Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][CH:4]=1.[Al+3].[Cl-].[Cl-].[Cl-].[Cl:15][CH2:16][C:17](Cl)=[O:18].Cl>ClCCl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=1[C:17](=[O:18])[CH2:16][Cl:15]
Reactant: COc1ccc(OC)cc1
Reactant: O=C(Cl)CCl
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: COc1ccc(OC)c(C(=O)CCl)c1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 63.3 %

Procedure:
In a three-neck round bottom 2 liter flask, 60.0 g (0.434 mol) of 1,4-dimethoxybenzene is added. To the flask is added 300 mL dry dichloromethane to dissolve the solid. When the solution is clear, 63.7 g (0.477 mol) of anhydrous AlCl3 is added through a powder funnel and the funnel is washed with dichloromethane. The resulting solution is yellowish in color. This solution is stirred at room temperature for 5 minutes and 40.0 mL (0.50 mol) chloroacetylchloride in 5 mL dichloromethane is added dropwise (total addition time 1 hour 30 minutes) and is stirred vigorously at room temperature. The color of the solution became is orange-red and then like red wine. The solution is stirred for 4 hours after addition at room temperature and then poured in to a mixture of crushed ice and 126 mL conc. HCl and stirred for 20 minutes again. The organic phase is separated and the aqueous phase is extracted with CH2Cl2 (100 mL×3). Total dichloromethane fractions are combined and washed with H2O (100 mL×2), cold 10% aq. NaOH (200 mL×1) and H2O (100 mL×2) and dried over anhydrous sodium sulfate. The organic phase is evaporated under reduced pressure and the thick solution is cooled to room temperature yielding a yellow solid (59.0 g, yield 64%). The crude product is crystallized from methanol (m.p. 89-91° C.).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([O:14][CH2:15][CH:16]=[C:17]([Cl:19])[Cl:18])[CH:5]=[C:6]([Cl:13])[C:7]=1[O:8][CH2:9][CH2:10][CH2:11]Br.[Cl:20][C:21]1[CH:31]=[CH:30][C:24]([O:25][CH2:26][C:27]([OH:29])=[O:28])=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[Cl:1][C:2]1[CH:3]=[C:4]([O:14][CH2:15][CH:16]=[C:17]([Cl:19])[Cl:18])[CH:5]=[C:6]([Cl:13])[C:7]=1[O:8][CH2:9][CH2:10][CH2:11][O:29][C:27](=[O:28])[CH2:26][O:25][C:24]1[CH:30]=[CH:31][C:21]([Cl:20])=[CH:22][CH:23]=1
Reactant: O=C(O)COc1ccc(Cl)cc1
Reactant: ClC(Cl)=CCOc1cc(Cl)c(OCCCBr)c(Cl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C(COc1ccc(Cl)cc1)OCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Temperature: 25 °C
Reaction time: 12 h
Yield: 91.4 %

Procedure:
In a reaction vessel were placed 0.20 g of 3,5-dichloro-4-(3-bromopropyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene, 0.11 g of 4-chlorophenoxyacetic acid, 0.08 g of potassium carbonate and 5 ml of N,N-dimethylformamide, followed by stirring at room temperature for 12 hours. The reaction mixture was poured into water, and extracted twice with 30 ml of diethyl ether. The combined ether layer was washed with water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude product was subjected to silica gel chromatography, which afforded 0.23 g of 3,5-dichloro-4-(3-(4-chlorophenoxyacetyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy) benzene (91% yield), nD22.0 1.5709.
Reaction SMILES: [OH:1][C:2]1([C:7]([OH:9])=O)[CH2:6][CH2:5][CH2:4][CH2:3]1.S(Cl)(Cl)=O.[C:14]1([S:20]([C:23]2[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][CH:24]=2)(=[O:22])=[O:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C>CC(N(C)C)=O>[C:14]1([S:20]([C:23]2[CH:24]=[CH:25][C:26]([NH:27][C:7]([C:2]3([OH:1])[CH2:3][CH2:4][CH2:5][CH2:6]3)=[O:9])=[CH:28][CH:29]=2)(=[O:21])=[O:22])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: Nc1ccc(S(=O)(=O)c2ccccc2)cc1
Reactant: O=C(O)C1(O)CCCC1
Agent: C
Solvent: O=S(Cl)Cl
Solvent: CC(=O)N(C)C
Product: O=C(Nc1ccc(S(=O)(=O)c2ccccc2)cc1)C1(O)CCCC1
Temperature: -10 °C
Reaction time: 1 h

Procedure:
A solution of 1-hydroxycyclopentanecarboxylic acid (0.76 g, 6.4 mmol) in dry dimethylacetamide (15 ml) was stirred under a nitrogen atmosphere at -10° C. Thionyl chloride (0.76 g, 6.4 mmol) was added and the resulting mixture was allowed to stir at -10° C. for 1 hour. 4-Phenylsulfonylaniline (1.0 g, 4.29 mmol) was then added and the reaction mixture was stirred at -10° C. for a further 15 mins. The solution was then allowed to warm to room temperature where it was stirred overnight. The reaction mixture was poured onto water, extracted with ethyl acetate, and the combined ethyl acetate portions were washed with water, and brine. After drying (Na2SO4) the ethyl acetate was removed by evaporation. Crystallization from ethyl acetate/hexane yielded the title tertiary carbinol (0.70 g, 47%) as a white solid; mp=214.0°-216.0° C. 1H--NMR (300 MHz, d6 --DMSO): 1.73 (m, 6 H, CH2), 1.97 (m, 2H, CH2), 5.67 (s, 1H, OH), 7.64 (m, 3H, ArH), 7.94 (m, 6H, ArH), 10.13 (s, 1H, NH). MS (CI, CH4): 346(M+1, 100).
Reaction SMILES: [CH3:1][C:2]1[C:3]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH:12]2[CH3:17])=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=O.O[N:19]=[C:20]([C:22]1[CH:30]=[CH:29][C:25]2[NH:26][CH:27]=[N:28][C:24]=2[CH:23]=1)[NH2:21]>>[CH3:1][C:2]1[CH:10]=[C:6]([C:7]2[O:9][N:19]=[C:20]([C:22]3[CH:30]=[CH:29][C:25]4[NH:26][CH:27]=[N:28][C:24]=4[CH:23]=3)[N:21]=2)[CH:5]=[N:4][C:3]=1[N:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH:12]1[CH3:17]
Reactant: NC(=NO)c1ccc2[nH]cnc2c1
Reactant: Cc1cc(C(=O)O)cnc1N1CCCCC1C
Product: Cc1cc(-c2nc(-c3ccc4[nH]cnc4c3)no2)cnc1N1CCCCC1C

Procedure:
Title compound was prepared following general procedure 1 starting from Intermediate 13 (120 mg; 0.51 mmol) and Intermediate 1 (90 mg; 0.51 mmol). Reaction mixture was filtered over a SPE-NH2 column, washed with THF followed by evaporation of the solvent under reduced pressure. Purification by silica column chromatography (EtOAc/c-Hex, 30/70 to 100/0) afforded the title compound as a brown powder. 1H NMR (DMSO, d6): δ 12.78 (s, 1H), 8.39-8.37 (m, 2H), 8.31 (s, 1H), 8.24 (dd, J=8.8, 2.2 Hz, 1H), 7.95-7.92 (m, 1H), 7.78-7.75 (m, 1H), 7.32 (d, J=8.8 Hz, 1H), 4.23-4.22 (m, 1H), 3.38-3.35 (m, 2H), 1.82-1.57 (m, 6H), 1.17 (d, 6.6 Hz, 3H). HPLC (Method A) Rt 2.71 min (Purity: 86.6%). LC/MS (method B): 358.3 (M+H)+.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:7]2)([O-:3])=[O:2].[H-].[Na+].[CH2:20](I)[CH2:21][CH3:22].O>CS(C)=O>[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:20][CH2:21][CH3:22])[C:8]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:7]2)([O-:3])=[O:2]
Reactant: CCCI
Reactant: CCOC(=O)c1cc2cc([N+](=O)[O-])ccc2[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CCCn1c(C(=O)OCC)cc2cc([N+](=O)[O-])ccc21
Temperature: 50 °C
Reaction time: 0.5 h

Procedure:
Under argon, 937 mg (4.00 mmol) of ethyl 5-nitro-1H-indole-2-carboxylate (A. Guy, J. -P. Guetté, Synthesis 1980, 222–223) are initially charged in 12 ml of dimethyl sulphoxide. 4.40 mmol of sodium hydride (176 mg of a 60% dispersion in paraffin) are added a little at a time, and the mixture is stirred at 50° C. for 30 min. After cooling to RT, 170 mg (4.40 mmol) of propyl iodide are added, and the mixture is stirred at RT for another 3 h. The reaction mixture is poured into 30 ml of water and extracted with ethyl acetate (6×30 ml). The combined organic phases are washed with 50 ml of sat. sodium chloride sol., dried over sodium sulphate and freed from the solvent using a rotary evaporator. The resulting brown crude product is purified by column chromatography (silica gel 60, mobile phase gradient cyclohexane→cyclohexane-ethyl acetate 3:1), giving the product as second fraction.
Reaction SMILES: [C:1]1([C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([OH:16])[CH:14]=3)[N:9]3[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:8]=23)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:22]([O:24][C:25](=[O:30])[C:26](Br)([CH3:28])[CH3:27])[CH3:23]>>[CH2:22]([O:24][C:25](=[O:30])[C:26]([O:16][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[N:9]1[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:8]1=[C:7]2[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)([CH3:28])[CH3:27])[CH3:23]
Reactant: Oc1ccc2c(c1)c(-c1ccccc1)c1n2CCCCC1
Reactant: CCOC(=O)C(C)(C)Br
Product: CCOC(=O)C(C)(C)Oc1ccc2c(c1)c(-c1ccccc1)c1n2CCCCC1

Procedure:
In accordance with a procedure analogous to that of Example 10, the above compound was prepared from 7,8,9,-10-tetrahydro-11-phenyl-6H-azepino[1,2-a]-indole-2-ol and 2-bromo-2-methyl-propanoic acid ethylester.
Reaction SMILES: Cl.[CH3:2][N:3]([CH2:5][CH:6]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]1=[O:15])[CH3:4].CCC(C)[BH-](C(C)CC)C(C)CC.[Li+].[OH-].[Na+]>O1CCCC1>[CH3:4][N:3]([CH2:5][C@H:6]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C@H:7]1[OH:15])[CH3:2]
Reactant: CN(C)CC1Cc2ccccc2C1=O
Agent: CCC(C)[BH-](C(C)CC)C(C)CC
Agent: Cl
Agent: [Li+]
Solvent: C1CCOC1
Product: CN(C)C[C@H]1Cc2ccccc2[C@H]1O
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 48.3 %

Procedure:
To an ice-cooled suspension of 2.25 g (0.01M) of 2,3-dihydro-2-(N,N-dimethylaminomethyl)-1H-inden-1-one hydrochloride in 50 ml of dry tetrahydrofuran add 25 ml of a 1M solution of L-Selectride®. Stir the mixture for 1.5 hours and decompose with 5 ml of 10% sodium hydroxide solution. Evaporate the solvent at reduced pressure and distribute the residue between ether and water. Separate the ether layer and extract with dilute hydrochloric acid. Basify the acid extract to yield an oil. Extract the oil into ethyl acetate. Evaporate the solvent and Kugelrohr distill at 90°-100°/0.4 mm to yield 0.92 g (48% yield) of the title compound.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:14]([OH:16])=[O:15])=[N:4][C:5]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)=[CH:6][N:7]=1.OS(O)(=O)=O.[CH3:22]O>>[NH2:1][C:2]1[C:3]([C:14]([O:16][CH3:22])=[O:15])=[N:4][C:5]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)=[CH:6][N:7]=1
Reactant: Nc1ncc(-c2cccnc2)nc1C(=O)O
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)c1nc(-c2cccnc2)cnc1N
Yield: 97 %

Procedure:
To 3-amino-6-(3-pyridyl)pyrazine-2-carboxylic acid (2 g, 9.251 mmol) in MeOH (50 mL) was added conc. H2SO4 (907.3 mg, 493.1 μL, 9.251 mmol) and the mixture heated to reflux for 2 hours. The solvent was removed in vacuo and the mixture neutralised with aq. Na2CO3. The resulting brown solid was collected by filtration and dried (2.08 g, 97% Yield). MS (ES+) 231
Reaction SMILES: Br[CH2:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=1.[C:13]1(=[O:23])[NH:17][C:16](=[O:18])[C:15]2=[CH:19][CH:20]=[CH:21][CH:22]=[C:14]12.[K]>CN(C)C=O>[CH:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:11]=[CH:12][C:3]=1[CH2:2][N:17]1[C:16](=[O:18])[C:15]2=[CH:19][CH:20]=[CH:21][CH:22]=[C:14]2[C:13]1=[O:23]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: BrCc1ccc2ccccc2c1
Agent: [K]
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1Cc1ccc2ccccc2c1
Temperature: 50 °C
Reaction time: 2 h
Yield: 58.5 %

Procedure:
To a solution of 2-(bromomethyl)naphthalene (0.500 g) in N,N-dimethylformamide (11 mL) was added potassium phthalimide (0.461 g), and the resulting mixture was stirred at 50° C. for 2 hours. The reaction mixture was partitioned between ethyl acetate (50 mL) and water (15 mL). The organic layer was washed successively with water (15 mL×2) and brine (15 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound (0.380 g).
Reaction SMILES: [CH3:1][C@:2]12[C@@:19]3([CH3:20])[C@@H:10]([C@:11]4([CH3:33])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:22])([CH3:21])[C:14]([C:23]3[CH:32]=[CH:31][C:26]([C:27]([O:29]C)=[O:28])=[CH:25][CH:24]=3)=[CH:13][CH2:12]4)[CH2:9][CH2:8][C@@H:7]1[C@H:6]1[C@H:34]([C:37]([CH3:39])=[CH2:38])[CH2:35][CH2:36][C@:5]1([NH:40][CH2:41][CH2:42][C:43]([F:46])([F:45])[F:44])[CH2:4][CH2:3]2.[OH-].[Na+]>O1CCOCC1.CO>[CH3:1][C@:2]12[C@@:19]3([CH3:20])[C@@H:10]([C@:11]4([CH3:33])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:21])([CH3:22])[C:14]([C:23]3[CH:24]=[CH:25][C:26]([C:27]([OH:29])=[O:28])=[CH:31][CH:32]=3)=[CH:13][CH2:12]4)[CH2:9][CH2:8][C@@H:7]1[C@H:6]1[C@H:34]([C:37]([CH3:39])=[CH2:38])[CH2:35][CH2:36][C@:5]1([NH:40][CH2:41][CH2:42][C:43]([F:44])([F:45])[F:46])[CH2:4][CH2:3]2
Reactant: C=C(C)[C@@H]1CC[C@]2(NCCC(F)(F)F)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)OC)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1COCCO1
Product: C=C(C)[C@@H]1CC[C@]2(NCCC(F)(F)F)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Temperature: 75 °C
Yield: 66 %

Procedure:
To a solution of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-((3,3,3-trifluoropropyl)amino)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate (0.032 g, 0.050 mmol) in 1,4-dioxane (1 mL) was added NaOH (1N) (0.2 mL, 0.200 mmol). The mixture was heated to 75° C. for 22.5 h then was cooled to rt. The mixture was diluted with methanol, was filtered through a plug of glass wool and was purified by Prep HPLC. The fractions containing the expected product were combined and concentrated under reduced pressure to give 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-((3,3,3-trifluoropropyl)amino)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acid (0.022 g, 0.033 mmol, 66.8% yield) as a white solid. LCMS: m/e 626.6 (M+H)+, 1.87 min (method 2). 1H NMR (400 MHz, Acetic acid d4) 67.99 (d, J=8.28 Hz, 2H), 7.25 (d, J=8.28 Hz, 2H), 5.33 (d, J=4.77 Hz, 1H), 4.82 (s, 1H), 4.70 (s, 1H), 3.36-3.51 (m, 2H), 2.81-2.97 (m, 3H), 2.12-2.28 (m, 4H), 1.72 (s, 3H), 1.17 (s, 3H), 1.09 (s, 3H), 1.05 (s, 3H), 0.98 (s, 3H), 0.96 (s, 3H), 0.82-2.11 (m, 18H).
Reaction SMILES: [Cl:1][C:2]1[CH:22]=[C:21]([CH:23]=[CH2:24])[CH:20]=[CH:19][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][C:11]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH:13]=[C:8]2[N:7]=[C:6]1[CH3:18].C(Cl)(Cl)Cl.C(OCC)(=O)C>O1CCOCC1.[Pt](=O)=O>[Cl:1][C:2]1[CH:22]=[C:21]([CH2:23][CH3:24])[CH:20]=[CH:19][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][C:11]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH:13]=[C:8]2[N:7]=[C:6]1[CH3:18]
Reactant: C=Cc1ccc(Cn2c(C)nc3ccc(C(=O)OC)nc32)c(Cl)c1
Agent: O=[Pt]=O
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Solvent: ClC(Cl)Cl
Product: CCc1ccc(Cn2c(C)nc3ccc(C(=O)OC)nc32)c(Cl)c1
Yield: 92.5 %

Procedure:
To a solution of methyl 3-(2-chloro-4-vinylbenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine-5-carboxylate (230 mg, 0.67 mmol) in 1,4-dioxane (4.6 ml) was added platinum dioxide (23 mg) and the mixture was subjected to catalytic reduction at normal temperature. Six hours later, the reaction mixture was filtered through Celite and the filtrate was concentrated to give black crystals. The obtained crystals were subjected to flash silica gel chromatography (silica gel 40 ml, eluent: chloroform/ethyl acetate=5/1-4/1) and crystallized from diisopropyl ether to give the object compound (213 mg) as colorless crystals.
Reaction SMILES: [F:1][C:2]1[C:3]([O:29]C)=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]([NH:12][C:13]1[CH:21]=[CH:20][CH:19]=[C:18]3[C:14]=1[CH:15]=[N:16][NH:17]3)[C:7]([C:23]([F:26])([F:25])[F:24])([OH:22])[CH2:6][C:5]2([CH3:28])[CH3:27].B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>ClCCl>[F:1][C:2]1[CH:11]=[CH:10][C:9]2[CH:8]([NH:12][C:13]3[CH:21]=[CH:20][CH:19]=[C:18]4[C:14]=3[CH:15]=[N:16][NH:17]4)[C:7]([C:23]([F:25])([F:26])[F:24])([OH:22])[CH2:6][C:5]([CH3:27])([CH3:28])[C:4]=2[C:3]=1[OH:29]
Reactant: COc1c(F)ccc2c1C(C)(C)CC(O)(C(F)(F)F)C2Nc1cccc2[nH]ncc12
Agent: BrB(Br)Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CC1(C)CC(O)(C(F)(F)F)C(Nc2cccc3[nH]ncc23)c2ccc(F)c(O)c21
Temperature: 25 °C
Yield: 92.8 %

Procedure:
200 mg (0.472 mmol) of the above-described (−)-6-fluoro-5-methoxy-1-[(1H-indazol-4-yl)amino]-4,4-dimethyl-2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalen-2-ol is mixed at room temperature with 4.7 ml of a 1 M solution of BBr3 in dichloromethane and stirred for three and three-quarters hours at room temperature. The reaction mixture is mixed drop by drop at −30° C. with saturated sodium bicarbonate solution, specifically until a pH of 8 is reached. After dilution with ethyl acetate, the cold bath is removed, and the batch is stirred vigorously for 15 minutes. After 2× shaking with ethyl acetate, the combined organic extracts are washed with water and saturated brine. After drying on sodium sulfate, and after the solvent is filtered and spun off, the residue is chromatographed on silica gel (mobile solvent dichloromethane/methanol). 179.4 mg (92.8%) of the desired compound is obtained. The angle of rotation, measured at room temperature, is [α]D=−7.8 (c=1, MeOH).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:6](Cl)=[O:7].[CH3:14][C:15]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][C:16]=1[NH2:17].N1C=CC=CC=1>C(Cl)Cl>[CH3:14][C:15]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][C:16]=1[NH:17][C:6](=[O:7])[C:5]1[CH:9]=[CH:10][C:11]([O:12][CH3:13])=[C:3]([O:2][CH3:1])[CH:4]=1
Reactant: Cc1ccc([N+](=O)[O-])cc1N
Reactant: COc1ccc(C(=O)Cl)cc1OC
Solvent: c1ccncc1
Solvent: ClCCl
Product: COc1ccc(C(=O)Nc2cc([N+](=O)[O-])ccc2C)cc1OC
Temperature: 25 °C
Reaction time: 18 h
Yield: 87.7 %

Procedure:
A solution of 3,4-dimethoxybenzoyl chloride (11.5 g) in methylene chloride (100 ml) was added dropwise to a stirred mixture of 2-methyl-5-nitroaniline (8.74 g), pyridine (18.6 ml) and methylene chloride (200 ml) and the mixture was stirred at ambient temperature for 18 hours. The mixture was washed with 2M hydrochloric acid and with water, dried over magnesium sulphate, filtered and evaporated to dryness. The resultant solid was dried under vacuum at 60° C. to yield N-(2-methyl-5-nitrophenyl)-3,4-dimethoxybenzamide (15.9 g); m.p.>300° C.; NMR: (CDCl3) 2.43 (s, 3H), 3.94 (m, 6H), 6.93 (m, 1H), 7.38 (m, 2H), 7.51 (m, 1H), 7.75 (broad s, 1H), 7.94 (d, 1H), 8.89 (broad m, 1H).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.[O:11]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14][C:12]1=[O:13]>>[OH:11][C:21]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH2:15][CH2:14][C:12]([NH:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1)=[O:13]
Reactant: O=C1CCc2ccccc2O1
Reactant: NCCCN1CCOCC1
Product: O=C(CCc1ccccc1O)NCCCN1CCOCC1
Temperature: 70 °C
Reaction time: 1 h
Yield: 116.5 %

Procedure:
N-(3-Aminopropyl)morpholine (1.77 g) was added to 3,4-dihydrocoumarine (1.81 g) and stirred for 1 hours at 70° C., thereby yielding the entitled compound (4.16 g) as pale yellow syrup.
Reaction SMILES: [C:1]([S@:5](/[N:7]=[CH:8]/[C:9]1[CH:21]=[CH:20][C:12]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[CH:11][CH:10]=1)=[O:6])([CH3:4])([CH3:3])[CH3:2].[F:22][C:23]([Si](C)(C)C)([F:25])[F:24]>C1COCC1>[C:1]([S@:5]([NH:7][C@@H:8]([C:9]1[CH:10]=[CH:11][C:12]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[CH:20][CH:21]=1)[C:23]([F:25])([F:24])[F:22])=[O:6])([CH3:4])([CH3:2])[CH3:3]
Reactant: C[Si](C)(C)C(F)(F)F
Reactant: CC(C)(C)OC(=O)c1ccc(/C=N/[S@](=O)C(C)(C)C)cc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)c1ccc([C@H](N[S@](=O)C(C)(C)C)C(F)(F)F)cc1
Temperature: -30 °C
Reaction time: 2 h
Yield: 71.7 %

Procedure:
To a 50-mL oven-dried round-bottom flask charged with tert-butyl 4-[(E)-{[(R)-tert-butylsulfinyl]imino}methyl]benzoate (0.16 g, 0.5 mmol), tetra-n-butylammoniumdifluoro-triphenylsilicate (0.30 g, 0.55 mmol), THF (8 mL) was slowly added (trifluoromethyl)trimethylsilane (0.94 mL, 0.60 mmol) in THF (2 mL) slowly at −45° C. The mixture was stirred at this temperature for 2 h, then warmed to −30° C. and stirred for 1 h. The reaction was quenched with addition of sat. NH4Cl (5 mL) and EtOAc (10 mL) at −30° C. After warming to rt, the mixture was extracted with EtOAc (2×20 mL). The combined organic phases were washed with brine (10 mL), dried (MgSO4), and concentrated. Purification via flash chromatography (10% EtOAc-hexanes to 20% EtOAc-hexanes) afforded tert-butyl 4-[(1S)-1-{[(R)-tert-butylsulfinyl]amino}-2,2,2-trifluoroethyl]benzoate (0.136 g, 72%) as a white solid. 1H NMR (Methanol-d4, 300 MHz) δ 7.98 (d, J=8.5 Hz, 2H), 7.65 (d, J=8.3 Hz, 2H), 5.15 (d, J=7.9 Hz, 1H), 1.59 (s, 9H), 1.23 (s, 9H).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6](Cl)=[O:7].[NH2:9][C:10]1[CH:11]=[C:12]([C:16]2[C:25]3[CH2:24][CH2:23][CH2:22][CH2:21][C:20]=3[C:19](=[O:26])[NH:18][N:17]=2)[CH:13]=[CH:14][CH:15]=1.C(=O)([O-])[O-].[K+].[K+].Cl>O1CCCC1.O>[Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]([NH:9][C:10]1[CH:11]=[C:12]([C:16]2[C:25]3[CH2:24][CH2:23][CH2:22][CH2:21][C:20]=3[C:19](=[O:26])[NH:18][N:17]=2)[CH:13]=[CH:14][CH:15]=1)=[O:7]
Reactant: Nc1cccc(-c2n[nH]c(=O)c3c2CCCC3)c1
Reactant: O=C(Cl)CCCCCl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: O=C(CCCCCl)Nc1cccc(-c2n[nH]c(=O)c3c2CCCC3)c1
Reaction time: 0.5 h

Procedure:
5-chloropentanoyl chloride (171 mg) was added dropwise to a mixed solution of the compound prepared in Example 1 (241 mg) and potassium carbonate (89.8 mg) in tetrahydrofuran (3.00 mL) and water (1.00 mL) in ice bath and the mixture was stirred for 30 minutes. Moreover, potassium carbonate (45.0 mg) and 5-chloropentanoyl chloride (85.5 mg) was added the reaction mixture, which was stirred for 30 minutes. 1N hydrochloric acid was added to the reaction mixture, which was adjusted to pH 2. Water was added thereto and the deposited crystal was collected by filtration. It was washed with water and hexane sequentially and dried under reduced pressure to give the compound of the present invention (347 mg) having the following physical data.
Reaction SMILES: [CH:1]1([C:6]2[CH:7]=[CH:8][C:9]3[O:13][C:12]([C:14]4[CH:15]=[C:16]5[C:21](=[CH:22][CH:23]=4)[CH2:20][N:19]([CH2:24][CH2:25][C:26]([O:28]C(C)(C)C)=[O:27])[CH2:18][CH2:17]5)=[CH:11][C:10]=3[CH:33]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:1]1([C:6]2[CH:7]=[CH:8][C:9]3[O:13][C:12]([C:14]4[CH:15]=[C:16]5[C:21](=[CH:22][CH:23]=4)[CH2:20][N:19]([CH2:24][CH2:25][C:26]([OH:28])=[O:27])[CH2:18][CH2:17]5)=[CH:11][C:10]=3[CH:33]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: CC(C)(C)OC(=O)CCN1CCc2cc(-c3cc4cc(C5CCCC5)ccc4o3)ccc2C1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(O)CCN1CCc2cc(-c3cc4cc(C5CCCC5)ccc4o3)ccc2C1
Temperature: 25 °C
Reaction time: 3 h
Yield: 87.1 %

Procedure:
To a stirring solution of tert-butyl 3-(6-(5-cyclopentylbenzofuran-2-yl)-3,4-dihydroisoquinolin-2(1H)-yl)propanoate (25 mg, 0.056 mmole) in CH2Cl2 (0.5 ml) was added TFA (0.5 ml). The mixture was stirred at room temperature for 3 hours. Under reduced pressure, solvents and excess of TFA were removed affording a yellow oil which was rinsed with a mixture of CH2Cl2/Hexane (1:4) followed by ether. The solvents were removed under vacuum to give the title compound (19 mg, 90%). 1H NMR (400 MHz, CD3OD) δ 7.82 (m, 2H), 7.47 (s, 1H), 7.40 (d, 1H), 7.30 (d, 1H), 7.20 (d, 1H), 7.19 (s, 1H), 4.54 (br, 2H), 3.69 (br, 2H), 3.60 (dd, 2H), 3.28 (m, 2H), 3.10 (m, 1H), 2.96(dd, 2H), 2.10 (m, 2H), 1.85 (m, 2H), 1.74 (m, 2H), 1.65 (m, 2H). MS (ESI) m/z: Calculated: 389.2; Observed: 390.20 (M++1).