Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[C:9]([CH2:13]O)[CH:10]=[CH:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[BrH:15]>>[C:1]1([C:7]2[CH:8]=[C:9]([CH2:13][Br:15])[CH:10]=[CH:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: OCc1cccc(-c2ccccc2)c1
Reactant: Br
Product: BrCc1cccc(-c2ccccc2)c1
Temperature: 0 °C

Procedure:
Under a nitrogen atmosphere a stirred solution of 12.9 grams of 3-phenylphenylmethanol in 50 mL of 47-49% hydrobromic acid was heated at reflux for two hours. Thin layer chromatographic analysis of the reaction mixture indicated that the reaction was incomplete. An additional 50 mL of 47-49% hydrobromic acid was added, and the stirred reaction mixture was heated at reflux for an additional two hours. After this time the reaction mixture was poured into ice-water, and the mixture was extracted with 100 mL of diethyl ether. The extract was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, yielding 16.2 grams of 3-phenylphenylmethyl bromide. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C@@H:11]([O:13][C:14]3[C:15]4[O:23][CH:22]=[C:21]([C:24]5[CH:25]=[N:26][N:27]([CH:29]6[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]6)[CH:28]=5)[C:16]=4[CH:17]=[N:18][C:19]=3[NH2:20])[CH3:12])=[N:9][N:10]=2)[N:7]=1.[C:35]1(B(O)O)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C([O-])([O-])=O.[K+].[K+].O1CCOCC1>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:35]1([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([C@@H:11]([O:13][C:14]4[C:15]5[O:23][CH:22]=[C:21]([C:24]6[CH:25]=[N:26][N:27]([CH:29]7[CH2:30][CH2:31][NH:32][CH2:33][CH2:34]7)[CH:28]=6)[C:16]=5[CH:17]=[N:18][C:19]=4[NH2:20])[CH3:12])=[N:9][N:10]=3)[N:7]=2)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1
Reactant: OB(O)c1ccccc1
Reactant: C[C@H](Oc1c(N)ncc2c(-c3cnn(C4CCNCC4)c3)coc12)c1nnc2ccc(Cl)nn12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: C[C@H](Oc1c(N)ncc2c(-c3cnn(C4CCNCC4)c3)coc12)c1nnc2ccc(-c3ccccc3)nn12
Temperature: 100 °C

Procedure:
A suspension of 7-[(S)-1-(6-Chloro[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethoxy]-3-(1-piperidin-4-yl-1H-pyrazol-4-yl)furo[3,2-c]pyridin-6-ylamine (0.289 mmol, 1 eq), phenylboronic acid (0.507 mmol, 2.7 eq), Pd(PPh3)4 (83.6 mg, 0.0723 mmol, 25 mol %), and K2CO3 (200.4 mg, 1.45 mmol, 5.0 eq) in a 4:1 ratio of dioxane (4 mL) to H2O (1 mL) was evacuated and charged with nitrogen several times. The reaction sample was then heated in a microwave reactor at 100° C. for 0.5 h. CH2Cl2 and H2O were added and a standard aqueous workup was performed. The crude material was purified by chromatography on an SCX column and HPLC giving the title compound as a diformate salt. 1H NMR (400 MHz, CD3OD): δ=2.18 (d, J=6.8 Hz, 3H), 2.24-2.40 (m, 4H), 3.18-3.27 (m, 2H), 3.59 (dt, J=12.8, 3.3 Hz, 2H), 4.59 (dddd, J=10.0, 5.1, 4.9 Hz, 1H), 6.42 (q, J=6.7 Hz, 1H), 7.38-7.50 (m, 3H), 7.73-7.83 (m, 4H), 7.88 (d, J=9.9 Hz, 1H), 8.01 (s, 1H), 8.05 (s, 1H), 8.25 (d, J=9.9 Hz, 1H), 8.35 (br s, 2H). MS (ES+): m/z 522.20 (20) [MH+]. HPLC: tR=2.12 min (ZQ3, polar—5 min).
Reaction SMILES: [ClH:1].Cl.C(NC1CNC1)C.Cl.Cl.C([N:25]1[CH2:28][CH:27]([NH:29][CH:30]2[CH2:32][CH2:31]2)[CH2:26]1)(C1C=CC=CC=1)C1C=CC=CC=1>>[ClH:1].[ClH:1].[CH:30]1([NH:29][CH:27]2[CH2:28][NH:25][CH2:26]2)[CH2:32][CH2:31]1
Reactant: c1ccc(C(c2ccccc2)N2CC(NC3CC3)C2)cc1
Agent: CCNC1CNC1
Agent: Cl
Product: C1CC1NC1CNC1

Procedure:
3-(Cyclopropylamino)azetidine dihydrochloride was prepared under the conditions described in Example 9 for 3-(ethylamino)azetidine dihydrochloride, but starting with 5.4 g of 1-benzhydryl-3-(cyclopropylamino)azetidine dihydrochloride. 2.25 g of 3-(cyclopropylamino)azetidine dihydrochloride are obtained in the form of a colorless solid, melting point 140° C.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]([CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:7](=[O:13])[NH:8]2)([O-])=O>CO.[Pd]>[NH2:1][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]([CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:7](=[O:13])[NH:8]2
Reactant: CCOC(=O)CC1C(=O)Nc2cccc([N+](=O)[O-])c21
Agent: [Pd]
Solvent: CO
Product: CCOC(=O)CC1C(=O)Nc2cccc(N)c21
Reaction time: 16 h

Procedure:
A mixture of (±)-ethyl (4-nitro-2-oxo-2,3-dihydro-1H-indol-3-yl)acetate from Step A (2.56 g, 9.69 mmol) and 10% Pd/C (500 mg) was stirred vigorously in MeOH (50 mL) under an atmosphere of hydrogen (ca. 1 atm). After 16 h, the mixture was filtered through a pad of Celite, washing with MeOH, and the filtrate was concentrated in vacuo to give the title compound. MS: m/z=235 (M+1).
Reaction SMILES: [NH2:1][C:2]1[CH:6]=[C:5]([C:7]([CH3:10])([CH3:9])[CH3:8])[NH:4][N:3]=1.C(N(CC)CC)C.[CH3:18][N:19]([CH3:23])[C:20](Cl)=[O:21]>C(Cl)Cl>[CH3:18][N:19]([CH3:23])[C:20]([NH:1][C:2]1[CH:6]=[C:5]([C:7]([CH3:10])([CH3:9])[CH3:8])[NH:4][N:3]=1)=[O:21]
Reactant: CC(C)(C)c1cc(N)n[nH]1
Reactant: CN(C)C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CN(C)C(=O)Nc1cc(C(C)(C)C)[nH]n1
Yield: 32 %

Procedure:
4.2 g of Compound [II] and 3.2 g of triethylamine were dissolved in 50 ml of methylene chloride, and 3.2 g of N,N-dimethylcarbamoyl chloride was added to the solution. The mixture was heated under refluxing and cooled, followed by washing with water. The organic layer was collected, and the solvent was distilled off. The residue was solidified by the addition of a mixed solvent of hexane and benzene. The solid obtained was collected by filtration and dried to obtain 2.0 g of N,N-dimethyl N'-(5-t-butyl-3-pyrazolyl)urea. This compound was recrystallized from hydrous methanol and found to have a melting point of 220° C. to 222° C.
Reaction SMILES: [C:1]1([P:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.ClCCCl.NC1C=CC=CC=1N.C(=O)C1C(=CC=CC=1)[OH:35]>[Co].N1C=CC=CC=1>[C:14]1([P:7](=[O:35])([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: O=Cc1ccccc1O
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Agent: [Co]
Agent: Nc1ccccc1N
Solvent: c1ccncc1
Solvent: ClCCCl
Product: O=P(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 60 °C
Reaction time: 18 h

Procedure:
81.7 mg. (0.164 mmol) of cobalt (saloph) pyridine nitro complex and 187 mg. (0.713 mmol) of triphenylphosphine were dissolved in 20 ml. of 1,2-dichloroethane together with 0.5 ml. of pyridine. (The saloph ligand is the tetradentate ligand [1,2-(ortho-OC6H4CH=N)2C6H4 ]2- obtained by condensation reaction of o-diaminobenzene with salicylaldehyde). The resulting solution was stirred under an oxygen atmosphere for 18 hours at 60° C. The resulting reaction product was analyzed by infrared spectroscopy showing a quantitative yield of triphenylphosphine oxide, i.e. 0.713 mmol. This example is illustrative of catalytic oxidation by a cobalt nitro complex having a tetradentate ligand and a monodentate basic ligand in accordance with this invention.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH:12]([NH:19][C:20](=O)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]>P(Cl)(Cl)(Cl)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:6](=[CH:7][C:8]=1[O:9][CH3:10])[C:20]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[N:19][CH:12]([C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1)[CH2:11]2
Reactant: COc1ccc(CC(NC(=O)c2ccccc2)c2cccnc2)cc1OC
Solvent: O=P(Cl)(Cl)Cl
Product: COc1cc2c(cc1OC)C(c1ccccc1)=NC(c1cccnc1)C2
Yield: 93.5 %

Procedure:
1.8 g of N-[2-(3,4-dimethoxyphenyl)-1-(3-pyridyl)ethyl]benzamide in 20 ml of phosphorus oxychloride are stirred at 60° C. for 5 hours and at 120° C. for 1.5 hours. The yellow precipitate is filtered off with suction, dissolved in 200 ml of water, and the solution is made alkaline with potassium carbonate and extracted twice with methylene chloride. 1.6 g of dihydroisoquinoline compound of melting point 180°-182° C. are isolated.
Reaction SMILES: IC1SC(C(=O)C)=CC=1.[C:10]([C:12]1[S:16][C:15]([C:17](=[O:19])[CH3:18])=[CH:14][CH:13]=1)#[N:11]>>[C:17]([C:15]1[S:16][C:12]([CH2:10][NH2:11])=[CH:13][CH:14]=1)(=[O:19])[CH3:18]
Reactant: CC(=O)c1ccc(C#N)s1
Agent: CC(=O)c1ccc(I)s1
Product: CC(=O)c1ccc(CN)s1

Procedure:
Starting with the readily available compound, denoted 2, 5-iodo-2-acetylthiophene ##STR2## and using a procedure described by S. Nishimura and E. Imoto, Nippon Kagaku Zasshi 82, 1411 (1961), incorporated by reference herein, one generates 5-cyano-2-acetylthiophene denoted 3 below, ##STR3## The "blocked" form is then generated according to standard methods. See for example W. S. Johnson et al., J. Amer. Chem. Soc. 78, 6300, (1956), incorporated by reference herein. This results in a compound, denoted 4 below, ##STR4## Compound 4 is then reduced with available methods such as the one described by R. F. Nystrom and W. G. Brown, J. Amer. Chem. Soc. 70, 3738 (1948), incorporated by reference herein, and then "deblocked" (see for example W. S. Johnson et al. above) to give 2-acetyl-5-(aminomethyl)thiophene, 5,: ##STR5## Then using standard Claisen condensation techniques, such as described by J. C. Reid and M. Calvin, J. Amer. Chem. Soc. 72, 2948 (1950), incorporated by reference herein, the chelating ligand 1 is synthesized, abbreviated hereafter as TTFA-NH2.
Reaction SMILES: C1O[C:4]2([CH:8](OS(C)(=O)=O)[CH2:7][C:6]3([CH2:18][CH2:17][C:16](=[O:19])[CH2:15][CH2:14]3)[N:5]2[CH3:20])[O:3]C1.[I-].[Na+].CC(C)=O.Cl>C(O)(=O)C.O>[CH3:20][N:5]1[C:6]2([CH2:18][CH2:17][C:16](=[O:19])[CH2:15][CH2:14]2)[CH2:7][CH2:8][C:4]1=[O:3]
Reactant: CN1C2(CCC(=O)CC2)CC(OS(C)(=O)=O)C12OCCO2
Agent: Cl
Agent: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: CC(=O)O
Solvent: O
Product: CN1C(=O)CCC12CCC(=O)CC2
Temperature: 110 °C
Reaction time: 1.5 h

Procedure:
A mixture of 3-Mesyloxy-1-methyl-1-azaspiro[4.5]decane-2,8-dione ethylene ketal (1.28 g), sodium iodide (1.8 g) and acetone (20 mL) was refluxed with stirring for 90 min. The solvent was removed in vacuo and the residue was dissolved in methylene chloride and washed with water. After drying over magnesium sulfate the solvent was removed in vacuo. The residue was dissolved in toluene (20 mL) and treated with tri-n-butyltin hydride (1.75 g) and AIBN (20 mg) and the resulting mixture was heated at 110° C. for 1 h. After removal of the solvent the residue was chromatographed on silica gel with ethyl acetate as the eluent. The resulting produce was stirred with a mixture of water (5 mL), 3N HCl (1.5 mL) and acetic acid (2 mL) for 16 h. The resulting product was extracted 3 times with methylene chloride, washed with sodium bicarbonate solution, dried over magnesium sulfate and the solvent was removed in vacuo to afford 1 -Methyl-1-azaspiro[4.5]decane-2,8-dione as an oil.
Reaction SMILES: [C:1]([O:4][CH2:5][C@H:6]([N:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH:21]3[CH2:23][CH2:22]3)[C:14]=2[N+:18]([O-])=O)[C:9]1=[O:24])[CH3:7])(=[O:3])[CH3:2].C(O)C>[Pd]>[C:1]([O:4][CH2:5][C@H:6]([N:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH:21]3[CH2:22][CH2:23]3)[C:14]=2[NH2:18])[C:9]1=[O:24])[CH3:7])(=[O:3])[CH3:2]
Reactant: CC(=O)OC[C@@H](C)n1ccc2c([N+](=O)[O-])c(C3CC3)ccc2c1=O
Agent: [Pd]
Solvent: CCO
Product: CC(=O)OC[C@@H](C)n1ccc2c(N)c(C3CC3)ccc2c1=O
Reaction time: 2 h

Procedure:
A round bottom flask was charged with (R)-2-(6-cyclopropyl-5-nitro-1-oxoisoquinolin-2(1H)-yl)propyl acetate (28 mg, 0.000085 mol), ethanol (10 mL, 0.2 mol) and palladium, 10% weight on charcoal (1.0 mg, 0.0000085 mol) was added. The flask was evacuated and flushed with hydrogen two times and the reaction was stirred under hydrogen (1 atm) for 2 hours. The reaction was filtered over celite and the solvent was removed to afford the product.
Reaction SMILES: C(N(CC)CC)C.[OH:8][CH:9]1[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:10]1.S(=O)(=O)=O.N1C=CC=CC=1>CS(C)=O>[O:8]=[C:9]1[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:10]1
Reactant: CC(C)(C)OC(=O)N1CC(O)C1
Agent: O=S(=O)=O
Solvent: c1ccncc1
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: CC(C)(C)OC(=O)N1CC(=O)C1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 100.7 %

Procedure:
Triethylamine (2.47 mL) was added to a solution of tert-butyl 3-hydroxyazetidine-1-carboxylate (0.5 g, 2.9 mmol) in DMSO (5 mL). To this mixture, a solution of pyridine sulphur trioxide (1.8 g, 11.3 mmol) in DMSO (6.5 mL) was added drop-wise and the mixture was stirred at room temperature for 1.5 hrs. The mixture was poured onto ice-water and extracted with ethyl acetate (3×50 mL), organics combined dried with sodium sulfate, filtered and concentrated to afford tert-butyl 3-oxoazetidine-1-carboxylate as white solid (500 mg, 100%). 1H NMR (300 MHz, CDCl3): δ 4.68 (s, 4H), 1.48 (s, 9H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12](C(C)OCC)[CH:11]=[N:10][C:9]=2[C:18]2[CH:23]=[CH:22][C:21]([S:24][CH3:25])=[CH:20][CH:19]=2)=[CH:4][CH:3]=1.CN(C)CCN(C)C.C([Li])CCC.CN(C)[CH:41]=[O:42]>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[NH:12][C:11]([CH:41]=[O:42])=[N:10][C:9]=2[C:18]2[CH:23]=[CH:22][C:21]([S:24][CH3:25])=[CH:20][CH:19]=2)=[CH:6][CH:7]=1
Reactant: CN(C)C=O
Reactant: CCOC(C)n1cnc(-c2ccc(SC)cc2)c1-c1ccc(F)cc1
Agent: CN(C)CCN(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CSc1ccc(-c2nc(C=O)[nH]c2-c2ccc(F)cc2)cc1
Temperature: -70 °C
Reaction time: 0.25 h
Yield: 80 %

Procedure:
A solution of the compound from step 2 (500 mg, 1.4 mmol) and tetramethylethylenediamine (TMEDA) (186 mg, 1.6 mmol) in tetrahydrofuran (8 ml) was cooled to −70° C. under an argon atmosphere. n-Butyllithium (1.2 ml of 1.6M solution in hexane, 1.9 mmol) was added and the solution stirred at −70° C. for 15 minutes. Dimethylformamide (DMF) (140 mg, 1.9 mmol) was added and the solution was warmed to 0° C. The reaction was quenched by the addition of saturated NaHCO3 solution (2 ml) and extracted with diethyl ether. The organic phase was separated and dried (Na2SO4). The drying agent was filtered and the filtrate concentrated in vacuo. The residue was treated with 2N HCl (5 ml) in EtOH (10 ml) at room temperature for 24 hours. The reaction solution was made basic with NaHCO3, diluted with water (20 ml) and extracted with methylene chloride. After evaporation, the residue was purified by chromatography on silica gel, eluting with toluene/methanol (90/10), to give 350 mg (70%) of titled compound which was used immediately without further purification.
Reaction SMILES: Br[C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([C:16]4[C:17]([F:22])=[N:18][CH:19]=[CH:20][CH:21]=4)=[CH:9][CH:10]=3)[C@@:5]3([CH2:26][O:25][C:24]([NH2:27])=[N:23]3)[C:4]=2[CH:3]=1.[CH3:28][C:29]1[CH:33]=[C:32]([Sn](CCCC)(CCCC)CCCC)[O:31][N:30]=1.CC(N)CC1C=CC=CC=1.OP(O)(O)=O>>[F:22][C:17]1[C:16]([C:8]2[CH:9]=[CH:10][C:11]3[O:12][C:13]4[C:4](=[CH:3][C:2]([C:32]5[O:31][N:30]=[C:29]([CH3:28])[CH:33]=5)=[CH:15][CH:14]=4)[C@:5]4([CH2:26][O:25][C:24]([NH2:27])=[N:23]4)[C:6]=3[CH:7]=2)=[CH:21][CH:20]=[CH:19][N:18]=1
Reactant: NC1=N[C@]2(CO1)c1cc(Br)ccc1Oc1ccc(-c3cccnc3F)cc12
Reactant: CCCC[Sn](CCCC)(CCCC)c1cc(C)no1
Agent: CC(N)Cc1ccccc1
Agent: O=P(O)(O)O
Product: Cc1cc(-c2ccc3c(c2)[C@]2(COC(N)=N2)c2cc(-c4cccnc4F)ccc2O3)on1
Temperature: 100 °C

Procedure:
A resealable was charged with (S)-2′-bromo-7′-(2-fluoropyridin-3-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine (300 mg, 0.704 mmol), 3-methyl-5-(tributylstannyl)isoxazole (786 mg, 2.111 mmol), amphos (18.68 mg, 0.070 mmol) and argon purged dry dioxane (3 mL). The tube was purged with argon, sealed and heated with microwave at 100° C. for 1 h. The solution was concentrated. The crude product was purified via silica gel column chromatography (RediSep 12 g column) using 10-50% 90/10/1 DCM/MeOH/ammonia in DCM to afford (S)-2′-(2-fluoropyridin-3-yl)-7′-(3-methylisoxazol-5-yl)-5H-spiro[oxazole-4,9′-xanthen]-2-amine as a white solid. MS m/z=429.2 [M+H]+. Calcd for C24H17FN4O3: 428.42.
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[C:9]([CH:14]=[CH:15][N:16]=2)[C:10]([O:12][CH3:13])=[O:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>C(O)(=O)C.[Pt](=O)=O>[C:1]1([CH:7]2[CH2:8][CH:9]([C:10]([O:12][CH3:13])=[O:11])[CH2:14][CH2:15][NH:16]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: COC(=O)c1ccnc(-c2ccccc2)c1
Agent: O=[Pt]=O
Solvent: CC(=O)O
Product: COC(=O)C1CCNC(c2ccccc2)C1
Reaction time: 2.5 h
Yield: 113.3 %

Procedure:
Methyl 2-phenylisonicotinate (1.83 g, 8.58 mmol) was dissolved in acetic acid (20 mL) and platinum(IV) oxide (0.097 g, 0.43 mmol) added. The resulting mixture was hydrogenated in a Büchi hydrogenator at room temperature and 5 bar for 2.5 h. The catalyst was filtered off and washed with MeOH and the eluate evaporated. DCM and 10% K2CO3 were added and the phases separated. The water phase was extracted with DCM and the combined organic phase washed with brine, passed through a phase separator and evaporated to yield crude methyl 2-phenylpiperidine-4-carboxylate (2.131 g) as a yellow oil. MS m/z 220 (M+H)+
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH:4]([CH2:7][NH:8][C:9]([C:11]2[C:12]([C:18]([F:21])([F:20])[F:19])=[N:13][C:14](Cl)=[N:15][CH:16]=2)=[O:10])[CH2:3][CH2:2]1.[F:22][C:23]([F:33])([F:32])[C:24]1[CH:30]=[C:29]([Br:31])[CH:28]=[CH:27][C:25]=1[NH2:26]>>[O:1]1[CH2:6][CH2:5][CH:4]([CH2:7][NH:8][C:9]([C:11]2[C:12]([C:18]([F:21])([F:20])[F:19])=[N:13][C:14]([NH:26][C:25]3[CH:27]=[CH:28][C:29]([Br:31])=[CH:30][C:24]=3[C:23]([F:33])([F:22])[F:32])=[N:15][CH:16]=2)=[O:10])[CH2:3][CH2:2]1
Reactant: Nc1ccc(Br)cc1C(F)(F)F
Reactant: O=C(NCC1CCOCC1)c1cnc(Cl)nc1C(F)(F)F
Product: O=C(NCC1CCOCC1)c1cnc(Nc2ccc(Br)cc2C(F)(F)F)nc1C(F)(F)F

Procedure:
2-Chloro-4-trifluoromethyl-pyrimidin-5-carboxylic acid (tetrahydro-pyran-4-ylmethyl)-amide (80 mg) in 2-trifluoromethyl-4-bromoaniline (0.5 ml) was heated at 190° C. under microwave irradiation for 20 minutes. The sample was purified by mass directed auto-purification to afford the title compound (21 mg).
Reaction SMILES: [C:1]1([S:7][C:8]2[CH:9]=[C:10]([CH:13]=[CH:14][CH:15]=2)[CH:11]=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[BH4-].[Na+].O>C(O)C>[C:1]1([S:7][C:8]2[CH:9]=[C:10]([CH2:11][OH:12])[CH:13]=[CH:14][CH:15]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=Cc1cccc(Sc2ccccc2)c1
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: OCc1cccc(Sc2ccccc2)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 68 %

Procedure:
3-Phenylsulfanyl-benzaldehyde described in Preparation Example 92 (321 mg, 1.49 mmol) was dissolved in ethanol (6 mL), sodium borohydride (113 mg, 2.98 mmol) was added thereto at 0° C., followed by stirring at room temperature for 3 hours. Water was added to the reaction solution, which was then extracted with ethyl acetate, the organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo, the residue was purified by silica gel column chromatography (hexane:ethyl acetate=5:1), and the title compound (220 mg, 1.02 mmol, 68%) was obtained as a colorless oil.
Reaction SMILES: [B-](F)(F)(F)F.[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+]([F:21])(CC2)C1.[F:22][C:23]1[CH:24]=[C:25]2[C:29](=[C:30]([F:32])[CH:31]=1)[C:28](=[O:33])[CH2:27][CH2:26]2>CO>[F:21][CH:27]1[CH2:26][C:25]2[C:29](=[C:30]([F:32])[CH:31]=[C:23]([F:22])[CH:24]=2)[C:28]1=[O:33]
Reactant: O=C1CCc2cc(F)cc(F)c21
Reactant: F[N+]12CC[N+](CCl)(CC1)CC2
Agent: F[B-](F)(F)F
Solvent: CO
Product: O=C1c2c(F)cc(F)cc2CC1F
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Selectfluor™ (1.16 g, 3.27 mmol) was added to a solution of 5,7-difluoro-1-indanone (CAS No. 84315-25-3, 500 mg, 2.97 mmol) in MeOH (20 mL) at room temperature. The mixture was refluxed for 2 hours and cooled to room temperature. Then the solvent was distilled off under reduced pressure. The residue was treated with DCM and the insoluble matter was filtered off. Then the solvent was distilled off under reduced pressure. The residue was dissolved in MeCN (10 mL) and 5 N HCl (5 mL). The solution was stirred at room temperature for 1 hour, and then concentrated in vacuo. The residue was partitioned between AcOEt and H2O. The organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo to afford the title compound (547 mg, 2.94 mmol). 1H NMR (400 MHz, CDCl3)
Reaction SMILES: Cl[Si:2]([CH3:13])([CH3:12])[CH:3]1[C:7]([CH3:8])=[C:6]([CH3:9])[C:5]([CH3:10])=[C:4]1[CH3:11].[C:14]([NH-:18])([CH3:17])([CH3:16])[CH3:15].[Li+]>O1CCCC1>[C:14]([NH:18][Si:2]([CH:3]1[C:7]([CH3:8])=[C:6]([CH3:9])[C:5]([CH3:10])=[C:4]1[CH3:11])([CH3:13])[CH3:12])([CH3:17])([CH3:16])[CH3:15]
Reactant: CC(C)(C)[NH-]
Reactant: CC1=C(C)C([Si](C)(C)Cl)C(C)=C1C
Agent: [Li+]
Solvent: C1CCOC1
Product: CC1=C(C)C([Si](C)(C)NC(C)(C)C)C(C)=C1C
Reaction time: 2 h
Yield: 81 %

Procedure:
2,3,4,5-tetramethylcyclopenta-2,4-diene (3.67 g, 30 mmol) was added into a flask containing tetrahydrofuran (100 mL), n-butyl lithium (12 mL) was added in droplets thereto at 0° C., and the reaction temperature was gradually increased to room temperature so that the reaction was carried out for 8 hours. This solution was cooled to −78° C., dichloromethylsilane (3.87g, 30 mmol) was slowly added in droplets thereto, and then the reaction was carried out for 12 hours. After the reaction, the volatile material was removed, and the resultant product was extracted with hexane (100 mL), after which the volatile material was removed, thereby obtaining as pale yellow oil 5.5 g of (chloro) (dimethyl) (2,3,4,5-tetramethylcyclopentadienyl)silane. The (chloro)(dimethyl)(2,3,4,5-tetramethylcyclopentadienyl)silane thus obtained was dissolved in tetrahydrofuran (100 mL) without additional purification, after which lithium tert-butylamide (2.02 g) was added in droplets thereto at 0° C. and the reaction was carried out at room temperature for 2 hours. After the reaction, the volatile material was removed, and the resultant product was extracted with hexane (100 mL), thus obtaining as pale yellow oil 6.09 g (yield 81%) of (tert-butylamino) (2,3,4,5-tetramethylcyclopenta-2,4-dienyl)dimethylsilane.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[O:7]1[CH2:11][CH2:10][CH2:9][CH:8]1[C:12](O)=[O:13]>>[O:7]1[CH2:11][CH2:10][CH2:9][CH:8]1[C:12]([N:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1)=[O:13]
Reactant: O=C(O)C1CCCO1
Reactant: C1CNCCN1
Product: O=C(C1CCCO1)N1CCNCC1
Temperature: 25 °C
Yield: 45.6 %

Procedure:
A suspension of piperazine (7.23 g, 0.084 mol) in xylenes (50 mL) was added tetrahydro 2-furanoic acid (4.85 g, 0.042 mol). The mixture was heated to reflux for 28 hours. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated to give 3.53 g of product (46% yield).
Reaction SMILES: [CH2:1]=[CH:2][CH:3]([OH:11])[CH2:4][CH2:5][CH2:6][CH:7]([OH:10])[CH2:8][CH3:9].C1(C=CC(O)=CC=1)O>ClCCCl.[O-2].[O-2].[Mn+4]>[OH:11][CH:3]([CH2:2][CH3:1])[CH2:4][CH2:5][CH2:6][C:7](=[O:10])[CH:8]=[CH2:9]
Reactant: C=CC(O)CCCC(O)CC
Agent: [Mn+4]
Agent: Oc1ccc(O)cc1
Agent: [O-2]
Solvent: ClCCCl
Product: C=CC(=O)CCCC(O)CC
Reaction time: 1 h
Yield: 70.1 %

Procedure:
To a solution of 25 grams of 1-nonene-3,7-diol in 1,250 milliliters of 1,2-dichloroethane was added 0.25 gram of hydroquinone and 300 grams of manganese dioxide. The resulting slurry was stirred vigorously for 1 hour without heating, during which time the reaction temperature rose to about 30°C. The resulting reaction mixture was filtered and the manganese dioxide filter cake was washed thoroughly with 500 milliliters of 1,2-dichloroethane. The combined filtrates were evaporated in vacuo at 40°C. to yield 17.3 grams of 7-hydroxy-1-nonen-3-one. This compound is reacted with hydrogen chloride to produce 1-chloro-7-hydroxynonan-3-one, with dimethylamine to produce 1-(N,N-dimethylamino)-7-hydroxy-nonan-3-one, with water to produce 1,7-dihydroxynonan-3-one, or with ethanol to produce 1-ethoxy-7-hdyroxynonan-3-one.