Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[N+:4]([O-:11])[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].CNC.O.[CH3:16][N:17]([CH3:20])[CH:18]=O>>[CH3:16][N:17]([CH3:20])/[CH:18]=[CH:1]/[C:2]1[CH:3]=[N+:4]([O-:11])[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9]
Reactant: Cc1c[n+]([O-])ccc1[N+](=O)[O-]
Reactant: CN(C)C=O
Agent: CNC
Solvent: O
Product: CN(C)/C=C/c1c[n+]([O-])ccc1[N+](=O)[O-]
Temperature: 90 °C
Reaction time: 15 h
Yield: 50 %

Procedure:
To the stirred solution of 3-methyl-4-nitropyridine 1-oxide (600 mg, 3.8 mmol, Step b) in dimethylformamide was added dimethylformamide and dimethylamine (1.14 mL, 8.5 mmol) drop wise at room temperature. After complete addition, the reaction mixture was stirred at 90° C. for 15 hours. The reaction mixture was poured on cold water and the precipitated solid was filtered, washed with water and dried to get (E)-N,N-dimethyl-2-(4-nitro-1-oxidopyridin-3-yl)ethenamine (470 mg, 50%).
Reaction SMILES: C([Li])CCC.[CH2:6]([O:8][CH:9]1[NH:13][C:12](=[O:14])[CH:11]=[CH:10]1)[CH3:7].[C:15]1([S:21](Cl)(=[O:23])=[O:22])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CCCCCC.O1CCCC1>[C:15]1([S:21]([N:13]2[CH:9]([O:8][CH2:6][CH3:7])[CH:10]=[CH:11][C:12]2=[O:14])(=[O:23])=[O:22])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: CCOC1C=CC(=O)N1
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCOC1C=CC(=O)N1S(=O)(=O)c1ccccc1
Temperature: -35 °C
Reaction time: 0.33 h
Yield: 36.5 %

Procedure:
7.37 cm3 of a 1.6M solution of n-butyllithium in n-hexane is added to a solution of 1.5 g of 1,5-dihydro-5-ethoxy-2H-pyrrol-2-one in 40 cm3 of tetrahydrofuran cooled to -35° C., operating at -35°/-30° C. The mixture is agitated for 20 minutes, then cooled to -40° C., and while maintaining the temperature between -38° C. and -40° C., a solution is added of 2.08 g of benzene sulphonyl chloride in 10 cm3 of tetrahydrofuran. The temperature is allowed to return to the ambient, the solvent is evaporated under reduced pressure, and the residue is chromatographed on silica (eluent: ethyl acetate-n-hexane, 1--1). 1.15 g of the expected product is obtained. m.p. 117°-119° C., crystallized from ethyl ether.
Reaction SMILES: [O:1]=[C:2]1[C:7]2([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][NH:3]1.Br[C:21]1[CH2:25][O:24][C:23](=[O:26])[CH:22]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:1]=[C:2]1[C:7]2([CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:11][CH2:12]2)[CH2:6][CH2:5][CH2:4][N:3]1[C:21]1[CH2:25][O:24][C:23](=[O:26])[CH:22]=1
Reactant: O=C1C=C(Br)CO1
Reactant: CC(C)(C)OC(=O)N1CCC2(CCCNC2=O)CC1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Product: CC(C)(C)OC(=O)N1CCC2(CCCN(C3=CC(=O)OC3)C2=O)CC1
Temperature: 90 °C

Procedure:
A microwave vial was charged with commercially available tert-butyl 1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylate (Shanghai AQ BioPharma Co., Ltd, catalog #ABP3640, 100 mg, 0.373 mmol), 4-bromofuran-2(5H)-one (72.9 mg, 0.447 mmol), Pd2(dba)3 (17.06 mg, 0.019 mmol), Xantphos (32.3 mg, 0.056 mmol), and cesium carbonate (182 mg, 0.559 mmol). The vial was sealed, degassed, and filled with toluene (1.5 mL). The reaction mixture was heated at 90° C. overnight, and was filtered through CELITE®. The filtrate was evaporated to give the crude product, which was purified by column chromatograph (0-10% MeOH/DCM) to afford the title compound. LC/MS: [(M+1−56)]+=295
Reaction SMILES: [CH2:1]([C:4]1[CH:13]=[CH:12][C:7]2[C:8](=[O:11])[O:9][CH2:10][C:6]=2[CH:5]=1)[CH:2]=C.[O:14]=[O+][O-].[BH4-].[Na+]>C(Cl)Cl.CO>[OH:14][CH2:2][CH2:1][C:4]1[CH:13]=[CH:12][C:7]2[C:8](=[O:11])[O:9][CH2:10][C:6]=2[CH:5]=1
Reactant: C=CCc1ccc2c(c1)COC2=O
Reactant: O=[O+][O-]
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: O=C1OCc2cc(CCO)ccc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 5-prop-2-en-1-yl-2-benzofuran-1(3H)-one (13.5 g, 45.2 mmol) in 200 mL DCM/MeOH (V/V=1:1) was bubbled O3 at −78° C. for 30 min, and N2 was bubbled for another 15 min at −78° C. Then 20 mL of Me2S were added, and the mixture was stirred at RT overnight before concentrating to dryness. The residue was dissolved in MeOH (100 mL) and then cooled to 0° C. NaBH4 (5.90 g, 155 mmol) was added in portions. The resulting mixture was stirred at 0° C. for 1 h, then quenched with citric acid (aq.) and extracted three times with EtOAc. The combined organic layers were washed with NaHCO3 (aq.) and brine, dried over anhydrous Na2SO4 and concentrated to dryness. The residue was purified via column chromatography (EtOAc/Pet Ether=1:5) to give 5-(2-hydroxyethyl)-2-benzofuran-1(3H)-one.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][CH:3]=[N:2]1.C(=O)([O-])[O-].[K+].[K+].[CH2:12]([O:14][CH2:15]Cl)[CH3:13]>CC(C)=O>[CH2:12]([O:14][CH2:15][N:1]1[CH:5]=[CH:4][CH:3]=[N:2]1)[CH3:13]
Reactant: CCOCCl
Reactant: c1cn[nH]c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOCn1cccn1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 50 %

Procedure:
To a mixture of pyrazole (10 g, 0.150 mol) and potassium carbonate (22.3 g, 0.162 mol) in acetone (200.0 mL), cooled to 0° C. under nitrogen, was added chloromethyl ethyl ether (15.0 mL, 0.162 mol) via syringe over a period of 20 minutes. The reaction was stirred for 30 minutes at 0° C. and then for 2 hours at room temperature. The mixture was filtered, washing the solid with acetone (200.0 mL). The filtrate was carefully concentrated in vacuo (at 400 mbar). The crude material was purified by flash column chromatography eluting with pentane:diethylether (1:1, by volume) to afford the title compound as a colourless oil, 9.3 g, 50% yield.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=[CH:15][N:16]([CH3:18])[CH3:17])[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:5][CH:4]=1.O>C(O)C.[Pt]>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]([CH2:15][N:16]([CH3:18])[CH3:17])[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:7][CH:8]=1
Reactant: CCOC(=O)C(=CN(C)C)c1ccc(OC)cc1
Agent: [Pt]
Solvent: CCO
Solvent: O
Product: CCOC(=O)C(CN(C)C)c1ccc(OC)cc1
Reaction time: 23 h
Yield: 74 %

Procedure:
19.8 g (0.0795 mol) of ethyl α-(p-methoxyphenyl)-β-(dimethylamino)acrylate were dissolved in 740 ml of ethanol, in a 1 liter glass reactor, 30.6 9 of Pt/C type 18 catalyst (4.83% Pt and 59.70% water) were added, the mixture was first purged with nitrogen and then with hydrogen and finally a pressure of 600 psi H2 was applied. The mixture was left hydrogenating for 23 hours, was then filtered through Celite® 535 and was washed with 2×165 ml of ethanol. The ethanol was then removed under vacuum. The residue was dissolved in 30 ml of dichloromethane and was extracted with 50 ml and 2×15 ml of 2N hydrochloric acid. The operation continued with the acid aqueous phase that was basified with 40 ml of aqueous sodium hydroxide solution to pH 11. The product was extracted with 4×35 ml of ethyl acetate. The pooled organic phases were dried with sodium sulfate, filtered and evaporated to dryness under vacuum to give a pale yellow oil weighing 14.7 g, corresponding to ethyl α-(p-methoxyphenyl)-β-(dimethylamino)propionate (Yield: 74%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([OH:12])=[O:11])[CH:5]=[C:6]([OH:8])[CH:7]=1.[Cl:13][C:14]1[CH:31]=[CH:30][C:17]([CH2:18][S:19]([C:22]2[CH:27]=[CH:26][C:25](F)=[C:24]([F:29])[CH:23]=2)(=[O:21])=[O:20])=[CH:16][CH:15]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([OH:12])=[O:11])[CH:5]=[C:6]([O:8][C:25]2[CH:26]=[CH:27][C:22]([S:19]([CH2:18][C:17]3[CH:30]=[CH:31][C:14]([Cl:13])=[CH:15][CH:16]=3)(=[O:20])=[O:21])=[CH:23][C:24]=2[F:29])[CH:7]=1
Reactant: O=C(O)Cc1cc(O)cc(Cl)c1
Reactant: O=S(=O)(Cc1ccc(Cl)cc1)c1ccc(F)c(F)c1
Product: O=C(O)Cc1cc(Cl)cc(Oc2ccc(S(=O)(=O)Cc3ccc(Cl)cc3)cc2F)c1

Procedure:
The title compound was prepared as described in example 2 step (iii) but instead using the product from example 18 step (iv) and the product from step (i).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:50]=[CH:51][CH:52]=1)[CH2:5][N:6]1[C:10]([CH3:11])=[C:9]([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[C:18]([C:21]4[CH:26]=[CH:25][C:24]([N:27]5[CH2:32][CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29][CH2:28]5)=[CH:23][CH:22]=4)[CH:19]=3)[N:14]([S:40]([C:43]3[CH:49]=[CH:48][C:46]([CH3:47])=[CH:45][CH:44]=3)(=[O:42])=[O:41])[CH:13]=2)[CH:8]=[N:7]1.[ClH:53]>CCOCC>[ClH:53].[F:1][C:2]1[CH:3]=[C:4]([CH:50]=[CH:51][CH:52]=1)[CH2:5][N:6]1[C:10]([CH3:11])=[C:9]([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[C:18]([C:21]4[CH:26]=[CH:25][C:24]([N:27]5[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]5)=[CH:23][CH:22]=4)[CH:19]=3)[N:14]([S:40]([C:43]3[CH:49]=[CH:48][C:46]([CH3:47])=[CH:45][CH:44]=3)(=[O:41])=[O:42])[CH:13]=2)[CH:8]=[N:7]1
Reactant: Cc1ccc(S(=O)(=O)n2cc(-c3cnn(Cc4cccc(F)c4)c3C)c3cc(-c4ccc(N5CCN(C(=O)OC(C)(C)C)CC5)cc4)cnc32)cc1
Agent: Cl
Solvent: CCOCC
Product: Cc1ccc(S(=O)(=O)n2cc(-c3cnn(Cc4cccc(F)c4)c3C)c3cc(-c4ccc(N5CCNCC5)cc4)cnc32)cc1
Yield: 96.1 %

Procedure:
Using similar reaction conditions as described in step-ii of example-7, tert-butyl 4-(4-(3-(1-(3-fluorobenzyl)-5-methyl-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)piperazine-1-carboxylate (example 44, step 1) (290 mg, 0.40 mmol) was deprotected with HCl in ether (5 ml). This afforded 240 mg (96.1% yield) of the titled compound. MS: m/z=621.2 (M+1).
Reaction SMILES: [C:1]1(=[O:12])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C:2]1=[N:10]O.O1CCOCC1>CCO>[NH2:10][C@@H:2]1[CH2:3][C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[C@H:1]1[OH:12]
Reactant: O=C1C(=NO)Cc2ccccc21
Solvent: C1COCCO1
Solvent: CCO
Product: N[C@@H]1Cc2ccccc2[C@H]1O
Yield: 171.9 %

Procedure:
A solution of indan-1,2-dione-2-oxime (6.2g, 39mmol) in EtOH (470 ml) and 4MHCl/Dioxane (36 ml) was hydrogenated at room temperature and 40 psi. The reaction mixture was filtered through celite, washed with EtOH (30 ml) and concentrated under reduced pressure to give 10 g of an off-white solid which was recrystallised from EtOH to give the title compound (5 g, 86%) as a white solid.
Reaction SMILES: [CH:1]1([CH2:6][C@H:7]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([Cl:26])[CH:20]=2)[C:8](N2[C@@H](C(C)C)COC2=O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH:27]O.[OH-].[Li+]>O1CCCC1.O>[CH:1]1([CH2:6][C@H:7]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[C:21]([Cl:26])[CH:20]=2)[C:8]([OH:9])=[O:27])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: OO
Reactant: CC(C)[C@H]1COC(=O)N1C(=O)[C@H](CC1CCCC1)c1ccc(Cl)c(Cl)c1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)[C@H](CC1CCCC1)c1ccc(Cl)c(Cl)c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 70 %

Procedure:
A solution of 3-[3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-propionyl]-4(S)-isopropyl-oxazolidin-2-one (1.88 g, 4.72 mmol) in tetrahydrofuran (73 mL) and water (22 mL) cooled to 0° C. was treated with a 30% aqueous hydrogen peroxide solution (2.1 mL) and lithium hydroxide (394 mg, 9.4 mmol). The reaction was stirred at 0° C. for 1 h. At this time, the reaction was quenched with a saturated aqueous sodium sulfite solution (16 mL) followed by the addition of a 0.5N aqueous sodium bicarbonate solution (50 mL). The tetrahydrofuran was then removed in vacuo. The residue was diluted with water (40 mL) and extracted with methylene chloride (3×20 mL). The aqueous layer was then acidified to pH=2 with 5N aqueous hydrochloric acid solution and extracted with ethyl acetate (4×25 mL). The combined organic layers were then dried over sodium sulfate, filtered, and concentrated in vacuo to afforded of 3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-propionic acid (928 mg, 70%) as a white solid: mp 75.1-78.3° C.; [α]23589=−50.3° (c=0.100, chloroform); EI-HRMS m/e calcd for C14H16Cl2O2 (M+) 286.0527, found 286.0535.
Reaction SMILES: [OH:1][CH2:2][P:3](=[O:12])([O:8][CH:9]([CH3:11])[CH3:10])[O:4][CH:5]([CH3:7])[CH3:6].C(N(CC)CC)C.[Cl:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:22]=1[S:28](Cl)(=[O:30])=[O:29]>CCOCC.C(OCC)(=O)C.C(Cl)Cl>[Cl:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:22]=1[S:28]([O:1][CH2:2][P:3](=[O:12])([O:4][CH:5]([CH3:7])[CH3:6])[O:8][CH:9]([CH3:11])[CH3:10])(=[O:30])=[O:29]
Reactant: O=S(=O)(Cl)c1c(Cl)cccc1Cl
Reactant: CC(C)OP(=O)(CO)OC(C)C
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CC(C)OP(=O)(COS(=O)(=O)c1c(Cl)cccc1Cl)OC(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 51.8 %

Procedure:
A solution of 20.6 g of diisopropyl P-(hydroxymethyl)-phosphonate, prepared in Example 17, and 14.7 ml of triethylamine diluted in 35 ml of ether was added dropwise over 60 minutes to a mixture of 23.97 g of 2,6-dichlorobenzenesulfonyl chloride and 140 ml of ether. The addition was mildly exothermic. The reaction was allowed to stir at room temperature overnight and then was diluted with 220 ml of ethyl acetate, the ethyl acetate solution washed with two 80 ml portions of water, dried with magnesium sulfate, filtered, and concentrated to yield 35.1 g of the crude desired product as a yellow oil. The oil was dissolved in 25 ml of methylene chloride and flash chromatographed using ethyl acetate and hexanes. Similar fractions were combined to yield 20.5 g of the desired product as an oil.
Reaction SMILES: Cl.[CH3:2][C:3]1([CH3:25])[CH2:8][CH:7]([N:9]2[C:13](=[O:14])[C:12]3=[CH:15][C:16]([C:19](Cl)=[O:20])=[CH:17][CH:18]=[C:11]3[C:10]2=[O:22])[CH2:6][C:5]([CH3:24])([CH3:23])[NH:4]1.[CH2:26]=[CH:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[CH2:34]([OH:37])[CH:35]=[CH2:36].C(N(CC)CC)C.[OH-].[Na+].[K+].[Br-]>C(Cl)Cl.CN(C)C=O>[CH2:26]=[CH:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[CH2:13]([OH:14])[CH:12]=[CH2:11].[CH3:2][C:3]1([CH3:25])[CH2:8][CH:7]([N:9]2[C:13](=[O:14])[C:12]3=[CH:15][C:16]([C:19]([O:37][CH2:34][CH:35]=[CH2:36])=[O:20])=[CH:17][CH:18]=[C:11]3[C:10]2=[O:22])[CH2:6][C:5]([CH3:24])([CH3:23])[NH:4]1
Reactant: CC1(C)CC(N2C(=O)c3ccc(C(=O)Cl)cc3C2=O)CC(C)(C)N1
Agent: Cl
Agent: [Br-]
Agent: [K+]
Solvent: C=CCO
Solvent: CN(C)C=O
Solvent: C=Cc1ccccc1
Product: C=CCOC(=O)c1ccc2c(c1)C(=O)N(C1CC(C)(C)NC(C)(C)C1)C2=O

Procedure:
Into a 125 ml reaction flask equipped with a magnetic stirrer, thermometer, condenser and nitrogen atmosphere were placed 5.0 g (0.013 mol) of acid chloride of Example 2 and 50 ml of 2% dimethylformamide in methylene chloride. This mixture was stirred during the addition of 2.9 g (about 0.013 hydroxy equivalents) of RJ® 101 (a styrene/allyl alcohol copolymer from Monsanto having 7.7±0.3 wt % hydroxy content). 2.8 g (0.028 mol) triethylamine were added. The reaction was refluxed for 1.5 hours. The mixture was transferred to a separatory funnel with 150 ml methylene chloride and 100 ml of 5% sodium hydroxide. The phases were separated and the organic phase was further extracted with three 50 ml portions of 5% sodium hydroxide and 50 ml water. The organic solution was dried with anhydrous magnesium sulfate and the solvent stripped using aspirator and high vacuum systems. The product was 4.3 g of light yellow crystals. The solid was redissolved in a minimum amount of methylene chloride and precipitated by dropwise addition to 800 ml of hexane. The solid was isolated by filtration yielding 3.9 g. The infrared spectrum (KBr pellet) showed the carbonyl absorption at 1715 cm-1 (imide and ester). The Tg was determined to be 87.6° C. Molecular weight data obtained from gel permeation chromatography indicated an Mn of 1400 and an Mw of 2100 (based on polystyrene standard). The NMR spectrum demonstrated the presence of the HALS moiety in the high molecular weight material (two singlets at 1.2 and 1.3 ppm) and the presence of aromatic hydrogens from the pendant phenyl groups.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][N:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][CH2:12][CH2:13][C:14]#[N:15].[H][H]>[Pd].C(O)C>[N:1]1[C:10]2[NH:9][CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][C:2]=1[CH2:11][CH2:12][CH2:13][C:14]#[N:15]
Reactant: [H][H]
Reactant: N#CCCCc1ccc2cccnc2n1
Agent: [Pd]
Solvent: CCO
Product: N#CCCCc1ccc2c(n1)NCCC2

Procedure:
A mixture of 8-2 (14 g, 71 mmol), 10% Pd/C (2 g) and ethanol (200 mL) was stirred under a balloon of hydrogen gas for 1 h. Filtration and evaporation produced 8-3 as a white solid.
Reaction SMILES: [CH2:1]([NH:8][S:9]([C:12]1[C:17]([Cl:18])=[CH:16][CH:15]=[C:14]([N+:19]([O-:21])=[O:20])[C:13]=1C(=O)C)(=[O:11])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[Si](C)(C)C.C([OH:32])C>S(=O)(=O)(O)O>[CH2:1]([NH:8][S:9]([C:12]1[C:17]([Cl:18])=[CH:16][CH:15]=[C:14]([N+:19]([O-:21])=[O:20])[C:13]=1[OH:32])(=[O:11])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCO
Reactant: CC(=O)c1c([N+](=O)[O-])ccc(Cl)c1S(=O)(=O)NCc1ccccc1
Agent: C[Si](C)(C)Cl
Agent: O=S(=O)(O)O
Product: O=[N+]([O-])c1ccc(Cl)c(S(=O)(=O)NCc2ccccc2)c1O
Yield: 94 %

Procedure:
A solution of N-benzyl-2-acetyl-6-chloro-3-nitrobenzenesulfonamide (225 mg, 0.59 mmol), 0.1 mL of chlorotrimethylsilane and 2 drops of fuming sulfuric acid in ethanol was heated to reflux for 20 hours. The solvent was evaporated. The residue was diluted with ethyl acetate and washed with water. The organic layer was then dried (Na2SO4) and concentrated to give the desired product (189 mg, 94%). 1H NMR (DMSO-d6): δ 7.92 (d, 1H), 7.18 (m, 5H), 6.93 (d, 1H), 4.15 (s, 2H).
Reaction SMILES: C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:15]1([CH:21]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C@H:22]2[C@@H:27]([NH2:28])[CH:26]3[CH2:29][CH2:30][N:23]2[CH2:24][CH2:25]3)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[CH2:37]([P:39]([C:43]1[CH:44]=[CH:45][C:46]([O:51][CH3:52])=[C:47]([CH:50]=1)[CH:48]=O)([CH2:41][CH3:42])=[O:40])[CH3:38].S(=O)(=O)(O)[O-].[Na+]>C(Cl)Cl.C(Cl)CCl>[C:31]1([CH:21]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[C@H:22]2[C@@H:27]([NH:28][CH2:48][C:47]3[CH:50]=[C:43]([P:39]([CH2:41][CH3:42])([CH2:37][CH3:38])=[O:40])[CH:44]=[CH:45][C:46]=3[O:51][CH3:52])[CH:26]3[CH2:29][CH2:30][N:23]2[CH2:24][CH2:25]3)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1
Reactant: CCP(=O)(CC)c1ccc(OC)c(C=O)c1
Reactant: N[C@H]1C2CCN(CC2)[C@H]1C(c1ccccc1)c1ccccc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=S(=O)([O-])O
Agent: [Na+]
Solvent: ClCCCl
Solvent: ClCCl
Product: CCP(=O)(CC)c1ccc(OC)c(CN[C@H]2C3CCN(CC3)[C@H]2C(c2ccccc2)c2ccccc2)c1
Reaction time: 16 h

Procedure:
Sodium triacetoxyborohydride (202 mg, 0.95 mmol) was added to a solution of (2S,3S)-2-diphenylmethyl-1-azabicyclo[2.2.2]octane-3-amine (150 mg, 0.51 mmol) and 5-diethylphosphoryl-2-methoxybenzaldehyde (150 mg, 0.55 mmol) dissolved in methylene chloride (5 ml) at rt, and the resulting solution was stirred for 16 h. Ethylene chloride and 1N sodium bisulfate were added to the reaction mixture. After 5 min the organic layer was washed with aq. sodium bicarbonate solution and brine. The extracts were dried over magnesium sulfate, and concentrated by evaporation. The residual oil was purified by following process: (1) silica-gel chromatography (4-14% methanol-methylene chloride), (2) Merck Lobar Li Chroprep NH2 (25-70%), (3) crystallization from diisopropyl ether. The title compound was obtained in a pure form (11 mg). IR (CH2Cl2) 1270 cm-1 1 H NMR δ: 7.66 (ddd, J=13, 8, 2 Hz, 1H), 7.39 (dd, J=13, 2 Hz, 1H), 7.31-7.03 (m, 10H), 6.75 (dd, J=8, 3.5 Hz, 1H), 4.47 (d, 12.2 Hz, 1H), 4.10 (m, 4H), 3.69-3.57 (m, 2H), 3.54 (s, 3H), 3.25-3.10 (m, 1H), 3.19 (d, J=13 Hz, 1H), 1H), 2.87 (dd Hz, 1H), 2.75 (m, 2H), 2.60 (m, 1H), 2.05 (m, 1H), 1.88 (m, 1H), 1.70-1.20 (m, 3H), 1.35 (t, J=7 Hz, 3H), 1.34 (t, J=7 Hz, 3H).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[C:8]([CH3:10])[CH:7]=[C:6]([N+:11]([O-:13])=[O:12])[C:5]=1OC)([O-:3])=[O:2].[NH2:16][CH2:17][CH:18]([OH:21])[CH2:19][OH:20]>O>[N+:1]([C:4]1[CH:9]=[C:8]([CH3:10])[CH:7]=[C:6]([N+:11]([O-:13])=[O:12])[C:5]=1[NH:16][CH2:17][CH:18]([OH:21])[CH2:19][OH:20])([O-:3])=[O:2]
Reactant: NCC(O)CO
Reactant: COc1c([N+](=O)[O-])cc(C)cc1[N+](=O)[O-]
Solvent: O
Product: Cc1cc([N+](=O)[O-])c(NCC(O)CO)c([N+](=O)[O-])c1

Procedure:
0.05 mol (10.6 g) of 2,6-dinitro-4-methylanisole is dissolved in 50 ml of absolute alcohol. 0.1 mol (9.1 g) of 1-aminopropane-2,3-diol is added gradually to this solution, whilst stirring. The solution is heated under reflux for 3 hours 30 minutes. The alcohol is driven off in vacuo and 40 ml of iced water are added to the residual red oil. The expected product crystallises. It is filtered off and washed with water. After recrystallisation from an aqueous-alcoholic mixture and drying in vacuo, it melts at 118° C.
Reaction SMILES: [CH:1]1[CH2:6][CH2:5][CH:4]=[CH:3][CH:2]=1.[Li]C(CC)C.CN(CCN(C)C)C.[CH3:20][C:21]([Si:24](Cl)([CH3:26])[CH3:25])([CH3:23])[CH3:22]>C1COCC1>[C:21]([Si:24]([CH:2]1[CH:1]=[CH:6][CH2:5][CH:4]=[CH:3]1)([CH3:26])[CH3:25])([CH3:23])([CH3:22])[CH3:20]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: C1=CCCC=C1
Agent: CN(C)CCN(C)C
Agent: [Li]C(C)CC
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)C1C=CCC=C1
Temperature: -45 °C
Reaction time: 1 h
Yield: 77.5 %

Procedure:
1,4,-Cyclohexadiene (3.76 mL, 40 mmol, 1 eq.) was dissolved in THF (64 mL) and cooled to −78° C. s-BuLi (40 mL, 44 mmol, 1.1 eq.) was added dropwise and the resulting suspension was treated with TMEDA (6.12 mL, 40 mmol, 1 eq.). The reaction mixture was allowed to warm to −45° C. over 2 hours, TBDMSCl (6.6 g, 44 mmol, 1.1 eq.) in THF (20 mL) was added dropwise and the reaction stirred at room temperature for 1 hour. The reaction was quenched with Et2O and H2O and then extracted with Et2O (3×100 mL). The combined organic layers were washed with sat. NH4.Cl (aq.) (100 mL) and brine (100 mL), dried over MgSO4 and the solvent removed in vacuo. Distillation using Kugelrohr apparatus (125° C., 43 mbar) afforded the product as a colourless oil (5.9 g, 31 mmol, 77% yield). 1H NMR (CDCl3) δ 5.74 (2H, m, H-5), 5.55 (2H, m, H-6), 2.70 (2H, m, H-7), 2.41 (1H, m, H-4), 0.95 (9H, s, H-1), 0.01 (6H, s, H-3); C13 NMR (100 MHz, CDCl3) δ 134.5 (C-4), 121.2 (C-5), 29.3 (C-4), 27.2 (C-7), 26.2 (C-1), 17.7 (C-2), −6.2 (C-3); IR (neat, cm−1) 3029 (m, C—H), 2956 (m, C—H), 1667 (w, C═C); MS (CI, m/z) 195.16 [M+H+].
Reaction SMILES: [CH:1]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([SH:11])[C:5]=2[CH:4]=[CH:3][N:2]=1.C(=O)([O-])[O-].[K+].[K+].F[C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][C:20]=1[N+:26]([O-:28])=[O:27]>CN(C=O)C>[CH:1]1[C:10]2[C:5](=[C:6]([S:11][C:19]3[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][C:20]=3[N+:26]([O-:28])=[O:27])[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1
Reactant: Sc1cccc2cnccc12
Reactant: Nc1ccc(F)c([N+](=O)[O-])c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Nc1ccc(Sc2cccc3cnccc23)c([N+](=O)[O-])c1
Temperature: 100 °C
Reaction time: 2 h
Yield: 96.5 %

Procedure:
5-Isoquinolinethiol 1.00 g (6.2 mmol) was dissolved in DMF 14 ml, potassium carbonate 1.01 g (7.3 mmol) and 4-fluoro-3-nitroaniline 0.96 g (6.1 mmol) were added and the mixture was heated with stirring for 2 hours at 100° C. The reaction solution was concentrated under reduced pressure, the resulting residue was washed with water to obtain 4-(5-isoquinolylsulfanyl)-3-nitroaniline 1.75 g (96.5%).