Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([N:7]2[CH2:12][CH2:11][CH:10]([N:13]3[C:21](=[O:22])[C:20]4[C:19]([C:23](O)=[O:24])=[CH:18][CH:17]=[CH:16][C:15]=4[C@@H:14]3[CH3:26])[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH4+].OC1C2N=N[NH:34]C=2C=CC=1.C(N(CC)CC)C>O1CCCC1>[CH:1]1([N:7]2[CH2:8][CH2:9][CH:10]([N:13]3[C:21](=[O:22])[C:20]4[C:19]([C:23]([NH2:34])=[O:24])=[CH:18][CH:17]=[CH:16][C:15]=4[C@@H:14]3[CH3:26])[CH2:11][CH2:12]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: C[C@H]1c2cccc(C(=O)O)c2C(=O)N1C1CCN(C2CCCCC2)CC1
Reactant: Oc1cccc2[nH]nnc12
Agent: [NH4+]
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: C[C@H]1c2cccc(C(N)=O)c2C(=O)N1C1CCN(C2CCCCC2)CC1
Reaction time: 16 h
Yield: 40.2 %

Procedure:
(1S)-2-(1-Cyclohexylpiperidin-4-yl)-1-methyl-3-oxo-2,3-dihydro-1H-isoindole-4-carboxylic acid (0.15 gr, 0.42 mmol), hydroxybenzotriazole ammonium salt (0.13 gr, 0.84 mmol) and 1-ethyl-3-(3′-dimethylamino) carbodiimide hydrochloric acid salt (0.16 gr, 0.84 mmol) were dissolved in a mixture of tetrahydrofuran (6 mL) and triethylamine (0.23 mL, 1.68 mmol) and stirred under nitrogen atmosphere for 16 hours. Volatiles were evaporated and the crude was dissolved in dichloromethane and washed with 15% ammonium hydroxide. The organic phase was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude was purified by flash chromatography (dichloromethane/methanol/7N ammonia in methanol 100:3:1) to afford the title compound (0.060 g, 40%) as a white solid.
Reaction SMILES: CO[C:3]1[CH:4]=[C:5](C=[CH:12][CH:13]=1)[CH:6]=[CH:7][N+:8]([O-:10])=[O:9].[CH2:14]([O:16][C:17](=O)[CH:18]=[C:19](N1CCCC1)[CH3:20])C.C([OH:29])C>>[N+:8]([CH2:7][CH2:6][CH2:5][C:4](=[O:29])[CH2:3][C:13]1[CH:20]=[CH:19][CH:18]=[C:17]([O:16][CH3:14])[CH:12]=1)([O-:10])=[O:9]
Reactant: CCO
Reactant: COc1cccc(C=C[N+](=O)[O-])c1
Reactant: CCOC(=O)C=C(C)N1CCCC1
Product: COc1cccc(CC(=O)CCC[N+](=O)[O-])c1
Temperature: 25 °C

Procedure:
A mixture of 3-methoxynitrostyrene (6.96 g, 39 mmol) and ethyl-3-pyrrolidino-2-butenoate (7.10 g, 39 mmol) was refluxed in ethanol (100 mL) for 4.0 h. The solvent was then removed and the residue refluxed in 10% HCl (50 mL) for 2.0 h. After cooling to ambient temperature the reaction mixture was extracted with ethyl ether (3×25 mL). The extract was dried (MgSO4) and the solvent removed to yield 9.40 g of crude material as an oil. This was distilled twice using a Kugelrohr oven (225° C. C/0.4mm Hg) yielding 4.83 g of product. This was further purified by flash chromatography (n-hexane/ethyl acetate 1/1), yielding 3.25 g (35%) of a colorless oil.: MS (EI) m/e 237.15 (M+, 22), 190.05 (100), 175.05 (32), 149.05 (35), 148.05 (37), 134.05 (36), 115 (10, 20), 91.00 (28), 77.00 (21).
Reaction SMILES: [Cl:1][C:2]1[C:3]2[C:8]([N:9]=[C:10]3[C:15]=1[CH2:14][CH2:13][CH2:12][CH2:11]3)=[CH:7][CH:6]=[C:5]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH:4]=2.[CH2:28]([NH2:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.CCOCC.[OH-].[Na+]>C1(O)C=CC=CC=1>[ClH:1].[CH2:28]([NH:35][C:2]1[C:3]2[C:8]([N:9]=[C:10]3[C:15]=1[CH2:14][CH2:13][CH2:12][CH2:11]3)=[CH:7][CH:6]=[C:5]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[CH:4]=2)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: CCCCCCCCCCCCc1ccc2nc3c(c(Cl)c2c1)CCCC3
Reactant: NCc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Solvent: Oc1ccccc1
Product: CCCCCCCCCCCCc1ccc2nc3c(c(NCc4ccccc4)c2c1)CCCC3
Product: Cl

Procedure:
9-Chloro-7-dodecyl-1,2,3,4-tetrahydroacridine (2.85 g) was heated at 150° in 60 mL of phenol containing 2.46 g of benzylamine. After 3 hours the reaction mixture was distributed between Et2O and 10% NaOH aqueous solution. The organic phase was washed once more with 10% NaOH, once with H2O, and then treated with 5% HCl. The insoluble hydrochloride was filtered off and recrystallized from isopropanol to give 2.15 g of analytically pure product, mp 194°-195°.
Reaction SMILES: C([O:3][C:4]([CH:6]1[CH2:27][CH2:26][C:9]2[N:10]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=3)[C:11]3[N:12]=[CH:13][CH:14]=[CH:15][C:16]=3[C:17](=[O:18])[C:8]=2[CH2:7]1)=[O:5])C.[OH-].[K+].C(O)C.Cl>O>[C:4]([CH:6]1[CH2:27][CH2:26][C:9]2[N:10]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=3)[C:11]3[N:12]=[CH:13][CH:14]=[CH:15][C:16]=3[C:17](=[O:18])[C:8]=2[CH2:7]1)([OH:5])=[O:3]
Reactant: CCOC(=O)C1CCc2c(c(=O)c3cccnc3n2-c2cccc(Cl)c2)C1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=C(O)C1CCc2c(c(=O)c3cccnc3n2-c2cccc(Cl)c2)C1
Reaction time: 21 h

Procedure:
Saponify 7-ethoxycarbonyl-10-(3-chlorophenyl)-6,7,8,9-tetrahydrobenzo[b][1,8]naphthyridin-5(10H)-one (7.1 g) with potassium hydroxide (1.10 g) in a solvent of ethanol and water (142 ml, 9:1 by volume). After 21 hours at 25° C., add water (200 ml), cool the resulting solution in ice, and acidify (pH 2) the solution with concentrated hydrochloric acid. Collect the resulting precipitate on a filter, and crystallize it from ethanol to provide 7-carboxy-10-(3-chlorophenyl)-6,7,8,9-tetrahydrobenzo[b][1,8]naphthyridin-5(10H)-one, m.p. 279°-280.5° C.
Reaction SMILES: [CH3:1][C:2]1[NH:3][CH:4]=[CH:5][C:6]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8].[CH3:12]I.[H-].[Na+]>CN(C)C=O.C(OCC)(=O)C>[CH3:12][N:3]1[CH:4]=[CH:5][C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[C:2]1[CH3:1]
Reactant: CCOC(=O)c1cc[nH]c1C
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCOC(=O)c1ccn(C)c1C
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of 10 g of ethyl 2-methyl-1H-pyrrole-3-carboxylate (65.3 mmol) and 8.95 mL (130.6 mmol) of methyl iodide in 70 mL of dimethylformamide placed at 0° C. there are added, in three portions, 2.61 g (65.3 mmol) of sodium hydride (NaH) 60% . The batch is then stirred at 0° C. for 1 hour. Then, the reaction mixture is hydrolysed by the addition of 420 mL of ice-cold water. The reaction mixture is then diluted with ethyl acetate, successively washed with 0.1M aqueous hydrochloric acid (HCl) solution, saturated aqueous LiCl solution and then brine. The organic phase is then dried over MgSO4, filtered, concentrated to dryness and purified by chromatography over silica gel (petroleum ether/AcOEt gradient).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:20])[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=2)[CH:5]=[CH:6][CH:7]=1.Cl.[Cl:22][C:23]1[N:28]=[C:27](Cl)[C:26]([Cl:30])=[CH:25][N:24]=1.C(=O)([O-])[O-].[K+].[K+].C(N(CC)CC)C>CN(C=O)C>[Cl:22][C:23]1[N:28]=[C:27]([NH:1][C:2]2[CH:3]=[C:4]([NH:8][C:9](=[O:20])[CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=3)[CH:5]=[CH:6][CH:7]=2)[C:26]([Cl:30])=[CH:25][N:24]=1
Reactant: Clc1ncc(Cl)c(Cl)n1
Reactant: Nc1cccc(NC(=O)Cc2cccc([N+](=O)[O-])c2)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: O=C(Cc1cccc([N+](=O)[O-])c1)Nc1cccc(Nc2nc(Cl)ncc2Cl)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 54.7 %

Procedure:
To a solution of N-(3-aminophenyl)-2-(3-nitrophenyl)acetamide-hydrogen chloride (0.11 g, 0.35 mmol) and 2,4,5-trichloropyrimidine (0.065 g, 0.35 mmol) in DMF (1 mL) was added potassium carbonate (0.20 g, 1.4 mmol). The resulting mixture was stirred overnight at room temperature. Additional triethylamine (0.099 mL, 0.71 mmol) was then added an stirred overnight again. The reaction was quenched with sat'd NH4Cl and water. EtOAc was added and the layers separated. The aqueous was extracted with EtOAc. The combined organics were washed with water and brine then dried (MgSO4), filtered, and concentrated. The resulted mixture was purified by column chromatography to give the desired product (0.080 g, 53%). LCMS for C18H13Cl2N5O3 (M+H)+: m/z=418.0, 419.9. 1H NMR (400 MHz, DMSO-d6): δ 10.33 (s, 1H), 9.53 (s, 1H), 8.35 (s, 1H), 8.23 (t, J=2.0 Hz, 1H), 8.12 (ddd, J=8.2, 2.4, 1.0 Hz, 1H), 7.82 (t, J=2.0 Hz, 1H), 7.78 (dt, J=7.8, 1.4 Hz, 1H), 7.62 (t, J=7.9 Hz, 1H), 7.36 (dt, J=8.0, 1.7 Hz, 1H), 7.30 (t, J=7.8 Hz, 1H), 7.25 (dt, J=8.0, 1.7 Hz, 1H).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=O)[C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1)#[N:2].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:28])=CC=1>C1(C)C=CC=CC=1>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[S:28])[C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1)#[N:2]
Reactant: Cc1ccc(C(=O)Nc2ccc(C#N)cc2)cc1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: Cc1ccccc1
Product: Cc1ccc(C(=S)Nc2ccc(C#N)cc2)cc1
Temperature: 25 °C
Yield: 135.4 %

Procedure:
The compound (1.26 g) obtained in Example 43-1 was dissolved in toluene (20 ml) and added with a Lawesson's reagent (1.29 g) and the whole was refluxed under heating for 2 hours. The reaction solution was cooled to room temperature and the precipitated solid was filtrated out. The resultant solid was subjected to recrystallization (methanol), thereby obtaining the subject compound (1.09 g) as a yellow solid.
Reaction SMILES: C1COCC1.CO.[F:8][C:9]([F:40])([F:39])[O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:18]=[C:19]([O:27][CH2:28][C:29]3[CH:38]=[CH:37][C:32]([C:33]([O:35]C)=[O:34])=[CH:31][CH:30]=3)[C:20]3[C:25]([CH:26]=2)=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:13][CH:12]=1>O>[F:8][C:9]([F:39])([F:40])[O:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]2[CH:18]=[C:19]([O:27][CH2:28][C:29]3[CH:38]=[CH:37][C:32]([C:33]([OH:35])=[O:34])=[CH:31][CH:30]=3)[C:20]3[C:25]([CH:26]=2)=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:15][CH:16]=1
Reactant: COC(=O)c1ccc(COc2cc(-c3ccc(OC(F)(F)F)cc3)cc3ccccc23)cc1
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: O=C(O)c1ccc(COc2cc(-c3ccc(OC(F)(F)F)cc3)cc3ccccc23)cc1

Procedure:
To a THF/MeOH solution (ca. 1/1, 2 mL) of the intermediate from Step C (40 mg, 0.09 mmol) was added LiOH monohydrate (20 mg, 0.49 mmol) in 1 mL water. The solution was stirred at room temperature until no ester remained by HPLC analysis. The solution was concentrated and partitioned between ethyl acetate and aqueous 1N HCl. The organic phase was washed with brine, dried over MgSO4 and filtered. The solution was then concentrated to give the title compound which was used without further purification. LCMS1 4.27 min. (M+H)=439
Reaction SMILES: [C:1]1([N:7]2[C:15]3[CH:14]=[CH:13][N:12]=[CH:11][C:10]=3[N:9]=[C:8]2[CH:16]([NH2:18])[CH3:17])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:20]1[N:28]=[CH:27][N:26]=[C:25]2[C:21]=1[N:22]=[CH:23][N:24]2C1CCCCO1.CCN(C(C)C)C(C)C>C(O)CCC>[C:1]1([N:7]2[C:15]3[CH:14]=[CH:13][N:12]=[CH:11][C:10]=3[N:9]=[C:8]2[CH:16]([NH:18][C:20]2[N:28]=[CH:27][N:26]=[C:25]3[C:21]=2[N:22]=[CH:23][NH:24]3)[CH3:17])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(N)c1nc2cnccc2n1-c1ccccc1
Reactant: Clc1ncnc2c1ncn2C1CCCCO1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCCCO
Product: CC(Nc1ncnc2[nH]cnc12)c1nc2cnccc2n1-c1ccccc1
Temperature: 90 °C
Reaction time: 16 h
Yield: 6.2 %

Procedure:
A mixture of 1-(1-phenyl-1H-imidazo[4,5-c]pyridin-2-yl)ethylamine (184 mg, 0.77 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (256 mg, 1.08 mmol) and DIPEA (0.25 mL, 1.39 mmol) in 1-butanol (2 mL) was stirred at 90° C. in a sealed microwave tube for 16 h. The resulting mixture was loaded onto an Isolute® SCX-2 cartridge and washed with MeOH. The product was eluted with 2M NH3/MeOH then concentrated in vacuo. The resulting residue was purified by chromatography (SiO2 0-10% (2M ammonia in methanol) in DCM), then by preparative HPLC (Phenomenex Gemini 5 μm C18 on a 60 min gradient 20-98% 0.1% HCO2H in acetonitrile/water) to give 236 as a white solid (0.017 g, 6%). LCMS (method K): Rt 2.04 min, [M+H]+ 357. 1H NMR (DMSO-d6): δ 12.89 (1H, s), 8.94 (1H, s), 8.30 (1H, d, J=5.54 Hz), 8.09-8.00 (2H, m), 7.65-7.50 (5H, m), 7.12 (1H, d, J=5.57 Hz), 5.53 (1H, s), 1.58 (4H, d, J=7.36 Hz)
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([I:16])=[CH:12][C:11]=2[F:17])[C:5]([NH2:18])=[CH:4][CH:3]=1.[Cl:19][C:20]1[S:24][C:23]([S:25](Cl)(=[O:27])=[O:26])=[CH:22][CH:21]=1>>[Cl:19][C:20]1[S:24][C:23]([S:25]([NH:18][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[C:7]([F:8])[C:6]=2[NH:9][C:10]2[CH:15]=[CH:14][C:13]([I:16])=[CH:12][C:11]=2[F:17])(=[O:27])=[O:26])=[CH:22][CH:21]=1
Reactant: Nc1ccc(F)c(F)c1Nc1ccc(I)cc1F
Reactant: O=S(=O)(Cl)c1ccc(Cl)s1
Product: O=S(=O)(Nc1ccc(F)c(F)c1Nc1ccc(I)cc1F)c1ccc(Cl)s1

Procedure:
According to the general procedure B, 5,6-difluoro-N1-(2-fluoro-4-iodophenyl)benzene1,2-diamine was reacted with 5-chlorothiophene-2-sulfonyl chloride to obtain the title compound. 1H NMR (300 MHz, CDCl3): δ 7.38 (dd, J=1.5 & 10.2 Hz, 1H), 7.32 (ddd, J=2.1, 5.1 & 9.3 Hz, 1H), 7.25 (d, J=3.9 Hz, 1H), 7.10 (dd, J=9.0 & 18.6 Hz, 3H), 6.84 (d, 4.2 Hz, 1H), 5.86 (dt, J=1.8, 8.7 & 17.4 Hz, 1H), 5.49 (br s, D2O exchangeable, 1H).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5]/[C:4](=[C:12]2/[C:13]([CH2:18][CH3:19])=[N:14][NH:15][C:16]/2=[O:17])/[CH:3]=1.[C:20]([NH:23][C:24]1[CH:29]=[CH:28][C:27]([SH:30])=[CH:26][CH:25]=1)(=[O:22])[CH3:21]>>[CH2:18]([C:13]1=[N:14][NH:15][C:16](=[O:17])/[C:12]/1=[C:4]1\[NH:5][C:6]2[C:11]([C:2]([S:30][C:27]3[CH:26]=[CH:25][C:24]([NH:23][C:20](=[O:22])[CH3:21])=[CH:29][CH:28]=3)=[CH:3]\1)=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH3:19]
Reactant: CCC1=NNC(=O)/C1=C1/C=C(Cl)c2ccccc2N1
Reactant: CC(=O)Nc1ccc(S)cc1
Product: CCC1=NNC(=O)/C1=C1/C=C(Sc2ccc(NC(C)=O)cc2)c2ccccc2N1

Procedure:
The title compound was prepared from (Z)-4-(4-chloroquinolin-2(1H)-ylidene)-3-ethyl-1H-pyrazol-5(4H)-one and 4-acetamidothiophenol using the procedure described in Example 6. 1H NMR (400 MHz, DMSO-D6) δ ppm 0.82 (t, J=7.45 Hz, 3H) 2.06-2.16 (s, 3H) 2.17-2.25 (m, 2H) 6.63 (s, 1H) 7.57 (t, J=7.96 Hz, 1H) 7.67 (d, J=8.59 Hz, 2H) 7.78-7.89 (m, 4H) 8.08 (d, J=8.34 Hz, 1H) 10.32 (s, 1H); ESI-MS: m/z calc'd for C22H20N4O2S 404.13. found 405.2 (M+H)+.
Reaction SMILES: C(OCC1C=CC=CC=1)(=O)C.[CH3:12][C:13]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([N:24]=[C:25]=O)([CH3:23])[CH3:22])[CH:16]=1)=[CH2:14].[C:27]1([N:33]=C=O)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.N=C=N.C1(N=C=NC2C=CC=CC=2)C=CC=CC=1>>[C:27]1([N:33]=[C:25]=[N:24][C:21]([C:17]2[CH:18]=[CH:19][CH:20]=[C:15]([C:13]([CH3:12])=[CH2:14])[CH:16]=2)([CH3:23])[CH3:22])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: C=C(C)c1cccc(C(C)(C)N=C=O)c1
Reactant: O=C=Nc1ccccc1
Agent: C(=Nc1ccccc1)=Nc1ccccc1
Agent: N=C=N
Solvent: CC(=O)OCc1ccccc1
Product: C=C(C)c1cccc(C(C)(C)N=C=Nc2ccccc2)c1
Temperature: 150 °C
Reaction time: 6 h

Procedure:
We combined 0.0982 g TPAO, 19.30 g benzyl acetate (internal standard), 60.40 g of m-TMI, and 35.77 g phenyl isocyanate. Heating at 150° C. was carried out for 6 hours; at 2 hours IR showed nearly complete conversion of isocyanates to carbodiimides. GC-FID showed that product was predominantly the title carbodiimide (89.3%), unreacted TMI (4.2%), 1,3-bis[2-(3-isopropenylphenyl-2-propyl]carbodiimide (4.2%) and 1,3-diphenylcarbodiimide (2.9%) versus internal standard. Material from this Example was distilled to obtain in 71% recovery on products of a purified sample (92% pure) of the title product and in 6% recovery on products of a crude (66% purity) sample of the same product.
Reaction SMILES: [C:1]12([C:11]3[CH:12]=[C:13](B4OCC(C)(C)CO4)[CH:14]=[CH:15][C:16]=3[O:17][CH3:18])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.FC(F)(F)S(O[C:33]1[CH:42]=[CH:41][C:40]2[C:35](=[CH:36][CH:37]=[C:38]([Br:43])[CH:39]=2)[CH:34]=1)(=O)=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1COCC1>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>[C:1]12([C:11]3[CH:12]=[C:13]([C:33]4[CH:34]=[C:35]5[C:40](=[CH:41][CH:42]=4)[CH:39]=[C:38]([Br:43])[CH:37]=[CH:36]5)[CH:14]=[CH:15][C:16]=3[O:17][CH3:18])[CH2:2][CH:3]3[CH2:4][CH:5]([CH2:6][CH:7]([CH2:9]3)[CH2:8]1)[CH2:10]2
Reactant: O=S(=O)(Oc1ccc2cc(Br)ccc2c1)C(F)(F)F
Reactant: COc1ccc(B2OCC(C)(C)CO2)cc1C12CC3CC(CC(C3)C1)C2
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: COc1ccc(-c2ccc3cc(Br)ccc3c2)cc1C12CC3CC(CC(C3)C1)C2
Yield: 23.5 %

Procedure:
[3-(1-adamantyl)-4-methoxyphenyl]-5,5-dimethyl-1,3,2-dioxaborinane (100 mg, 0.28 mmol), 6-bromo-2-naphthalenyl trifluoromethanesulphonate (67 mg, 0.19 mmol), K3PO4 (160 mg, 0.75 mmol), THF (2 ml) and H2O (0.4 ml) were introduced in a Schlenk tube. The reaction mixture was deoxygenated (3 froze/thaw cycles). Next, Pd(PPh3)4 (11 mg, 0.009 mmol) was added and the mixture was again deoxygenated (2 froze/thaw cycles). After heating at reflux for 17 h, the mixture was diluted in toluene (5 ml) while it was still hot. The solution was filtered through celite and it was washed with hot toluene (2×5 ml). The joined organic phases were washed with hot H2O (2×5 ml). The organic phase was evaporated and a crude (59 mg) was obtained, which was recrystallized with the minimum volume of toluene at reflux (0.55 ml), giving the title compound (20 mg, 24%) as a pale yellow powder. The spectroscopic data coincide with those of the Example 4.
Reaction SMILES: [CH2:1]([Sn:5]([CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1)([CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)[CH:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1)[CH2:2][CH2:3][CH3:4].[CH2:24]([Sn:28]([Cl:31])(Cl)[Cl:29])[CH2:25][CH2:26][CH3:27]>C1(C)C(C)=CC=CC=1>[CH:18]1([Sn:5]([Cl:29])([CH:6]2[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]2)[CH:12]2[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]2)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1.[CH2:1]([Sn:28]([Cl:31])([Cl:29])[CH2:24][CH2:25][CH2:26][CH3:27])[CH2:2][CH2:3][CH3:4]
Reactant: CCCC[Sn](C1CCCCC1)(C1CCCCC1)C1CCCCC1
Reactant: CCCC[Sn](Cl)(Cl)Cl
Solvent: Cc1ccccc1C
Product: CCCC[Sn](Cl)(Cl)CCCC
Product: Cl[Sn](C1CCCCC1)(C1CCCCC1)C1CCCCC1

Procedure:
A solution of equimolar amounts of butyl tricyclohexyltin and butyltin trichloride in commercial xylene was refluxed for 221/2 hours. Analysis of the reaction mixture obtained showed that the reaction had gone to about 89% completion to form predominantly tricyclohexyltin chloride and dibutyltin dichloride.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][C:12]([NH:14][CH2:15][CH2:16][NH:17][C:18]2[CH:23]=[C:22]([CH3:24])[N:21]=[C:20]([O:25][C:26]3[C:31]([CH3:32])=[CH:30][C:29]([CH3:33])=[CH:28][C:27]=3[CH3:34])[C:19]=2[CH3:35])=O)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]>C1COCC1.Cl.CO.C(Cl)(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][NH:14][CH2:15][CH2:16][NH:17][C:18]2[CH:23]=[C:22]([CH3:24])[N:21]=[C:20]([O:25][C:26]3[C:31]([CH3:32])=[CH:30][C:29]([CH3:33])=[CH:28][C:27]=3[CH3:34])[C:19]=2[CH3:35])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: COc1ccc(CC(=O)NCCNc2cc(C)nc(Oc3c(C)cc(C)cc3C)c2C)cc1OC
Agent: Cl
Solvent: C1CCOC1
Solvent: ClC(Cl)Cl
Solvent: CO
Product: COc1ccc(CCNCCNc2cc(C)nc(Oc3c(C)cc(C)cc3C)c2C)cc1OC

Procedure:
Add BH3 in THF (1 M solution, 0.3 mmol, 0.3 mL) to a solution of the crude 2-(3,4-dimethoxyphenyl)-N-(2-{[3,6-dimethyl-2-(2,4,6-trimethylphenoxy)(4-pyridyl)]amino}ethyl) acetamide in THF (2.0 mL) at ambient temperature. Heat the reaction mixture under reflux for 15 h, dilute with a solution of 10% aq HCl/MeOH (1:1, 2 mL) and heat again under reflux (1 h). Dilute the reaction mixture with CHCl3 (10 mL), wash with saturated aq NaHCO3 (1×5 mL), dry and concentrate in vacuo. Chromatograph the crude residue on SiO2-gel using a gradient of 100% EtOAc to 10% Et2NH/EtOAc to obtain the title compound as a colorless oil. Immediately dissolve the product in Et2O (1 mL), treat with excess 4 M HCl/dioxane and concentrate in vacuo to obtain the hydrochloride salt of the title compound as a colorless solid. 1H NMR (d4-MeOH, Unity 400): d 6.99-6.77 (6H, m), 3.81 (3H, s), 3.78 (3H, s), 3.62 (2H, m), 2.98 (2H, t), 2.39 (3H, s), 2.29 (3H, s), 2.16 (3H, s), 2.07 (6H, s). M+1: 464.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:23](=[O:35])[NH:24][CH2:25][C:26]2[C:31](=[O:32])[CH:30]=[C:29]([CH3:33])[NH:28][C:27]=2[CH3:34])[C:5]([CH3:22])=[C:6]([CH:21]=1)[O:7][CH:8]1[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]1.Cl.O1CCOCC1>C(Cl)Cl>[Cl:1][C:2]1[CH:21]=[C:6]([O:7][CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[C:5]([CH3:22])=[C:4]([CH:3]=1)[C:23]([NH:24][CH2:25][C:26]1[C:31](=[O:32])[CH:30]=[C:29]([CH3:33])[NH:28][C:27]=1[CH3:34])=[O:35]
Reactant: Cc1cc(=O)c(CNC(=O)c2cc(Cl)cc(OC3CCN(C(=O)OC(C)(C)C)CC3)c2C)c(C)[nH]1
Agent: Cl
Solvent: C1COCCO1
Solvent: ClCCl
Product: Cc1cc(=O)c(CNC(=O)c2cc(Cl)cc(OC3CCNCC3)c2C)c(C)[nH]1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of tert-butyl 4-(5-chloro-3-(((2,6-dimethyl-4-oxo-1,4-dihydropyridin-3-yl)methyl)carbamoyl)-2-methylphenoxy)piperidine-1-carboxylate (80 mg, 158 mmol) in DCM (2 mL) was treated with 4 M HCl/dioxane (2 mL). The reaction stirred for 2 h at RT, then was concentrated in vacuo and triturated with EtOAc to give 5-chloro-N-((2,6-dimethyl-4-oxo-1,4-dihydropyridin-3-yl)methyl)-2-methyl-3-(piperidin-4-yloxy)benzamide as the hydrogen chloride salt (0.050 g, 113 mmol, 72% yield). 1H NMR (400 MHz, DMSO-d6) δ 1.74-1.90 (m, 2 H) 2.07 (s, 3 H) 2.11 (d, J=4.80 Hz, 2 H) 2.57 (s, 3 H) 2.72 (s, 3 H) 3.09 (br. s., 2 H) 3.17 (s, 2 H) 4.38 (d, J=4.80 Hz, 2 H) 4.60-4.87 (m, 1 H) 6.89 (s, 1 H) 7.12 (s, 1 H) 7.23 (d, J=1.77 Hz, 1 H) 8.69 (t, J=5.05 Hz, 1 H) 8.98 (br. s., 2 H) 14.42 (br. s., 1 H). MS(ES) [M+H]+ 404.3.
Reaction SMILES: CCN(C(C)C)C(C)C.[CH3:10][O:11][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:21]=1[O:20][C:19](=[O:22])[C:18]([C:23]([OH:25])=O)=[CH:17]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[O:50]=[C:51]1[C:60]2[C:55](=[CH:56][CH:57]=[C:58]([C:61]3[CH:62]=[C:63]([NH2:67])[CH:64]=[CH:65][CH:66]=3)[CH:59]=2)[O:54][CH:53]=[CH:52]1>CN(C=O)C>[O:50]=[C:51]1[C:60]2[C:55](=[CH:56][CH:57]=[C:58]([C:61]3[CH:62]=[C:63]([NH:67][C:23]([C:18]4[C:19](=[O:22])[O:20][C:21]5[C:16]([CH:17]=4)=[CH:15][CH:14]=[CH:13][C:12]=5[O:11][CH3:10])=[O:25])[CH:64]=[CH:65][CH:66]=3)[CH:59]=2)[O:54][CH:53]=[CH:52]1
Reactant: COc1cccc2cc(C(=O)O)c(=O)oc12
Reactant: Nc1cccc(-c2ccc3occc(=O)c3c2)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COc1cccc2cc(C(=O)Nc3cccc(-c4ccc5occc(=O)c5c4)c3)c(=O)oc12
Temperature: 25 °C
Yield: 98 %

Procedure:
DIEA (0.012 mL, 0.071 mmol) was added to 8-methoxy-3-carboxy-coumarin (0.014 g, 0.065 mmol) and HATU (0.027 g, 0.071 mmol) in 0.5 mL of DMF with constant stirring at room temperature until a clear solution resulted. Subsequently, 3-(4-oxo-4H-chromen-6-yl)-phenylamine (0.015 g, 0.065 mmol) was added and allowed to react overnight when a solid precipitated out of solution. The resulting precipitate was filtered, dried under suction, and finally dried overnight in vacuo to give 0.028 g of product in 100% yield: LCMS (ESI) m/z 440 (MH+).
Reaction SMILES: Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].F[C:14](OB([O-])[O-])=[C:15](F)F.[K+].[K+]>C(O)(C)C.O.C(N)(C)(C)C>[F:10][C:9]([F:12])([F:11])[C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][C:2]=1[CH:14]=[CH2:15])[NH2:6]
Reactant: Nc1ccc(Br)c(C(F)(F)F)c1
Reactant: [O-]B([O-])OC(F)=C(F)F
Agent: [K+]
Solvent: O
Solvent: CC(C)(C)N
Solvent: CC(C)O
Product: C=Cc1ccc(N)cc1C(F)(F)F
Temperature: 80 °C
Reaction time: 20 h
Yield: 79.2 %

Procedure:
In 20 mL of isopropanol, 10 mL of water and 5 mL of t-butylamine, 4.0 g (16.7 mmol) of 4-bromo-3-(trifluoromethyl)aniline was dissolved, and 4.0 g (29.9 mmol) of potassium (trifluoro)vinylborate and 300 mg (0.37 mmol) of PdCl2(dppf)2•2(dichloromethane) complex were added thereto, and the mixture solution was stirred in an argon atmosphere at 80° C. for 20 hours. The reaction solution was concentrated and the residue was partitioned between water and ethyl acetate, and the organic layer was washed with a saturated sodium chloride solution and concentrated under reduced pressure. The product was purified by a silica gel column (n-hexane:ethyl acetate=6:1) to obtain 2.475 g (79%) of a target product as a pale yellow oil.