Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.C([Li])CCC.CCCCCC.[CH3:21][N:22]([CH3:36])[C:23]1([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:28][CH2:27][C:26](=[O:29])[CH2:25][CH2:24]1>C1COCC1>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:26]1([OH:29])[CH2:27][CH2:28][C:23]([N:22]([CH3:21])[CH3:36])([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:24][CH2:25]1
Reactant: CN(C)C1(c2ccccc2)CCC(=O)CC1
Reactant: c1ccc2scnc2c1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CN(C)C1(c2ccccc2)CCC(O)(c2nc3ccccc3s2)CC1
Temperature: -80 °C
Reaction time: 2 h
Yield: 46 %

Procedure:
A solution of benzothiazole (622 mg, 4.60 mmol) in dry THF (30 ml) was cooled to −85° C. under a stream of argon. n-butyllithium (5.52 mmol, 3.45 ml of a 1.6 molar hexane solution) was added dropwise in such a way that a reaction temperature of −78° C. was not exceeded. Once all the substance had been added, the reaction mixture was stirred for 2 hours at −80° C. A solution of 4-dimethylamino-4-phenylcyclohexanone (1.00 g, 4.61 mmol) in dry THF (8 ml) was added dropwise at −80° C. The mixture was stirred for 30 minutes at −80° C. and then 3 days at ambient temperature. The reaction mixture was quenched with saturated ammonium chloride solution (30 ml), the organic phase was separated and the aqueous phase extracted four times with dichloromethane (30 ml). The combined organic phases were dried over sodium sulfate, filtered and the solvent removed under vacuum. Purification was carried out b y flash chromatography with cyclohexane/ethylacetate (V:V=7:3) over silica gel. 746 mg 1-benzothiazol-2-yl-4-dimethylamino-4-phenylcyclohexanol with a melting point of 155–157° C. were obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([N:13]1[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])=[CH:5]2.[Cl:20]N1C(=O)CCC1=O>ClCCl.CCOCC>[Cl:20][C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([Cl:1])[CH:3]=2)[NH:7][C:6]=1[C:11]([N:13]1[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12]
Reactant: CN1CCN(C(=O)c2cc3cc(Cl)ccc3[nH]2)CC1
Reactant: O=C1CCC(=O)N1Cl
Solvent: ClCCl
Solvent: CCOCC
Product: CN1CCN(C(=O)c2[nH]c3ccc(Cl)cc3c2Cl)CC1
Reaction time: 18 h
Yield: 50.3 %

Procedure:
(5-Chloro-1H-indol-2-yl)-(4-methyl-piperazin-1-yl)-methanone (Example 1, 0.23 g) in dichloromethane (3 mL) at ambient temperature was treated with N-chlorosuccinimide (0.123 g) and stirred for 18 h. The reaction mixture was diluted with ether, washed with water, saturated sodium hydrogencarbonate solution and then brine, dried over sodium sulfate, filtered, and concentrated to give crude product. Purification via silica gel chromatography, eluting with 1-8% methanol/dichloromethane afforded the title compound (0.13 g). 1H NMR (400 MHz, CDCl3): δ 2.36 (3H), 2.53 (4H), 3.79 (4H), 7.22 (1H), 7.29 (1H), 7.58 (1H), 10.39 (1H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4](/[CH:8]=[CH:9]/[CH:10]=[CH:11]/[CH:12]([OH:21])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[N:3]=1.C([Li])CCC.[CH3:27][O:28][C:29](=[O:35])[CH2:30][CH2:31][CH2:32][CH:33]=[O:34]>O1CCCC1>[CH3:27][O:28][C:29](=[O:35])[CH2:30][CH2:31][CH2:32][CH:33]([OH:34])[C:2]1[CH:7]=[CH:6][CH:5]=[C:4](/[CH:8]=[CH:9]/[CH:10]=[CH:11]/[CH:12]([OH:21])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[N:3]=1
Reactant: COC(=O)CCCC=O
Reactant: CCCCCCCCC(O)/C=C/C=C/c1cccc(Br)n1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCCCCCCCC(O)/C=C/C=C/c1cccc(C(O)CCCC(=O)OC)n1
Yield: 5.4 %

Procedure:
Under the conditions of example 1B, 470 mg of 2-bromo-6-[(1E, 3E)-(5RS)-5-hydroxy-1,3-tridecadienyl]-pyridine in 7 ml of tetrahydrofuran is mixed with 1.84 ml of n-butyllithium (1.6 molar in hexane) and 200 mg of 5-oxo-pentanoic acid methyl ester in 1.5 ml of tetrahydrofuran, worked up and chromatographed on silica gel with hexane/ethyl acetate=95/5. 29 mg of the title compound is obtained as colorless oil.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:5]2[C:10]=1[CH:9]=[N:8][NH:7][C:6]2=[S:11].S(OC)(O[CH3:22])(=O)=O>C(=O)(O)[O-].[Na+]>[CH3:22][N:7]1[C:6](=[S:11])[N:5]2[C:4]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)=[N:3][C:2]([CH3:1])=[C:10]2[CH:9]=[N:8]1
Reactant: COS(=O)(=O)OC
Reactant: Cc1nc(-c2ccccc2)n2c(=S)[nH]ncc12
Agent: O=C([O-])O
Agent: [Na+]
Product: Cc1nc(-c2ccccc2)n2c(=S)n(C)ncc12
Reaction time: 15.5 h
Yield: 7 %

Procedure:
8-Methyl-6-phenyl-imidazo[1,5-d]-as-triazin-4(3H)-thione (3.76 g, 0.014 mole) is dissolved in aqueous sodium bicarbonate (125 ml, 6.7%). Dimethyl sulfate (1.85 g, 0.0147 mole) is added at room temperature and the reaction mixture stirred overnight (appr. 15-16 hours). The precipitated solid is collected by filtration and washed thoroughly with water. The dried solid (3.84 g) is extracted with benzene. The benzene solution is evaporated to dryness, and the residual red solid obtained is extracted with hexane. Evaporation of the hexane solution yields a tan solid (0.25 g). Recrystallization of this tan solid from methanol yields pale yellow crystals, m.p. 194°-195° C.
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:12][CH2:13][CH3:14])[C:5]#[C:6][C:7](=O)[CH:8]([CH3:10])[CH3:9])[CH3:2].[C:15]([O:19][CH3:20])(=[O:18])[CH2:16][SH:17].CO.C([O-])([O-])=O.[Cs+].[Cs+].[O-]S([O-])(=O)=O.[Mg+2]>C1COCC1>[CH3:20][O:19][C:15]([C:16]1[S:17][C:5]([CH:4]([O:12][CH2:13][CH3:14])[O:3][CH2:1][CH3:2])=[CH:6][C:7]=1[CH:8]([CH3:10])[CH3:9])=[O:18]
Reactant: CCOC(C#CC(=O)C(C)C)OCC
Reactant: COC(=O)CS
Agent: O=C([O-])[O-]
Agent: O=S(=O)([O-])[O-]
Agent: [Cs+]
Solvent: CO
Solvent: C1CCOC1
Product: CCOC(OCC)c1cc(C(C)C)c(C(=O)OC)s1
Temperature: 0 °C
Reaction time: 1 h
Yield: 30.4 %

Procedure:
A solution of 6,6-Diethoxy-2-methyl-hex-4-yn-3-one (1.32 g, 6.66 mmol) in THF (20 ml) was cooled to 0° C. (ice bath). Methyl thioglycolate (0.6 ml, 6.66 mmol) was added in one portion and the mixture was stirred at 0° C. for 1 h. Methanol (3 ml) and Cs2CO3/MgSO4 (1 g/2 g, pre-dried at 200° C. in vacuum) were added at 0° C. The mixture was stirred at 0° C. for 15 min and then at rt for 15 h. The reaction mixture was quenched by pouring into EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatography with 0-20% EtOAc in hexane to afford the desired product (0.58 g, 30% yield).
Reaction SMILES: [F-].[K+].CN(C)C=O.[CH2:8]([O:10][C:11]([C:13]1[N:17]([CH3:18])[N:16]=[C:15]([CH:19]2[CH2:21][CH2:20]2)[C:14]=1I)=[O:12])[CH3:9].C[Si](C)(C)[C:25]([F:28])([F:27])[F:26]>C(OCC)(=O)C.[Cu]I.O>[CH:19]1([C:15]2[C:14]([C:25]([F:28])([F:27])[F:26])=[C:13]([C:11]([O:10][CH2:8][CH3:9])=[O:12])[N:17]([CH3:18])[N:16]=2)[CH2:21][CH2:20]1
Reactant: CCOC(=O)c1c(I)c(C2CC2)nn1C
Reactant: C[Si](C)(C)C(F)(F)F
Agent: [Cu]I
Agent: [F-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: O
Product: CCOC(=O)c1c(C(F)(F)F)c(C2CC2)nn1C
Temperature: 80 °C
Yield: 86.9 %

Procedure:
268 mg (1.40 mmol) of copper(I) iodide and 65.3 mg (1.12 mmol) of potassium fluoride are initially introduced into a heat-dried vial under argon, and 3 ml of N,N-dimethylformamide and 300 mg (0.93 mmol) of ethyl-3-cyclopropyl-4-iodo-1-methyl-1H-pyrazole-5-carboxylate and 0.28 ml (1.87 mmol) of trimethyl(trifluoromethyl)silane are added. The reaction mixture is degassed in the ultrasound, flushed with argon and the closed via is heated at 80° C. for three hours. The cooled reaction solution is admixed with a small amount of water, diluted with ethyl acetate, filtered over silica gel (ethyl acetate) and concentrated by evaporation on a rotary evaporator. Chromatographic purification on silica gel gives 212 mg of ethyl 3-cyclopropyl-1-methyl-4-(trifluoromethyl)-1H-pyrazole-5-carboxylate (86%).
Reaction SMILES: N(OC(C)(C)C)=O.C[Si]([Cl:12])(C)C.N[C:14]1[C:18]([CH:19]2[CH2:21][C:20]2([Br:23])[Br:22])=[CH:17][N:16]([C:24]2[C:29]([Cl:30])=[CH:28][C:27]([C:31]([F:34])([F:33])[F:32])=[CH:26][C:25]=2[Cl:35])[N:15]=1>ClCCl>[Cl:12][C:14]1[C:18]([CH:19]2[CH2:21][C:20]2([Br:23])[Br:22])=[CH:17][N:16]([C:24]2[C:25]([Cl:35])=[CH:26][C:27]([C:31]([F:34])([F:33])[F:32])=[CH:28][C:29]=2[Cl:30])[N:15]=1
Reactant: Nc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)cc1C1CC1(Br)Br
Reactant: C[Si](C)(C)Cl
Agent: CC(C)(C)ON=O
Solvent: ClCCl
Product: FC(F)(F)c1cc(Cl)c(-n2cc(C3CC3(Br)Br)c(Cl)n2)c(Cl)c1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
t-Butyl nitrite (0.07 ml) was added dropwise to a stirred solution of trimethylsilyl chloride (0.08 ml) in anhydrous dichloromethane (2.5 ml) at about -5° C. After a further 5 minutes, a solution of the title compound of Example 8 (0.10 g) in anhydrous dichloromethane (4.5 ml) was added dropwise, whilst maintaining the reaction temperature below -5° C. Next, the reaction mixture was allowed to warm to room temperature, stirred for 45 minutes more and then evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, using mixtures of hexane:dichloromethane (9:1 then 4:1) as eluants, to afford the title compound as a colourless gum. δ (CDCl3): 1.85 (t,1H), 2.25 (dd,1H), 2.70 (dd,1H), 7.35 (s,1H), 7.75 (s,2H). MS (thermospray): M/Z [M+H] 510.7; C13H6Br2Cl3F3N2 +H requires 510.80.
Reaction SMILES: [F:1][C:2]1[CH:29]=[CH:28][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][N:17]4[C:21](=[O:22])[C:20]5=[CH:23][CH:24]=[CH:25][CH:26]=[C:19]5[C:18]4=[O:27])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.[BH4-].[Na+]>CO.C(Cl)Cl>[F:1][C:2]1[CH:29]=[CH:28][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][N:17]4[CH:21]([OH:22])[C:20]5[C:19](=[CH:26][CH:25]=[CH:24][CH:23]=5)[C:18]4=[O:27])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1
Reactant: O=C1c2ccccc2C(=O)N1CCN1CCC(c2noc3cc(F)ccc23)CC1
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: O=C1c2ccccc2C(O)N1CCN1CCC(c2noc3cc(F)ccc23)CC1
Reaction time: 0.5 h
Yield: 89.4 %

Procedure:
To a suspension of N-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]phthalimide (7.8 g, 19.8 mmol) in methanol (250 ml) and DCM (30 ml) was added NaBH4 (1.7 g, 45.5 mmol) at room temperature under nitrogen. After stirring for 0.5 hours the homogeneous reaction mixture was concentrated. The remaining solid was purified on a flash chromatography column (SiO2, 1:1 EtOAc/DCM, increased to 10% MeOH) to give 7.0 g (90%) of the desired product as a solid which was recrystallized from EtOAc, m.p.=172-173° C.
Reaction SMILES: [CH:1](/[C:5]1([CH2:17][CH2:18][C:19](=[O:22])[CH2:20][CH3:21])[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:14][CH3:15])[CH:11]=2)[C:6]1=O)=[CH:2]\[CH2:3][CH3:4].[OH-].[Na+]>CO>[CH:1](/[C:5]12[CH2:17][CH2:18][C:19](=[O:22])[C:20]([CH3:21])=[C:6]1[C:7]1[C:12](=[CH:11][C:10]([O:14][CH3:15])=[CH:9][CH:8]=1)[CH2:13]2)=[CH:2]\[CH2:3][CH3:4]
Reactant: CC/C=C/C1(CCC(=O)CC)Cc2cc(OC)ccc2C1=O
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CC/C=C/C12CCC(=O)C(C)=C1c1ccc(OC)cc1C2
Temperature: 85 °C
Yield: 35.8 %

Procedure:
A solution of 2-[(1E)-1-butenyl]-5-methoxy-2-(3-oxopentyl)-1-indanone (199 mg, 0.663 mmol) in methanol (5 mL) was treated with 2N aqueous NaOH (1.6 mL) and the resulting mixture was stirred and heated in an oil bath at 85° C. for 7 hours. After cooling to room temperature, the brown solution was partitioned between EtOAc (20 mL) and 0.4N HCl (10 mL). The organic phase was separated, washed with brine (15 ml), dried over MgSO4, filtered, and evaporated under vacuum to a brown oil (208 mg). The crude product was purified by silica gel chromatography on a Biotage FLASH 12S column (1.2×7.5 cm), eluting with 5:1 hexanes:EtOAc, to afford 9a-[(1E)-1-butenyl]-7-methoxy-4-methyl-1,2,9,9a-tetrahydro-3H-fluoren-3-one (67 mg) as an oil.
Reaction SMILES: Cl[C:2]1[C:6]([S:7][CH2:8][CH2:9][CH3:10])=[N:5][S:4][N:3]=1.[OH-:11].[Na+]>CS(C)=O>[CH2:8]([S:7][C:6]1[C:2]([OH:11])=[N:3][S:4][N:5]=1)[CH2:9][CH3:10]
Reactant: CCCSc1nsnc1Cl
Reactant: [OH-]
Agent: [Na+]
Solvent: CS(C)=O
Product: CCCSc1nsnc1O

Procedure:
A mixture of 3-chloro-4-propylthio-1,2,5-thiadiazole (10 g), 2 N NaOH (100 mL), and DMSO (10 mL) was heated to reflux for 24 h. The solution was cooled and extracted with ether. The aqueous fraction was acidified with conc. HCl and cooled in ice-water for 3 h. The resulting solid was collected, washed with a small amount of cold water to give a white solid (8.15 g). Recrystallization from heptane gave white crystals, m.p. 84-85° C.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][CH2:10][CH2:11][N:12]2[CH:16]=[CH:15][N:14]=[CH:13]2)[CH:5]=[CH:6][CH:7]=1.Cl[CH2:18][C:19]1[N:20]=[C:21](/[CH:24]=[CH:25]/[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[O:22][CH:23]=1>>[N:12]1([CH2:11][CH2:10][CH2:9][CH2:8][C:4]2[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=2)[O:1][CH2:18][C:19]2[N:20]=[C:21](/[CH:24]=[CH:25]/[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[O:22][CH:23]=2)[CH:16]=[CH:15][N:14]=[CH:13]1
Reactant: Oc1cccc(CCCCn2ccnc2)c1
Reactant: ClCc1coc(/C=C/c2ccccc2)n1
Product: C(=C/c1nc(COc2cccc(CCCCn3ccnc3)c2)co1)\c1ccccc1
Yield: 70 %

Procedure:
In substantially the same manner as in Working Example 72, 1-[4-(3-hydroxyphenyl)butyl]imidazole was allowed to react with 4-chloromethyl-2-[(E)-2-phenylethenyl]oxazole to give 4-[3-[4-(1-imidazolyl)butyl]phenoxymethyl]-2-[(E)-2-phenylethenyl]oxazole. The yield was 70%. Recrystallization from ethyl acetate-hexane gave colorless prisms, mp 75-76° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8](O)[CH2:9][O:10][C@H:11]1[CH2:16][CH2:15][C@H:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:13][CH2:12]1.C(S(F)(F)([F:32])(CC)N)C>ClCCl>[F:32][CH:8]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[F:1])[CH2:9][O:10][C@H:11]1[CH2:16][CH2:15][C@H:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:13][CH2:12]1
Reactant: CCS(N)(F)(F)(F)CC
Reactant: CC(C)(C)OC(=O)N[C@H]1CC[C@H](OCC(O)c2ccccc2F)CC1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N[C@H]1CC[C@H](OCC(F)c2ccccc2F)CC1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
A solution of 18 g of tert-butyl {trans-4-[2-(2-fluorophenyl)-2-hydroxyethoxy]-cyclohexyl}carbamate in 200 mL of dichloromethane was added over 30 min to a solution of 23 g of diethyl-amino sulfur-trifluoride in 800 mL of dichloromethane cooled to −78° C. under nitrogen atmosphere. The mixture was allowed stir for 1 h at −78° C. then quenched with 100 mL of saturated sodium carbonate. After stirring for 15 min the layers were separated. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. Chromatography over silica gel eluting with a gradient of 2%-25% ethyl acetate in hexane gave 12 g of product as a white crystalline solid: 1H NMR (400 MHz, CDCl3) 7.45 (m, 1H), 7.3 (m, 1H), 7.2 (m, 1H), 7.06 (m, 1H), 5.15 (dm, JH-F=48 Hz), 4.18 (br s, 1H), 3.65 (complex m, 2H), 3.42 (br s, 1H), 3.3 (m, 1H), 2.0 (d, 4H), 1.42 (s, 9H), 1.4 (q, 2H), 1.15 (q, 2H).
Reaction SMILES: [OH-].[B+3].[Na+].[OH-].[OH-].[OH-].[F:7][C:8]1[C:16]([N+:17]([O-:19])=[O:18])=[CH:15][C:14]([F:20])=[C:13]([F:21])[C:9]=1[C:10](O)=[O:11].B(F)(F)F.CCOCC>O1CCCC1>[F:7][C:8]1[C:16]([N+:17]([O-:19])=[O:18])=[CH:15][C:14]([F:20])=[C:13]([F:21])[C:9]=1[CH2:10][OH:11]
Reactant: O=C(O)c1c(F)c(F)cc([N+](=O)[O-])c1F
Agent: FB(F)F
Agent: [B+3]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: O=[N+]([O-])c1cc(F)c(F)c(CO)c1F
Temperature: 25 °C
Reaction time: 1 h
Yield: 67.9 %

Procedure:
To a solution of sodium boron hydroxide (44 g) in anhydrous tetrahydrofuran is added a solution of 2,5,6-trifluoro-3-nitrobenzoic acid (22 g) in anhydrous tetrahydrofuran (40 ml) at below 10° C., and thereto is further added dropwise a solution of boron trifluoride etherate (20 ml) in anhydrous tetrahydrofuran (40 ml) at below 10° C. After the addition, the mixture is stirred at room temperature for one hour. The reaction mixture is poured into ice water and extracted with diethyl ether. The extract is dried, and then the solvent is distilled off to give 2,5,6-trifluoro-3-nitrobenzyl alcohol (14 g).
Reaction SMILES: [C:1]([O:4][CH:5]1[NH:8][C:7](=[O:9])[CH:6]1[CH2:10][CH2:11][CH2:12][NH:13][C:14]([NH:26][C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28])=[N:15][C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])(=[O:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[C:47](Cl)(=[O:54])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1>C1COCC1>[C:1]([O:4][CH:5]1[N:8]([C:47]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)=[O:54])[C:7](=[O:9])[CH:6]1[CH2:10][CH2:11][CH2:12][NH:13][C:14]([NH:26][C:27]([O:29][CH2:30][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)=[O:28])=[N:15][C:16]([O:18][CH2:19][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)=[O:17])(=[O:3])[CH3:2]
Reactant: O=C(Cl)c1ccccc1
Reactant: CC(=O)OC1NC(=O)C1CCCNC(=NC(=O)OCc1ccccc1)NC(=O)OCc1ccccc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(=O)OC1C(CCCNC(=NC(=O)OCc2ccccc2)NC(=O)OCc2ccccc2)C(=O)N1C(=O)c1ccccc1
Reaction time: 0.25 h
Yield: 33.3 %

Procedure:
To a -78° C. THF (4 mL) of compound 13 (500 mg, 1 mmol) was added 1N THF solution of sodium bis(trimethylsilyl)amide (1.0 mL, 1.0 mmol), and the resultant reaction mixture was stirred for 15 min. Benzoyl chloride (140 mg, 1 mmol) was added, and the mixture was stirred for 30 min at -78° C. and for 90 min at room temperature. The solution was subsequently partitioned between ether and aqueous pH 4.0 buffer. The organic layer was dried (MgSO4) and concentrated. The residue was purified by silica gel chromatography (Et2O:hexane/2:1) to afford 200 mg (33%) of the title product as a mixture of trans and cis (3:1) isomers.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([C:10]2[C:15]([CH3:16])=[CH:14][N:13](O)[CH2:12][C:11]=2[CH3:18])=[C:5]([CH3:19])[CH:4]=1.O.[PH2]([O-])=O.[Na+]>C(O)(=O)C.[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH3:19])[C:6]([C:10]2[C:15]([CH3:16])=[CH:14][N:13]=[CH:12][C:11]=2[CH3:18])=[C:7]([CH3:9])[CH:8]=1
Reactant: COc1cc(C)c(C2=C(C)CN(O)C=C2C)c(C)c1
Agent: [Pd]
Agent: O=[PH2][O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: COc1cc(C)c(-c2c(C)cncc2C)c(C)c1
Temperature: 80 °C
Reaction time: 12 h
Yield: 97.7 %

Procedure:
To a mixture of 3 (6.55 g, 25.5 mmol) and palladium (10 wt. % on activated carbon; 3.05 g, 2.8 mmol) in acetic acid (150 mL) was added sodium hypophosphite hydrate (6.7 g, 63 mmol) in a single portion at 80° C. The reaction mixture was stirred at 80° C. under N2 for 12 h, then filtered and concentrated in vacuo. The resulting light-yellow oil was dissolved in chloroform (250 mL) and washed successively with saturated NaHCO3 (aq.), water, and brine. The organic layer was then separated, dried over MgSO4, filtered, and concentrated in vacuo. The resulting pale-yellow solid was purified by flash chromatography on silica gel eluting with 1:1 hexane:ethyl acetate, to give 6.01 g (97.9%) of the title compound as colorless solid: mp 87-88° C.; 1H NMR (400 MHz, CD2Cl2): δ 8.334 (s, 2H), 6.707 (s, 2H), 3.804 (s, 3H), 1.892 (s, 6H), 1.851 (s, 6H); 13C NMR (100 MHz, CD2Cl2): δ 159.330, 148.939, 148.420, 136.373, 131.905, 129.958, 113.489, 55.556, 20.188, 16.831; MS (APCI): m/z 242.2 [(M+H)+,100]; Anal. Calcd. For C16H19NO: C, 79.63; H, 7.94; N, 5.80. Found: C, 79.39; H, 7.94; N, 5.75.
Reaction SMILES: [S:1]([O:8]S(C(F)(F)F)(=O)=O)([C:4]([F:7])([F:6])[F:5])(=[O:3])=[O:2].[CH2:16]([C:19]1[CH:24]=[C:23]([N+:25]([O-:27])=[O:26])[CH:22]=[CH:21][C:20]=1O)[CH:17]=[CH2:18].CC1C=CC=C(C)N=1>ClCCl>[O:8]([C:20]1[CH:21]=[CH:22][C:23]([N+:25]([O-:27])=[O:26])=[CH:24][C:19]=1[CH2:16][CH:17]=[CH2:18])[S:1]([C:4]([F:7])([F:6])[F:5])(=[O:3])=[O:2]
Reactant: C=CCc1cc([N+](=O)[O-])ccc1O
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: Cc1cccc(C)n1
Solvent: ClCCl
Product: C=CCc1cc([N+](=O)[O-])ccc1OS(=O)(=O)C(F)(F)F
Reaction time: 3 h

Procedure:
Triflic anhydride (1.63 ml) was added dropwise to a mixture of 2-allyl-4-nitrophenol (1.79 g) and 2,6-dimethylpyridine (1.18 g) in dry dichloromethane (15 ml) at -20° C. under an atmosphere of argon. The reaction mixture was allowed to reach ambient temperature over 3 hours. The mixture was partitioned between water and dichloromethane. The organic phase was separated, washed with 1M aqueous sodium hydroxide solution, water, dried (MgSO4) and evaporated to give 2-allyl-4-nitrophenyl triflate (2.71 g) as an oil; microanalysis, found: C, 38.7; H, 2.6; N, 4.2%; C10H8F3NO5S requires: C, 38.6; H, 2.59; N, 4.5%; NMR: 3.7(2H,d), 5.19-5.35(2H,m), 5.97-6.17(1H,m), 7.84(1H,d), 8.36-8.55(2H,m); m/z 311(M).
Reaction SMILES: C12BC(CCC1)CCC2.[CH3:10][O:11][C:12]1[CH:17]=[C:16]([N+:18]([O-:20])=[O:19])[CH:15]=[CH:14][C:13]=1[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH:27]=[CH2:28])[C:22]1=[O:29].[OH-].[Na+].OO.S(OS([O-])=O)([O-])=[O:35].[Na+].[Na+]>O1CCCC1>[OH:35][CH2:28][CH2:27][C:23]1[C:22](=[O:29])[N:21]([C:13]2[CH:14]=[CH:15][C:16]([N+:18]([O-:20])=[O:19])=[CH:17][C:12]=2[O:11][CH3:10])[CH:26]=[CH:25][CH:24]=1
Reactant: C=Cc1cccn(-c2ccc([N+](=O)[O-])cc2OC)c1=O
Reactant: O=S([O-])OS(=O)[O-]
Agent: B1C2CCCC1CCC2
Agent: OO
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1cc([N+](=O)[O-])ccc1-n1cccc(CCO)c1=O
Reaction time: 0.08 h

Procedure:
At 0° C., a solution of 36 g (299 mmol) of 9-borabicyclo[3.3.1]nonane in 600 ml of tetrahydrofuran is added over a period of 45 min to 37 g (136 mmol) of the compound from Example 20A. After a further hour at this temperature, a solution of 27 g (680 mmol) of sodium hydroxide (1N in water) is added over the course of 15 min. The mixture is stirred for a further 5 min, and 125 ml of a 30% strength hydrogen peroxide solution are then added such that the temperature does not exceed 30° C. Cooling is removed, and the mixture is stirred for another 30 min. The mixture is extracted repeatedly with ethyl acetate, the combined organic phases are washed with a solution of 730 g (1.50 mol) of sodium disulphite, the organic phase is separated off and the aqueous phase is reextracted with ethyl acetate. The combined organic phases are washed with saturated sodium chloride solution, dried over magnesium sulphate and evaporated to dryness under reduced pressure. The residue is absorbed on silica gel and chromatographed using a gradient of cyclohexane and ethyl acetate. The product fractions are combined and evaporated to dryness under reduced pressure. For crystallization, tert-butyl methyl ether is added. The crystals are filtered off and dried under reduced pressure. This gives 24 g (60% of theory) of the desired product.
Reaction SMILES: C[Al](C)C.C(O[C:8]([C:10]1[C:11]([CH3:31])=[C:12]([C:24]([O:26]C(C)(C)C)=O)[NH:13][C:14]=1[CH2:15][CH2:16][CH2:17][CH2:18][N:19]([CH2:22][CH3:23])CC)=[O:9])C>C1(C)C=CC=CC=1>[CH2:12]([N:13]([CH2:14][CH3:10])[CH2:23][CH2:22][N:19]1[CH2:18][CH2:17][CH2:16][CH2:15][C:14]2[NH:13][C:12]([CH:24]=[O:26])=[C:11]([CH3:31])[C:10]=2[C:8]1=[O:9])[CH3:11]
Reactant: CCOC(=O)c1c(CCCCN(CC)CC)[nH]c(C(=O)OC(C)(C)C)c1C
Agent: C[Al](C)C
Solvent: Cc1ccccc1
Product: CCN(CC)CCN1CCCCc2[nH]c(C=O)c(C)c2C1=O
Yield: 47.9 %

Procedure:
Trimethyl aluminum (489 μl, 2 mol/L) was dissolved in 3 ml of toluene under stirring, and added with the solution of 5-(4-diethylamino-butyl)-3-methyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester 60d (345 mg, 0.82 mmol) in 6 ml of toluene to the above solution at room temperature. Upon completion of the addition, the reaction mixture was stirred for 30 minutes at room temperature, heated to reflux for 2 hours in an oil bath, added with another trimethyl aluminum (900 μl, 2 mol/L) and refluxed for another 7 hours. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was quenched with water, added with hydrochloric acid solution (1 ml, 2 mol/L) and stirred for 30 minutes at room temperature. The mixture was adjusted to about pH 10 with aqueous sodium hydroxide solution (10%) and extracted with ethyl acetate (25 ml×3). The combined organic extracts were washed with saturated brine (25 ml), dried over anhydrous magnesium sulfate, filtered to remove the drying agent and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound 5-(2-diethylamino-ethyl)-3-methyl-4-oxo-4,5,6,7,8,9-hexahydro-1H-1,5-diaza-cyclopentacyclooctene-2-carbaldehyde 60e (60 mg, yield 26.7%) as a white solid.