Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: F[C:2]1[CH:16]=[CH:15][C:5]([C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[N:9]=2)=[O:7])=[CH:4][CH:3]=1.[N-:17]=[N+]=[N-].[Na+].O>CS(C)=O>[NH2:17][C:2]1[CH:16]=[CH:15][C:5]([CH:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[N:9]=2)[OH:7])=[CH:4][CH:3]=1
Reactant: Cc1cccc(C(=O)c2ccc(F)cc2)n1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: Cc1cccc(C(O)c2ccc(N)cc2)n1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 72.3 %

Procedure:
A solution of 2-(4-fluorobenzoyl)-6-methylpyridine (2.0 g) and sodium azide (3.36 g) in DMSO (40 ml) and the mixture was stirred for 24 hours at 90° C. To the reaction mixture was added water, and the mixture was extracted with diethylether. The organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated under reduced pressure, and a solution of the residue (1.88 g) in THF (40 ml) was added dropwise to a suspension of aluminum lithium hydride (0.60 g) in. THF (20 ml) at 0° C. The mixture was stirred at room temperature for 30 minutes, and water (0.6 ml), 15% aqueous solution of sodium hydroxide (0.6 ml) and water (1.8 ml) were sequentially and slowly added dropwise to the solution at 0° C. The mixture was stirred at room temperature for 4 days, magnesium sulfate was added to the mixture, and the precipitates were removed by filtration (Celite). The reaction mixure was concentrated under reduced pressure, and the obtained residue was separated and purified by column chromatography (ethyl acetate), to give (4-aminophenyl)(6-methylpyridin-2-yl)methanol (1.44 g) as pale yellow crystals.
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:7][O:8][C:9]1[CH:10]=[C:11]([SH:17])[CH:12]=[CH:13][C:14]=1[O:15][CH3:16].[C:18]1([S:24]([CH2:27][CH2:28][CH:29]2[CH:32]([CH2:33][CH2:34][CH2:35][CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[O:31][C:30]2=[O:43])(=[O:26])=[O:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN(C=O)C.C(OCC)C>[C:18]1([S:24]([CH2:27][CH2:28][CH:29]([CH:32]([S:17][C:11]2[CH:12]=[CH:13][C:14]([O:15][CH3:16])=[C:9]([O:8][CH3:7])[CH:10]=2)[CH2:33][CH2:34][CH2:35][CH2:36][C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[C:30]([OH:43])=[O:31])(=[O:26])=[O:25])[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: COc1ccc(S)cc1OC
Reactant: O=C1OC(CCCCc2ccccc2)C1CCS(=O)(=O)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOCC
Solvent: CN(C)C=O
Product: COc1ccc(SC(CCCCc2ccccc2)C(CCS(=O)(=O)c2ccccc2)C(=O)O)cc1OC
Yield: 78.4 %

Procedure:
To a vigorously stirring suspension of cesium carbonate (0.88 g, 2.69 mmol) in anhydrous DMF (10 mL) under a nitrogen atmosphere is added 3,4-dimethoxythiophenol (0.45 g, 2.69 mmol) in a dropwise fashion. The white heterogeneous mixture is stirred for 15 minutes then a solution containing (-)-3-(2-benzenesulfonylethyl)-4-(4-phenylbutyl)-oxetan-2-one (0.50 g, 1.34 mmol) in anhydrous DMF (4 mL) is added. The pale yellow heterogeneous mixture is stirred at room temperature for 2.5 hours then partitioned between water (50 mL) and diethyl ether (50 mL). Aqueous HCl (1 N, 5 mL) is added and the layers are separated. The aqueous phase is extracted with diethyl ether (2×20 mL) and the combined organic extracts are washed with water (10×10 mL), brine (20 mL), dried over anhydrous MgSO4, filtered and concentrated to afford a pale yellow oil. The crude product is chromatographed on silica gel (CH2Cl2 →CH2Cl2 :MeOH, 19:1) to afford a colorless oil which is dissolved in diethyl ether (100 mL) and washed with water (10×30 mL) to remove residual DMF. The organic phase is washed with brine (30 mL), dried over anhydrous MgSO4, filtered and concentrated to afford (-)-2-(2-benzenesulfonylethyl)-3-(3,4-dimethoxyphenyl-sulfanyl)-7-phenylheptanoic acid (0.57 g, 78%) as a white foam. TLC analysis [hexane/EtOAc, 2:1, Rf (lactone)=0.65, Rf (acid)=0.05]. [α]23D -35.3° (c 1.0, CHCl3); 1H NMR (300 MHz, CDCl3) δ 1.31-1.70 (m, 6H), 2.00 (m, 1H), 2.30 (m, 1H), 2.56 (m, 3H), 2.95 (m, 1H), 3.25 (m, 2H), 3.84 (s, 3H), 3.85 (s, 3H), 6.77 (d, J=8.2 Hz, 1H), 6.95 (m, 2H), 7.15 (m, 3H), 7.25 (m, 2H), 7.55 (m, 2H), 7.65 (m, 1H), 7.90 (m, 2H) ppm. Mass spectrum (FAB) m/z 542 (M)+.
Reaction SMILES: [CH2:1]1[CH:5]2[CH2:6][NH:7][CH2:8][CH:4]2[CH2:3][N:2]1[C:9]1[CH:10]=[CH:11][C:12]([N+:19]([O-:21])=[O:20])=[C:13]([CH:18]=1)[C:14]([NH:16][CH3:17])=[O:15].C=O.[C:24]([BH3-])#N>C(#N)C.C(O)(=O)C>[CH3:17][NH:16][C:14](=[O:15])[C:13]1[CH:18]=[C:9]([N:2]2[CH2:3][CH:4]3[CH:5]([CH2:6][N:7]([CH3:24])[CH2:8]3)[CH2:1]2)[CH:10]=[CH:11][C:12]=1[N+:19]([O-:21])=[O:20]
Reactant: CNC(=O)c1cc(N2CC3CNCC3C2)ccc1[N+](=O)[O-]
Reactant: [BH3-]C#N
Agent: C=O
Solvent: CC#N
Solvent: CC(=O)O
Product: CNC(=O)c1cc(N2CC3CN(C)CC3C2)ccc1[N+](=O)[O-]
Temperature: 130 °C
Yield: 48.3 %

Procedure:
5-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-N-methyl-2-nitrobenzamide (1.78 g, 6.13 mmol) (Intermediate 10B) was dissolved in acetonitrile (45 mL) before addition of formaldehyde (0.6 g, 7.36 mmol) and MP-cyanoborohydride (3.6 g, 9.25 mmol) followed by 6 drops of acetic acid. The resulting mixture was split into 3 microwave vials and heated at 130° C. for 20 minutes. The reaction mixture was filtered and concentrated. The resultant crude material was purified by a 50 g silica column in 100% dichloromethane, 20% methanol in dichloromethane, 100% methanol (Biotage Snap cartridge). Fractions of the product were combined and reduced to dryness under reduced pressure to afford N-methyl-5-(5-methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-2-nitrobenzamide (900 mg, 2.96 mmol).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([C:19]([CH3:23])([CH3:22])[CH2:20][NH2:21])[NH:11][C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[CH:4][C:3]=1[O:24][CH3:25].N1C=CC=CC=1.[CH3:32][S:33](Cl)(=[O:35])=[O:34]>ClCCl.C(=O)([O-])O.[Na+]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([C:19]([CH3:23])([CH3:22])[CH2:20][NH:21][S:33]([CH3:32])(=[O:35])=[O:34])[NH:11][C:12]=2[C:13]2[CH:14]=[CH:15][N:16]=[CH:17][CH:18]=2)=[CH:4][C:3]=1[O:24][CH3:25]
Reactant: COc1cc(-c2nc(C(C)(C)CN)[nH]c2-c2ccncc2)ccc1Cl
Reactant: CS(=O)(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Solvent: ClCCl
Product: COc1cc(-c2nc(C(C)(C)CNS(C)(=O)=O)[nH]c2-c2ccncc2)ccc1Cl
Temperature: 0 °C
Reaction time: 1 h
Yield: 39.1 %

Procedure:
A solution of Example 2 (178 mg, 0.5 mmol) in dichloromethane (10 ml) containing pyridine (0.12 ml, 1.5 mmol) at 0° C. was treated with a solution of methanesulfonyl chloride (57.3 mg, 0.5 mmol) in dichloromethane (1 ml). The solution was stirred at 0° C. for 1 hour followed by 30 min at room temperature before being diluted with dichloromethane and saturated sodium hydrogen carbonate solution. The aqueous layer was then separated and extracted with additional dichloromethane. The combined organic extracts were washed with brine, dried over anhydrous magnesium sulphate, filtered and concentrated at reduced pressure. The residue was chromatographed on silica gel eluting with dichloromethane/methanol/0.880 ammonia solution (8:1:0.1) to give the title compound (85 mg, 40%) as a pale yellow solid; MS(ES+) m/e 435/437 [M+H]+.
Reaction SMILES: [N+:1]([O-:4])([OH:3])=[O:2].[NH2:5][N:6]=[C:7]([NH2:11])[N:8](N)[NH2:9].[N+:12]([O-:15])([OH:14])=[O:13].NC(N)=N.NN>>[N+:1]([O-:4])([OH:3])=[O:2].[NH2:5][N:6]=[C:7]([NH2:11])[NH2:8].[N+:12]([O-:15])([OH:14])=[O:13].[NH2:5][NH:6][C:7]([NH:8][NH2:9])=[NH:11]
Reactant: NN=C(N)N(N)N
Agent: N=C(N)N
Agent: NN
Solvent: O=[N+]([O-])O
Product: N=C(NN)NN
Product: NN=C(N)N

Procedure:
A process for preparing triaminoguanidine nitrate from relatively impure -99 percent)/commercial guanidine nitrate and commercial grade aqueous hydrazine (50-64 weight percent) in alcohol by: (1) adding enough hydrazine to form monoaminoguanidine nitrate, diaminoguanidine nitrate, or mixtures thereof, (2) physically removing the alcohol insoluble, solid impurities from the solution, (3) adding the remainder of the hydrazine needed to form triaminoguanidine nitrate, (4) adding nitric acid to adjust the pH to from 4.5 to 5.5, and (6) isolating the product triaminoguanidine nitrate.
Reaction SMILES: [CH3:1][OH:2].Cl[C:4]1[N:5]=[C:6]2[S:16][C:15]([S:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=[N:14][N:7]2[C:8](=[O:13])[C:9]=1[N+:10]([O-:12])=[O:11].N1C=CC=CC=1>O>[CH2:18]([S:17][C:15]1[S:16][C:6]2=[N:5][C:4]([O:2][CH3:1])=[C:9]([N+:10]([O-:12])=[O:11])[C:8](=[O:13])[N:7]2[N:14]=1)[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23]
Reactant: CCCCCCSc1nn2c(=O)c([N+](=O)[O-])c(Cl)nc2s1
Reactant: CO
Solvent: c1ccncc1
Solvent: O
Product: CCCCCCSc1nn2c(=O)c([N+](=O)[O-])c(OC)nc2s1
Yield: 63 %

Procedure:
To 50 ml of methanol, 3.0 g of 7-chloro-2-hexylthio-6-nitro-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one and 1.0 g of pyridine were added, and the mixture was stirred under refluxing for 30 minutes. Water was added to the reaction mixture and the organic layer was extracted with ethyl acetate The ethyl acetate solution was dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was purified by silica gel column chromatography using an ethyl acetate/hexane mixture as an eluent. Thus 1.9 g of brown transparent viscous liquid of 2-hexylthio-7-methoxy-6-nitro-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one was obtained. Yield 63%.
Reaction SMILES: Br[C:2]1[CH:42]=[C:41]([CH3:43])[CH:40]=[CH:39][C:3]=1[CH2:4][O:5][CH:6]1[CH:11]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[O:30][CH3:31])=[CH:14][CH:13]=2)[CH2:10][CH2:9][N:8]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:7]1.C(=[NH:57])(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+].C1(C)C=CC=CC=1>[Cl-].[Na+].O>[NH2:57][C:2]1[CH:42]=[C:41]([CH3:43])[CH:40]=[CH:39][C:3]=1[CH2:4][O:5][CH:6]1[CH:11]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[O:30][CH3:31])=[CH:14][CH:13]=2)[CH2:10][CH2:9][N:8]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:7]1
Reactant: N=C(c1ccccc1)c1ccccc1
Reactant: COc1ccccc1COCCCOc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2OCc2ccc(C)cc2Br)cc1
Agent: CC(C)(C)[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Product: COc1ccccc1COCCCOc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2OCc2ccc(C)cc2N)cc1
Temperature: 80 °C
Reaction time: 72 h

Procedure:
The mixture of 0.800 g of tert-butyl 3-(2-bromo-4-methylbenzyloxy)-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate, 0.250 ml of benzophenone imine, 0.0037 g of dipalladiumtris(dibenzylidenacetone)-chloroform complex, 0.0051 g of (R)-(+)-2,2′-bis(diphenylphosphine)-1,1′-binaphthyl and 0.168 g of sodium tert-butoxide is admixed with 6.0 ml of toluene and stirred under argon at 80° C. over 72 hours. The reaction mixture is cooled, admixed with brine (20 ml) and extracted with ethyl acetate (2×80 ml). The organic phases are dried over sodium sulphate, filtered and concentrated by evaporation. The residue is dissolved in 6.0 ml of methanol, admixed with 0.090 g of 5% Pd/C and 1.15 g of ammonium formate, and stirred at 60° C. over 72 hours. The reaction mixture is diluted with methanol (20 ml) and clarified by filtration, and the filtrate is concentrated by evaporation. The residue is admixed with 0.1M NaOH (100 ml) and extracted with ethyl acetate (2×100 ml). The organic phases are washed successively with 0.1M NaOH (100 ml) and brine (100 ml), dried over sodium sulphate, filtered and concentrated by evaporation. The title compound is obtained as a yellowish oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.30 (1:2 EtOAc-heptane); Rt=5.32.
Reaction SMILES: [CH3:1][N+:2]([CH2:5][C:6]([OH:8])=O)([CH3:4])[CH3:3].C[N+](CC[CH2:15][C:16]([O-:18])=[O:17])(C)C.[Cl-:19]>>[CH3:1][N+:2]([CH2:5][CH:6]([OH:8])[CH2:15][C:16]([OH:18])=[O:17])([CH3:4])[CH3:3].[Cl-:19]
Reactant: C[N+](C)(C)CCCC(=O)[O-]
Reactant: C[N+](C)(C)CC(=O)O
Agent: [Cl-]
Product: C[N+](C)(C)CC(O)CC(=O)O
Temperature: 4 °C
Reaction time: 20 h
Yield: 99.2 %

Procedure:
A fermentor equipped for continuous culture which contained 1.5 l of a vitamin containing mineral medium (according to Example 1) with 1.5 percent of betaine and 1.0 percent of γ-butyrobetaine-chloride was inoculated with 150 ml of strain 13 (DSM 2903) preculture of the same medium. After 20 hours of aerobic cultivation at 30° C. and pH 7.0, the culture had grown up and the continuous operation was started at a flow rate of 0.1 l/h. The culture solution flowing out of the fermentor was caught in a vessel cooled at 4° C. the cells were removed by centrifugation. According to enzymatic analysis, the supernatant contained 8.8 g of L-carnitine per 1 of culture. This corresponded to a yield of 99.2 percent (proven analytically), calculated on the concentration of the γ-butyrobetaine-chloride used. The solid L-carnitine chloride was isolated from the solution by means of ion chromatography and water separation.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)=[C:4]([F:21])[CH:3]=1.[C:22](=[NH:35])([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1>[C:23]1([C:22](=[N:35][C:2]2[CH:7]=[CH:6][C:5]([C@H:8]3[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]3)=[C:4]([F:21])[CH:3]=2)[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: CC(C)(C)OC(=O)N1CCO[C@H](c2ccc(Br)cc2F)C1
Reactant: N=C(c1ccccc1)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1CCO[C@H](c2ccc(N=C(c3ccccc3)c3ccccc3)cc2F)C1
Temperature: 90 °C
Reaction time: 1.5 h

Procedure:
To a stirred solution of (+)-(R)-tert-butyl 2-(4-bromo-2-fluorophenyl)morpholine-4-carboxylate (4.3 g) and benzophenone imine (2.2 ml) in toluene (20 ml) was added sodium tert-butoxide (1.84 g). The reaction mixture was purged with argon for 10 min. (R)-(+)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (743 mg) and tris(dibenzylideneacetone)dipalladium(0) (328 mg) were added and the reaction mixture was heated to 90° C. and stirred for 90 min. The reaction mixture was poured into water and extracted twice with EtOAc. The organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel; gradient: 0% to 40% EtOAc in hexanes) to afford (R)-tert-butyl 2-(4-(diphenylmethyleneamino)-2-fluorophenyl)morpholine-4-carboxylate 5.95 g, quant.) as a yellow amorphous solid. MS (ISP): 461.2 ([M+H]+).
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].C([Li])CCC.Br[C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:15][CH:14]=1.BrC1C=CC([C:32]2[N:37]=[C:36]([C:38]3[C:47]4[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=4)[CH:41]=[CH:40][CH:39]=3)[N:35]=[C:34]([C:48]3[C:57]4[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=4)[CH:51]=[CH:50][CH:49]=3)[N:33]=2)=CC=1>O1CCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:38]1([C:36]2[N:35]=[C:34]([C:48]3[C:57]4[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=4)[CH:51]=[CH:50][CH:49]=3)[N:33]=[C:32]([C:13]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][C:22]([C:3]5[CH:2]=[CH:1][CH:6]=[CH:5][CH:4]=5)=[CH:21][CH:20]=4)=[CH:15][CH:14]=3)[N:37]=2)[C:47]2[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH:41]=[CH:40][CH:39]=1
Reactant: CCCCCC
Reactant: Brc1ccc(-c2nc(-c3cccc4ccccc34)nc(-c3cccc4ccccc34)n2)cc1
Reactant: Brc1ccc(-c2ccccc2)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: c1ccc(-c2ccc(-c3ccc(-c4nc(-c5cccc6ccccc56)nc(-c5cccc6ccccc56)n4)cc3)cc2)cc1
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 71 %

Procedure:
Under a stream of argon, 2.8 ml of a hexane solution containing 4.3 mmol of butyl lithium was slowly added to 15 ml of tetrahydrofuran cooled to −78° C. in which prepared by dissolving 0.91 g of 4-bromobiphenyl. After stirring at −78° C. for 15 minutes, 1.19 g of dichloro(tetramethylethylenediamine)zinc(II) was added thereto and stirred at −78° C. for 10 minutes and then at room temperature for 2 hours. A 1.47 g portion of 2-(4-bromophenyl)-4,6-bis(1-naphthyl)-1,3,5-triazine prepared in Reference Example 4 and 0.14 g of tetrakis(triphenylphosphine)palladium(0) were dissolved in 80 ml of tetrahydrofuran and added to this solution, followed by stirring under heating reflux for 13 hours. The reaction solution was concentrated under a reduced pressure and the thus obtained solid was washed with chloroform to obtain a white solid of the intended 2,4-bis(1-naphthyl)-6-[1,1′:4′,1″]terphenyl-4-yl-1,3,5-triazine (1.19 g, yield 71%).
Reaction SMILES: [O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[C:10]([O:11][CH2:12][CH:13]3[O:15][CH2:14]3)[C:5]=2[O:4][CH2:3][CH2:2]1.[CH2:16]([NH2:19])[CH2:17][NH2:18]>>[NH2:18][CH2:17][CH2:16][NH:19][CH2:14][CH:13]([OH:15])[CH2:12][O:11][C:10]1[C:5]2[O:4][CH2:3][CH2:2][O:1][C:6]=2[CH:7]=[CH:8][CH:9]=1
Reactant: c1cc2c(c(OCC3CO3)c1)OCCO2
Reactant: NCCN
Product: NCCNCC(O)COc1cccc2c1OCCO2

Procedure:
A mixture of 20.8 g. of 1-(benzodioxan-5-yloxy)-2,3-epoxypropane and 120 g. of ethylenediamine is heated at 90° C. for 18 hours and is then evaporated to dryness under reduced pressure. The residue is stirred with 100 ml. of water and the mixture is extracted four times with 100 ml. of chloroform each time. The combined chloroform extracts are dried and evaporated to dryness under reduced pressure and there is thus obtained as residue 3-β-aminoethylamino-1-(benzodioxan-5-yloxy)-2-propanol.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[CH:22][C:4]=1[CH2:5][NH:6][C@@:7]([C@H:16]1[CH2:20][O:19][CH2:18][C@H:17]1[OH:21])([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[F:15])[CH3:8].N1C=CC=CC=1.[S:34](Cl)(Cl)=[O:35]>ClCCl>[CH3:1][O:2][C:3]1[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[CH:22][C:4]=1[CH2:5][N:6]1[C@@:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[F:15])([CH3:8])[C@@H:16]2[C@@H:17]([CH2:18][O:19][CH2:20]2)[O:21][S:34]1=[O:35]
Reactant: COc1ccc(CN[C@](C)(c2ccccc2F)[C@H]2COC[C@H]2O)c(OC)c1
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: COc1ccc(CN2S(=O)O[C@@H]3COC[C@@H]3[C@@]2(C)c2ccccc2F)c(OC)c1
Yield: 94.9 %

Procedure:
Under a dry atmosphere of argon, a solution of rel-(3S,4S)-4-[(S)-1-(2,4-dimethoxy-benzylamino)-1-(2-fluoro-phenyl)-ethyl]-tetrahydro-furan-3-ol (6.8 g, 18.1 mmol) in pyridine (7.32 ml, 90.5 mmol) and dichloromethane (120 ml) was cooled to −77° C. The colorless solution was treated dropwise with thionyl chloride (2.15 g, 18.1 mmol) over about 10 minutes while the temperature rose to −73° C. After removal of the cooling bath the reaction mixture was allowed to reach room temperature. For the workup, the reaction mixture was diluted with dichloromethane (150 ml) and washed consecutively with hydrochloric acid (1N) and a saturated solution of sodium hydrogencarbonate. The organic layer was dried over sodium sulphate and evaporated. The (3aS,7S,7aS)-rel-6-(2,4-dimethoxy-benzyl)-7-(2-fluoro-phenyl)-7-methyl-hexahydro-2,4-dioxa-5-thia-6-aza-indene 5-oxide (7.24 g, 95% yield) was obtained as a white solid. MS (ISP): m/z=422.0 [M+H]+.
Reaction SMILES: [Br:1][C:2]1[C:8]([O:9][CH3:10])=[CH:7][C:5]([NH2:6])=[C:4]([F:11])[CH:3]=1.[C:12]1(=O)[O:17][C:15](=[O:16])[C:14]2[CH2:18][CH2:19][CH2:20][CH2:21][C:13]1=2.O>C(O)(=O)C>[Br:1][C:2]1[C:8]([O:9][CH3:10])=[CH:7][C:5]([N:6]2[C:15](=[O:16])[C:14]3[CH2:18][CH2:19][CH2:20][CH2:21][C:13]=3[C:12]2=[O:17])=[C:4]([F:11])[CH:3]=1
Reactant: O=C1OC(=O)C2=C1CCCC2
Reactant: COc1cc(N)c(F)cc1Br
Solvent: O
Solvent: CC(=O)O
Product: COc1cc(N2C(=O)C3=C(CCCC3)C2=O)c(F)cc1Br
Temperature: 25 °C
Yield: 33.9 %

Procedure:
4-Bromo-2-fluoro-5-methoxyaniline (1.1 g) and 3,4,5,6-tetrahydrophthalic anhydride (0.8 g) were dissolved in acetic acid (5 ml) and refluxed for 3 hours. The resultant mixture was allowed to cool to room temperature and poured into water, followed by extraction with ether. The ether extract was washed with water, dried over anhydrous sodium sulfate and subjected to filtration. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromatography to obtain 0.6 g of N-(4-bromo-2-fluoro-5-methoxyphenyl)-3,4,5,6-tetrahydrophthalimide (Compound No. 12).
Reaction SMILES: [CH:1]([S:4]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]3[C:21]([C:22]#[C:23][Si](C)(C)C)=[CH:20][N:19](S(C4C=CC(C)=CC=4)(=O)=O)[C:16]3=[N:17][CH:18]=2)=[CH:9][CH:8]=1)(=[O:6])=[O:5])([CH3:3])[CH3:2].O.O.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[C:22]([C:21]1[C:15]2[C:16](=[N:17][CH:18]=[C:13]([C:10]3[CH:9]=[CH:8][C:7]([S:4]([CH:1]([CH3:3])[CH3:2])(=[O:6])=[O:5])=[CH:12][CH:11]=3)[N:14]=2)[NH:19][CH:20]=1)#[CH:23]
Reactant: Cc1ccc(S(=O)(=O)n2cc(C#C[Si](C)(C)C)c3nc(-c4ccc(S(=O)(=O)C(C)C)cc4)cnc32)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Solvent: C1CCOC1
Product: C#Cc1c[nH]c2ncc(-c3ccc(S(=O)(=O)C(C)C)cc3)nc12
Temperature: 25 °C
Reaction time: 16 h
Yield: 60.9 %

Procedure:
2-[2-(4-Isopropylsulfonylphenyl)-5-(p-tolylsulfonyl)pyrrolo[2,3-b]pyrazin-7-yl]ethynyl-trimethyl-silane (248 mg, 0.4495 mmol) in THF (5 mL) was treated with 1M tetrabutylammonium fluoride trihydrate (674.3 μL, 0.6743 mmol) and the reaction mixture allowed to stir at ambient temperature for 16 hours. A further portion of 1M tetrabutylammonium fluoride trihydrate (449.5 μL, 0.4495 mmol) was added and the reaction mixture warmed to 40° C. for 6 hours. The reaction was cooled to ambient temperature and added dropwise to a mixture of EtOAc/ice water and the layers separated. The organic layer was washed with 2M NaOH (×2), brine (×1), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column silica gel chromatography eluting with 15-20% EtOAc/DCM to give the sub-title compound as colourless crystals (89 mg, 61% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.20 (d, 6H), 3.40-3.50 (m, 1H), 4.20 (s, 1H), 8.00 (d, 2H), 8.33 (s, 1H), 8.44 (d, 2H), 9.06 (s, 1H) and 12.70 (s, 1H) ppm; MS (ES+) 326.0.
Reaction SMILES: [O-:1][CH2:2][CH3:3].[Na+].[N+:5]([C:8]1[CH:22]=[CH:21][C:11]([CH2:12]P(=O)(OCC)OCC)=[CH:10][CH:9]=1)([O-:7])=[O:6].Br[C:24]1[CH:31]=C[CH:29]=[CH:28][C:25]=1[CH:26]=O>C(O)C>[CH:2]([C:3]1[CH:29]=[CH:28][C:25](/[CH:26]=[CH:12]/[C:11]2[CH:10]=[CH:9][C:8]([N+:5]([O-:7])=[O:6])=[CH:22][CH:21]=2)=[CH:24][CH:31]=1)=[O:1]
Reactant: CCOP(=O)(Cc1ccc([N+](=O)[O-])cc1)OCC
Reactant: CC[O-]
Reactant: O=Cc1ccccc1Br
Agent: [Na+]
Solvent: CCO
Product: O=Cc1ccc(/C=C/c2ccc([N+](=O)[O-])cc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 93 %

Procedure:
Sodium ethoxide in ethanol (0.23 g Na in 10 mL ethanol) was added to a solution containing diethyl p-nitrobenzylphosphonate (2.73 g, 0.01 mole), -bromobenzaldehyde (1.85 g, 0.01 mole) and ethanol (50 mL) at 0° C. The mixture was warmed to room temperature and stirred overnight. The product was filtered, washed with ethanol and vacuum-dried overnight to give trans-4-formyl-4'-nitrostilbene (2.826 g, 0.0093 mole, 93%, m.p. 251-219° C.).