Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[N:2]1[C:6]2[N:7]=[C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH2:9][NH:10][C:5]=2[CH:4]=[CH:3]1.[CH3:17][O:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][C:24]=1[O:25][CH3:26].C(=O)([O-])[O-].[Na+].[Na+].C(=O)(O)[O-].[Na+]>Cl[Pd-2](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.ClCCl.C(#N)C>[CH3:17][O:18][C:19]1[CH:20]=[C:21]([N:2]2[C:6]3[N:7]=[C:8]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=4)[CH2:9][NH:10][C:5]=3[CH:4]=[CH:3]2)[CH:22]=[CH:23][C:24]=1[O:25][CH3:26]
Reactant: In1ccc2c1N=C(c1ccccc1)CN2
Reactant: COc1ccc(B(O)O)cc1OC
Agent: Cl[Pd-2](Cl)([PH](c1ccccc1)(c1ccccc1)c1ccccc1)[PH](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])O
Agent: O=C([O-])[O-]
Solvent: ClCCl
Solvent: CC#N
Product: COc1ccc(-n2ccc3c2N=C(c2ccccc2)CN3)cc1OC
Yield: 26.9 %

Procedure:
50 mg (0.16 mmol) of 5-iodo-3-phenyl-1H-pyrrolo[2,3-b]pyrazine, 38 mg (0.20 mmol) of 3,4-dimethoxyphenylboronic acid and 6 mg (5 mol %) of dichlorobis(triphenylphosphino)palladium(II) were placed in a vial and 1 ml of acetonitrile and 1 ml of a 2 M aqueous solution of sodium carbonate were added and the mixture irradiated in a Personal Chemistry® microwave reactor to 165° C. for 1200 sec. The resulting mixture was distributed between 15 ml of a saturated aqueous solution of sodium bicarbonate and 75 ml of dichloromethane. The organic phase was dried over sodium sulfate and evaporated. The crude was purified via flash chromatography on silica gel using a gradient of methanol in dichloromethane. The product isolated was crystallized from hot ethanol to afford 14 mg (43 μmol, 27% yield) of 5-(3,4-dimethoxy-phenyl)-3-phenyl-1H-pyrrolo[2,3-b]pyrazine as an orange powder. 1H-NMR (d6-DMSO) δ: 12.30 [1H] s, 8.92 [1H] s, 8.43 [1H] s, 8.35 [2H] d, 7.80 [1H] (m), 7.79 [1H] d(m), 7.46 [2H] dd, 7.25 [1H] dd(d), 7.13 [1H] d, 3.92 [3H] s, 3.84 [3H] s. MS: m/z 332 [MH+].
Reaction SMILES: S(O[CH2:12][CH:13]1[CH2:16][CH2:15][O:14]1)(C1C=CC(C)=CC=1)(=O)=O.[C:17]1(=[O:27])[NH:21][C:20](=[O:22])[C:19]2=[CH:23][CH:24]=[CH:25][CH:26]=[C:18]12.[K]>CN(C=O)C>[C:17]1(=[O:27])[N:21]([CH2:12][CH:13]2[CH2:16][CH2:15][O:14]2)[C:20](=[O:22])[C:19]2=[CH:23][CH:24]=[CH:25][CH:26]=[C:18]12
Reactant: Cc1ccc(S(=O)(=O)OCC2CCO2)cc1
Reactant: O=C1NC(=O)c2ccccc21
Agent: [K]
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1CC1CCO1
Temperature: 120 °C
Reaction time: 18 h

Procedure:
A solution of 2-(tosyloxymethyl)oxetane (27 g, 111.4 mmol) (prepared according to A. O. Fitton et al., Synthesis 1987, (12), 1140-2) and potassium phtalimide (20.64 g, 111.4 mmol) in DMF (200 ml) is stirred at a temperature of 120° C. for 18 hours, then evaporated in vacuo. The residue is taken up in ethyl acetate, the organic layer washed with water and brine, dried (Na2SO4), filtered, and evaporated to dryness. The crude solid product (19.8 g, 82%) is used in the next step without further purification.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:17])([O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[CH3:9])=[C:4]([F:18])[CH:3]=1.C([O-])(=O)C.[K+].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.[CH3:42][O:43][C:44]([C:46]1[CH:47]=[C:48]2[CH:54]=[C:53]([C:55](OS(C3C=CC(C)=CC=3)(=O)=O)=[CH:56][CH:57]3[CH2:61][CH2:60][CH2:59][CH2:58]3)[N:52]([S:73]([C:76]3[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=3)(=[O:75])=[O:74])[C:49]2=[N:50][CH:51]=1)=[O:45].C(=O)([O-])[O-].[Na+].[Na+]>CS(C)=O.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[CH3:42][O:43][C:44]([C:46]1[CH:47]=[C:48]2[CH:54]=[C:53]([C:55]([C:2]3[CH:7]=[CH:6][C:5]([C:8]([CH3:17])([O:10][CH:11]4[CH2:16][CH2:15][CH2:14][CH2:13][O:12]4)[CH3:9])=[C:4]([F:18])[CH:3]=3)=[CH:56][CH:57]3[CH2:58][CH2:59][CH2:60][CH2:61]3)[N:52]([S:73]([C:76]3[CH:77]=[CH:78][CH:79]=[CH:80][CH:81]=3)(=[O:74])=[O:75])[C:49]2=[N:50][CH:51]=1)=[O:45]
Reactant: COC(=O)c1cnc2c(c1)cc(C(=CC1CCCC1)OS(=O)(=O)c1ccc(C)cc1)n2S(=O)(=O)c1ccccc1
Reactant: CC(C)(OC1CCCCO1)c1ccc(Br)cc1F
Agent: Cl[Pd]Cl
Agent: [Fe]
Agent: CC(=O)[O-]
Solvent: CS(C)=O
Product: COC(=O)c1cnc2c(c1)cc(C(=CC1CCCC1)c1ccc(C(C)(C)OC3CCCCO3)c(F)c1)n2S(=O)(=O)c1ccccc1
Temperature: 80 °C
Reaction time: 3 h
Yield: 59.8 %

Procedure:
To a stirred solution of 2-[1-(4-bromo-2-fluoro-phenyl)-1-methyl-ethoxy]-tetrahydro-pyran (9.7 g, 30.6 mmol), potassium acetate (9 g, 91.8 mmol) and bis(pinacolato)diboron (9.7 g, 38.2 mmol) in dimethylsulfoxide (65 mL) was added 1,1-bis(diphenylphosphino)ferrocenedichloropalladium(II) (2.5 g, 3.06 mmol) at room temperature. The mixture was heated at 80° C. and stirred for 3 h and then cooled to room temperature and then 1-benzenesulfonyl-2-[2-cyclopentyl-1-(toluene-4-sulfonyloxy)-vinyl]-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methyl ester (prepared as in Example 3, 9 g, 15.52 mmol) and an aqueous sodium carbonate solution (2 M, 17.85 mL) were added. The mixture was heated at 100° C. and stirred for 3 h. The resulting mixture was cooled to room temperature, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (QingDao silica gel, 200-300 mesh, 20% ethyl acetate/hexanes) to afford 1-benzenesulfonyl-2-(2-cyclopentyl-1-{3-fluoro-4-[1-methyl-1-(tetrahydro-pyran-2-yloxy)-ethyl]-phenyl}-vinyl)-1H-pyrrolo[2,3-b]pyridin-5-carboxylic acid methyl ester (6 g, 60%) as a light yellow oil: LC/MS m/e calcd for C36H39FN2O6S [M+H]+ 647.78, observed 647.0.
Reaction SMILES: [C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH3:23])=[CH:13][C:12]([CH2:24][O:25]C(=O)C1C=CC=CC=1)=[CH:11][CH:10]=2)(=[O:5])[CH2:2][CH2:3][CH3:4].[OH-].[Na+]>CO>[C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH3:23])=[CH:13][C:12]([CH2:24][OH:25])=[CH:11][CH:10]=2)(=[O:5])[CH2:2][CH2:3][CH3:4]
Reactant: CCCC(=O)c1cnc2ccc(COC(=O)c3ccccc3)cc2c1Nc1ccccc1C
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCCC(=O)c1cnc2ccc(CO)cc2c1Nc1ccccc1C

Procedure:
3-butyryl-4-(2-methylphenylamino)-6-benzoyloxymethylquinoline (3.0 g, 6.8 mol) was dissolved in methanol (50 ml) and 2 M sodium hydroxide solution (50 ml) was added. The mixture was heated under reflux for 45 minutes until a clear solution was obtained. The mixture was partitioned between chloroform and water, the aqueous layer re-extracted with chloroform and the combined organic solutions washed with brine, dried filtered and evaporated. Crystallization from ether afforded 3-butyryl-4-(2-methylphenylamino)-6-hydroxymethylquinoline; (1.9 g, 83%), m.p. 139° C.-41° C.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][O:11][C:12]3[CH:20]=[CH:19][CH:18]=[C:14]([C:15]([OH:17])=O)[C:13]=3[C:21]([OH:23])=O)=[CH:9][C:4]=2[O:3][CH2:2]1.Cl.[NH2:25][CH:26]1[CH2:32][CH2:31][C:30](=[O:33])[NH:29][C:27]1=[O:28]>N1C=CC=CC=1>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][O:11][C:12]3[CH:20]=[CH:19][CH:18]=[C:14]4[C:13]=3[C:21](=[O:23])[N:25]([CH:26]3[CH2:32][CH2:31][C:30](=[O:33])[NH:29][C:27]3=[O:28])[C:15]4=[O:17])=[CH:9][C:4]=2[O:3][CH2:2]1
Reactant: NC1CCC(=O)NC1=O
Reactant: O=C(O)c1cccc(OCc2ccc3c(c2)OCO3)c1C(=O)O
Agent: Cl
Solvent: c1ccncc1
Product: O=C1CCC(N2C(=O)c3cccc(OCc4ccc5c(c4)OCO5)c3C2=O)C(=O)N1
Yield: 29 %

Procedure:
A mixture of 3-(benzo[1,3]dioxol-5-ylmethoxy)-phthalic acid (1.2 g, 3.8 mmol), alpha-amino-glutarimide hydrochloride (0.66 g, 4.0 mmol) in pyridine was refluxed overnight. The mixture was evaporated and the residue was purified by flash column chromatography (methanol/methylene chloride) to give 4-(benzo[1,3]dioxol-5-ylmethoxy)-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione as a white solid (0.45 g, 29% yield); HPLC: Waters Symmetry C18, 5 μm. 3.9×150 mm, 1 mL/min, 240 nm, 50/50 CH3CN/0.1% H3PO4, 4.06 min (98.6%); mp, 229-231° C.; 1H NMR (DMSO-d6) δ 2.02-2.05 (m, 1H, CHH), 2.55-2.62 (m, 2H, CH2), 2.82-2.94 (m, 1H, CHH), 5.10 (dd, J=6, 12 Hz, 1H, CH), 5.26 (s, 2H, CH2), 6.03 (s, 2H, CH2), 6.93-7.85 (m, 6H, Ar), 11.11 (s, 1H, NH); 13C NMR (DMSO-d6) δ 21.95, 30.91, 48.74, 70.00, 101.05, 108.10, 108.18, 115.49, 116.61, 120.28, 121.25, 129.78, 133.24, 136.95, 147.04, 147.38, 155.44, 165.30, 166.76, 169.89, 172.74. Anal Calcd For C21H16N2O7: C, 61.77; H, 3.95; N, 6.86. Found: C, 61.44; H, 3.72; N, 6.79.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH2:9][C:10]([N:12]1[C:20]2[C:15](=[CH:16][C:17]([C:21]3[C:25]4[C:26]([NH2:31])=[N:27][CH:28]=[C:29](I)[C:24]=4[S:23][CH:22]=3)=[CH:18][CH:19]=2)[CH2:14][CH2:13]1)=[O:11].[NH:32]1[CH:36]=[CH:35][C:34](B(O)O)=[N:33]1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>C(OCC)(=O)C.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH2:9][C:10]([N:12]1[C:20]2[C:15](=[CH:16][C:17]([C:21]3[C:25]4[C:26]([NH2:31])=[N:27][CH:28]=[C:29]([C:36]5[CH:35]=[CH:34][NH:33][N:32]=5)[C:24]=4[S:23][CH:22]=3)=[CH:18][CH:19]=2)[CH2:14][CH2:13]1)=[O:11]
Reactant: Nc1ncc(I)c2scc(-c3ccc4c(c3)CCN4C(=O)Cc3cc(F)ccc3F)c12
Reactant: OB(O)c1cc[nH]n1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: Nc1ncc(-c2cc[nH]n2)c2scc(-c3ccc4c(c3)CCN4C(=O)Cc3cc(F)ccc3F)c12
Temperature: 120 °C
Reaction time: 0.08 h
Yield: 35.9 %

Procedure:
To a 25 mL microwave reactor vial was charged 3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-iodothieno[3,2-c]pyridin-4-amine (150 mg, 0.274 mmol), 1H-pyrazol-3-ylboronic acid (30.7 mg, 0.274 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (11.19 mg, 0.014 mmol), and sodium carbonate (58.1 mg, 0.548 mmol) followed by dioxane (5 mL), and water (1 mL). The reaction was heated at 120° C. for 30 min in microwave reactor. Ethyl acetate (20 mL) was added and the layers were separated. The organic layer was washed with brine, concentrated, and the residue purified by silica gel chromatography (0%-100% EtOAc in hexanes). Product came out at 100% EtOAc in 5 minutes, the fractions with the product were combined and evaporated to dryness to afford the title compound as a light gray solid (48 mg). LC/MS (ES) m/z=488.2 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.99 (s, 1H) 8.36 (s, 1H) 8.12 (d, J=8.1 Hz, 1H) 7.85 (s, 1H) 7.48 (s, 1H) 7.38 (s, 1H) 7.14-7.31 (m, 4H) 6.84 (s, 1H) 5.50 (br. s., 2H) 4.32 (t, J=8.5 Hz, 2H) 3.96 (s, 2H) 3.25-3.32 (m, 2H).
Reaction SMILES: [H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:16][CH2:15][C:14]2[C:17]([OH:22])=[C:18]([Cl:21])[CH:19]=[CH:20][C:13]=2[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Br.Br[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=1>CN(C=O)C>[C:3]([O:7][C:8]([N:10]1[CH2:16][CH2:15][C:14]2[C:17]([O:22][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)=[C:18]([Cl:21])[CH:19]=[CH:20][C:13]=2[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]
Reactant: BrCc1ccccn1
Reactant: CC(C)(C)OC(=O)N1CCc2ccc(Cl)c(O)c2CC1
Agent: Br
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCc2ccc(Cl)c(OCc3ccccn3)c2CC1
Temperature: 65 °C
Reaction time: 1 h

Procedure:
Prepare a slurry of sodium hydride (60% in mineral oil, 168 mg, 4.2 mmol) in DMF (4 mL) and heat to 65° C. Add dropwise a solution of 3-tert-butoxycarbonyl-7-chloro-6-hydroxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (250 mg, 0.84 mmol) in DMF (5 mL) and stir for 1 h. Add a solution of 2-(bromomethyl)-pyridine hydrobromide (256 mg, 1 mmol) in DMF (1 mL), stir at 65° C. for 0.5 h and cool to ambient temperature. Add water (1 mL) and concentrate the reaction mixture to an oily residue. Partition the residue between EtOAc/hexane (1:1) and water. Dry the organic layer over Na2SO4, filter and concentrate. Purify by chromatography on silica gel eluting with hexane/EtOAc (10:1, 5:1 and 3:1) to give 3-tert-butoxycarbonyl-7-chloro-6-(pyridin-2-ylmethoxy)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as an oil.
Reaction SMILES: [CH:1]([O:8][CH2:9][CH3:10])([O:5][CH2:6][CH3:7])OCC.[NH:11]([C:19]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20])[C@H:12](C=O)[CH2:13][CH:14]([CH3:16])[CH3:15].C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C>[CH2:9]([O:8][CH:1]([O:5][CH2:6][CH3:7])[C@H:12]([CH2:13][CH:14]([CH3:16])[CH3:15])[NH:11][C:19]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20])[CH3:10]
Reactant: CCOC(OCC)OCC
Reactant: CC(C)C[C@@H](C=O)NC(=O)OCc1ccccc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCO
Product: CCOC(OCC)[C@H](CC(C)C)NC(=O)OCc1ccccc1
Reaction time: 0.5 h

Procedure:
104 mL of triethyl orthoformate was added over a period of 30 min to a solution of CBZ-Leu-H (12 g) and p-toluenesulfonic acid (0.9 g) in 100 mL of anhydrous ethanol (EtOH). The mixture was stirred for 30 min, and then was evaporated and diluted with 500 mL of ether. The ether layer was washed consecutively with saturated solutions of NaHCO3 and sodium chloride. The yellowish brown semisolid was recrystallized from cold hexane to yield off-white needles of CBZ-Leucinal diethylacetal. 1H NMR (300 MHz, CDCl3) δ: 7.28(m, 5H), 5.03(s, 2H), 4.77(d, 1H), 4.27(d, 1H), 3.8(m, 1H), 3.63(m, 2H), 3.43(m, 2H), 1.6(dd, 2H), 1.30(m, 2H), 1.12(m, 6H), 0.83(d, 6H)
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[CH:9]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=1)[OH:10].[C:18](OCC)(=[O:20])C>>[Cl:8][C:4]1[C:3]2[CH:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:10][C:18](=[O:20])[NH:1][C:2]=2[CH:7]=[CH:6][CH:5]=1
Reactant: Nc1cccc(Cl)c1C(O)c1ccc(F)cc1
Reactant: CCOC(C)=O
Product: O=C1Nc2cccc(Cl)c2C(c2ccc(F)cc2)O1
Yield: 45 %

Procedure:
This compound was prepared using General Method 2 (EXAMPLE 1) from (±)-1-(2-amino-6-chlorophenyl)-(4-fluorophenyl)methanol (0.28 g, 1.1 mmol) to afford 0.14 g (45%) of (±)-5-chloro-4-(4-fluorophenyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one after flash chromatography (4:1 hexanes:ethyl acetate).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:32]=[CH:33][CH:34]=1)[C:7]([NH:9][C:10]1[CH:31]=[CH:30][C:13]2[N:14]([CH:17]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:18][C:19]([O:21]CC)=[O:20])[CH:15]=[N:16][C:12]=2[CH:11]=1)=[O:8])([O-:3])=[O:2]>Cl>[N+:1]([C:4]1[CH:5]=[C:6]([CH:32]=[CH:33][CH:34]=1)[C:7]([NH:9][C:10]1[CH:31]=[CH:30][C:13]2[N:14]([CH:17]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:18][C:19]([OH:21])=[O:20])[CH:15]=[N:16][C:12]=2[CH:11]=1)=[O:8])([O-:3])=[O:2]
Reactant: CCOC(=O)CC(c1ccccc1)n1cnc2cc(NC(=O)c3cccc([N+](=O)[O-])c3)ccc21
Agent: Cl
Product: O=C(O)CC(c1ccccc1)n1cnc2cc(NC(=O)c3cccc([N+](=O)[O-])c3)ccc21

Procedure:
A solution of ethyl 3-{5-[(3-nitrobenzoyl)amino]-1H-benzimidazol-1-yl}-3-phenylpropanoate (40 mg, 87 μmol) in hydrochloric acid (20 mL of a 5N solution) was stirred at room temperature for 110 hours. The solution was then evaporated in vacuo, and purified by RP-HPLC to give the title compound, [LCMS (Method A, Mobile Phase II) RT=3.91 min, MH+ 431].
Reaction SMILES: [C:1]1([C@H:11]([NH:13][CH2:14]/[CH:15]=[CH:16]/[C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=2)[CH3:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[H][H]>CO.Cl[Pd]Cl>[CH3:12][C@@H:11]([NH:13][CH2:14][CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:24])([F:25])[F:26])[CH:18]=1)[C:1]1[CH:2]=[CH:3][CH:4]=[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:10]=12
Reactant: C[C@@H](NC/C=C/c1cccc(C(F)(F)F)c1)c1cccc2ccccc12
Reactant: [H][H]
Agent: Cl[Pd]Cl
Solvent: CO
Product: C[C@@H](NCCCc1cccc(C(F)(F)F)c1)c1cccc2ccccc12
Reaction time: 10 h
Yield: 66.3 %

Procedure:
A mixture of compound (VI) (3.0 g), PdCl2 (0.01 g), in methanol (10 mL) was pressurized with 1 bar hydrogen and stirred for 10 hrs at +25° C. The mixture was then filtered through a Celite® pad and concentrated to give Cinacalcet free base, compound (I) (2.0 g).