1.CO>[F:1][C:2]1[CH:28]=[CH:27][C:26]([C:29]([NH:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[CH:33]=2)=[O:30])=[CH:25][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([C:11]2[NH:15][CH:14]=[C:13]([C:16]([NH:18][CH2:19][CH2:20][C:21]([OH:23])=[O:22])=[O:17])[CH:12]=2)[CH:6]=1
Reactant: COC(=O)CCNC(=O)c1c[nH]c(-c2cc(Oc3cc(C(=O)Nc4cccc(C)c4)ccc3F)ccn2)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: Cc1cccc(NC(=O)c2ccc(F)c(Oc3ccnc(-c4cc(C(=O)NCCC(=O)O)c[nH]4)c3)c2)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a stirred solution of methyl 3-[({5-[4-(2-fluoro-5-{[(3-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]propanoate (80 mg, 0.16 mmol) in a mixture of THF/MeOH (5 ml/5 ml) was added 1M NaOH solution (1 ml, 1 mmol). The mixture was stirred at room temperature for 3 hours and poured into 50 ml of water. 1M HCl was added dropwise until pH=4. The precipitates were filtered, washed with water and dried in vacuo to give 3-[({5-[4-(2-fluoro-5-{[(3-methylphenyl)amino]carbonyl}phenoxy)pyridin-2-yl]-1H-pyrrol-3-yl}carbonyl)amino]propanoic acid as white solid. Yield: 70 mg, 90%.
Reaction SMILES: [N:1]1[C:8](Cl)=[N:7][C:5](Cl)=[N:4][C:2]=1[Cl:3].[CH2:10]([CH:12]([CH2:25][CH2:26][CH2:27][CH3:28])[CH2:13][NH:14][CH:15]1[CH2:20][C:19]([CH3:22])([CH3:21])[NH:18][C:17]([CH3:24])([CH3:23])[CH2:16]1)[CH3:11].[OH-].[Na+]>CC(C)=O.O>[Cl:3][C:2]1[N:1]=[C:8]([N:14]([CH2:13][CH:12]([CH2:10][CH3:11])[CH2:25][CH2:26][CH2:27][CH3:28])[CH:15]2[CH2:16][C:17]([CH3:24])([CH3:23])[NH:18][C:19]([CH3:21])([CH3:22])[CH2:20]2)[N:7]=[C:5]([N:14]([CH:15]2[CH2:16][C:17]([CH3:24])([CH3:23])[NH:18][C:19]([CH3:21])([CH3:22])[CH2:20]2)[CH2:13][CH:12]([CH2:10][CH3:11])[CH2:25][CH2:26][CH2:27][CH3:28])[N:4]=1
Reactant: CCCCC(CC)CNC1CC(C)(C)NC(C)(C)C1
Reactant: Clc1nc(Cl)nc(Cl)n1
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)=O
Solvent: O
Product: CCCCC(CC)CN(c1nc(Cl)nc(N(CC(CC)CCCC)C2CC(C)(C)NC(C)(C)C2)n1)C1CC(C)(C)NC(C)(C)C1
Reaction time: 4 h

Procedure:
A suspension of 9.2 g of cyanuric chloride in 60 ml of acetone and 20 ml of water was added dropwise, with stirring, at 20°-25° C. to a solution of 29.5 g of 4-(2-ethylhexylamino)-2,2,6,6-tetramethylpiperidine in 50 ml of acetone, after which a solution of 4.2 g of sodium hydroxide in 20 ml of water was added to the mixture. The resulting reaction mixture was then stirred for 4 hours at 45°-50° C. At the end of this time, the acetone was distilled off and the oily residue was extracted with ethyl acetate. The extract was dried over anhydrous potassium carbonate, and the ethyl acetate was distilled off. The resulting oil was purified by column chromatography through silica gel, eluted with a 4:1 by volume mixture of hexane and ethyl acetate, to give the title compound as a colourless oil. The Rf value of this compound on thin layer chromatography was 0.62, using silica gel and using, as developing solvent, a 4:1:0.4 by volume mixture of ethyl acetate, methanol and triethylamine.
Reaction SMILES: [B:1]([OH:4])([OH:3])[OH:2].[OH-].[Ca+2:6].[OH-]>>[Ca:6].[B:1]([O-:4])([O-:3])[O-:2].[B:1]([O-:4])([O-:3])[O-:2].[B:1]([O-:4])([O-:3])[O-:2].[B:1]([O-:4])([O-:3])[O-:2].[Ca+2:6].[Ca+2:6].[Ca+2:6].[Ca+2:6].[Ca+2:6].[Ca+2:6]
Reactant: OB(O)O
Agent: [Ca+2]
Agent: [OH-]
Product: [Ca]
Product: [O-]B([O-])[O-]

Procedure:
Referring now to the drawing, which despicts the preferred process of this invention, the boric acid liquid wastes, commonly referred to as "evaporator bottoms", generated by a typical pressure water reactor (PWR) are evaporated and concentrated to about a 10 weight percent boric acid solution. The steam resulting from this evaporation process is directed to a vapor clean-up system for ultimate discharge or recycling. The boric acid solution is neutralized with a stoichiometric amount of calcium hydroxide or a similar calcium compound to yield a precipitate of insoluble calcium tetraborate according to the following equation:
Reaction SMILES: [CH2:1]([C:3]1[N:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[N:9]=[C:8]2[C:4]=1[N:5]=[CH:6][N:7]2[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([OH:24])=O)[CH:17]=1)[CH3:2].[CH3:25][S:26]([NH2:29])(=[O:28])=[O:27]>CN(C)C1C=CN=CC=1.CN(C)C=O>[CH2:1]([C:3]1[N:11]=[C:10]([C:12]([F:14])([F:15])[F:13])[N:9]=[C:8]2[C:4]=1[N:5]=[CH:6][N:7]2[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([NH:29][S:26]([CH3:25])(=[O:28])=[O:27])=[O:24])[CH:17]=1)[CH3:2]
Reactant: CCc1nc(C(F)(F)F)nc2c1ncn2-c1cccc(C(=O)O)c1
Reactant: CS(N)(=O)=O
Agent: CN(C)c1ccncc1
Solvent: CN(C)C=O
Product: CCc1nc(C(F)(F)F)nc2c1ncn2-c1cccc(C(=O)NS(C)(=O)=O)c1
Temperature: 55 °C
Reaction time: 12 h
Yield: 59.5 %

Procedure:
A mixture of 6-ethyl-9-(3-carboxyphenyl)-2-trifluoromethylpurine (450 mg, 1.24 mmol), methylsulfonamide (238 mg, 2.48 mmol), N-ethyl-N′-3-dimethylaminopropylcarbodimide (238 mg, 1.24 mmol), 4-dimethylaminopyridine (151 mg, 1.24 mmol) and N,N -dimethylformamide (3 ml) were stirred at 50-60° C. for 12 hours. The solvent was concentrated under vacuum, and the residue was dissolved in 30 ml of ethyl acetate, washed with sodium bicarbonate (1×30 mL), brine (1×30 mL), dried (MgSO4), and concentrated. The residue was purified by chromatography over silica gel using a gradient elution from 10% to 20% MeOH/DCM to give 305 mg (56% yield) of 6-ethyl-9-(3-methylsulfonylaminocarbonylphenyl)-2-trifluromethylpurine. 1H NMR (300 MHz, CDCl3) δ 9.43 (b, 1H), 8.59 (s, 1H), 8.30 (s, 1H), 8.18 (d, J=7.5 Hz, 1H), 7.98 (d, J=7.5 Hz, 1H), 7.78 (t, J=7.5 Hz, 1H), 3.48 (s, 3H), 3.35 (q, J=7.2 Hz, 2H), 1.52 (t, J=7.5 Hz, 3H). [ESMS m/z (414.1 (M+H)+)]
Reaction SMILES: C([O-])(=O)C([O-])=O.[Ag+2:7].[C:8]([OH:27])(=[O:26])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]/[CH:16]=[CH:17]\[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]>>[C:8]([O-:27])(=[O:26])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]/[CH:16]=[CH:17]\[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25].[Ag:7]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Reactant: [Ag+2]
Agent: O=C([O-])C(=O)[O-]
Product: CCCCCCCC/C=C\CCCCCCCC(=O)[O-]
Product: [Ag]
Temperature: 25 °C

Procedure:
An oleate coated silver powder was synthesized as follows: Silver oxalate (doped with 1% copper for heat stabilization) (20 g) is slurried into oleic acid (250 mL) by stirring with a magnetic stir bar. The solution is then heated on a hot plate with stirring to 185° C. for 90 minutes. The solution is then allowed to cool to room temperature and the dark gray precipitate settles to the bottom. The solvent is then carefully removed by pipette from the top of the precipitate. Then to remove the remaining solvent the precipitate is washed with 3×50 mL tetrahydrofuran (THF) by stirring the precipitate with the THF then allowing it to settle and then removing the THF by pipette from the top of the precipitate. The precipitate is then washed 3×50 ml with Isopar H in the same manner. Finally, the wet precipitate is dispersed in Isopar H (80 g) and treated ultrasonically for 30 minutes. This method gives a dispersion of silver particles with approximately 10% Ag (wt/wt).
Reaction SMILES: [CH3:1][N:2]1[C:7]([CH3:9])([CH3:8])[CH2:6][CH:5]([OH:10])[CH2:4][C:3]1([CH3:12])[CH3:11].[Cl:13][C:14]1[CH:19]=[C:18](F)[CH:17]=[CH:16][C:15]=1[F:21]>>[ClH:13].[Cl:13][C:14]1[CH:19]=[C:18]([CH:17]=[CH:16][C:15]=1[F:21])[O:10][CH:5]1[CH2:6][C:7]([CH3:8])([CH3:9])[N:2]([CH3:1])[C:3]([CH3:12])([CH3:11])[CH2:4]1
Reactant: CN1C(C)(C)CC(O)CC1(C)C
Reactant: Fc1ccc(F)c(Cl)c1
Product: CN1C(C)(C)CC(Oc2ccc(F)c(Cl)c2)CC1(C)C
Product: Cl

Procedure:
Was prepared according to method B from 1,2,2,6,6-pentamethyl-piperidin-4-ol and 1-chloro-2,5-difluorobenzene. Mp 198.0-200.9° C.
Reaction SMILES: [C:1]12([CH2:11][CH2:12][C:13]3[NH:17][C:16]([C:18]4[CH:27]=[CH:26][C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[CH:19]=4)=[N:15][C:14]=3[C:28](O)=[O:29])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.C([O:38][C:39](=[O:47])[C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([NH2:46])[CH:41]=1)C1C=CC=CC=1>>[C:1]12([CH2:11][CH2:12][C:13]3[NH:17][C:16]([C:18]4[CH:27]=[CH:26][C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[CH:19]=4)=[N:15][C:14]=3[C:28]([NH:46][C:42]3[CH:41]=[C:40]([CH:45]=[CH:44][CH:43]=3)[C:39]([OH:47])=[O:38])=[O:29])[CH2:8][CH:7]3[CH2:6][CH:5]([CH2:4][CH:3]([CH2:9]3)[CH2:2]1)[CH2:10]2
Reactant: Nc1cccc(C(=O)OCc2ccccc2)c1
Reactant: O=C(O)c1nc(-c2ccc3ccccc3c2)[nH]c1CCC12CC3CC(CC(C3)C1)C2
Product: O=C(O)c1cccc(NC(=O)c2nc(-c3ccc4ccccc4c3)[nH]c2CCC23CC4CC(CC(C4)C2)C3)c1

Procedure:
5-(2-Adamantan-1-yl-ethyl)-2-naphthalen-2-yl-1H-imidazole-4-carboxylic acid (Example 44) was reacted with 3-amino-benzoic acid benzyl ester according to the procedure of Example 20, step d. The benzyl ester was deprotected according to the procedure of Example 20, step e to afford the title compound. 1H NMR (300 MHz, d6-DMSO) 12.91 (1H, br s), 9.90 (1H, br s), 8.54 (2H, d), 8.27 (1H, dd), 8.04-7.94 (4H, m), 7.65-7.44 (4H, m), 3.04 (2H, m), 1.98 (3H, br s), 1.66 (6H, m), 1.58 (6H, s), 1.45 (2H, m). The acid was converted to the N-methyl-D-glucamine salt and lyophilised from water/dioxan. Found: C, 63.85; H, 7.57; N, 7.80%; C40H50N4O8.1.9 H2O requires: C, 64.12; H, 7.24; N, 7.48%.
Reaction SMILES: Cl.[CH3:2][O:3][C:4](=[O:7])[CH2:5][NH2:6].C(N(CC)CC)C.[N+:15]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[S:24](Cl)(=[O:26])=[O:25])([O-:17])=[O:16]>ClCCl>[CH3:2][O:3][C:4](=[O:7])[CH2:5][NH:6][S:24]([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[N+:15]([O-:17])=[O:16])(=[O:25])=[O:26]
Reactant: O=[N+]([O-])c1ccccc1S(=O)(=O)Cl
Reactant: COC(=O)CN
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)CNS(=O)(=O)c1ccccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Glycine methyl ester hydrochloride (15.0 g) was dissolved in dichloromethane, and to the solution triethylamine (26.48 g) was added at 0° C. A solution of 2-nitrobenzenesulfonyl chloride (23.57 g) in dichloromethane (50 mL) was then gradually added dropwise. After the mixture was stirred at room temperature for 2 hours, the reaction mixture was concentrated under reduced pressure, and ethyl acetate was added to the residue. The resultant mixture was washed with 2 M hydrochloric acid, water and saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resultant crystals were recrystallized from ethyl acetate-hexane to obtain the title compound.
Reaction SMILES: [OH:1][N:2]=[C:3]([C:14]#[N:15])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[C:6]([O:12][CH3:13])[CH:5]=1.[CH3:16][CH:17]([S:19](Cl)(=[O:21])=[O:20])[CH3:18]>C(N(CC)CC)C>[CH3:16][CH:17]([S:19]([O:1][N:2]=[C:3]([C:14]#[N:15])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[C:6]([O:12][CH3:13])[CH:5]=1)(=[O:21])=[O:20])[CH3:18]
Reactant: COc1ccc(C(C#N)=NO)cc1OC
Reactant: CC(C)S(=O)(=O)Cl
Solvent: CCN(CC)CC
Product: COc1ccc(C(C#N)=NOS(=O)(=O)C(C)C)cc1OC
Yield: 87.6 %

Procedure:
As described under 1.2, 16.5 g (0.08 mol) of α-hydroxyimino-3,4-dimethoxybenzyl cyanide are reacted with 12.6 g (0.088 mol) of 2-propanesulfonyl chloride in the presence of triethylamine. Recrystallisation of the crude product from ethyl acetate/hexane yields 21.9 g (88%) of α-(2-propylsulfonyloxyimino)-3,4-dimethoxybenzyl cyanide in the form of beige crystals having a melting point of 90.5-93.5° C. The 1H-NMR spectrum of the compound shows that it is a pure stereoisomer. The UV spectrum (acetonitrile) of the substance shows a broad absorption band with a maximum at 346 nm (ε=1165034) that extends to 434 nm. Elemental analysis: C13H16N2O5S (312.34)
Reaction SMILES: CC1(C)[O:7][CH2:6][C:5]([NH:11]C(=O)OC(C)(C)C)([CH2:8][S:9][CH3:10])[CH2:4][O:3]1.[ClH:20]>CO>[ClH:20].[NH2:11][C:5]([CH2:8][S:9][CH3:10])([CH2:6][OH:7])[CH2:4][OH:3]
Reactant: CSCC1(NC(=O)OC(C)(C)C)COC(C)(C)OC1
Agent: Cl
Solvent: CO
Product: CSCC(N)(CO)CO
Yield: 100 %

Procedure:
A solution of tert-butyl 2,2-dimethyl-5-(methylthiomethyl)-1,3-dioxan-5-ylcarbamate (2.64 g, 9.06 mmol) in methanol (10 mL) was added to a solution of concentrated hydrochloric acid (8 mL) in methanol (100 mL) and concentrated under reduced pressure to give a yellow oil, which was purified by flash column chromatography (CH2Cl2:methanol:7 M methanolic ammonia, 5:2:1). The residue was reconverted to the hydrochloride salt by treatment with a solution of concentrated hydrochloric acid (1 mL) and methanol (5 mL) and concentration under reduced pressure to give the 2-amino-2-(methylthiomethyl)propane-1,3-diol, hydrochloride salt (1.37 g, 9.06 mmol, 100%). 1H NMR (D2O): δ 3.74 (s, 4H), 2.88 (s, 2H), 2.19 (s, 3H). 13C NMR (DMSO), δ ppm, 64.4 (2×CH2), 57.9, 48.9, 17.5. +ESMS Found 152.0744 (M—Cl−) C5H14NO2S requires 152.0745.
Reaction SMILES: [CH3:1][C:2]1[C:11]2([CH2:13][CH2:12]2)[C@:10]([OH:15])([CH3:14])[C:8](=[O:9])[C:7]2[C:3]=1[C@@H:4]([OH:18])[C:5]([CH3:17])([CH3:16])[CH:6]=2.[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>ClCCl.C(OCC)C>[CH3:1][C:2]1[C:11]2([CH2:12][CH2:13]2)[C@:10]([OH:15])([CH3:14])[C:8](=[O:9])[C:7]2=[CH:6][C:5]([CH3:16])([CH3:17])[C:4](=[O:18])[C:3]=12
Reactant: CC1=C2C(=CC(C)(C)[C@@H]2O)C(=O)[C@](C)(O)C12CC2
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Solvent: CCOCC
Product: CC1=C2C(=O)C(C)(C)C=C2C(=O)[C@](C)(O)C12CC2
Temperature: 25 °C
Reaction time: 20 h

Procedure:
A mixture of illudin M (200 mg) and pyridinium dichromate (1 g) in dry dichloromethane (60 ml) was stirred at room temperature in a flask equipped with a rubber septum so that an atmosphere of argon could be maintained. After 20 hours, the reaction mixture was diluted with diethyl ether (20 ml) and filtered through a short column of silica gel. The column was further eluted with more diethyl ether and the combined filtrate was concentrated, giving a residue which was chromatographed on silica gel with hexane-ethyl acetate (10:1) as eluent. The desired compound was obtained in early fractions from the chromatography. The yield was 140 mg of white crystals melting at 64°-65° C. NMR spectral data were recorded for this compound.
Reaction SMILES: [Br:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]=[O:9])=[CH:4][CH:3]=1.[CH2:10]([Mg]Cl)[CH3:11]>C1COCC1.[Cl-].[NH4+]>[Br:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]([OH:9])[CH2:10][CH3:11])=[CH:4][CH:3]=1
Reactant: CC[Mg]Cl
Reactant: O=Cc1ccc(Br)nc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CCC(O)c1ccc(Br)nc1
Reaction time: 4 h

Procedure:
To a chilled (0° C.) solution of 6-bromo-pyridine-3-carboxaldehyde (15.0 g, 80.6 mmol) in a 1:1 mixture of ether-toluene (400 mL) was added a 2 M solution of ethyl magnesium chloride (40.0 mL, 80.0 mmol) in THF over a 15 minute period. The solution was stirred for 4 hours, and a more polar product was observed by TLC (ethyl acetate-hexanes 3:7). The mixture was diluted with saturated aqueous ammonium chloride (300 mL) and the organic phase separated. The aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with brine (2×50 mL), dried over magnesium sulfate, filtered and concentrated. The crude material was passed through a pad of silica gel eluting 0-100% dichloromethane in hexanes. The material from the pad was purified by silica gel chromatography eluting with a gradient of 2-15% ethyl acetate in hexanes to afford 1-(6-bromo-pyridin-3-yl)-propan-1-ol.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH2:12][CH:13]([CH3:15])[CH3:14])[CH2:10][CH2:9][C:8]([C:16]([O:18][CH3:19])=[O:17])=[CH:7][C:6]=2[CH:20]=1.B([O-])([O-])O[C:23]1[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][O:32][CH2:33][CH2:34][CH2:35][CH3:36])=[CH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+].O>C1(C)C=CC=CC=1.C(O)C.O.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>[CH2:33]([O:32][CH2:31][CH2:30][O:29][C:26]1[CH:25]=[CH:24][C:23]([C:2]2[CH:3]=[CH:4][C:5]3[N:11]([CH2:12][CH:13]([CH3:15])[CH3:14])[CH2:10][CH2:9][C:8]([C:16]([O:18][CH3:19])=[O:17])=[CH:7][C:6]=3[CH:20]=2)=[CH:28][CH:27]=1)[CH2:34][CH2:35][CH3:36]
Reactant: COC(=O)C1=Cc2cc(Br)ccc2N(CC(C)C)CC1
Reactant: CCCCOCCOc1ccc(OB([O-])[O-])cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: O
Solvent: Cc1ccccc1
Product: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)OC)CCN3CC(C)C)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 62.4 %

Procedure:
Methyl 7-bromo-1-isobutyl-2,3-dihydro-1-benzazepine-4-carboxylate (0.90 g) was dissolved in toluene/ethanol/water (=10/1/1, 41 ml). To the solution were added 4-(2-butoxyethoxy)phenyl borate (0.76 g) and potassium carbonate (0.18 g), and the mixture was stirred under argon atmosphere for 30 minutes. To the mixture was added tetrakistriphenylphosphinepalladium (123 mg), and the mixture was heated to reflux for 14 hours. After cooled to room temperature, the reaction solution was added to water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried with magnesium sulfate. The solvent was removed under reduced pressure, and the resulting residue was purified with silica gel column chromatography (hexane/ethyl acetate=8/1) to give methyl 7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-2,3-dihydro-1-benzazepine-4-carboxylate (0.75 g).
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][C:8]([O:12][C:13]1[C:14]([C:19]([CH3:23])([CH3:22])[CH:20]=[O:21])=[N:15][CH:16]=[CH:17][CH:18]=1)=[CH:7]2.[CH3:24][Mg]Cl.O>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][C:8]([O:12][C:13]1[C:14]([C:19]([CH3:23])([CH3:22])[CH:20]([OH:21])[CH3:24])=[N:15][CH:16]=[CH:17][CH:18]=1)=[CH:7]2
Reactant: C[Mg]Cl
Reactant: CC(C)(C=O)c1ncccc1Oc1cnc2c(F)cccc2c1
Solvent: C1CCOC1
Solvent: O
Product: CC(O)C(C)(C)c1ncccc1Oc1cnc2c(F)cccc2c1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
0.10 g of 2-[3-(8-fluoro-quinolin-3-yloxy)-pyridin-2-yl]-2-methyl-propioaldehyde were dissolved in 3 ml of tetrahydrofuran. 0.2 ml of a 3.0 M tetrahydrofuran solution of methylmagnesium chloride were added thereto followed by stirring for 30 minutes at 0° C. Subsequently, water was added thereto to stop the reaction. The resultant was then extracted with ethyl acetate followed by distilling off the solvent of the organic layer and purifying by silica gel column chromatography to obtain 0.07 g of 3-[3-(8-fluoro-quinolin-3-yloxy)-pyridin-2-yl]-3-methyl-butan-2-ol.