Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]2[CH2:11][CH2:10][CH2:9][CH2:8][C:7]=2[N:6]=[C:5]([NH2:13])[N:4]=1.Br[CH2:15][C:16](=O)[C:17]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:18]>CCOCC>[CH3:1][O:2][C:3]1[C:12]2[CH2:11][CH2:10][CH2:9][CH2:8][C:7]=2[N:6]2[CH:15]=[C:16]([C:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:18])[N:13]=[C:5]2[N:4]=1
Reactant: COc1nc(N)nc2c1CCCC2
Reactant: O=C(CBr)C(=O)c1ccccc1
Solvent: CCOCC
Product: COc1nc2nc(C(=O)c3ccccc3)cn2c2c1CCCC2

Procedure:
A solution of 20 g of 4-methoxy-5,6,7,8-tetrahydro-2-quinazolinamine, 28.6 g of 3-bromo-1-phenyl-propane- 1,2-dione and 400 ml of ether was stirred overnight at room temperature and was filtered. The 29.5 g of 4-methoxy-1-(3-phenyl-2,3-dioxopropyl)-5,6,7,8-tetrahydro-2-quinazolinium bromide were washed with ether and suspended in methanol. The suspension was refluxed for 2 hours and the solution was evaporated to dryness under reduced pressure. The residue was shaken with a mixture of aqueous potassium carbonate and chloroform and the decanted organic phase was washed with water, dried over magnesium sulfate and evaporated to dryness under reduced pressure. The residue was triturated with ethanol and filtered to obtain 18 g of (5-methoxy-6,7,8,9-tetrahydroimidazo[1,2-a]quinazolin-2-yl-phenylmethanone in the form of pale yellow crystals melting at 234° C.
Reaction SMILES: Cl.[CH:2]([NH2:4])=[NH:3].[O-]CC.[Na+].CN([CH:12]=[C:13]1[CH2:17][N:16](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH2:15][C:14]1=O)C>C(O)C.C(OCC)(=O)C>[N:3]1[C:14]2[CH2:15][NH:16][CH2:17][C:13]=2[CH:12]=[N:4][CH:2]=1
Reactant: N=CN
Reactant: CN(C)C=C1CN(C(c2ccccc2)(c2ccccc2)c2ccccc2)CC1=O
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CCO
Product: c1ncc2c(n1)CNC2
Temperature: 80 °C
Reaction time: 2.5 h

Procedure:
To a solution of formamidine hydrochloride (190 mg) in anhydrous ethanol (25.0 mL) under nitrogen were added sodium ethoxide (21% wt in ethanol, 1.2 mL) and 4-[(dimethylamino)methylene]-1-tritylpyrrolidin-3-one (300 mg, prepared as described for Step B, Intermediate 4). The mixture was refluxed at 80° C. for 8 h. The reaction mixture was cooled to ambient temperature and diluted with ethyl acetate. The organic layer was washed sequentially with 5% aqueous citric acid solution and brine, dried over anhydrous sodium sulfate, filtered, concentrated. The crude residue was deprotected by treatment with 4N methanolic hydrogen chloride for 2.5 h. The mixture was concentrated and the residue purified by chromatography on a Biotage® system (silica, gradient 15% to 25% of 10% concentrated ammonium hydroxide in methanol/dichloromethane) to give the title compound. LC-MS=243.1 (M+1).
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[CH:7]2.[Si:13]([O:20][CH2:21][CH2:22]Br)([C:16](C)(C)C)([CH3:15])C>CN(C=O)C>[CH2:5]([CH:21]([O:20][SiH:13]([CH3:15])[CH3:16])[CH2:22][N:9]1[C:10]2[C:6](=[CH:5][C:4]([Br:3])=[CH:12][CH:11]=2)[CH:7]=[CH:8]1)[CH2:4][CH2:12][CH3:11]
Reactant: Brc1ccc2[nH]ccc2c1
Reactant: CC(C)(C)[Si](C)(C)OCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCC(Cn1ccc2cc(Br)ccc21)O[SiH](C)C
Reaction time: 1 h
Yield: 151.8 %

Procedure:
To a slurry of sodium hydride (12 g, 0.3 mol, 60% dispersion in oil) in DMF (200 mL) was added dropwise a solution of 5-bromoindole (50 g, 0.255 mol) in DMF (300 mL). After stirring for 15 minutes 2-t-butyldimethylsilyloxyethyl bromide (60 g, 0.255 mol, neat) was added dropwise and the reaction mixture stirred for 1 hour. The reaction mixture was partitioned between ice water and ethyl ether. The organic fraction was washed with water, dried over Na2SO4, filtered and concentrated in vacuo. The product was purified by column chromatography (silica, 3:1 hexane/acetone) to give 68.6 g of the title compound as a light yellow oil.
Reaction SMILES: Cl.[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH2:16][CH2:17][CH2:18][N:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[CH:5][CH:4]=1.[Cl:24][C:25]1[C:31]([OH:32])=[CH:30][C:28]([NH2:29])=[C:27]([F:33])[CH:26]=1>CC(O)CCC.CN(C=O)C>[ClH:2].[Cl:24][C:25]1[C:31]([OH:32])=[CH:30][C:28]([NH:29][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:15][CH2:16][CH2:17][CH2:18][N:19]4[CH2:23][CH2:22][CH2:21][CH2:20]4)=[C:10]([O:13][CH3:14])[CH:11]=3)[N:6]=[CH:5][CH:4]=2)=[C:27]([F:33])[CH:26]=1
Reactant: COc1cc2c(Cl)ccnc2cc1OCCCN1CCCC1
Reactant: Nc1cc(O)c(Cl)cc1F
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCCC(C)O
Product: COc1cc2c(Nc3cc(O)c(Cl)cc3F)ccnc2cc1OCCCN1CCCC1
Yield: 54.4 %

Procedure:
A solution of 4-chloro-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinoline hydrochloride (325 mg, 0.82 mmol) and 4-chloro-2-fluoro-5-hydroxyaniline (133 mg, 0.82 mmol), (as described in EP 61741 A2), in 2-pentanol (10 ml) and DMF (1 ml) was heated at reflux for 5 hours. The volatiles were removed by evaporation and the residue was purified by column chromatography eluting with acetonitrile/water containing 1% TFA (30/70). Concentrated hydrochloric acid was added to the fractions and the solvents were removed by evaporation. The residue was azeotroped with toluene, and triturated with isopropanol. The solid was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinoline hydrochloride (215 mg, 50%).
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][NH:8]2)=[CH:4][C:3]=1[C:11]#[C:12][CH2:13][CH2:14][CH2:15][OH:16].C(N(C(C)C)C(C)C)C.Cl[C:27]([O:29][C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=1)=[O:28].O>C(Cl)Cl>[Cl:36][C:33]1[CH:34]=[CH:35][C:30]([O:29][C:27]([N:8]2[C:9]3[C:5](=[CH:4][C:3]([C:11]#[C:12][CH2:13][CH2:14][CH2:15][OH:16])=[C:2]([F:1])[CH:10]=3)[CH2:6][CH2:7]2)=[O:28])=[CH:31][CH:32]=1
Reactant: O=C(Cl)Oc1ccc(Cl)cc1
Reactant: OCCCC#Cc1cc2c(cc1F)NCC2
Solvent: ClCCl
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(Oc1ccc(Cl)cc1)N1CCc2cc(C#CCCCO)c(F)cc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 74.3 %

Procedure:
A solution of 99 mg (0.45 mmol) 5-(6-Fluoro-2,3-dihydro-1H-indol-5-yl)-pent-4-yn-1-ol and 0.155 ml (0.90 mmol) N-Ethyldiisopropylamine in 2 ml CH2Cl2 was treated with 0.125 ml (0.90 mmol) 4-chlorophenyl chloroformate and stirred at room temperature during 1 hour. The mixture was poured into water, extracted with EtOAc and the combined organic layers were dried with MgSO4. Evaporation of the solvent, chromatography on silica gel with CH2Cl2/MeOH 49:1 gave 125 mg (74%) of 6-Fluoro-5-(5-hydroxy-pent-1-ynyl)-2,3-dihydro-indole-1-carboxylic acid 4-chloro-phenyl ester as a viscous light yellow oil, MS: 374 (MH+, 1Cl).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH2:9][C:10]2[CH:15]=[C:14]([O:16][CH2:17][C:18]3([CH2:21][O:22][CH3:23])[CH2:20][CH2:19]3)[C:13]([C:24]3[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=3)=[C:12]([O:31][CH2:32][CH3:33])[CH:11]=2)=[CH:4][N:3]=1.O>C(O)C.C(O)(=O)C.O=[Pt]=O>[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH2:9][C:10]2[CH:11]=[C:12]([O:31][CH2:32][CH3:33])[C:13]([C:24]3[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=3)=[C:14]([O:16][CH2:17][C:18]([CH3:19])([CH3:20])[CH2:21][O:22][CH3:23])[CH:15]=2)=[CH:4][N:3]=1
Reactant: CCOc1cc(Cc2cnc(N)nc2N)cc(OCC2(COC)CC2)c1-c1ccc(O)cc1
Agent: O=[Pt]=O
Solvent: CC(=O)O
Solvent: O
Solvent: CCO
Product: CCOc1cc(Cc2cnc(N)nc2N)cc(OCC(C)(C)COC)c1-c1ccc(O)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 44.2 %

Procedure:
4′-(2,4-Diamino-pyrimidin-5-ylmethyl)-2′-ethoxy-6′-(1-methoxymethyl-cydopropylmethoxy)-biphenyl-4-ol (235 mg; 0.52 mmol) is hydrogenated in ethanol/acetic acid conc./water (4/1/0.1) (10 ml) over PtO2 (6×35 mg) at 100° C. The reaction mixture is cooled to room temperature, the catalyst is filtered off with suction and the filtrate is concentrated. The residue is stirred in water, the pH is adjusted to pH 9 by addition of NH4OH conc., stirring is continued for 30 minutes and the mixture is filtered with suction. The grey crude product is then chromatographed over silica gel (20 g) with methylene chloride/methanol/NH4OH conc. (19/1/0.05). 104 mg (44%) 4′-(2,4-diamino-pyrimidin-5-ylmethyl)-6′-ethoxy-2′-(3-methoxy-2,2-dimethyl-propoxy)-biphenyl-4-ol are obtained as a colourless powder.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([CH2:18][C:19](OCC)=[O:20])[N:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Li+].[Cl-].[NH4+]>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([CH2:18][CH2:19][OH:20])[N:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCOC(=O)Cc1ccc2c(n1)N(C(=O)OC(C)(C)C)CCC2
Agent: [BH4-]
Agent: [Cl-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCCc2ccc(CCO)nc21
Yield: 49 %

Procedure:
7-Ethoxycarbonylmethyl-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester (synthetic methodology described in Publsihed International Patent Appl. WO 00/33838) (6.11 g, 19.0 mmol) was dissolved in tetrahydrofuran (40 mL) at room temperature. The solution was place under argon. Lithium borohydride [2M in tetrahydrofuran] (22.8 mmol, 11.43 mL) was carefully added and the reaction was refluxed overnight (16 h). The mixture was poured into a solution of saturated ammonium chloride and extracted with ethyl acetate. The organic layer was dried over Na2SO4, filtered, and evaporated under vacuum to give a crude mixture, which was purified via column chromatography to give 7-(2-hydroxy-ethyl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester (49% yield). 1H NMR (Cl3CD), δ: 7.30 (d, 1H, J=7.6 Hz), 7.76(d, 1H, J=7.6 Hz), 3.98 (m, 2H), 3.78 (m, 2H), 2.92 (m, 2H), 2.71 (m, 2H), 1.92(m, 2H), 1.54 (s, 9H).
Reaction SMILES: [CH2:1]([NH2:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].Cl[CH2:11][CH:12]([OH:23])[CH2:13][N:14]([CH2:20][CH2:21][OH:22])[CH2:15][CH:16]([OH:19])[CH2:17]Cl>C1(C)C(C)=CC=CC=1>[OH:23][CH:12]([CH2:13][N:14]([CH2:20][CH2:21][OH:22])[CH2:15][CH:16]([OH:19])[CH2:17][NH:9][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH2:11][NH:9][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCCCCN
Reactant: OCCN(CC(O)CCl)CC(O)CCl
Solvent: Cc1ccccc1C
Product: CCCCCCCCNCC(O)CN(CCO)CC(O)CNCCCCCCCC
Temperature: 70 °C
Yield: 69.1 %

Procedure:
A reactor was charged with 275 g (2.2 moles) of octylamine, and the contents were heated to 70° C. To the contents, a solution with 36 g (0.17 mole) of N,N-bis(3-chloro-2-hydroxypropyl)hydroxyethylamine dissolved in 30 g of xylene was then added dropwise over 40 minutes. The resultant mixture was aged further for 4 hours. Thereafter, xylene was distilled off under reduced pressure, and unreacted octylamine was then distilled off at 70° C. and 0.5 mmHg. A mixture of 500 ml of xylene and 500 ml of 5% aqueous sodium hydroxide was added to the residue to subject it to extraction and washing. Thereafter, a xylene layer was taken out and concentrated, thereby obtaining 50.7 g (yield: 69%) of 11,15-dihydroxy-13-hydroxyethyl-9,13,17-triazapentacosane represented by the following formula. ##STR13##
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]([CH3:18])([CH3:17])[CH2:9][C@:10]1([C:13]([F:16])([F:15])[F:14])[CH2:12][O:11]1.[Br:19]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[Br:19][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]([CH3:18])([CH3:17])[CH2:9][C@:10]1([C:13]([F:14])([F:16])[F:15])[CH2:12][O:11]1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1ccccc1C(C)(C)C[C@]1(C(F)(F)F)CO1
Solvent: ClC(Cl)(Cl)Cl
Product: CC(C)(C[C@]1(C(F)(F)F)CO1)c1ccccc1CBr
Temperature: 70 °C

Procedure:
To a stirred solution of (R)-2-[2-(2-methylphenyl)-2-methylpropyl]-2-trifluoromethyloxirane (37 g, 0.143 mmol) in 500 mL of anhydrous CCl4 at room temperature was added N-bromosuccinimide (26 g, 0.146 mmol). The reaction mixture was heated to 70° C. and the reaction flask was irradiated with a UV light (500 W) for 1 hour. The reaction mixture, after cooling to normal room temperature, was washed with saturated aqueous sodium bicarbonate solution followed by water, dried over anhydrous sodium sulfate, and the solvent evaporated in vacuo to give (R)-2-[2-(2-bromomethylphenyl)-2-methylpropyl]-2-trifluoromethyloxirane as a light yellow oil (46.6 g, 81%; ˜85% pure) which was used for the next reaction without purification.
Reaction SMILES: [CH2:1]([N:8]1[C:21](=[O:22])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]2[CH:13]=[C:12]([CH:23]=[C:24]3[S:28][C:27](=[O:29])[NH:26][C:25]3=[O:30])[CH:11]=[CH:10][C:9]1=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.[BH4-].[Li+].Cl>C1COCC1>[CH2:1]([N:8]1[C:21](=[O:22])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]2[CH:13]=[C:12]([CH2:23][CH:24]3[S:28][C:27](=[O:29])[NH:26][C:25]3=[O:30])[CH:11]=[CH:10][C:9]1=2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1NC(=O)C(=Cc2ccc3c(c2)c2ccccc2c(=O)n3Cc2ccccc2)S1
Agent: Cl
Agent: [BH4-]
Agent: [Li+]
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: O=C1NC(=O)C(Cc2ccc3c(c2)c2ccccc2c(=O)n3Cc2ccccc2)S1
Yield: 37.2 %

Procedure:
620 mg of 5-[1-(5-benzyl-6-oxo-5,6-dihydrophenanthridin-2-yl)methylidene]thiazolidine-2,4-dione was dissolved in 2.31 ml of THF. 2.31 ml of pyridine and 2.31 ml of a THF solution of 2 M lithium borohydride were added to the solution, followed by heating and refluxing for 4 hours. The reaction liquid was cooled, acidified with diluted hydrochloric acid, and extracted with dichloromethane. The organic layer was washed with water, then with saturated sodium chloride solution, and dried over sodium sulfate. After filtration, the solvent was distilled off under reduced pressure, the residue was crystallized using dichloromethane, and the solid thus obtained was separated by filtration. The solid separated by filtration was air-dried, giving 232 mg (36% yield) of 5-[1-(5-benzyl-6-oxo-5,6-dihydrophenanthridin-2-yl)methyl]thiazolidine-2,4-dione as white crystals.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[F:11][C:12]([F:26])([F:25])[CH:13]([OH:24])[CH2:14][C:15]([CH3:23])([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1)[CH3:16].C(N(CC)CC)C>ClCCl>[F:26][C:12]([F:11])([F:25])[C:13](=[O:24])[CH2:14][C:15]([CH3:16])([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1)[CH3:23]
Reactant: CC(C)(CC(O)C(F)(F)F)c1ccccn1
Agent: O=C(Cl)C(=O)Cl
Solvent: CS(C)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(CC(=O)C(F)(F)F)c1ccccn1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 86.5 %

Procedure:
A solution of 516 μL (1.03 mmol, 1.2 eq) of oxalyl chloride (2.0 M solution in dichloromethane) was diluted with 2 mL of dichloromethane. To this solution was added a solution of 146 μL (2.06 mmol, 2.4 eq.) of DMSO in 0.2 mL of dichloromethane at −60° C. and the mixture was stirred for 10 minutes at this temperature. Then to this mixture was added a solution of 200 mg (0.86 mmol) of 1,1,1-trifluoro-4-methyl-4-pyridin-2-ylpentan-2-ol in 2 mL of dichloromethane at −60° C. The resulting mixture was stirred at −60° C. for 15 minutes and then 600 μL (4.3 mmol, 5.0 eq.) of triethylamine was added. The cooling bath was removed and the reaction mixture was allowed to warm to room temperature and quenched with water. The organic layer was separated. The aqueous layer was extracted three times with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography, providing 172 mg (86%) 1,1,1-trifluoro-4-methyl-4-pyridin-2-ylpentan-2-one as a brown oil.
Reaction SMILES: [C:1]1([C@H:7]2[CH2:12][CH2:11][C@H:10]([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Al+3].[Cl-].[Cl-].[Cl-].C(Cl)(=O)[C:24]([Cl:26])=[O:25].[Cl-].[Ca+2].[Cl-]>ClCCl.O>[Cl:26][C:24]([C:4]1[CH:5]=[CH:6][C:1]([C@H:7]2[CH2:8][CH2:9][C@H:10]([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:11][CH2:12]2)=[CH:2][CH:3]=1)=[O:25]
Reactant: O=C(Cl)C(=O)Cl
Reactant: CCOC(=O)C[C@H]1CC[C@H](c2ccccc2)CC1
Agent: [Al+3]
Agent: [Ca+2]
Agent: [Cl-]
Solvent: O
Solvent: ClCCl
Product: CCOC(=O)C[C@H]1CC[C@H](c2ccc(C(=O)Cl)cc2)CC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution containing the product of example 1B (2.46 g, 10.0 mmol) and AlCl3 (2.66 g, 20.0 mmol) in 30 mL of dichloromethane at 0° C. was added oxalyl chloride (5 mL, 2 M solution in dichloromethane, 10 mmol). The mixture was stirred at room temperature for 30 minutes. After this time the reaction mixture was poured into an ice-cold solution containing calcium chloride (3 g) in 100 mL of water. The reaction mixture was stirred for 2 h and was extracted with dichloromethane (2×100 mL). The combined organic layer was washed with brine, and dried over anhydrous sodium sulfate. After filtration, the solvent was removed under reduced pressure, and the resulting oil was purified by flash chromatography (ethyl acetate/hexane, 1/8) to afford the title compound as a colorless oil. 1H NMR (500 MHz, DMSO-d6) δ ppm 1.15 (m, 2H), 1.19 (t, J=7.06 Hz, 3H), 1.47 (m, 2H), 1.57-1.85 (m, 5H), 2.22 (d, J=6.75 Hz, 2H), 2.47 (m, 1H), 4.07 (q, J=7.06 Hz, 2H), 7.35 (d, J=8.29 Hz, 2H), 7.85 (d, J=8.29 Hz, 2H).
Reaction SMILES: [NH2:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C@H:12]([C:21](OC)=[O:22])[CH2:13][S:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:7]([N+:25]([O-:27])=[O:26])[CH:6]=1)(=[O:4])=[O:3].[BH4-].[Li+]>C1COCC1.CO.C(OCC)(=O)C>[OH:22][CH2:21][CH:12]([NH:11][C:8]1[CH:9]=[CH:10][C:5]([S:2]([NH2:1])(=[O:3])=[O:4])=[CH:6][C:7]=1[N+:25]([O-:27])=[O:26])[CH2:13][S:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: COC(=O)[C@H](CSc1ccccc1)Nc1ccc(S(N)(=O)=O)cc1[N+](=O)[O-]
Agent: [BH4-]
Agent: [Li+]
Solvent: CO
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: NS(=O)(=O)c1ccc(NC(CO)CSc2ccccc2)c([N+](=O)[O-])c1
Reaction time: 3 h

Procedure:
A solution of Example 434A (1.42 g, 3.45 mmol) in THF (10 mL) and methanol (1 mL) at room temperature was slowly treated with lithium borohydride (100 mg), stirred for 3 hours, as diluted with ethyl acetate (100 mL), washed with water (45 mL) and brine (10 mL), dried (MgSO4), filtered, and concentrated to provide the desired product. MS (ESI(+)) m/e 384 (M+H).
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.CC(C)([O-])C.[K+].[CH2:12]([O:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=1[C:27]1([CH3:30])[CH2:29][O:28]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>CN(C)C=O>[CH2:12]([O:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=1[C:27]([OH:28])([CH3:29])[CH2:30][N:1]1[CH:5]=[CH:4][N:3]=[CH:2]1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: CC1(c2cc(Cl)ccc2OCc2ccccc2)CO1
Reactant: c1c[nH]cn1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(O)(Cn1ccnc1)c1cc(Cl)ccc1OCc1ccccc1
Temperature: 80 °C
Reaction time: 12 h
Yield: 91.1 %

Procedure:
Imidazole (4.0 g, 58.8 mmol) and potassium t-butoxide (6.5 g, 57.9 mmol) were added to a solution of 2-(2-(benzyloxy)-5-chlorophenyl)-2-methyloxirane [compound (10-1), obtained in Referential Example 8] (4.4 g) in dimethylformamide (60 mL), and the mixture was stirred for 12 hours at 80° C. After the mixture was cooled to room temperature, ice-water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with water and dried over magnesium sulfate. The solvent was removed under reduced pressure. The residue was purified through silica gel column chromatography and dried under reduced pressure, to thereby yield 2-(2-(benzyloxy)-5-chlorophenyl)-1-(1H-1-imidazolyl)-2-propanol as colorless crystals (5.0 g, yield: 75.8%).
Reaction SMILES: C([O:3][C:4](=[O:33])[CH:5]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[C:6]1[C:7]([CH3:27])=[N:8][C:9]2[C:14]([C:15]=1[C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1)=[CH:13][C:12]1[CH2:23][CH2:24][CH2:25][CH2:26][C:11]=1[CH:10]=2)C.[OH-].[Na+]>C(O)C.O1CCCC1>[C:29]([O:28][CH:5]([C:6]1[C:7]([CH3:27])=[N:8][C:9]2[C:14]([C:15]=1[C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1)=[CH:13][C:12]1[CH2:23][CH2:24][CH2:25][CH2:26][C:11]=1[CH:10]=2)[C:4]([OH:33])=[O:3])([CH3:32])([CH3:31])[CH3:30]
Reactant: CCOC(=O)C(OC(C)(C)C)c1c(C)nc2cc3c(cc2c1-c1ccc(C)cc1)CCCC3
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: Cc1ccc(-c2c(C(OC(C)(C)C)C(=O)O)c(C)nc3cc4c(cc23)CCCC4)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 68 %

Procedure:
A 50 mL flask containing a solution of tert-butoxy-(2-methyl-4-p-tolyl-6,7,8,9-tetrahydro-benzo[g]quinolin-3-yl)-acetic acid ethyl ester (11.1 mg 25.0 μmol) in ethanol (1 mL) and tetrahydrofuran (1 mL) under nitrogen was added sodium hydroxide solution (1.0 M, 250 μL, 250 μmol) and stirred at ambient temperature overnight. Complete conversion was then achieved by heating to 60 C for 30 min. Evaporated in vacuo and azeotroped with toluene (2×5 mL). Residue was taken up in water (10 mL) and acidified to pH=2 with hydrochloric acid solution (2 M) then extracted into ethyl acetate (2×10 mL). Organics were dried with magnesium sulfate and evaporated onto silica gel. Chromatographed using ISCO Companion with a Redisep silica gel 4 g cartridge with an isocratic gradient of ethyl acetate:acetic acid (90:10). Evaporation gave tert-butoxy-(2-methyl-4-p-tolyl-6,7,8,9-tetrahydro-benzo[g]quinolin-3-yl)-acetic acid as a colorless solid 7.1 mg (68% Yield). LCMS (12 min acidic) 5.32 min 100% pure by ELSD and UV AP+ and ES+ 418. HNMR (CDCl3) >95% pure 7.77 (br-s, 1H), 7.59 (br-d, 1H), 7.36-7.32 (br-m, 2H), 7.22 (br-d, 1H), 7.10 (br-s, 1H), 5.29 (br-s, 1H), 2.99 (br-t, 2H), 2.85-2.78 (m, 4H), 2.49 (s, 3H), 2.18 (s, 3H), 1.86-1.81 (m, 4H), 0.98 (s, 9H)
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].Br[C:8]1[C:16]2[C:11](=[CH:12][C:13]([NH2:17])=[CH:14][CH:15]=2)[N:10]([S:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)(=[O:20])=[O:19])[CH:9]=1.[N+:27]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)([O-:29])=[O:28]>O1CCCC1.C(=O)(O)[O-].[Na+].C(OCC)(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[N+:27]([C:30]1[CH:35]=[CH:34][C:33]([C:8]2[C:16]3[C:11](=[CH:12][C:13]([NH2:17])=[CH:14][CH:15]=3)[N:10]([S:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)(=[O:20])=[O:19])[CH:9]=2)=[CH:32][CH:31]=1)([O-:29])=[O:28]
Reactant: Nc1ccc2c(Br)cn(S(=O)(=O)c3ccccc3)c2c1
Reactant: O=[N+]([O-])c1ccc(B(O)O)cc1
Agent: [Pd]
Agent: O=C([O-])O
Agent: O=C([O-])[O-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Nc1ccc2c(-c3ccc([N+](=O)[O-])cc3)cn(S(=O)(=O)c3ccccc3)c2c1
Temperature: 130 °C
Yield: 65.1 %

Procedure:
A 1.0 M aqueous potassium carbonate solution (9.96 mL, 9.96 mmol) was added to a mixture of 3-bromo-1-(phenylsulfonyl)-1H-indol-6-amine (1.00 g, 2.84 mmol), (4-nitrophenyl)boronic acid (1.19 g, 7.12 mmol) and palladium tetrakis(triphenylphosphine) (164 mg, 0.14 mmol) in tetrahydrofuran (13.7 mL). The biphasic mixture was heated in a microwave at 130° C. for 10 min and was then diluted with a saturated solution of sodium bicarbonate (10.0 mL) and ethyl acetate (10.0 mL). The organic layer was washed with a saturated solution of sodium bicarbonate (2×10.0 mL), and the combined aqueous layers were extracted with ethyl acetate (3×30.0 mL). The combined organic phases were dried over magnesium sulfate, filtered and concentrated. The crude residue was purified by flash chromatography (10-25-50-71% ethyl acetate/hexane) to give an orange solid for 3-(4-nitrophenyl)-1-(phenylsulfonyl)-1H-indol-6-amine (726 mg, 1.85 mmol, 65%).