Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [S:1]1[CH2:5][CH2:4][N:3]=[C:2]1[N:6]1[C:10]2[CH:11]=[C:12]([C:15](=[CH2:22])[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[NH2:23].[Br:24]N1C(=O)CCC1=O>O1CCCC1>[S:1]1[CH2:5][CH2:4][N:3]=[C:2]1[N:6]1[C:10]2[CH:11]=[C:12]([C:15](=[CH:22][Br:24])[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[NH2:23]
Reactant: O=C1CCC(=O)N1Br
Reactant: C=C(c1ccccc1)c1ccc2nc(N)n(C3=NCCS3)c2c1
Solvent: C1CCOC1
Product: Nc1nc2ccc(C(=CBr)c3ccccc3)cc2n1C1=NCCS1
Temperature: 25 °C
Yield: 30 %

Procedure:
To a stirred solution of 1.6 g. (5 mM) of 1-(thiazolin-2-yl)-2-amino-6-(α-methylenebenzyl)benzimidazole in 150 ml. of tetrahydrofuran were added in one portion 900 mg. (0.5 mM) of N-bromosuccinimide. The reaction mixture was stirred at room temperature for seventy-two hours, and then was concentrated to a volume of about 10 ml. by evaporation of the solvent under reduced pressure. The reaction mixture was diluted with 20 ml. of water, and the crystalline precipitate that formed was collected by filtration and identified as 600 mg. of 1-(thiazolin-2-yl)-2-amino-6-(α-bromomethylenebenzyl)benzimidazole. M.P. 197°-199° C. Yield 30%.
Reaction SMILES: [OH:1][CH2:2][CH2:3][NH:4][C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[CH:7][C:6]=1[N+:13]([O-:15])=[O:14].N[CH2:17][CH2:18][O:19]CCO.C(CN)O>>[OH:19][CH2:18][CH2:17][O:1][CH2:2][CH2:3][NH:4][C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[CH:7][C:6]=1[N+:13]([O-:15])=[O:14]
Reactant: NCCOCCO
Reactant: N#Cc1ccc(NCCO)c([N+](=O)[O-])c1
Solvent: NCCO
Product: N#Cc1ccc(NCCOCCO)c([N+](=O)[O-])c1

Procedure:
Preparation is similar to the synthesis in (a) above, except that 2-(2-aminoethoxy)ethanol is used in lieu of monoethanolamine.
Reaction SMILES: [C:1]1([C:7]2[C:12]([C:13]([O:15]C)=[O:14])=[CH:11][N:10]=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].Cl>CO>[C:1]1([C:7]2[C:12]([C:13]([OH:15])=[O:14])=[CH:11][N:10]=[CH:9][CH:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: COC(=O)c1cnccc1-c1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)c1cnccc1-c1ccccc1
Temperature: 25 °C
Reaction time: 6 h
Yield: 132.5 %

Procedure:
To a solution containing methyl 4-phenylnicotinate (3.8 g, 17.8 mmol) from the previous step in methyl alcohol (20 mL) was added 1 N sodium hydroxide (21.4 mL). The mixture was stirred at room temperature for 6 hours, neutralized with 1 N hydrochloric acid, evaporated in vacuo and dried overnight to yield the solid 4-phenylnicotinic acid (4.7 g, Theo. Yield=3.6 g, balance is NaCl); HPLC RT=1.80 min, method A; LC-MS m/z=200; 1H NMR, 400 MHz, CD3OD, 8.91 ppm (s, 1H), 8.66 ppm (d, 1H), 7.48 ppm (d, 1H), 7.46-7.41 ppm (m, 5H).
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:12]([CH2:31][O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[O:11][C@H:10]1[C:40]1[C:48]2[C:43](=[C:44]([CH3:49])[CH:45]=[CH:46][CH:47]=2)[NH:42][CH:41]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:53][C:54]1[CH:63]=[CH:62][C:57]([C:58]([O:60][CH3:61])=[O:59])=[CH:56][CH:55]=1.Cl>CN(C)C=O>[CH2:1]([O:8][C@@H:9]1[C@@H:14]([O:15][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@H:12]([CH2:31][O:32][CH2:33][C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[O:11][C@H:10]1[C:40]1[C:48]2[C:43](=[C:44]([CH3:49])[CH:45]=[CH:46][CH:47]=2)[N:42]([CH2:53][C:54]2[CH:55]=[CH:56][C:57]([C:58]([O:60][CH3:61])=[O:59])=[CH:62][CH:63]=2)[CH:41]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)c1ccc(CBr)cc1
Reactant: Cc1cccc2c([C@@H]3O[C@H](COCc4ccccc4)[C@@H](OCc4ccccc4)[C@H](OCc4ccccc4)[C@H]3OCc3ccccc3)c[nH]c12
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(Cn2cc([C@@H]3O[C@H](COCc4ccccc4)[C@@H](OCc4ccccc4)[C@H](OCc4ccccc4)[C@H]3OCc3ccccc3)c3cccc(C)c32)cc1
Reaction time: 0.25 h
Yield: 93.2 %

Procedure:
To a solution of 3-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-7-methyl-1H-indole (0.28 g) in N,N-dimethyl-formamide (4 mL) was added 55% sodium hydride (22 mg) under ice-cooling, and the mixture was stirred at the same temperature for 15 minutes. To this mixture was added methyl 4-(bromo-methyl)benzoate (0.12 g) at the same temperature, and the mixture was stirred at the same temperature for 15 minutes, and stirred at room temperature for 1 hour. The reaction mixture was poured into 0.5 mol/L hydrochloric acid, and the resulting mixture was extracted with diethyl ether. The extract was washed with water and brine successively, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=5/1-3/1) to give 3-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-1-[4-(methoxycarbonyl)benzyl]-7-methyl-1H-indole (0.32 g). This material was dissolved in a mixed solvent of ethanol (5 mL) and tetra hydrofuran (2.5 mL). To the solution was added potassium hydroxide (0.45 g), and the mixture was stirred at 50° C. overnight. The reaction mixture was poured into 1 mol/L hydrochloric acid (10 mL), and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine successively, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give the title compound (0.31 g)
Reaction SMILES: [OH:1][CH:2]([C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1)[C:3]#[C:4][C:5]1([OH:15])[CH2:14][CH2:13][C:8]2([O:12][CH2:11][CH2:10][O:9]2)[CH2:7][CH2:6]1>ClCCl.[O-2].[O-2].[Mn+4]>[OH:15][C:5]1([C:4]#[C:3][C:2]([C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)=[O:1])[CH2:14][CH2:13][C:8]2([O:12][CH2:11][CH2:10][O:9]2)[CH2:7][CH2:6]1
Reactant: Cc1ccc(C(O)C#CC2(O)CCC3(CC2)OCCO3)cc1
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCl
Product: Cc1ccc(C(=O)C#CC2(O)CCC3(CC2)OCCO3)cc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 82.2 %

Procedure:
To a solution of 8-(3-hydroxy-3-(p-tolyl)propyn-1-yl)-1,4-dioxaspiro[4.5]decan-8-ol (Reference Example 3) (17.5 g, 57.9 mmol) in dichloromethane (289 mL), manganese dioxide (29.6 g, 289 mmol) was added, and the obtained solution was stirred at room temperature for 15 hours. The reaction solution was filtered through Celite and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, n-hexane/ethyl acetate) to obtain the captioned compound (14.3 g, 47.6 mmol, 82%) as an oily product.
Reaction SMILES: [F:1][C:2]([F:28])([F:27])[C:3]([CH2:18][NH:19]CC1C=CC=CC=1)([OH:17])[CH2:4][C:5]([C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[O:15][CH3:16])([CH3:7])[CH3:6].[H][H]>C(O)C.[Pd]>[NH2:19][CH2:18][C:3]([OH:17])([CH2:4][C:5]([C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[O:15][CH3:16])([CH3:7])[CH3:6])[C:2]([F:28])([F:27])[F:1]
Reactant: COc1ccc(F)cc1C(C)(C)CC(O)(CNCc1ccccc1)C(F)(F)F
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: COc1ccc(F)cc1C(C)(C)CC(O)(CN)C(F)(F)F
Yield: 97.2 %

Procedure:
1,1,1-Trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-4-methyl-2-{[(phenylmethyl)amino]methyl}-2-pentanol (Intermediate 17, 63 g, 0.158 mol) was added to a stirred solution of 10% Pd/C (12.6 g, 50% wet) in ethanol (1.07 L) at 20° C. in a nitrogen purged vessel. The mixture was hydrogenated at 20° C. and atmospheric pressure until there was no further hydrogen uptake. The suspension was then filtered through Celite and glass fibre filter paper to remove the catalyst, and the cake washed with ethanol (120 mL). The combined filtrate and washings were evaporated under reduced pressure to give the title compound as a light grey solid (47.5 g).
Reaction SMILES: [CH2:1]([C:3]([CH3:6])=[N:4][OH:5])[CH3:2].[N:7]1[C:14](Cl)=[N:13][C:11](Cl)=[N:10][C:8]=1Cl>N1C=CC=CC=1>[CH3:6]/[C:3](=[N:4]\[O:5][C:8]1[N:10]=[C:11]([O:5]/[N:4]=[C:3](/[CH3:6])\[CH2:1][CH3:2])[N:13]=[C:14]([O:5][N:4]=[C:3]([CH2:1][CH3:2])[CH3:6])[N:7]=1)/[CH2:1][CH3:2]
Reactant: CCC(C)=NO
Reactant: Clc1nc(Cl)nc(Cl)n1
Solvent: c1ccncc1
Product: CCC(C)=NOc1nc(O/N=C(/C)CC)nc(O/N=C(\C)CC)n1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a cold (0° C.) solution of ethylmethyl-ketoxime (4.18 g, 0.048 mol) in dry pyridine (16 ml) is added cyanuric chloride (2.21 g, 0.012 mol). An exothermic reaction occurs and the temperature rises to 16° C. The solution is then stirred 12 h at room temperature and then poured into 150 ml of ice-cold water. The resulting emulsion is extracted with dichloromethane (3×30 ml), the extracts are dried over MgSO4 and the solvent is evaporated. The residue is chromatographed (silica gel, CH2Cl2—C2H5O(CO)CH3 8:3) to afford 3.72 g of the title compound as a colorless oil which slowly solidifies on standing, mp. 51-56° C.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[I:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1.CS(O[CH:20]([CH3:42])[CH2:21][O:22][C:23]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)(=O)=O>O>[I:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH:20]([CH3:42])[CH2:21][O:22][C:23]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[CH:10][CH:9]=1
Reactant: CC(COC(c1ccccc1)(c1ccccc1)c1ccccc1)OS(C)(=O)=O
Reactant: Oc1ccc(I)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: CC(COC(c1ccccc1)(c1ccccc1)c1ccccc1)Oc1ccc(I)cc1
Reaction time: 24 h
Yield: 46.1 %

Procedure:
To a solution of potassium carbonate (0.63 g, 4.5 mmol) in dimethylformaide (10 mL) was purged with nitrogen for 10 min at 75° C. 4-iodophenol (0.55 g, 2.5 mmol) was added to the mixture and the solution was purged with nitrogen for additional 10 min. To the reaction mixture 1-(trityloxy)propan-2-yl methanesulfonate (1.00 g, 2.53 mmol) was added and stirred for 24 hours at the same temperature. The reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (20 mL*3). The combined organic layer was dried over sodium sulfate and concentrated. The crude product was purified by combiflash silica gel chromatography (petroleum ether:ethyl acetate=10:1) to give the title compound (600 mg, 46%) as colorless oil.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[C:7]2[CH3:12].[C:13](OC(=O)C)(=[O:15])[CH3:14]>N1C=CC=CC=1>[C:13]([O:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[C:7]2[CH3:12])(=[O:15])[CH3:14]
Reactant: Cc1nccc2c(O)cccc12
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)Oc1cccc2c(C)nccc12

Procedure:
For example, 5-hydroxy-1-methylisoquinoline 64.9, prepared as described in J. Med. Chem., 1968, 11, 700, is reacted with acetic anhydride in pyridine to afford 5-acetoxy-1-methylisoquinoline 64.10. The latter compound is reacted with N-bromosuccinimide in refluxing ethyl acetate to yield 5-acetoxy-1-bromomethylisoquinoline 64.11. The product is then reacted with five molar equivalents of a trialkyl phosphite at 120° to give the phosphonate product 64.12. The acetoxy group is hydrolyzed by reaction with sodium bicarbonate in aqueous methanol as described in J. Am. Chem. Soc., 93, 746, 1971, to produce the phenol 64.13.
Reaction SMILES: [CH:1]1([N:4]([CH2:39][C:40]2[CH:45]=[C:44]([CH2:46][CH2:47][CH2:48][O:49][CH3:50])[CH:43]=[C:42]([OH:51])[CH:41]=2)[C:5]([C@@H:7]2[C@@H:12]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][O:22][C:23]4[C:28]([Cl:29])=[CH:27][C:26]([CH3:30])=[CH:25][C:24]=4[Cl:31])=[CH:15][CH:14]=3)[CH2:11][CH2:10][N:9]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:8]2)=[O:6])[CH2:3][CH2:2]1.Br[CH2:53][CH2:54][CH2:55][C:56]([O:58][CH2:59][CH3:60])=[O:57].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O>[CH:1]1([N:4]([CH2:39][C:40]2[CH:45]=[C:44]([CH2:46][CH2:47][CH2:48][O:49][CH3:50])[CH:43]=[C:42]([O:51][CH2:53][CH2:54][CH2:55][C:56]([O:58][CH2:59][CH3:60])=[O:57])[CH:41]=2)[C:5]([C@@H:7]2[C@@H:12]([C:13]3[CH:14]=[CH:15][C:16]([O:19][CH2:20][CH2:21][O:22][C:23]4[C:28]([Cl:29])=[CH:27][C:26]([CH3:30])=[CH:25][C:24]=4[Cl:31])=[CH:17][CH:18]=3)[CH2:11][CH2:10][N:9]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:8]2)=[O:6])[CH2:3][CH2:2]1
Reactant: COCCCc1cc(O)cc(CN(C(=O)[C@H]2CN(C(=O)OC(C)(C)C)CC[C@@H]2c2ccc(OCCOc3c(Cl)cc(C)cc3Cl)cc2)C2CC2)c1
Reactant: CCOC(=O)CCCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCOC(=O)CCCOc1cc(CCCOC)cc(CN(C(=O)[C@H]2CN(C(=O)OC(C)(C)C)CC[C@@H]2c2ccc(OCCOc3c(Cl)cc(C)cc3Cl)cc2)C2CC2)c1
Temperature: 80 °C

Procedure:
To a solution of tert-butyl (3R,4S)-3-({cyclopropyl[3-hydroxy-5-(3-methoxy-propyl)benzyl]amino}carbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]-phenyl}piperidine-1-carboxylate (1 eq.) from Example 1/Step 2 in DMF (0.2 M) was added ethyl 4-bromobutanoate (1.6 eq.) and cesium carbonate (1.3 eq.). The reaction was heated to 80° C. for 3 h. After cooling down to rt, the reaction was diluted with EtOAc. The organic extract was washed with water, brine, dried over MgSO4, and concentrated in vacuo. The crude product was purified by flash column chromatography (SiO2, 50% EtOAc in Hex) to afford the title compound as an oil.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1)#[N:2].[N-:10]=[N+:11]=[N-:12].[Na+].Cl>C1(C)C=CC=CC=1>[NH:10]1[C:1]([C:3]2[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=2)=[N:2][N:12]=[N:11]1
Reactant: N#Cc1ccc(O)cc1
Reactant: [N-]=[N+]=[N-]
Agent: Cl
Agent: [Na+]
Solvent: Cc1ccccc1
Product: Oc1ccc(-c2nnn[nH]2)cc1
Temperature: 100 °C
Yield: 109.8 %

Procedure:
A 50 mL round bottomed flask equipped with a Teflon coated magnetic stirring bar, and a rubber septum was charged with 4-cyanophenol (596 mg, 5.0 mmol), sodium azide (975 mg, 15 mmol), triethylamineo.HCl (2.06 g, 15 mmol) and toluene (25 mL). The reaction mixture was heated at 100° C. for 18 h with vigorous stirring. The reaction mixture was cooled to ambient temperature and poured into a separatory funnel and extracted with H2O (3×10 mL). The combined aqueous phases were treated dropwise with HCl (conc.) to precipitate the product from the reaction mixture. The precipitate was collected by vacuum filtration and dried under vacuum to afford the title compound as an off-white solid (890 mg, 94%).
Reaction SMILES: [CH:1]1[C:11]2[CH2:10][CH2:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[C:6](=[CH:16][C:17]3[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[C:24](Cl)(=[O:31])[C:25]1[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=1>>[CH:1]1[C:11]2[CH2:10][CH2:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[C:6](=[CH:16][C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24](=[O:31])[C:25]4[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=4)=[CH:19][CH:18]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: Nc1ccc(C=C2c3ccccc3CCc3ccccc32)cc1
Reactant: O=C(Cl)c1ccncc1
Product: O=C(Nc1ccc(C=C2c3ccccc3CCc3ccccc32)cc1)c1ccncc1
Yield: 17 %

Procedure:
Following procedures essentially as described in Example 90, 4-(10,11-dihydro-dibenzo[a,d]cyclohepten-5-ylidenemethyl)-phenylamine and isonicotinoyl chloride give the title compound in 17% yield as a yellow solid, mp 252.1° C. 1H NMR (DMSO-d6) δ 2.94 (br s, 2H), 3.87 (br s, 2H), 6.82 (s, 1H), 6.90-7.62 (m, 12H), 7.83 (d, 2H), 8.79 (d, 2H), 10.47 (s, 1H); MS (ES) 403 (M+H), 401 (M−H). HPLC shows 93% purity.
Reaction SMILES: [N:1]1([C:7]([N:9]2[CH2:14][CH:13]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=3)[CH2:12][CH:11]([C:26](O)=[O:27])[CH2:10]2)=[O:8])[CH2:6][CH2:5][S:4][CH2:3][CH2:2]1.O[N:30]=[C:31]([CH:33]1[CH2:35][CH2:34]1)[NH2:32]>>[CH:33]1([C:31]2[N:32]=[C:26]([CH:11]3[CH2:12][CH:13]([C:15]4[CH:16]=[CH:17][C:18]([CH2:21][C:22]([F:25])([F:24])[F:23])=[CH:19][CH:20]=4)[CH2:14][N:9]([C:7]([N:1]4[CH2:6][CH2:5][S:4][CH2:3][CH2:2]4)=[O:8])[CH2:10]3)[O:27][N:30]=2)[CH2:35][CH2:34]1
Reactant: O=C(O)C1CC(c2ccc(CC(F)(F)F)cc2)CN(C(=O)N2CCSCC2)C1
Reactant: NC(=NO)C1CC1
Product: O=C(N1CCSCC1)N1CC(c2ccc(CC(F)(F)F)cc2)CC(c2nc(C3CC3)no2)C1

Procedure:
According to General Method 6A, 300 mg (0.720 mmol) of the compound from Example 45A and 79.3 mg (0.792 mmol) of N′-hydroxycyclopropanecarboximidamide were reacted Yield: 160 mg (45% of theory)
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:10]3[CH2:12][CH:13]([CH3:16])[CH2:14][CH2:15][C:9]=3[C:8]([CH3:18])([CH3:17])[O:7][C:6]=2[CH:5]=[C:4]([CH3:19])[CH:3]=1.[C:20](OC(=O)C)(=[O:22])[CH3:21]>N1C=CC=CC=1>[C:20]([O:1][C:2]1[C:11]2[C:10]3[CH2:12][CH:13]([CH3:16])[CH2:14][CH2:15][C:9]=3[C:8]([CH3:18])([CH3:17])[O:7][C:6]=2[CH:5]=[C:4]([CH3:19])[CH:3]=1)(=[O:22])[CH3:21]
Reactant: CC(=O)OC(C)=O
Reactant: Cc1cc(O)c2c(c1)OC(C)(C)C1=C2CC(C)CC1
Solvent: c1ccncc1
Product: CC(=O)Oc1cc(C)cc2c1C1=C(CCC(C)C1)C(C)(C)O2
Temperature: 25 °C

Procedure:
A solution of 1-hydroxy-7,8,9,10-tetrahydro-3,6,6,9-tetramethyl-6H-dibenzo[ b,d]pyran (9.07 g., 0.035 mole) and acetic anhydride (7.1 g., 0.07 mole) in 25 ml. of pyridine was warmed over a steam bath for 2 hours. The reaction mixture was allowed to cool to room temperature and pyridine was removed by evaporation under reduced pressure. Water was added to the residue and the aqueous mixture was extracted with three portions of ether. The ethereal extracts were combined, washed with water, 6N HCl, again with water, dried over Na2SO4 and concentrated under reduced pressure to 9.5 g. (90%) of a colorless solid, m.p. 115°-119° C.
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]1[CH:19]=[CH:18][C:7]([C:8]([NH:10][CH2:11][CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[O:9])=[CH:6][CH:5]=1.[F:20][C:21]([F:33])([F:32])[O:22][C:23]1[CH:28]=[CH:27][C:26]([N:29]=[C:30]=[O:31])=[CH:25][CH:24]=1>C(#N)C.C(N(C(C)C)CC)(C)C>[CH2:16]([O:15][C:13](=[O:14])[CH2:12][CH2:11][NH:10][C:8](=[O:9])[C:7]1[CH:6]=[CH:5][C:4]([CH2:3][NH:2][C:30]([NH:29][C:26]2[CH:27]=[CH:28][C:23]([O:22][C:21]([F:20])([F:32])[F:33])=[CH:24][CH:25]=2)=[O:31])=[CH:19][CH:18]=1)[CH3:17]
Reactant: O=C=Nc1ccc(OC(F)(F)F)cc1
Reactant: CCOC(=O)CCNC(=O)c1ccc(CN)cc1
Agent: Cl
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)CCNC(=O)c1ccc(CNC(=O)Nc2ccc(OC(F)(F)F)cc2)cc1
Temperature: 25 °C

Procedure:
Ethyl 3-(4-Aminomethylbenzoylamino)propanoate hydrochloride (0.25 g, 0.87 mmol) in acetonitrile (5 mL) and diisopropylethylamine (0.15 mL) was allowed to react with 4-trifluoromethoxyphenylisocyanate (0.37 g, 1.74 mmol) at 50° C. overnight. Upon cooling to 25° C. the product precipitated and was collected by filtration.
Reaction SMILES: [Cl:1][C:2]1[N:19]=[C:5]2[N:6]([CH2:10][C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[O:12])[CH:7]=[CH:8][CH:9]=[C:4]2[C:3]=1[CH2:20][C:21]#[N:22].[BH4-].[Na+]>CO>[Cl:1][C:2]1[N:19]=[C:5]2[N:6]([CH2:10][CH:11]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[OH:12])[CH:7]=[CH:8][CH:9]=[C:4]2[C:3]=1[CH2:20][C:21]#[N:22]
Reactant: N#CCc1c2cccn(CC(=O)c3ccccc3)c-2nc1Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: N#CCc1c2cccn(CC(O)c3ccccc3)c-2nc1Cl
Yield: 44.9 %

Procedure:
A solution of 2-chloro-3-cyanomethyl-7-phenacylpyrrolo(2,3-b]pyridine (15 mg 0.05 mmol) in 3 ml MeOH was treated with 10 mg NaBH4 and allowed to react for 30 min at room temperature. The solvent was evaporated and the residue partitioned between CH2Cl2 and water. The organic layer was separated, dried over Na2SO4 and evaporated. Chromatography on silica gel eluting with ether gave the desired product (7 mg 46%).
Reaction SMILES: Cl[C:2](=[Ti:4]([CH:10]1[CH:14]=[CH:13][CH:12]=[CH:11]1)[CH:5]1[CH:9]=[CH:8][CH:7]=[CH:6]1)Cl.C1(C)C=CC=CC=1.[CH3:22][Al:23]1[CH2:28][CH2:27][CH2:26][CH2:25][O:24]1.CCCCCC>C1C=CC=CC=1>[CH2:2]=[Ti:4]([CH:5]1[CH:6]=[CH:7][CH:8]=[CH:9]1)[CH:10]1[CH:14]=[CH:13][CH:12]=[CH:11]1.[CH3:22][Al:23]1[CH2:28][CH2:27][CH2:26][CH2:25][O:24]1
Reactant: ClC(Cl)=[Ti](C1C=CC=C1)C1C=CC=C1
Agent: C[Al]1CCCCO1
Solvent: c1ccccc1
Solvent: CCCCCC
Solvent: Cc1ccccc1
Product: C=[Ti](C1C=CC=C1)C1C=CC=C1
Temperature: -20 °C
Reaction time: 1 h
Yield: 82 %

Procedure:
In a nitrogen-purged Schlenk reaction vessel, 97.4 mg (0.37 mmol) of dichloromethylenebis(cyclopentadienyl)titanium was weighted out. Thereto 20 ml of dried toluene was added, and the mixture was cooled to -20° C. A solution of 1.4 mmol of methylalumoxane (tetramer) in benzene was added thereto dropwise with stirring over one hour. The reaction solution was gradually brought to room temperature, and then stirred continuously for 2 days. The reaction solution changed gradually its color from violet to reddish brown. Hexane was added thereto, and the formed precipitate was collected by filtration, dried and recrystallized. The yield was 82%.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].Br[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]Br.[F:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2([NH2:28])[CH2:26][CH:25]3[CH2:27][CH:22]2[CH2:23][CH2:24]3)=[CH:17][CH:16]=1>CN(C=O)C>[F:14][C:15]1[CH:16]=[CH:17][C:18]([C:21]2([N:28]3[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]3)[CH2:26][CH:25]3[CH2:27][CH:22]2[CH2:23][CH2:24]3)=[CH:19][CH:20]=1
Reactant: NC1(c2ccc(F)cc2)CC2CCC1C2
Reactant: BrCCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Fc1ccc(C2(N3CCCCC3)CC3CCC2C3)cc1
Temperature: 50 °C
Reaction time: 8 h
Yield: 69.9 %

Procedure:
Anhydrous potassium carbonate (0.94 g, 6.8 mmol) and 1,5-dibromopentane (0.47 ml, 3.4 mmol) were added to a crude base of (±)2-(4-fluoro-phenyl)-bicyclo[2.2.1]hept-2-ylamine (compound 2; Table 1) (0.70 g, 3.4 mmol) in dry DMF (30 ml). The mixture was heated to 50° C. and incubated for 8 hours. The mixture was then stirred overnight at room temperature and subsequently quenched with water. The resultant mixture was extracted with chloroform (3×20 ml). The chloroform extracts were combined and the chloroform was removed using a rotary evaporator. The remaining residue was extracted with ether (2×25 ml), and the ethereal extract was washed with water (2×20 ml) and dried over anhydrous sodium sulfate. A pale yellow oil was obtained after removing the ether. Purification by TLC with a mobile phase of chloroform and diethyl ether (9:1) resulted in a colorless crystalline compound (0.65 g, 70% yield, m.p. 58-59° C.).
Reaction SMILES: [B:1].[CH2:2](O)[CH2:3][CH:4]([CH3:6])[CH3:5]>>[CH2:2]([B:1]([CH2:2][CH2:3][CH:4]([CH3:6])[CH3:5])[CH2:2][CH2:3][CH:4]([CH3:6])[CH3:5])[CH2:3][CH:4]([CH3:6])[CH3:5]
Reactant: CC(C)CCO
Reactant: [B]
Product: CC(C)CCB(CCC(C)C)CCC(C)C

Procedure:
An intended product having a boron content of 4.3% by weight (calculated: 4.50%) and a purity of 95.5% was obtained from 226 parts by weight of triisoamyl boron and 88 parts by weight of isoamyl alcohol in the same manner as in Referential Example 1.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:18])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([S:12][CH2:13][C:14](=O)[CH3:15])[C:7]=1[F:17])[CH3:2].Cl.[Cl:20][C:21]1[C:22]([F:29])=[C:23]([NH:27]N)[CH:24]=[CH:25][CH:26]=1>>[CH2:1]([O:3][C:4](=[O:18])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([S:12][C:13]2[C:24]3[C:23](=[C:22]([F:29])[C:21]([Cl:20])=[CH:26][CH:25]=3)[NH:27][C:14]=2[CH3:15])[C:7]=1[F:17])[CH3:2]
Reactant: NNc1cccc(Cl)c1F
Reactant: CCOC(=O)Cc1cccc(SCC(C)=O)c1F
Agent: Cl
Product: CCOC(=O)Cc1cccc(Sc2c(C)[nH]c3c(F)c(Cl)ccc23)c1F

Procedure:
Prepared according to the procedure described in Example 2, Step 1, using the following starting materials: [2-Fluoro-3-(2-oxo-propylsulfanyl)-phenyl]-acetic acid ethyl ester and (3-chloro-2-fluoro-phenyl) hydrazine hydrochloride.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:26])[CH2:5][C:6]1[CH:7]=[C:8]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][C:15]=2[CH2:24]Br)[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:2].[F:27][C:28]([F:32])([F:31])[CH2:29][SH:30]>>[CH2:1]([O:3][C:4](=[O:26])[CH2:5][C:6]1[CH:7]=[C:8]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][C:15]=2[CH2:24][S:30][CH2:29][C:28]([F:32])([F:31])[F:27])[C:9]([O:12][CH3:13])=[CH:10][CH:11]=1)[CH3:2]
Reactant: FC(F)(F)CS
Reactant: CCOC(=O)Cc1ccc(OC)c(-c2ccc(C(F)(F)F)cc2CBr)c1
Product: CCOC(=O)Cc1ccc(OC)c(-c2ccc(C(F)(F)F)cc2CSCC(F)(F)F)c1

Procedure:
Prepared according to the procedure described in Example 1, Step 6, using the following starting materials: (2′-bromomethyl-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid ethyl ester and 2,2,2-trifluoroethanethiol.