Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([C:12]([F:15])([F:14])[F:13])=[N:7]2.[F:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][C:18]=1[C:26]1[CH:31]=[CH:30][N:29]=[CH:28][N:27]=1>>[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:2]2[CH:11]=[CH:10][N:9]=[C:8]3[C:3]=2[CH:4]=[CH:5][C:6]([C:12]([F:15])([F:14])[F:13])=[N:7]3)=[CH:19][C:18]=1[C:26]1[CH:31]=[CH:30][N:29]=[CH:28][N:27]=1
Reactant: OB(O)c1ccc(F)c(-c2ccncn2)c1
Reactant: FC(F)(F)c1ccc2c(Cl)ccnc2n1
Product: Fc1ccc(-c2ccnc3nc(C(F)(F)F)ccc23)cc1-c1ccncn1
Yield: 24.5 %

Procedure:
5-Chloro-2-trifluoromethyl[1,8]naphthyridine (50 mg, 0.22 mmol) was coupled to 4-fluoro-3-pyrimidin-4-yl-phenylboronic acid (61 mg, 0.28 mmol) as described in Example 7 part g), affording 5-(4-fluoro-3-pyrimidin-4-ylphenyl)-2-trifluoromethyl[1,8]naphthyridine (20 mg, 25%). δH (360 MHz, CDCl3) 7.46 (1H, dd, J 8.4 and 11.2), 7.60-7.64 (2H, m), 7.85 (1H, d, J 8.8), 7.96-7.98 (1H, m), 8.42 (1H, dd, J 2.5 and 7.4), 8.53 (1H, d, J 8.4), 8.87 (1H, d, J 5.3), 9.30 (1H, s), 9.31 (1H, s). m/z (ES+) 371 [MH]+.
Reaction SMILES: [C:1]1([C:7]#[C:8][CH2:9][OH:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.C(N(CC)CC)C.CN(C1C=CC=CN=1)C.[CH:27]([SiH:30]([CH:32]([CH3:34])[CH3:33])Cl)([CH3:29])[CH3:28]>>[C:1]1([C:7]#[C:8][CH2:9][O:10][SiH:30]([CH:32]([CH3:34])[CH3:33])[CH:27]([CH3:29])[CH3:28])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1
Reactant: OCC#CC1=CCCCC1
Reactant: CC(C)[SiH](Cl)C(C)C
Agent: CN(C)c1ccccn1
Solvent: CCN(CC)CC
Product: CC(C)[SiH](OCC#CC1=CCCCC1)C(C)C
Yield: 52.7 %

Procedure:
3-Cyclohexenylprop-2-yn-1-ol (61) (1.236 g, 12.86 mmol), triethylamine (1.30 g, 12.85 mmol), dimethylaminopyridine (0.152 g, 1.267 mmol) and diisopropylchlorosilane (1.918 g, 12.73 mmol) were used to yield compound 7e (1.680 g, 6.71 mmol, 52.7%) as a colorless, clear oily substance after purification by flash chromatography: Rf 0.85 (hexanes/Et2O, 4:1); 1H NMR (500 MHz, CDCl3) δ 6.08 (h, J=1.8 Hz, 1H, H-5), 4.48 (s, 2H, H-1), 4.20 (s, 2H, H-10), 1.98-2.17 (m, 4H, H6-9), 1.49-1.71 (m, 4H, H6-9), 0.96-1.12 (m, 14H, H-11, 12). 13C NMR (300 MHz, CDCl3) δ 134.8 (C-5), 120.3 (C-4), 87.1 (C-2/3), 84.4 (C-2/3), 54.3 (C-1), 29.0 (C6-9), 25.6 (C6-9), 22.2 (C6-9), 21.5 (C6-9), 17.3 (C-12), 17.2 (C-12), 12.3 (C-11); HRMS calcd for C15H26NaOSi (M+Na)+ 273.1651. found 273.1639.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:17]=[C:16]3[C:12]([N:13]=[C:14]([C:19]4[CH:24]=[CH:23][N:22]=[C:21]([C:25](OCC)=[O:26])[CH:20]=4)[N:15]3[CH3:18])=[CH:11][N:10]=2)=[CH:4][CH:3]=1.[BH4-].[Na+]>C(O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]2[N:17]=[C:16]3[C:12]([N:13]=[C:14]([C:19]4[CH:24]=[CH:23][N:22]=[C:21]([CH2:25][OH:26])[CH:20]=4)[N:15]3[CH3:18])=[CH:11][N:10]=2)=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1cc(-c2nc3cnc(Nc4ccc(F)cc4)nc3n2C)ccn1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: Cn1c(-c2ccnc(CO)c2)nc2cnc(Nc3ccc(F)cc3)nc21
Temperature: 25 °C
Reaction time: 16 h
Yield: 3.3 %

Procedure:
To a solution of 30 mg (0.077 mmol, 1.0 eq.) of ethyl 4-(2-(4-fluorophenylamino)-9-methyl-9H-purin-8-yl)picolinate (I-15) in 3 mL of ethanol was added 58 mg (1.5 mmol, 20 eq.) of sodium borohydride. The mixture was stirred at room temperature for 16 h. The volatiles were removed in vacuo and the resulting residue was purified by semi-preparative HPLC to afford 0.9 mg (3%) of (4-(2-(4-fluorophenylamino)-9-methyl-9H-purin-8-yl)pyridine-2-yl)methanol (I-16).
Reaction SMILES: CS(O)(=O)=O.[Br:6][C:7]1[CH:12]=[CH:11][C:10]([O:13]N)=[C:9]([I:15])[CH:8]=1.O=[C:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1.CS(O)(=O)=O.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>C(O)(=O)C>[Br:6][C:7]1[CH:8]=[C:9]([I:15])[C:10]2[O:13][C:17]3[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][C:18]=3[C:11]=2[CH:12]=1
Reactant: NOc1ccc(Br)cc1I
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Agent: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Agent: CS(=O)(=O)O
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)N1CCc2oc3c(I)cc(Br)cc3c2C1
Temperature: 110 °C
Reaction time: 12 h
Yield: 12.3 %

Procedure:
A mixture of the product of step B (7.0 g, 17.0 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (3.73 g, 18.7 mmol) was suspended in a mixture of glacial acetic acid (63 mL) and methanesulfonic acid (7 mL). The suspension was heated to 110° C. for 3 h. After cooling to ambient temperature the reaction mixture was concentrated in vacuo, cooled to 0° C., quenched with 5% KOH solution and suspended in 2-propanol (100 mL) followed by addition of di-tert-butyl dicarbonate (4.45 g, 20.4 mmol). After stirring for 12 h, the mixture was concentrated in vacuo and extracted with dichloromethane. The organic layer was concentrated in vacuo and the residue purified by flash column chromatography (SiO2, 95:5 hexanes/ethyl acetate) to give tert-butyl 8-bromo-6-iodo-3,4-dihydrobenzofuro[3,2-c]pyridine-2(1H)-carboxylate (1.0 g, 9%) as a yellow brown solid: 1H NMR (CDCl3, 300 MHz) δ 7.71 (d, J=1.8 Hz, 1H), 7.50 (br s, 1H), 4.49 (br s, 2H), 3.87-3.78 (m, 2H), 2.94-2.87 (m, 2H), 1.50 (s, 9H).
Reaction SMILES: [F:1][C:2]1[CH:28]=[CH:27][C:5]([C:6]([CH2:8][CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][CH:14]([N:17]3[C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=4[N:19]=[C:18]3[SH:26])[CH2:13][CH2:12]2)=[O:7])=[CH:4][CH:3]=1.[OH-].[Na+].S(OC)(O[CH3:35])(=O)=O>O.CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([CH2:8][CH2:9][CH2:10][N:11]2[CH2:12][CH2:13][CH:14]([N:17]3[C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=4[N:19]=[C:18]3[S:26][CH3:35])[CH2:15][CH2:16]2)=[O:7])=[CH:27][CH:28]=1
Reactant: COS(=O)(=O)OC
Reactant: O=C(CCCN1CCC(n2c(S)nc3ccccc32)CC1)c1ccc(F)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CSc1nc2ccccc2n1C1CCN(CCCC(=O)c2ccc(F)cc2)CC1
Reaction time: 0.33 h

Procedure:
15.9 g of 1-[1-(3-(4-fluorobenzoyl)propyl)-4-piperidyl]-2-mercaptobenzimidazole and 3.2 g of sodium hydroxide were dissolved in a mixture of 24 ml of water and 200 ml of methanol. To the solution, 7.06 g of dimethyl sulfate was added through 4 hours at room temperature (i.e., about 20°-30°C) and then the solution was stirred for an additional 20 minutes. After the reaction, the solution was concentrated and a diluted sodium hydroxide solution was added thereto, followed by extracting with chloroform. The chloroform solution was washed with water, dried and concentrated. The residue was recrystallized from ethanol to give colorless crystals of 1-[1-(3-(4-fluorobenzoyl)-propyl)-4-piperidyl]-2-methylmercaptobenzimidazole having a melting point of 98° to 98.5°C.
Reaction SMILES: C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH2:32][CH2:33][CH2:34][C:35]([OH:37])=O)[CH:27]=[CH:28][C:29]=1[O:30][CH3:31].[NH2:38][C:39]1[CH:44]=[CH:43][C:42]([CH2:45][C:46]2[S:61][C:49]3[N:50]([CH2:57][CH:58]([CH3:60])[CH3:59])[C:51](=[O:56])[N:52]([CH3:55])[C:53](=[O:54])[C:48]=3[CH:47]=2)=[CH:41][CH:40]=1>ClCCl>[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH2:32][CH2:33][CH2:34][C:35]([NH:38][C:39]2[CH:44]=[CH:43][C:42]([CH2:45][C:46]3[S:61][C:49]4[N:50]([CH2:57][CH:58]([CH3:59])[CH3:60])[C:51](=[O:56])[N:52]([CH3:55])[C:53](=[O:54])[C:48]=4[CH:47]=3)=[CH:41][CH:40]=2)=[O:37])[CH:27]=[CH:28][C:29]=1[O:30][CH3:31]
Reactant: COc1ccc(CCCC(=O)O)cc1OC
Reactant: CC(C)Cn1c(=O)n(C)c(=O)c2cc(Cc3ccc(N)cc3)sc21
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: ClCCl
Product: COc1ccc(CCCC(=O)Nc2ccc(Cc3cc4c(=O)n(C)c(=O)n(CC(C)C)c4s3)cc2)cc1OC
Reaction time: 8 h
Yield: 26.4 %

Procedure:
To a solution of N-ethyl-N′-[3-(dimethylamino)propyl]carbodiimide (37 mg), 1-hydroxybenzotriazole (26 mg) and 4-(3,4-dimethyloxyphenyl)butanoic acid (36 mg) in dichloromethane (6 ml) was added 6-(4-aminophenylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-(1H,3H)-dione (45 mg) in dichloromethane (2 ml). The reaction mixture was stirred overnight and then washed with half saturated sodium hydrogen carbonate and extracted into ethyl acetate. The organic layer was dried over magnesium sulfate, evaporated and the residue was purified by normal phase HPLC (isohexane:ethyl acetate 50-0:50-100) to give the title compound (19 mg) as a foam.
Reaction SMILES: [OH:1][C:2]1[C:6]2([CH2:11][CH2:10][N:9]([O:12][CH3:13])[CH2:8][CH2:7]2)[S:5][C:4](=[O:14])[C:3]=1[C:15]1[C:20]([CH3:21])=[CH:19][C:18]([CH3:22])=[CH:17][C:16]=1[CH3:23].C(N(CC)CC)C.Cl[C:32]([O:34][CH2:35][CH3:36])=[O:33]>O1CCCC1>[CH3:13][O:12][N:9]1[CH2:10][CH2:11][C:6]2([S:5][C:4](=[O:14])[C:3]([C:15]3[C:20]([CH3:21])=[CH:19][C:18]([CH3:22])=[CH:17][C:16]=3[CH3:23])=[C:2]2[O:1][C:32](=[O:33])[O:34][CH2:35][CH3:36])[CH2:7][CH2:8]1
Reactant: CON1CCC2(CC1)SC(=O)C(c1c(C)cc(C)cc1C)=C2O
Reactant: CCOC(=O)Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CCOC(=O)OC1=C(c2c(C)cc(C)cc2C)C(=O)SC12CCN(OC)CC2
Temperature: 25 °C
Reaction time: 18 h
Yield: 29.7 %

Procedure:
94 mg 4-Hydroxy-8-methoxy-3-(2,4,6-trimethyl-phenyl)-1-thia-8-aza-spiro[4.5]dec-3-en-2-one (from Step 7) and 43 mg triethylamine were dissolved in 10 ml tetrahydrofuran, and a solution of 32 mg ethyl chloroformate in 5 ml tetrahydrofuran was added dropwise. The mixture was stirred at ambient temperature for 18 hours, then partitioned between saturated aqueous sodium bicarbonate and t-butylmethyl ether, the organic layer dried over sodium sulfate, and the solvent evaporated. The residue was purified by chromatography on silica gel with ethylacetate/cyclohexane (1:2) as a solvent, to give 34 mg carbonic acid ethyl ester 8-methoxy-2-oxo-3-(2,4,6-trimethyl-phenyl)-1-thia-8-aza-spiro[4.5]dec-3-en-4-yl ester (title compound P1.7) as a solid, mp 87-89° C.
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2([C:15](Cl)=[O:16])[CH2:12][C:11]2([Cl:14])[Cl:13])=[CH:6][CH:5]=1.[O:20]([C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][C:34]=1[F:35])[CH:30]=[O:31])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[C-:36]#[N:37].[Na+].O>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.CCCCCC>[O:20]([C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][C:34]=1[F:35])[CH:30]([O:31][C:15]([C:10]1([C:7]2[CH:8]=[CH:9][C:4]([O:3][C:2]([F:19])([F:18])[F:1])=[CH:5][CH:6]=2)[CH2:12][C:11]1([Cl:14])[Cl:13])=[O:16])[C:36]#[N:37])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: O=C(Cl)C1(c2ccc(OC(F)(F)F)cc2)CC1(Cl)Cl
Reactant: [C-]#N
Reactant: O=Cc1ccc(F)c(Oc2ccccc2)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [Na+]
Solvent: CCCCCC
Solvent: O
Solvent: Cc1ccccc1
Product: N#CC(OC(=O)C1(c2ccc(OC(F)(F)F)cc2)CC1(Cl)Cl)c1ccc(F)c(Oc2ccccc2)c1
Yield: 76.2 %

Procedure:
5.67 g (0.017 mole) of (±)-1-(4-trifluoromethoxyphenyl)-2,2-dichlorocyclopropane-1-carboxylic acid chloride and 3.67 g (0.017 mole) of 3-phenoxy-4-fluoro-benzaldehyde were together added dropwise to a mixture of 1.13 g of sodium cyanide, 1.7 ml of water, 100 ml of n-hexane and 0.6 g of tetrabutylammonium bromide at 20°-25° C., while stirring, and the mixture was then stirred at 20° to 25° C. for 4 hours. 300 ml of toluene were then added to the reaction mixture and the mixture was extracted twice by shaking with 300 ml of water each time. The organic phase was separated off and dried over magnesium sulphate and the solvent was distilled off under a waterpump vacuum. Last residues of solvent were removed by brief incipient distillation at a bath temperature of 60° C./1 mm Hg. 7 g (76.3% of theory) of (±)-1-(4-trifluoromethoxy-phenyl)-2,2-dichlorocyclopropane-1-carboxylic acid 3-phenoxy-4-fluoro-(±)-α-cyano-benzyl ester were obtained as a yellow oil. The structure was confirmed by the 1H-NMR spectrum.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:33]=[CH:32][CH:31]=[CH:30][C:16]=1[CH2:17][O:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[CH2:25][C:26]([O:28]C)=[O:27].O1CCCC1.[OH-].[Na+].Cl>O.CO>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:33]=[CH:32][CH:31]=[CH:30][C:16]=1[CH2:17][O:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[CH2:25][C:26]([OH:28])=[O:27]
Reactant: COC(=O)Cc1ccccc1OCc1ccccc1OCc1nc(-c2ccccc2)oc1C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: Cc1oc(-c2ccccc2)nc1COc1ccccc1COc1ccccc1CC(=O)O
Temperature: 50 °C
Reaction time: 1.5 h
Yield: 90.2 %

Procedure:
To a mixture of methyl 2-[2-[2-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]benzyloxy]phenyl]acetate (0.71 g), tetrahydrofuran (3.0 mL) and methanol (3.0 mL) was added a 1N aqueous sodium hydroxide solution (3.2 mL) and the mixture was stirred at 50° C. for 1.5 hrs. 1N Hydrochloric acid (3.2 mL) and water were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated to give crystals (0.62 g, 90%) of 2-[2-[2-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]benzyloxy]phenyl]acetic acid. Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 145-146° C.
Reaction SMILES: [F:1][C:2]1[C:3]([NH:17][C:18]([C:20]2[N:24]([CH3:25])[N:23]=[CH:22][C:21]=2[C:26](O)=[O:27])=[O:19])=[CH:4][C:5]2[N:6]([N:8]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[N:10]=2)[CH:7]=1.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.CCCP(=O)=O.C(N(C(C)C)CC)(C)C>O1CCCC1>[F:1][C:2]1[C:3]([NH:17][C:18]([C:20]2[N:24]([CH3:25])[N:23]=[CH:22][C:21]=2[C:26]([N:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)=[O:27])=[O:19])=[CH:4][C:5]2[N:6]([N:8]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[N:10]=2)[CH:7]=1
Reactant: C1COCCN1
Reactant: Cn1ncc(C(=O)O)c1C(=O)Nc1cc2nc(-c3ccccc3)nn2cc1F
Agent: CCCP(=O)=O
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: Cn1ncc(C(=O)N2CCOCC2)c1C(=O)Nc1cc2nc(-c3ccccc3)nn2cc1F
Temperature: 70 °C
Reaction time: 60 h
Yield: 41.1 %

Procedure:
A mixture of 5-(6-fluoro-2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-ylcarbamoyl)-1-methyl-1H-pyrazole-4-carboxylic acid (138 mg, 363 μmol), morpholine (253 μl, 2.9 mmol), propylphosphonic anhydride (50% in ethyl acetate, 534 μl, 907 μmol) and diisopropylethylamine (190 μl, 1.09 mmol) in tetrahydrofuran (10 ml) was stirred for 2.5 days (weekend) at 70° C. under nitrogen atmosphere. The solvent was evaporated, the residue was triturated with saturated aqueous sodium hydrogencarbonate solution and the precipitated solid was filtered off and dried in vacuum. The crude material was applied on silica and purified by flash chromatography over a 20 g silica column using heptane/ethyl acetate 10-100% as eluent, affording 2-methyl-4-(morpholine-4-carbonyl)-2H-pyrazole-3-carboxylic acid (6-fluoro-2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-amide (67 mg, 41.1%) as white solid. Mp.: 224-225° C. MS: m/z=450.0 (M+H+).
Reaction SMILES: C([Li])CCC.[C:6]1([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[C:17]1([CH:23]([CH3:26])[CH:24]=[O:25])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.Cl>CCCCCC.O1CCCC1>[C:17]1([CH:23]([CH3:26])[CH:24]([C:14]2[S:13][C:12]([C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=3)=[CH:16][CH:15]=2)[OH:25])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: CC(C=O)c1ccccc1
Reactant: c1ccc(-c2cccs2)cc1
Agent: Cl
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CC(c1ccccc1)C(O)c1ccc(-c2ccccc2)s1
Temperature: -78 °C
Reaction time: 1.5 h
Yield: 96.2 %

Procedure:
Under a nitrogen atmosphere 13.7 mL of a 2.6M solution of n-butyllithium in n-hexane was added to a cold (-78° C.) stirred solution of 5.2 grams (0.0325 mole) of 2-phenylthiophene in 61 mL of tetrahydrofuran. This mixture was stirred at -78° C. for 1.5 hours. To this cold mixture was added 2-phenylpropionaldehyde (4.6 gram, 0.0336 mole), and the mixture was stirred for 15 minutes. The mixture was allowed to warm to room temperature and stir for two days. The mixture was cooled to 0° C., and approximately 45 mL of 1.2 N hydrochloric acid was added. The organic phase was separated from the aqueous phase and the aqueous phase, was extracted with chloroform. The chloroform extract was combined with the organic phase and washed with an aqueous, ammonium chloride solution. The washed organic phase was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure leaving a residue. This residue was purified by column chromatography on silica gel, eluting with ethyl acetate:n-hexane (10:90), to yield 9.2 g of 2-phenyl-1-(5-phenylthien-2-yl)-1-propanol as an oil.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:28]=[C:11]3[CH:12]=[C:13]([NH:16][C:17]([C:19]4[N:23]([CH3:24])[N:22]=[CH:21][C:20]=4[C:25](O)=[O:26])=[O:18])[CH:14]=[CH:15][N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:29][N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1>>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:28]=[C:11]3[CH:12]=[C:13]([NH:16][C:17]([C:19]4[N:23]([CH3:24])[N:22]=[CH:21][C:20]=4[C:25]([N:33]4[CH2:34][CH2:35][N:30]([CH3:29])[CH2:31][CH2:32]4)=[O:26])=[O:18])[CH:14]=[CH:15][N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: Cn1ncc(C(=O)O)c1C(=O)Nc1ccn2nc(-c3cccc(F)c3)nc2c1
Reactant: CN1CCNCC1
Product: CN1CCN(C(=O)c2cnn(C)c2C(=O)Nc2ccn3nc(-c4cccc(F)c4)nc3c2)CC1
Yield: 47.9 %

Procedure:
The product was prepared in the same manner as described in example 3 using 5-(2-(3-fluorophenyl)-[1,2,4]triazolo[1,5-a]pyridin-7-ylcarbamoyl)-1-methyl-1H-pyrazole-4-carboxylic acid (60 mg, 158 μmol) and 1-methylpiperazine (52.6 μl, 473 μmol) as starting materials. The reaction affords 2-methyl-4-(4-methyl-piperazine-1-carbonyl)-2H-pyrazole-3-carboxylic acid [2-(3-fluoro-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-7-yl]-amide (35 mg, 48%) as light grey solid. mp.: 224-227° C., MS: m/z=263.0 (M+H+).