Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[O:13][C:12]3[CH:14]=[CH:15][CH:16]=[CH:17][C:11]=3[NH:10][C:9](=[O:18])[C:8]=2[CH:19]=1)([O-])=O.Cl[Sn]Cl>C(O)C>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]2[O:13][C:12]3[CH:14]=[CH:15][CH:16]=[CH:17][C:11]=3[NH:10][C:9](=[O:18])[C:8]=2[CH:19]=1
Reactant: O=C1Nc2ccccc2Oc2ccc([N+](=O)[O-])cc21
Agent: Cl[Sn]Cl
Solvent: CCO
Product: Nc1ccc2c(c1)C(=O)Nc1ccccc1O2
Yield: 52.1 %

Procedure:
A mixture of 2-nitro-10H-dibenzo[b,f][1,4]oxazepin-11-one (Example 3, 2.0 g, 7.8 mmol) and SnCl2 in 50 mL of denatured ethanol (85% ethanol, 15% wood alcohol) was stirred under reflux for 1 hr. The solvent was evaporated and the solid residue was washed with 200 mL of ethyl acetate. The ethyl acetate layer was washed with 1.0 N sodium hydroxide (2×100 mL)and water (2×100 mL), then dried over magnesium sulfate, filtered and evaporated to give an off white solid (yield 0.92 g, 52.3%).
Reaction SMILES: [C:1](NC1C=CC(S(N=[N+]=[N-])(=O)=O)=CC=1)(=O)C.C(=O)([O-])[O-].[K+].[K+].O=C(C)CP(=O)(OC)OC.[CH3:33][C:34]([C:38]1[CH:39]=[C:40]([CH:45]=[CH:46][CH:47]=1)[C:41]([O:43][CH3:44])=[O:42])([CH3:37])[CH:35]=O>C(#N)C.CO>[CH3:33][C:34]([C:38]1[CH:39]=[C:40]([CH:45]=[CH:46][CH:47]=1)[C:41]([O:43][CH3:44])=[O:42])([CH3:37])[C:35]#[CH:1]
Reactant: CC(=O)Nc1ccc(S(=O)(=O)N=[N+]=[N-])cc1
Reactant: COC(=O)c1cccc(C(C)(C)C=O)c1
Agent: COP(=O)(CC(C)=O)OC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: CC#N
Product: C#CC(C)(C)c1cccc(C(=O)OC)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 61 %

Procedure:
To a suspension of p-acetamidobenzenesulfonyl azide (5.25 g, 21.9 mmol) and potassium carbonate (7.55 g, 54.6 mmol) in acetonitrile (100 mL) was added dimethyl (2-oxopropyl)phosphonate (3.00 mL, 21.9 mmol), and the mixture was stirred at room temperature for 2 hr. Then, to the reaction mixture was added a solution of methyl 3-(1,1-dimethyl-2-oxoethyl)benzoate in methanol (20 mL), and the mixture was stirred at room temperature for 16 hr. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. To the obtained residue was added saturated aqueous sodium hydrogen carbonate solution (70 mL), and the mixture was extracted with ethyl acetate (100 mL). The combined organic layer was washed with saturated brine (20 mL), and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=100/0→90/10), and the fractions containing the object product were concentrated under reduced pressure to give the title compound (2.26 g, 61%) as a colorless oil.
Reaction SMILES: [C:1](=[O:8])([O:5][CH2:6][CH3:7])OCC.CC(C)([O-])C.[K+].[CH3:15][C:16]([C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=1)=[O:17]>C1(C)C=CC=CC=1>[F:24][C:21]1[CH:22]=[CH:23][C:18]([C:16](=[O:17])[CH2:15][C:1]([O:5][CH2:6][CH3:7])=[O:8])=[CH:19][CH:20]=1
Reactant: CCOC(=O)OCC
Reactant: CC(=O)c1ccc(F)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: CCOC(=O)CC(=O)c1ccc(F)cc1
Temperature: 78 °C
Reaction time: 8 h
Yield: 65.7 %

Procedure:
Diethyl carbonate (801 mL, 6.79 mole) was added dropwise over a 30 minute period to a stirring slurry of potassium t-butoxide (609.2 g, 5.43 mole) in toluene (9.5 L) under a nitrogen atmosphere. The reaction mixture was heated to 78° C. and 4-fluoroacetophenone (250 g, 1.81 mole) in toluene (250 mL) was added over a one hour time period. Heating of the reaction mixture was continued overnight. Then the reaction mixture was quenched with 1.5 N HCl(aq) and extracted with ethyl acetate (3×1 L). The combined organic extracts were washed with saturated sodium bicarbonate, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo leaving a brown liquid. The liquid was distilled to give the title compound as a colorless liquid (250 g, 79%). MS m/z 209 (M−H)−.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[C:14]4[C@:19]([C:21](OC)=[O:22])([CH2:20][C:11]=3[CH:10]=[N:9]2)[CH2:18][N:17]([S:25]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=2)(=[O:27])=[O:26])[CH2:16][CH2:15]4)=[CH:4][CH:3]=1.[H-].C([Al+]CC(C)C)C(C)C.C(=O)(O)[O-].[Na+].S([O-])([O-])(=O)=O.[Na+].[Na+]>ClCCl.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3[CH:13]=[C:14]4[C@:19]([CH:21]=[O:22])([CH2:20][C:11]=3[CH:10]=[N:9]2)[CH2:18][N:17]([S:25]([C:28]2[CH:29]=[CH:30][C:31]([C:34]([F:37])([F:35])[F:36])=[CH:32][CH:33]=2)(=[O:27])=[O:26])[CH2:16][CH2:15]4)=[CH:4][CH:3]=1
Reactant: COC(=O)[C@]12Cc3cnn(-c4ccc(F)cc4)c3C=C1CCN(S(=O)(=O)c1ccc(C(F)(F)F)cc1)C2
Agent: CC(C)C[Al+]CC(C)C
Agent: O=C([O-])O
Agent: O=S(=O)([O-])[O-]
Solvent: ClCCl
Solvent: O
Product: O=C[C@]12Cc3cnn(-c4ccc(F)cc4)c3C=C1CCN(S(=O)(=O)c1ccc(C(F)(F)F)cc1)C2
Temperature: -78 °C
Reaction time: 1 h
Yield: 31 %

Procedure:
A solution of (R)-methyl 1-(4-fluorophenyl)-6-((4-(trifluoromethyl)phenyl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinoline-4a-carboxylate (2.12 g, 3.96 mmol) was dissolved in dry dichloromethane and cooled to −78° C. under nitrogen. A solution of diisobutylaluminium hydride (1.0 M in dichloromethane, 16 mmol, 16 mL) was added dropwise maintaining the reaction temperature at <−70° C. and the reaction mixture was stirred at −78° C. for 1 hour. The reaction mixture was treated with water (6 mL), stirred at −78° C. for 5 minutes then warmed to >0° C. over 15 minutes. Solid sodium bicarbonate (5.5 g) was added and the mixture stirred vigorously for 5 minutes. Excess sodium sulfate was added (˜20 g) and the resultant mixture was stirred vigorously for a further 15 minutes. The solid materials were removed by filtration and rinsed with a little dichloromethane. The filtrate was concentrated under reduced pressure and the residue purified by column chromatography on silica gel eluting with a mixture of ethyl acetate and cyclohexane (3:7 by volume) followed by ethyl acetate to afford (R)-1-(4-fluorophenyl)-6-((4-(trifluoromethyl)phenyl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinoline-4a-carbaldehyde as a white foam (0.62 g). 1H NMR (400 MHz, CDCl3): 9.48 (s, 1 H); 7.93 (d, J=8.2 Hz, 2 H); 7.84 (d, J=8.3 Hz, 2 H); 7.39-7.40 (m, 3 H); 7.17 (t, J=8.5 Hz, 2 H); 6.52 (d, J=2.5 Hz, 1 H); 4.32 (d, J=12.3 Hz, 1 H); 3.90 (br s, 1 H); 3.14 (d, J=16.4 Hz, 1 H); 2.65-2.80 (m, 1H); 2.51-2.52 (m, 4 H) and (R)-(1-(4-fluorophenyl)-6-((4-(trifluoromethyl)phenyl) sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)methanol as a white solid (1.0 g). 1H NMR (400 MHz, CDCl3): δ 7.94 (d, J=8.2 Hz, 2 H); 7.83 (d, J=8.3 Hz, 2 H); 7.40-7.41 (m, 3 H); 7.14-7.15 (m, 2 H); 6.31 (d, J=2.4 Hz, 1 H); 4.11-4.12 (m, 1 H); 4.02 (dd, J=11.4, 5.9 Hz, 1 H); 3.78 (dd, J=11.5, 5.6 Hz, 1 H); 3.34 (dd, J=11.4, 8.1 Hz, 1 H); 3.13 (d, J=15.8 Hz, 1 H); 2.74-2.76 (m, 1 H); 2.59-2.60 (m, 1 H); 2.41 (d, J=15.5 Hz, 1 H); 2.24-2.25 (m, 2 H); 2.04 (s, 1 H).
Reaction SMILES: C([N:8]1[C:12]2[CH2:13][CH:14]([O:16][CH2:17][CH2:18][CH3:19])[CH2:15][C:11]=2[C:10]([C:20]2[N:21]=[N:22][NH:23][N:24]=2)=[N:9]1)C1C=CC=CC=1.CC(C)([O-])C.[K+]>CS(C)=O>[CH2:17]([O:16][CH:14]1[CH2:15][C:11]2=[C:10]([C:20]3[NH:24][N:23]=[N:22][N:21]=3)[NH:9][N:8]=[C:12]2[CH2:13]1)[CH2:18][CH3:19]
Reactant: CCCOC1Cc2c(-c3nn[nH]n3)nn(Cc3ccccc3)c2C1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: CCCOC1Cc2n[nH]c(-c3nnn[nH]3)c2C1

Procedure:
To a solution of the intermediate from step B (26 mg, 0.08 mmol) in DMSO (0.6 mL) was added potassium-t-butoxide (0.6 mL, 0.6 mmol, 1.0 M in THF). Oxygen gas was bubbled through the reaction mixture for 15 minutes. The reaction was quenched with HCl (3 mL, 3N). The resulting mixture was extracted with ethyl acetate (5×) dried over anhydrous Na2SO4 filtered and concentrated in vacuo. The residue was purified by reverse phase HPLC to afford the title compound. 1H NMR (CDCl3) δ 4.80 (m, 1H), 3.51 (m, 2H), 3.24 (dd, J=6.8, 15.5 Hz, 1H), 3.18 (dd, J=6.9, 16.0 Hz, 1H), 2.85 (dd, J=4.1, 15.6 Hz, 1H), 2.79 (dd, J=4.4, 16.1 Hz, 1H), 1.62 (m, 2H), 0.96 (t, J=7.6 Hz, 3H). LC-MS: 2.15 min; (M+H)=235.
Reaction SMILES: [CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[NH:12][C:11](=[O:16])[C:10]3=[O:17])=[C:5]([CH3:18])[O:4][N:3]=1.[C:19]1(=[O:25])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1.CNC>CO>[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[NH:12][C:11](=[O:16])[C:10]3([OH:17])[CH:20]2[CH2:21][CH2:22][CH2:23][CH2:24][C:19]2=[O:25])=[C:5]([CH3:18])[O:4][N:3]=1
Reactant: Cc1noc(C)c1-c1ccc2c(c1)C(=O)C(=O)N2
Reactant: O=C1CCCCC1
Agent: CNC
Solvent: CO
Product: Cc1noc(C)c1-c1ccc2c(c1)C(O)(C1CCCCC1=O)C(=O)N2
Temperature: 25 °C
Reaction time: 4 h

Procedure:
5-(3,5-dimethylisoxazol-4-yl)indoline-2,3-dione (242 mg, 1.0 mmol) is dissolved in MeOH (20 ml), cyclohexanone (196 mg, 2.0 mmol) and dimethylamine (0.4 mmol) are added and the reaction mixture is stirred for 4 h at room temperature. After that, the mixture is concentrated in vacuo and the residue was purified with chromatography on column to give two isomers (The first 50 mg, 14.7%, the second 30 mg, 8.8% and mixture 100 mg, 29.3%). The fast isomer (50 mg, 14.7%): 1H NMR (400 MHz, DMSO-d6): δ 10.25 (s, 1H), 7.29 (d, J=1.6 Hz, 1H), 7.17 (dd, J=1.6, 8.0 Hz, 1H), 6.84 (d, J=8.0 Hz, 1H), 5.83 (s, 1H), 3.32-3.41 (m, 1H), 2.30-2.40 (m, 5H), 2.19 (s, 3H), 1.98-2.06 (m, 2H), 1.80-1.83 (m, 2H), 1.44-1.64 (m, 2H), MS (ESI) m/e [M+1]+ 341.0; the slow isomer (30 mg, 8.8%): 1H NMR (400 MHz, DMSO-d6): δ 10.31 (s, 1H), 7.16-7.20 (m, 2H), 6.88 (d, J=8.0 Hz, 1H), 5.92 (s, 1H), 3.08-3.12 (m, 1H), 2.59-2.62 (m, 1H), 2.36 (s, 3H), 2.29-2.35 (m, 1H), 2.19 (s, 3H), 1.77-2.00 (m, 4H), 1.62-1.68 (m, 1H), 1.42-1.50 (m, 1H), MS (ESI) m/e [M+1]+ 341.
Reaction SMILES: O[CH2:2][CH:3]1[N:8]([C:9](=[S:21])[NH:10][C:11]2[CH:20]=[CH:19][CH:18]=[C:17]3[C:12]=2[CH:13]=[CH:14][N:15]=[CH:16]3)[CH2:7][C:6]2[S:22][CH:23]=[CH:24][C:5]=2[CH2:4]1.C.C(O)(C)C>Cl>[CH:16]1[C:17]2[C:12](=[C:11]([N:10]=[C:9]3[N:8]4[CH2:7][C:6]5[S:22][CH:23]=[CH:24][C:5]=5[CH2:4][CH:3]4[CH2:2][S:21]3)[CH:20]=[CH:19][CH:18]=2)[CH:13]=[CH:14][N:15]=1
Reactant: OCC1Cc2ccsc2CN1C(=S)Nc1cccc2cnccc12
Agent: Cl
Solvent: CC(C)O
Product: c1cc(N=C2SCC3Cc4ccsc4CN23)c2ccncc2c1
Reaction time: 20 h
Yield: 69.7 %

Procedure:
A suspension of (RS)-5-hydroxymethyl-6-[(isoquinol-5-yl)thiocarbamoyl]-4,5,6,7-tetrahydrothieno[2,3-c]pyridine (21 g) in 6 N hydrochloric acid (220 cc) is heated under reflux for 1.5 hours. The resulting brown solution is cooled, decolorised with animal charcoal and filtered. The filtrate is rendered alkaline to pH 11 with a 15% aqueous solution of potassium carbonate and extracted with methylene chloride (300 cc and then 3×200 cc). The organic extracts are combined and dried over sodium sulphate. After filtering and concentrating the filtrate to dryness under reduced pressure (25 mm Hg; 3.3 kPa) at 40° C., a pale yellow solid is obtained. This solid is dissolved in boiling isopropanol (800 cc); the resulting solution is cooled to +5° C. and kept at that temperature for 20 hours. The solid formed is filtered off and taken up in boiling isopropanol (500 cc); the resulting solution is cooled to +5° C. and kept at that temperature for 20 hours. The solid formed is filtered off, washed with diisopropyl ether (2×50 cc) and dried at 60° C. under reduced pressure (0.1 mm Hg; 0.013 kPa). (RS)-7-[(Isoquinol-5-yl)imino]-4,4a,5,9-tetrahydrothiazolo[3,4-a]thieno[3,2-d]pyridine (13.9 g) is thus obtained in the form of pale yellow crystals melting at 171° C.
Reaction SMILES: O[C:2]1([C:15]2[CH:16]=[C:17]([CH3:21])[CH:18]=[CH:19][CH:20]=2)[CH2:7][NH:6][C:5](=[O:8])[CH:4]=[C:3]1[C:9]1[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=1.OS(O)(=O)=O>C(Cl)(Cl)Cl>[C:17]1([CH3:21])[CH:18]=[CH:19][CH:20]=[C:15]([C:2]2[C:3]([C:9]3[CH:10]=[CH:11][N:12]=[CH:13][CH:14]=3)=[CH:4][C:5](=[O:8])[NH:6][CH:7]=2)[CH:16]=1
Reactant: Cc1cccc(C2(O)CNC(=O)C=C2c2ccncc2)c1
Agent: O=S(=O)(O)O
Solvent: ClC(Cl)Cl
Product: Cc1cccc(-c2c[nH]c(=O)cc2-c2ccncc2)c1
Temperature: 55 °C

Procedure:
To a solution of 5-hydroxy-5-m-tolyl-5,6-dihydro-1H-[4,4′]bipyridinyl-2-one (280 mg, 1.0 mmole) in CHCl3 (5 mL) at r.t. was added 1 ml of conc. H2SO4. The resulting mixture was heated to 55° C. for 1 hr. The mixture was cooled down to r.t. and was carefully quenched with aqueous sodium carbonate. Standard work up (extraction of compound with methylene chloride), followed by purification (silica gel, methanol/methylene chloride) gave the title compound. MS (m/z): Calcd. C17H14N2O(M+): 262, found (M+H)+: 263.3.
Reaction SMILES: [Na].[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[C:12]([SH:20])[C:13]3[CH:14]=[CH:15][N:16]=[CH:17][C:18]=3[CH:19]=2)=[CH:6][CH:5]=1.[C:21]([O:25][C:26](=[O:31])[NH:27][CH2:28][CH2:29]Br)([CH3:24])([CH3:23])[CH3:22].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[C:21]([O:25][C:26](=[O:31])[NH:27][CH2:28][CH2:29][S:20][C:12]1[CH:11]=[C:10]([C:7]2[CH:8]=[CH:9][C:4]([O:3][CH3:2])=[CH:5][CH:6]=2)[CH:19]=[C:18]2[C:13]=1[CH:14]=[CH:15][N:16]=[CH:17]2)([CH3:24])([CH3:23])[CH3:22]
Reactant: CC(C)(C)OC(=O)NCCBr
Reactant: COc1ccc(-c2cc(S)c3ccncc3c2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na]
Solvent: CC(C)=O
Product: COc1ccc(-c2cc(SCCNC(=O)OC(C)(C)C)c3ccncc3c2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 85.3 %

Procedure:
To 7-(4-methoxy-phenyl)-isoquinoline-5-thiol sodium salt (0.29 g, 1 mmol) in acetone (10 mL), add (2-bromo-ethyl)-carbamic acid tert-butyl ester (0.22 g, 1 mmol) and potassium carbonate (0.14 g, 1 mmol). Stir the mixture at room temperature for 4 hr then load onto a silica gel column, and elute with 65% ethyl acetate in hexane to afford the title compound (0.35 g, 86%). Mass spectrum (LCMS) m/z=355.2 (M+H+).
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[CH:14][CH:13]=2)=[CH:4][C:5]2[O:9][C:8]([CH3:10])=[N:7][C:6]=2[CH:11]=1.[F:19][C:20]1[CH:28]=[CH:27][CH:26]=[CH:25][C:21]=1[C:22](Cl)=[O:23].CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+].C(Cl)Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:1][C:2]1[C:3]([C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:22]([C:21]3[CH:25]=[CH:26][CH:27]=[CH:28][C:20]=3[F:19])=[O:23])=[CH:14][CH:13]=2)=[CH:4][C:5]2[O:9][C:8]([CH3:10])=[N:7][C:6]=2[CH:11]=1
Reactant: O=C(Cl)c1ccccc1F
Reactant: Cc1nc2cc(Cl)c(-c3ccc(N)cc3)cc2o1
Agent: CN(C)c1ccncc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1nc2cc(Cl)c(-c3ccc(NC(=O)c4ccccc4F)cc3)cc2o1
Temperature: 25 °C
Reaction time: 3 h
Yield: 57.5 %

Procedure:
To a solution of 4-(5-chloro-2-methylbenzoxazol-6-yl)phenylamine (56) (23 mg, 0.089 mmol) and 2 mg DMAP in 2 ml DCM was added 2-fluorobenzoyl chloride (21 μl, 0.18 mmol) followed by addition of DIEA (78 μl). The resulting brown solution was stirred at r.t. for 3 h. The reaction mixture was worked up with aq. NaHCO3/DCM. DCM phase was washed with brine, concentrated to dryness. The residue was dissolved in 2 ml THF/MeOH/H2O (5:4:1) and stirred with 1N NaOH (200 μl) at r.t. for 2 h before worked up with EA/aq. NaHCO3. Silica gel flash chromatography furnished 19.5 mg 57 as off-white solid. (yield: 57.5%).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([O:11][CH2:12][CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21]C)[CH:16]=2)=[N:8][C:7]=1[CH3:23])=[O:5])[CH3:2].B(Br)(Br)Br>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([O:11][CH2:12][CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([OH:21])[CH:16]=2)=[N:8][C:7]=1[CH3:23])=[O:5])[CH3:2]
Reactant: CCOC(=O)c1sc(OCCCc2cccc(OC)c2)nc1C
Agent: BrB(Br)Br
Solvent: ClCCl
Product: CCOC(=O)c1sc(OCCCc2cccc(O)c2)nc1C
Temperature: 25 °C
Yield: 78.4 %

Procedure:
To a stirred and cooled solution of 2-[3-(3-Methoxy-phenyl)-propoxy]-4-methyl-thiazole-5-carboxylic acid ethyl ester (0.84 g, 2.5 mmol) in Methylene chloride (10 mL) at 0° C. was added 1M solution of boron tribromide in dichloromethane drop wise over a minute. The reaction was warmed gently to ambient temperature over 2 hrs. The resultant reaction is poured gently on ice water (25 mL) and extracted with Methylene chloride (3×75 mL). The organic layers are combined, washed with sodium bicarbonate (50 mL), brine (50 mL), dried over anhydrous MgSO4, filtered and concentrated to give 2-[3-(3-Hydroxy-phenyl)-propoxy]-4-methyl-thiazole-5-carboxylic acid ethyl ester (0.63 g, 78.3%) as a light pink oil. MS m/e 322.4 (M+H+).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13](/[CH:14]=[CH:15]/[CH:16]([OH:25])[CH2:17][C:18](=[O:24])[CH2:19][C:20]([O:22][CH3:23])=[O:21])=[C:12]([CH:26]([CH3:28])[CH3:27])[CH:11]=[C:10]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[N:9]=2)=[CH:4][CH:3]=1.C(B(CC)CC)C.[BH4-].[Na+].CO>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:13]([CH:14]=[CH:15][CH:16]([OH:25])[CH2:17][CH:18]([OH:24])[CH2:19][C:20]([O:22][CH3:23])=[O:21])=[C:12]([CH:26]([CH3:28])[CH3:27])[CH:11]=[C:10]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[N:9]=2)=[CH:6][CH:7]=1
Reactant: COC(=O)CC(=O)CC(O)/C=C/c1c(C(C)C)cc(-c2ccccc2)nc1-c1ccc(F)cc1
Agent: CCB(CC)CC
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: COC(=O)CC(O)CC(O)C=Cc1c(C(C)C)cc(-c2ccccc2)nc1-c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 86.8 %

Procedure:
A solution of (E)-7-[2-(4-fluorophenyl)-4-(1-methylethyl)-6-phenyl-3-pyridinyl]-5-hydroxy-3-oxo-6-heptenoic acid, methyl ester (182 mg, 0.39 mmol) in THF (5.5 ml) was treated with triethylborane (1.0N in THF, 830 ul, 0.83 mmol). Twenty milliliters of air was bubbled through the solution and the mixture was stirred at room temperature for 30 minutes. The solution was cooled to -78° C. and treated with NaBH4 (15.0 mg, 0.40 mmol) followed by dropwise addition of dry methanol (0.9 ml). After stirring at -78° C. for 1.75 hours, the mixture was quenched with 30% H2 O2 (2.8 ml) in H2O (6 ml). The mixture was kept at -78° C. for 15 minutes, then warmed to room temperature and stirred for 45 minutes. The solution was poured into 50% saturated NaHCO3 and extracted with Et2O (2×). The combined Et2O extracts were washed with saturated NaHCO3, H2O, and brine, then dried (Na2SO4), filtered and stripped. Purification of the resulting oil (flash, Merck SiO2, 50% EtOAc in hexane) gave (3R*, 5S*, 6E)-7-[2-(4-fluorophenyl)-4-(1-methylethyl)-6-phenyl-3-pyridinyl]-3,5-dihydroxy-6-heptenoic acid, methyl ester (157 mg, 86%) as a colorless oily foam.
Reaction SMILES: [Si]([O:8][CH:9]1[CH:22]([O:23][Si](C(C)(C)C)(C)C)[C:21]2C=C(I)C=C[C:16]=2[C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][CH:14]=2)(C(C)(C)C)(C)C.O1[CH2:36][CH2:35][CH2:34][CH2:33]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(O)C>[C:9]1(=[O:8])[C:10]2[CH:11]=[CH:12][C:13]3[C:14](=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:15]=2[CH:16]=[CH:21][C:22]1=[O:23]
Reactant: CC(C)(C)[Si](C)(C)OC1c2ccccc2-c2ccc(I)cc2C1O[Si](C)(C)C(C)(C)C
Reactant: C1CCOC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CCO
Product: O=C1C=Cc2c(ccc3ccccc23)C1=O
Temperature: 25 °C
Yield: 76 %

Procedure:
Into a 20 mL volume eggplant-shaped flask, 80 mg of the above-prepared 9,10-bis(t-butyldimethylsilyloxy)-2-iodo-9,10-dihydro-phenanthrene dimer, 10 mL of tetrahydrofuran, 43 mg of ethanol, and 0.4 mL of tetrabutylammonium fluoride were added and stirred at room temperature in air. The resultant reaction mixture was allowed to stand. Thereafter, the precipitate was collected by filtration and washed, thereby to give 28 mg of a phenanthrenequinone compound represented by the following chemical structural formula (1b-1) (hereinafter referred to as a “phenanthrenequinone compound (1b-1)”) (yield 76%) as a reddish brown-colored solid.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[N:4][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)=[CH:12][CH:11]=2)=[O:9])=[N:6][CH:7]=1.[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26]O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][O:1][C:2]1[CH:3]=[N:4][C:5]([C:8]([C:10]2[CH:11]=[CH:12][C:13]([O:16][CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)=[CH:14][CH:15]=2)=[O:9])=[N:6][CH:7]=1
Reactant: O=C(c1ccc(OC2CCCCO2)cc1)c1ncc(O)cn1
Reactant: CN(C)CCO
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CN(C)CCOc1cnc(C(=O)c2ccc(OC3CCCCO3)cc2)nc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 80 %

Procedure:
To a mixture of (5-hydroxypyrimidin-2-yl)(4-(tetrahydro-2H-pyran-2-yloxy) phenyl)methanone (300 mg, 1 mmol), 2-(dimethylamino)ethanol (180 mg, 2 mmol) and PPh3 (524 mg, 2 mmol) in 50 mL of THF was added DIAD (404 mg, 2 mmol) dropwise and the mixture was stirred overnight at rt. The mixture was concentrated and purified by flash chromatography to give the product (297 mg, 80% yield)
Reaction SMILES: [Cl:1][CH2:2][C:3](Cl)=[O:4].[NH2:6][C:7]1[CH:13]=[C:12]([OH:14])[CH:11]=[CH:10][C:8]=1[OH:9].N(CCO)CCO.Cl>CC(C)=O.O>[Cl:1][CH2:2][C:3]([NH:6][C:7]1[CH:13]=[C:12]([OH:14])[CH:11]=[CH:10][C:8]=1[OH:9])=[O:4]
Reactant: Nc1cc(O)ccc1O
Reactant: O=C(Cl)CCl
Agent: Cl
Solvent: OCCNCCO
Solvent: CC(C)=O
Solvent: O
Product: O=C(CCl)Nc1cc(O)ccc1O

Procedure:
α-chloroacetylchloride (10.1 g, 0.128 mole) was added dropwise under stirring at room temperature to the 2-aminohydroquinone (4.16 g, 0.128 mole) in dry acetone (400 ml) and diethanolamine (2.04 ml, 0.128 mole). The reaction mixture was poured into water and hydrochloride acid (2,000 ml, pH 1), then extracted with ethylacetate (500 ml). The solvent was evaporated to dryness and the solid residue (4.20 g, 80%) was used without any further purification. The structure of the 2-(α-chloroacetamido)-hydroquinone was confirmed by NMR analysis.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[N+:8]([C:11]1[CH:19]=[CH:18][C:14]([C:15](Cl)=[O:16])=[CH:13][CH:12]=1)([O-])=O.N1C=CC=CC=1>C(O)C>[NH2:8][C:11]1[CH:19]=[CH:18][C:14]([C:15]([N:4]2[CH:5]=[CH:6][CH:7]=[C:2]([NH2:1])[CH2:3]2)=[O:16])=[CH:13][CH:12]=1
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Reactant: Nc1cccnc1
Solvent: CCO
Solvent: c1ccncc1
Product: NC1=CC=CN(C(=O)c2ccc(N)cc2)C1

Procedure:
3-Aminopyridine, 60, is first reacted with 4-nitrobenzoyl chloride in the presence of pyridine at 80° C. (step 1) and the product, 62, is subsequently hydrogenated in the presence of ethanol (step 2) to give N-(p-aminobezoyl) -3-aminopyridine, 64. In a separate reaction, 2,5-dimethyl-1,4-phenylenediamine, 66, is converted to 2,5-dimethyl-1,4-dinitrobenzene in a "reverse" Sandmeyer reaction with isoamyl nitrite and acetic acid (step 3), and subsequently treated with copper sulfate in the presence of sodium nitrite (step 4) to produce the intermediate, 68. This intermediate, 68, is oxidized with CrO3 and chlorinated with SOCl2 (step 5) to give 2,5-dinitroterephthaloyl chloride 70. One equivalent of N-(p-aminobezoyl)-3-aminopyridine, 64, and 0.5 equivalent of 2,5-dinitroterephthaloyl chloride, 70, are reacted in pyridine (step 6) to produce a bis-anilide derivative of 2,5-dinitroterephthaloyl chloride 72, and the product is again hydrogenated and activated with isoamyl nitrite (step 7) to yield the final activated product 74.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:39])[CH:19]([O:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([C:33]3[N:37]=C(C)O[N:34]=3)[CH:28]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:13][CH:12]=1)(=[O:4])=[O:3].O.[C:41]([OH:44])(=[O:43])[CH3:42]>CO>[C:41]([OH:44])(=[O:43])[CH3:42].[C:33]([C:29]1[CH:28]=[C:27]([CH:32]=[CH:31][CH:30]=1)[O:26][CH:19]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:18]([NH:17][C:14]1[CH:13]=[CH:12][C:11]([C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[S:2]([CH3:1])(=[O:4])=[O:3])=[CH:16][CH:15]=1)=[O:39])(=[NH:34])[NH2:37]
Reactant: Cc1nc(-c2cccc(OC(C(=O)Nc3ccc(-c4ccccc4S(C)(=O)=O)cc3)c3ccccc3)c2)no1
Solvent: CC(=O)O
Solvent: O
Solvent: CO
Product: CS(=O)(=O)c1ccccc1-c1ccc(NC(=O)C(Oc2cccc(C(=N)N)c2)c2ccccc2)cc1
Reaction time: 18 h

Procedure:
A solution of 150 mg (0.278 mmol) of N-(2′-methanesulfonylbiphenyl-4-yl)-2-[3-(5-methyl-[1,2,4]oxadiazol-3-yl)phenoxy]-2-phenylacetamide in 7 ml of methanol is treated with 100 mg of water-moist Raney nickel and 70 mg of acetic acid and hydrogenated for 18 hours at room temperature and normal pressure. The reaction mixture is filtered, the filtrate is evaporated and the residue is stirred with diethyl ether. A colourless solid is obtained; FAB 500