Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](=[O:15])[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.[H][H]>[Pd].C1(C)C=CC=CC=1>[OH:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH:9]([OH:15])[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:6][CH:7]=1
Reactant: [H][H]
Reactant: CCOC(=O)C(=O)Cc1ccc(O)cc1
Agent: [Pd]
Solvent: Cc1ccccc1
Product: CCOC(=O)C(O)Cc1ccc(O)cc1
Temperature: 50 °C
Reaction time: 1 h
Yield: 98.1 %

Procedure:
10 g of ethyl 3-(4-hydroxyphenyl)pyruvate and 30 ml of toluene were charged to a pressure reactor to form a solution, and 0.25 g of 5% palladium on charcoal was added thereto. The atmosphere was displaced with hydrogen, and the mixture was stirred at 50° C. under a hydrogen pressure of 5 kg/cm2 for 1 hour. After completion of the reaction, the reaction mixture was filtered to remove the catalyst, and the filtrate was concentrated under reduced pressure to give 9.9 g of ethyl 3-(4-hydroxyphenyl)lactate as a colorless oily substance.
Reaction SMILES: Br[N:2]1C(=O)CC[C:3]1=O.[Br:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([CH3:20])([CH3:19])[C:17]#[N:18])=[CH:12][C:11]=1[CH3:21]>C(Cl)(Cl)(Cl)Cl>[Br:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([CH3:19])([CH3:20])[C:17]#[N:18])=[CH:12][C:11]=1[CH2:21][C:3]#[N:2]
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1cc(C(C)(C)C#N)ccc1Br
Solvent: ClC(Cl)(Cl)Cl
Product: CC(C)(C#N)c1ccc(Br)c(CC#N)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
N-bromosuccinimide (1.04 g) and 2,2′-azobis(isobutylnitrile) (30 mg) were added to the carbon tetrachloride solution (7 ml) of 2-(4-bromo-3-methylphenyl)-2-methylpropionitrile (1.26 g) and then the solution was refluxed with heating for an hour. The solution was cooled on ice, then after removing the insoluble substances by filtration, the filtrate was concentrated under reduced pressure. The obtained residue was dissolved in ethanol (10 ml) and water (1 ml) and a solution of potassium cyanide (0.41 g) was added to the solution. The reaction mixture was stirring overnight at room temperature. To the reaction mixture was added the ice-cold water and ethyl acetate, and the organic layer was separated. The obtained organic layer was sequentially washed with water (twice) and brine. After drying over anhydrous magnesium sulfate, the organic layer was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier; Wakogel™ C-200; elution solvent; heptane:ethyl acetate, 19:1→5:1) to obtain the title compound. (917 mg) The property values of the obtained compound are as follows; 1H-NMR (CDCl3) δ (ppm): 1.74 (s, 6H), 3.87 (s, 2H), 7.38 (dd, J=8.4, 2.4 Hz, 1H), 7.57 (d, J=2.4 Hz, 1H), 7.64 (d, J=8.4 Hz, 1H).
Reaction SMILES: [CH:1]([C:3]1[N:7]([CH:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11](=[O:18])[O:10][C:9]2([CH3:20])[CH3:19])[CH:6]=[N:5][CH:4]=1)=[CH2:2]>CO.[Pd]>[CH2:1]([C:3]1[N:7]([CH:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11](=[O:18])[O:10][C:9]2([CH3:19])[CH3:20])[CH:6]=[N:5][CH:4]=1)[CH3:2]
Reactant: C=Cc1cncn1C1c2ccccc2C(=O)OC1(C)C
Agent: [Pd]
Solvent: CO
Product: CCc1cncn1C1c2ccccc2C(=O)OC1(C)C
Reaction time: 3 h

Procedure:
To a solution of 4-(5-vinyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one (0.049 g, 0.173 mmol) (Example 3) in methanol (1 mL) is added Pd/C (10% wt, 0.009 g, 0.009 mmol) and the flask is flushed with hydrogen. The mixture is stirred under balloon pressure. After 3 h, another portion of catalyst (0.009 g) is added. After 7 h, the mixture is filtered and concentrated in vacuo to give 4-(5-ethyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one as a white solid; MS (ESI) m/z 271.2 (M+H); 1H NMR (400 MHz, MeOD) δ ppm 1.25 (s, 3 H), 1.43 (br. s., 3 H), 1.56 (s, 3 H), 2.87 (br. s, 2 H), 5.55 (br. s, 1 H), 6.83 (s, 1 H), 7.17 (br. s, 1 H), 7.45 (d, J=7.6 Hz, 1 H), 7.67 (td, J=7.6, 1.0 Hz, 1 H), 7.78 (td, J=7.6, 1.3 Hz, 1 H), 8.24 (dd, J=7.6, 1.0 Hz, 1 H).
Reaction SMILES: C(O)C(F)(F)F.FC(F)(F)[CH2:9][O:10][C:11]1[S:12][C:13]([C:16](=[O:18])[CH3:17])=[CH:14][N:15]=1>>[CH3:9][O:10][C:11]1[S:12][C:13]([C:16](=[O:18])[CH3:17])=[CH:14][N:15]=1
Reactant: CC(=O)c1cnc(OCC(F)(F)F)s1
Solvent: OCC(F)(F)F
Product: COc1ncc(C(C)=O)s1

Procedure:
The following compound was prepared using trifluoroethanol according to the procedure used in preparing compound 192: 1-[2-(2,2,2-trifluoroethoxy)-1,3-thiazol-5-yl]ethanone (compound 204)
Reaction SMILES: [NH2:1][C:2]1[NH:3][C:4](=O)[N:5]=[C:6]([C:8]#[N:9])[N:7]=1.P(Cl)(Cl)([Cl:13])=O.C(=O)([O-])[O-].[Na+].[Na+]>>[NH2:1][C:2]1[N:3]=[C:4]([Cl:13])[N:5]=[C:6]([C:8]#[N:9])[N:7]=1
Reactant: N#Cc1nc(N)[nH]c(=O)n1
Reactant: O=P(Cl)(Cl)Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: N#Cc1nc(N)nc(Cl)n1
Temperature: 25 °C

Procedure:
To 2-amino-4-cyano-6-oxo-1,3,5-triazine (J. Am. Chem. Soc., 1961, 83, 1261-2, 2.30 g, 16.8 mmol) was added phosphoryl trichloride (50 mL, 547 mmol) and the mixture heated at 90 C for 2 h. The reaction mixture was cooled to room temperature before pouring onto ice-water (250 mL) and basifying to pH 8 with solid sodium carbonate. The mixture was then extracted into DCM (3×250 mL) and the combined organics were dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford the desired compound, which was used crude without further purification (343 mg, 13%). Method C HPLC-MS: 2 MH+ requires m/z=311. Found: m/z=311, Rt=0.74 min (100%).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[CH:11]=[C:10]([C:12]3[CH:17]=[N:16][N:15]4[C:18]([C:21]5[CH:22]=[C:23]([NH:27][C:28]([NH:30][CH2:31][C:32]([F:35])([F:34])[F:33])=[O:29])[CH:24]=[CH:25][CH:26]=5)=[CH:19][N:20]=[C:14]4[CH:13]=3)[CH:9]=[N:8]2)[CH2:3][CH2:2]1.[N:36]1([C:42](Cl)=[O:43])[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1>>[N:36]1([C:42]([N:1]2[CH2:6][CH2:5][CH:4]([N:7]3[CH:11]=[C:10]([C:12]4[CH:17]=[N:16][N:15]5[C:18]([C:21]6[CH:22]=[C:23]([NH:27][C:28]([NH:30][CH2:31][C:32]([F:33])([F:35])[F:34])=[O:29])[CH:24]=[CH:25][CH:26]=6)=[CH:19][N:20]=[C:14]5[CH:13]=4)[CH:9]=[N:8]3)[CH2:3][CH2:2]2)=[O:43])[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1
Reactant: O=C(Cl)N1CCOCC1
Reactant: O=C(NCC(F)(F)F)Nc1cccc(-c2cnc3cc(-c4cnn(C5CCNCC5)c4)cnn23)c1
Product: O=C(NCC(F)(F)F)Nc1cccc(-c2cnc3cc(-c4cnn(C5CCN(C(=O)N6CCOCC6)CC5)c4)cnn23)c1

Procedure:
This compound was prepared by using procedures analogous to those described for the synthesis of Example 30 (Step 6) starting from N-{3-[7-(1-piperidin-4-yl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-3-yl]phenyl}-N′-(2,2,2-trifluoroethyl)urea and morpholine-4-carbonyl chloride (Aldrich, Cat. No. 348295). LCMS (M+H)+: m/z=598.2.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C:14]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)(O)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.O=S(Cl)Cl.Cl>C(Cl)Cl>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH:13]=[C:14]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(OCc1ccccc1)N1CCC(O)(Cc2ccccc2)CC1
Agent: Cl
Solvent: c1ccncc1
Solvent: ClCCl
Solvent: O=S(Cl)Cl
Product: O=C(OCc1ccccc1)N1CC=C(Cc2ccccc2)CC1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 95.9 %

Procedure:
To a solution of 40.0 g (123 mmol) of 4-benzyl-4-hydroxy-piperidine-1-carboxylic acid benzyl ester in 250 ml CH2Cl2 were added 39.6 ml (492 mmol) pyridine and at 0° C. 17.8 ml (246 mmol) of SOCl2. The reaction mixture was stirred for 30 min. at 0° C. and then 250 ml of aqueous (2N) HCl were added. The aqueous phase was extracted twice with CH2Cl2 and the combined organic layers were washed with water, dried over MgSO4 and the solvent was removed under reduced pressure to give 36.3 g (118 mmol, 96%) of 4-benzyl-3,6-dihydro-2H-pyridine-1-carboxylic acid benzyl ester as an orange oil.
Reaction SMILES: Cl[CH:2]([SiH3:4])Cl.[CH:5]([C:22]1[CH:27]=[C:26]([C:28]([CH3:31])([CH3:30])[CH3:29])[CH:25]=[C:24]([C:32]([CH3:35])([CH3:34])[CH3:33])[C:23]=1[OH:36])([C:7]1[CH:12]=[C:11]([C:13]([CH3:16])([CH3:15])[CH3:14])[CH:10]=[C:9]([C:17]([CH3:20])([CH3:19])[CH3:18])[C:8]=1[OH:21])[CH3:6].C(N(CC)CC)C>>[C:28]([C:26]1[CH:25]=[C:24]([C:32]([CH3:33])([CH3:35])[CH3:34])[C:23]2[O:36][SiH:4]([CH3:2])[O:21][C:8]3[C:9]([C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:10][C:11]([C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:12][C:7]=3[CH:5]([CH3:6])[C:22]=2[CH:27]=1)([CH3:31])([CH3:29])[CH3:30]
Reactant: CC(c1cc(C(C)(C)C)cc(C(C)(C)C)c1O)c1cc(C(C)(C)C)cc(C(C)(C)C)c1O
Reactant: [SiH3]C(Cl)Cl
Solvent: CCN(CC)CC
Product: CC1c2cc(C(C)(C)C)cc(C(C)(C)C)c2O[SiH](C)Oc2c1cc(C(C)(C)C)cc2C(C)(C)C
Yield: 51 %

Procedure:
Utilizing the procedure of Example 1, this compound is prepared from 23.0 grams (0.20 mole) dichloromethylsilane, 87.7 grams (0.20 mole) 2,2'-ethylidene-bis(4,6-di-t-butylphenol) and 40.5 grams (0.40 mole) of triethylamine. Recrystallization twice from acetonitrile-toluene gives 49.0 g (51% yield) of white crystals, mp 189°-194° C.
Reaction SMILES: [CH3:1][CH:2]([C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:16][CH2:17][C:18]3[CH:27]=[CH:26][C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[N:19]=3)[CH:12]=2)[CH:7]=1)[C:3]([OH:5])=O.[CH3:28][O:29][NH3+:30].[Cl-].C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>O1CCCC1>[CH3:28][O:29][NH:30][C:3](=[O:5])[CH:2]([CH3:1])[C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:16][CH2:17][C:18]3[CH:27]=[CH:26][C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[N:19]=3)[CH:12]=2)[CH:7]=1
Reactant: CC(C(=O)O)c1ccc2cc(OCc3ccc4ccccc4n3)ccc2c1
Reactant: CO[NH3+]
Agent: CCN=C=NCCCN(C)C
Agent: [Cl-]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CONC(=O)C(C)c1ccc2cc(OCc3ccc4ccccc4n3)ccc2c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a mixture of the acid of Example 1 (2.32 g, 6.5 mmol), 0-methylhydroxylamine hydrochloride (0.54 g, 6.5 mmol) and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (1.25 g, 6.5 mmol) in tetrahydrofuran (100 ml) is added triethylamine (2.0 ml, 2 equiv). After overnight stirring at room temperature, the solvent is removed and methylene chloride is added. This is followed by sequential washings with 0.05N hydrochloric acid and water (2x). After drying over magnesium sulfate, the solvent is removed to afford a crude solid which is recrystallized from ethyl acetate to afford a white crystalline solid, 0.6 g(24%), m.p. 162°-164° C.
Reaction SMILES: [C:1]1([S:7][CH2:8][C:9]2[NH:10][CH2:11][CH2:12][N:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:14]1([N:20]=[C:21]=[O:22])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C(Cl)Cl>[C:14]1([NH:20][C:21]([N:13]2[CH2:12][CH2:11][N:10]=[C:9]2[CH2:8][S:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[O:22])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=C=Nc1ccccc1
Reactant: c1ccc(SCC2=NCCN2)cc1
Solvent: ClCCl
Product: O=C(Nc1ccccc1)N1CCN=C1CSc1ccccc1
Temperature: -15 °C
Reaction time: 2 h

Procedure:
2-Phenylthiomethyl-2-imidazoline (4.8 g; 0.025 mole) was dissolved in CH2Cl2 (200 ml) and the solution cooled to -15° C. before treating dropwise with fresh phenyl isocyanate (3.0 g; 0.025 moles) over 15 minutes. The mixture was allowed to warm to room temperature and stirring continued for a further 2 hours. The solvent was then evaporated in vacuo and the residue recrystallised from ethyl acetate, to give a solid, m.p. 117.4° to 119.0° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[O:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.C1(C2[C:27](C3N=CN(C4C=CC=CC=4)C=3)=[C:26](C(F)(F)F)[O:25]N=2)C=CC=CC=1>>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:12]([C:26](=[O:25])[CH3:27])=[C:11]([C:13]([F:14])([F:15])[F:16])[O:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: FC(F)(F)c1onc(-c2ccccc2)c1-c1cn(-c2ccccc2)cn1
Reactant: Fc1cccc(-c2cc(C(F)(F)F)on2)c1
Product: CC(=O)c1c(-c2cccc(F)c2)noc1C(F)(F)F
Yield: 51 %

Procedure:
As described for Example 1e, 3-(3-fluoro-phenyl)-5-trifluoromethyl-isoxazole (20 g, 86.5 mmol), instead of 3-phenyl-4-(1-phenyl-1H-imidazol-4-yl)-5-trifluoromethyl-isoxazole, was converted to the title compound (12.2 g, 51%) which was obtained as a light yellow oil. MS: m/e=272.1 [M−H]−.
Reaction SMILES: [CH3:1][N:2]1[C:11](=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[Cl:13])[NH:4][C:3]1=O.[CH:15]1([C:18]2[O:22][N:21]=[C:20]([CH2:23][N+:24]#[C-:25])[N:19]=2)[CH2:17][CH2:16]1>>[CH:15]1([C:18]2[O:22][N:21]=[C:20]([C:23]3[N:24]=[CH:25][N:4]4[C:5]5[C:10](=[C:9]([Cl:13])[CH:8]=[CH:7][CH:6]=5)[C:11](=[O:12])[N:2]([CH3:1])[C:3]=34)[N:19]=2)[CH2:17][CH2:16]1
Reactant: [C-]#[N+]Cc1noc(C2CC2)n1
Reactant: Cn1c(=O)[nH]c2cccc(Cl)c2c1=O
Product: Cn1c(=O)c2c(Cl)cccc2n2cnc(-c3noc(C4CC4)n3)c12

Procedure:
M.p. 230°-240° C. (decomp.) by reaction between 3-methyl-5-chloro-1,2,3,4-tetrahydro-2,4-dioxo-quinazoline and 5-cyclopropyl-3-isocyanomethyl-1,2,4-oxadiazole.
Reaction SMILES: [Si:1]([O:8][CH:9]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:22][S:23](Cl)(=[O:25])=[O:24]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Si:1]([O:8][CH:9]1[CH2:13][CH2:12][CH:11]([O:14][S:23]([CH3:22])(=[O:25])=[O:24])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)OC1CCC(O)C1
Reactant: CS(=O)(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)OC1CCC(OS(C)(=O)=O)C1
Temperature: 0 °C
Reaction time: 16 h
Yield: 53.1 %

Procedure:
To a solution of 3-(tert-butyldimethylsilanyloxy)cyclopentanol (3.5 g, 16 mmol) in DCM (30 mL) was added triethylamine (2.65 mL, 19.4 mmol) and DMAP (20 mg, 0.16 mmol). The reaction mixture was cooled to 0° C. and methanesulfonyl chloride (1.34 mL, 16.5 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was washed with water and the organic layer was dried over sodium sulfate, filtered, and concentrated. Purification of the residue by column chromatography (20% diethyl ether:hexanes) afforded 2.5 g (53%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 5.19-5.3 (m, 1H), 4.4 (m, 1H), 3.0 (s, 3H), 1.8-2.3 (m, 4H), 1.5-1.7 (m, 2H), 0.86 (s, 9H), 0.05 (s, 6H).
Reaction SMILES: [Li+].[OH-].C[O:4][C:5](=[O:27])[C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([CH3:14])[C:7]=1[NH:15][C:16]([C:18]1[S:19][CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[N:22]=1)=[O:17].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CCO.O>[CH3:13][O:12][C:9]1[CH:10]=[CH:11][C:6]([C:5]([OH:27])=[O:4])=[C:7]([NH:15][C:16]([C:18]2[S:19][CH:20]=[C:21]([C:23]([F:26])([F:24])[F:25])[N:22]=2)=[O:17])[C:8]=1[CH3:14]
Reactant: COC(=O)c1ccc(OC)c(C)c1NC(=O)c1nc(C(F)(F)F)cs1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [Li+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: COc1ccc(C(=O)O)c(NC(=O)c2nc(C(F)(F)F)cs2)c1C
Temperature: 60 °C
Reaction time: 3 h
Yield: 88 %

Procedure:
LiOH (240 mg, 1.2 eq.) was added to a mixture of compound 204 (3 g, 1 eq.) in EtOH/H2O (20 mL/20 mL) at room temperature. The reaction mixture was stirred at 60° C. for 3 hrs and was allowed to cooled down to room temperature. A 5% aqueous solution of citric acid was added and the mixture was extracted with EtOAc. Organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure to yield compound 205 as a white solid in 88% yield. 1H NMR (CDCl3, 400 MHz) δ (ppm) 1.51 (s, 3H), 3.85 (s, 3H), 6.75 (d, J=8.75 Hz, 1H), 7.87 (d, J=8.75 Hz, 1H), 7.95 (s, 1H), 10.48 (s, 1H).
Reaction SMILES: [N:1]1([C:7]2[S:8][C:9]3[CH:15]=[C:14]([C:16]([O:18][CH3:19])=[O:17])[CH:13]=[CH:12][C:10]=3[N:11]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH3:20][C:21]([O:24][C:25]([NH:27][C@H:28]([C:35](O)=[O:36])[CH2:29][C:30]1[S:34][CH:33]=[CH:32][CH:31]=1)=[O:26])([CH3:23])[CH3:22].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[C:21]([O:24][C:25]([NH:27][C@@H:28]([CH2:29][C:30]1[S:34][CH:33]=[CH:32][CH:31]=1)[C:35]([N:4]1[CH2:5][CH2:6][N:1]([C:7]2[S:8][C:9]3[CH:15]=[C:14]([C:16]([O:18][CH3:19])=[O:17])[CH:13]=[CH:12][C:10]=3[N:11]=2)[CH2:2][CH2:3]1)=[O:36])=[O:26])([CH3:23])([CH3:20])[CH3:22]
Reactant: COC(=O)c1ccc2nc(N3CCNCC3)sc2c1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1cccs1)C(=O)O
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1ccc2nc(N3CCN(C(=O)[C@H](Cc4cccs4)NC(=O)OC(C)(C)C)CC3)sc2c1
Reaction time: 8 h

Procedure:
Methyl 2-(piperazin-1-yl)benzo[d]thiazole-6-carboxylate (0.35 g, 1.26 mmol), Boc-L-2-thienylalanine (0.34 g, 1.26 mmol), diisopropylethylamine (0.88 ml, 5.06 mmol) and HBTU (0.62 g, 1.64 mmol) were dissolved in DMF (36 ml) and the resulting mixture stirred overnight. The resulting mixture was then diluted with ethyl acetate (78 ml), washed with 1N HCl (3×39 ml), washed with brine (39 ml), dried (MgSO4) and concentrated in vacuo. The resulting residue was chromatographed eluting with dichloromethane/methanol (97:3) to yield (S)-methyl 2-(4-(2-(tert-butoxycarbonylamino)-3-(thiophen-2-yl)propanoyl)piperazin-1-yl)benzo[d]thiazole-6-carboxylate.
Reaction SMILES: [CH3:1][C:2]1[CH2:6][CH2:5][CH2:4][CH:3]=1.Cl[N-:8][S:9]([C:12]1[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=1)(=[O:11])=[O:10].[Na+].[Br-].[Br-].[Br-].C[N+](C)(C)C1C=CC=CC=1.C[N+](C1C=CC=CC=1)(C)C.C[N+](C1C=CC=CC=1)(C)C.O>C1COCC1>[CH3:1][C:2]12[N:8]([S:9]([C:12]3[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=3)(=[O:10])=[O:11])[CH:6]1[CH2:5][CH2:4][CH2:3]2
Reactant: Cc1ccc(S(=O)(=O)[N-]Cl)cc1
Reactant: CC1=CCCC1
Agent: C[N+](C)(C)c1ccccc1
Agent: [Br-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: Cc1ccc(S(=O)(=O)N2C3CCCC32C)cc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of 1-methylcyclopent-1-ene (CAS number 693-89-0; 50.0 g, 609.75 mmol) iii and sodium chloro(4-methylbenzenesulfonyl)azanide (CAS number 127-65-1; 192 g, 680.85 mmol) in THF (2500 ml) was added trimethylphenylammonium tribromide (13.3 g, 61.57 mmol). The reaction was stirred vigorously at 25° C. for 12 hours. The reaction mixture was poured into water (1500 ml) and the organics were extracted with ethyl acetate (3×1000 ml). The combined organics were washed with water (500 ml), brine (500 ml), dried over sodium sulfate and concentrated in vacuo. This was then purified by column chromatography (silica, 0-2.5% ethyl acetate/n-hexane) to afford the title compound.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[CH:20][CH:21]=3)[NH:16][CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.Br[CH2:24][C:25]1[O:26][CH:27]=[CH:28][CH:29]=1>C(OCC)C>[O:26]1[CH:27]=[CH:28][CH:29]=[C:25]1[CH2:24][N:16]1[C:17]2=[N:18][CH:19]=[CH:20][CH:21]=[C:22]2[C:14]([CH:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)=[CH:15]1
Reactant: CC(C)(C)OC(=O)N1CCC(c2c[nH]c3ncccc23)CC1
Reactant: BrCc1ccco1
Solvent: CCOCC
Product: c1coc(Cn2cc(C3CCNCC3)c3cccnc32)c1

Procedure:
This compound was prepared following the procedure described in example 7, parts E and F, starting with 0.3 g (1 mmol) of 4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-piperidine-1-carboxylic acid tert-butyl ester and 2.12 ml of a freshly prepared 0.61 M solution of 2-bromomethylfuran in ethyl ether. After standard work-up, 0.28 g (97% of yield) of the expected product were isolated.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([CH3:13])=[C:5]([OH:12])[C:6]([N+:9]([O-:11])=[O:10])=[CH:7][CH:8]=1.[H-].[Na+].CN(C=O)C.[CH3:21][CH2:22][CH2:23]Br>O>[CH3:1][O:2][C:3]1[C:4]([CH3:13])=[C:5]([O:12][CH2:21][CH2:22][CH3:23])[C:6]([N+:9]([O-:11])=[O:10])=[CH:7][CH:8]=1
Reactant: CCCBr
Reactant: COc1ccc([N+](=O)[O-])c(O)c1C
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCCOc1c([N+](=O)[O-])ccc(OC)c1C
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 96.3 %

Procedure:
2.0 g (10.93 mmol) of 3-methoxy-2-methyl-6-nitrophenol (prepared according to R. A. Raphael, P. Ravenscoft, J. Chem. Soc. Perkin Trans. I, (1988), 1823-1828) were added in portions under an argon atmosphere to a suspension of 525 mg (1 2.02 mmol) of NaH in 30 ml of abs. DMF cooled to 0° C. After stirring at 0° C. for 30 min, 1.17 ml (12.70 mmol) of n-propyl bromide were added dropwise. The reaction solution was stirred at 70° C. for 8 h. Subsequently, 70 ml of H2O were added with ice cooling, and the mixture was then concentrated to dryness. The residue was taken up in EA, and the solution was washed 3× with H2O, dried over Na2SO4, and concentrated. Drying in a high vacuum afforded 2.37 g of the title compound in the form of a brown oil.
Reaction SMILES: [CH3:1][C:2]1([CH3:17])[C:10]2[C:5](=[CH:6][C:7]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[CH:8][CH:9]=2)[NH:4][CH2:3]1.Cl[C:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]=[C:21]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[F:35])[C:20]=1[CH3:36].C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][C:2]1([CH3:17])[C:10]2[C:5](=[CH:6][C:7]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[CH:8][CH:9]=2)[N:4]([C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[N:22]=[C:21]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[F:35])[C:20]=2[CH3:36])[CH2:3]1
Reactant: CC1(C)CNc2cc(N3CCOCC3)ccc21
Reactant: Cc1c(-c2ccccc2F)nc2ccccc2c1Cl
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: Cc1c(-c2ccccc2F)nc2ccccc2c1N1CC(C)(C)c2ccc(N3CCOCC3)cc21

Procedure:
Prepared according to procedure T using 4-(3,3-dimethylindolin-6-yl)morpholine (0.043 g, 0.184 mmol), 4-chloro-2-(2-fluorophenyl)-3-methylquinoline (0.050 g, 0.184 mmol), cesium carbonate (0.12 g, 0.368 mmol), Pd2(dba)3 (0.017 g, 0.018 mmol) and (±) BINAP (0.0174 g, 0.028 mmol) in 1,4-dioxane (1 mL). After purification by HPLC 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-indol-1-yl)-2-(2-fluorophenyl)-3-methylquinoline was obtained. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.00 (1H, d, J=7.8 Hz), 7.82 (1H, d, J=8.2 Hz), 7.69 (1H, t, J=7.6 Hz), 7.52 (3H, m), 7.30 (2H, m), 6.98 (1H, d, J=8.2 Hz), 6.20 (1H, dd, J=8.2, 2.0 Hz), 5.46 (1H, d, J=2.0 Hz), 3.75 (1H, d, J=9.0 Hz), 3.60 (1H, d, J=9.4 Hz), 3.51 (4H, m), 2.77 (4H, m), 1.99 (3H, s), 1.39 (3H, s), 1.30 (3H, s). Mass Spectrum (ESI) m/e=468 (M+1).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][CH2:20][CH2:21][CH3:22])=[C:6]([C:8]2[NH:13][C:12](=[O:14])[C:11]([CH2:15][CH3:16])=[C:10]([CH2:17][CH3:18])[N:9]=2)[CH:7]=1.C([O-])=O.[NH4+].[C:27](#N)[CH3:28]>[Pd]>[CH2:15]([C:11]1[C:12](=[O:14])[NH:13][C:8]([C:6]2[CH:7]=[C:2]([NH:1][CH2:27][CH3:28])[CH:3]=[CH:4][C:5]=2[O:19][CH2:20][CH2:21][CH3:22])=[N:9][C:10]=1[CH2:17][CH3:18])[CH3:16]
Reactant: CC#N
Reactant: CCCOc1ccc(N)cc1-c1nc(CC)c(CC)c(=O)[nH]1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Product: CCCOc1ccc(NCC)cc1-c1nc(CC)c(CC)c(=O)[nH]1
Temperature: 25 °C
Reaction time: 20 h
Yield: 79 %

Procedure:
The compound (2.2 g, 7.3 mmol) of example 42 was dissolved in 50 ml of 80% acetonitrile aqueous solution, and added with 0.14 g of 5% Pd/C and 5 g of ammonium formate, followed by stirring at room temperature for 20 h under nitrogen atmosphere. The reaction mixture was filtered off Pd/C and distilled off the solvent. The residue was dissolved in CH2Cl2 (50 ml), washed with water (50 ml) and saturated saline (50 ml), dried with anhydrous Na2SO4, and concentrated to dryness to give a white solid crude, which was passed through a silica gel column (eluant: 10% petroleumether-ethyl acetate) to afford the title compound (1.9 g, yield: 79%). 1H NMR (CDCl3) δ: 8.38 (1H, d), 7.33 (1H, dd), 7.04 (1H, d), 4.19 (2H, t), 4.04 (2H, q), 2.66 (2H, q), 2.59 (2H, q), 2.01 (2H, m), 1.28 (3H, t), 1.19 (3H, t), 1.15 (3H, t), 1.06 (3H, t).