Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[Br-].[F:13][C:14]1[CH:15]=[C:16]([CH:19]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=1)[CH2:17][Zn+]>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>[F:13][C:14]1[CH:15]=[C:16]([CH:19]=[C:20]([C:22]([F:23])([F:24])[F:25])[CH:21]=1)[CH2:17][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6]
Reactant: Fc1cc(C[Zn+])cc(C(F)(F)F)c1
Reactant: COC(=O)c1ccnc(Cl)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Br-]
Solvent: C1CCOC1
Product: COC(=O)c1ccnc(Cc2cc(F)cc(C(F)(F)F)c2)c1
Temperature: 60 °C
Yield: 74.9 %

Procedure:
Methyl 2-chloroisonicotinate (3.0 g, 17.48 mmol) and Pd(PPh3)4 (0.606 g, 0.52 mmol) were dissolved in THF (50 mL) under nitrogen. Freshly prepared (3-fluoro-5-(trifluoromethyl)benzyl)zinc(II) bromide (5.41 g, 19.45 mmol) in THF (25 mL) was added to the yellow solution and the flask was warmed to 60° C. overnight. The reaction mixture was quenched by adding methanol. The solution was diluted with ethyl acetate and washed with NH4Cl and water. The organic layer was dried with Na2SO4, filtered through celite, and the solvent was evaporated. The residue was chromatographed using the Biotage equipment. Eluent ethyl acetate-heptane, started 20-80 and linear gradient until 60-40. Methyl 2-(3-fluoro-5-(trifluoromethyl)benzyl)isonicotinate (4.1 g, 75% yield) was isolated. 1H NMR (400 MHz, cdcl3) δ 3.94 (s, 3H), 4.25 (s, 2H), 7.13-7.22 (m, 2H), 7.33 (s, 1H), 7.69-7.75 (m, 2H), 8.70-8.74 (m, 1H). MS m/z 314 (M+H)+
Reaction SMILES: [N:1]1([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH:17]1([C:20](O)=[O:21])[CH2:19][CH2:18]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O.O>[CH:17]1([C:20]([N:4]2[CH2:5][CH2:6][N:1]([C:7]([O:9][CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[O:8])[CH2:2][CH2:3]2)=[O:21])[CH2:19][CH2:18]1
Reactant: O=C(O)C1CC1
Reactant: O=C(OCc1ccccc1)N1CCNCC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: O=C(OCc1ccccc1)N1CCN(C(=O)C2CC2)CC1
Reaction time: 3 h
Yield: 93.2 %

Procedure:
In 35 mL of N,N-dimethylformamide were dissolved benzyl 1-piperazinecarboxylate (5.00 g, 22.7 mmol) and cyclopropanecarboxylic acid (2.54 g, 29.5 mmol), and 1-ethyl-3-(3-(N,N-dimethylamino)propyl)-carbodiimide hydrochloride (6.53 g, 34.1 mmol), 1-hydroxybenzotriazole (4.52 g, 29.5 mmol) and triethylamine (3.60 g, 35.9 mmol) were added thereto at room temperature, followed by stirring at the same temperature for three hours. The reaction mixture was mixed with water, and extracted twice with ethyl acetate. The organic layer was sequentially washed with water twice, with a saturated aqueous solution of sodium bicarbonate once and with brine once, and then dried over anhydrous sodium sulfate. The organic layer was passed through a silica gel column (Fuji Silysia, NH Silica gel) and evaporated to give the title compound (6.10 g, 93.1%) as a white amorphous.
Reaction SMILES: [BH4-].[Na+].[CH2:3]([O:5][C:6]1[N:11]=[C:10]([C:12](OCC)=[O:13])[CH:9]=[CH:8][CH:7]=1)[CH3:4]>CCO>[CH2:3]([O:5][C:6]1[N:11]=[C:10]([CH2:12][OH:13])[CH:9]=[CH:8][CH:7]=1)[CH3:4]
Reactant: CCOC(=O)c1cccc(OCC)n1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: CCOc1cccc(CO)n1
Temperature: 25 °C
Reaction time: 48 h
Yield: 93.9 %

Procedure:
Sodium borohydride (16.0 g, 424 mmol) was added in portions over 35 minutes to ethyl 6-ethoxypicolinate (4.14 g, 21.2 mmol) in EtOH (0.2M, 200 mL). The resulting mixture was stirred at ambient temperature for two days. The mixture was concentrated and the residue was distributed between water and DCM. The organic layer was dried (phase separator silicone treated filter paper), and concentrated to give (6-ethoxypyridin-2-yl)methanol (3.05 g, 94% yield) as a pale yellow oil.
Reaction SMILES: [NH2:1][C:2]1([C:15]([O-:17])=[O:16])[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[CH:18](N(C(C)C)CC)(C)C.C[Si](C=[N+]=[N-])(C)C>C(#N)C.CO>[NH2:1][C:2]1([C:15]([O:17][CH3:18])=[O:16])[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9])[CH2:4][CH2:3]1
Reactant: CCN(C(C)C)C(C)C
Reactant: CC(C)(C)OC(=O)N1CCC(N)(C(=O)[O-])CC1
Agent: C[Si](C)(C)C=[N+]=[N-]
Solvent: CC#N
Solvent: CO
Product: COC(=O)C1(N)CCN(C(=O)OC(C)(C)C)CC1
Reaction time: 8 h
Yield: 76 %

Procedure:
4-Amino-1-tert-butoxycarbonylpiperidine-4-carboxylate (5 g) in acetonitrile (22 ml) and methanol (2 ml) was treated with diisopropylethylamine (3.65 ml) and trimethylsilyldiazomethane (2M in hexane, 13.9 ml). After overnight stirring and evaporation of solvent, the crude product was chromatographed on silica gel (0–50% ethyl acetate/petrol) to give a yellow oil (4 g, 76%).
Reaction SMILES: [N+:1](=[CH2:3])=[N-:2].CN(N=O)/C(/N)=N/[N+]([O-])=O.[OH-].[K+].[Br:16][CH2:17][CH2:18][CH:19]([C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=1)[C:20](Cl)=[O:21]>CCOCC>[Br:16][CH2:17][CH2:18][CH:19]([C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=1)[C:20](=[O:21])[CH:3]=[N+:1]=[N-:2]
Reactant: C=[N+]=[N-]
Reactant: O=C(Cl)C(CCBr)c1ccc(Cl)c(Cl)c1
Agent: CN(N=O)/C(N)=N/[N+](=O)[O-]
Agent: [K+]
Agent: [OH-]
Solvent: CCOCC
Product: [N-]=[N+]=CC(=O)C(CCBr)c1ccc(Cl)c(Cl)c1
Temperature: 0 °C

Procedure:
Prepare a solution of diazomethane from 15 g of MNNG by reaction with 45 ml of 40% aqueous KOH topped with 150 ml. of Et2O and cool in an ice bath. Add an Et2O solution (40 ml.) of the product of Step 3 (8.2 g, 24.8 mmoles) in small volumes, stir the solution in the ice bath for 15 min, then heat to reflux for 30 min. Remove the solvent in vacuo. Purify the resulting mixture by flash chromatography on silica gel using CH2Cl2 as eluent. Yield: 7.0 g (IR: 2100 cm-1, 1630 cm-1).
Reaction SMILES: Br[C:2]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C:9]2[C:8](=[O:19])[N:7]([CH2:20][CH2:21][CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[C:6](=[O:31])[N:5]([CH3:32])[C:4]=2[N:3]=1.C([Li])CCC.[CH:38](=[O:40])[CH3:39]>C1COCC1.O>[Si:24]([O:23][CH2:22][CH2:21][CH2:20][N:7]1[C:8](=[O:19])[C:9]2[N:10]([CH2:11][C:12]3[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=3)[C:2]([CH:38]([OH:40])[CH3:39])=[N:3][C:4]=2[N:5]([CH3:32])[C:6]1=[O:31])([C:27]([CH3:28])([CH3:29])[CH3:30])([CH3:25])[CH3:26]
Reactant: Cn1c(=O)n(CCCO[Si](C)(C)C(C)(C)C)c(=O)c2c1nc(Br)n2Cc1ccc(Cl)cc1
Reactant: CC=O
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Product: CC(O)c1nc2c(c(=O)n(CCCO[Si](C)(C)C(C)(C)C)c(=O)n2C)n1Cc1ccc(Cl)cc1
Temperature: -78 °C
Reaction time: 0.08 h
Yield: 22.3 %

Procedure:
Step 1 8-Bromo-1-(3-((tert-butyldimethylsilyl)oxy)propyl)-7-(4-chlorobenzyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (0.25 g, 0.46 mmol, intermediate 77) was dissolved in THF (5 mL) and cooled to −78° C. To the clear solution was added 2.5 M n-butyllithium in hexanes (0.20 mL, 0.51 mmol) dropwise. The reaction was stirred in the cold for 5 min and acetaldehyde (0.13 mL, 2.31 mmol) was added. The reaction was warmed to room temperature and stirred for 1 h. The reaction was diluted with water (100 mL) and extracted with ethyl acetate (3×75 mL). The combined extracts were dried with magnesium sulfate, filtered and the solvent was removed under reduced pressure to leave a golden oil. The oil was purified using two 1000 microns preparative TLC plates eluted with 50% ethyl acetate/hexanes. Target band was extracted with ethyl acetate and the solvent was removed under reduced pressure to give 1-(3-((tert-butyldimethysilyl)oxy)propyl)-7-(4-chlorobenzyl)-8-(1-hydroxyethyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (0.052 g, 30% yield) as a clear oil. LCMS retention time=4.490 min and 97% purity, LCMS MH+ 507.
Reaction SMILES: B.O1CCCC1.[CH3:7][C:8]([O:11][C:12](=[O:23])[NH:13][CH2:14][CH2:15][C:16](=[O:22])[C:17]1[S:18][CH:19]=[CH:20][N:21]=1)([CH3:10])[CH3:9].CO.C(OCC)(=O)C>O1CCCC1.CCCC(C)C>[CH3:10][C:8]([O:11][C:12](=[O:23])[NH:13][CH2:14][CH2:15][C@H:16]([OH:22])[C:17]1[S:18][CH:19]=[CH:20][N:21]=1)([CH3:7])[CH3:9]
Reactant: CC(C)(C)OC(=O)NCCC(=O)c1nccs1
Agent: B
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CCCC(C)C
Product: CC(C)(C)OC(=O)NCC[C@H](O)c1nccs1
Temperature: -10 °C
Reaction time: 0.25 h
Yield: 66.6 %

Procedure:
To a solution of (R)-3-methyl-CBS-oxazaborolidine (1M solution in toluene, 0.43 ml) in dry tetrahydrofuran (30 ml) at −10° C. under nitrogen, was added borane-tetrahydrofuran complex (1M in tetrahydrofuran, 2.58 ml) and the mixture was stirred at −10° C. for 15 minutes. A solution of [3-oxo-3-(2-thiazolyl)propyl]carbamic acid 1,1-dimethylethyl ester (1.1 g, 4.3 mmol) in dry tetrahydrofuran (20 ml) was added dropwise over 45 minutes and the resulting mixture was allowed to warm up to room temperature over 16 h. Methanol (10 ml) was added and the mixture was stirred at room temperature for 15 minutes before the solvent was removed at reduced pressure. Methanol (10 ml) was again added and removed at reduced pressure to leave a crude yellow oil. Flash chromatography (silica, 25 to 100% ethyl acetate in isohexane) afforded a clear gum (0.74 g, 67%).
Reaction SMILES: Cl[C:2]1[C:3]([N+:8]([O-:10])=[O:9])=[N:4][CH:5]=[CH:6][CH:7]=1.[C:11]1([SH:17])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.O>[N+:8]([C:3]1[C:2]([S:17][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:7][CH:6]=[CH:5][N:4]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1ncccc1Cl
Reactant: Sc1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CS(C)=O
Solvent: O
Product: O=[N+]([O-])c1ncccc1Sc1ccccc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 70 %

Procedure:
3-chloro-2-nitropyridine (30.6 g, 193 mmol) was dissolved in DMSO (200 mL). Benzenethiol (20.7 mL, 203 mmol) was added followed by cesium carbonate (69.3 g, 212 mmol) and stirred at ambient temperature for 1.5 hours. The solution was diluted with water (750 mL) and the solids filtered. The crude material was recrystallized from EtOAc (400 mL) and with adding hexanes (1 L) to give an A-crop of 23.5 g. The filtrate was concentrated and recrystallized from EtOAc/hexanes to give 7.87 g. The solids were dried on high vacuum to provide the title compound (31.38 g, 69.8% yield).
Reaction SMILES: [N:1]([CH:4]([CH3:7])[CH2:5][OH:6])=[N+:2]=[N-:3].[H-].[Na+].Cl[CH2:11][C:12](=[O:19])[CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15]>O1CCCC1>[N:1]([CH:4]([CH3:7])[CH2:5][O:6][CH2:11][C:12](=[O:19])[CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])=[N+:2]=[N-:3]
Reactant: CCOC(=O)CC(=O)CCl
Reactant: CC(CO)N=[N+]=[N-]
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)CC(=O)COCC(C)N=[N+]=[N-]
Reaction time: 0.25 h
Yield: 87.6 %

Procedure:
A solution of the 2-azidopropan-1-ol (10.1 g) in tetrahydrofuran (100 ml) was added over two minutes to a stirred, ice-cooled suspension of sodium hydride (6.6 g; 80% dispersion in oil) in tetrahydrofuran (50 ml). The mixture was stirred for 15 minutes with ice-cooling and then treated over 20 minutes with a solution of ethyl 4-chloroacetoacetate (16.4 g) in tetrahydrofuran (150 ml). The mixture was stirred at room temperature for 16 hours and evaporated. The residue was diluted with water, washed twice with ether, acidified with 2M hydrochloric acid, and extracted three times into ether. The combined ether extracts were dried (Na2SO4) and evaporated to give crude ethyl 4-(2-azidoprop-1-oxy)acetoacetate (20 g), used directly.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.[CH:10]([O:13][C:14]1[CH:15]=[C:16]([CH:28]=[C:29]([NH2:31])[CH:30]=1)[C:17]([NH:19][C:20]1[S:21][C:22]([C:25]([OH:27])=[O:26])=[CH:23][N:24]=1)=[O:18])([CH3:12])[CH3:11].C([BH3-])#N.[Na+]>CO>[CH:10]([O:13][C:14]1[CH:15]=[C:16]([CH:28]=[C:29]([NH:31][CH2:4][C:3]2[CH:6]=[CH:7][CH:8]=[CH:9][C:2]=2[Cl:1])[CH:30]=1)[C:17]([NH:19][C:20]1[S:21][C:22]([C:25]([OH:27])=[O:26])=[CH:23][N:24]=1)=[O:18])([CH3:12])[CH3:11]
Reactant: O=Cc1ccccc1Cl
Reactant: CC(C)Oc1cc(N)cc(C(=O)Nc2ncc(C(=O)O)s2)c1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: CC(C)Oc1cc(NCc2ccccc2Cl)cc(C(=O)Nc2ncc(C(=O)O)s2)c1
Reaction time: 16 h
Yield: 55 %

Procedure:
2-Chlorobenzaldehyde (0.012 ml, 0.11 mM) was added to 2-[(3-isopropoxy-5-aminobenzoyl)amino]-5-thiazolecarboxylic acid (29 mg 0.09 mM) and 4A molecular sieves (90 mg) in methanol under an inert atmosphere at room temperature. After 1 hr sodium cyanoborohydride (7 mg, 0.11 mM) was added and the reaction mixture stirred for 16 hrs. The reaction mixture was filtered, concentrated in vacuo, the residue stirred with water then extracted with ethyl acetate (3×10 ml). The organic extracts were washed with brine (20 ml), dried (MgSO4), filtered and concentrated in vacuo to give the title compound as a pale yellow solid (22 mg, 55%); 1H nmr (d6-DMSO, δ values): 1.22 (6H, d); 4.36 (2H, m); 4.58 (1H, m); 6.24 (1H, s); 6.47 (1H, m); 6.84 (2H, m); 7.26 (3H, m); 7.37 (2H, m); 7.45 (1H, m); 7.76 (1H, br s). MS [M-CO2H]−400, 402.
Reaction SMILES: [C:1]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH:13]=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:15]C(C)([O-])C.[K+].C(OP(C=[N+]=[N-])(=O)OCC)C>CCOCC>[C:1]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[C:13]#[CH:15])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]
Reactant: CC(C)(C)[O-]
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H]1C=O
Agent: CCOP(=O)(C=[N+]=[N-])OCC
Agent: [K+]
Solvent: CCOCC
Product: C#C[C@H]1CCCN1C(=O)OC(C)(C)C

Procedure:
(R)-N-Boc-2-Ethynyl-pyrrolidine was prepared according to Method X above by the treatment of (R)-N-Boc-2-formyl-pyrrolidine (700 mg, 3.51 mmol) (Example 89A) with potassium tert-butoxide (510 mg, 4.56 mmol) and diazomethyl-phosphonic-acid-diethylester (820 mg, 4.56 mmol) (also prepared according to Method X). (R)-N-Boc-2-Ethynyl-pyrrolidine was obtained after silica gel coloumn chromatography with 10% Et2O in hexanes. (Yield 150 mg, 25%).
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[CH:4][CH:3]=1.[O:10]1[CH:14]=[CH:13][CH2:12][C:11]1=O>>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:7]2[CH2:14][CH2:13][CH2:12][C:11]2=[O:10])=[CH:4][CH:3]=1
Reactant: NCc1ccc(F)cc1
Reactant: O=C1CC=CO1
Product: O=C1CCCN1Cc1ccc(F)cc1
Yield: 74.8 %

Procedure:
47 g (0.376 mol) of p-fluorobenzylamine, 30.4 g (0.353 mol) of furan-2-one and 0.4 g of hyddroquinone are introduced into a 125 ml autoclave. After driving the air out of the apparatus by passing a stream of nitrogen through it, the mixture is heated to 250° for 6 hours. It is then cooled and distilled under reduced pressure. 51 g (yield=74.8%) of 1-p-fluorobenzyl-pyrrolidin-2-one are collected as a colourless liquid distilling at 103°-105° under a pressure of 0.01 mm of mercury and solidifying slowly. Melting point=37°-38°.
Reaction SMILES: [NH:1]([C:8]1[S:9][CH:10]=[C:11]([CH:13]=[CH:14][CH2:15][OH:16])[N:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.O.Cl>CS(C)=O>[NH:1]([C:8]1[S:9][CH:10]=[C:11](/[CH:13]=[CH:14]/[CH:15]=[O:16])[N:12]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: OCC=Cc1csc(Nc2ccccc2)n1
Agent: Cl
Solvent: O
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: O=C/C=C/c1csc(Nc2ccccc2)n1
Reaction time: 0.5 h

Procedure:
2.6 g of the crude alcohol thus obtained were dissolved in 20 ml of dimethyl sulfoxide, and 3.4 g of triethylamine were added to the resulting solution. Next, a solution of 5.3 g of a sulfur trioxide pyridine complex in dimethyl sulfoxide (10 ml) was added dropwise to the reaction mixture at room temperature, and the mixture was stirred at the same temperature for 30 minutes. The reaction mixture was then poured into water, acidified with 3N hydrochloric acid, and extracted with ethyl acetate. After the extract was dried over anhydrous sodium sulfate, the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography, using as eluent a 10:1 mixture of benzene and ethyl acetate, giving the desired compound as pale yellow crystals.
Reaction SMILES: Cl[C:2]1[N:22]=[C:5]2[C:6]([C:10]3[CH:11]=[N:12][N:13]([C:15]4[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=4)[CH:14]=3)=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][CH:33]([C:36]2[CH:41]=[CH:40][C:39]([NH2:42])=[CH:38][CH:37]=2)[CH2:32][CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][CH:33]([C:36]2[CH:41]=[CH:40][C:39]([NH:42][C:2]3[N:22]=[C:5]4[C:6]([C:10]5[CH:11]=[N:12][N:13]([C:15]6[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=6)[CH:14]=5)=[CH:7][CH:8]=[CH:9][N:4]4[N:3]=3)=[CH:38][CH:37]=2)[CH2:32][CH2:31]1)=[O:29])([CH3:26])([CH3:24])[CH3:25]
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(N)cc2)CC1
Reactant: Cc1ccc(-n2cc(-c3cccn4nc(Cl)nc34)cn2)cc1
Agent: c1ccc(P(C2CCCCC2)C2CCCCC2)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c1
Product: Cc1ccc(-n2cc(-c3cccn4nc(Nc5ccc(C6CCN(C(=O)OC(C)(C)C)CC6)cc5)nc34)cn2)cc1

Procedure:
4-{4-[8-(1-p-Tolyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridine-2-ylamino]-phenyl}-piperidine-1-carboxylic acid tert-butyl ester was prepared from 2-chloro-8-(1-p-tolyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridine and 4-(4-amino-phenyl)-piperidine-1-carboxylic acid tert-butyl ester with 2,2′-bis-dicyclohexylphosphanyl-biphenyl as the ligand in a manner analogous to Example 2d (0.265 g, 40%). MP=124-125° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.60 (s, 1H), 9.24 (s, 1H), 8.68 (d, 1H), 8.64 (s, 1H), 7.98 (m, 1H), 7.77 (m, 2H), 7.66 (m, 2H), 7.40 (m, 2H), 7.21 (m, 2H), 4.08 (m, 2H), 2.80 (m, 2H), 2.62 (m, 1H), 2.38 (s, 3H), 1.73 (m, 2H), 1.48 (m, 2H), 1.41 (s, 3H). MS=550 (MH)+.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][N:3]=1.[Cl:12][C:13]1[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=1[C:20]1[C:25]([C:26]2[NH:27][CH:28]=[C:29]([CH3:31])[N:30]=2)=[CH:24][N:23]=[C:22]([NH:32][CH2:33][CH2:34][NH:35]C2N=CC(C#N)=CC=2)[N:21]=1>>[Cl:12][C:13]1[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=1[C:20]1[C:25]([C:26]2[NH:27][CH:28]=[C:29]([CH3:31])[N:30]=2)=[CH:24][N:23]=[C:22]([NH:32][CH2:33][CH2:34][NH:35][C:2]2[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][N:3]=2)[N:21]=1
Reactant: FC(F)(F)c1ccc(Cl)nc1
Reactant: Cc1c[nH]c(-c2cnc(NCCNc3ccc(C#N)cn3)nc2-c2ccc(Cl)cc2Cl)n1
Product: Cc1c[nH]c(-c2cnc(NCCNc3ccc(C(F)(F)F)cn3)nc2-c2ccc(Cl)cc2Cl)n1

Procedure:
[4-(2,4-dichlorophenyl)-5-(4-methylimidazol-2-yl)pyrimidin-2-yl](2-{[5-(trifluoromethyl)(2-pyridyl)]amino}ethyl)amine was prepared from 2-chloro-5-(trifluoromethyl)pyridine using the general method for 6-[(2-{[4-(2,4-dichlorophenyl)-5-(4-methylimidazol-2-yl)pyrimidin-2-yl]amino}ethyl)amino]pyridine-3-carbonitrile.
Reaction SMILES: [Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([O:9][CH2:10][CH3:11])=[C:5]([Cl:12])[C:4]=1[F:13].[CH:14]([CH:16]1[CH2:21][CH2:20][C:19](=[O:22])[CH2:18][CH2:17]1)=[CH2:15].Cl>C1COCC1.C1(C)C=CC=CC=1>[Cl:12][C:5]1[C:4]([F:13])=[C:3]([C:19]2([OH:22])[CH2:20][CH2:21][CH:16]([CH:14]=[CH2:15])[CH2:17][CH2:18]2)[CH:8]=[CH:7][C:6]=1[O:9][CH2:10][CH3:11]
Reactant: C=CC1CCC(=O)CC1
Reactant: CCOc1ccc(Br)c(F)c1Cl
Agent: Cl
Agent: [Mg]
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: C=CC1CCC(O)(c2ccc(OCC)c(Cl)c2F)CC1
Temperature: 40 °C
Reaction time: 0.5 h
Yield: 133 %

Procedure:
1.5 g of well dried magnesium and 30 mL of THF were placed in a reactor under nitrogen atmosphere, and heated to 40° C. 15.3 g of the compound (1) dissolved in 30 mL of THF was slowly added dropwise thereto at a temperature range of from 35 to 49° C., followed by stirring for 30 minutes. Thereafter, 5.0 g of the compound (23) dissolved in 5 mL of THF was slowly added dropwise thereto at a temperature range of from 30 to 40° C., followed by stirring for 30 minutes. After cooling the resulting reaction mixture to 25° C., the reaction mixture was poured into and mixed with a mixture of 100 mL of 1N hydrochloric acid and 100 mL of toluene. The mixture was separated into an organic layer and an aqueous layer by standing still, so as to attain extraction to the organic layer. The resulting organic layer was fractionated and washed with water, a 2N sodium hydroxide aqueous solution, a saturated sodium bicarbonate aqueous solution and water, followed by drying over anhydrous magnesium sulfate. Thereafter, the solvent was removed by distillation under reduced pressure to obtain 16.0 g of 1-(3-chloro-4-ethoxy-2-fluorophenyl)-4-vinylcyclohexanol (24) as a yellow liquid.
Reaction SMILES: [Br:1]Br.[C:3]([O:9][CH2:10][C:11]1[CH:12]=[C:13]([C:24](=[O:26])[CH3:25])[CH:14]=[CH:15][C:16]=1[O:17][C:18](=[O:23])[CH2:19][CH2:20][CH2:21][CH3:22])(=[O:8])[CH2:4][CH2:5][CH2:6][CH3:7].C(=O)=O>C(Cl)(Cl)Cl>[C:3]([O:9][CH2:10][C:11]1[CH:12]=[C:13]([C:24](=[O:26])[CH2:25][Br:1])[CH:14]=[CH:15][C:16]=1[O:17][C:18](=[O:23])[CH2:19][CH2:20][CH2:21][CH3:22])(=[O:8])[CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: BrBr
Reactant: CCCCC(=O)OCc1cc(C(C)=O)ccc1OC(=O)CCCC
Agent: O=C=O
Solvent: ClC(Cl)Cl
Product: CCCCC(=O)OCc1cc(C(=O)CBr)ccc1OC(=O)CCCC
Yield: 57.1 %

Procedure:
A solution of bromine (4.2 g.) in chloroform (20 ml.) was added dropwise to a cooled stirred solution of 3'-valeryloxymethyl-4'-valeryloxyacetophenone (8.5 g.) in chloroform (100 ml.). During the addition, the temperature was maintained at 0°-5° C. by the addition of small pieces of solid carbon dioxide. The solution was then washed with 10% w/v sodium carbonate solution (3×100 ml.) water (2×100 ml.) and saturated brine (100 ml.). The organic phase was dried (MgSO4), filtered, and evaporated yielding 3'-valeryloxymethyl-4'-valeryloxy-2-bromoacetophenone (6 g., 57%), which was judged to be sufficiently pure by IR and TLC [SiO2 : 50 v/v EtOAc/petrol (60°-80°)] for use without further purification or characterisation.
Reaction SMILES: C([N:4]1[C:12]2[C:7](=[CH:8][C:9]([N+:13]([O-:15])=[O:14])=[CH:10][CH:11]=2)[C:6](=[C:16](OCC)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:5]1=[O:26])(=O)C.[CH3:27][N:28]([CH3:38])[CH2:29][CH2:30][C:31]1[CH:37]=[CH:36][C:34]([NH2:35])=[CH:33][CH:32]=1.[OH-].[Na+]>CN(C=O)C.CO>[CH3:38][N:28]([CH3:27])[CH2:29][CH2:30][C:31]1[CH:37]=[CH:36][C:34]([NH:35]/[C:16](=[C:6]2\[C:5](=[O:26])[NH:4][C:12]3[C:7]\2=[CH:8][C:9]([N+:13]([O-:15])=[O:14])=[CH:10][CH:11]=3)/[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)=[CH:33][CH:32]=1
Reactant: CN(C)CCc1ccc(N)cc1
Reactant: CCOC(=C1C(=O)N(C(C)=O)c2ccc([N+](=O)[O-])cc21)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: CO
Product: CN(C)CCc1ccc(N/C(=C2\C(=O)Nc3ccc([N+](=O)[O-])cc32)c2ccccc2)cc1

Procedure:
Prepared analogously to Example 82 from 1-acetyl-3-(1-ethoxy-1-phenyl-methylidene)-5-nitro-2-indolinone and 4-(2-dimethylamino-ethyl)-aniline in DMF and subsequent treatment with sodium hydroxide solution in methanol.