Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][N:3]=1.F[C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][CH:11]=1.C([O-])([O-])=O.[Cs+].[Cs+].O>CN1CCCC1>[N+:16]([C:13]1[CH:14]=[CH:15][C:10]([O:8][C:6]2[CH:5]=[CH:4][NH:3][C:2](=[O:1])[CH:7]=2)=[CH:11][CH:12]=1)([O-:18])=[O:17]
Reactant: Oc1ccnc(O)c1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Agent: CN1CCCC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Product: O=c1cc(Oc2ccc([N+](=O)[O-])cc2)cc[nH]1
Temperature: 100 °C
Reaction time: 3 h

Procedure:
A suspension of 2,4-dihydroxy-pyridine (2.33 g, 21 mmol), 4-fluoro-nitrobenzene (2.22 ml, 21 mmol) and Cs2CO3 (10.2 g, 31.3 mmol) in N-methyl-pyrrolidine (30 ml) is stirred for 3 h at 100° C. under N2-atmosphere. The reaction mixture is poured into water and the precipitate filtered off and washed with water. The solid is dissolved in CH2Cl2/MeOH. Then SiO2 (≈20 g) is added and the mixture Is concentrated in vacuo. The resulting powder is put on top of a SiO2-column and eluted with toluene/AcOEt 3:1→AcOEt→AcOEt/EtOH 9:1, yielding the title compound: m.p.: 227-228° C.; 1H-NMR (DMSO-d6): 11.60 (s, HN), 8.31 (d, 2H), 7.47 (d, 1H), 7.39 (d, 2H), 6.07 (dd, 1H), 5.67 (d, 1H).
Reaction SMILES: FC1C=C(CN)C=[N:6]C=1.[CH3:10][N:11]1[CH:15]=[C:14]([CH3:16])[CH:13]=[N:12]1.[CH2:17]([N:21]1[CH2:25][CH2:24][N:23]([C:26]2[S:27][C:28]([C:32](O)=[O:33])=[C:29]([CH3:31])[N:30]=2)[C:22]1=[O:35])[CH:18]([CH3:20])[CH3:19]>>[CH2:17]([N:21]1[CH2:25][CH2:24][N:23]([C:26]2[S:27][C:28]([C:32]([NH:6][CH2:16][C:14]3[CH:13]=[N:12][N:11]([CH3:10])[CH:15]=3)=[O:33])=[C:29]([CH3:31])[N:30]=2)[C:22]1=[O:35])[CH:18]([CH3:20])[CH3:19]
Reactant: Cc1nc(N2CCN(CC(C)C)C2=O)sc1C(=O)O
Reactant: Cc1cnn(C)c1
Reactant: NCc1cncc(F)c1
Product: Cc1nc(N2CCN(CC(C)C)C2=O)sc1C(=O)NCc1cnn(C)c1
Yield: 58 %

Procedure:
Following the procedure as describe in Example 12, making variations as required to replace (5-fluoropyridin-3-yl)methanamine with (1-methyl-1H-pyrazol-4-yl)methane to react with 2-(3-isobutyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid in place of 2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid, the title compound was obtained as a colorless solid in 58% yield: mp 155-158° C. (dichloromethane/hexanes); 1H NMR (300 MHz, CDCl3) δ 7.43 (s, 1H), 7.37 (s, 1H), 5.80-5.77 (m, 1H), 4.39 (d, J=5.3 Hz, 2H), 4.12-4.07 (m, 2H), 3.87 (s, 3H), 3.60-3.55 (m, 2H), 3.11 (d, J=7.4 Hz, 2H), 2.60 (s, 3H), 1.96-1.87 (m, 1H), 0.93 (d, J=7.4 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 162.3, 157.4, 155.6, 152.8 152.6, 138.6, 129.4, 118.3, 117.0, 51.5, 42.8, 41.9, 38.8, 34.3, 26.7, 19.9, 17.1; MS (ES+) m/z 377.1 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([S:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]2[CH:16]=[CH:17][C:18]3[NH:23][C:22](=[O:24])[O:21][C:20]([CH2:27][CH3:28])([CH2:25][CH3:26])[C:19]=3[CH:29]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[OH:30]O>>[Cl:1][C:2]1[CH:3]=[C:4]([S:9]([CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]2[CH:16]=[CH:17][C:18]3[NH:23][C:22](=[O:24])[O:21][C:20]([CH2:25][CH3:26])([CH2:27][CH3:28])[C:19]=3[CH:29]=2)=[O:30])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: CCC1(CC)OC(=O)Nc2ccc(OCCCCSc3ccc(Cl)c(Cl)c3)cc21
Reactant: OO
Product: CCC1(CC)OC(=O)Nc2ccc(OCCCCS(=O)c3ccc(Cl)c(Cl)c3)cc21

Procedure:
Prepared analogously to Example 2 from 6-[4-(3,4-dichloro-phenylmercapto)-butoxy]-4,4-diethyl-4H-3,1-benzoxazin-2-one and hydrogen peroxide.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)=O)=[CH:4][C:3]=1[O:15][CH3:16].CO>O1CCCC1>[CH3:16][O:15][C:3]1[CH:4]=[C:5]([CH2:8][N:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:6]=[CH:7][C:2]=1[NH2:1]
Reactant: COc1cc(C(=O)N2CCCC2)ccc1N
Solvent: C1CCOC1
Solvent: CO
Product: COc1cc(CN2CCCC2)ccc1N
Temperature: 60 °C
Reaction time: 4 h

Procedure:
To a solution of the product of Example 49A (220 mg, 3.64 mmol) in tetrahydrofuran (20 mL) at 0° C. was added borane tetrahydrofuran complex (18 mL, 18 mmol) and the mixture was stirred at 0° C. for 2 hours and at 60° C. for 4 hours. After cooling to ambient temperature, methanol (20 mL) was added and stirring was continued for 30 minutes. The organic phase was concentrated and the residue was purified via preparative HPLC using a gradient of 10/90 to 80/20 acetonitrile/water (containing 0.1% trifluoroacetic acid) to give the title compound. MS: 207 (M+H+).
Reaction SMILES: [Cl-:1].[Cl-].[Cl-].[Cl-].[Hf+4:5].[C:6]1([CH:12]([CH2:16][CH3:17])[C:13]([OH:15])=[O:14])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>C1(C)C=CC=CC=1.[Hf]>[C:6]1([CH:12]([CH2:16][CH3:17])[C:13]([O-:15])=[O:14])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[Cl-:1].[Hf+2:5]
Reactant: [Hf+4]
Reactant: CCC(C(=O)O)c1ccccc1
Agent: [Hf]
Agent: [Cl-]
Solvent: Cc1ccccc1
Product: CCC(C(=O)[O-])c1ccccc1
Product: [Hf+2]

Procedure:
16.4 g (51.1 mmoles) of hafnium tetrachloride (HfCl4) are suspended in 200 ml of toluene in a stirred 500 ml reactor. 16.8 g (102.2 mmoles) of 2-phenylbutyric acid dissolved in 100 ml of toluene, with a molar ratio 2-phenylbutyric acid/HfCl4 of 2.0, are added, under stirring, to the suspension, kept at room temperature. At the end of the addition, nitrogen is bubbled in for 3 hours, at room temperature, to facilitate the removal of hydrochloric acid. After this period, the suspension is filtered while hot and a solution is obtained which shows the following analysis: Hf=812 mmoles/l, Cl=1476 mmoles/l, with an atomic ratio Cl/Hf of 1.8. The yield in hafnium in solution is equal to 95.1% with respect to the initial hafnium.
Reaction SMILES: [CH3:1][O:2][CH2:3][C@H:4]([CH3:52])[CH2:5][O:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C@@H:14]2[C@@H:19]([O:20][CH2:21][C:22]3[CH:23]=[CH:24][C:25]4[O:30][CH2:29][CH2:28][N:27]([CH2:31][CH2:32][CH2:33][O:34][CH3:35])[C:26]=4[CH:36]=3)[CH2:18][N:17]([S:37]([C:40]3[CH:45]=[CH:44][C:43]([CH3:46])=[CH:42][CH:41]=3)(=[O:39])=[O:38])[C@@H:16]([CH2:47][C:48]([NH2:51])([CH3:50])[CH3:49])[CH2:15]2)=[CH:10][CH:9]=1.CCN(CC)CC.[C:60](Cl)(=[O:62])[CH3:61]>C(Cl)Cl.O>[CH3:1][O:2][CH2:3][C@H:4]([CH3:52])[CH2:5][O:6][CH2:7][C:8]1[CH:9]=[CH:10][C:11]([C@@H:14]2[C@@H:19]([O:20][CH2:21][C:22]3[CH:23]=[CH:24][C:25]4[O:30][CH2:29][CH2:28][N:27]([CH2:31][CH2:32][CH2:33][O:34][CH3:35])[C:26]=4[CH:36]=3)[CH2:18][N:17]([S:37]([C:40]3[CH:41]=[CH:42][C:43]([CH3:46])=[CH:44][CH:45]=3)(=[O:39])=[O:38])[C@@H:16]([CH2:47][C:48]([NH:51][C:60](=[O:62])[CH3:61])([CH3:49])[CH3:50])[CH2:15]2)=[CH:12][CH:13]=1
Reactant: COCCCN1CCOc2ccc(CO[C@H]3CN(S(=O)(=O)c4ccc(C)cc4)[C@@H](CC(C)(C)N)C[C@@H]3c3ccc(COC[C@@H](C)COC)cc3)cc21
Reactant: CC(=O)Cl
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: COCCCN1CCOc2ccc(CO[C@H]3CN(S(=O)(=O)c4ccc(C)cc4)[C@@H](CC(C)(C)NC(C)=O)C[C@@H]3c3ccc(COC[C@@H](C)COC)cc3)cc21
Reaction time: 1 h

Procedure:
To a solution of 1.0 mmol of 2-[(2R,4R,5R)-4-[4-((S)-3-methoxy-2-methyl-propoxymethyl)-phenyl]-5-[4-(3-methoxy-propyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-1-(toluene-4-sulfonyl)-piperidin-2-yl]-1,1-dimethyl-ethylamine, 3.0 mmol of Et3N in 10 ml of CH2Cl2 are added 1.5 mmol of acetyl chloride at 0° C. and the resulting mixture is stirred for 1 h. The reaction mixture is diluted with water and extracted with CH2Cl2. The organic phases are combined, dried over Na2SO4 and concentrated under reduced pressure. The residue is purified by flash chromatography (SiO2 60 F) to afford the title compound which is identified based on its Rf-value.
Reaction SMILES: [F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:16][CH3:17])=[CH:7][C:8](=[O:15])[N:9]2[CH2:12][CH:13]=C)=[CH:4][CH:3]=1.I([O-])(=O)(=O)=[O:19].[Na+].O>O1CCOCC1.[Os](=O)(=O)(=O)=O>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:16][CH3:17])=[CH:7][C:8](=[O:15])[N:9]2[CH2:12][CH:13]=[O:19])=[CH:4][CH:3]=1
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: C=CCn1c(=O)cc(OC)c2ccc(F)cc21
Agent: O=[Os](=O)(=O)=O
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: COc1cc(=O)n(CC=O)c2cc(F)ccc12
Reaction time: 5 h
Yield: 93.2 %

Procedure:
A solution of 7-fluoro-4-(methyloxy)-1-(2-propen-1-yl)-2(1H)-quinolinone (0.386 g, 1.66 mmol), sodium periodate (0.83 g, 3.7 mmol) and osmium tetroxide (1.7 ml, 4% in water) in 1,4-dioxane (15 ml) containing water (3 ml) was stirred for 5 h. The mixture was separated between dichloromethane and water. The organics were isolated, dried and concentrated to provide the title compound (0.364 g, 93%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([O-:11])=[O:10])=[CH:5][CH:4]=1.[Na+].C([O-])(=O)C.[Na+].B(O)(O)O.Cl[C:23](=[CH2:26])[C:24]#[N:25]>O.C(O)(C)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([S:9]([CH:26]=[CH:23][C:24]#[N:25])(=[O:11])=[O:10])=[CH:7][CH:8]=1
Reactant: C=C(Cl)C#N
Reactant: COc1ccc(S(=O)[O-])cc1
Agent: CC(=O)[O-]
Agent: OB(O)O
Agent: [Na+]
Solvent: CC(C)O
Solvent: O
Product: COc1ccc(S(=O)(=O)C=CC#N)cc1

Procedure:
In a flask, 59.5 g. (0.31 mole) sodium 4-methoxybenzenesulfinate, 25.4 g. (0.31 mole) sodium acetate and 19.2 g. (0.31 mole) boric acid were dissolved in a mixture of 150 ml. water and 275 ml. isopropyl alcohol. There was then added, with stirring, dropwise, 33.9 g. (31 ml., 0.39 mole) 2-chloroacrylonitrile. The mixture was stirred for some time at room temperature. Water was then added and the mixture stirred for one hour. A precipitate formed, which was filtered, washed with water and ethanol, and dried.
Reaction SMILES: N1C(C)=CC=CC=1C.[Br:9][C:10]1[CH:11]=[C:12]([N+:20]([O-:22])=[O:21])[C:13]([O:18][CH3:19])=[C:14]([CH:17]=1)[CH2:15]O.[Br-:23].[Li+].CS(OS(C)(=O)=O)(=O)=O>O1CCCC1>[Br:9][C:10]1[CH:11]=[C:12]([N+:20]([O-:22])=[O:21])[C:13]([O:18][CH3:19])=[C:14]([CH:17]=1)[CH2:15][Br:23]
Reactant: [Br-]
Reactant: COc1c(CO)cc(Br)cc1[N+](=O)[O-]
Agent: CS(=O)(=O)OS(C)(=O)=O
Agent: [Li+]
Solvent: Cc1cccc(C)n1
Solvent: C1CCOC1
Product: COc1c(CBr)cc(Br)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 16 h
Yield: 118.6 %

Procedure:
2,6-Lutidine (10.5 mL) was added to a stirring solution of 5-bromo-2-methoxy-3-nitrobenzyl alcohol (13.6 g) and lithium bromide (11.75 g) in anhydrous tetrahydrofuran (200 mL) at 0° C. A solution of methanesulfonic anhydride (11.8 g) in anhydrous tetrahydrofuran (20 mL) was added dropwise. The resulting mixture was left to stir at room temperature for 16 h. It was partitioned between diethyl ether (250 mL) and saturated sodium hydrogen carbonate (150 mL). The organic layer was dried (sodium sulfate) and evaporated in vacuo. Silica gel chromatography of the crude residue eluting with diethyl ether in petroleum ether gave the title compound (20 g) as an amber oil.
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6](=[O:22])[N:7]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:8]2=[O:13].[N:23]1[CH:28]=[CH:27][N:26]=[CH:25][C:24]=1[C:29](Cl)=[O:30].C(N(CC)CC)C>C1COCC1>[O:21]=[C:15]1[CH:14]([N:7]2[C:6](=[O:22])[C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH2:3][NH:2][C:29]([C:24]3[CH:25]=[N:26][CH:27]=[CH:28][N:23]=3)=[O:30])[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1
Reactant: O=C(Cl)c1cnccn1
Reactant: NCc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=C1CCC(N2C(=O)c3cccc(CNC(=O)c4cnccn4)c3C2=O)C(=O)N1
Temperature: 25 °C
Reaction time: 18 h
Yield: 61 %

Procedure:
A mixture of 4-aminomethyl-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione hydrochloride (0.63 g, 1.9 mmol), 2-pyrazinecarbonylchloride (0.25 g, 1.9 mmol) and triethylamine (0.61 g, 6.0 mmol) in THF (30 mL) was stirred at ambient temperature under nitrogen for 18 hours. The mixture was evaporated, and the residue was chromatographed using a methylene chloride-methanol gradient, eluting the product with 95:5 methylene chloride-methanol. This material dissolved in 4 mL acetonitrile, and this solution was poured into 50 mL of water, resulting in precipitation of the product, which was filtered, washed with additional water (20 mL), and dried, providing 0.46 g (61% yield): mp>260° C.; 1H NMR (DMSO-d6) δ 2.06-2.10 (m, 1H), 2.54-2.65 (m, 2H), 2.84-2.91 (m, 1H), 4.97 (d, J=6.3 Hz, 2H), 5.18 (dd, J=12.0 Hz, d=5.4 Hz, 1H), 7.69-7.83 (m, 3H), 8.29 (t, J=1.9 Hz, 1H), 8.91 (d, J=2.5 Hz, 1H), 9.21 (d, J=1.4 Hz, 1H), 9.61 (t, J=6.3 Hz, 1H), 11.15 (s, 1H); 13C NMR (DMSO-d6) δ 22.0, 30.9, 38.3, 48.9, 121.9, 127.2, 131.2, 131.6, 133.0, 134.7, 143.5, 143.6, 144.5, 147.7, 163.4, 167.0, 167.6, 169.8, 172.8; Anal. calcd for C19H15N5O5.0.5H2O: C, 56.71; H, 4.01; N, 17.41. Found: C, 56.64; H, 3.75; N, 17.28.
Reaction SMILES: C[O:2][CH:3](OC)[CH2:4][S:5]([C:7]1[S:8][C:9]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[N:11]=1)=[O:6].S(=O)(=O)(O)O.O>C(O)(=O)C.C(Cl)Cl>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([C:10]2[N:11]=[C:7]([S:5]([CH2:4][CH:3]=[O:2])=[O:6])[S:8][C:9]=2[C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)=[CH:13][CH:14]=1
Reactant: COc1ccc(-c2nc(S(=O)CC(OC)OC)sc2-c2ccc(OC)cc2)cc1
Agent: O=S(=O)(O)O
Solvent: CC(=O)O
Solvent: ClCCl
Solvent: O
Product: COc1ccc(-c2nc(S(=O)CC=O)sc2-c2ccc(OC)cc2)cc1
Temperature: 0 °C

Procedure:
5.75 g of 2-[4,5-bis-(p-methoxyphenyl)-thiazol-2-ylsulphinyl]-acetaldehyde-dimethylacetal are dissolved in 5 ml of acetic acid. Then, while stirring, 30 ml of a mixture of 2 parts acetic acid, 1 part sulphuric acid and 1 part water are added dropwise over a period of 5 minutes. The mixture is stirred at room temperature for 30 minutes, diluted with 100 ml of methylene chloride and poured into 200 ml of ice-water. The organic layer is removed and washed with 200 ml of ice-water. The aqueous phase is extracted by shaking three times with 50 ml of methylene chloride each time. The organic phases are combined, dried over magnesium sulphate and concentrated to dryness by evaporation. The crude product is dissolved in 200 ml of methylene chloride and stirred with 5 g of silica gel. The mixture is filtered, concentrated to dryness by evaporation and dried under reduced pressure. 2-[4,5-bis-(p-methoxyphenyl)-thiazol-2-ylsulphinyl]-acetaldehyde is obtained in the form of a highly viscous oil, IR-spectrum: νC=O =1720 cm-1, νS=O =1080 cm-1 (CCl4).
Reaction SMILES: I[CH2:2][CH2:3][OH:4].C(=O)([O-])[O-].[K+].[K+].[F:11][C:12]1[CH:13]=[N:14][C:15]2[C:20]([C:21]=1[CH2:22][CH2:23][CH2:24][C:25]1([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1)=[CH:19][CH:18]=[CH:17][CH:16]=2>C(#N)C>[F:11][C:12]1[CH:13]=[N:14][C:15]2[C:20]([C:21]=1[CH2:22][CH2:23][CH2:24][C:25]1([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:30][CH2:29][N:28]([CH2:2][CH2:3][OH:4])[CH2:27][CH2:26]1)=[CH:19][CH:18]=[CH:17][CH:16]=2
Reactant: CCOC(=O)C1(CCCc2c(F)cnc3ccccc23)CCNCC1
Reactant: OCCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCOC(=O)C1(CCCc2c(F)cnc3ccccc23)CCN(CCO)CC1

Procedure:
1.14 cm3 of 2-iodoethanol and 1.9 g of potassium carbonate were added to a solution of 4.4 g of ethyl 4-[3-(3-fluoroquinolin-4-yl)propyl]piperidine-4-carboxylate in 100 cm3 of anhydrous acetonitrile, with vigorous stirring and under an inert atmosphere. The reaction mixture was stirred for 18 hours in the region of 20° C., filtered and washed with 3 times 30 cm3 of acetonitrile. The filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 50° C. The evaporation residue was purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 20-45μ; diameter 5 cm; height 32 cm), eluting with dichloromethane/methanol/aqueous ammonia (40/5/0.5 by volume) and collecting 100-cm3 fractions. Fractions 8 to 12 were combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 3.5 g of ethyl 4-[3-(3-fluoroquinolin-4-yl)-propyl]-1-(2-hydroxyethyl)piperidine-4-carboxylate were obtained in the form of a viscous orange-colored oil.
Reaction SMILES: [C:1]1([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.[H][H]>>[CH:7]1([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]1
Reactant: [H][H]
Reactant: C1=C(c2ccccc2)CCCC1
Product: c1ccc(C2CCCCC2)cc1

Procedure:
The invention also relates to a hydrogenation and oxidation process in which a feed comprising cyclohexenylbenzene is contacted with hydrogen in the presence of a hydrogenation catalyst under hydrogenation conditions to form cyclohexylbenzene. The cyclohexylbenzene is then reacted with oxygen (e.g., air) in the presence of an oxidation catalyst under oxidation conditions to form cyclohexylbenzene hydroperoxide.
Reaction SMILES: [CH2:1]([O:4][C:5]1[CH:15]=[CH:14][CH:13]=[CH:12][C:6]=1[O:7][CH2:8][CH:9]1[O:11][CH2:10]1)[CH:2]=[CH2:3].[NH2:16][CH2:17][CH2:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:27]([CH3:33])[CH2:28][C:29](=[O:32])[NH:30][N:31]=2)=[CH:22][CH:21]=1>>[CH2:1]([O:4][C:5]1[CH:15]=[CH:14][CH:13]=[CH:12][C:6]=1[O:7][CH2:8][CH:9]([OH:11])[CH2:10][NH:16][CH2:17][CH2:18][O:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]2[CH:27]([CH3:33])[CH2:28][C:29](=[O:32])[NH:30][N:31]=2)=[CH:24][CH:25]=1)[CH:2]=[CH2:3]
Reactant: C=CCOc1ccccc1OCC1CO1
Reactant: CC1CC(=O)NN=C1c1ccc(OCCN)cc1
Product: C=CCOc1ccccc1OCC(O)CNCCOc1ccc(C2=NNC(=O)CC2C)cc1

Procedure:
Prepared analogously to Example 1 from 1-(2-allyloxy-phenoxy)-2,3-epoxypropane and 6-[4-(2-aminoethoxy)phenyl]-4,5-dihydro-5-methyl-3(2H)-pyridazinone.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][O:8][CH2:9][C:10]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)([F:12])[F:11].[C:19]1(=[O:29])[NH:23][C:22](=[O:24])[C:21]2=[CH:25][CH:26]=[CH:27][CH:28]=[C:20]12.[K]>CN(C)C=O.[Br-].C([P+](CCCC)(CCCC)CCCC)CCCCCCCCCCCCCCC>[F:11][C:10]([F:12])([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:9][O:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N:23]1[C:19](=[O:29])[C:20]2[C:21](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:22]1=[O:24]
Reactant: FC(F)(COCCCCCCBr)c1ccccc1
Reactant: O=C1NC(=O)c2ccccc21
Agent: CCCCCCCCCCCCCCCC[P+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [K]
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1CCCCCCOCC(F)(F)c1ccccc1
Temperature: 70 °C
Yield: 48.7 %

Procedure:
To a solution of Intermediate 7 (10.9 g, 34 mmol) in dimethylformamide (23 mL) was added potassium phthalimide (7.56 g, 40.8 mmol) and a catalytic amount of (n-hexadecyl)tri-n-butylphosphonium bromide. The mixture was heated at 70° C. for 3 hours. The solvent was removed under reduced pressure. Purification by column chromatography with silica gel, eluting with methylene chloride yielded the title compound (6.41 g, 49%) as oil.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([NH:11][C:12](=[O:22])[O:13][CH:14]2[CH:19]3[CH2:20][CH2:21][N:16]([CH2:17][CH2:18]3)[CH2:15]2)([CH3:10])[CH3:9])=[CH:4][CH:3]=1.[N:23]1[CH:28]=[C:27](B(O)O)[CH:26]=[N:25][CH:24]=1>>[N:23]1[CH:28]=[C:27]([C:2]2[CH:7]=[CH:6][C:5]([C:8]([NH:11][C:12](=[O:22])[O:13][CH:14]3[CH:19]4[CH2:20][CH2:21][N:16]([CH2:17][CH2:18]4)[CH2:15]3)([CH3:10])[CH3:9])=[CH:4][CH:3]=2)[CH:26]=[N:25][CH:24]=1
Reactant: OB(O)c1cncnc1
Reactant: CC(C)(NC(=O)OC1CN2CCC1CC2)c1ccc(Br)cc1
Product: CC(C)(NC(=O)OC1CN2CCC1CC2)c1ccc(-c2cncnc2)cc1
Yield: 40.4 %

Procedure:
Using general procedure E, quinuclidin-3-yl 2-(4-bromophenyl)propan-2-ylcarbamate (200 mg, 0.540 mmol), pyrimidin-5-ylboronic acid (136 mg, 1.12 mmol) and [PdCl2 (pddf)]CH2Cl2 gave the title compound as a white solid (80 mg, 40%). 1H NMR (500 MHz, CDCl3) δ 9.17 (s, 1H), 8.92 (s, 2H), 7.58-7.51 (m, 4H), 5.34 (s, 1H), 4.61 (m, 1H), 3.20-3.10 (m, 1H), 2.92-2.41 (m, 5H), 2.00-1.76 (m, 2H), 1.72-1.53 (m, 7H), 1.52-1.32 (m, 2H) ppm. 13C NMR (125 MHz, CDCl3) δ 157.4, 154.8, 154.5, 148.2, 134.0, 132.5, 127.0, 126.0, 71.2, 55.6, 55.0, 47.4, 46.3, 29.7, 29.4, 25.4, 24.5, 19.5 ppm. Purity: >96% LCMS (214 nm & 254 nm); retention time 1.34 min; (M+1) 366.
Reaction SMILES: [C:1]([O:5][C:6](=[O:20])[C@@H:7]1[CH2:11][C@@H:10](N)[CH2:9][N:8]1[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])([CH3:4])([CH3:3])[CH3:2].[C:21]([O:25][C:26]([NH:28][C:29](=[N:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])SC)=[O:27])([CH3:24])([CH3:23])[CH3:22].C[N:41](C)C=O>C(OCC)C>[C:1]([O:5][C:6](=[O:20])[C@@H:7]1[CH2:11][C@H:10]([N:28]([C:26]([O:25][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:27])[C:29]([NH2:41])=[N:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:9][N:8]1[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)[C@@H]1C[C@@H](N)CN1C(=O)OC(C)(C)C
Reactant: CN(C)C=O
Reactant: CSC(=NC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C
Solvent: CCOCC
Product: CC(C)(C)OC(=O)N=C(N)N(C(=O)OC(C)(C)C)[C@H]1C[C@@H](C(=O)OC(C)(C)C)N(C(=O)OC(C)(C)C)C1

Procedure:
A solution of (4R)-1-(tert-butyloxycarbonyl)-4-amino-L-proline tert-butyl ester (134 mg, 0.468 mmol) and N,N'-bis(tert-butyloxycarbonyl)-S-methyl-isothiourea (150 mg, 0.515 mmol) in N,N-dimethylformamide (2 mL) was heated for 15 hours at 55° C. and 2 days at room temperature under a nitrogen atmosphere. The reaction mixture was diluted with diethyl ether, washed with water, dried (Na2SO4), and evaporated. The title compound was obtained pure by flash silica gel chromatography eluting with 10% ethyl acetate/hexane; yield 60.2 mg (24%). Mass spectrum: m/z 529 (M+1); 400 MHz 1H NMR (CD3OD): δ1.44-1.52 (4s, 36H); 2.08 (m, 1H); 2.59 (m, 1H); 3.42 (m, 1H); 3.78 (m, 1H); 4.23 (dd, 1H); 4.57 (m, 1H).
Reaction SMILES: [H-].[Na+].[CH2:3]([C:5]1[CH:35]=[C:34]([CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49])[CH:33]=[CH:32][C:6]=1[O:7][CH2:8][CH:9]([OH:31])[CH2:10][O:11][C:12]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH3:4].[CH2:50](Br)[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1>CN(C)C=O>[CH2:3]([C:5]1[CH:35]=[C:34]([CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49])[CH:33]=[CH:32][C:6]=1[O:7][CH2:8][CH:9]([O:31][CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)[CH2:10][O:11][C:12]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)[CH3:4]
Reactant: BrCc1ccccc1
Reactant: CCCCCCCCCCCCCCc1ccc(OCC(O)COC(c2ccccc2)(c2ccccc2)c2ccccc2)c(CC)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCCc1ccc(OCC(COC(c2ccccc2)(c2ccccc2)c2ccccc2)OCc2ccccc2)c(CC)c1
Reaction time: 0.25 h
Yield: 98.2 %

Procedure:
To a suspension of 2.016 g of prewashed sodium hydride in 125 ml of dimethylformamide was added dropwise a solution of 17.75 g of 1-(2-ethyl-4-tetradecylphenoxy)-3-(triphenylmethoxy)-2-propanol in 125 ml of dimethylformamide. This mixture was stirred 15 minutes, then 7.198 g of benzyl bromide was added and stirring was continued for an additional 3 hours. The reaction mixture was quenched slowly with water and then extracted several times with ether. The ether extracts were combined, washed with water, dried and the solvent evaporated, giving 19.9 g of the desired compound.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1F)[C:5]#[N:6].O.O.O.O.O.O.O.O.O.[S-2:20].[Na+].[Na+]>CN(C)C=O>[Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[SH:20])[C:5]#[N:6]
Reactant: [S-2]
Reactant: N#Cc1ccc(F)c(Br)c1
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: N#Cc1ccc(S)c(Br)c1
Temperature: 0 °C
Reaction time: 8 h
Yield: 88.8 %

Procedure:
3-Bromo-4-fluorobenzonitrile (100 g) was dissolved in dimethylformamide (DMF) (500 ml), and sodium sulfide nonahydrate (132 g) was added thereto at 0° C. and then stirred overnight at room temperature. The reaction mixture was poured to ice water (1 L) and the insoluble material was filtered off. The filtrate was added to a 1N aqueous hydrochloric acid solution (700 ml) under ice-cooling and the precipitate was collected by filtration. The crystals thus obtained were washed with hexane/diisopropyl ether and water and then dried to obtain 3-bromo-4-mercaptobenzonitrile (95.0 g) as a light-yellow solid.