Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8]Cl)=[CH:4][C:3]=1[F:10].[F:11][CH:12]([F:15])[CH2:13][NH2:14].C(N(CC)CC)C>C(#N)C>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][NH:14][CH2:13][CH:12]([F:15])[F:11])=[CH:4][C:3]=1[F:10]
Reactant: Fc1cc(CCl)cnc1Cl
Reactant: NCC(F)F
Solvent: CCN(CC)CC
Solvent: CC#N
Product: Fc1cc(CNCC(F)F)cnc1Cl
Reaction time: 16 h
Yield: 57 %

Procedure:
At 45° C., 520 mg (2.89 mmol) of 6-chloro-3-chloromethyl-5-fluoropyridine (Va-4), 1.05 ml (14.44 mmol) of 2,2-difluoroethylamine and 400 μl (2.89 mmol) of triethylamine in 50 ml of acetonitrile are stirred for about 48 hours. During the reaction, after about 16 hours and 32 hours, a further 0.42 ml (5.78 mmol) of 2,2-difluoroethylamine are added in each case. The reaction mixture is concentrated under reduced pressure and then taken up in 1 N aqueous hydrochloric acid and washed with ethyl acetate. The aqueous phase is made alkaline using 2.5 N aqueous sodium hydroxide solution and extracted repeatedly with ethyl acetate. Drying of the combined organic phases over sodium sulphate and concentration under reduced pressure gives 370 mg (57% of theory) of N-[(6-chloro-5-fluoropyridin-3-yl)methyl]-2,2-difluoroethylamine.
Reaction SMILES: [CH3:1][O-:2].[Na+].Cl[C:5]1[CH:6]=[CH:7][C:8]([N+:12]([O-:14])=[O:13])=[C:9]([CH:11]=1)[NH2:10]>O1CCOCC1>[CH3:1][O:2][C:5]1[CH:6]=[CH:7][C:8]([N+:12]([O-:14])=[O:13])=[C:9]([CH:11]=1)[NH2:10]
Reactant: C[O-]
Reactant: Nc1cc(Cl)ccc1[N+](=O)[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: COc1ccc([N+](=O)[O-])c(N)c1

Procedure:
70 ml of a 28% w/v methanolic solution of sodium methoxide were added at room temperature to a solution of 25 g of 5-chloro-2-nitroaniline in 500 ml of 1,4-dioxane, and the resulting mixture was heated under reflux for 4 hours, after which the solvent was removed by distillation under reduced pressure. The resulting residue was diluted with water, and the resulting aqueous mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, after which the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through silica gel using a gradient elution method, with mixtures of ethyl acetate and hexane in ratios ranging from 1:4 to 1:2 by volume as the eluent, to give 16.3 g of the title compound, melting at 124-128° C.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].C(N(CC)C(C)C)(C)C.[C:20]([O:24][C:25](=[O:33])[NH:26][CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)([CH3:23])([CH3:22])[CH3:21]>O1CCOCC1>[C:20]([O:24][C:25](=[O:33])[NH:26][CH:27]1[CH2:32][CH2:31][N:30]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[N+:8]([O-:10])=[O:9])[CH2:29][CH2:28]1)([CH3:23])([CH3:21])[CH3:22]
Reactant: O=[N+]([O-])c1ccccc1F
Reactant: CC(C)(C)OC(=O)NC1CCNCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)NC1CCN(c2ccccc2[N+](=O)[O-])CC1
Temperature: 25 °C
Yield: 74.7 %

Procedure:
A solution of 1-fluoro-2-nitro-benzene (0.50 mmol, 53 μL), N,N-diisopropylethylamine (0.50 mmol, 87 μL) and Piperidin-4-yl-carbamic acid tert-butyl ester (0.50 mmol, 0.10 g) in 1,4-dioxane (2 mL) was irradiated using microwave for 10 minutes at a temperature of 180° C. The solution was then cooled to room temperature and concentrated in vacuo and the resulting residue was purified using column chromatography on silica gel to provide [1-(2-Nitro-phenyl)-piperidin-4-yl]-carbamic acid tert-butyl ester (0.12 g, 77% yield). To the solution of this nitro compound in EtOAc (15 mL) was added Pd on carbon (5% Pd, 55 mg). The resulting reaction mixture was stirred under a hydrogen atmosphere at room temperature for about 15 hours. The reaction mixture was filtered through a pad of celite and the filtrate was concentrated in vacuo to provide Intermediate Compound 42A (97 mg, 86% yield).
Reaction SMILES: N1C=CC=CC=1.[NH2:7][C:8]1[CH:9]=[C:10]([CH:15]=[CH:16][CH:17]=1)[C:11]([O:13][CH3:14])=[O:12].[Cl:18][C:19]1[CH:20]=[CH:21][C:22]2[S:26][C:25]([S:27](Cl)(=[O:29])=[O:28])=[C:24]([CH3:31])[C:23]=2[CH:32]=1>CC#N>[Cl:18][C:19]1[CH:20]=[CH:21][C:22]2[S:26][C:25]([S:27]([NH:7][C:8]3[CH:9]=[C:10]([CH:15]=[CH:16][CH:17]=3)[C:11]([O:13][CH3:14])=[O:12])(=[O:29])=[O:28])=[C:24]([CH3:31])[C:23]=2[CH:32]=1
Reactant: COC(=O)c1cccc(N)c1
Reactant: Cc1c(S(=O)(=O)Cl)sc2ccc(Cl)cc12
Solvent: CC#N
Solvent: c1ccncc1
Product: COC(=O)c1cccc(NS(=O)(=O)c2sc3ccc(Cl)cc3c2C)c1
Temperature: 25 °C
Yield: 88 %

Procedure:
Pyridine (200 μL, 2.48 mmol) was added to a solution of methyl 3-aminobenzoate (188 mg, 1.24 mmol) and 5-chloro-3-methyl-benzothiophene-2-sulfonyl chloride (349 mg, 1.24 mmol) in MeCN (10 mL). The reaction mixture was stirred at room temperature over night. After removal of the solvents, the residue was dissolved in EtOAc and water. The phases were separated, and the organic solution was washed with 1M HCl twice, water twice and brine then dried (MgSO4). The crude product, obtained after evaporation of the solvents, was crystallized from MeOH (ca 5 mL). The solid product was triturated using heptane, giving the intermediate methyl 3-{[(5-chloro-3-methyl-1-benzothien-2-yl)sulfonyl]amino}benzoate as an off-white solid (432 mg, 88%). 1H NMR (500 MHz, CDCl3) δ ppm 2.46 (s, 3 H) 2.45 (s, 3 H) 6.91 (s, 1 H) 7.37 (t, J=7.81 Hz, 1 H) 7.43-7.47 (m, 2 H) 7.72 (d, J=1.96 Hz, 1 H) 7.72 (d, J=8.76 Hz, 1 H) 7.76 (t, J=1.83 Hz, 1 H) 7.85 (dt, J=7.81, 1.34 Hz, 1 H). MS (ESI+) 396 m/z [M+H]+.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[NH2:12])[C:7]#[N:8])([O-])=O.[BH4-].[Na+].O.[OH-].[Na+]>C(O)C>[NH2:1][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[NH2:12])[C:7]#[N:8]
Reactant: N#Cc1ccc(N)c([N+](=O)[O-])c1
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: N#Cc1ccc(N)c(N)c1
Temperature: 60 °C
Reaction time: 8 h
Yield: 45.3 %

Procedure:
3-Nitro-4-aminobenzonitrile (3.00 g) was dissolved in ethanol (300 ml) and added with stannous chloride dihydrate (20.7 g) and the whole was heated to 60° C. Sodium borohydride (348 mg) was gradually added thereto and the whole was stirred overnight at 60° C. After completion of the reaction, the resultant was added with water (300 ml) and neutralized with a 5 mol/l sodium hydroxide aqueous solution. After ethanol was distilled off under reduced pressure, the aqueous layer was added with ethyl acetate for extraction. The organic layer was washed with a saturated saline solution and then dried with anhydrous sodium sulfate. After filtration, the solvent was distilled off under reduced pressure. The residue was recrystallized, thereby obtaining the subject compound (1.11 g) as a brown crystal.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][N:5]=1)([O-:3])=[O:2].[C:11]([N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[N+:1]([C:4]1[N:5]=[CH:6][C:7]([N:21]2[CH2:20][CH2:19][N:18]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:23][CH2:22]2)=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc(Br)cn1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)OC(=O)N1CCN(c2ccc([N+](=O)[O-])nc2)CC1
Temperature: 120 °C
Reaction time: 36 h
Yield: 33 %

Procedure:
A solution is prepared of 1 g (4.9 mM) of 2-nitro-5-bromopyridine and 917 mg (4.9 mM) of N-Boc-piperazine in 10 ml of dimethylformamide and 1.02 g (7.4 mM) of potassium carbonate are added. The reaction mixture is agitated at 120° C. for 36 hours and then cooled. 50 ml of water are then added and extraction is carried out with ethyl acetate. The organic phase obtained is washed with water, dried and concentrated under reduced pressure. The crude product is purified by silica gel chromatography in eluting with the aid of a toluene/isopropanol mixture (98/2; v/v). The product sought after is thus obtained as a yellow solid (yield=33%).
Reaction SMILES: [C:1]1([C:7]2[CH:16]=[CH:15][C:14]3[C:9](=[CH:10][C:11]([CH:17]=O)=[CH:12][CH:13]=3)[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(C2C=CC3C(=CC(CO)=CC=3)N=2)C=CC=CC=1>C(Cl)(Cl)Cl.O=[Mn]=O>[CH3:17][C:11]1[CH:10]=[C:9]2[C:14]([CH:15]=[CH:16][C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[N:8]2)=[CH:13][CH:12]=1
Reactant: O=Cc1ccc2ccc(-c3ccccc3)nc2c1
Agent: O=[Mn]=O
Agent: OCc1ccc2ccc(-c3ccccc3)nc2c1
Solvent: ClC(Cl)Cl
Product: Cc1ccc2ccc(-c3ccccc3)nc2c1
Reaction time: 20 h

Procedure:
Additionally, 2-phenylquinoline-7-carbaldehyde could be prepared as follows: To a solution of (2-phenylquinolin-7-yl)methanol (75 mg, 0.319 mmol) in chloroform (1 mL) was added MnO2 (277 mg, 3.19 mmol). The mixture was stirred at it for 20 h and filtered through a Celite pad. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromatography. (1% MeOH in dichloromethane) to afford the title compound. 1H-NMR (CDCl3, 400 MHz) δ 7.50-7.59 (m, 3H), 7.95 (d, J=8.8 Hz, 1H), 8.04 (dd, J=2.4, 8.8 Hz, 2H), 8.19-8.22 (m, 2H), 8.31 (d, J=8.8 Hz, 1H), 8.69 (s, 1H), 10.26 (s, 1H). MS (ES+): m/z 234 [MH+]. HPLC: tR=3.59 min (OpenLynx, polar—5 min).
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][N:5]=2.[Li][CH2:12]CCC.CC([O-])(C)C.[K+].CI>C(OCC)C>[CH2:1]([C:2]1[NH:3][C:4]2=[N:5][CH:6]=[CH:7][CH:8]=[C:9]2[CH:10]=1)[CH3:12]
Reactant: [Li]CCCC
Reactant: Cc1cc2cccnc2[nH]1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CI
Solvent: CCOCC
Product: CCc1cc2cccnc2[nH]1
Temperature: 25 °C
Reaction time: 0.67 h

Procedure:
To a solution of 2-methyl-7-azaindole (1.32 g, 10 mmol) in dry diethyl ether (60 ml) at room temperature under an inert atmosphere is added n-BuLi (18.8 ml of a 1.6 M solution in hexanes, 30 mmol) followed by t-BuOK (2.24 g, 20 mmol). The reaction mixture is stirred at room temperature for 40 minutes and then cooled to −70° C. whereupon methyl iodide (1.25 ml, 20 mmol) is added dropwise. Stirring continues for a further 2 hours after which time, the reaction mixture is quenched with water (2 ml) and is allowed to slowly warm to room temperature. The cooled solution is poured onto water (200 ml), neutralized with 1N HCl and then extracted with diethyl ether (80 ml). The organic portion is washed with water (2×60 ml), dried (Na2SO4) and concentrated in vacuo to yield the titled compound as orange crystals. [MH+CH3CN]+=188)
Reaction SMILES: S(Cl)([Cl:3])=O.[C:5]([OH:17])(=O)[C:6]1[CH:15]=[CH:14][C:11]([O:12][CH3:13])=[C:8]([O:9][CH3:10])[CH:7]=1>C1C=CC=CC=1.N1C=CC=CC=1>[C:5]([Cl:3])(=[O:17])[C:6]1[CH:15]=[CH:14][C:11]([O:12][CH3:13])=[C:8]([O:9][CH3:10])[CH:7]=1
Reactant: O=S(Cl)Cl
Reactant: COc1ccc(C(=O)O)cc1OC
Solvent: c1ccncc1
Solvent: c1ccccc1
Product: COc1ccc(C(=O)Cl)cc1OC
Temperature: 25 °C
Reaction time: 0.05 h
Yield: 99.9 %

Procedure:
In a 2-neck 100 ml-round bottom flask, 10.0 g (54.9 m mol) of veratric acid was dissolved in 50 ml of benzene, and after adding 2 to 3 drops of pyridine to the solution, 13 g (109 m mol) of thionyl chloride was dropped into the solution while stirring the solution at room temperature within 3 min. Then the content was heated to 70° to 80° C. on a water bath, and maintained at the temperature for 2 hours under a reflux condenser and agitation. Then, the solvent and excess thionyl chloride were evaporated off under a reduced pressure to obtain 11.0 g of veratroyl chloride as colourless powder in a yield of 100%.
Reaction SMILES: [CH2:1]1[O:3][C@H:2]1[CH2:4]Cl.[OH-:6].[Na+]>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.CN(C)C=O>[CH2:4]([O:6][CH2:4][CH:2]1[O:3][CH2:1]1)[CH:2]1[O:3][CH2:1]1
Reactant: ClC[C@H]1CO1
Reactant: [OH-]
Agent: CC[N+](CC)(CC)Cc1ccccc1
Agent: [Cl-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C(OCC1CO1)C1CO1
Temperature: 25 °C
Reaction time: 0.67 h

Procedure:
The starting formula derivative (2.50 g) of the following formula: ##STR17## and the same R-(-)-epichlorohydrin (4.25 g) and benzyltriethylammonium chloride (20 mg) as used in Preparation 2 are dissolved in dimethylformamide (3 ml) and thereto is added dropwise 24 wt. % aqueous sodium hydroxide (1.2 equivalent) at 60° C. After reacting at the same temperature for 40 minutes, the reaction mixture is cooled to room temperature and extracted with ether. The extract is distilled under reduced pressure to remove the solvent. The residue is purified by silica gel chromatography to give S isomer of glycidyl ether (1.62 g) of the following formula: ##STR18##
Reaction SMILES: O[C:2]1[CH:3]=[C:4]([CH:7]=[C:8](O)[CH:9]=1)[CH2:5][OH:6].C(O)C1C=CC=CC=1.[C:19]([O-:27])(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[C:5]([O:27][C:19](=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)(=[O:6])[C:4]1[CH:7]=[CH:8][CH:9]=[CH:2][CH:3]=1
Reactant: OCc1cc(O)cc(O)c1
Reactant: O=C([O-])c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Solvent: OCc1ccccc1
Product: O=C(OC(=O)c1ccccc1)c1ccccc1

Procedure:
The synthesis of organotelluride catalysts based on 3,5-dihydroxybenzyl alcohol (1) is shown in FIG. 11. 3,5-Bis[3-(tert-butyldimethylsilyloxy)propyl-1-oxy]benzyl alcohol (5) (Francavilla et al., J. Am. Chem. Soc., 123:57 et al. (2001), which is hereby incorporated by reference in its entirety) was converted to the corresponding benzoate 6 in 99% isolated yield with benzoic anhydride and pyridine in the presence of catalytic DMAP. The silyl protecting groups were removed with HF-pyridine to give diol 7 in 89% isolated yield. Diol 7 was converted to the corresponding dibromide 8 in two steps (Wendler et al., Tetrahedron, 3:144 et al. (1958), which is hereby incorporated by reference in its entirety). The mesylate was first prepared, but not isolated, and was then treated in situ with lithium bromide to give dibromide 8 in 87% isolated yield. The addition of PhTeNa to 8 gave 9a with two phenyltelluro groups in 65% isolated yield; 4-Me2NC6H4TeNa, 9b with two dimethylaminophenyltelluro groups in 92% isolated yield; and n-C6H13TeNa, 9c with two hexyltelluro groups in 62% isolated yield.
Reaction SMILES: [Cl:1][CH:2]([CH2:6][C:7]1[CH:12]=[C:11]([N:13]2[C:17](=[O:18])[N:16]([CH:19]([F:21])[F:20])[C:15]([CH3:22])=[N:14]2)[C:10]([F:23])=[CH:9][C:8]=1[Cl:24])[C:3]([OH:5])=[O:4].[CH2:25](O)[CH3:26].CC1C=CC(S(O)(=O)=O)=CC=1>CC1C=CC=CC=1C>[CH3:25][CH2:26][O:4][C:3]([CH:2]([Cl:1])[CH2:6][C:7]1[CH:12]=[C:11]([N:13]2[N:14]=[C:15]([CH3:22])[N:16]([CH:19]([F:20])[F:21])[C:17]2=[O:18])[C:10]([F:23])=[CH:9][C:8]=1[Cl:24])=[O:5]
Reactant: CCO
Reactant: Cc1nn(-c2cc(CC(Cl)C(=O)O)c(Cl)cc2F)c(=O)n1C(F)F
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1C
Product: CCOC(=O)C(Cl)Cc1cc(-n2nc(C)n(C(F)F)c2=O)c(F)cc1Cl
Yield: 93 %

Procedure:
To a flask was added 140 g of the 2-chloro-3-{2-chloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorophenyl}propionic acid, obtained according to the Example 1, 140 g of ethanol, 1.9 g of 4-methylbenzenesulfonic acid and 400 g of dimethyl benzene. The mixture was refluxed for 15 hours to remove water. The excess ethanol was recovered by distillation. At room temperature the mixture was washed with 200 g of water, with 200 g of a 4% (wt/wt) aqueous solution of sodium hydroxide and finally with water. The solvent was completely removed under reduced pressure to give carfentrazone-ethyl as a faint yellow transparent and viscous liquid in a yield of 93% with a purity of 99%. A HNMR spectrum of the carfentrazone-ethyl is showed in FIG. 1 and a mass spectrum thereof is showed in FIG. 2.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[C:16](Cl)(=[O:18])[CH3:17]>ClCCl>[C:16]([O:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=1)(=[O:18])[CH3:17]
Reactant: Oc1cccc(Br)c1
Reactant: CC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)Oc1cccc(Br)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 99.4 %

Procedure:
3-Bromophenol (100 g, 580 mmol) and triethylamine (104 mL, 750 mmol) were dissolved in dichloromethane (500 mL), and the solution was cooled in an ice bath. Acetyl chloride (49.7 g, 630 mmol) was added dropwise. After 1 h the cooling bath was removed and the mixture was stirred overnight (approx 16 h) at room temperature. The mixture was washed with hydrochloric acid (1N, 250 mL), water (250 mL), 5% NaHCO3 (250 mL), and brine (250 mL). The organic layer was dried and evaporated to provide 124 g (99%) of 3-bromophenyl acetate as a light brown liquid; 1H NMR (CDCl3) δ7.36 (d, 1H), 7.32-7.20 (m, 2H), 7.05 (d, 1H), 2.28 (s, 3H).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([O:10][CH3:11])[N:3]=1.C(=O)([O-])[O-].[F:16][C:17](=[C:22]([F:24])[F:23])[CH2:18][C:19](Cl)=[O:20]>ClCCl.O>[F:16][C:17](=[C:22]([F:24])[F:23])[CH2:18][C:19]([NH:1][C:2]1[N:3]=[C:4]([O:10][CH3:11])[CH:5]=[C:6]([O:8][CH3:9])[N:7]=1)=[O:20]
Reactant: O=C(Cl)CC(F)=C(F)F
Reactant: COc1cc(OC)nc(N)n1
Agent: O=C([O-])[O-]
Solvent: ClCCl
Solvent: O
Product: COc1cc(OC)nc(NC(=O)CC(F)=C(F)F)n1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 10.7 %

Procedure:
To an ice-cooled stirred suspension of 2-amino-4,6-dimethoxypyrimidine (1.55 g, 10 mmol) in dichloromethane (50 mL) and potassinm carbonate (2.76 g, 20 mmol) in water (20 mL) was added 3,4,4-trifluoro-3-butenoyl chloride (3.17 g, 20 mmol). The reaction mixture was stirred in cold for 10 min and at r.t. for 15 min. The organic layer was washed with 3N HCl (2×25 mL), saturated sodium bicarbonate (25 mL) and brine, and dried. Evaporation of the solvent gave 0.296 g (10%) of the title compound as a white solid. m.p. 127°-130° C.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10]O)=[CH:4][CH:3]=1.[Br:12]C(Br)(Br)Br.O>ClCCl>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][Br:12])=[CH:4][CH:3]=1
Reactant: BrC(Br)(Br)Br
Reactant: OCCCc1ccc(O)cc1
Solvent: O
Solvent: ClCCl
Product: Oc1ccc(CCCBr)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 3-(4-hydroxyphenyl)-1-propanol 3A (4.0 g) and tripohenylphosphine (7.96 g) in anhydrous dichloromethane (77 mL), cooled to 0° C., is added, dropwise, a solution of tetrabromomethane (9.59 g) in anhydrous dichloromethane (15.4 mL). The reaction mixture gradually warmed to room temperature and allowed to stir overnight. The solution is then poured into water and extracted with ethyl acetate. The combined organic layers are washed with brine and dried over magnesium sulfate. The solution is concentrated in vacuo.
Reaction SMILES: [C:1]([O:6][CH:7]([O:9][C:10]([O:12][CH:13]1[CH2:18][C:17](=[O:19])[NH:16][C:14]1=[O:15])=[O:11])[CH3:8])(=[O:5])[CH:2]([CH3:4])[CH3:3].ON1C(=O)CCC1=O.[Cl:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([O:37]O)=[O:36])[CH:30]=1>C(Cl)Cl.CCOCC>[C:1]([O:6][CH:7]([O:9][C:10]([O:12][CH:13]1[CH2:18][C:17](=[O:19])[NH:16][C:14]1=[O:15])=[O:11])[CH3:8])(=[O:5])[CH:2]([CH3:4])[CH3:3].[Cl:28][C:29]1[CH:30]=[C:31]([CH:32]=[CH:33][CH:34]=1)[C:35]([OH:37])=[O:36]
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: CC(OC(=O)OC1CC(=O)NC1=O)OC(=O)C(C)C
Agent: O=C1CCC(=O)N1O
Solvent: ClCCl
Solvent: CCOCC
Product: O=C(O)c1cccc(Cl)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
In an alternative synthesis of (10), N-hydroxysuccinimide (558 mg, 4.8 mmol) was added to a solution of compound (6) (500 mg, 2.4 mmol) in CH2Cl2 (10 mL) and the reaction mixture cooled to 0° C. m-Chloroperbenzoic acid (1.62 g, 7.2 mmol, commercial grade: 77% in water) was added over a period of 10 min and the mixture allowed to stir at room temperature for 16 h. The reaction mixture was diluted with ether (50 mL) and washed with water (2×10 mL), saturated sodium bicarbonate solution (10 mL) and brine (10 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give the title compound (10) together with m-chlorobenzoic acid. The crude product mixture was purified by column chromatography on silica gel, eluting with 4:6 EtOAc:hexane. Residual m-chlorobenzoic acid was removed by repeated crystallizations from a mixture of tert-butyl methyl ether and hexane, resulting in analytically pure product (66 mg, 10%).
Reaction SMILES: [CH2:1]([C:5]1[NH:6][C:7]2[C:12]([C:13](=[O:15])[N:14]=1)=[CH:11][C:10]([C:16]#[CH:17])=[CH:9][CH:8]=2)[CH2:2][CH2:3][CH3:4].O.S(=O)(=O)(O)[OH:20]>C(O)(=O)C>[C:16]([C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][CH:9]=1)[NH:6][C:5]([CH2:1][CH2:2][CH2:3][CH3:4])=[N:14][C:13]2=[O:15])(=[O:20])[CH3:17]
Reactant: O=S(=O)(O)O
Reactant: C#Cc1ccc2[nH]c(CCCC)nc(=O)c2c1
Solvent: CC(=O)O
Solvent: O
Product: CCCCc1nc(=O)c2cc(C(C)=O)ccc2[nH]1
Temperature: 25 °C

Procedure:
To a solution of 1.20 g of 2-butyl-6-ethynyl-4(1H)-quinazolinone in 90 ml of acetic acid is added 0.45 g of mercuric sulfate, 0.9 ml of water and 0.3 ml of sulfuric acid. The reaction mixture is heated at reflux for 5 hours, cooled to room temperature and quenched with 150 ml of water. The resulting mixture is concentrated in vacuo, diluted with 150 ml of water and extracted with 6:1 chloroform-methanol. The combined organics are dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by flash chromatography on silica gel, eluting with 1:1 ethyl acetate-hexanes to give 0.67 g of the desired product as a white solid. CI MASS SPEC 245(MH+).
Reaction SMILES: [CH3:1][N:2]=[C:3]=[S:4].[Cl:5][C:6]1[CH:28]=[CH:27][C:9]([C:10]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[C:14]([CH2:23][NH:24][OH:25])=[C:13]2[CH3:26])=[O:11])=[CH:8][CH:7]=1>O1CCOCC1.O>[Cl:5][C:6]1[CH:28]=[CH:27][C:9]([C:10]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[C:14]([CH2:23][N:24]([OH:25])[C:3]([NH:2][CH3:1])=[S:4])=[C:13]2[CH3:26])=[O:11])=[CH:8][CH:7]=1
Reactant: CN=C=S
Reactant: COc1ccc2c(c1)c(CNO)c(C)n2C(=O)c1ccc(Cl)cc1
Solvent: C1COCCO1
Solvent: O
Product: CNC(=S)N(O)Cc1c(C)n(C(=O)c2ccc(Cl)cc2)c2ccc(OC)cc12
Reaction time: 8 h
Yield: 54.1 %

Procedure:
A solution of methyl isothiocyanate (1.36 g, 18.56 mmol) in 2 ml of dioxane is added dropwise to a suspension of 1-(4-chlorobenzoyl)-N-hydroxy-5-methoxy-2-methyl-1H-indole-3-methanamine (2.01 g, 5.84 mmol) in 60 ml of dioxane and 60 ml of H2O at 0° C. The ice bath is removed. After one hour 0.5 g (6.84 mmol) additional methyl isothiocyanate is added and the reaction mixture is stored in a freezer overnight. The solids are collected by filtration and recrystallized from THF/hexane, rinsed with ether, and dried under high vacuum over P2O5 to give pure 1-(4-chlorobenzoyl)-N-hydroxy-5-methoxy-2-methyl-N-[(methylamino)thioxomethyl]-1H-indole-3- methanamine (1.32 g, 54%); mp 198°-198.5° C. (dec).
Reaction SMILES: [CH:1]1([N:5]2[CH2:11][CH2:10][C:9]3[CH:12]=[C:13]([OH:16])[CH:14]=[CH:15][C:8]=3[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.Cl[C:18]1[N:23]=[CH:22][C:21]([C:24](=[O:26])[CH3:25])=[CH:20][CH:19]=1.C1(C2NCC3C=CC(OC4C=CC(C#N)=CN=4)=CC=3CC2)CCC1>>[CH:1]1([N:5]2[CH2:6][CH2:7][C:8]3[CH:15]=[CH:14][C:13]([O:16][C:18]4[N:23]=[CH:22][C:21]([C:24](=[O:26])[CH3:25])=[CH:20][CH:19]=4)=[CH:12][C:9]=3[CH2:10][CH2:11]2)[CH2:4][CH2:3][CH2:2]1
Reactant: CC(=O)c1ccc(Cl)nc1
Reactant: Oc1ccc2c(c1)CCN(C1CCC1)CC2
Agent: N#Cc1ccc(Oc2ccc3c(c2)CCC(C2CCC2)NC3)nc1
Product: CC(=O)c1ccc(Oc2ccc3c(c2)CCN(C2CCC2)CC3)nc1

Procedure:
Example 214 (E214) was prepared from 3-cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ol (E3) and 1-(6-chloropyridin-3-yl)ethanone using the method described for Example 100 (E100); MS (ES+) m/e 337 [M+H]+.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[CH:10]=[O:11].C1COCC1.[BH4-].[Na+]>CO>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[CH2:10][OH:11]
Reactant: O=Cc1cc2ccccc2o1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: OCc1cc2ccccc2o1
Temperature: 25 °C

Procedure:
To benzofuran-2-carbaldehyde (4 g, 27.4 mmol, 1 eq.), THF (50 mL) and methanol (50 mL) were added, under argon, and the reaction was cooled using an ice-salt bath. Then sodium borohydride (3.11 g, 82.1 mmol, 3 eq.) was added in several portions, and the reaction was allowed to warm slowly to room temperature for 1 hour. After work-up, benzofuran-2-yl-methanol was obtained in quantitative yield. 1H NMR (400 MHz, DMSO-d6) δ ppm 4.6 (d, J=5.8 Hz, 2 H) 5.5 (t, J=5.9 Hz, 1 H) 6.8 (s, 1 H) 7.3 (m, 2 H) 7.6 (m, 2 H).