Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[C:3](=[O:31])[N:4]([C:20]2[CH:21]=[C:22]([CH:27]=[CH:28][C:29]=2[CH3:30])[C:23]([NH:25][CH3:26])=[O:24])[C:5]([CH2:18][OH:19])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].N1C=CC=CC=1.[C:38](OC(=O)C)(=[O:40])[CH3:39]>C(Cl)Cl>[C:38]([O:19][CH2:18][C:5]1[N:4]([C:20]2[CH:21]=[C:22]([C:23]([NH:25][CH3:26])=[O:24])[CH:27]=[CH:28][C:29]=2[CH3:30])[C:3](=[O:31])[C:2]([Br:1])=[C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[F:17])[CH:6]=1)(=[O:40])[CH3:39]
Reactant: CC(=O)OC(C)=O
Reactant: CNC(=O)c1ccc(C)c(-n2c(CO)cc(OCc3ccc(F)cc3F)c(Br)c2=O)c1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CNC(=O)c1ccc(C)c(-n2c(COC(C)=O)cc(OCc3ccc(F)cc3F)c(Br)c2=O)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 56 %

Procedure:
To a solution of 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-(hydroxymethyl)-2-oxopyridin-1(2H)-yl]-N,4-dimethylbenzamide, (225 mg, 0.50 mmol) stirred in CH2Cl2 was added pyridine (55 μL, 0.69 mmol). To the resulting homogeneous solution was then added acetic anhydride (47 μL, 0.51 mmol). The mixture was stirred at rt for 3 h. Additional pyridine (150 μL, 1.8 mmol) and acetic anhydride (100 μL, 1.05 mmol) were then added and the reaction was allowed to stir overnight at rt. The reaction was then quenched with 1N NHCl4 and diluted with CH2Cl2. The layers were separated and the organic layer was then extracted with CH2Cl2 (3×). The organics were then combined, dried, and concentrated in vacuo. The residue was then triturated with Et2O and filtered to give (150 mg, 61%) an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.48 (br s, 1H), 7.87 (app d, J=7.8 Hz, 1H), 7.74-7.69 (m, 2H), 7.52 (d, J=7.5 Hz, 1H), 7.40 (app t, J=8.1 Hz, 1H), 7.28-7.19 (m, 1H), 6.91 (s, 1H), 5.43 (s, 2H), 4.60 (s, 2H), 2.79 (s, 3H), 2.06 (s, 3H), 1.94 (s, 3H). ES-HRMS m/z 535.0676 (M+H calcd for C24H22N2F2BrO5 requires 535.0675).
Reaction SMILES: [CH2:1]([CH:8]([CH2:15][C:16]([N:18]1[CH2:26][C@H:25]2[C@H:20]([CH2:21][CH:22]=[CH:23][CH2:24]2)[CH2:19]1)=[O:17])[C:9]([O:11]CCC)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>C(O)C>[CH2:1]([CH:8]([CH2:15][C:16]([N:18]1[CH2:19][C@H:20]2[C@H:25]([CH2:24][CH:23]=[CH:22][CH2:21]2)[CH2:26]1)=[O:17])[C:9]([OH:11])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCCOC(=O)C(CC(=O)N1C[C@H]2CC=CC[C@H]2C1)Cc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)C(CC(=O)N1C[C@H]2CC=CC[C@H]2C1)Cc1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 68.7 %

Procedure:
To a solution of propyl 2-benzyl-3-(cis-3a,4,7,7a-tetrahydro-2-isoindolinylcarbonyl)propionate (198 mg) in ethanol (2 ml) was added 1N sodium hydroxide solution (668 μl) and the mixture was stirred at room temperature for 16 hours. After the solvent was evaporated under reduced pressure, the residue was dissolved in water and extracted with ethyl acetate. The aqueous layer was acidified with hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with brine and dried over MgSO4. After the solvent was evaporated under reduced pressure, the residue was crystallized from diethyl ether to give 120 mg of 2-benzyl-3-(cis-3a,4,7,7a-tetrahydro-2-isoindolinylcarbonyl)propionic acid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5](I)=[CH:4][C:3]=1[CH:11]1[CH2:13][CH2:12]1.[SH:14][CH2:15][C:16]([O:18][CH3:19])=[O:17].CCN(CC)CC>CN1C(=O)CCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[Cl:1][C:2]1[C:3]([CH:11]2[CH2:13][CH2:12]2)=[CH:4][C:5]([S:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])=[C:6]([O:8][CH3:9])[CH:7]=1
Reactant: COC(=O)CS
Reactant: COc1cc(Cl)c(C2CC2)cc1I
Agent: [Fe+2]
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CCN(CC)CC
Solvent: CN1CCCC1=O
Product: COC(=O)CSc1cc(C2CC2)c(Cl)cc1OC
Temperature: 80 °C
Reaction time: 24 h
Yield: 96.4 %

Procedure:
A mixture of 1-chloro-2-cyclopropyl-4-iodo-5-methoxybenzene (380 mg, 1.23 mmol), Pd2(dba)3 (56 mg, 0.061 mmol), methyl 2-mercaptoacetate (196 mg, 1.85 mmol), 1,1′-Bis(diphenylphosphino)ferrocene (136 mg, 0.246 mmol), Et3N (372 mg, 3.69 mmol) in NMP (8 mL) was stirred under argon at 80° C. for 24 h. After cooled to RT, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate=20:1) to afford the desired product (340 mg, 92% yield). 1H NMR (400 MHz, DMSO-d6) δ: 7.05 (s, 1H), 6.81 (s, 1H), 3.84 (s, 2H), 3.82 (s, 3H), 3.62 (s, 3H), 2.00 (m, 1H), 0.94 (m, 2H), 0.64 (m, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][C:5]2=[N:6][N:7]([C:9]3[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=3[OH:16])[N:8]=[C:4]2[CH:3]=1.Br[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27].C(=O)([O-])[O-].[K+].[K+].CC(C)=O>C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2=[N:6][N:7]([C:9]3[CH:14]=[CH:13][C:12]([O:15][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])=[CH:11][C:10]=3[OH:16])[N:8]=[C:4]2[CH:3]=1
Reactant: CCCCCCCCBr
Reactant: Oc1ccc(-n2nc3ccc(Cl)cc3n2)c(O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Solvent: O
Product: CCCCCCCCOc1ccc(-n2nc3ccc(Cl)cc3n2)c(O)c1
Yield: 9.7 %

Procedure:
A mixture of 6.5 g of 5-chloro-2-(2,4-dihydroxyphenyl)-2H-benzotriazole, 7.1 g of 1-bromooctane, 5.2 g of anhydrous potassium carbonate and 100 mL of acetone is refluxed for 24 hours. To the resulting mixture, about 100 mL of water and ethyl acetate are added, and petroleum eg of crude product is isolated. Column chromatography using petroleum ether yields 0.9 g of the title compound whose structure is confirmed by Hnmr and mass spectrometry.
Reaction SMILES: C(O[C:4]([C:6]1[CH:11]=[C:10]([C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=2)[CH:9]=[C:8]([CH3:20])[N:7]=1)=[O:5])C.[NH2:21][C:22]1[S:23][CH:24]=[C:25]([CH2:27][C:28]#[N:29])[N:26]=1>>[C:28]([CH2:27][C:25]1[N:26]=[C:22]([NH:21][C:4]([C:6]2[CH:11]=[C:10]([C:12]3[CH:13]=[C:14]([F:19])[CH:15]=[C:16]([F:18])[CH:17]=3)[CH:9]=[C:8]([CH3:20])[N:7]=2)=[O:5])[S:23][CH:24]=1)#[N:29]
Reactant: N#CCc1csc(N)n1
Reactant: CCOC(=O)c1cc(-c2cc(F)cc(F)c2)cc(C)n1
Product: Cc1cc(-c2cc(F)cc(F)c2)cc(C(=O)Nc2nc(CC#N)cs2)n1

Procedure:
The title compound, was prepared from 4-(3,5-Difluorophenyl)-6-methyl-pyridine-2-carboxylic acid ethyl ester in accordance with the general method of example 26, step 6 using (2-Amino-thiazol-4-yl)-acetonitrile instead of 3-chloroaniline to yield the final compound as a off-white solid, MS (ISP): m/e=371.2 (M+H)+.
Reaction SMILES: C(OC(=O)C([O:12][NH:13][C:14](=[NH:23])[C:15]([CH3:22])([CH3:21])[CH2:16][O:17][CH2:18][CH2:19][Cl:20])=CC(OCC)=O)C.ClCCOCC(C1NC(=O)C(O)=C(C(OCC)=O)N=1)(C)C>CC1C=CC(C)=CC=1C>[Cl:20][CH2:19][CH2:18][O:17][CH2:16][C:15]([CH3:22])([CH3:21])[C:14]([NH:13][OH:12])=[NH:23]
Reactant: CCOC(=O)C=C(ONC(=N)C(C)(C)COCCCl)C(=O)OCC
Agent: CCOC(=O)c1nc(C(C)(C)COCCCl)[nH]c(=O)c1O
Agent: Cc1ccc(C)c(C)c1
Product: CC(C)(COCCCl)C(=N)NO
Temperature: 157.5 °C
Yield: 43 %

Procedure:
Ethyl 2-(1-(2-chloroethoxy)-2-methylpropan-2-yl)-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxylate Diethyl 2-(3-(2-chloroethoxy)-2,2-dimethylpropanimidamidooxy)but-2-enedioate was dissolved in 150 mL 1,2,4-trimethylbenzene and heated at 155-160° C. for 2.5 hrs with stirring under N2. The solvent was evaporated at reduced pressure and the residue was dissolved in EtOAc and extracted 2× with dil NaHCO3. The aqueous extracts were acidified with HCl and extracted with CH2Cl2. After drying (MgSO4), filtration and concentration provided the title compound (1.9 g, 43%) as a white solid. 1H NMR (300 MHz, CDCl3) δ: 1.31 (s, 6H), 1.41 (t, J=7.1 Hz, 3H), 3.54 (s, 2H), 3.63-3.72 (m, 2H), 3.75-3.83 (m, 2H), 4.42 (q, J=7.3 Hz, 2H). LC/MS (M+H): 319.
Reaction SMILES: [CH:1]1([CH2:6][C@H:7]([CH2:25][N:26]([CH:35]=[O:36])[O:27]CC2C=CC=CC=2)[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][N:19]=3)=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1>[OH-].[OH-].[Pd+2].CO>[CH:1]1([CH2:6][C@H:7]([CH2:25][N:26]([CH:35]=[O:36])[OH:27])[C:8]([N:10]2[C@H:14]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][N:19]=3)=[O:16])[CH2:13][CH:12]=[N:11]2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: O=CN(C[C@@H](CC1CCCC1)C(=O)N1N=CC[C@H]1C(=O)Nc1ccc(F)cn1)OCc1ccccc1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: O=CN(O)C[C@@H](CC1CCCC1)C(=O)N1N=CC[C@H]1C(=O)Nc1ccc(F)cn1
Reaction time: 2 h
Yield: 82.4 %

Procedure:
A mixture of (5S)-1-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-N-(5-fluoro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide (104 mg, 0.210 mmol) and Pearlman's catalyst (29.5 mg, 0.042 mmol) in methanol (12.3 ml) was degassed and placed under 1 atm of H2 at ambient temperature. After 2 hrs, the reaction mixture was filtered and concentrated to give a residue which was purified by RP-HPLC to give (5S)-1-((2R)-3-cyclopentyl-2-{[formyl(hydroxy)amino]methyl}propanoyl)-N-(5-fluoro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxamide (71 mg, 0.173 mmol, 83% yield). MS (ES+) m/z 406.1 (MH+) 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.12 (dq, J=11.78, 8.12 Hz, 2H) 1.37-1.67 (m, 5H) 1.70-1.99 (m, 4H) 3.05-3.19 (m, 1H) 3.27 (s, 1H) 3.54 (dd, J=14.15, 4.55 Hz, 1H) 3.75-3.89 (m, 1H) 3.89-4.03 (m, 1H) 4.97 (dd, J=11.87, 5.81 Hz, 1H) 7.11 (s, 1H) 7.50-7.62 (m, 1H) 7.89 (s, 0.7H) 8.12 (dd, J=9.09, 4.04 Hz, 1H) 8.18 (d, J=3.03 Hz, 1H) 8.22 (s, 0.3H)
Reaction SMILES: [CH3:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5][C:4](=[O:12])[CH:3]=1.[CH2:13]([Li])CCC.IC>O1CCCC1>[CH2:1]([C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5][C:4](=[O:12])[CH:3]=1)[CH3:13]
Reactant: [Li]CCCC
Reactant: Cc1cc(=O)[nH]c2ccccc12
Solvent: CI
Solvent: C1CCOC1
Product: CCc1cc(=O)[nH]c2ccccc12
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a suspension of 4-methylquinolin-2(1H)-one (5 g, 31 mmol) in anhydrous tetrahydrofuran (100 mL) under a nitrogen atmosphere cooled in an acetone/dry ice bath was added dropwise by syringe a 1.6N solution of n-butyl lithium in hexanes (49 mL, 78 mol). The resulting solution was warmed to r.t. for 2 h at which time iodomethane (3 mL, 47 mmol) was added by syringe. The reaction mixture was stirred at r.t. for 0.5 h then cooled in an ice bath. The reaction mixture was quenched by the addition of aq. 2N HCl and then extracted with excess chloroform. The combined organic extracts were washed with saturated sodium bicarbonate, dried over sodium sulfate, filtered and the solvent removed under vacuum to provide a solid.
Reaction SMILES: Cl[C:2]1[C:3]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([C:18]#[N:19])=[CH:10][CH:9]=2)=[N:4][CH:5]=[CH:6][N:7]=1.[C:20]([O:24][CH3:25])(=[O:23])[CH2:21][SH:22].C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[C:18]([C:11]1[C:12]2[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:8]([C:3]2[C:2]([S:22][CH2:21][C:20]([O:24][CH3:25])=[O:23])=[N:7][CH:6]=[CH:5][N:4]=2)=[CH:9][CH:10]=1)#[N:19]
Reactant: N#Cc1ccc(-c2nccnc2Cl)c2ccccc12
Reactant: COC(=O)CS
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)CSc1nccnc1-c1ccc(C#N)c2ccccc12
Temperature: 130 °C
Yield: 63.1 %

Procedure:
A mixture of 4-(3-chloropyrazin-2-yl)-1-naphthonitrile (0.16 g, 0.6 mmol), methyl thioglycolate (0.127 g, 1.2 mmol) and sodium carbonate (0.082 g, 0.78 mmol) in DMF (1 mL) was heated under microwave irradiation to 130° C. for 1 hour. The mixture was washed with water, extracted with ethyl acetate and purified by chromatography to yield methyl 2-(3-(4-cyanonaphthalen-1-yl)pyrazin-2-ylthio)acetate (0.127 g, 63%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:27])[C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=1[N:19]1[C:23]([CH3:24])=[N:22][N:21]=[C:20]1[CH2:25]O.P(Br)(Br)[Br:29]>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:27])[C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][C:10]=1[N:19]1[C:23]([CH3:24])=[N:22][N:21]=[C:20]1[CH2:25][Br:29]
Reactant: Cc1nnc(CO)n1-c1ccc(C(F)(F)F)cc1C(=O)c1ccccc1Cl
Reactant: BrP(Br)Br
Solvent: ClC(Cl)Cl
Product: Cc1nnc(CBr)n1-c1ccc(C(F)(F)F)cc1C(=O)c1ccccc1Cl

Procedure:
In the manner given in Example 5, 2'-chloro-5-(trifluoromethyl)-2-[3-(hydroxymethyl)-5-methyl-4H-1,2,4-triazol-4-yl]benzophenone is treated with phosphorus tribromide in chloroform to give 2'-chloro-5-(trifluoromethyl)-2-[3-(bromomethyl)-5-methyl-4H-1,2,4-triazol-4-yl] -benzophenone.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:14]([CH3:15])=[C:13]([CH3:16])[C:12]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:11]([CH3:25])[C:10]=1[CH2:26][CH2:27][CH2:28][CH2:29][OH:30])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C([O-])(O)=O.[Na+].CCOC(C)=O>C(Cl)Cl>[CH2:1]([O:8][C:9]1[C:14]([CH3:15])=[C:13]([CH3:16])[C:12]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:11]([CH3:25])[C:10]=1[CH2:26][CH2:27][CH2:28][CH:29]=[O:30])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1c(C)c(OCc2ccccc2)c(CCCCO)c(C)c1OCc1ccccc1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: Cc1c(C)c(OCc2ccccc2)c(CCCC=O)c(C)c1OCc1ccccc1
Temperature: 25 °C
Reaction time: 1.25 h

Procedure:
A stirred solution of 4-(2,5-bis(benzyloxy)-3,4,6-trimethylphenyl)butan-1-ol (640 mg, 1.58 mmol) in 10 mL CH2Cl2 at 0° C. was treated with a suspension of Dess-martin periodonate (860 mg, 2.03 mmol) in CH2Cl2 (4 mL) and the pale yellow cloudy solution stirred at room temperature for 1.25 h. The cloudy white solution was poured over a solution of 10 mL 1.0 M NaHCO3 containing ˜0.5 g Na2S2O3 and 20 mL EtOAc added, the layers separated and the aqueous phase extracted 3×20 mL EtOAc. The combined organics were washed with 20 mL saturated aqueous NaCl, dried over Na2SO4 and concentrated to a yellow-white solid. The solid was dissolved into 5 mL EtOAc, filtered and the residual solids rinsed with EtOAc. The combined washings were stored overnight at 2° C., concentrated and purified by flash chromatography (gradient elution, 0-20% EtOAc/heptanes) collecting 530 mg of 4-(2,5-bis(benzyloxy)-3,4,6-trimethylphenyl)butanal. MS M++H at 403 m/z; 1H NMR (400 MHz, CDCl3) δ=9.67 (t, 1H), 7.52-7.48 (m, 2H), 7.45-7.36 (m, 6H), 4.75 (s, 2H), 4.74 (s, 2H), 2.69 (t, 2H), 2.44 (td, 2H), 2.27 (s, 3H), 2.24 (s, 6H), 1.84 (pent, 2H) ppm.
Reaction SMILES: N1C=CC=CC=1.Cl.[NH2:8][OH:9].[CH3:10][C:11]1[C:15]([C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=O)=[N:14][O:13][N:12]=1>C(OCC)(=O)C>[CH3:10][C:11]1[C:15](/[C:16](/[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[N:8]/[OH:9])=[N:14][O:13][N:12]=1
Reactant: Cc1nonc1C(=O)c1ccccc1
Reactant: NO
Agent: Cl
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: Cc1nonc1/C(=N/O)c1ccccc1
Temperature: 70 °C
Yield: 21.6 %

Procedure:
A pyridine (55 ml) solution of hydroxylamine hydrochloride (5.19 g, 73.0 mmol) was added to (3-methyl-1, 2, 5-oxadiazol-4-yl) phenylmethanone (3.43 g, 18.0 mmol) and heated to 70° C. for 21 hours with stirring. After the reacted solution was condensed, the residue was dissolved in ethyl acetate. After washing with diluted hydrochloride and subsequent washing with water, the residue was dried with magnesium carbonate. After removing the solvent and purifying the residue by column chromatography, (Z)-(3-methyl-1, 2, 5-oxadiazol-4-yl) phenylmethanone oxime (2.13 g) and (E)-(3-methyl-1, 2, 5-oxadiazol-4-yl)phenylmethanone oxime (0.79 g) were obtained.
Reaction SMILES: [Na].Cl.[C:3]([NH2:10])(=[NH:9])[CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]=[C:19]=[O:20])=[CH:14][CH:13]=1>CC(C)=O>[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19]([NH:9][C:3](=[NH:10])[CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])=[O:20])=[CH:14][CH:13]=1
Reactant: CCCCCC(=N)N
Reactant: O=C=Nc1ccc(Cl)cc1
Agent: Cl
Agent: [Na]
Solvent: CC(C)=O
Product: CCCCCC(=N)NC(=O)Nc1ccc(Cl)cc1

Procedure:
Following a procedure similar to that described in Example 1 but using 3.2 g. sodium in 200 ml. dry acetone, 21. g. hexanamidine hydrochloride, and 21.4 g. 4-chlorophenyl isocyanate in 100 ml. dry acetone, there was obtained after recrystallization from acetone 13.9 g. of the hydrochloride of 1-(4-chlorophenyl)-3-(hexanimidoyl)urea; m.p. 175°-179°C.
Reaction SMILES: C([C@@H]1C[O:7]C(C2C=CC=CC=2NC2C(NC3C=CC=CC=3C3OC[C@@H](C(C)C)N=3)=CC=CC=2)=N1)(C)C.[CH:37]1([C:40]2[CH:45]=[CH:44][N:43]=[C:42]([C:46]3[CH:47]=[N:48][C:49]([N:52]4[C:60]5[C:55](=[CH:56][CH:57]=[C:58]([C:61]([O:63][CH3:64])=[O:62])[CH:59]=5)[C:54]([S:65][CH3:66])=[CH:53]4)=[N:50][CH:51]=3)[CH:41]=2)[CH2:39][CH2:38]1.C(O)(=O)C.OO>ClCCl>[CH:37]1([C:40]2[CH:45]=[CH:44][N:43]=[C:42]([C:46]3[CH:51]=[N:50][C:49]([N:52]4[C:60]5[C:55](=[CH:56][CH:57]=[C:58]([C:61]([O:63][CH3:64])=[O:62])[CH:59]=5)[C:54]([S:65]([CH3:66])=[O:7])=[CH:53]4)=[N:48][CH:47]=3)[CH:41]=2)[CH2:38][CH2:39]1
Reactant: CC(C)[C@@H]1COC(c2ccccc2Nc2ccccc2Nc2ccccc2C2=N[C@H](C(C)C)CO2)=N1
Reactant: COC(=O)c1ccc2c(SC)cn(-c3ncc(-c4cc(C5CC5)ccn4)cn3)c2c1
Agent: OO
Solvent: CC(=O)O
Solvent: ClCCl
Product: COC(=O)c1ccc2c(S(C)=O)cn(-c3ncc(-c4cc(C5CC5)ccn4)cn3)c2c1
Temperature: 6.5 °C
Reaction time: 0.5 h

Procedure:
N1,N2-bis(2-((R)-4-isopropyl-4,5-dihydrooxazol-2-yl)phenyl)benzene-1,2-diamine (6.95 mg, 0.014 mmol) and Mn(OTf)2 (5.09 mg, 0.014 mmol; for synthesis and application of this ligand see: Dai. W. et al. Org. Lett. 2013, 15, 5658; Dai. W. et al. Org. Lett. 2013, 15, 4138) in dichloromethane (10 mL) were stirred at room temperature for 3 h. 333a) (0.3 g, 0.721 mmol), acetic acid (0.263 mL, 4.61 mmol) and 30% aqueous hydrogen peroxide solution (0.147 mL, 1.47 mmol) were added at room temperature and the resulting mixture was immediately cooled with an ice bath to 5-8° C. The reaction mixture was stirred at this temperature for 30 min, quenched with saturated sodium sulfite solution (10 mL) and further stirred for 15 min. The mixture was then diluted with dichloromethane (30 mL) and washed with brine (20 mL). The combined organic layers were dried over sodium sulfate and evaporated. The residue was purified by flash column chromatography [silica; dichloromethane with 1.5% methanol]. White solid. Yield: 0.14 g (45% of theory). Enantiomeric excess: >99% (chiral HPLC)
Reaction SMILES: [CH:1]([CH2:3][SiH:4](Cl)Cl)=[CH2:2].[C:7]([OH:15])(=[O:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>CCCCCC>[CH:1]([CH2:3][SiH:4]([O:15][C:7](=[O:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[O:14][C:7](=[O:15])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[CH2:2]
Reactant: O=C(O)c1ccccc1
Reactant: C=CC[SiH](Cl)Cl
Solvent: CCCCCC
Product: C=CC[SiH](OC(=O)c1ccccc1)OC(=O)c1ccccc1

Procedure:
705 g (5 moles) of vinylmethyldichlorosilane and 1000 ml of hexane are placed in the apparatus of Example 1. The reaction with 1245 g of benzoic acid (=10.2 moles) is performed as described under Example 1; the distillation of the raw product is performed in the same manner. At a pressure of 0.5 mbar and a head temperature of 141° C., 1295 g (4.15 moles) of a colorless liquid is distilled off. The yield amounts to 83%.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[O:10])[NH:8][C:6](=[O:7])[C:5]2=[CH:11][C:12]=1[S:13](=[O:16])(=[O:15])[NH2:14].N[CH:18]1[CH2:23][CH2:22][N:21]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[CH3:31])[CH2:20][CH2:19]1.C(O)CCCC.O=C1C2C(=CC=CC=2)C(=O)N1>CCCCCCC>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5]([C:6](=[O:7])[N:8]([CH:18]3[CH2:19][CH2:20][N:21]([CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[CH3:31])[CH2:22][CH2:23]3)[C:9]2=[O:10])=[CH:11][C:12]=1[S:13]([NH2:14])(=[O:16])=[O:15]
Reactant: Cc1ccccc1CN1CCC(N)CC1
Reactant: NS(=O)(=O)c1cc2c(cc1Cl)C(=O)NC2=O
Agent: O=C1NC(=O)c2ccccc21
Solvent: CCCCCO
Solvent: CCCCCCC
Product: Cc1ccccc1CN1CCC(N2C(=O)c3cc(Cl)c(S(N)(=O)=O)cc3C2=O)CC1

Procedure:
A mixture of 4-chloro-5-sulfamoylphthalimide (5.74 g., 0.022 mole) and 4-amino-1-[(2-methylphenyl)methyl]piperidine (4.5 g., 0.022 mole) in 85 ml. of n-pentanol was reacted according to the procedure of Example 1(a). Addition of n-heptane to the reaction mixture afforded 7.9 g. (80%) of the 1,3-dioxoisoindole product, m.p. 283°-243°. Crystallization of this material from DMF-methanol provided analytically pure 6-chloro-2,3-dihydro-2-[1-[(2-methylphenyl)methyl]-4-piperidinyl]-1,3-dioxo-1H-isoindole-5-sulfonamide, m.p. 244°-245° (dec.).
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5]([C:7]([OH:9])=O)[N:4]=[CH:3]1.O[NH:11][C:12](=[NH:24])[C:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C=O)C>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[O:9][N:24]=[C:12]([C:13]3[CH:14]=[CH:15][C:16]([O:19][C:20]([F:21])([F:22])[F:23])=[CH:17][CH:18]=3)[N:11]=2)[N:4]=[CH:3]1
Reactant: Cn1cnc(C(=O)O)c1
Reactant: N=C(NO)c1ccc(OC(F)(F)F)cc1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: Cn1cnc(-c2nc(-c3ccc(OC(F)(F)F)cc3)no2)c1
Temperature: 140 °C
Reaction time: 8 h
Yield: 48.8 %

Procedure:
To a solution of 1-methyl-1H-imidazole-4-carboxylic acid (1.5 g, 11.9 mmol) in DMF (30 mL), N-hydroxy-4-(trifluoromethoxy)benzimidamide (3.1 g, 14.3 mmol), HOBT (2.2 g, 14.3 mmol) and EDCI (2.7 g, 14.3 mmol) were added in sequence. The mixture was stirred at 140° C. overnight, then cooled to RT, quenched by water (100 mL), and extracted with EtOAc (2×50 mL). The combined organic phases were washed by water (3×50 mL) and brine (50 mL), dried over Na2SO4, filtered, and concentrated to afford the crude product, which was purified by silica gel column chromatography (EtOAc:Petroleum ether=1:5) to give 5-(1-methyl-1H-imidazol-4-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole as a white solid (1.8 g, 40.0%). MS (ES+) C13H9F3N4O2 requires: 310, found: 311 [M+H]+.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][CH:4]=1.[OH2:11]>[Cu]>[NH2:8][CH2:7][C:6]1[CH:9]=[CH:10][C:3]([C:2]([NH2:1])=[O:11])=[CH:4][CH:5]=1
Reactant: O
Reactant: N#Cc1ccc(CN)cc1
Agent: [Cu]
Product: NCc1ccc(C(N)=O)cc1
Temperature: 5 °C
Reaction time: 6 h
Yield: 70.3 %

Procedure:
In a 100 ml autoclave (manufactured by Nitto Koatsu Co., Ltd., material: SUS-316), 43 g of water, 11.5 g of a water-containing p-aminomethylbenzonitrile (10 g as p-aminomethylbenzonitrile, purity: 86.7%.) and 2.0 g of sponge copper (R-300C, manufactured by NIKKO RICA CORPORATION) were charged and, after sealing the autoclave, the atmosphere in the autoclave was replaced by nitrogen and the reaction was conducted at 100° C. for 6 hours. After the completion of the reaction, the catalyst was collected by filtration and the filtrate was cooled to 5° C., and then the crystal was collected by filtration. 10.0 g of the resulting crystal (wet form, containing 8.05 g of p-aminomethylbenzamide) was suspended in 43 g of water and dissolved with heating to 70° C., followed by cooled again to 5° C., filtration and further drying to obtain 7.99 g of p-aminomethylbenzamide (yield based on p-aminomethylbenzonitrile: 71%). The purity of p-aminomethylbenzamide determined by analyzing using high-performance liquid chromatograph was 99% or higher.