Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:4]1[CH:8]=[CH:7][N:6]=[C:5]1[C:9]1[S:10][C:11]([Sn](CCCC)(CCCC)CCCC)=[CH:12][C:13]=1[C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[Cl:21])[CH:2]=[CH2:3].Br[C:36]1[C:37]([CH3:45])=[N:38][N:39]2[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=12>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([N:4]1[CH:8]=[CH:7][N:6]=[C:5]1[C:9]1[S:10][C:11]([C:36]2[C:37]([CH3:45])=[N:38][N:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=23)=[CH:12][C:13]=1[C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=1[Cl:21])[CH:2]=[CH2:3]
Reactant: Cc1nn2ccccc2c1Br
Reactant: C=CCn1ccnc1-c1sc([Sn](CCCC)(CCCC)CCCC)cc1-c1ccc(Cl)cc1Cl
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Product: C=CCn1ccnc1-c1sc(-c2c(C)nn3ccccc23)cc1-c1ccc(Cl)cc1Cl
Temperature: 100 °C
Reaction time: 1 h

Procedure:
To a solution of 1-allyl-2-[3-(2,4-dichlorophenyl)-5-(tributylstannyl)-2-thienyl]-1H-imidazole (180 mg, 0.29 mmol) in DMF (4.0 mL) was added [3-bromo-2-methylpyrazolo[1,5-a]pyridine (50 mg, 0.2 mmol) (azeotroped from toluene) and Bis(triphenylphosphine)palladium(II) chloride (8.5 mg, 0.012 mmol). The resulting mixture was degassed and stirred for 1 h at 100° C. under an atmosphere of argon. The reaction mixture was allowed to cool, concentrated and the residue was partially purified by silica gel column chromatography (40 g, eluting with 30% EtOAc in hexanes to EtOAc to give 3-[5-(1-allyl-1H-imidazol-2-yl)-4-(2,4-dichlorophenyl)-2-thienyl]-2-methylpyrazolo[1,5-a]pyridine, 82 mg. To a solution of [A] 3-[5-(1-allyl-1H-imidazol-2-yl)-4-(2,4-dichlorophenyl)-2-thienyl]-2-methylpyrazolo[1,5-a]pyridine (70 mg, 0.2 mmol), tetrakis(triphenylphosphine)palladium(0) (8.5 mg, 0.0074 mmol) and acetic acid (0.4 mL, 7 mmol) in DCM (1.5 mL) was added slowly phenylsilane (0.1 mL, 0.8 mmol) and the reaction mixture stirred at 40° C. for 2 h. The reaction mixture was concentrated and the product was purified by column chromatography on silica gel eluting with 1-3% MeOH in DCM. The product was further purified by preparative hplc, formic acid gradient. The title compound was isolated as a colorless lyophilized solid, 25 mg. LC/MS (FA) ES+ 425.0, 427.6, 428.4, 429.3. 1H NMR (400 MHz, d4-MeOH) δ: 8.48 (d, J=8.3 Hz, 1H), 7.85-7.87 (m, 1H), 7.50-7.60 (m, 1H), 7.31-7.39 (m, 3H), 7.18 (s, 1H), 7.04 (s, 2H), 6.90-6.95 (m, 1H), 2.62 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1([CH3:23])[CH2:20][C:6]2[N:7]=[C:8]([NH:10][C:11]([NH:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])=[O:12])[S:9][C:5]=2[C:4]([CH3:22])([CH3:21])[CH2:3]1.[CH2:24]1OCO[CH2:26][O:25]1.S(=O)(=O)(O)O.[OH-].[Na+]>O>[CH3:23][C:2]1([CH3:1])[CH2:20][C:6]2[N:7]=[C:8]([N:10]3[C:11](=[O:12])[N:13]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[CH2:26][O:25][CH2:24]3)[S:9][C:5]=2[C:4]([CH3:22])([CH3:21])[CH2:3]1
Reactant: C1OCOCO1
Reactant: CCCCCCNC(=O)Nc1nc2c(s1)C(C)(C)CC(C)(C)C2
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCCCCCN1COCN(c2nc3c(s2)C(C)(C)CC(C)(C)C3)C1=O
Temperature: 5 °C
Reaction time: 16 h

Procedure:
Sulfuric acid, 85% concentration, (40 grams) is charged into a glass reaction vessel fitted with a mechanical stirrer and thermometer and is cooled to about 5° C. N-(5,5,7,7-tetramethyl-4,5,6,7-tetrahydrobenzothiazol-2-yl)-N'-hexylurea (0.015 mole) and s-trioxane (0.015 mole) are added portionwise, with stirring to the cold sulfuric acid. Stirring is continued for a period of about 16 hours at room temperature. The reaction mixture is then diluted 1:1 with water and neutralized with aqueous 40% sodium hydroxide. The neutralized mixture is filtered and the filtered-off solid is washed with 3-100 ml portions of water and air dried to yield the desired product 3-(5,5,7,7-tetramethyl-4,5,6,7-tetrahydrobenzothiazol-2-yl)-5-hexyltetrahydro-1,3,5-oxadiazin-4-one.
Reaction SMILES: C([O:4][S:5]([C:8]1[C:17]([N:18]=[N:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)=[C:16]([OH:28])[C:15]2[C:10](=[CH:11][C:12]([NH:29][C:30](=[O:41])[C:31]3[C:36]([O:37][CH3:38])=[CH:35][CH:34]=[CH:33][C:32]=3[O:39][CH3:40])=[CH:13][CH:14]=2)[CH:9]=1)(=[O:7])=[O:6])(C)C.[I-].[Na+]>CC(=O)CC>[CH3:38][O:37][C:36]1[CH:35]=[CH:34][CH:33]=[C:32]([O:39][CH3:40])[C:31]=1[C:30]([NH:29][C:12]1[CH:11]=[C:10]2[C:15]([C:16]([OH:28])=[C:17]([N:18]=[N:19][C:20]3[CH:21]=[CH:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=3)[C:8]([S:5]([OH:7])(=[O:4])=[O:6])=[CH:9]2)=[CH:14][CH:13]=1)=[O:41]
Reactant: COc1ccc(N=Nc2c(S(=O)(=O)OC(C)C)cc3cc(NC(=O)c4c(OC)cccc4OC)ccc3c2O)cc1
Agent: [I-]
Agent: [Na+]
Solvent: CCC(C)=O
Product: COc1ccc(N=Nc2c(S(=O)(=O)O)cc3cc(NC(=O)c4c(OC)cccc4OC)ccc3c2O)cc1
Temperature: 60 °C
Reaction time: 24 h
Yield: 88.3 %

Procedure:
7-(2,6-Dimethoxy-benzoylamino)-4-hydroxy-3-(4-methoxy-phenylazo)-napthalene-2-sulfonic acid isopropyl ester (Example 17, 35 mg, 0.06 mmol) was suspended in 2-butanone (3 m) and sodium iodide (18 mg, 0.12 mmol) was added. The reaction mixture was allowed to stir under nitrogen at 60° C. for 24 h. The solvent was removed under a stream of nitrogen, acetone was added and the suspension was filtered to provide the title compound (30 mg, 0.053 mmol, 89%) as a red solid: NMR (DMSO-d6): δ 16.38 (s, 1H), 10.71 (s, 1H), 8.35 (d, J=9 Hz, 1H), 8.11 (s, 1H), 7.90 (m, 3H), 7.52 (s, 1H), 7.44 (t, J=9 Hz, 1H), 7.07 (d, J=9 Hz, 2H), 6.67 (d, J=9 Hz, 2H), 3.92 (s, 3H), 3.87 (s, 6H); Analytical HPLC: 87% pure; MS (ES-NEG): [M−H] 536; Anal. Calc. for C26H23N3O8SNa: C, 55.81, H, 3.96, N, 7.51. Found: C, 50.83, H, 4.07, N, 6.42.
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=1.[F:13][C:14]1[CH:15]=[CH:16][C:17]([CH3:24])=[C:18]([S:20](Cl)(=[O:22])=[O:21])[CH:19]=1>>[F:13][C:14]1[CH:15]=[CH:16][C:17]([CH3:24])=[C:18]([S:20]([NH:1][C:2]2[S:3][CH:4]=[C:5]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=2)(=[O:22])=[O:21])[CH:19]=1
Reactant: Cc1ccc(F)cc1S(=O)(=O)Cl
Reactant: CCOC(=O)Cc1csc(N)n1
Product: CCOC(=O)Cc1csc(NS(=O)(=O)c2cc(F)ccc2C)n1

Procedure:
The title compound was prepared from ethyl 2-amino-4-thiazolylacetate and 5-fluoro-2-methylbenzenesulfonyl chloride as described in the synthetic METHOD B to give a white solid (32.7 mg) with purity >90%. LCMS (pos) m/z 359.2.
Reaction SMILES: C([O:8][C:9](=[O:36])[CH:10]([NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:11][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:14]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:13]=1)C1C=CC=CC=1.[OH-].[K+].C1COCC1>CO.O>[CH2:21]([N:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:12]([CH2:11][C@@H:10]([NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:9]([OH:36])=[O:8])=[CH:13]1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: CC(C)(C)OC(=O)NC(Cc1cn(Cc2ccccc2)c2ccccc12)C(=O)OCc1ccccc1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)N[C@H](Cc1cn(Cc2ccccc2)c2ccccc12)C(=O)O
Reaction time: 2 h

Procedure:
To 3-(1-benzyl-1H-indol-3-yl)-2-tert-butoxycarbonylamino-propionic acid benzyl ester (2.1 g. 4.3 mmol) in MeOH (10 mL) was added KOH (0.740 g, 12.9 mmol) in water (5 mL). THF (5 mL) was added until the solution became homogenous. The solution was stirred until completion (about 2 h). Volatile solvents were removed and the residue taken up into CH2Cl2 and water. The aqueous layer was carefully acidified with dilute aqueous HCl and extracted with Et2O. The Et2O was washed with water and brine and then dried with MgSO4. The solution was filtered and the solvent removed to afford the required material without further purification (1.555 g, 91%). ESMS 395 (M+H+), mp 163.8-165.4° C. (EtOAc/petroleum ether). 1H NMR (DMSO-d6) δ 7.56 (1H, d, J=7.83 Hz), 7.39-6.99 (10H, m), 6.65 (1H, d), 4.18 (1H, m), 5.36 (2H, s), 3.15 (1H, dd, J=4.67, 14.56 Hz), 2.99 (1H, dd, J=9.18, 14.56 Hz), 1.32 (9H, s). 13C NMR (DMSO-d6) δ 174.0, 155.2, 137.6, 136.4, 128.7, 127.5, 127.2, 126.7, 126.6, 121.7, 119.3, 119.2, 109.7, 109.6, 79.4, 54.1, 49.9, 28.3, 27.7. ISMS: 395 (M+H),
Reaction SMILES: [C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]([Br:21])=[CH:13][CH:12]=1.C(COC)OC.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.C1(C)C=CC=CC=1>[Br:21][C:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:11]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:12][CH:13]=1
Reactant: OB(O)c1ccccc1
Reactant: Brc1ccc(Br)c2ccccc12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: COCCOC
Solvent: O
Product: Brc1ccc(-c2ccccc2)c2ccccc12
Temperature: 78 °C
Reaction time: 24 h
Yield: 41.1 %

Procedure:
Under an argon gas atmosphere, 128.0 g (1.049 mol) of phenylboronic acid, 300.0 g (1.163 mol) of 1.4-dibromonaphthalene, 24.2 g (21.0 mmol) of tetrakis(triphenylphosphine)palladium(0), 4.3 L of dimethoxyethane and 1.60 L of 2M sodium carbonate solution were mixed, and stirred for 24 hours at 78 degrees C. The reaction mixture was further added with toluene and water, and then aqueous phase thereof was eliminated. After organic phase thereof was cleansed by water and dried with magnesium sulfate, toluene was distilled away under reduced pressure. By refining residue thereof by silica-gel column chromatography and by recrystallizing the residue by hexane, 122 g of 1-bromo-4-phenyl naphthalene was obtained with an yield of 41%.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[N:4][C:5]([C:13]2[CH:18]=[CH:17][C:16]([C:19]#[N:20])=[CH:15][CH:14]=2)=[CH:6][C:7]=1C(OCC)=O>O>[Cl:1][C:2]1[N:3]=[N:4][C:5]([C:13]2[CH:18]=[CH:17][C:16]([C:19]#[N:20])=[CH:15][CH:14]=2)=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1cc(-c2ccc(C#N)cc2)nnc1Cl
Solvent: O
Product: N#Cc1ccc(-c2ccc(Cl)nn2)cc1

Procedure:
3-chloro-6-(4-cyanophenyl)-4-(ethoxycarbonyl)-pyridazine After the reaction solution has been stirred into water the aqueous phase is extracted with ethyl acetate. The organic phase is dried, evaporated down and the residue is chromatographed. Rf value: 0.37 (silica gel; cyclohexane/ethyl acetate=2:1)
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH2:20]([C:25]1C=C(C)C=C[C:26]=1S([O-])(=O)=O)[CH2:21][CH2:22]CC.O>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH:21]([CH2:20][CH2:25][CH3:26])[CH3:22])[CH:13]=[CH:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: c1ccc(COc2ccc3[nH]ccc3c2)cc1
Reactant: CCCCCc1cc(C)ccc1S(=O)(=O)[O-]
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCCC(C)n1ccc2cc(OCc3ccccc3)ccc21
Temperature: 0 °C
Reaction time: 18 h

Procedure:
5-Benzyloxyindole (7) (8.81 g, 39.5 mmol, 1.0 equiv., supplied by Combi-Blocks) was dissolved in anhydrous DMF (100 mL) and the solution was cooled to 0° C. Dry sodium hydride (1.89 g, 78.9 mmol, 2.0 equiv.) was added slowly. The mixture was warmed to room temperature over 30 minutes. 2-Pentyl-tosylate was added dropwise. The mixture was stirred for 18 h. Water was added slowly (dropwise at first) to quench excess NaH. The resulting mixture was extracted once with ether, and then washed with water and brine, respectively. The organic phase was dried with MgSO4, and concentrated on a rotary evaporator to yield a crude oil. The crude product was purified by flash column chromatography (3:1 hexanes/ethyl acetate) to yield 5-(benzyloxy)-1-(pentan-2-yl)-1H-indole (8) as an amber oil (10.67 g) of approximately 90% purity, which was used in the next step without any further purification. 1H NMR (500 MHz, CDCl3) δ7.50 (d, J=7.3 Hz, 2H), 7.40 (t, J=7.3 Hz, 2H), 7.34 (d, J=7.3 Hz, 1H), 7.29 (d, J=9.0 Hz, 1H), 7.17 (dd, J=8.9, 2.4 Hz, 1H), 6.96 (dd, J=8.9, 2.4 Hz, 1H), 6.44 (d, J=3.1 Hz, 1H), 5.12 (s, 2H), 4.44 (m, 1H), 1.88 (m, 1H), 1.77 (m, 1H), 1.50 (d, J=6.8 Hz, 3H), 1.23 (m, 2H), 0.89 (t, J=7.4 Hz, 3H).
Reaction SMILES: [Br:1][C:2]1[CH:13]=[C:12]([Cl:14])[C:11]([N:15]2[C:20](=[O:21])[C:19]3[CH2:22][CH2:23][CH2:24][C:18]=3[NH:17][C:16]2=[O:25])=[CH:10][C:3]=1[C:4]([O:6][CH:7]([CH3:9])[CH3:8])=[O:5].S(OC)(O[CH3:30])(=O)=O.[Na]>C(O)(C)C>[Br:1][C:2]1[CH:13]=[C:12]([Cl:14])[C:11]([N:15]2[C:20](=[O:21])[C:19]3[CH2:22][CH2:23][CH2:24][C:18]=3[N:17]([CH3:30])[C:16]2=[O:25])=[CH:10][C:3]=1[C:4]([O:6][CH:7]([CH3:9])[CH3:8])=[O:5]
Reactant: COS(=O)(=O)OC
Reactant: CC(C)OC(=O)c1cc(-n2c(=O)[nH]c3c(c2=O)CCC3)c(Cl)cc1Br
Agent: [Na]
Solvent: CC(C)O
Product: CC(C)OC(=O)c1cc(-n2c(=O)c3c(n(C)c2=O)CCC3)c(Cl)cc1Br

Procedure:
using isopropyl 2-bromo-4-chloro-5-(1,2,4,5,6,7-hexahydro-2,4-dioxo-3H-cyclopenta[d]pyrimidin-3-yl)-benzoate and dimethyl sulphate with sodium isopropylate in isopropanol there is obtained isopropyl 2-bromo-4-chloro-5-(1,2,4,5,6,7-hexahydro-1-methyl-2,4-dioxo-3H-cyclopenta[d]pyrimidin-3-yl)-benzoate, 1H--NMR (CDCl3, 400 MHz) 7.86 ppm (s, 1H), 7.74 ppm (s, 1H), 5.23 ppm (m, 1H), 3.42 ppm (s, 3H), 2.96 ppm (m, 2H), 2.82 ppm (m, 2H), 2.18 ppm (m, 2H), 1.35 ppm (d, 6H),
Reaction SMILES: C([O:3][C:4](=[O:46])[C:5]([CH3:45])([O:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:37][CH:36]=1)[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH2:14][CH2:15][CH:16]2[CH2:20][N:19]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=3)[C:18](=[O:32])[N:17]2[CH3:33])[CH:8]=1)C.[OH-].[Na+]>C(O)C>[CH3:45][C:5]([O:34][C:35]1[CH:36]=[CH:37][C:38]([C:41]([F:43])([F:42])[F:44])=[CH:39][CH:40]=1)([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH2:14][CH2:15][CH:16]2[CH2:20][N:19]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]([F:29])([F:30])[F:31])=[CH:24][CH:23]=3)[C:18](=[O:32])[N:17]2[CH3:33])[CH:8]=1)[C:4]([OH:46])=[O:3]
Reactant: CCOC(=O)C(C)(Cc1cccc(OCCC2CN(Cc3ccc(C(F)(F)F)cc3)C(=O)N2C)c1)Oc1ccc(C(F)(F)F)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CN1C(=O)N(Cc2ccc(C(F)(F)F)cc2)CC1CCOc1cccc(CC(C)(Oc2ccc(C(F)(F)F)cc2)C(=O)O)c1
Yield: 100 %

Procedure:
A solution of 2-methyl-3-(3-{2-[3-methyl-2-oxo-1-(4-trifluoromethyl-benzyl)-imidazolidin-4-yl]-ethoxy}-phenyl)-2-(4-trifluoromethyl-phenoxy)-propionic acid ethyl ester (0.113 g, 0.173 mmol) in ethanol (12 mL) was treated with aqueous 5 N NaOH (2 mL) and heated to reflux 1 h. The reaction mixture was cooled, the solvent removed in vacuo. The resultant residue was acidified with aqueous 1 N HCl (15 mL) and extracted with CH2Cl2. The organic layer was dried (Na2SO4) and the solvent removed in vacuo to afford 0.108 g (100%) 2-methyl-3-(3-{2-[3-methyl-2-oxo-1-(4-trifluoromethyl-benzyl)-imidazolidin-4-yl]-ethoxy}-phenyl)-2-(4-trifluoromethyl-phenoxy)-propionic acid. 1H NMR. HRMS (ES+) m/z exact mass calc'd for C31H31N2O5F6 (M+1) 625.2137. Found m/z 625.2134.
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][C:7](OB(O)O)=[CH:6][CH:5]=1)[CH2:2][CH3:3].FC(F)(F)S(O[C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][CH:29]=1)[C:26]([F:30])=[C:25]([O:31][C:32]([F:35])([F:34])[F:33])[C:24]([F:36])=[CH:23]2)(=O)=O.O.C1(C)C=CC=CC=1>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:30][C:26]1[C:27]2[C:22](=[CH:21][C:20]([C:7]3[CH:8]=[CH:9][C:4]([CH2:1][CH2:2][CH3:3])=[CH:5][CH:6]=3)=[CH:29][CH:28]=2)[CH:23]=[C:24]([F:36])[C:25]=1[O:31][C:32]([F:35])([F:33])[F:34]
Reactant: O=S(=O)(Oc1ccc2c(F)c(OC(F)(F)F)c(F)cc2c1)C(F)(F)F
Reactant: CCCc1ccc(OB(O)O)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: CCCc1ccc(-c2ccc3c(F)c(OC(F)(F)F)c(F)cc3c2)cc1
Temperature: 85 °C
Reaction time: 8 h
Yield: 61.9 %

Procedure:
7.3 g of 4-propylphenylboric acid and 11 g of 1,3-difluoro-2-trifluoromethoxynaphthalene-6-yl trifluoromethanesulfonate (obtained by triflating 1,3-difluoro-2-trifluoromethoxynaphthalene-6-ol with trifluoromethanesulfonic anhydride) were dissolved in 50 ml of DMF. To the solution was then added 0.4 g of tetrakis(triphenylphosphine)palladium (0). The reaction mixture was stirred at a temperature of 85° C. for 8 hours. To the reaction solution were then added water and toluene. The resulting aqueous phase was then extracted with toluene. The material thus extracted and the organic phase were together washed with water and then with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was then distilled off under reduced pressure to obtain an oily matter. The oily matter thus obtained was purified through silica gel column chromatography (hexane/ethyl acetate=9/1), and then recrystallized from ethanol to obtain 6.3 g of 1,3-difluoro-2-trifluoromethoxy-6-(4-propylphenyl)naphthalene in crystal form.
Reaction SMILES: CN(C)C=O.[CH2:6]([O:10][CH2:11][C:12]([N:14]1[CH2:22][C:21]2[CH:20]=[N:19][C:18]([NH:23][CH:24]3[CH2:32][C:31]4[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH2:25]3)=[N:17][C:16]=2[CH2:15]1)=[O:13])[CH2:7][C:8]#[CH:9].[Na].O=C1O[C@H]([C@H](CO)O)C(O)=C1O.[N:46]([Si](C)(C)C)=[N+:47]=[N-:48]>O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2].O>[CH2:25]1[C:26]2[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:32][CH:24]1[NH:23][C:18]1[N:19]=[CH:20][C:21]2[CH2:22][N:14]([C:12](=[O:13])[CH2:11][O:10][CH2:6][CH2:7][C:8]3[N:46]=[N:47][NH:48][CH:9]=3)[CH2:15][C:16]=2[N:17]=1
Reactant: C#CCCOCC(=O)N1Cc2cnc(NC3Cc4ccccc4C3)nc2C1
Reactant: C[Si](C)(C)N=[N+]=[N-]
Agent: [Cu+2]
Agent: O=C1O[C@H]([C@@H](O)CO)C(O)=C1O
Agent: O=S(=O)([O-])[O-]
Solvent: O
Solvent: CN(C)C=O
Product: O=C(COCCc1c[nH]nn1)N1Cc2cnc(NC3Cc4ccccc4C3)nc2C1
Temperature: 23 °C
Yield: 30.2 %

Procedure:
Add dimethylformamide (27 mL) and water (27 mL) to a flask containing 2-(but-3-yn-1-yloxy)-1-[2-(2,3-dihydro-1H-inden-2-ylamino)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidin-6-yl]ethanone (2.90 g, 8.00 mmol). Add copper (II) sulfate pentahydrate (400 mg, 1.60 mmol) and L-ascorbic acid sodium salt (3.17 g, 16.0 mmol). Evacuate flask and backfill with nitrogen (×2), then add azidotrimethylsilane (7.37 g, 8.53 mL, 64.0 mmol) and heat the reaction to 90° C. for 70 minutes. Cool the reaction mixture to 23° C. and remove all solvent in vacuo. Suspend the residue in methanol/dichloromethane and then add silica gel and remove solvent in vacuo. Load this material onto a loading column and purify via silica gel column chromatography (gradient elution: 0-9% methanol in ethyl acetate) to give the title compound (980 mg, 30%). MS (m/z): 406(M+1).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:19][CH2:18][C:8]3([C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[NH:10][C:9]3=[O:17])[C:6]=2[CH:7]=1.N1C2C(=CC=CC=2)C2(C3=CC4OCOC=4C=C3OC2)C1=O.[Cl:41][C:42]1[S:43][C:44]([CH2:47]Cl)=[CH:45][CH:46]=1.FC1C=CC(CBr)=CC=1>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:19][CH2:18][C:8]3([C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[N:10]([CH2:47][C:44]4[S:43][C:42]([Cl:41])=[CH:46][CH:45]=4)[C:9]3=[O:17])[C:6]=2[CH:7]=1
Reactant: O=C1Nc2ccccc2C12COc1ccc(Br)cc12
Reactant: ClCc1ccc(Cl)s1
Agent: Fc1ccc(CBr)cc1
Agent: O=C1Nc2ccccc2C12COc1cc3c(cc12)OCO3
Product: O=C1N(Cc2ccc(Cl)s2)c2ccccc2C12COc1ccc(Br)cc12

Procedure:
Following the procedure described in EXAMPLE 10, and making non-critical variations using 5-bromospiro[1-benzofuran-3,3′-indol]-2′(1′H)-one to replace spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)one, and 2-chloro-5-(chloromethyl)thiophene to replace 4-fluorobenzyl bromide, the title compound was obtained (95%) as a white solid: mp 140-142° C.; 1H NMR (300 MHz, CDCl3) δ 7.33-7.26 (m, 2H), 7.16-7.02 (m, 2H), 6.94 (d, 1H), 6.97-6.75 (m, 4H), 5.07-4.91 (m, 3H), 4.68 (d, 1H); MS (ES+) m/z 446.7 (M+1), 448.7 (M+1).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][C:19]([OH:21])=O)=[O:12].[CH:22]1[CH:23]=[CH:24][C:25]2[N:30](O)N=[N:28][C:26]=2[CH:27]=1.C(Cl)CCl.C1(N)C=CC=CC=1N>CN(C=O)C>[NH2:28][C:26]1[CH:27]=[CH:22][CH:23]=[CH:24][C:25]=1[NH:30][C:19](=[O:21])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][C:11]([C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:1]=1)=[O:12]
Reactant: O=C(O)CCCCCCC(=O)c1ccc2ccccc2c1
Reactant: On1nnc2ccccc21
Agent: Nc1ccccc1N
Solvent: CN(C)C=O
Solvent: ClCCCl
Product: Nc1ccccc1NC(=O)CCCCCCC(=O)c1ccc2ccccc2c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 42.3 %

Procedure:
To a solution of 7-(2-naphthoyl)heptanoic acid 50 g (1.00 g, 3.52 mmol) in DMF (15 mL) were added HOBT (950 mg, 7.04 mmol) and EDC (1.00 g, 5.28 mmol). The mixture was stirred at room temperature for 1 hour, after which 1,2-phenylenediamine (760 mg, 7.04 mmol) was added and the solution was stirred at room temperature for 16 hours. The DMF was evaporated under high vacuum, deionized water was added, and the mixture was extracted with ethyl acetate (2×30 mL). The combined organic layers were washed with saturated sodium bicarbonate (20 mL), washed with brine (20 mL), and dried (MgSO4). The solvents were removed in vacuo and the title compound 63 (558 mg, 42%) was isolated by recrystallization from acetone and dichloromethane. 1H NMR (300 MHz, 20% CD3OD in CDCl3): δ 8.47 (s, 1H), 8.10-7.85 (m, 4H), 7.63-7.50 (m, 2H), 7.14-6.70 (m, 4H), 3.11 (t, J=7.2 Hz, 2H), 2.39 (t, J=7.5 Hz, 2H), 1.77 (m, 4H), 1.46 (m, 4H). 13C NMR (75 MHz, 20% CD3OD in CDCl3): δ 23.99, 25.40, 28.66, 28.74, 36.08, 38.23, 117.69, 119.09, 123.45, 124.01, 125.34, 126.53 126.86, 127.45, 128.19, 128.23, 129.28, 129.56, 132.23, 133.85, 135.32, 140.58, 172.81, 201.11.
Reaction SMILES: [Mg].Br[C:3]1[S:4][CH:5]=[CH:6][CH:7]=1.II.[CH3:10][O:11][Si:12](OC)(OC)[O:13][CH3:14]>O1CCCC1>[S:4]1[CH:5]=[CH:6][CH:7]=[C:3]1[Si:12]([C:3]1[S:4][CH:5]=[CH:6][CH:7]=1)([O:13][CH3:14])[O:11][CH3:10]
Reactant: Brc1cccs1
Reactant: CO[Si](OC)(OC)OC
Agent: II
Agent: [Mg]
Solvent: C1CCOC1
Product: CO[Si](OC)(c1cccs1)c1cccs1
Temperature: 25 °C

Procedure:
With protection of nitrogen gas, 3.50 g magnesium powder, 1.30 g bromothiophene and 20 ml tetrahydrofuran were added to a 250 ml three-necked flask equipped with a stirrer, a reflux condenser tube and a thermometer. After the mixed system was refluxed for 0.5 hour, 0.26 g iodine was added until the reaction got severe. After the reaction was stable, a mixed solution of 20.74 g bromothiophene, 60 ml tetrahydrofuran and 9.99 g tetramethoxysilane was added dropwise from an upper part of tube within about 2 hours. After being heated with stirring and refluxing for 5 hours, the mixed system was slowly cooled to room temperature, filtered by a filter tube with protection of nitrogen gas, and the solid substance was washed with tetrahydrofuran several times. The resulting filtrate was subjected to distillation at normal pressure and solvent recovery, and then subjected to distillation at reduced pressure. The product at 130° C. to 131° C. and 25 mmHg column pressure were collected. Te infrared spectrum and 13C nuclear magnetic resonance spectrum of the synthesized compound are substantially identical with that in FIG. 1 and FIG. 2. The infrared spectrum preliminarily approves the occurrence of the synthetic reaction, and the 13C nuclear magnetic resonance spectrum effectively demonstrates the formation of the product.