Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([CH:3]([CH2:39][CH3:40])[CH2:4][C:5]1([C:11]([NH:13][C:14]2[C:15]([S:24]C(C3(CC(CC)CC)CCCCC3)=O)=[CH:16][C:17]3[C:22]([CH:23]=2)=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)[CH3:2].[OH-].[K+].O>CO.O1CCCC1>[SH:24][C:15]1[C:14]([NH:13][C:11]([C:5]2([CH2:4][CH:3]([CH2:39][CH3:40])[CH2:1][CH3:2])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]2)=[O:12])=[CH:23][C:22]2[C:17]([CH:16]=1)=[CH:18][CH:19]=[CH:20][CH:21]=2
Reactant: CCC(CC)CC1(C(=O)Nc2cc3ccccc3cc2SC(=O)C2(CC(CC)CC)CCCCC2)CCCCC1
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: CCC(CC)CC1(C(=O)Nc2cc3ccccc3cc2S)CCCCC1
Reaction time: 1 h

Procedure:
The crude product obtained in step A) is dissolved in a mixture of methanol and tetra-hydrofuran (1:1). Then 3.5 mol equivalents of potassium hydroxide are added at room temperature and the mixture is stirred for 1 hour. Then water is added and the mixture is washed with n-hexane. The aqueous layer is then acidified by addition of KHSO4 and extracted with chloroform. The combined extracts are washed with water and brine, dried (Na2SO4) and concentrated to obtain 1-(2-ethyl-butyl)-cyclohexanecarboxylic acid (3-mercapto-naphthalen-2-yl)-amide.
Reaction SMILES: [CH2:1]([Mg]Cl)[CH2:2][CH3:3].[CH:6]([C:8]1[C:16]2[O:15][CH2:14][CH:13]([C:17]3[CH:22]=[CH:21][C:20]([CH:23]([CH3:25])[CH3:24])=[CH:19][CH:18]=3)[C:12]=2[C:11]([CH3:26])=[C:10]([NH:27][C:28](=[O:34])[CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:9]=1[CH3:35])=[O:7]>O>[OH:7][CH:6]([C:8]1[C:16]2[O:15][CH2:14][CH:13]([C:17]3[CH:22]=[CH:21][C:20]([CH:23]([CH3:25])[CH3:24])=[CH:19][CH:18]=3)[C:12]=2[C:11]([CH3:26])=[C:10]([NH:27][C:28](=[O:34])[CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:9]=1[CH3:35])[CH2:1][CH2:2][CH3:3]
Reactant: CCC[Mg]Cl
Reactant: Cc1c(C=O)c2c(c(C)c1NC(=O)CC(C)(C)C)C(c1ccc(C(C)C)cc1)CO2
Solvent: O
Product: CCCC(O)c1c(C)c(NC(=O)CC(C)(C)C)c(C)c2c1OCC2c1ccc(C(C)C)cc1
Reaction time: 1 h
Yield: 25.7 %

Procedure:
To propylmagnesium chloride (2.0 M, THF solution 10.0 mL, 20.0 mmol) was added N-(7-formyl-3-(4-isopropylphenyl)-4,6-dimethyl-2,3-dihydro-1-benzofuran-5-yl)-3,3-dimethylbutanamide (2.2 g, 5.40 mmol) obtained in Example 20 at 0° C. and the reaction solution was stirred at the same temperature for 1 hour. The reaction solution was added to water and the product was extracted with ethyl acetate. The organic layer was washed with water and 1 N hydrochloric acid, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to obtain 627 mg (yield: 26%) of the title compound as a low polarity isomer. Melting point: 162-163° C. (hexane-ethyl acetate).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].CC(C)([O-])C.[Na+].C1(C)C=CC=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].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOCC>[F:14][C:11]1[CH:12]=[CH:13][C:8]([C:5]2[CH:6]=[CH:7][C:2]([N:25]3[CH2:24][CH2:23][N:22]([C:20]([O:19][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:21])[CH2:27][CH2:26]3)=[CH:3][CH:4]=2)=[CH:9][CH:10]=1
Reactant: Fc1ccc(-c2ccc(Br)cc2)cc1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: CC(C)(C)OC(=O)N1CCN(c2ccc(-c3ccc(F)cc3)cc2)CC1
Yield: 87.8 %

Procedure:
4-Bromo-4′-fluorobiphenyl (4.46 g, 17.8 mmol), N-tert-butoxycarbonyl piperazine (3.97 g, 21.3 mmol), sodium tert-butoxide (2.39 g, 24.9 mmol), racemic 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (rac-BINAP) (0.082 g, 0.131 mmol), bis-(dibenzylideneacetone)palladium(0) (0.041 g, 0.045 mmol) and dry toluene (45 mL) were stirred at 80° C. under nitrogen atmosphere for six hours. The warm mixture was filtered, the solids were washed twice with warm toluene and the filtrate was concentrated in vacuo giving an orange-red crude, which was stirred with ether (50 mL) for two hours. The solid was filtered off, washed with small volumes of ether and dried in vacuo at 45° C. over night to give 5.57 g (88% yield) of tert-butyl 4-(4′-fluoro[1,1′-biphenyl]-4-yl)-1-piperazinecarboxylate. This product (5.52 g, 15.5 mmol) was dissolved in dioxane (150 mL) and stirred with 4M hydrochloric acid (8.1 mL) at RT over night. Concentrated hydrochloric acid (3.0 mL) was added and stirring was continued at 45° C. for 1.5 hours and at 60° C. for 1 hour. The solution was concentrated to dryness and the solid was triturated with ether (100 mL), filtered, washed with small volumes of ether and dried in vacuo at 45° C. for two hours to give 5.26 g (103% yield) of 1-(4′-fluoro[1,1′-biphenyl]-4-yl)piperazine dihydrochloride as a light-yellow salt.
Reaction SMILES: Cl.Cl.[NH2:3][CH:4]1[CH:9]2[CH2:10][CH2:11][N:6]([CH2:7][CH2:8]2)[CH2:5]1.[S:12]1[CH:16]=[CH:15][CH:14]=[C:13]1[C:17]([NH:19][C:20](N)=[O:21])=[O:18].C(N(C(C)C)CC)(C)C.C([O-])(=O)/C=C\C([O-])=O>N1C=CC=CC=1>[N:6]12[CH2:11][CH2:10][CH:9]([CH2:8][CH2:7]1)[CH:4]([NH:3][C:20]([NH:19][C:17]([C:13]1[S:12][CH:16]=[CH:15][CH:14]=1)=[O:18])=[O:21])[CH2:5]2
Reactant: NC(=O)NC(=O)c1cccs1
Reactant: NC1CN2CCC1CC2
Agent: Cl
Agent: O=C([O-])/C=C\C(=O)[O-]
Solvent: c1ccncc1
Solvent: CCN(C(C)C)C(C)C
Product: O=C(NC(=O)c1cccs1)NC1CN2CCC1CC2

Procedure:
The above compound was prepared, following the procedure of Example 14b, from 3-aminoquinuclidine dihydrochloride (1.0 g, 5 mmol), 2-thienoylurea (0.85 g, 5 mmol) and diisopropylethylamine (1.3 g, 10 mmol) in pyridine (20 ml). The product (0.79 g) was converted to hydrochloride half hydrate, mp 232°-233° C.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][NH:4][C:5]([N:7]([CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH:8]1[O:16][C@H:15]([CH2:17][OH:18])[C@@H:13]([OH:14])[C@H:11]([OH:12])[C@H:9]1[OH:10])=[O:6].C(=O)([O-])[O-].[Na+].[Na+].[N+:31]([O-])([N+]([O-])=O)=[O:32]>O1CCCC1.C(Cl)Cl>[Cl:1][CH2:2][CH2:3][N:4]([N:31]=[O:32])[C:5]([N:7]([CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH:8]1[O:16][C@H:15]([CH2:17][OH:18])[C@@H:13]([OH:14])[C@H:11]([OH:12])[C@H:9]1[OH:10])=[O:6]
Reactant: CCCCCCN(C(=O)NCCCl)C1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Reactant: O=[N+]([O-])[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: C1CCOC1
Product: CCCCCCN(C(=O)N(CCCl)N=O)C1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Yield: 77.7 %

Procedure:
3.7 g of 1-(2-chloroethyl)-3-n-hexyl-3-D-glucopyranosylurea are dissolved in a mixture of 60 ml of tetrahydrofuran and 60 ml of methylene chloride, and 15 g of sodium carbonate anhydrate are added thereto. 5 g of nitrogen tetroxide gas are introduced into the mixture for 10 minutes under ice-cooling. The mixture is treated in the same manner as described in Example 2. 3.1 g of 1-(2-chloroethyl)-1-nitroso-3-n-hexyl-3-D-glucopyranosylurea are thereby obtained as a yellow oil.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[C:5](F)[CH:4]=1)#[N:2].C(C1C=C(F)C(O)=C(F)C=1)#N.C(Cl)(Cl)(Cl)F>>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1)#[N:2]
Reactant: N#Cc1ccc(O)c(F)c1
Agent: N#Cc1cc(F)c(O)c(F)c1
Solvent: FC(Cl)(Cl)Cl
Product: N#Cc1ccc(O)cc1

Procedure:
A stirred reaction vessel charged with 4-cyanophenol (11.9 g, 0.1 mol) and 96% formic acid (200 cm3) was purged with nitrogen and cooled to 10° C. Fluorine (0.2 mol), diluted with nitrogen to 10%, was passed through the cooled, stirred solution over a period of about 6 hours. The vessel was purged with nitrogen and allowed to warm to ambient temperature. The reaction mixture was poured into water and extracted with diethyl ether. The extracts were dried and the solvent was removed by distillation to leave a tan solid (12.4 g). Short path distillation of the crude product (3.9 g) at reduced pressure gave an off white solid (3.4 g) which was shown to comprise three main compounds by nmr and GC analysis. The mixture was shown to contain 4-cyano-2-fluorophenol (δF -134.7 ppm[d6 -Me2CO]) and 4-cyano-2,6-difluorophenol (δF -131.0 ppm[d6 -Me2CO]) in yields of 64% and 10%, respectively, with a conversion of 84%. (NB The chemical shifts in this and all other examples were relative to CFCl3.)
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH2:9]Br)[C:5]([I:8])=[N:6][CH:7]=1.C([O-])([O-])=[O:12].[Ca+2]>O1CCOCC1.O>[Br:1][C:2]1[CH:3]=[C:4]([CH2:9][OH:12])[C:5]([I:8])=[N:6][CH:7]=1
Reactant: O=C([O-])[O-]
Reactant: BrCc1cc(Br)cnc1I
Agent: [Ca+2]
Solvent: O
Solvent: C1COCCO1
Product: OCc1cc(Br)cnc1I
Temperature: 25 °C
Yield: 45.6 %

Procedure:
To a stirred solution of 5-bromo-3-bromomethyl-2-iodo-pyridine (25.0 g, crude, 66.313 mmol, 1 eq) in 1,4-dioxane (200 mL) was added suspension of CaCO3 (34.5 mL, 345 mmol, 5.2 eq) in water (200 mL) at room temperature. Resulting reaction mixture was refluxed for 10 hours. After complete consumption of starting material, reaction mixture was cooled to room temperature and filtered through celite bed over Buchner funnel, celite bed was washed with DCM (2×300 mL). Combined filtrate was washed with water (300 mL) and aqueous sodium bicarbonate (120 mL), dried over sodium sulfate and concentrated under reduced pressure to afford off white solid (15.3 g, crude). Crude compound was purified by washing with n-pentane (2×150 mL) to get desired compound as white solid (9.5 g, impure). Impure title compound was used as such for the next reaction. 1H NMR (400 MHz, CDCl3) δ: 2.14 (t, J=5.8 Hz, 1H), 4.62 (d, J=5.8, 2H), 7.86 (d, J=1.32 Hz, 1H), 8.33 (d, J=3.32, 1H). LC-MS (m/z): 313.9 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[C:12]([O:16][C:17](=[O:27])[N:18]([CH2:22][CH2:23][C:24](=O)[CH3:25])[CH2:19][CH2:20]C)([CH3:15])([CH3:14])[CH3:13].N1CCCC1>CC(O)C>[C:12]([O:16][C:17]([N:18]1[CH2:19][CH2:20][CH2:25][C:24](=[C:6]2[C:5]3[C:9](=[CH:10][C:2]([Cl:1])=[CH:3][CH:4]=3)[NH:8][C:7]2=[O:11])[CH2:23][CH2:22]1)=[O:27])([CH3:13])([CH3:14])[CH3:15]
Reactant: O=C1Cc2ccc(Cl)cc2N1
Reactant: CCCN(CCC(C)=O)C(=O)OC(C)(C)C
Solvent: CC(C)O
Solvent: C1CCNC1
Product: CC(C)(C)OC(=O)N1CCCC(=C2C(=O)Nc3cc(Cl)ccc32)CC1
Temperature: 90 °C

Procedure:
A suspension of 6-chlorooxindole (0.71 g, 4.24 mmol) (Cresent Chem.), (3-oxo-butyl)-propyl-carbamic acid tert-butyl ester (1 g, 4.69 mmol) (Tyger Sci.), and pyrrolidine (0.1 g) (Aldrich) in 2-propanol (15 mL) was heated at 90° C. for 2 days. The mixture was allowed to cool to room temperature. The solvent was removed and the residue was purified by chromatography to give 4-(6-chloro-2-oxo-1,2-dihydro-indol-3-ylidene)-azepane-1-carboxylic acid tert-butyl ester as a brown solid. (Yield: 1.36 g, 88%).
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([Cl:11])[CH:3]=1.[F:12][C:13]1[CH:14]=[CH:15][C:16]([O:22][CH3:23])=[C:17](B(O)O)[CH:18]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:11][C:4]1[CH:3]=[C:2]([C:15]2[CH:14]=[C:13]([F:12])[CH:18]=[CH:17][C:16]=2[O:22][CH3:23])[CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=[O:7]
Reactant: O=C(O)c1ccc(Br)cc1Cl
Reactant: COc1ccc(F)cc1B(O)O
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Solvent: Cc1ccccc1
Product: COc1ccc(F)cc1-c1ccc(C(=O)O)c(Cl)c1
Temperature: 95 °C
Yield: 95.3 %

Procedure:
4-Bromo-2-chlorobenzoic acid (1.1 g) and 5-fluoro-2-methoxyphenylboronic acid (0.94 g) were suspended in toluene (20 mL) and ethanol (20 mL). Aqueous 2M sodium carbonate solution (16 mL) and tetrakis(triphenylphosphine) palladium(0) (0.14 g) were added and the reaction was heated at 95° C. for 20 h. The mixture was diluted with water, extracted with diethyl ether (discarded). The aqueous layer was acidified with aqueous 2M hydrochloric acid, extracted with ethyl acetate, dried (MgSO4) and concentrated under reduced pressure to give the sub titled product as a cream solid (1.25 g).
Reaction SMILES: [NH2:1][C@:2]([CH2:10][CH3:11])([CH2:6][CH2:7][CH2:8][CH3:9])[C:3](O)=[O:4].[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[NH2:1][C@:2]([CH2:10][CH3:11])([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:3][OH:4]
Reactant: CCCC[C@](N)(CC)C(=O)O
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CCCC[C@](N)(CC)CO
Temperature: 25 °C
Reaction time: 16 h
Yield: 82 %

Procedure:
The product (20 g) from step (e) was added to a 1M solution of lithium aluminum hydride (1.5 molar equivalents) in THF and the mixture was refluxed for 3 hours, then stirred for 16 hours at room temperature. The mixture was cooled to about 0° C., then quenched with water and 1N aqueous NaOH. The resulting solid was broken up with additional water and the suspension was heated at 50° C. for 5 minutes, then cooled to room temperature. Diethyl ether (100 ml) was added, the mixture was stirred and filtered. The diethyl ether layer was separated, dried and concentrated in vacuo to give the desired product as an oil (82% yield), 1H NMR consistent with the proposed structure.
Reaction SMILES: [C:1]1([CH:7]([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[C:8]([O:10][CH3:11])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[C:25](Cl)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>CC#N.C(OCC)(=O)C>[C:25]([N:15]1[CH2:16][CH2:17][CH:12]([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:8]([O:10][CH3:11])=[O:9])[CH2:13][CH2:14]1)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: COC(=O)C(c1ccccc1)C1CCNCC1
Solvent: CCOC(C)=O
Solvent: CC#N
Solvent: CCN(CC)CC
Product: COC(=O)C(c1ccccc1)C1CCN(C(=O)c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 85.2 %

Procedure:
To a stirring solution of compound 92 (0.159 g, 0.682 mmol) and triethylamine (0.2 mL, 1.435 mmol) in MeCN (10 mL) was added benzoyl chloride (0.10 mL, 0.862 mmol) and the reaction mixture was stirred for 2 h at room temperature. The reaction was diluted with ethyl acetate, washed with sat. aq. Na2CO3, water, brine, dried over Na2SO4, filtered and concentrated to afford the desired compound (0.196 g, 85%) as a colorless oil. LRMS (ESI): (calc) 337.41 (found) 338.35 (MH)+
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N+:10]([O-:12])=[O:11])[CH:5]=[CH:6][CH:7]=1.[BH4-].[Na+]>O1CCOCC1.C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][N+:10]([O-:12])=[O:11])[CH:5]=[CH:6][CH:7]=1
Reactant: O=[N+]([O-])C=Cc1cccc(Cl)c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: C1COCCO1
Product: O=[N+]([O-])CCc1cccc(Cl)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 47.1 %

Procedure:
A solution of 13.5 g (72 mmol) of 2-(3-Chlorophenyl)-1-nitroethene, from Step 2, in 200 mL of dioxane was added dropwise to a stirred suspension of 6 g (157 mmol) of sodium borohydride in a mixture of 140 mL of dioxane and 60 mL of ethanol. The reaction mixture was stirred at ambient temperature for 2 h and then the excess borohydride was quenched with acid. The reaction mixture was concentrated in vacuo and the residue was partitioned between methylene chloride and water (4:1). The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified on silica gel eluted with 20% methylene chloride in hexane to afford 6.3 g (48% yield) of the title compound; MS DCl--NH3M/Z: 203 (M+NH4)+ ; 1H NMR (CDCl3) δ3.3 (2H, t, J=7.5 Hz), 4.6 (2H, t, J= 7.5 Hz), 7.05-7.3 (4H, m).
Reaction SMILES: CO.[OH-].[K+].[CH2:5]([Si:8]([CH3:25])([CH3:24])[Si:9]([CH3:23])([CH3:22])[C:10]1[CH:15]=[CH:14][C:13]([C:16]#[C:17][Si](C)(C)C)=[CH:12][CH:11]=1)[CH:6]=[CH2:7]>Cl>[CH2:5]([Si:8]([CH3:24])([CH3:25])[Si:9]([C:10]1[CH:15]=[CH:14][C:13]([C:16]#[CH:17])=[CH:12][CH:11]=1)([CH3:23])[CH3:22])[CH:6]=[CH2:7]
Reactant: C=CC[Si](C)(C)[Si](C)(C)c1ccc(C#C[Si](C)(C)C)cc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: C#Cc1ccc([Si](C)(C)[Si](C)(C)CC=C)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 65 %

Procedure:
45 mL of methanol containing 1.98 g (30 mmol) of potassium hydroxide was added to 45 mL of methanol containing 9.92 g (30 mmol) of 1-allyl-1,1,2,2-tetramethyl-2-(4-trimethylsilanylethynylphenyl) disilane to obtain a mixture, which was stirred for 30 minutes at a temperature of 0° C. Further, the resultant solution was turned acidic by adding 30 mL of 1M hydrochloric acid thereto and subjected to extraction using ether. The organic layer thus created was then washed with saturated sodium hydrogen carbonate and also with saturated brine and dried using magnesium sulfate as a desiccating agent. After the desiccating agent was removed by filtration, the solvent was removed by a rotary evaporator to obtain a crude product, which was then purified by silica gel column chromatography (developing solvent: hexane) to obtain 5.03 g (19.44 mmol) of 1-allyl-2-(4-ethynyl-phenyl)-1,1,2,2-tetramethyl-disilane (4a) which was colorless and oily. The yield was 65%.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[C:9]([C:11](O)=[O:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.B>>[Br:1][C:2]1[CH:10]=[C:9]([CH2:11][OH:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2
Reactant: O=C(O)c1cc(Br)c2cn[nH]c2c1
Agent: B
Product: OCc1cc(Br)c2cn[nH]c2c1
Yield: 88.1 %

Procedure:
According to the method of A52A, 4-bromo-1H-indazole-6-carboxylic acid (1 g, 4 mmol) was reacted with borane (6 ml, 6 mmol) to give the title compound as a pale yellow solid (800 mg, 88%). MS ESI [M+H]+, calcd for [C8H7BrN2O+H]+ 227.0, 229.0; found m/z 226.9, 228.9.
Reaction SMILES: [C:1]([NH:4][C:5]([CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1)([CH2:13][CH2:14][CH:15]=[CH2:16])[C:6]([NH:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])(=[O:3])[CH3:2].[CH3:25][C:26]1([CH3:33])[C:30]([CH3:32])([CH3:31])[O:29][BH:28][O:27]1.O>ClCCl.[Ir+].ClC1CCC=CCCC=1.C1(P(C2C=CC=CC=2)CCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([NH:4][C:5]([CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1)([CH2:13][CH2:14][CH2:15][CH2:16][B:28]1[O:29][C:30]([CH3:32])([CH3:31])[C:26]([CH3:33])([CH3:25])[O:27]1)[C:6]([NH:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])(=[O:3])[CH3:2]
Reactant: CC1(C)OBOC1(C)C
Reactant: C=CCCC(CCc1ccccn1)(NC(C)=O)C(=O)NC(C)(C)C
Agent: [Ir+]
Agent: ClC1=CCCC=CCC1
Agent: c1ccc(P(CCP(c2ccccc2)c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: O
Product: CC(=O)NC(CCCCB1OC(C)(C)C(C)(C)O1)(CCc1ccccn1)C(=O)NC(C)(C)C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 69.9 %

Procedure:
A solution of 2-acetamido-N-tert-butyl-2-(2-(pyridin-2-yl)ethyl)hex-5-enamide (810 mg, 2.45 mmol) in dichloromethane (4 mL), was treated with chloro-1,5-cyclooctadiene iridium(I) dimer (35 mg, 2 mol %) and 1,2-bis(diphenylphosphino)ethane (42 mg, 4 mol %). The solution was stirred at room temperature for 30 minutes and then 4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (0.76 mL, 5.20 mmol) was added dropwise, and the reaction was then stirred overnight at room temperature. The reaction was poured into water and extracted with ethyl acetate (3×). The combined organic phase was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated. Purification by flash column chromatography (silica gel, 0-10% methanol in dichloromethane) gave 2-acetamido-N-tert-butyl-2-(2-(pyridin-2-yl)ethyl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanamide as a colorless oil (787 mg, 70%). ESI MS found for C25H42BN3O4 m/z [460.3 (M+1)].
Reaction SMILES: [CH2:1]=[CH:2][CH2:3][CH3:4].[Al].Cl>C1(C)C=CC=CC=1.CO.[Cr]>[CH2:1]=[CH:2][CH2:3][CH2:4][CH2:1][CH2:2][CH2:3][CH2:4][CH2:1][CH2:2][CH2:3][CH3:4]
Reactant: C=CCC
Agent: [Cr]
Agent: Cl
Agent: [Al]
Solvent: Cc1ccccc1
Solvent: CO
Product: C=CCCCCCCCCCC
Temperature: 40 °C
Reaction time: 1 h

Procedure:
42.1 μmol of (1,3,5-tris-n-dodecyl-1,3,5-triazacyclohexane)CrCl3 together with 250 ml of toluene were placed under an argon atmosphere in a one liter four-necked flask provided with contact thermometer, stirrer, heating metal and gas inlet tube at 40° C. The solution was saturated with butene. 14.74 mmol of methylaluminoxane (MAO), corresponding to a molar ratio of aluminum:chromium of 350, were then added in the form of a 1.6 M solution in toluene. 1-butene was passed through the light-green/yellow solution obtained after the addition of the MAO. After one hour, a further 40.2 μmol of chromium complex were added, so that the molar ratio of aluminum:chromium was now 180. After a further hour, another 40.5 μmol of chromium complex were added and the molar ratio of aluminum:chromium was then 120. After a total of 3 hours, the reaction was stopped by addition of 15 ml of concentrated hydrochloric acid in 50 ml of methanol and the reaction mixture was stirred for another 15 minutes. 250 ml of methanol were then added and the mixture was stirred for a further 15 minutes. The product was washed three times with water and dried over sodium sulfate. The yield of dodecene was determined by gas-chromatographic analysis of the solution obtained in this way. A total of 25.8 g of dodecene had been formed.
Reaction SMILES: C[O:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19]C)[CH:14]=3)[CH:9]=2)[CH:4]=1.Cl.[NH+]1C=CC=CC=1>>[OH:19][C:15]1[CH:14]=[C:13]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[CH:4]=[C:3]([OH:2])[CH:12]=[CH:11]3)[CH:18]=[CH:17][CH:16]=1
Reactant: COc1cccc(-c2ccc3cc(OC)ccc3c2)c1
Agent: Cl
Agent: c1cc[nH+]cc1
Product: Oc1cccc(-c2ccc3cc(O)ccc3c2)c1

Procedure:
The title compound was prepared by reacting 2-methoxy-6-(3-methoxyphenyl)naphthalene (0.51 g, 1.90 mmol) with pyridinium HCl (6 g) at 190° C. according to method B to yield 0.21 g (47%) of an off white solid: mp 192-194° C.; 1H NMR (DMSO-d6): δ 6.75-6.78 (1H, m), 7.10-7.14 (3H, m), 7.16-7.18 (1H, m), 7.65 (1H, dd, J=1.79 Hz, J=8.57 Hz), 7.75 (1H, d, J=8.77 Hz), 7.84 (1H, d, J=8.77 Hz), 8.01 (1H, d, J=1.59 Hz), 9.51 (1H, s), 9.78, (1H, s); MS (ESI) m/z 235 (M−H)−. Anal. for C16H12O2:
Reaction SMILES: [OH-].[Li+].[C:3]([O:7][C:8]([NH:10][CH2:11][CH2:12][CH2:13][N:14]1[C:18]2[CH:19]=[C:20]([C:23]([O:25]C)=[O:24])[CH:21]=[CH:22][C:17]=2[N:16]=[C:15]1[NH:27][C:28]1[CH:33]=[C:32]([O:34][CH3:35])[C:31]([O:36][CH3:37])=[C:30]([O:38][CH3:39])[CH:29]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4]>O1CCCC1.O>[C:3]([O:7][C:8]([NH:10][CH2:11][CH2:12][CH2:13][N:14]1[C:18]2[CH:19]=[C:20]([C:23]([OH:25])=[O:24])[CH:21]=[CH:22][C:17]=2[N:16]=[C:15]1[NH:27][C:28]1[CH:29]=[C:30]([O:38][CH3:39])[C:31]([O:36][CH3:37])=[C:32]([O:34][CH3:35])[CH:33]=1)=[O:9])([CH3:5])([CH3:4])[CH3:6]
Reactant: COC(=O)c1ccc2nc(Nc3cc(OC)c(OC)c(OC)c3)n(CCCNC(=O)OC(C)(C)C)c2c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: COc1cc(Nc2nc3ccc(C(=O)O)cc3n2CCCNC(=O)OC(C)(C)C)cc(OC)c1OC
Temperature: 25 °C

Procedure:
Lithium hydroxide (2.18 g, 6 eq) is added to a solution of methyl 1-{3-[(tert-butoxycarbonyl)amino]propyl}-2-[(3,4,5-trimethoxyphenyl)amino]-1H-benzimidazole-6-carboxylate (4.4 g, 1 eq) in a mixture of tetrahydrofuran (40 ml) and water (30 ml). The mixture is heated under reflux for 18 hours then cooled down to ambient temperature and concentrated under reduced pressure at 40° C. Dichloromethane (150 ml) and water (100 ml) are added to the residue. The mixture is acidified by the addition of acetic acid to pH 5. After decantation and extractions, the combined organic phases are dried over sodium sulphate and concentrated under reduced pressure. The solid obtained is washed with ethyl ether (3.95 g; 93%).