Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2([NH2:12])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[F:46][C:47]1[CH:52]=[CH:51][C:50]([C:53]2[O:54][C:55]3[CH:65]=[CH:64][C:63]([C:66]4[CH:67]=[C:68]([CH:72]=[CH:73][CH:74]=4)[C:69](O)=[O:70])=[CH:62][C:56]=3[C:57]=2[C:58](=[O:61])[NH:59][CH3:60])=[CH:49][CH:48]=1>CN(C=O)C.CCOC(C)=O>[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2([NH:12][C:69]([C:68]3[CH:67]=[C:66]([C:63]4[CH:64]=[CH:65][C:55]5[O:54][C:53]([C:50]6[CH:51]=[CH:52][C:47]([F:46])=[CH:48][CH:49]=6)=[C:57]([C:58]([NH:59][CH3:60])=[O:61])[C:56]=5[CH:62]=4)[CH:74]=[CH:73][CH:72]=3)=[O:70])[CH2:10][CH2:11]2)=[CH:7][CH:8]=1
Reactant: CNC(=O)c1c(-c2ccc(F)cc2)oc2ccc(-c3cccc(C(=O)O)c3)cc12
Reactant: NC1(c2ccc(Cl)cc2)CC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: CNC(=O)c1c(-c2ccc(F)cc2)oc2ccc(-c3cccc(C(=O)NC4(c5ccc(Cl)cc5)CC4)c3)cc12
Reaction time: 1 h
Yield: 14.4 %

Procedure:
1-(4-Chlorophenyl)cyclopropanamine hydrochloride (25 mg, 0.123 mmol) was added to a stirring solution of HATU (59 mg, 0.154 mmol), DIEA (54 μL, 0.308 mmol), and 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)benzoic acid (40 mg, 0.103 mmol) in DMF (1 mL) at rt. It was allowed to stir for 1 hour. The mixture was diluted with EtOAc and washed with sat NaHCO3, and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated and was purified by preparative reverse phase HPLC on a C18 column using a suitably buffered H2O/CH3CN gradient, and concentrated to give the titled compound (8 mg, 14%). 1H NMR (500 MHz, DMSO-d6) δ ppm 9.37 (1H, s), 8.46-8.55 (1H, m), 8.22 (1H, s), 7.95-8.05 (2H, m), 7.86-7.95 (3H, m), 7.74-7.83 (2H, m), 7.59 (1H, t, J=7.63 Hz), 7.38-7.44 (2H, m), 7.30-7.36 (2H, m), 7.20-7.28 (2H, m), 2.86 (3H, d, J=4.58 Hz), 1.26-1.36 (4H, m). LC-MS retention time: 1.92 min; m/z (MH+): 539. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® Luna 10u C18 3.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 10% MeOH/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% MeOH/0.1% trifluoroacetic acid. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. Additional HPLC method: Solvent A=5% CH3CN/95% H2O/0.1% TFA, Solvent B=95% CH3CN/5% H2O/0.1% TFA, Start % B=10, Final % B=100, Gradient time=15 min, Stop time=18 min, Flow Rate=1 ml/min. Column: Waters Sunfire C-18, 4.6×150 mm, 3.5 mm, Rt=14.56 min, purity=99%; Column: Waters XBridge phenyl column 4.6×150 mm, 3.5 mm, Rt=13.20 min, purity=97%.
Reaction SMILES: C1(N[C:8]2[CH:9]=[C:10]3[CH:16]=[CH:15][NH:14][C:11]3=[N:12][CH:13]=2)C=CC=CC=1.[CH3:17][O-:18].[Na+].O.[Cl-].[NH4+].[OH-].[NH4+]>CN(C)C=O.CO.C(OCC)(=O)C.[Cu]I.[Cu]Br>[CH3:17][O:18][C:8]1[CH:9]=[C:10]2[CH:16]=[CH:15][NH:14][C:11]2=[N:12][CH:13]=1
Reactant: c1ccc(Nc2cnc3[nH]ccc3c2)cc1
Reactant: C[O-]
Agent: [Cu]Br
Agent: [Cu]I
Agent: [Cl-]
Solvent: CO
Solvent: O
Solvent: CN(C)C=O
Product: COc1cnc2[nH]ccc2c1
Temperature: 120 °C
Reaction time: 8 h

Procedure:
To 5-bromo-7-azaindole (1, 500.0 mg, 2.53 mmol) in N,N-dimethylformamide (8 mL) were added copper(I) iodide (966 mg, 5.08 mmol) and sodium methoxide in methanol (3 M, 5 mL). The reaction was stirred overnight at 120° C. under an atmosphere of Argon. The reaction was poured into water, and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered. The filtrate was concentrated and purified with silica gel column chromatograph eluting with 20% ethyl acetate in hexane to give white solid (17, 140 mg, 28%). MS (ESI)[M+H+]+=149.1. In an alternative method, 2.3 g (11.7 mmol) 5-bromo-7-azaindole (1, 2.3 g, 11.7 mmol) was dissolved in 75 mL N,N-dimethylformamide and 50 mL methanol (50 mL), adding sodium methoxide (32 g, 0.6 mol) and copper-(1) bromide (3.2 g, 22.4 mmol) at room temperature. The reaction was stirred for three hours at 100° C. under an atmosphere of argon. The mixture was diluted with ethyl acetate and poured into a solution of ammonium chloride:ammonium hydroxide (4:1). The organic layer was extracted with ammonium chloride:ammonium hydroxide (4:1), washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The desired compound was isolated by silica gel column chromatography eluting with 30% to 70% ethyl acetate in hexanes to give a yellow solid (17, 0.27 g, 15.6%). MS (ESI) [M+H+]+=149.2.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][C:10]=2[O:18][CH3:19])=[CH:4][C:3]=1[Cl:20].[Cl-].[NH4+]>O1CCCC1.O.[Fe]>[Cl:20][C:3]1[CH:4]=[C:5]([CH:6]=[CH:7][C:2]=1[Cl:1])[O:8][C:9]1[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][C:10]=1[O:18][CH3:19]
Reactant: COc1cc([N+](=O)[O-])ccc1Oc1ccc(Cl)c(Cl)c1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: O
Product: COc1cc(N)ccc1Oc1ccc(Cl)c(Cl)c1
Temperature: 60 °C
Reaction time: 8 h
Yield: 73.9 %

Procedure:
A mixture of 1,2-dichloro-4-(2-methoxy-4-nitrophenoxy)benzene (60 g, 190.40 mmol, 1.00 equiv), Fe(53 g, 946.43 mmol, 4.97 equiv) and ammonium chloride (10 g, 188.68 mmol, 0.99 equiv) in tetrahydrofuran/water (1/2) (600 mL) was stirred overnight at 60° C. under an inert atmosphere of nitrogen. The mixture was filtered through Celite and the filtrate was concentrated under vacuum. The resulting solution was extracted with 3×500 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 3×500 mL of brine. The mixture was dried over anhydrous magnesium sulfate and concentrated under vacuum to give 40 g (74%) of 4-(3,4-dichlorophenoxy)-3-methoxyaniline as a light gray solid.
Reaction SMILES: O.[OH-].[Li+].[CH2:4]([N:7]1[C:11]([CH2:12][CH:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:10][C:9]([C:19]([O:21]CC)=[O:20])=[N:8]1)[CH2:5][CH3:6].C(O)(=O)C>CO.O>[CH2:4]([N:7]1[C:11]([CH2:12][CH:13]2[CH2:14][CH2:15][O:16][CH2:17][CH2:18]2)=[CH:10][C:9]([C:19]([OH:21])=[O:20])=[N:8]1)[CH2:5][CH3:6]
Reactant: CCCn1nc(C(=O)OCC)cc1CC1CCOCC1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Solvent: CO
Product: CCCn1nc(C(=O)O)cc1CC1CCOCC1
Temperature: 0 °C
Reaction time: 20 h
Yield: 84.5 %

Procedure:
Lithium hydroxide monohydrate (3.8 g, 92 mmol) was added to a solution of ethyl 1-propyl-5-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazole-3-carboxylate (6.43 g, 22.9 mmol) in methanol (30 mL) and water (10 mL). The mixture was stirred for 20 hours. Most of the volatiles were removed under reduced pressure, and water (100 mL) and acetic acid (52 mL, 910 mmol) were sequentially added. The solution was cooled to approximately 0° C. After five minutes, a white solid formed, and more water (100 mL) was added. The mixture was stirred for 30 minutes, and the solid was isolated by filtration, washed with water, and dried on the vacuum filter funnel to provide 4.88 g of 1-propyl-5-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazole-3-carboxylic acid as a white solid.
Reaction SMILES: Cl.[F:2][C:3]1[C:4]([C:15]([F:18])([F:17])[F:16])=[C:5]([CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:6]=[CH:7][CH:8]=1.[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][C:29]2[C:32]([C:35](O)=[O:36])=[N:33][NH:34][C:28]=2[CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].C(N(C(C)C)CC)(C)C.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.O>[F:2][C:3]1[C:4]([C:15]([F:18])([F:16])[F:17])=[C:5]([CH:9]2[CH2:10][CH2:11][N:12]([C:35]([C:32]3[C:29]4[CH2:30][CH2:31][N:26]([C:24]([O:23][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:25])[CH2:27][C:28]=4[NH:34][N:33]=3)=[O:36])[CH2:13][CH2:14]2)[CH:6]=[CH:7][CH:8]=1
Reactant: Fc1cccc(C2CCNCC2)c1C(F)(F)F
Reactant: CC(C)(C)OC(=O)N1CCc2c(C(=O)O)n[nH]c2C1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCc2c(C(=O)N3CCC(c4cccc(F)c4C(F)(F)F)CC3)n[nH]c2C1
Temperature: 25 °C
Reaction time: 24 h
Yield: 47.5 %

Procedure:
To a solution of 4-(3-fluoro-2-trifluoromethyl)phenylpiperidine hydrochloride (5, 0.080 g, 0.28 mmol), 6-(tert-butoxycarbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid (0.098 g, 0.67 mmol), and diisopropylethylamine (0.15 mL, 0.85 mmol) in DMF (5.3 mL) was added EDCI (0.065 mg, 0.34 mmol) and HOBt (46 mg, 0.34 mmol), and the mixture stirred at ambient temperature for 24 h. The mixture was diluted with H2O (30 mL) and extracted with EtOAc (4×30 mL). The combined organic extracts were washed with a saturated brine solution (4×30 mL) and concentrated to dryness under reduced pressure. The obtained residue was chromatographed over silica gel (Isco CombiFlash Rf unit, 12 g Redisep column, 0% to 10% CH3OH in CH2Cl2 with 0.1% NH4OH in CH2Cl2) to provide tert-butyl 3-(4-(3-fluoro-2-(trifluoromethyl)phenyl)piperidine-1-carbonyl)-4,5-dihydro-1H-pyrazolo[3,4-c]pyridine-6(7H)-carboxylate (29) as a white solid (66 mg, 47%): 1H NMR (300 MHz, DMSO-d6) δ 13.20-12.78 (m, 1H), 7.73-7.59 (m, 1H), 7.46 (d, J=7.2 Hz, 1H), 7.37-7.24 (m, 1H), 4.90-4.60 (m, 2H), 4.53-4.43 (m, 2H), 3.60-3.48 (m, 2H), 3.28-2.98 (m, 2H), 2.85-2.69 (m, 1H), 2.65-2.50 (m, 2H, overlaps with solvent), 1.87-1.56 (m, 4H), 1.42 (s, 9H); ESI MS m/z 497 [M+H]+.
Reaction SMILES: [H-].[Na+].[C:3]([CH:11]1[C:20](=[O:21])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[NH:13][CH2:12]1)(=[O:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[F:22][C:23]1[CH:30]=[CH:29][CH:28]=[CH:27][C:24]=1[CH2:25]Br>CN(C)C=O>[C:3]([C:11]1[C:20](=[O:21])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:13]([CH2:25][C:24]2[CH:27]=[CH:28][CH:29]=[CH:30][C:23]=2[F:22])[CH:12]=1)(=[O:10])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: Fc1ccccc1CBr
Reactant: O=C(c1ccccc1)C1CNc2ccccc2C1=O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C(c1ccccc1)c1cn(Cc2ccccc2F)c2ccccc2c1=O
Yield: 37.9 %

Procedure:
Compound 4u was prepared following the procedure outlined in Step 3 of Example 1 using 16 mg (0.4 mmol) of sodium hydride (60%), 75 mg (0.31 mmol) of 3-benzoyl-2,3-dihydro-1H-quinolin-4-one, 3 mL of anhydrous dimethylformamide, and 74 mg (0.40 mmol) of 2-fluorobenzylbromide. The crude product was purified by flash chromatography to yield 42 mg of a colorless solid 4u: LC-MSD, m/z for C23H16FNO2, [M+H]+=358.4, [M+2H]+=359.4; Reverse phase HPLC (gradient acetonitrile 0.1% TFA 20-95% in 4 min) retention time =2.291 min; 1H NMR (400 MHz, CDCl3/HCl): δ 5.42 (s, 2H), 7.00-7.20 (m, 3H), 7.28-7.46 (m, 5H), 7.51 (t, 1H), 7.61 (t, 1H), 7.78-7.86 (m, 2H), 8.32 (d, 1H), 8.46 (m, 1H).
Reaction SMILES: [O:1]1[C:6]2[CH:7]=[CH:8][C:9]([S:11][C:12]3[CH:17]=[CH:16][C:15](/[CH:18]=[CH:19]/[C:20]([N:22]4[CH2:27][CH2:26][NH:25][CH2:24][CH:23]4[C:28]([O:30]C)=[O:29])=[O:21])=[CH:14][C:13]=3[C:32]([F:35])([F:34])[F:33])=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1.Cl[C:37]([O:39][CH3:40])=[O:38].N1C=CC=CC=1.[OH-].[Na+].CCO>C(Cl)Cl.O>[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([S:11][C:12]3[CH:17]=[CH:16][C:15](/[CH:18]=[CH:19]/[C:20]([N:22]4[CH2:27][CH2:26][N:25]([C:37]([O:39][CH3:40])=[O:38])[CH2:24][CH:23]4[C:28]([OH:30])=[O:29])=[O:21])=[CH:14][C:13]=3[C:32]([F:35])([F:33])[F:34])=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1
Reactant: COC(=O)C1CNCCN1C(=O)/C=C/c1ccc(Sc2ccc3c(c2)OCCO3)c(C(F)(F)F)c1
Reactant: COC(=O)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Solvent: ClCCl
Product: COC(=O)N1CCN(C(=O)/C=C/c2ccc(Sc3ccc4c(c3)OCCO4)c(C(F)(F)F)c2)C(C(=O)O)C1

Procedure:
The title compound was prepared by treating the compound of Example 255 with methyl chloroformate and pyridine in CH2Cl2 at room temperature, and followed by hydrolysis under basic conditions (aq. NaOH/EtOH), producing a white solid, mp 102° C. (dec.). 1H NMR (DMSO-d6, 300 MHz) δ 2.85 (m, 1H), 3.02 (m, 1H), 3.20 (m, 1H), 3.40 (m, 1H), 3.62 (s, 3H), 3.88 (m, 1H), 4.29 (s, 4H), 4.35 (m, 1H), 5.15 (m, 1H), 6.90-7.10 (m, 3H), 7.30 (d, J=15.0 Hz, 1H), 7.40 (d, J=15.0 Hz, 1H), 7.54 (d, J=15.0 Hz, 1H), 7.82 (m, 1H), 8.15 (m, 1H). MS (ESI) m/z 553 (M+H)+. Anal. calcd. for C25H23F3N2O7S.0.25 H2O: C, 53.91; H, 4.25; N, 5.03. Found: 53.91; H, 4.35; N, 5.05.
Reaction SMILES: [Sn](Cl)(Cl)(Cl)Cl.C(O[C@@H:10]1[O:27][C@H:26]([CH2:28][O:29][C:30](=[O:32])[CH3:31])[C@@H:21]([O:22][C:23](=[O:25])[CH3:24])[C@H:16]([O:17][C:18](=[O:20])[CH3:19])[C@H:11]1[O:12][C:13](=[O:15])[CH3:14])(=O)C.[CH2:33]([O:35][C:36]1[CH:41]=[CH:40][C:39]([CH3:42])=[CH:38][C:37]=1[O:43][CH2:44][CH3:45])[CH3:34].C(=O)(O)[O-].[Na+]>ClCCCl.FC(F)(F)C([O-])=O.[Ag+].ClCCl>[C:13]([O:12][C@@H:11]1[C@@H:16]([O:17][C:18](=[O:20])[CH3:19])[C@H:21]([O:22][C:23](=[O:25])[CH3:24])[C@@H:26]([CH2:28][O:29][C:30](=[O:32])[CH3:31])[O:27][C@H:10]1[C:41]1[CH:40]=[C:39]([CH3:42])[CH:38]=[C:37]([O:43][CH2:44][CH3:45])[C:36]=1[O:35][CH2:33][CH3:34])(=[O:15])[CH3:14]
Reactant: CC(=O)OC[C@H]1O[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: CCOc1ccc(C)cc1OCC
Agent: [Ag+]
Agent: Cl[Sn](Cl)(Cl)Cl
Agent: O=C([O-])C(F)(F)F
Solvent: ClCCCl
Solvent: ClCCl
Product: CCOc1cc(C)cc([C@@H]2O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]2OC(C)=O)c1OCC
Temperature: 25 °C
Reaction time: 1 h
Yield: 35.9 %

Procedure:
A 1.0 M dichloromethane solution of tin tetrachloride (16.5 ml) was added to a suspension of 1,2,3,4,6-penta-O-acetyl-β-D-glucopyranose (6.41 g), 1,2-diethoxy-4-methylbenzene (2.47 g), and silver trifluoroacetate (3.63 g) in 1,2-dichloroethane (70 ml) at 0° C. and the mixture was stirred at the same temperature for one hour. After heating to room temperature and stirring for 15 hours, saturated aqueous solution of sodium bicarbonate was added to the mixture. The reaction mixture was filtered through celite and the filtrate was extracted with chloroform. The organic layer was washed with water and saturated brine and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure. Methanol (200 ml) and a catalytic amount of sodium methoxide were added to the resulting residue and the mixture was stirred at room temperature overnight. The solvent was evaporated under reduced pressure and the resulting residue was purified by silica gel column chromatography (chloroform-methanol). Pyridine (30 ml), acetic anhydride (5 ml), and a catalytic amount of 4-dimethylaminopyridine were added to the resulting residue and the mixture was stirred at room temperature for two days. Toluene was added to the reaction mixture and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate-n-hexane) to obtain (1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-(2,3-diethoxy-5-methylphenyl)-D-glucitol (2.51 g).
Reaction SMILES: [CH3:1][NH:2][NH2:3].[CH:4]([C:7]1[CH:23]=[CH:22][C:10]([C:11]([C:13]2[CH:21]=[CH:20][CH:19]=[CH:18][C:14]=2[C:15](O)=[O:16])=O)=[CH:9][CH:8]=1)([CH3:6])[CH3:5].O>C1(C)C=CC=CC=1>[CH3:1][N:2]1[N:3]=[C:11]([C:10]2[CH:9]=[CH:8][C:7]([CH:4]([CH3:5])[CH3:6])=[CH:23][CH:22]=2)[C:13]2[C:14](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:15]1=[O:16]
Reactant: CNN
Reactant: CC(C)c1ccc(C(=O)c2ccccc2C(=O)O)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: CC(C)c1ccc(-c2nn(C)c(=O)c3ccccc23)cc1
Yield: 67 %

Procedure:
Methyl hydrazine (8.05 g, 0.175 mol) was added to a mixture of 2-(4-isopropylbenzoyl)benzoic acid (40.2 g, 0.15 mol) in toluene (350 mL) and the mixture was heated to reflux for 3 hours with the removal of water with a Dean Stark trap. The reaction mixture was hot filtered through celite, the filtrate was concentrated to 125 mL and the filtrate was diluted with hexane (100 mL) and cooled. A solid was collected by filtration to afford 27.97 g (67%) of 2-methyl-4-(4-isopropylphenyl)-1-(2H)-phthalazinone, m.p. 107°-107.5° C.
Reaction SMILES: [C:1]1([O:7][CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:9](O)(=[O:12])CC.[Na].[OH-].[K+].S([O-])([O-])(=O)=O.[C:22]([N+](C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C)(C)[CH3:23].C([N+](C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C)(C)C.S([O-])([O-])(=O)=O.C([P+](CC)(C(C)(C)C)C(C)(C)C)C.C([P+](C(C)(C)C)(C(C)(C)C)CC)C>[Cl-].C([P+](CC)(CC)CC)C.[Pt].O>[C:1]1([O:7][CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:8]([O:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[O:12][CH3:9])[CH2:22][CH3:23]
Reactant: CC(C)(C)[N+](C(C)(C)C)(C(C)(C)C)C(C)(C)C
Reactant: CCC(=O)O
Agent: [Pt]
Agent: CC[P+](CC)(C(C)(C)C)C(C)(C)C
Agent: CC[P+](CC)(CC)CC
Solvent: COc1ccccc1
Solvent: O
Product: CCCOc1ccccc1OC

Procedure:
The treatment of anisole with propionic acid, sodium or potassium hydroxide, water and other phase transfer agents such as tetra-t-butylammonium sulfate, tetraethylphosphonium chloride, diethyldi-t-butylphosphonium sulfate, etc., in an electrochemical cell utilizing platinum anodes and stainless steel or graphite cathodes and utilizing electrical energy within the range hereinbefore set forth may produce similar results in the conversion of anisole to propoxyanisole.
Reaction SMILES: [CH2:1]([CH:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:31])[C:15]([NH:17][C:18]2[C:27]([N+:28]([O-])=O)=[CH:26][C:21]3[NH:22][C:23](=[O:25])[O:24][C:20]=3[CH:19]=2)=[O:16])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>[Pd].CO>[NH2:28][C:27]1[C:18]([NH:17][C:15](=[O:16])[C:14]([N:11]2[CH2:10][CH2:9][CH:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH2:13][CH2:12]2)=[O:31])=[CH:19][C:20]2[O:24][C:23](=[O:25])[NH:22][C:21]=2[CH:26]=1
Reactant: O=C(Nc1cc2oc(=O)[nH]c2cc1[N+](=O)[O-])C(=O)N1CCC(Cc2ccccc2)CC1
Agent: [Pd]
Solvent: CO
Product: Nc1cc2[nH]c(=O)oc2cc1NC(=O)C(=O)N1CCC(Cc2ccccc2)CC1
Reaction time: 8 h
Yield: 34.9 %

Procedure:
A mixture of 3.3 g(7.7 mmol) of 2-(4-benzylpiperidin-1-yl)-N-(5-nitro-2-oxo-2,3-dihydro-benzoxazol-6-yl)-2-oxo-acetamide, 100 ml of methanol and 0.3 g of 10% Pd/C catalyst is hydrogenated for 8 h. The catalyst is filtered off and the filtrate is concentrated. The residue is purified by column chromatography using Kieselgel 60 as adsorbent (Merck) and toluene:acetone=2:1 as eluent to yield 1.06 g (34.5%) of the title compound. Mp.: 296° C. (toluene-acetone).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:5]=[C:4]2[N:14]([CH3:18])[N:15]=[C:16]([CH3:17])[C:3]=12.[CH3:19][NH:20][CH3:21]>>[CH3:19][N:20]([CH3:21])[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:5]=[C:4]2[N:14]([CH3:18])[N:15]=[C:16]([CH3:17])[C:3]=12
Reactant: Cc1nn(C)c2nc(-c3ccccc3)cc(Cl)c12
Reactant: CNC
Product: Cc1nn(C)c2nc(-c3ccccc3)cc(N(C)C)c12
Temperature: 25 °C

Procedure:
15.5 gms. of 4-chloro-1,3-dimethyl-6-phenyl-1H-pyrazolo[3,4-b]pyridine (0.06 mol.) are added to 132 ml. of a solution of dimethylamine (40%). The reaction mixture is heated at 190°-200° C. for 16 hours in an autoclave and after cooling to room temperature is evaporated in vacuo. The residue is treated with water and extracted with ether. After evaporation of the extract, the 4-dimethylamino-1,3-dimethyl-6-phenyl-1H-pyrazolo[3,4-b]pyridine (15.6 gms. = 98%) is recrystallized from ligroin, m.p. 90°-91° C.
Reaction SMILES: [C:1]1([C:7]2[CH:12]=[CH:11][C:10](C(=O)C)=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CS(C)=O.[OH2:20]>>[C:7]1([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:8]=[CH:9][CH:10]=[CH:11][C:12]=1[C:2]([OH:20])([C:1]#[CH:6])[CH3:3]
Reactant: O
Reactant: CC(=O)c1ccc(-c2ccccc2)cc1
Solvent: CS(C)=O
Product: C#CC(C)(O)c1ccccc1-c1ccccc1
Reaction time: 18 h

Procedure:
To a solution of 46.6 g of p-phenylacetophenone in 250 ml. of dimethyl sulfoxide, there is added 65.5 g of lithium acetylide - ethylene diamine complex. After 18 hours at room temperature, the mixture is poured on 2 liters of iced water. The initial oil solidifies on standing, is filtered off and recrystallized from 150 ml of isopropyl alcohol to give 2-(p-biphenylyl)-3-butyn-2-ol, mp 75°-80° C.
Reaction SMILES: [BH4-].[Na+].[C:3]([O:6][C@H:7]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH2:8][N:9]1[CH2:14][CH2:13][C:12]([CH2:15][CH2:16][O:17][CH:18]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:11][CH2:10]1)(=[O:5])[CH3:4].[OH-:37].[Na+].OO>C(O)C.O.C1COCC1>[C:3]([O:6][C@H:7]([C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[CH2:8][N:9]1[CH2:14][CH2:13][CH:12]([CH2:15][CH2:16][O:17][CH:18]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:11]([OH:37])[CH2:10]1)(=[O:5])[CH3:4]
Reactant: [OH-]
Reactant: CC(=O)O[C@@H](CN1CC=C(CCOC(c2ccccc2)c2ccccc2)CC1)c1ccccc1
Agent: OO
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: C1CCOC1
Solvent: O
Product: CC(=O)O[C@@H](CN1CCC(CCOC(c2ccccc2)c2ccccc2)C(O)C1)c1ccccc1

Procedure:
With reference to FIG. 8, general procedure II was used. The quantities of the chemicals in order of addition are as follows: NaBH4 (0.116 g, 3.08 mmol), THF (20 ml), BF3-ether complex (0.4 ml, 3.265 mmol), (R)-2-(4-(2-(benzhydryloxy)ethyl)-5,6-dihydropyridin-1(2H)-yl)-1-phenylethyl acetate 7a (0.7 g, 1.536 mmol), water (2 ml), ethanol (2 ml), 3N NaOH (1.1 ml) and 30% H2O2 (0.8 ml, 7.68 mmol).
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([NH2:24])[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:27])[F:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:29]([C:36]1[CH:37]=[C:38]([CH:41]=[CH:42][CH:43]=1)[CH:39]=O)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>>[CH2:1]([C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1[C:18]1[CH:19]=[C:20]([NH:24][CH2:39][C:38]3[CH:41]=[CH:42][CH:43]=[C:36]([O:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[CH:37]=3)[CH:21]=[CH:22][CH:23]=1)=[CH:15][CH:14]=[CH:13][C:12]=2[C:25]([F:28])([F:26])[F:27])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Nc1cccc(-c2c(Cc3ccccc3)cnc3c(C(F)(F)F)cccc23)c1
Reactant: O=Cc1cccc(Oc2ccccc2)c1
Product: FC(F)(F)c1cccc2c(-c3cccc(NCc4cccc(Oc5ccccc5)c4)c3)c(Cc3ccccc3)cnc12

Procedure:
The title compound was prepared from {3-[3-benzyl-8-(trifluoromethyl)quinolin-4-yl]phenyl}amine and 3-phenoxy-benzaldehyde according to the procedure of Example 66. MS (ES) m/z 561.1.
Reaction SMILES: [F:1][C:2]([F:26])([F:25])[C@H:3]([N:12]1[CH2:16][CH2:15][C@H:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:13]1)[C:4]1[CH:5]=[N:6][C:7]([NH:10][NH2:11])=[CH:8][CH:9]=1.[CH3:27][O:28][CH2:29][CH2:30][O:31][C:32]1[CH:41]=[C:40]2[C:35]([CH:36]=[CH:37][C:38]([CH:42]=O)=[N:39]2)=[CH:34][CH:33]=1.C(O)C.C(O)(=O)C.C(O)(=O)C.I(C1C=CC=CC=1)=O.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[F:26][C:2]([F:25])([F:1])[C@H:3]([N:12]1[CH2:16][CH2:15][C@H:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:22])([CH3:23])[CH3:21])[CH2:13]1)[C:4]1[CH:9]=[CH:8][C:7]2[N:6]([C:42]([C:38]3[CH:37]=[CH:36][C:35]4[C:40](=[CH:41][C:32]([O:31][CH2:30][CH2:29][O:28][CH3:27])=[CH:33][CH:34]=4)[N:39]=3)=[N:11][N:10]=2)[CH:5]=1
Reactant: CC(C)(C)OC(=O)N[C@H]1CCN([C@H](c2ccc(NN)nc2)C(F)(F)F)C1
Reactant: COCCOc1ccc2ccc(C=O)nc2c1
Agent: O=C([O-])O
Agent: O=Ic1ccccc1
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Solvent: CCO
Product: COCCOc1ccc2ccc(-c3nnc4ccc([C@@H](N5CC[C@H](NC(=O)OC(C)(C)C)C5)C(F)(F)F)cn34)nc2c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 64.3 %

Procedure:
A solution of tert-butyl (S)-1-((R)-2,2,2-trifluoro-1-(6-hydrazinylpyridin-3-yl)ethyl)pyrrolidin-3-ylcarbamate (0.20 g, 0.53 mmol) and 7-(2-methoxyethoxy)quinoline-2-carbaldehyde (0.12 g, 0.53 mmol) in ethanol (2.7 mL, 0.53 mmol) was allowed to stir at ambient temperature for 12 hours. The solvent was removed under reduced pressure. The residue was dissolved in dichloromethane (2.7 mL) and iodosobenzene diacetate (0.19 g, 0.59 mmol) was added. The reaction mixture was stirred at ambient temperature for 1 hour. Ethyl acetate (20 mL) and saturated sodium bicarbonate (10 mL) were added. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by reverse phase chromatography on C18 (0-100% acetonitrile/water) to give the title compound (0.20 g, 63%).