Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([CH3:21])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([CH:12]=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1.[Cl:22]Cl>C(O)(=O)C>[CH3:21][C:16]1[CH:17]=[C:18]([F:20])[CH:19]=[C:2]([CH3:1])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([Cl:22])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1
Reactant: Cc1cn2cccc(OCc3c(C)cc(F)cc3C)c2n1
Reactant: ClCl
Solvent: CC(=O)O
Product: Cc1cc(F)cc(C)c1COc1cccn2c(Cl)c(C)nc12
Temperature: 25 °C
Reaction time: 2 h
Yield: 45 %

Procedure:
To a solution of 8-(2,6-dimethyl-4-fluorobenzyloxy)-2-methylimidazo[1,2-a]pyridine (0.6 g, 2.1 mmol) in acetic acid (13 ml) was added dropwise 1.1 M Cl2 in acetic acid (2.2 ml, 2.43 mmol). The reaction mixture was stirred for 2 h. at room temperature and the solvent was evaporated under reduced pressure. The residue was solved in methylene chloride and was washed with water. The organic layer was separated, dried and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using methylene chloride:ethyl acetate (100:4) as eluent. Treating the residue with diethyl ether and filtration gave 0.3 g (45%) of the title compound.
Reaction SMILES: [C:1]([O:5][C:6](=[O:19])[NH:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([NH2:18])=[CH:14][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:27][S:28](Cl)(=[O:30])=[O:29]>C1COCC1.CN(C)C1C=CN=CC=1>[C:1]([O:5][C:6](=[O:19])[NH:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:13]=[CH:14][C:15]([N:18]([S:28]([CH3:27])(=[O:30])=[O:29])[S:28]([CH3:27])(=[O:30])=[O:29])=[CH:16][CH:17]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)NCCCCc1ccc(N)cc1
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)NCCCCc1ccc(N(S(C)(=O)=O)S(C)(=O)=O)cc1
Temperature: -10 °C
Reaction time: 0.5 h
Yield: 83 %

Procedure:
Compound 52 (0.16 g, 0.605 mmol) was dissolved in anhydrous THF (5 mL). To the clear solution were sequentially added triethylamine (0.18 mL, 1.21 mmol) and 4-dimethylaminopyridine (15 mg, 0.121 mmol). The mixture was cooled to about −10° C. for 15 min by a methanol-ice bath. To the cold solution was slowly added methanesulfonyl chloride (51 μL). The solution was further stirred at the temperature (about −10° C.) for an additional 30 min, then allowed to slowly warm up to room temperature by removing the cooling bath. The reaction mixture was concentrated under reduced pressure. The residue was chromatographed over silica gel, eluting with a mixture of ethyl acetate (0-35%) and hexanes (100-65%), to afford 0.212 g (83%) of the product 53 as a white solid. 1H NMR (CDCl3) δ 1.44 (s, 9H), 1.52-1.70 (m, 4H), 2.68 (t, J=7.4 Hz, 2H), 3.13-3.18 (m, 2H), 3.40 (s, 6H), 4.53 (br s, 1H), 7.27 (s, 4H). m/z (APCI)=321 [C17H28N2O6S2−Boc+H]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1.Cl[C:24](Cl)([O:26][C:27](=[O:33])OC(Cl)(Cl)Cl)Cl.[CH3:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1CO.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(N(CC)CC)C.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:27](=[O:33])[O:26][CH2:24][C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=2[CH3:35])=[CH:18][CH:17]=1
Reactant: Cc1ccccc1CO
Reactant: COc1cc2ncnc(Oc3ccc(N)cc3)c2cc1OC
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: COc1cc2ncnc(Oc3ccc(NC(=O)OCc4ccccc4C)cc3)c2cc1OC
Yield: 105.5 %

Procedure:
4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was added to toluene (5 ml), and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (77 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, (2-methylphenyl)methanol (32 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (79 mg, yield 90%).
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10](=[O:18])[CH2:11][C:12]3[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=3)=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[Br:19]Br.C(OCC)C>C(O)(=O)C.C(#N)C>[BrH:19].[Br:19][CH:11]([C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)[C:10]([C:6]1[CH:5]=[C:4]2[C:9](=[CH:8][CH:7]=1)[CH2:1][CH2:2][CH2:3]2)=[O:18]
Reactant: BrBr
Reactant: O=C(Cc1cccnc1)c1ccc2c(c1)CCC2
Solvent: CCOCC
Solvent: CC#N
Solvent: CC(=O)O
Product: Br
Product: O=C(c1ccc2c(c1)CCC2)C(Br)c1cccnc1
Reaction time: 1 h
Yield: 86 %

Procedure:
In 20 ml of acetic acid was dissolved 4.3 g of 1-(5-indanyl)-2-(3-pyridyl)ethanone. To the solution was added 0.93 ml of bromine, which was stirred for one hour at 80°, then the reaction solution was cooled. Addition of 80 ml of ethylether gives a layer of oily substance. The supernatant was discorded, and the remainder was dissolved in 50 ml of acetonitrile. The solution was cooled to give 6.2 g of 2-bromo-1-(5-indanyl)-2-(3-pyridyl)ethanone hydrobromide, m.p. 176°-177° C. The yield was 86%.
Reaction SMILES: [CH2:1]([C:8]1[C:9]([NH:26][C:27](=[O:29])[CH3:28])=[N:10][C:11]([CH:24]=[CH2:25])=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=2C=C)[N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>CC1C=C(C)C(N2C(=[Ru](Cl)(Cl)=CC3C=CC=CC=3OC(C)C)N(C3C(C)=CC(C)=CC=3C)CC2)=C(C)C=1>[CH2:1]([C:8]1[C:9]([NH:26][C:27](=[O:29])[CH3:28])=[N:10][C:11]2[CH:24]=[CH:25][C:15]3[CH:16]=[C:17]([O:20][CH3:21])[CH:18]=[CH:19][C:14]=3[C:12]=2[N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C=Cc1cc(OC)ccc1-c1nc(Cc2ccccc2)c(NC(C)=O)nc1C=C
Agent: Cc1cc(C)c(N2CCN(c3c(C)cc(C)cc3C)C2=[Ru](Cl)(Cl)=Cc2ccccc2OC(C)C)c(C)c1
Product: COc1ccc2c(ccc3nc(NC(C)=O)c(Cc4ccccc4)nc32)c1
Temperature: 90 °C
Reaction time: 17 h
Yield: 85.8 %

Procedure:
Under an argon atmosphere, to a solution of Hoveyda-Grubbs second generation catalyst (61.3 mg, 97.8 μmol) in 1,2-dichloromethane (150 mL) was added N-(3-benzyl-5-(4-methoxy-2-vinylphenyl)-6-vinylpyrazin-2-yl)acetamide (10) (348 mg, 903 μmol) at room temperature. The mixture was then heated to 90° C. and stirred overnight (17 hours). After cooling to room temperature and concentration under reduced pressure, the residue was purified by silica gel flash column chromatography (n-hexane/ethyl acetate=4/3→1/1) to give N-(2-benzyl-8-methoxybenzo[f]quinoxalin-3-yl)acetamide (11) (277 mg, 775 μmol, 85.8%) as a white solid. TLC Rf=0.27 (n-hexane/ethyl acetate=1/1); 1H NMR (400 MHz, CDCl3) δ 2.33 (s, 3H), 4.00 (s, 3H), 4.50 (s, 2H), 7.24-7.34 (m, 5H), 7.38 (dd, 1H, J=2.6, 8.8 Hz), 7.42 (br, 1H), 7.90 (d, 1H, J=8.8 Hz), 7.93 (d, 1H, J=8.8 Hz), 9.01 (d, 1H, J=8.8 Hz).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([C:16]34[CH2:23][CH2:22][C:19]([CH2:24][C:25]([O:27][CH3:28])=[O:26])([CH2:20][CH2:21]3)[O:18][CH2:17]4)=[CH:12][CH:11]=2)=[CH:6][CH:5]=1)([O-])=O.CCOC(C)=O.[H][H]>[OH-].[OH-].[Pd+2].CO>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[CH:11]=[CH:12][C:13]([C:16]34[CH2:21][CH2:20][C:19]([CH2:24][C:25]([O:27][CH3:28])=[O:26])([CH2:22][CH2:23]3)[O:18][CH2:17]4)=[CH:14][CH:15]=2)=[CH:8][CH:9]=1
Reactant: [H][H]
Reactant: COC(=O)CC12CCC(c3ccc(-c4ccc([N+](=O)[O-])cc4)cc3)(CC1)CO2
Agent: [Pd+2]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CO
Product: COC(=O)CC12CCC(c3ccc(-c4ccc(N)cc4)cc3)(CC1)CO2
Yield: 90 %

Procedure:
To a round bottom flask containing methyl 2-(4-(4′-nitrobiphenyl-4-yl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate (716 mg, 1.88 mmol) was added Pd(OH)2 on activated carbon (395 mg, 2.82 mmol). EtOAc (15 ml) and MeOH (3 ml) were added and the mixture was stirred under 1 atm. of hydrogen at room temperature for 2 hours. The resulting mixture was filtered through a pad of celite and concentrated to afford a crude residue. Column purification affords the title compound as off-white solid after drying (595 mg, 90% yield). LC/MS, ESI-MS(+): 352.3, RT: 1.29 (Condition E).
Reaction SMILES: [CH:1]([N:4]=[C:5]=[N:6][CH:7]([CH3:9])[CH3:8])([CH3:3])[CH3:2].[CH2:10]([OH:28])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]/[CH:18]=[CH:19]\[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]>>[CH2:10]([O:28][C:5](=[N:6][CH:7]([CH3:9])[CH3:8])[NH:4][CH:1]([CH3:3])[CH3:2])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]/[CH:18]=[CH:19]\[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]
Reactant: CCCCCCCC/C=C\CCCCCCCCO
Reactant: CC(C)N=C=NC(C)C
Product: CCCCCCCC/C=C\CCCCCCCCOC(=NC(C)C)NC(C)C
Temperature: 25 °C
Reaction time: 4 h
Yield: 91.7 %

Procedure:
A mixture of N,N'-diisopropylcarbodiimide (12.6 g, 0.1 mole), oleyl alcohol (26.8 g, 0.1 mole) and cuprous chloride (60 mg) is stirred at room temperature for 4 hours. Infrared analysis shows the reaction to be virtually complete. The reaction mixture is placed on a column of alumina (454 g) and eluted with methylene chloride to give 36.2 g of O-oleyl-N,N'-diisopropylisourea. The product is identified by mass spectrometry (molecular ion at m/e 394), infrared spectroscopy (the C=N band at 1660 cm-1) and nuclear magnetic resonance in deuterated chloroform; resonances are given in δ relative to tetramethylsilane: 0.9-2.2 (multiplet 37 protons); 2.9-3.8 (multiplet 3 protons); 4.0 (triplet, 2 protons) 5.3 (multiplet, 2 protons).
Reaction SMILES: C([O-])(O)=O.[Na+].Cl.[NH2:7][OH:8].ClCCl.Cl[C:13]([O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:14]>O.C(OCC)(=O)C>[C:16]1([O:15][C:13](=[O:14])[NH:7][OH:8])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: NO
Reactant: O=C(Cl)Oc1ccccc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Solvent: CCOC(C)=O
Product: O=C(NO)Oc1ccccc1
Temperature: 5 °C
Reaction time: 1 h
Yield: 78.1 %

Procedure:
To a stirred solution of NaHCO3 (60.5 g) in water (200 mL) in a 2 L beaker was added portion-wise over 15 min 27.5 g of hydroxylamine hydrochloride. Once the bubbling subsided, dichloromethane (200 mL) was added to the reaction mixture and cooled to 5° C. Phenyl chloroformate (50 g) was then added at a steady rate to the reaction mixture. The reaction mixture was allowed to warm to room temperature and stirred for 1 h. Ethyl acetate (100 mL) was employed to bring the reaction mixture to a transparent solution. The organic layer was separated, washed with brine (200 mL) and dried over MgSO4. The organic solvent was removed under reduced pressure to give the title compound (38.20 g) as a white solid melting at 104-107° C.
Reaction SMILES: [CH2:1]([O:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]2[C:22]([CH3:23])=[CH:21][CH:20]=[C:19]2[C:24]2[CH:43]=[CH:42][C:27]([O:28][C@H:29]([CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:30]([O:32]CC)=[O:31])=[CH:26][CH:25]=2)=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[OH-].[K+].Cl>C1COCC1.CO>[CH2:1]([O:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]2[C:22]([CH3:23])=[CH:21][CH:20]=[C:19]2[C:24]2[CH:25]=[CH:26][C:27]([O:28][C@H:29]([CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:30]([OH:32])=[O:31])=[CH:42][CH:43]=2)=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCCCCCCCCCOc1ccc(-n2c(C)ccc2-c2ccc(O[C@H](Cc3ccccc3)C(=O)OCC)cc2)cc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CCCCCCCCCCOc1ccc(-n2c(C)ccc2-c2ccc(O[C@H](Cc3ccccc3)C(=O)O)cc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 92 %

Procedure:
To a mixed solution of ethyl (2R)-2-{4-[1-(4-decyloxyphenyl)-5-methyl-1H-pyrrol-2-yl]phenoxy}-3-phenylpropanoate (870 mg, 1.49 mmol) in THF (30 ml) and methanol (15 ml) was added 1N aqueous potassium hydroxide solution(8 ml, 8 mmol) and the mixture was stirred for 1 hour at room temperature. The reaction solution was neutralized with 1N hydrochloric acid and extracted with ethyl acetate. The extract was washed with water and dried over magnesium sulfate anhydride, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to give the object compound as an oily substance. 760 mg (yield: 92.0%)
Reaction SMILES: O=[C:2]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:3](OCCC1C=CC=CC=1)=[O:4].O=C(C1C=CC=CC=1)C([O:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])=O>O>[C:14]1([CH2:2][CH:3]=[O:4])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH:25](=[O:24])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]
Reactant: CCCCCCCCCCOC(=O)C(=O)c1ccccc1
Reactant: O=C(OCCc1ccccc1)C(=O)c1ccccc1
Solvent: O
Product: CCCCCCCCCC=O
Product: O=CCc1ccccc1

Procedure:
The APC (1 ml) was added to a freshly prepared dispersion of microcapsules A4 or E10 (each 0.012 mmol with respect to the total amount of fragrance to be released). The sample was then diluted by adding demineralized tap water (9 ml). Reference samples, containing either 2-phenylethyl 2-oxo-2-phenylacetate or decyl 2-oxo-2-phenylacetate as the corresponding non-encapsulated pro-fragrance of formula (I) from the prior art (WO 99/60990, obtained as described in Example 1) or unmodified 2-phenylacetaldehyde or decanal (each 0.012 mmol) were prepared in the same way. The samples were then deposited as a film onto a porous ceramic plate (ca. 5×10 cm) by carefully pipetting sample (0.75 ml) onto the surface of the substrate. The samples were then covered with a crystallizing dish (2 l) and exposed to ambient indoor daylight at room temperature.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([C:9]2[NH:13][C:12](=[O:14])[C:11]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:10]=2)[CH:6]=[CH:7][CH:8]=1)#[N:2].[H][H]>[Ni].CO>[NH2:2][CH2:1][C:3]1[CH:4]=[C:5]([C:9]2[NH:13][C:12](=[O:14])[C:11]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:10]=2)[CH:6]=[CH:7][CH:8]=1
Reactant: N#Cc1cccc(C2=NC(c3ccccc3)(c3ccccc3)C(=O)N2)c1
Reactant: [H][H]
Agent: [Ni]
Solvent: CO
Product: NCc1cccc(C2=NC(c3ccccc3)(c3ccccc3)C(=O)N2)c1
Reaction time: 8 h
Yield: 64.3 %

Procedure:
To a glass bomb was added 100 mg (0.296 mmol) of the compound of Example 2, the 3-cyanophenyl derivative, and 10 mg of freshly washed Raney nickel in 6 mL of a 5:1 MeOH:NH4OH(conc.) solution. The reaction vessel was charged with 50 psi hydrogen and shaken overnight. Upon completion the reaction was filtered through Celite and the solvent was evaporated in vacuo. Chromatography of the crude solid (Silica gel/Hexanes:Acetone 2:1) produced 65 mg (64%) of the desired amine as an off-white solid. LRMS m/z (ESI) 342.3 (M+H).
Reaction SMILES: Cl.[NH2:2][CH:3]([CH3:21])[C:4]([C:6]1[CH:11]=[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:9]([OH:16])=[C:8]([C:17]([CH3:20])([CH3:19])[CH3:18])[CH:7]=1)=O.C(O)C.Cl.[S-:26][C:27]#[N:28].[Na+]>O>[C:17]([C:8]1[CH:7]=[C:6]([C:4]2[NH:28][C:27](=[S:26])[NH:2][C:3]=2[CH3:21])[CH:11]=[C:10]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:9]=1[OH:16])([CH3:20])([CH3:19])[CH3:18]
Reactant: N#C[S-]
Reactant: CC(N)C(=O)c1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: Cc1[nH]c(=S)[nH]c1-c1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 71 %

Procedure:
To a mixed solution of 4.3 g of 4-(2-aminopropionyl)-2,6-di-tert-butylphenol hydrochloride, 50 ml of ethanol, and 1.2 ml of concentrated hydrochloric acid was added a solution of 2.2 g of sodium thiocyanate in 4 ml of water at room temperature. After stirring the mixture for 1.5 hours at room temperature and further refluxing the mixture for 2 hours, the solvent was distilled off under reduced pressure. Then, 30 ml of acetic acid was added to the residue and the mixture was refluxed for 2-3 hours. The reaction mixture thus formed was poured into water and the precipitates formed were recovered by filtration. The product was recrysltallized from isopropanol to provide 3.1 g of 4-(3,5-di-tert-butyl-4-hydroxyphenyl)-5-methyl-2-thioxo-4-imidazoline.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]([C:13]3[N:17]4[CH:18]=[CH:19][C:20]([CH:22]([OH:24])[CH3:23])=[CH:21][C:16]4=[N:15][CH:14]=3)[CH:10]=[CH:11][CH:12]=2)[CH:2]=1>ClCCCl.[O-2].[Mn+4].[O-2]>[NH3:1].[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]([C:13]3[N:17]4[CH:18]=[CH:19][C:20]([C:22](=[O:24])[CH3:23])=[CH:21][C:16]4=[N:15][CH:14]=3)[CH:10]=[CH:11][CH:12]=2)[CH:2]=1
Reactant: CC(O)c1ccn2c(-c3cccc(-c4cccnc4)c3)cnc2c1
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCCl
Product: CC(=O)c1ccn2c(-c3cccc(-c4cccnc4)c3)cnc2c1
Product: N
Temperature: 50 °C
Yield: 165.2 %

Procedure:
1-[3-(3-(Pyridin-3-yl)phenyl)imidazo[1,2-α]pyridin-7-yl]ethanol (53 mg, 0.17 mmol) was suspended in 1,2-dichloroethane (2 ml), manganese(IV) oxide (73 mg, 0.84 mmol) added and the mixture heated at 50° C. for 18 h. The mixture was cooled to room temperature, filtered through Celite®, diluted with 1,2-dichloroethane and pre-adsorbed onto silica. Purification by silica gel chromatography eluting with dichloromethane/methanol/conc. ammonia (98:2:0.2) gave the title compound (44 mg, 85%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δH 2.69 (3H, s), 7.40-7.48 (2H, m), 7.60-7.73 (3H, m), 7.77 (1H, d, J 1), 7.90-7.95 (2H, m), 8.30 (1H, s), 8.38 (1H, dd, J 1 and 7), 8.65-8.67 (1H, m), 8.91 (1H, s); m/z (ES+) 314 (M++H).
Reaction SMILES: [OH-:1].[Na+].OO.[Cl:5][C:6]1[CH:7]=[C:8]([S:12]([N:15]2[CH2:20][CH2:19][C:18]([NH:23][C:24]([CH:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)=O)([C:21]#[N:22])[CH2:17][CH2:16]2)(=[O:14])=[O:13])[CH:9]=[CH:10][CH:11]=1.O>C(O)C>[Cl:5][C:6]1[CH:7]=[C:8]([S:12]([N:15]2[CH2:20][CH2:19][C:18]3([N:23]=[C:24]([CH:26]4[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]4)[NH:22][C:21]3=[O:1])[CH2:17][CH2:16]2)(=[O:14])=[O:13])[CH:9]=[CH:10][CH:11]=1
Reactant: N#CC1(NC(=O)C2CCCCC2)CCN(S(=O)(=O)c2cccc(Cl)c2)CC1
Reactant: [OH-]
Agent: OO
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: O=C1NC(C2CCCCC2)=NC12CCN(S(=O)(=O)c1cccc(Cl)c1)CC2
Temperature: 25 °C
Yield: 52 %

Procedure:
A 6 M aqueous sodium hydroxide solution (0.74 mL) and a 30% aqueous hydrogen peroxide solution (0.25 mL) were added to a solution of cyclohexanecarboxylic[1-(3-chloro-benzenesulfonyl)-4-cyano-piperidin-4-yl]-amide (100 mg, 0.244 mmol) in ethanol (1.60 mL), and the mixture was heated under reflux for 4.5 hours. The reaction mixture was cooled to room temperature and water was then added, followed by concentration under reduced pressure. The residue was neutralized with a saturated aqueous ammonium chloride solution, followed by extraction with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane:methanol=90:10) to give 8-(3-chloro-benzenesulfonyl)-2-cyclohexyl-1,3,8-triaza-spiro[4.5]dec-1-en-4-one as a white solid (52 mg, 52%).
Reaction SMILES: [CH:1]1([NH:4][C:5]([C:7]2[N:8]=[N:9][N:10]([C:12]3[CH:17]=[CH:16][C:15]([C:18]([NH:20][CH2:21][CH3:22])=[O:19])=[CH:14][C:13]=3[OH:23])[CH:11]=2)=[O:6])[CH2:3][CH2:2]1.Br[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][F:30].C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[CH:1]1([NH:4][C:5]([C:7]2[N:8]=[N:9][N:10]([C:12]3[CH:17]=[CH:16][C:15]([C:18]([NH:20][CH2:21][CH3:22])=[O:19])=[CH:14][C:13]=3[O:23][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][F:30])[CH:11]=2)=[O:6])[CH2:3][CH2:2]1
Reactant: FCCCCCBr
Reactant: CCNC(=O)c1ccc(-n2cc(C(=O)NC3CC3)nn2)c(O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCNC(=O)c1ccc(-n2cc(C(=O)NC3CC3)nn2)c(OCCCCCF)c1
Temperature: 50 °C
Reaction time: 8 h
Yield: 58.6 %

Procedure:
To a solution of N-cyclopropyl-1-{4-[(ethylamino)carbonyl]-2-hydroxyphenyl}-1H-1,2,3-triazole-4-carboxamide (0.16 g) obtained in Example 139 in DMF (5 ml) were added 1-bromo-5-fluoropentane (0.11 g) and potassium carbonate (0.07 g), and the mixture was stirred at 50° C. overnight. The reaction mixture was allowed to cool to room temperature, and water was added to the reaction mixture. The deposited precipitate was collected by filtration, washed with water, and recrystallized from ethanol-water to give the title compound as a pale-brown powder (0.12 g, 60%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[N:11][OH:12])[C:9]#[N:10])=[CH:4][CH:3]=1.[C:13]1([CH3:23])[CH:18]=[CH:17][C:16]([S:19](Cl)(=[O:21])=[O:20])=[CH:15][CH:14]=1.O>N1C=CC=CC=1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8](=[N:11][O:12][S:19]([C:16]2[CH:17]=[CH:18][C:13]([CH3:23])=[CH:14][CH:15]=2)(=[O:21])=[O:20])[C:9]#[N:10])=[CH:6][CH:7]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: N#CC(=NO)c1ccc(F)cc1
Solvent: c1ccncc1
Solvent: O
Product: Cc1ccc(S(=O)(=O)ON=C(C#N)c2ccc(F)cc2)cc1
Reaction time: 1 h
Yield: 93.4 %

Procedure:
A stirred solution of 2-(4-fluorophenyl)-2-hydroxyiminoacetonitrile (42.8 g, 0.26 mole) in 200 ml of pyridine was cooled to 0° C., and p-toluenesulfonyl chloride (76.0 g, 0.39 mole) was added portionwise. Upon complete addition, the reaction mixture was stirred at 0°-5° C. for one hour and then stored in a refrigerator for 16 hours. The resultant slurry was poured into a mixture of ice and water and stirred for 30 minutes. The mixture was then filtered and the white filter cake dried under vacuum without heat to give 2-(4-fluorophenyl)-2-(4-methylphenylsulfonyloxy)iminoacetonitrile (77.3 g, mp 129°-140° C.).
Reaction SMILES: [Cl:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][C:5]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])=[C:4](I)[CH:3]=1.[F:18][C:19]([F:30])([F:29])[CH2:20][S:21][CH2:22][C:23]([OH:28])([CH2:26][CH3:27])[C:24]#[CH:25]>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9])[N:12]([S:13]([CH3:16])(=[O:15])=[O:14])[C:24]([C:23]([OH:28])([CH2:26][CH3:27])[CH2:22][S:21][CH2:20][C:19]([F:30])([F:18])[F:29])=[CH:25]2
Reactant: C#CC(O)(CC)CSCC(F)(F)F
Reactant: CS(=O)(=O)Nc1cc(C(F)(F)F)c(Cl)cc1I
Product: CCC(O)(CSCC(F)(F)F)c1cc2cc(Cl)c(C(F)(F)F)cc2n1S(C)(=O)=O

Procedure:
This compound was prepared using the standard Sonagashira procedure as described in General Procedures Example C, reacting from N-(4-chloro-2-iodo-5-trifluoromethyl-phenyl)-methanesulfonamide (0.60 g, 1.5 mmol) and 3-(2,2,2-Trifluoro-ethylsulfanylmethyl)-pent-1yn-3-ol (0.32 g, 1.5 mmol) to yield the title compound as a yellow sticky oil.