Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.[O:15]1[CH2:19][CH2:18]OC1=O.C(=O)([O-])[O-].[Cs+].[Cs+].C(=O)([O-])[O-]>C(OCC)(=O)C>[CH3:1][C:2]1([CH3:14])[C:6]([CH3:7])([CH3:8])[O:5][B:4]([C:9]2[CH:13]=[N:12][N:11]([CH2:18][CH2:19][OH:15])[CH:10]=2)[O:3]1
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Reactant: O=C1OCCO1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Product: CC1(C)OB(c2cnn(CCO)c2)OC1(C)C
Temperature: 25 °C
Reaction time: 0.58 h

Procedure:
4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (9.66 g, 49.8 mmol), 1,3-dioxolan-2-one (21 g, 238 mmol), and cesium carbonate (16 g, 49.1 mmol) were combined in a 100 mL round bottom flask At room temperature all reagents were solids. The reaction was warmed from room temperature to 100° C. in an oil bath, at which time the carbonate had melted and served as the solvent for the reaction, which then remained a slurry. After heating for 3.5 hours, the reaction was cooled to room temperature, diluted with ethyl acetate, and filtered through Celite® (diatomaceous earth) washing repeatedly with ethyl acetate. The filtrate was concentrated, and the residue was purified by chromatography on an Analogix® Intelliflash™ purification system using a SF60-200 g column at a flow rate of 80 mL/minute, eluting as follows: 5 minutes at 20% ethyl acetate/hexane, then ramped from 40% to 90% ethyl acetate/hexanes over 35 minutes, and then 100% ethyl acetate for another 20 minutes, to afford the title compound.
Reaction SMILES: [CH2:1](Br)[CH:2]=[CH2:3].[N:5]1[NH:6][N:7]=[N:8][C:9]=1[C:10]1[CH:11]=[C:12]([CH:25]=[CH:26][CH:27]=1)[CH2:13][CH2:14][O:15][CH2:16][CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].C(=O)([O-])[O-].[K+].[K+]>C(#N)C.C(OCC)(=O)C>[CH2:1]([N:6]1[N:7]=[N:8][C:9]([C:10]2[CH:11]=[C:12]([CH:25]=[CH:26][CH:27]=2)[CH2:13][CH2:14][O:15][CH2:16][CH2:17][C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])=[N:5]1)[CH:2]=[CH2:3].[CH2:1]([N:8]1[C:9]([C:10]2[CH:11]=[C:12]([CH:25]=[CH:26][CH:27]=2)[CH2:13][CH2:14][O:15][CH2:16][CH2:17][C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])=[N:5][N:6]=[N:7]1)[CH:2]=[CH2:3]
Reactant: C=CCBr
Reactant: CC(C)(C)OC(=O)CCOCCc1cccc(-c2nn[nH]n2)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CC#N
Product: C=CCn1nnc(-c2cccc(CCOCCC(=O)OC(C)(C)C)c2)n1
Product: C=CCn1nnnc1-c1cccc(CCOCCC(=O)OC(C)(C)C)c1
Temperature: 65 °C
Reaction time: 1 h

Procedure:
Allyl bromide (0.4 mL) was added in one portion to tert-butyl 3-(3-(2H-tetrazol-5-yl)phenethoxy)propanoate [Example 7, Step ii)] (1.05 g) and potassium carbonate (905 mg) in acetonitrile (10 mL). The resulting mixture was stirred at 65° C. for 1 h. After cooling to rt, the reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (1×20 mL). The organic was dried over magnesium sulfate, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 80% ethyl acetate in isohexane to afford the subtitled compounds tert-butyl 3-(3-(2-allyl-2H-tetrazol-5-yl)phenethoxy)propanoate (427 mg) and tert-butyl 3-(3-(1-allyl-1H-tetrazol-5-yl)phenethoxy)propanoate (136 mg). Tert-butyl 3-(3-(2-allyl-2H-tetrazol-5-yl)phenethoxy)propanoate: 1H NMR (300 MHz, CDCl3) δ 8.02-7.96 (m, 2H), 7.44-7.30 (m, 2H), 6.12 (m, 1H), 5.45-5.37 (m, 2H), 5.26 (dt, J=6.2, 1.4 Hz, 2H), 3.70 (t, J=7.1 Hz, 2H), 3.70 (t, J=6.5 Hz, 2H), 2.95 (t, J=7.1 Hz, 2H), 2.49 (t, J=6.5 Hz, 2H), 1.43 (s, 9H). Tert-butyl 3-(3-(1-allyl-1H-tetrazol-5-yl)phenethoxy)propanoate: 1H NMR (300 MHz, CDCl3) δ 7.59 (s, 1H), 7.56-7.39 (m, 3H), 6.07 (ddt, J=5.5, 10.6 and 17.2 Hz, 1H), 5.39 (dt, J=1.5 and 10.4 Hz, 1H), 5.16 (dt, J=1.8 and 17.1 Hz, 1H), 5.06 (dt, J=1.6 and 5.5 Hz, 2H), 3.70 (t, J=6.7 Hz, 2H), 3.68 (t, J=6.4 Hz, 2H), 2.95 (t, J=6.8 Hz, 2H), 2.46 (t, J=6.4 Hz, 2H), 1.41 (s, 9H).
Reaction SMILES: [Cl:1][CH2:2][CH:3]1[C:11]2[C:10]3[CH:12]=[CH:13][C:14]([S:16]([NH:19][CH2:20][CH2:21][OH:22])(=[O:18])=[O:17])=[CH:15][C:9]=3[C:8]([N+:23]([O-:25])=[O:24])=[CH:7][C:6]=2[NH:5][CH2:4]1.[CH3:26][O:27][C:28]1[CH:29]=[C:30]2[C:34](=[C:35]([O:39][CH3:40])[C:36]=1[O:37][CH3:38])[NH:33][C:32]([C:41](O)=[O:42])=[CH:31]2.CCN=C=NCCCN(C)C.CC1C=CC(S(O)(=O)=O)=CC=1>CO.Cl.O.CC(N(C)C)=O>[Cl:1][CH2:2][CH:3]1[C:11]2[C:10]3[CH:12]=[CH:13][C:14]([S:16]([NH:19][CH2:20][CH2:21][OH:22])(=[O:17])=[O:18])=[CH:15][C:9]=3[C:8]([N+:23]([O-:25])=[O:24])=[CH:7][C:6]=2[N:5]([C:41]([C:32]2[NH:33][C:34]3[C:30]([CH:31]=2)=[CH:29][C:28]([O:27][CH3:26])=[C:36]([O:37][CH3:38])[C:35]=3[O:39][CH3:40])=[O:42])[CH2:4]1
Reactant: O=[N+]([O-])c1cc2c(c3ccc(S(=O)(=O)NCCO)cc13)C(CCl)CN2
Reactant: COc1cc2cc(C(=O)O)[nH]c2c(OC)c1OC
Agent: CCN=C=NCCCN(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: Cl
Solvent: CO
Solvent: CC(=O)N(C)C
Solvent: O
Product: COc1cc2cc(C(=O)N3CC(CCl)c4c3cc([N+](=O)[O-])c3cc(S(=O)(=O)NCCO)ccc43)[nH]c2c(OC)c1OC
Temperature: 25 °C
Reaction time: 1 h
Yield: 75.7 %

Procedure:
Amine 121 (75 mg, 0.19 mmol) was dissolved in MeOH/HCl(g) at room temperature and the solution was evaporated to dryness under reduced pressure. 5,6,7-Trimethoxyindole-2-carboxylic acid (59 mg, 0.23 mmol), EDCI (149 mg, 0.78 mmol), anhydrous TsOH (30 mg, 0.17 mmol) and dry DMA (3 mL) were then added, and the mixture was stirred at room temperature for 1 h. The mixture was poured into water and the precipitate was collected and washed with water, dried, and dissolved in the minimum volume of DMW at room temperature. The solution was diluted with EtOAc, filtered, and then diluted with hexane and refrigerated to give 33 (89 mg, 74%): mp 257-258° C.; 1H NMR [(CD3)2SO] δ 11.61 (s, 1H), 9.24 (s, 1H), 8.86 (d, J=1.6 Hz, 1H), 8.43 (d, J=8.9 Hz, 1H), 8.02 (dd, J=8.9, 1.7 Hz, 1H), 7.91 (t, J=5.7 Hz, 1H), 7.20 (d, J=2.1 Hz, 1H), 6.99 (s, 1H), 4.93 (t, J=10.1 Hz, 1H), 4.70-4.58 (m, 3H), 4.18-4.07 (m, 2H), 3.94 (s, 3H), 3.83 (s, 3H), 3.81 (s, 3H, 3.39 (q, J=6.0 Hz, 2H), 2.88 (q, J=6.1 Hz, 2H). Anal. (C27H27ClN4O9S) C, H, N.
Reaction SMILES: Cl.Cl.C[O:4][C:5]1[CH:6]=[C:7]2[C:10](=[CH:11][C:12]=1[O:13]C)[CH:9]([CH2:15][NH:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][NH:23][CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:8]2.B(Br)(Br)[Br:33].CO>ClCCl>[C:26]1([CH2:25][CH2:24][NH:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][NH:16][CH2:15][CH:9]2[CH2:8][C:7]3[C:10]2=[CH:11][C:12]([OH:13])=[C:5]([OH:4])[CH:6]=3)[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1.[BrH:33]
Reactant: BrB(Br)Br
Reactant: COc1cc2c(cc1OC)C(CNCCCCCCNCCc1ccccc1)C2
Agent: Cl
Solvent: CO
Solvent: ClCCl
Product: Br
Product: Oc1cc2c(cc1O)C(CNCCCCCCNCCc1ccccc1)C2
Reaction time: 3 h

Procedure:
The product of step (b) (3.25 g) was dissolved in dry dichloromethane (10 ml) and cooled to -78°. Boron tribromide (3.5 ml) was added, and the solution stirred at -78° for 3 hours followed by 2 hours at room temperature. Methanol (about 25 ml) was added, and the mixture reduced to dryness. The resulting white solid was crystallised from dry methanol to give the title compound as the dihydrobromide salt, 2 HBr, m.p 210°-4° (dec).
Reaction SMILES: [C:1]([O:5][C:6](=[O:17])[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][OH:15])=[C:9]([NH2:16])[CH:8]=1)([CH3:4])([CH3:3])[CH3:2].[O:18]=[C:19](Cl)OC(Cl)(Cl)Cl>C1COCC1.ClCCl>[C:1]([O:5][C:6]([C:7]1[CH:12]=[CH:11][C:10]2[CH2:13][CH2:14][O:15][C:19](=[O:18])[NH:16][C:9]=2[CH:8]=1)=[O:17])([CH3:4])([CH3:2])[CH3:3]
Reactant: O=C(Cl)OC(Cl)(Cl)Cl
Reactant: CC(C)(C)OC(=O)c1ccc(CCO)c(N)c1
Solvent: C1CCOC1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)c1ccc2c(c1)NC(=O)OCC2
Temperature: 25 °C
Reaction time: 0.02 h

Procedure:
To a stirring solution of 3-amino-4-(2-hydroxy-ethyl)-benzoic acid tert-butyl ester (2.1 g, 8.86 mmol) in THF (150 mL) and dichloromethane (50 mL) at 0° C. was added diphosgene (0.65 mL, 5.38 mmol) all at once. The reaction turned milky and became clear after 1 minute. The reaction was warmed to room temperature and stirred for 150 minutes. The solvent evaporated to provide 6-oxo-5,6,8,9-tetrahydro-7-oxa-5-aza-benzocycloheptene-3-carboxylic acid tert-butyl ester: MS (m/e) 264 (M+1).
Reaction SMILES: [C:1]([C:4]1[C:13]([CH2:14]Br)=[N+:12]([O-:16])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N+:5]=1[O-:17])(=[O:3])[CH3:2].[C:18]([O-:21])(=[O:20])[CH3:19].[K+].[I-].[K+]>CN(C)C=O>[C:1]([C:4]1[C:13]([CH2:14][O:21][C:18](=[O:20])[CH3:19])=[N+:12]([O-:16])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N+:5]=1[O-:17])(=[O:3])[CH3:2]
Reactant: CC(=O)[O-]
Reactant: CC(=O)c1c(CBr)[n+]([O-])c2ccccc2[n+]1[O-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(=O)OCc1c(C(C)=O)[n+]([O-])c2ccccc2[n+]1[O-]
Reaction time: 0.33 h
Yield: 76 %

Procedure:
To a stirred slurry of 50.0 g. (0.168 mol.) of 2-acetyl-3-bromomethylquinoxaline 1,4 dioxide in 200 ml. of N,N-dimethylformamide, was added 18.2 g. (0.185 mol.) of potassium acetate, followed by 4.15 g. (0.025 mol.) of finely ground potassium iodide. Stirring was continued for 20 minutes at ambient temperature, and then the reaction mixture was filtered. The dark filtrate was added dropwise to 4,000 ml. of ether, and the solid which precipitated was removed by filtration and discarded. Evaporation of the ether in vacuo afforded a yellow solid which was recrystallized from methanol. This gave 31.6 g. (76% yield) of 2-acetyl-3-acetoxymethylquinoxaline 1,4-dioxide having m.p. 124°-125° C.
Reaction SMILES: [CH2:1]([OH:21])[CH2:2][CH2:3][CH2:4]/[CH:5]=[CH:6]\[CH2:7]/[CH:8]=[CH:9]\[CH2:10]/[CH:11]=[CH:12]\[CH2:13]/[CH:14]=[CH:15]\[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].[CH3:22][S:23](Cl)(=[O:25])=[O:24].O.CCOCC>N1C=CC=CC=1>[CH3:22][S:23]([O:21][CH2:1][CH2:2][CH2:3][CH2:4]/[CH:5]=[CH:6]\[CH2:7]/[CH:8]=[CH:9]\[CH2:10]/[CH:11]=[CH:12]\[CH2:13]/[CH:14]=[CH:15]\[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])(=[O:25])=[O:24]
Reactant: CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCCCO
Reactant: CS(=O)(=O)Cl
Solvent: CCOCC
Solvent: O
Solvent: c1ccncc1
Product: CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCCCOS(C)(=O)=O
Reaction time: 5 h
Yield: 59 %

Procedure:
Arachidonyl alcohol (0.34 mmol, 100 mg) in dry pyridine (5 ml) was cooled to 0° C. Methane sulfonyl chloride (0.52 mmol; 40 mg) was added to the above solution under a nitrogen atmosphere. The reaction mixture was slowly brought to room temperature at which the reaction was continued for 5 hours. Water (20 ml) and ether (20 ml) were then added to the reaction mixture after which the organic phase was separated, washed with 2N sulfuric acid, then with water and then with a 10% solution of potassium carbonate. The reaction mixture was dried by evaporation of the solvents to obtain an the oily product arachidonyl methane sulfonate, (75 mg; yield 59%) exhibiting the following: 1H HMR (CDCl3) δ 5.34-5.41 (m, 8H), 4.23 (t, J=6.6 Hz, 2H), 3.00 (s, 3H), 2.75-2.84 (m, 6H), 2.04-2.12 (m, 4H), 1.65-1.74 (m, 2H), 1.33-1.50 (m, 2H), 1.25-.130 (m, 6H), 0.89 (t, J=7.2 Hz, 3H). IR (cm−1): 2900, 2850, 1350, 1170, 940.
Reaction SMILES: [C:1]12([CH2:11][NH:12][CH2:13][CH:14]([C:16]3[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=3)[OH:15])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.CCN(CC)CC.Cl[C:31](Cl)([O:33]C(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)Cl>[C:1]12([CH2:11][N:12]3[CH2:13][CH:14]([C:16]4[CH:17]=[CH:18][C:19]([OH:22])=[CH:20][CH:21]=4)[O:15][C:31]3=[O:33])[CH2:10][CH:5]3[CH2:4][CH:3]([CH2:9][CH:7]([CH2:6]3)[CH2:8]1)[CH2:2]2
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: Oc1ccc(C(O)CNCC23CC4CC(CC(C4)C2)C3)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C1OC(c2ccc(O)cc2)CN1CC12CC3CC(CC(C3)C1)C2
Temperature: 0 °C
Reaction time: 8 h
Yield: 11.1 %

Procedure:
4-(2-((1-adamantylmethyl)amino)-1-hydroxyethyl)phenol (50 mg, 0.166 mmol) and Et3N (34 mg, 0.33 mmol) were dissolved in dry CH2Cl2 (1 mL) and the solution was cooled to 0° C. Triphosgene (19.7 mg, 0.066 mmol) in dry CH2Cl2 (1 mL) was added dropwise slowly. The mixture was allowed to warm to rt and stirred overnight. The solution was concentrated to give a residue, which was purified by preparative HPLC to afford 3-adamantan-1-ylmethyl-5-(4-hydroxy-phenyl)-oxazolidin-2-one (2.40 mg, 4.4%). 1H NMR: (CDCl3, 400 MHz): δ=1.54 (s, 6H), 1.58-1.65 (d, 3H), 1.66-1.75 (d, 3H), 1.99 (s, 3H), 2.80-2.87 (d, 1H), 3.02-3.08 (d, 1H), 3.50-3.56 (t, 1H), 3.93-4.00 (t, 1H), 5.40-5.48 (t, 1H), 6.82-6.90 (d, 1H), 7.20-7.26 (d, 1H); MS m/z=328
Reaction SMILES: [NH2:1][C:2]1[N:6]([CH:7]([CH3:17])[CH2:8][CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:5]=[N:4][C:3]=1[C:18]([NH2:20])=[O:19].[CH2:21]1[O:29][C:28]2[CH:27]=[CH:26][C:25]([CH2:30][C:31](OC)=O)=[CH:24][C:23]=2[O:22]1>>[O:29]1[C:28]2[CH:27]=[CH:26][C:25]([CH2:30][C:31]3[NH:20][C:18](=[O:19])[C:3]4[N:4]=[N:5][N:6]([CH:7]([CH3:17])[CH2:8][CH2:9][CH2:10][C:11]5[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=5)[C:2]=4[N:1]=3)=[CH:24][C:23]=2[O:22][CH2:21]1
Reactant: COC(=O)Cc1ccc2c(c1)OCO2
Reactant: CC(CCCc1ccccc1)n1nnc(C(N)=O)c1N
Product: CC(CCCc1ccccc1)n1nnc2c(=O)[nH]c(Cc3ccc4c(c3)OCO4)nc21

Procedure:
Analogously to the procedure of Example 5, the title compound is prepared from 18 mg (0.066 mmol) of 5-amino-1-(1-methyl-4-phenyl-butyl)-1H-[1,2,3]triazole-4-carboxamide and 40.8 g (0.21 mmol) of methyl 3,4-methylenedioxyphenylacetate.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[C:20]([CH3:21])=[CH:19][C:18]([N+:22]([O-:24])=[O:23])=[CH:17][C:16]=2[C:25](O)=[O:26])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC(OCC(C)C)=O.C([N:38](CC)CC)C.N>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([O:14][C:15]2[C:20]([CH3:21])=[CH:19][C:18]([N+:22]([O-:24])=[O:23])=[CH:17][C:16]=2[C:25](=[O:26])[NH2:38])[CH2:12][CH2:13]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]
Reactant: CCN(CC)CC
Reactant: Cc1cc([N+](=O)[O-])cc(C(=O)O)c1OC1CCN(C(=O)OC(C)(C)C)CC1
Agent: CC(C)COC(=O)Cl
Agent: N
Solvent: ClCCl
Product: Cc1cc([N+](=O)[O-])cc(C(N)=O)c1OC1CCN(C(=O)OC(C)(C)C)CC1
Reaction time: 0.5 h

Procedure:
To a solution of 4-(1-t-butoxycarbonylpiperidin-4-yloxy)-3-carboxy-5-methylnitrobenzene (3.6 g) in dichloromethane (60 ml) were added isobutyl chloroformate (1.4 ml) and triethylamine (1.6 ml) in an ice bath and the mixture was stirred at the same temperature for 0.5 hours. To the reaction mixture was added 28% aqueous ammonia (0.7 ml) and the resulting mixture was stirred at room temperature for 1.5 hours. The reaction mixture was concentrated in vacuo. The residue was purified by chromatography on a silica gel column using dichloromethane/methanol=19/1 as an eluant to give the desired compound (3.9 g, yield quantitative) as a yellow oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]([S:14][C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=2)[C:12]#[N:13])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[H-].[Na+].Br[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][Cl:30]>CN(C)C=O>[Cl:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][C:11]([S:14][C:15]1[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=1)([C:5]1[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=1)[C:12]#[N:13]
Reactant: COc1ccc(C(C#N)Sc2ccc(C)cc2)cc1OC
Reactant: ClCCCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc(C(C#N)(CCCCCCl)Sc2ccc(C)cc2)cc1OC
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 90 %

Procedure:
To a stirred solution of 5.00 g of 3,4-dimethoxy-α-[(4-methylphenyl)thio]benzeneacetonitrile in 50 mL of N,N-dimethylformamide, under an argon atmosphere, is added 0.73 g of 60% sodium hydride in oil. After 1.5 hours, 4.65 g of 1-bromo-5-chloropentane is added to the resulting solution and stirring continued for 3 hours. The reaction is poured into ice water, and twice extracted with diethyl ether. The combined organic extracts are dried (magnesium sulfate), and concentrated in vacuo to give a golden oil. Purification by chromatography on a silica gel column using diethyl ether/hexane (2:3), affords 6.07 g of the desired product as a colorless oil. MS(CI): m/z 421(M+NH4+). Calcd for C22H26NO2ClS 1/16H2O: C=65.22, H=8.17, N=3.46, Cl=8.75, S=7.82 Found C=64.92, H=6.49, N=3.46, Cl=8.19, S=8.22
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:17])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[F:16])=[CH:4][CH:3]=1.[Cl:18][C:19]1[C:20]([O:30][CH3:31])=[CH:21][C:22]([O:28][CH3:29])=[C:23]([N:25]=[C:26]=[O:27])[CH:24]=1>C(#N)C>[Cl:18][C:19]1[C:20]([O:30][CH3:31])=[CH:21][C:22]([O:28][CH3:29])=[C:23]([NH:25][C:26](=[O:27])[NH:1][C:2]2[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:17])[C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[F:16])=[CH:6][CH:7]=2)[CH:24]=1
Reactant: Nc1ccc(NC(=O)c2ccccc2F)cc1
Reactant: COc1cc(OC)c(N=C=O)cc1Cl
Solvent: CC#N
Product: COc1cc(OC)c(NC(=O)Nc2ccc(NC(=O)c3ccccc3F)cc2)cc1Cl
Reaction time: 12 h

Procedure:
A suspension of N-(4-amino-phenyl)-2-fluoro-benzamide (0.43 g) in acetonitrile (4 mL) is treated with 5-chloro-2,4-dimethoxyphenylisocyanate (0.40 g). The mixture becomes a solution and is allowed to stand for 12 hours. A white solid forms and is collected by filtration (0.79 g). [M+H] 444.
Reaction SMILES: [CH3:1][N:2]1[C:7](=[O:8])[CH:6]=[CH:5][C:4]([C:9](=O)[CH2:10][CH:11]([C:19]2[CH:33]=[CH:32][C:22]([C:23]([NH:25][CH2:26][CH2:27][S:28]([CH3:31])(=[O:30])=[O:29])=[O:24])=[CH:21][CH:20]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH3:18])=[CH:3]1.Cl.[NH2:36][OH:37].C(=O)([O-])O.[Na+]>>[OH:37]/[N:36]=[C:9](/[C:4]1[CH:5]=[CH:6][C:7](=[O:8])[N:2]([CH3:1])[CH:3]=1)\[CH2:10][CH:11]([C:19]1[CH:33]=[CH:32][C:22]([C:23]([NH:25][CH2:26][CH2:27][S:28]([CH3:31])(=[O:29])=[O:30])=[O:24])=[CH:21][CH:20]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH3:18]
Reactant: NO
Reactant: Cc1ccccc1C(CC(=O)c1ccc(=O)n(C)c1)c1ccc(C(=O)NCCS(C)(=O)=O)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Product: Cc1ccccc1C(C/C(=N\O)c1ccc(=O)n(C)c1)c1ccc(C(=O)NCCS(C)(=O)=O)cc1

Procedure:
In analogy to example 151, step 3, 4-(3-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-3-oxo-1-o-tolylpropyl)-N-(2-(methylsulfonyl)ethyl)benzamide was reacted with hydroxylamine hydrochloride in the presence of sodium hydrogencarbonate to give the title compound as an off-white solid containing <10% of the corresponding Z isomer, MS (ESI+): m/z=496.2 [M+H]+.
Reaction SMILES: C([Si:10]1(C2C=CC=CC=2)[CH2:15][CH2:14][CH:13]([C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[C:26]([F:28])[C:25]([OH:29])=[C:24]([F:30])[CH:23]=3)=[CH:18][CH:17]=2)[CH2:12][CH2:11]1)CCCCCCCC.[F:37][C@H:38]([CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46])[CH2:39]O>>[CH2:11]([Si@H:10]1[CH2:11][CH2:12][C@H:13]([C:16]2[CH:17]=[CH:18][C:19]([C:22]3[CH:27]=[C:26]([F:28])[C:25]([O:29][CH2:39][C@@H:38]([F:37])[CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46])=[C:24]([F:30])[CH:23]=3)=[CH:20][CH:21]=2)[CH2:14][CH2:15]1)[CH2:12][CH2:13][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: CCCCCC[C@@H](F)CO
Reactant: CCCCCCCCC[Si]1(c2ccccc2)CCC(c2ccc(-c3cc(F)c(O)c(F)c3)cc2)CC1
Product: CCCCCCCCC[Si@H]1CC[C@H](c2ccc(-c3cc(F)c(OC[C@@H](F)CCCCCC)c(F)c3)cc2)CC1

Procedure:
The general procedure of Example 1 was repeated using 4-(4-(4-n-nonyl-4-phenyl-4-silacyclohexyl)phenyl) -2,6-difluorophenol and (R)-2-fluoro-1-octanol, thereby obtaining the intended compound.
Reaction SMILES: [C:1]([O:4][C@H:5]1[CH2:22][C@@:20]2([CH3:21])[C@@H:16]([CH2:17][CH:18]=[C:19]2[S:23][CH2:24][CH3:25])[C@H:15]2[C@@:6]1([F:28])[C@:7]1([CH3:27])[C:12]([CH2:13][CH2:14]2)=[CH:11][C:10](=[O:26])[CH:9]=[CH:8]1)(=[O:3])[CH3:2].[CH3:29][SH:30].C(#N)C.C(=O)=O.B(F)(F)F.CCOCC>ClCCl>[C:1]([O:4][C@H:5]1[CH2:22][C@@:20]2([CH3:21])[C@@H:16]([CH2:17][CH2:18][C:19]2([S:23][CH2:24][CH3:25])[S:30][CH3:29])[C@H:15]2[C@@:6]1([F:28])[C@:7]1([CH3:27])[C:12]([CH2:13][CH2:14]2)=[CH:11][C:10](=[O:26])[CH:9]=[CH:8]1)(=[O:3])[CH3:2]
Reactant: CS
Reactant: CCSC1=CC[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](OC(C)=O)C[C@]12C
Agent: FB(F)F
Agent: O=C=O
Solvent: CC#N
Solvent: ClCCl
Solvent: CCOCC
Product: CCSC1(SC)CC[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](OC(C)=O)C[C@@]21C
Temperature: -40 °C
Reaction time: 3 h

Procedure:
A solution of 1.01 g (2.5 mmole) of 11β-acetyloxy-17-(ethylthio)-9-fluoroandrosta-1,4,16-trien-3-one in 15 ml of dry dichloromethane and 3.4 ml of a solution of methyl mercaptan in dichloromethane (1.82 g in 10 ml of dry dichloromethane) is cooled to about -40° C. (acetonitrile-dry ice bath) under nitrogen; boron trifluoride etherate (0.7 ml) is then added. The solution is stirred at approximately -40° C. under nitrogen for 3 hours, quenched with a saturated sodium bicarbonate solution at -40° C. under vigorous stirring, diluted with chloroform, washed with water, dried over anhydrous Na2SO4 and evaporated in vacuo to give 1.0 g of the title compound, melting point 185°-186° C., with consistent spectral data.
Reaction SMILES: I[CH2:2]C.[N+:4]([C:7]1[CH:8]=[C:9](O)[C:10]([O:13][CH3:14])=[CH:11][CH:12]=1)([O-:6])=[O:5].[C:16]([O-:19])([O-])=O.[K+].[K+]>CN(C=O)C.O.C(OC)(C)(C)C>[CH2:14]([O:13][C:10]1[CH:9]=[CH:8][C:7]([N+:4]([O-:6])=[O:5])=[CH:12][C:11]=1[O:19][CH3:16])[CH3:2]
Reactant: CCI
Reactant: O=C([O-])[O-]
Reactant: COc1ccc([N+](=O)[O-])cc1O
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Solvent: COC(C)(C)C
Product: CCOc1ccc([N+](=O)[O-])cc1OC
Temperature: 25 °C
Yield: 98.3 %

Procedure:
Iodoethane (1.93 mL, 38.4 mmol) was added dropwise over 15 min. to a stirred mixture of 4-nitroguaiacol 1 (5.00 g, 29.6 mmol) and K2CO3 (6.21 g, 44.3 mmol) in DMF (30 ml) at 60° C. under nitrogen. After 2 h the reaction was cooled to RT and diluted with water (100 ml) and methyl tert-butyl ether (250 ml). The organic layer was washed with water (25 ml), brine (2×20 ml), dried over Na2SO4, filtered and concentrated under vacuum to afford 2-ethoxy-5-nitroanisole (5.74 g) as a pale yellow solid. mp 88-90° C. 1H NMR (DMSO-d6) δ 7.89 (dd, 1H), 7.73 (d, 1H), 7.16 (d, 1H), 4.17 (q, 2H), 3.88 (s, 3H), 1.37 (t, 3H). 13C NMR (DMSO-d6) δ 153.9, 148.6, 140.5, 117.6, 111.5, 106.4, 64.6, 55.9, 14.4. MS (ESI+) for m/z 198 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:15](O)[C:10]3=[N:11][CH:12]=[CH:13][CH:14]=[C:9]3[CH2:8][CH2:7][C:6]=2[CH:17]=1.S(Cl)([Cl:20])=O.C(OCC)(=O)C.[OH-].[Na+]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:15]([Cl:20])[C:10]3=[N:11][CH:12]=[CH:13][CH:14]=[C:9]3[CH2:8][CH2:7][C:6]=2[CH:17]=1
Reactant: OC1c2ccc(Cl)cc2CCc2cccnc21
Reactant: O=S(Cl)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: Clc1ccc2c(c1)CCc1cccnc1C2Cl
Yield: 71.6 %

Procedure:
To a mixture of 13.3 g (54 mmol) of 8-chloro-6,11-dihydro-11-hydroxy-5H-benzo[5,6]cyclohepta[1,2-b]pyridine in 290 mL of toluene at -15° C. and under an atmosphere of nitrogen was added via syringe pump over a period of 1 hour 6.20 mL (85.7 mmol) of thionyl chloride. The extent of reaction was monitored by TLC (50% ethyl acetate in hexanes). When completed the mixture was poured into 300 mL of 1.0N aqueous NaOH and extracted with ethyl acetate (5X). The combined organic portions were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was taken up in ethyl acetate, quickly filtered through basic alumina, and concentrated again to yield a product which was triturated with pentane to yield 10.22 g of the title compound as a tan solid.