Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[C:4]([NH2:8])[CH:5]=[CH:6][CH:7]=1.[C:15]([C:17]1[O:21][C:20]([C:22](Cl)=[O:23])=[CH:19][CH:18]=1)#[N:16].CCN(C(C)C)C(C)C>>[CH3:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[C:4]([NH:8][C:22]([C:20]2[O:21][C:17]([C:15]#[N:16])=[CH:18][CH:19]=2)=[O:23])[CH:5]=[CH:6][CH:7]=1
Reactant: N#Cc1ccc(C(=O)Cl)o1
Reactant: Cc1cccc(N)c1N1CCCCC1
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cccc(NC(=O)c2ccc(C#N)o2)c1N1CCCCC1
Yield: 12 %

Procedure:
Using a procedure similar to example 3, step (d), 3-methyl-2-piperidin-1-yl-phenylamine (68 mg, 0.35 mmol, as prepared in the previous step) was allowed to react with 5-cyano-furan-2-carbonyl chloride (65 mg, 0.42 mmol) in the presence of DIEA (134 μL, 0.77 mmol) to afford 13 mg (12%) of the title compound as a waxy yellow solid. 1H-NMR (CDCl3, 400 MHz): δ 10.7 (br s, 1H), 8.33 (d, 1H, J=8.0 Hz), 7.27 (d, 1H, J=3.7 Hz), 7.22 (dd, 1H, 3.7 Hz), 7.12 (t, 1H, J=7.9 Hz), 6.87 (dd, 1H, J=0.7, 7.7 Hz), 3.22-3.28 (m, 2H), 2.88-2.91 (m, 1H), 2.41 (s, 3H), 2.01-2.04 (m, 1H), 1.80-1.86 (m, 4H), 1.43-1.47 (m, 1H); Mass spectrum (ESI, m/z): Calcd. for C18H19N3O2, 310.1 (M+H), found 310.2.
Reaction SMILES: [CH3:1][S:2]([CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([N+:12]([O-])=O)[CH:7]=1)(=[O:4])=[O:3].[OH-].[Na+]>Cl.C1COCC1.[Cl-].[Ti+3].[Cl-].[Cl-]>[CH3:1][S:2]([CH2:5][C:6]1[CH:7]=[C:8]([CH:9]=[CH:10][CH:11]=1)[NH2:12])(=[O:3])=[O:4]
Reactant: CS(=O)(=O)Cc1cccc([N+](=O)[O-])c1
Agent: [Ti+3]
Agent: Cl
Agent: [Cl-]
Solvent: C1CCOC1
Product: CS(=O)(=O)Cc1cccc(N)c1
Reaction time: 16 h
Yield: 102.1 %

Procedure:
Titanium(III)chloride solution (about 15%) in about 10% hydrochloric acid (162 mL; Merck Schuchardt OHG) was added to a stirred solution of 1-[(methylsulfonyl)methyl]-3-nitrobenzene (5.1 g; 23.8 mmol) in THF (250 mL) at room temperature and the batch was stirred for 16 hours. By adding 1N sodium hydroxide solution the pH value of the reaction mixture was raised to 10 before the batch was extracted with ethyl acetate (2×). The combined organic phases were washed with brine, filtered using a Whatman filter and concentrated to give the desired product (4.5 g) that was used without further purification.
Reaction SMILES: [CH:1]1[CH:6]=CC=C[CH:2]=1.[CH3:7][O:8][C:9]1[CH:10]=[C:11]([OH:28])[CH:12]=[C:13]([O:26][CH3:27])[C:14]=1[CH2:15][C@H:16]1[C@:18]([CH3:25])([CH2:19][CH2:20][CH:21]=[C:22]([CH3:24])[CH3:23])[O:17]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCCCCC>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(=O)(OC)OCC=C.CCOC(C)=O>[CH2:6]([C:14]1([CH2:15][C@H:16]2[C@:18]([CH3:25])([CH2:19][CH2:20][CH:21]=[C:22]([CH3:24])[CH3:23])[O:17]2)[C:9]([O:8][CH3:7])=[CH:10][C:11](=[O:28])[CH:12]=[C:13]1[O:26][CH3:27])[CH:1]=[CH2:2]
Reactant: c1ccccc1
Reactant: COc1cc(O)cc(OC)c1C[C@@H]1O[C@@]1(C)CCC=C(C)C
Agent: [Pd+2]
Agent: [Ti+4]
Agent: C=CCOC(=O)OC
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: C=CCC1(C[C@@H]2O[C@@]2(C)CCC=C(C)C)C(OC)=CC(=O)C=C1OC
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 65 %

Procedure:
Allyl methyl carbonate (18 μL, 0.16 mmol, 2.5 equiv.) and titanium(IV) isopropoxide (3.7 μL, 12 mmol, 0.2 equiv.) were added in sequence to a peach-colored PhH (0.5 mL) solution of 6 (19 mg, 62 mmol, 1 equiv.), triphenylphosphine (1.3 mg, 5.0 mmol, 0.08 equiv.), and palladium(II) acetate (0.3 mg, 1.2 mmol, 0.02 equiv.) at room temperature in a 10-mL heart-shaped flask, whereupon the solution turned an opaque dark red. After stirring at room temperature for 10 min, the solution was heated to 50° C. After 1 h of heating at this temperature, the solution turned clear dark red. After stirring for a total of 130 min at 50° C., the solution was cooled to room temperature and quenched with saturated aqueous NH4Cl. After diluting with PhH and stirring for 5 min, 1 N HCl was added, and the layers were separated. The aqueous layer was then extracted twice with EtOAc. The organic extracts were combined, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to an inhomogeneous green oil. Flash column chromatography (25 mL SiO2, 4:1 to 7:3 to 1:1 hexane:EtOAc) afforded 14 mg (40 mmol, 65% yield) of 7 as a clear, colorless oil. TLC Rf 0.22 (1:1 hexane:EtOAc). 1H NMR (600 MHz; CDCl3): δ 5.59 (d, J=7.7 Hz, 2H), 5.39 (ddt, J=17.1, 10.0, 7.2 Hz, 1H), 5.00-4.92 (m, 3H), 3.73 (s, 3H), 3.70 (s, 3H), 2.61-2.54 (m, 2H), 2.40 (t, J=5.9 Hz, 1H), 2.14 (dd, J=13.9, 5.3 Hz, 1H), 2.04 (dd, J=13.9, 6.6 Hz, 1H), 1.98-1.88 (m, 2H), 1.64 (s, 3H), 1.56 (s, 3H), 1.50 (ddd, J=13.7, 9.7, 6.3 Hz, 1H), 1.27 (ddd, J=13.7, 10.0, 6.5 Hz, 1H), 1.17 (s, 3H). 13C NMR (125 MHz; CDCl3): δ 188.0, 173.1, 172.6, 132.2, 131.9, 123.6, 118.4, 103.55, 103.45, 60.7, 59.3, 56.2, 56.0, 49.7, 41.7, 38.9, 35.7, 25.8, 23.9, 17.8, 16.7. IR (NaCl, thin film, cm−1) 2928, 1654, 1592, 1384, 1233, 1206, 1144. HRMS-ESI (m/z): [M+Na]+ calculated for C21H30O4, 369.2036. found, 369.2043.
Reaction SMILES: [O:1]1CCO[CH:2]1[C:6]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:7][NH:8][C:9](=[O:31])[C:10]1[C:15]([F:16])=[C:14]([S:17][C:18]2[S:22][C:21]([NH:23][C:24]3[CH:29]=[C:28]([CH3:30])[CH:27]=[CH:26][N:25]=3)=[N:20][CH:19]=2)[CH:13]=[CH:12][N:11]=1.C(=O)(O)[O-].[Na+]>CC(C)=O.O.C1COCC1.Cl>[F:16][C:15]1[C:10]([C:9]([NH:8][CH2:7][C:6]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH:2]=[O:1])=[O:31])=[N:11][CH:12]=[CH:13][C:14]=1[S:17][C:18]1[S:22][C:21]([NH:23][C:24]2[CH:29]=[C:28]([CH3:30])[CH:27]=[CH:26][N:25]=2)=[N:20][CH:19]=1
Reactant: Cc1ccnc(Nc2ncc(Sc3ccnc(C(=O)NCC(c4ccccc4)(c4ccccc4)C4OCCO4)c3F)s2)c1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Solvent: CC(C)=O
Product: Cc1ccnc(Nc2ncc(Sc3ccnc(C(=O)NCC(C=O)(c4ccccc4)c4ccccc4)c3F)s2)c1
Yield: 104.3 %

Procedure:
A solution of N-(2-(1,3-dioxolan-2-yl)-2,2-diphenylethyl)-3-fluoro-4-(2-(4-methylpyridin-2-ylamino)thiazol-5-ylthio)picolinamide (0.248 g, 0.4040 mmol, described in Example 50) in acetone (10 mL), water (5 mL), THF (5 mL) and conc. HCl (1 mL) was heated at gentle reflux for 10 hours. The reaction was then neutralized with aq. sat. sodium bicarbonate and the volatiles were evaporated. The solid was collected by filtration and vacuum dried to give the crude title material (0.240 g, 100%). 1H NMR (400 MHz, DMSO-d6) δ ppm: 2.30 (3H, s), 4.27 (2H, d, J=6.32 Hz), 6.83 (1H, d, J=4.55 Hz), 6.89 (1H, s), 7.03 (1H, t, J=5.31 Hz) 7.22 (4H, d, J=7.07 Hz) 7.31-7.37 (2H, m), 7.40 (4H, t, J=7.33 Hz) 7.77 (1H, s), 8.15 (1H, d, J=5.05 Hz), 8.19 (1H, d, J=5.05 Hz), 8.28 (1H, t, J=6.19 Hz). 9.99 (1H, s) 11.82 (1H, s).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[NH2:12])[C:5]([O:7][CH3:8])=[O:6].[N+:13]([C:16]1[CH:17]=[C:18]([CH:22]=[CH:23][CH:24]=1)[C:19](Cl)=[O:20])([O-:15])=[O:14]>>[CH3:8][O:7][C:5](=[O:6])[C:4]1[CH:9]=[CH:10][C:11]([NH:12][C:19](=[O:20])[C:18]2[CH:22]=[CH:23][CH:24]=[C:16]([N+:13]([O-:15])=[O:14])[CH:17]=2)=[C:2]([OH:1])[CH:3]=1
Reactant: O=C(Cl)c1cccc([N+](=O)[O-])c1
Reactant: COC(=O)c1ccc(N)c(O)c1
Product: COC(=O)c1ccc(NC(=O)c2cccc([N+](=O)[O-])c2)c(O)c1

Procedure:
Prepared by the method of Example 15b), from methyl 3-hydroxy-4-aminobenzoate (12.94 g, 77.0 mmol) and 3-nitrobenzoyl chloride (14.29 g, 77.0 mmol) the subtitle compound was obtained (22.45 g, 92%). The product was used directly in the next step without purification.
Reaction SMILES: [N+:1]1([O-])[CH:2]=[CH:3][C:4]2[C:9]=1[NH:8][CH:7]=[CH:6][CH:5]=2.CS([Cl:15])(=O)=O.[OH-].[Na+]>CN(C=O)C>[Cl:15][C:5]1[CH:6]=[CH:7][N:8]=[C:9]2[NH:1][CH:2]=[CH:3][C:4]=12
Reactant: [O-][n+]1ccc2ccc[nH]c1-2
Reactant: CS(=O)(=O)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Product: Clc1ccnc2[nH]ccc12
Temperature: 70 °C
Reaction time: 1.5 h
Yield: 70 %

Procedure:
7-Azaindole N-oxide (43.6 g, 325 mmol) was dissolved in anhydrous DMF (280 mL), and methanesulfonyl chloride (d=1.477, 80 mL, 1.03 mol) was dropwise added thereto under an argon atmosphere. The resulting mixture was stirred at 70° C. for 90 minutes. The reaction content was poured onto ice (1 kg) and was neutralized with a 5 N sodium hydroxide solution (400 mL). The precipitated solid was collected by filtration under reduced pressure, washed with iced-water, and dried under reduced pressure using an oil pump to give 34.7 g of 4-chloro-1H-pyrrolo[2,3-b]pyridine (yield: 70%).
Reaction SMILES: [Cl:1][C:2]1[C:3](=[O:16])[N:4]([CH:13]([CH3:15])[CH3:14])[N:5]=[CH:6][C:7]=1[O:8][CH2:9][CH:10]1[CH2:12][O:11]1.[CH2:17]([C:20]1[CH:25]=[C:24]([C:26]#[N:27])[CH:23]=[CH:22][C:21]=1[OH:28])[CH2:18][CH3:19].C(=O)([O-])[O-].[K+].[K+]>C(C(CC)=O)C>[Cl:1][C:2]1[C:3](=[O:16])[N:4]([CH:13]([CH3:15])[CH3:14])[N:5]=[CH:6][C:7]=1[O:8][CH2:9][CH:10]([OH:11])[CH2:12][O:28][C:21]1[CH:22]=[CH:23][C:24]([C:26]#[N:27])=[CH:25][C:20]=1[CH2:17][CH2:18][CH3:19]
Reactant: CCCc1cc(C#N)ccc1O
Reactant: CC(C)n1ncc(OCC2CO2)c(Cl)c1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(=O)CC
Product: CCCc1cc(C#N)ccc1OCC(O)COc1cnn(C(C)C)c(=O)c1Cl
Reaction time: 8 h

Procedure:
A mixture comprising 2.0 g of 4-chloro-5-(2-oxiranylmethoxy)-2-i-propyl-3(2H)pyridazinone prepared in Reference Example 5, 1.5 g of 2-n-propyl-4-cyanophenol, 1.35 g of potassium carbonate and 80 ml of diethyl ketone, was refluxed under stirring for 8 hours. Then, diethyl ketone was distilled off under reduced pressure, and the residue thereby obtained was extracted with ethyl acetate. The extract was washed with water and dried over sodium sulfate. Then, the solvent was distilled off. The residue was purified by silica gel column chromatography by using benzene-ethyl acetate (1:1, v/v) as the developer. The colorless crystals thereby obtained was recrystallized from ethyl ether to obtain 1.3 g of the above identified compound as colorless crystals having a melting point of from 118.5° to 121° C.
Reaction SMILES: [Na+].[Na+].[N+:3]([C:6]1[CH:7]=[C:8]([S:27]([O-:30])(=[O:29])=[O:28])[C:9]([CH:12]=[CH:13][C:14]2[C:15]([S:23]([O-:26])(=[O:25])=[O:24])=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=2)=[CH:10][CH:11]=1)([O-:5])=[O:4]>O>[N+:20]([C:17]1[CH:16]=[C:15]([S:23]([OH:26])(=[O:25])=[O:24])[C:14]([CH:13]=[CH:12][C:9]2[C:8]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:7][C:6]([N+:3]([O-:5])=[O:4])=[CH:11][CH:10]=2)=[CH:19][CH:18]=1)([O-:22])=[O:21]
Reactant: O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)[O-])c(S(=O)(=O)[O-])c1
Agent: [Na+]
Solvent: O
Product: O=[N+]([O-])c1ccc(C=Cc2ccc([N+](=O)[O-])cc2S(=O)(=O)O)c(S(=O)(=O)O)c1

Procedure:
Solid 4,4′-dinitro-2,2′-stilbenedisulfonic acid disodium salt (2550 parts) is dissolved in hot water to produce a nominal 8% w/w solution (7.8-8.2% expressed as 4,4′-dinitro-2,2′-stilbenedisulfonic acid). Then 2375 parts of 50% sodium hydroxide solution is added. The temperature of the solution is adjusted to 60-62° C. A self-condensation reaction is carried out in a pH range from about 11 to 13 and in the temperature range from 60 to 65° C. by the addition in equal increments over 2 hours of 700 parts of 93% paraformaldehyde. After the condensation is complete, the reaction mixture is then acidified with 90-96% sulfuric acid. For convenience half the reaction mass is fed to an extraction vessel containing methyl isobutyl ketone (12,850 parts) and triisooctylamine (11,600 parts) which is preheated to 55-60° C. The neutralized dye slurry is fed concurrently with concentrated sulfuric acid (1600 parts) to the extraction solvents with agitation. The vessel contents thus achieve a temperature of 65-80° C. After 15 minutes, the agitation is stopped and the phases separate immediately.
Reaction SMILES: [CH3:1][C:2]1[C:7]2[CH:8]=[CH:9][S:10][C:6]=2[CH2:5][CH2:4][N:3]=1>[C].[Pd].C1(C)C(C)=CC=CC=1>[CH3:1][C:2]1[C:7]2[CH:8]=[CH:9][S:10][C:6]=2[CH:5]=[CH:4][N:3]=1
Reactant: CC1=NCCc2sccc21
Agent: [Pd]
Solvent: Cc1ccccc1C
Product: Cc1nccc2sccc12
Temperature: 25 °C

Procedure:
To 4.43 g (0.0293 mol) of 4-methyl-6, 7-dihydrothieno[3, 2-c]pyridine (g-1) were added 244 ml of dry xylene and 3.42 g of 10% palladium carbon, and the mixture was refluxed for 34 hr. After being cooled down to room temperature, the solution was filtered. The filtrate was concentrated under reduced pressure and subjected to silica gel column chromatography, eluting with AcOEt - MeOH, whereby 1.47 g (Yield : 33.6%) of the objective product, 4-methylthieno[3, 2-c]pyridine (j-1) was obtained as brown liquid.
Reaction SMILES: [C:1]1([N:7]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:27][C:28]([CH3:31])([O-])[CH3:29].[Na+]>[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C1(C)C=CC=CC=1>[C:1]1([N:7]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:8]2[CH:13]=[CH:12][C:11]([N:14]([C:20]3[CH:15]=[CH:16][C:27]4[N:7]([C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=5)[C:8]5[C:29]([C:28]=4[CH:31]=3)=[CH:12][CH:11]=[CH:10][CH:9]=5)[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: c1ccc(Nc2ccc(N(c3ccccc3)c3ccccc3)cc2)cc1
Reactant: CC(C)(C)[O-]
Agent: [Pd]
Agent: O=C(C=Cc1ccccc1)C=Cc1ccccc1
Agent: [Na+]
Solvent: Cc1ccccc1
Product: c1ccc(N(c2ccccc2)c2ccc(N(c3ccccc3)c3ccc4c(c3)c3ccccc3n4-c3ccccc3)cc2)cc1
Temperature: 80 °C
Yield: 65 %

Procedure:
Specifically, 627.64 mg (1.7 mmol) of 3-iodine-9-phenylcarbazole, 672.86 mg (2.0 mmol) of N-(4-diphenylaminophenyl)-N-phenylamine, 57.5 mg (0.1 mmol) of bis(dibenzylidene acetone) palladium and 335 mg (3.5 mmol) of sodium tert-butoxide were mixed in a three-neck flask. Nitrogen was substituted for air inside of the three-neck flask. Then, 3.5 ml of dehydrated toluene was added in the mixture in the three-neck flask, and degassed for about 3 minutes. Subsequently, 0.4 ml of tri-tert-butyl phosphine (a 10 wt % hexane solution) was added to the mixture and the content was mixed by lightly shaking the container up and down. The content was stirred further for 10 minutes while being irradiated and heated at 80° C. with 200 W of microwave. After the reaction, saturated saline was added and a product was extracted with 100 ml of ethyl acetate. Further, magnesium sulfate was added to the product to remove moisture, and then the magnesium sulfate was filtered to be removed. The filtrate was concentrated, and a target matter was taken out by a silica gel column using a solvent containing ethyl acetate and hexane with a ratio of 1:1. Hexane was added to the thus-obtained solution and the resultant was heated to be recrystallized. Consequently, 650 mg (the yield: 65%) of a cream-colored powder was obtained. The NMR data is shown below. The 1H-NMR (300 MHz, DMSO-d); δ=6.89-7.05 (m, 13H), 7.21-7.28 (m, 9H), 7.32-7.43 (m, 3H), 7.50-7.69 (m, 5H), 8.02 (s, 1H), 8.14 (d, j=7.2, 1H). Also, a chart of 1H-NMR is shown in FIG. 13. Also, a chart of an enlarged portion of FIG. 13 in the range of 6.0 ppm and 9.0 ppm is shown in FIG. 14.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([OH:13])=O)[CH:10]=1)[NH:7][CH:6]=[CH:5]2.[C:14]([C:18]1[CH:34]=[CH:33][C:21]([CH2:22][NH:23][CH2:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)=[CH:20][CH:19]=1)([CH3:17])([CH3:16])[CH3:15].CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[C:14]([C:18]1[CH:34]=[CH:33][C:21]([CH2:22][N:23]([CH2:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[C:11]([C:9]2[CH:10]=[C:2]([F:1])[CH:3]=[C:4]3[C:8]=2[NH:7][CH:6]=[CH:5]3)=[O:13])=[CH:20][CH:19]=1)([CH3:17])([CH3:15])[CH3:16]
Reactant: CC(C)(C)c1ccc(CNCCc2ccc(F)cc2)cc1
Reactant: O=C(O)c1cc(F)cc2cc[nH]c12
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Product: CC(C)(C)c1ccc(CN(CCc2ccc(F)cc2)C(=O)c2cc(F)cc3cc[nH]c23)cc1
Temperature: 25 °C
Yield: 73.2 %

Procedure:
66 mg (0.33 mol) of 5-fluoro-1H-indol-7-carboxylic acid, 86 mg (0.30 mmol) of (4-tert-butyl-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amine and 63 mg (0.33 mmol) of EDC.HCl were dissolved in 3 ml DCM. The reaction mixture was stirred at rt over night. The solvent was evaporated and the residue was purified by column chromatography (20 g silica gel; heptane/EtOAc 7:3) to yield 98 mg (73%) product as a light yellow viscous oil. MS (ISP) 447.2 (M+H)+.
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[N:5][CH:6]=[CH:7][C:8]=1[C:9]1[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=1)[C:12]#[N:13])=[O:2].[CH3:17][O:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[Mg]Br>C1COCC1>[OH:2][CH:1]([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[O:18][CH3:17])[C:3]1[CH:4]=[N:5][CH:6]=[CH:7][C:8]=1[C:9]1[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=1)[C:12]#[N:13]
Reactant: N#Cc1cccc(-c2ccncc2C=O)c1
Reactant: COc1ccccc1[Mg]Br
Solvent: C1CCOC1
Product: COc1ccccc1C(O)c1cnccc1-c1cccc(C#N)c1

Procedure:
To a solution of 3-(3-formyl-pyridin-4-yl)-benzonitrile (30 mg, 0.15 mmol) in THF (1.5 mL) at −78° C. was added 1.0 M 2-methoxyphenylmagnesium bromide in THF (0.3 mL). The reaction mixture was quenched with ammonium chloride and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, concentrated, and the residue purified by flash chromatography eluted with 5% methanol in dichloromethane to yield 3-{3-[hydroxy-(2-methoxy-phenyl)-methyl]-pyridin-4-yl}-benzonitrile as white crystals.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]2[C:11]([O:13][C:14](=[O:15])[C:2]=12)=[O:12].[F:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[Cl-].[Al+3].[Cl-].[Cl-]>O>[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:11]([C:3]2[C:2]([C:14]([OH:13])=[O:15])=[CH:1][C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:4]=2)=[O:12])=[CH:19][CH:18]=1
Reactant: O=C1OC(=O)c2cc3ccccc3cc21
Reactant: Fc1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Product: O=C(O)c1cc2ccccc2cc1C(=O)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 6 h
Yield: 113.8 %

Procedure:
45.0 g (227 mmols) of 2,3-naphthalenedicarboxylic anhydride are suspended in 200 ml (2.1 mols) of fluorobenzene, and in the course of 5 minutes, with vigorous stirring, 75.5 g (565 mmols) of powdered aluminium chloride are added (exothermic reaction up to about 32° C.). The dark-red suspension is refluxed and stirred for 6 hours, and the solution is then allowed to cool to room temperature; it is subsequently poured onto about 500 g of ice, and is stirred until completion of hydrolysis. Excess fluorobenzene is evaporated off, and the product obtained is suspended in water. The suspension is filtered off, the filtrate is afterwards washed and the product is dried. There are obtained 76 g of crude 2-(4-fluorobenzoyl)-naphthalene-3-carboxylic acid. The crude product is stirred up with 2 liters of 10% sodium carbonate solution; the resulting solution is then acidified with hydrochloric acid, and the white precipitate is filtered off and dried. The yield is 54.2 g (81% of theory) of 2-(4-fluorobenzoyl)-naphthalene-3-carboxylic acid. MS: (M+ =294; M+ --COOH=249, M+ --COO=250, M+ --C6H4F=199); IR spectrum (KBr): OH about 3300 cm-1 ; C=O double bands 1695/1705 cm-1.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][C:3]([C@H:6]2[CH2:11][CH2:10][C@:9]3([OH:26])[C@H:12]4[C@H:22]([CH2:23][CH2:24][C@:7]23[CH3:8])[C@:20]2([CH3:21])[C@@H:15]([CH2:16][C@@H:17]([OH:25])[CH2:18][CH2:19]2)[CH2:14][CH2:13]4)=[CH:2]1.[H-].[Na+].[CH2:29](Br)[CH:30]=[CH2:31]>O1CCCC1>[CH2:31]([O:25][C@H:17]1[CH2:18][CH2:19][C@@:20]2([CH3:21])[C@H:15]([CH2:14][CH2:13][C@@H:12]3[C@@H:22]2[CH2:23][CH2:24][C@@:7]2([CH3:8])[C@:9]3([OH:26])[CH2:10][CH2:11][C@@H:6]2[C:3]2[CH:4]=[CH:5][O:1][CH:2]=2)[CH2:16]1)[CH:30]=[CH2:29]
Reactant: C[C@]12CC[C@H](O)C[C@H]1CC[C@@H]1[C@@H]2CC[C@]2(C)[C@@H](c3ccoc3)CC[C@]12O
Reactant: C=CCBr
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: C=CCO[C@H]1CC[C@@]2(C)[C@H](CC[C@@H]3[C@@H]2CC[C@]2(C)[C@@H](c4ccoc4)CC[C@]32O)C1
Reaction time: 20 h
Yield: 87 %

Procedure:
To a solution of 0.60 g of 17β-(3-furyl)-5β-androstane-3β,14β-diol (II-a: Ref. comp.) (Minato H. and Nagasaki T., J. Chem. Soc. (C), 1966, 377) in 50 ml of dry tetrahydrofuran, 0.44 g of sodium hydride (60% dispersion in mineral oil) were added under nitrogen atmosphere at room temperature and the resulting mixture was stirred at reflux temperature for 6 hrs; 1.4 g of allyl bromide were added and the reflux continued for further 20 hrs. The mixture was quenched with water and the organic solvent was distilled under reduced pressure. The residue was extracted with ethyl acetate, the organic solution was dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The residue was purified by flash-chromatography (SiO2) using n-hexane/ethyl acetate 80/20 as eluant to give 0.58 g of 3β-(prop-2-enoxy)-17β-(3-furyl)-5β-androstan-14β-ol as a white solid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[CH:11]=[CH:10][N:9]([CH3:12])[C:5]2=[C:6](Cl)[N:7]=1.[CH3:13][O-:14].[Na+].CO>>[Br:1][C:2]1[CH:3]=[C:4]2[CH:11]=[CH:10][N:9]([CH3:12])[C:5]2=[C:6]([O:14][CH3:13])[N:7]=1
Reactant: C[O-]
Reactant: Cn1ccc2cc(Br)nc(Cl)c21
Agent: [Na+]
Solvent: CO
Product: COc1nc(Br)cc2ccn(C)c12
Temperature: 130 °C
Yield: 97 %

Procedure:
The product from Example 91A (0.43 g, 1.752 mmol) and 0.5 M sodium methoxide in methanol (15 mL, 7.50 mmol) were combined in a sealed microwave tube, heated by microwave at 130° C. for 45 minutes, cooled and concentrated. The residue was partitioned between ethyl acetate and water adjusting the pH to 7 with 1 M HCl. The organic layer was washed with saturated aqueous sodium chloride, dried (anhydrous Na2SO4), filtered, and concentrated to afford the title compound (0.41 g, 97%).
Reaction SMILES: [F:1][C:2]1[C:3]([N:9]=[CH:10][N:11]([CH3:13])[CH3:12])=[N:4][C:5]([OH:8])=[N:6][CH:7]=1.CC(C)([O-])C.[K+].[CH3:20][S:21][CH2:22]Cl>CN(C=O)C>[F:1][C:2]1[C:3]([N:9]=[CH:10][N:11]([CH3:13])[CH3:12])=[N:4][C:5](=[O:8])[N:6]([CH2:20][S:21][CH3:22])[CH:7]=1
Reactant: CSCCl
Reactant: CN(C)C=Nc1nc(O)ncc1F
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CSCn1cc(F)c(N=CN(C)C)nc1=O
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 2.7 %

Procedure:
A 250 mL round bottom flask was charged with N′-(5-fluoro-2-hydroxypyrimidin-4-yl)-N,N-dimethylformamidine (1.00 g, 5.43 mmol) and DMF (55 mL) to give a white suspension. Solid potassium tert-butoxide (1.07 g, 9.53 mmol) was added, and the resulting pale yellow suspension was allowed to stir under nitrogen at room temperature for 20 min. Chloromethyl methyl sulfide (682 microliters (μL), 8.14 mmol) was then added, and the mixture was heated at 60° C. for 21 h. The crude reaction mixture was concentrated in vacuo at 55° C. to give an off-white residue which was purified by reverse phase column chromatography yielding N′-(5-fluoro-1-methylsulfanylmethyl-2-oxo-1,2-dihydropyrimidin-4-yl)-N,N-dimethylformamidine (36 mg, 25%) as a pale yellow solid: mp 132-136° C.; 1H NMR (400 MHz, CDCl3) δ 8.68 (s, 1H), 8.20 (d, J=3.2 Hz, 1H), 5.40 (s, 2H), 3.19 (s, 3H), 3.07 (s, 3H), 2.20 (s, 3H); IR 2960 (w), 2926 (w), 1640 (s), 1582 (s), 1447 (s), 1382 (m), 1319 (m), 1269 (m), 1108 (m), 1051 (m) cm−1; ESIMS m/z 267 ([M+Na]+).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([N+:9]([O-])=O)=[CH:7][CH:6]=[CH:5][C:4]=1[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([OH:20])=[O:19])[CH:13]=1.C([O-])=O.[NH4+]>C(O)C.[Pd]>[CH3:1][O:2][C:3]1[C:8]([NH2:9])=[CH:7][CH:6]=[CH:5][C:4]=1[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([OH:20])=[O:19])[CH:13]=1
Reactant: COc1c(-c2cccc(C(=O)O)c2)cccc1[N+](=O)[O-]
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CCO
Product: COc1c(N)cccc1-c1cccc(C(=O)O)c1
Temperature: 80 °C
Yield: 99.2 %

Procedure:
2′-Methoxy-3′-nitro-biphenyl-3-carboxylic acid 1d (0.48 g, 1.74 mmol) was dissolved in 60 mL of ethanol followed by addition of 0.5 g of palladium on carbon (10%) and ammonium formate (1.1 g, 17.4 mmol). The reaction mixture was heated to reflux at 80° C. for 20 minutes. The mixture was filtered and the filtrate was concentrated under reduced pressure and dried to obtain the title compound 2′-methoxy-3′-amino-biphenyl-3-carboxylic acid 1e (0.42 g, yield 93.3%) as a white solid.