Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[CH2:2][C:3]([O:5][CH3:6])=[O:4].C([O:10][C:11](=[O:34])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:18]1[C:19]2[C:24]([O:25][C:26]3[C:31]=1[CH:30]=[CH:29][C:28](=[O:32])[CH:27]=3)=[CH:23][C:22]([OH:33])=[CH:21][CH:20]=2)C=C.C([O-])([O-])=O.[K+].[K+].C1([SiH3])C=CC=CC=1>CN(C=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:6][O:5][C:3](=[O:4])[CH2:2][O:32][C:28]1[CH:29]=[CH:30][C:31]2[C:18]3([C:13]4[C:12](=[CH:17][CH:16]=[CH:15][CH:14]=4)[C:11](=[O:34])[O:10]3)[C:19]3[C:24]([O:25][C:26]=2[CH:27]=1)=[CH:23][C:22]([OH:33])=[CH:21][CH:20]=3
Reactant: C=CCOC(=O)c1ccccc1-c1c2ccc(=O)cc-2oc2cc(O)ccc12
Reactant: COC(=O)CBr
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)COc1ccc2c(c1)Oc1cc(O)ccc1C21OC(=O)c2ccccc21
Temperature: 90 °C
Reaction time: 4 h
Yield: 61.1 %

Procedure:
Methyl bromoacetate (0.25 mL, 2.65 mmol) was added dropwise to a stirred mixture of 21 (0.33 g, 0.89 mmol) and K2CO3 (0.36 g, 2.65 mmol) in dry DMF (20 mL) under argon. The resulting mixture was stirred for 4 h at 90° C. The mixture was concentrated, diluted with ethyl acetate, washed with 10% NaHCO3, brine, dried with anhydrous Na2SO4, and evaporated. The residue was dissolved in dry DCM (25 mL). Tetrakis(triphenylphosphine) palladium(0) (58 mg, 0.05 mmol) and phenylsilane (1.1 mL, 8.90 mmol) were added. The mixture was stirred for 2 h at room temperature and concentrated. The residue was purified by column chromatography (ethyl acetate/hexane=1:1) to give 22 as a yellow solid (0.22 g, 62%). TLC (ethyl acetate/hexane, 3:1): Rf=0.5. mp 236° C. 1H NMR (CDCl3/CD3OD, 500 MHz) δ 3.76 (s, 3H, CO2CH3), 4.69 (s, 2H, CH2), 6.68 (m, 6H), 7.19 (d, J=7.5 Hz, 1H), 7.66 (t, J=7.5 Hz, 1H), 7.71 (t, J=7.5 Hz, 1H), 8.01 (d, J=7.5 Hz, 1H). 13C NMR (CDCl3/CD3OD, 125 MHz) δ 52.33, 65.18, 101.86, 102.77, 109.84, 111.55, 112.37, 112.52, 124.05, 124.87, 126.67, 129.00, 129.24, 129.80, 135.21, 152.47, 152.56, 152.94, 159.34, 169.21, 170.15, 171.36, 172.03. ESIMS calcd for C23H17O7 [M+H]+ 405.1. Found 405.2.
Reaction SMILES: [F:1][C:2]1[C:3]([OH:13])=[C:4]([I:12])[C:5]2[O:9][CH2:8][C:7](=[O:10])[C:6]=2[CH:11]=1.[C:14](=O)([O-])[O-].[K+].[K+].S(OC)(OC)(=O)=O.O>CN(C=O)C>[F:1][C:2]1[C:3]([O:13][CH3:14])=[C:4]([I:12])[C:5]2[O:9][CH2:8][C:7](=[O:10])[C:6]=2[CH:11]=1
Reactant: O=C([O-])[O-]
Reactant: O=C1COc2c1cc(F)c(O)c2I
Agent: [K+]
Solvent: CN(C)C=O
Solvent: COS(=O)(=O)OC
Solvent: O
Product: COc1c(F)cc2c(c1I)OCC2=O
Reaction time: 12 h
Yield: 23.7 %

Procedure:
A solution of 5-fluoro-6-hydroxy-7-iodobenzofuran-3(2H)-one (0.256 g, 0.871 mmol) in DMF (5 mL) was added with potassium carbonate (0.110 g, 0.796 mmol). The mixture was added with dimethyl sulfate (0.0803 g, 0.637 mmol) at room temperature, and the mixture was stirred for 12 hours. The reaction mixture was added with water, the mixture was extracted with ethyl acetate, and the organic layer was washed with saturated brine. The organic layer was dried over anhydrous magnesium sulfate, then the solvent was evaporated, and the resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain 5-fluoro-7-iodo-6-methoxybenzofuran-3(2H)-one (0.0582 g, 21%).
Reaction SMILES: [CH3:1][N:2]([C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25])[N:3]([CH2:14][C:15]1[CH:23]=[CH:22][C:18]([C:19](Cl)=[O:20])=[CH:17][CH:16]=1)[C:4]([O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:5].Cl.[CH:35]1([NH2:38])[CH2:37][CH2:36]1.C(N(CC)CC)C>C1C=CC=CC=1>[CH:35]1([NH:38][C:19](=[O:20])[C:18]2[CH:22]=[CH:23][C:15]([CH2:14][N:3]([C:4]([O:6][CH2:7][C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)=[O:5])[N:2]([CH3:1])[C:24]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:25])=[CH:16][CH:17]=2)[CH2:37][CH2:36]1
Reactant: NC1CC1
Reactant: CN(C(=O)OCc1ccccc1)N(Cc1ccc(C(=O)Cl)cc1)C(=O)OCc1ccccc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Product: CN(C(=O)OCc1ccccc1)N(Cc1ccc(C(=O)NC2CC2)cc1)C(=O)OCc1ccccc1

Procedure:
16.5 g. of 4-[(2-methyl-1,2-dicarbobenzoxy-hydrazino)methyl]-benzoyl chloride were added to 100 ml. of absolute benzene and treated with 3.1 g. of cyclopropylamine hydrochloride. 7.5 g. of triethylamine and 50 ml. of benzene were then dropped into the reaction mixture at 20°-30° with stirring. The reaction mixture was worked up as in Example 3, yielding 4-[(2-methyl-1,2-dicarbobenzoxy-hydrazino)-methyl]-benzoic acid cyclopropylamide, the carbobenzoxy groups of which were then removed by treatment with hydrogen bromide/glacial acetic acid. The product, 4-[(2-methyl-hydrazino)-methyl]-benzoic acid cyclopropylamide hydrobromide, melted at 180°-182°.
Reaction SMILES: [Cl:1][C:2]1[CH:26]=[CH:25][C:5]2=[N:6][N:7]([C:9]3[CH:10]=[C:11]([CH:17]=[C:18]([C:21]([CH3:24])([CH3:23])[CH3:22])[C:19]=3[OH:20])[CH2:12][CH2:13][C:14]([OH:16])=[O:15])[N:8]=[C:4]2[CH:3]=1.[N+:27]([C:30]1[CH:47]=[C:46]([Cl:48])[CH:45]=[CH:44][C:31]=1[O:32][N:33]1[C:38]([CH3:40])([CH3:39])[CH2:37][CH:36](O)[CH2:35][C:34]1([CH3:43])[CH3:42])([O-:29])=[O:28]>>[Cl:1][C:2]1[CH:26]=[CH:25][C:5]2=[N:6][N:7]([C:9]3[CH:10]=[C:11]([CH:17]=[C:18]([C:21]([CH3:22])([CH3:23])[CH3:24])[C:19]=3[OH:20])[CH2:12][CH2:13][C:14]([O:16][CH:36]3[CH2:35][C:34]([CH3:43])([CH3:42])[N:33]([O:32][C:31]4[CH:44]=[CH:45][C:46]([Cl:48])=[CH:47][C:30]=4[N+:27]([O-:29])=[O:28])[C:38]([CH3:40])([CH3:39])[CH2:37]3)=[O:15])[N:8]=[C:4]2[CH:3]=1
Reactant: CC(C)(C)c1cc(CCC(=O)O)cc(-n2nc3ccc(Cl)cc3n2)c1O
Reactant: CC1(C)CC(O)CC(C)(C)N1Oc1ccc(Cl)cc1[N+](=O)[O-]
Product: CC(C)(C)c1cc(CCC(=O)OC2CC(C)(C)N(Oc3ccc(Cl)cc3[N+](=O)[O-])C(C)(C)C2)cc(-n2nc3ccc(Cl)cc3n2)c1O

Procedure:
The title compound is prepared according to the procedure of Example 3 using 3-(5-chlorobenzotriazol-2-yl)-5-tert-butyl-4-hydroxyhydrocinnamic acid and 1-(2-nitro-4-chloro-phenoxy)-2,2,6,6-tetramethyl-4-hydroxypiperidine.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]2[N:10]=[N:11][N:12]([CH3:14])[N:13]=2)=[N:6][CH:7]=1.[F:15][C:16]1[CH:17]=[C:18]([N:31]2[CH2:35][C@H:34]([CH2:36][OH:37])[O:33][C:32]2=[O:38])[CH:19]=[CH:20][C:21]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:15][C:16]1[CH:17]=[C:18]([N:31]2[CH2:35][C@H:34]([CH2:36][OH:37])[O:33][C:32]2=[O:38])[CH:19]=[CH:20][C:21]=1[C:2]1[CH:7]=[N:6][C:5]([NH:8][C:9]2[N:10]=[N:11][N:12]([CH3:14])[N:13]=2)=[CH:4][CH:3]=1
Reactant: Cn1nnc(Nc2ccc(Br)cn2)n1
Reactant: CC1(C)OB(c2ccc(N3C[C@H](CO)OC3=O)cc2F)OC1(C)C
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: C1COCCO1
Product: Cn1nnc(Nc2ccc(-c3ccc(N4C[C@H](CO)OC4=O)cc3F)cn2)n1
Yield: 29.9 %

Procedure:
5-bromo-N-(2-methyl-2H-tetrazol-5-yl)pyridine-2-amine (200 mg, 0.78 mmol), (R)-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-5-(hydroxylmethyl)oxazolidin-2-one (317 mg, 0.94 mmol), cesium carbonate (508 mg, 1.56 mmol) and Pd(dppf)Cl2 (90 mg, 0.16 mmol) were dissolved in 16 mL dioxane and 4 mL water, heated to 100° C. and reacted for 6 h. The solvent was evaporated to dryness, and the solid was separated by a silica gel column (dichloromethane:methanol=40:1) to obtain (R)-3-(3-fluoro-4-(6-((2-methyl-2H-tetrazol-5-yl)amino)pyridin-3-yl)phenyl)-5-(hydroxylmethyl)oxazolidin-2-one 90 mg, at a yield of 30%.
Reaction SMILES: [C:1]([O:5][C:6](=[O:16])[NH:7][CH2:8][CH2:9][C:10](=[O:15])NCOC)([CH3:4])([CH3:3])[CH3:2].[CH3:17][Mg+].[Br-].OS([O-])(=O)=O.[K+]>C1COCC1.CCOC(C)=O>[C:1]([O:5][C:6](=[O:16])[NH:7][CH2:8][CH2:9][C:10](=[O:15])[CH3:17])([CH3:2])([CH3:3])[CH3:4]
Reactant: C[Mg+]
Reactant: COCNC(=O)CCNC(=O)OC(C)(C)C
Agent: O=S(=O)([O-])O
Agent: [Br-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(=O)CCNC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of BOC-beta-alanine (20 g, 105 mmol), 10-2 (10.3 g, 105 mmol), BOP reagent (46.5 g, 105 mmol), and N-methylmorpholine (46 mL, 420 mmol) in acetonitrile (500 mL) was stirred for 15 h. The reaction was diluted with EtOAc, washed with H2O, 10% KHSO4(aq.), sat. NaHCO3, dried (MgSO4) and concentrated to give crude [2-(methoxymethyl-carbamoyl)-ethyl]-carbamic acid tert-butyl ester 10-3 as a yellow oil. TLC Rf=0.42 (silica, 20% EtOAc/hexanes). To a solution of this crude amide in THF (500 mL) at 0° C. was added CH3MgBr (100 mL of 3M in ether, 300 mmol) over 30 minutes. After 2 h, 10% KHSO4(aq.) was added, the mixture warmed to 25° C., and diluted with EtOAc. The organics were washed with sat. NaHCO3, dried (MgSO4) and concentrated. Flash chromatography (silica, 20% EtOAc/hexanes) gave 10-4 as a yellow oil.
Reaction SMILES: [CH:1]([S:14]([CH2:16][C:17]([OH:19])=O)=[O:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl>[N:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[CH2:21][NH:20][C:17](=[O:19])[CH2:16][S:14]([CH:1]([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:15]
Reactant: NCc1ccccn1
Reactant: O=C(O)CS(=O)C(c1ccccc1)c1ccccc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: ClCCl
Product: O=C(CS(=O)C(c1ccccc1)c1ccccc1)NCc1ccccn1

Procedure:
To a suspension of 15.44 g (0.06 mol) of benzhydrylsulphinylacetic acid in 90 ml of methylene chloride are added 6.48 g (0.06 mol, i.e. 6.17 ml) of 2-aminomethylpyridine and 12.36 g (0.06 mol) of dicyclohexylcarbodiimide are added to the solution thus obtained. The mixture is heated at reflux for about 3 to 4 hours, then left to cool.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:14]([C:15]([O:17]CC=C)=[O:16])=[C:13]([CH3:21])[N:12]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=3)[C:11](=[O:32])[NH:10]2)=[C:5]([S:33][CH3:34])[CH:4]=1)#[N:2].N1CCOCC1>C1COCC1.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>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:14]([C:15]([OH:17])=[O:16])=[C:13]([CH3:21])[N:12]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:30])([F:29])[F:31])[CH:23]=3)[C:11](=[O:32])[NH:10]2)=[C:5]([S:33][CH3:34])[CH:4]=1)#[N:2]
Reactant: C=CCOC(=O)C1=C(C)N(c2cccc(C(F)(F)F)c2)C(=O)NC1c1ccc(C#N)cc1SC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: C1COCCN1
Product: CSc1cc(C#N)ccc1C1NC(=O)N(c2cccc(C(F)(F)F)c2)C(C)=C1C(=O)O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Allyl (rac)-4-[4-cyano-2-(methylsulfanyl)phenyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate (750 mg, 1.54 mmol; Example 39) was dissolved in THF (10 ml), and morpholine (201 mg, 2.308 mmol) was added. The reaction solution was saturated with argon (argon was bubbled through the solution for 30 min). Tetrakis(triphenylphosphine)palladium(0) (7.47 mg, 0.006 mmol) was then added, and the mixture was stirred at RT overnight. Since, by HPLC control, only little conversion could be observed, more tetrakis(triphenylphosphine)palladium(0) (7.47 mg, 0.006 mmol) was added, and the mixture was stirred at RT for a further 3 h. The contents of the flask was then filtered through kieselguhr, and the residue was washed with THF. The filtrate was concentrated under reduced pressure and the residue was recrystallized from diethyl ether (15 ml). The crystals were filtered off with suction and dried under high vacuum. This gave 663 mg (96% of theory) of the target compound.
Reaction SMILES: [CH3:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C:3]1=[O:8].I[CH2:10][CH2:11][CH3:12].CC1(C)CCCCC1=O>>[CH3:1][C:2]1([CH2:10][CH2:11][CH3:12])[CH2:7][CH2:6][CH2:5][CH2:4][C:3]1=[O:8]
Reactant: CCCI
Reactant: CC1CCCCC1=O
Agent: CC1(C)CCCCC1=O
Product: CCCC1(C)CCCCC1=O

Procedure:
The alkylation of 2-methylcyclohexanone with 1-iodopropane takes place in a manner similar to that described above for the preparation of 2,2-dimethyl-cyclohexanone.
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].Br[C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([O:15][CH3:16])[CH:9]=1.[Cl:17][C:18]1[CH:19]=[C:20]([NH:28][C:29](=[O:32])[CH:30]=[CH2:31])[CH:21]=[CH:22][C:23]=1[C:24]([F:27])([F:26])[F:25].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N+](CCCC)(CCCC)(CCCC)CCCC.[Cl-].CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:14][C:11]1[CH:12]=[CH:13][C:8](/[CH:31]=[CH:30]/[C:29]([NH:28][C:20]2[CH:21]=[CH:22][C:23]([C:24]([F:25])([F:26])[F:27])=[C:18]([Cl:17])[CH:19]=2)=[O:32])=[CH:9][C:10]=1[O:15][CH3:16]
Reactant: C=CC(=O)Nc1ccc(C(F)(F)F)c(Cl)c1
Reactant: COc1cc(Br)ccc1Cl
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CN(C)C=O
Product: COc1cc(/C=C/C(=O)Nc2ccc(C(F)(F)F)c(Cl)c2)ccc1Cl
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 72 %

Procedure:
To a suspension of K2CO3 (0.936 g, 6.77 mmol) and n-Bu4NCl (0.753 g, 2.71 mmol) in DMF under an atmosphere of argon were added 4-bromo-1-chloro-2-methoxybenzene (0.600 g, 2.71 mmol), the amide from Step 1 (0.809 g, 3.25 mmol), and molecular sieves. The mixture was stirred for 10 min at rt before adding PPh3 (0.071 g, 0.271 mmol) and Pd(OAc)2 (0.0304 g, 0.135 mmol). The reaction mixture was heated at 80° C. overnight and then cooled to rt and filtered through Celite. The filtrate was diluted with EtOAc and washed with sat. NaHCO3 solution, water, and brine. The organic solution was dried over MgSO4, filtered, and concentrated. The residue was purified by column chromatography to give the desired acrylamide (0-0.755 g, 72%).
Reaction SMILES: C(OC([NH:11][C:12]([CH3:30])([CH3:29])[CH2:13][NH:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:22]([CH3:28])[CH2:23][C:24](=[O:27])[NH:25][N:26]=2)=[CH:17][CH:16]=1)=O)C1C=CC=CC=1.[H][H]>[C].[Pd].CO>[NH2:11][C:12]([CH3:29])([CH3:30])[CH2:13][NH:14][C:15]1[CH:16]=[CH:17][C:18]([C:21]2[CH:22]([CH3:28])[CH2:23][C:24](=[O:27])[NH:25][N:26]=2)=[CH:19][CH:20]=1
Reactant: CC1CC(=O)NN=C1c1ccc(NCC(C)(C)NC(=O)OCc2ccccc2)cc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: CC1CC(=O)NN=C1c1ccc(NCC(C)(C)N)cc1
Yield: 89.3 %

Procedure:
A mixture of 6-[4-(2-benzyloxycarbonylamino-2-methylpropylamino)phenyl]-5-methyl-4,5-dihydro-3(2H)-pyridazinone (0.50 g), 10% palladium-carbon (0.50 g) and methanol (40 ml) was stirred in a stream of hydrogen for 3 hours. The catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure to give 6-[4-(2-amino-2-methylpropyl amino)phenyl]-5-methyl-4,5-dihydro-3(2H)-pyridazinone(0.30 g).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:11]=[C:12]([N+:20]([O-])=O)[C:13]=1[N:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)[C:7]([O:9][CH3:10])=[O:8])([O-])=O>[Pd].CO>[NH2:1][C:4]1[CH:5]=[C:6]([CH:11]=[C:12]([NH2:20])[C:13]=1[N:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)[C:7]([O:9][CH3:10])=[O:8]
Reactant: COC(=O)c1cc([N+](=O)[O-])c(N2CCCCC2)c([N+](=O)[O-])c1
Agent: [Pd]
Solvent: CO
Product: COC(=O)c1cc(N)c(N2CCCCC2)c(N)c1

Procedure:
15.45 G. of methyl 3,5-dinitro-4-piperidinobenzoate [Rec. trav. chim. 73, 68 (1954)]dissolved in 200 ml. of methanol were hydrogenated under normal pressure and at room temperature in the presence of 1 g. of palladium/carbon (5%). After uptake of the theoretical amount of hydrogen, the solution was filtered off from the catalyst and evaporated. By recrystallization of the residue from ethyl acetate/petroleum ether, there was obtained methyl 3,5-diamino-4-piperidinobenzoate having a melting point 133°-134° C.
Reaction SMILES: [CH3:1][S:2]([C:4]1[NH:5][CH:6]=[C:7]([C:9](=[O:26])[CH2:10][C:11]2[CH:16]=[C:15]([C:17]([CH3:20])([CH3:19])[CH3:18])[C:14]([OH:21])=[C:13]([C:22]([CH3:25])([CH3:24])[CH3:23])[CH:12]=2)[CH:8]=1)=[O:3].ClC1C=CC=C(C(OO)=[O:35])C=1>>[CH3:1][S:2]([C:4]1[NH:5][CH:6]=[C:7]([C:9](=[O:26])[CH2:10][C:11]2[CH:16]=[C:15]([C:17]([CH3:18])([CH3:19])[CH3:20])[C:14]([OH:21])=[C:13]([C:22]([CH3:25])([CH3:24])[CH3:23])[CH:12]=2)[CH:8]=1)(=[O:35])=[O:3]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CS(=O)c1cc(C(=O)Cc2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)c[nH]1
Product: CC(C)(C)c1cc(CC(=O)c2c[nH]c(S(C)(=O)=O)c2)cc(C(C)(C)C)c1O

Procedure:
For example, using 2-methylsulfinyl-4-[2-(3,5-di-t-butyl-4-hydroxyphenyl)-1-oxo-ethyl]pyrrole in this general reaction together with one molar equivalent of m-chloroperbenzoic acid yields 2-methylsulfonyl-4-[2-(3,5-di-t-butyl-4-hydroxyphenyl)-1-oxo-ethyl]pyrrole (a compound according to Formula X wherein: m is 1; n is 1; R is H; and X is SO2CH3 ; and Y and Z are each H).
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[CH:12]=CC=C[C:8]=2OC)[N:5]=[CH:4][C:3]=1[C:15]#[N:16].C(NN)(C)C>>[NH2:1][C:2]1[N:6]([CH:7]([CH3:12])[CH3:8])[N:5]=[CH:4][C:3]=1[C:15]#[N:16]
Reactant: COc1ccccc1-n1ncc(C#N)c1N
Agent: CC(C)NN
Product: CC(C)n1ncc(C#N)c1N

Procedure:
Following the procedure for the preparation of 5-amino-1-(2-methoxyphenyl)-1H-pyrazole-4-carbonitrile but substituting 1-isopropylhydrazine provided the title compound. 400 MHz 1H NMR (CDCl3) δ 7.50 (s, 1H), 4.22-4.16 (m, 3H), 1.45 (d, J=6.6 Hz, 6H). MS: (M+H m/z=151.1).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH2:7]=[C:8]1[O:12][C:10](=[O:11])[CH2:9]1>O1CCCC1>[N:1]1([C:10](=[O:11])[CH2:9][C:8](=[O:12])[CH3:7])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1
Reactant: C=C1CC(=O)O1
Reactant: C1COCCN1
Solvent: C1CCOC1
Product: CC(=O)CC(=O)N1CCOCC1
Temperature: 0 °C
Reaction time: 1 h
Yield: 80.6 %

Procedure:
33 ml (0.38 mol) of morpholine were added dropwise at −5 to 0° C. to a solution of 30 g of diketene (0.36 mol) in 300 ml tetrahydrofuran. After 1 h stirring at 0° C. no more starting material was detected by thin layer chromatography. The reaction mixture was evaporated and the residue purified by column chromatography. This gave 49.48 g (0.29 mol, 81% yield) of a white solid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][CH:6]=[CH:5]2.[CH2:13](Br)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Ag+2]>[CH2:13]([O:12][C:8]1[C:9]2[C:4](=[CH:3][C:2]([Br:1])=[CH:11][CH:10]=2)[CH:5]=[CH:6][N:7]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: BrCc1ccccc1
Reactant: O=c1[nH]ccc2cc(Br)ccc12
Agent: [Ag+2]
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Product: Brc1ccc2c(OCc3ccccc3)nccc2c1
Temperature: 25 °C

Procedure:
To a solution of 3.93 g (17.5 mmol) 6-Bromo-2H-isoquinolin-1-one (6) in 150 ml Toluene were added 12.13 g (44.0 mmol) silver carbonate and 3.60 g (21.1 mmol) of benzyl bromide. The reaction mixture was refluxed for 1.5 h and then cooled to room temperature. The solution was filtered. The filtrate was washed with water and the aqueous phase extracted with ethyl acetate. The combined organic layers were dried over magnesium sulfate and evaporated. Final purification was achieved by preparative HPLC. Rt=2.47 min (Method B). Detected mass: 314.1/316.5 (M+H+).
Reaction SMILES: [CH3:1][C:2]1[C:6]([CH3:7])=[C:5]([NH:8][C:9](=[O:16])OCC(Cl)(Cl)Cl)[O:4][N:3]=1.[CH3:17][O:18][C:19]1[CH:20]=[C:21]([C:25]2[N:26]=[C:27]([N:30]3[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]3)[S:28][CH:29]=2)[CH:22]=[CH:23][CH:24]=1.C(N(C(C)C)CC)(C)C.O>CS(C)=O>[CH3:1][C:2]1[C:6]([CH3:7])=[C:5]([NH:8][C:9]([N:33]2[CH2:34][CH2:35][N:30]([C:27]3[S:28][CH:29]=[C:25]([C:21]4[CH:22]=[CH:23][CH:24]=[C:19]([O:18][CH3:17])[CH:20]=4)[N:26]=3)[CH2:31][CH2:32]2)=[O:16])[O:4][N:3]=1
Reactant: COc1cccc(-c2csc(N3CCNCC3)n2)c1
Reactant: Cc1noc(NC(=O)OCC(Cl)(Cl)Cl)c1C
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Product: COc1cccc(-c2csc(N3CCN(C(=O)Nc4onc(C)c4C)CC3)n2)c1
Temperature: 70 °C
Reaction time: 15 h
Yield: 43 %

Procedure:
A mixture of 2,2,2-trichloroethyl (3,4-dimethylisoxazol-5-yl)carbamate (230 mg, 0.799 mmol), 1-[4-(3-methoxyphenyl)-1,3-thiazol-2-yl]piperazine (200 mg, 0.726 mmol) and diisopropylethylamine (0.253 ml, 1.45 mmol) in dimethyl sulfoxide (2.5 ml) was stirred at 70° C. for 15 hours. Water was poured to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with water, and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1), and recrystallized from a mixed solvent of hexane and ethyl acetate to give 129 mg (42.8%) of the desired product as a solid. mp 158-159° C.
Reaction SMILES: [OH:1][CH2:2][CH:3]1[CH2:5][CH:4]1[C:6]1[C:11](=[O:12])[N:10]2[CH:13]=[CH:14][C:15]([CH2:17][CH2:18][C:19]3[S:20][CH:21]=[C:22]([CH:24]([CH3:26])[CH3:25])[N:23]=3)=[CH:16][C:9]2=[N:8][C:7]=1[N:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1.CC(C)=[O:35].OS(O)(=O)=O.O=[Cr](=O)=O.S([O-])([O-])(=O)=S.[Na+].[Na+]>CC(C)=O>[CH:24]([C:22]1[N:23]=[C:19]([CH2:18][CH2:17][C:15]2[CH:14]=[CH:13][N:10]3[C:11](=[O:12])[C:6]([CH:4]4[CH2:5][CH:3]4[C:2]([OH:35])=[O:1])=[C:7]([N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)[N:8]=[C:9]3[CH:16]=2)[S:20][CH:21]=1)([CH3:26])[CH3:25]
Reactant: CC(C)=O
Reactant: CC(C)c1csc(CCc2ccn3c(=O)c(C4CC4CO)c(N4CCOCC4)nc3c2)n1
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Agent: O=S([O-])([O-])=S
Product: CC(C)c1csc(CCc2ccn3c(=O)c(C4CC4C(=O)O)c(N4CCOCC4)nc3c2)n1
Reaction time: 2 h
Yield: 3.9 %

Procedure:
3-[2-(Hydroxymethyl)cyclopropyl]-8-[2-(4-isopropyl-1,3-thiazol-2-yl)ethyl]-2-morpholino-4H-pyrido[1,2-a]pyrimidin-4-one (55 mg, 0.121 mmol) dissolved in acetone (10 ml) was added dropwise with Jones' reagent (130 μl, 0.363 mmol) under ice cooling with and stirred for 2 hours. Then, the reaction solution was further added with Jones' reagent (165 μl) and stirred for 2 hours. Then, the reaction was stopped with saturated sodium thiosulfate, and the reaction solution was extracted with chloroform. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by thin layer silica gel chromatography (chloroform:methanol=10:1) to obtain 2.2 mg (4%) of the title compound as yellow crystals.