Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[CH:10][C:4]=1[CH2:5][NH:6][CH2:7][C:8]#[CH:9].I[C:17]1[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=1>CN(C)C=O.C(N(CC)CC)C.[Cu]I.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>[CH3:1][O:2][C:3]1[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[CH:10][C:4]=1[CH2:5][NH:6][CH2:7][C:8]#[C:9][C:17]1[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=1
Reactant: C#CCNCc1ccc(OC)cc1OC
Reactant: O=[N+]([O-])c1ccc(I)cc1
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COc1ccc(CNCC#Cc2ccc([N+](=O)[O-])cc2)c(OC)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of EXAMPLE 23A (12.47 g, 60.83 mmol) in a mixture of N,N-dimethylformamide (150 mL) and triethylamine (150 mL) was added 1-iodo-4-nitrobenzene (18.18 g, 73 mmol), CuI (2.33 g, 12.2 mmol) and tetrakis(triphenylphosphine)palladium(0) (3.51 g, 3.04 mmol). The reaction mixture was stirred at room temperature overnight, and partitioned between ethyl acetate and brine. The organic phase was washed with brine, and concentrated. The crude material was purified by flash chromatography (20% ethyl acetate in hexane) to afford the title compound 1H NMR (400 MHz, dimethylsulfoxide-d6): δ 2.36 (br s, 1H), 3.59 (s, 2H), 3.72 (s, 2H), 3.74 (s, 3H), 3.77 (s, 3H), 6.48 (dd, J=6.0, 2.4 Hz, 1H), 6.53 (d, J=2.0 Hz, 1H), 7.20 (d, J=8.4 Hz, 1H), 7.67 (d, J=8.8 Hz, 2H), 8.22 (d, J=8.8 Hz, 2H).
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[CH2:4][NH:5][NH2:6].Cl.Cl[CH:13](OCC)[C:14]([O:16][CH2:17][CH3:18])=[O:15].[OH-].[Na+]>O.O1CCOCC1>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[CH2:4][NH:5]/[N:6]=[CH:13]/[C:14]([O:16][CH2:17][CH3:18])=[O:15]
Reactant: NNCc1ccccc1F
Reactant: CCOC(=O)C(Cl)OCC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Product: CCOC(=O)/C=N/NCc1ccccc1F
Temperature: 25 °C
Reaction time: 1 h

Procedure:
(2-Fluorobenzyl)hydrazine (1.00 g, 7.14 mmol) is suspended in water (3 ml), and the mixture is brought to pH 4 with 4N hydrochloric acid. It is then cooled in an ice bath, and a solution of ethyl chloro(ethoxy)acetate (1.37 g, 8.21 mmol) in dioxane (10 ml) is added. The mixture is stirred at RT for 1 h, then made weakly alkaline (pH 8) with 1N sodium hydroxide solution and extracted with ethyl acetate. The organic phase is dried over sodium sulfate. The crude product is purified by chromatography on silica gel (eluent: dichloromethane with increasing methanol content). 1.40 g (88% of theory) of the desired compound are obtained.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[N:7]1([C:12]2[N:16]([C:17]([CH3:20])([CH3:19])[CH3:18])[N:15]=[CH:14][C:13]=2[C:21](OCC)=[O:22])[CH:11]=[CH:10][CH:9]=[CH:8]1.O>O1CCCC1>[N:7]1([C:12]2[N:16]([C:17]([CH3:18])([CH3:19])[CH3:20])[N:15]=[CH:14][C:13]=2[CH2:21][OH:22])[CH:8]=[CH:9][CH:10]=[CH:11]1
Reactant: CCOC(=O)c1cnn(C(C)(C)C)c1-n1cccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)n1ncc(CO)c1-n1cccc1
Reaction time: 8 h
Yield: 94 %

Procedure:
1.30 g of lithium aluminum hydride was suspended in 50 ml of tetrahydrofuran and thereto, under a nitrogen atmosphere, a solution of 8.95 g of ethyl 5-(1H-pyrrol-1-yl)-1-t-butyl-1H-pyrazole-4-carboxylate in 20 ml of tetrahydrofuran was added dropwise over 15 minutes under ice-cooling. The mixture was stirred for 8 hours under ice-cooling. After water was added, the reaction mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 7.06 g of [5-(1H-pyrrol-1-yl)-1-t-butyl-1H-pyrazol-4-yl]methanol.
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[C:6]#[N:7].[CH2:11]([OH:13])[CH3:12]>>[ClH:2].[Cl:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[C:6](=[NH:7])[O:13][CH2:11][CH3:12]
Reactant: N#Cc1cccc(Cl)c1
Reactant: CCO
Agent: Cl
Product: CCOC(=N)c1cccc(Cl)c1
Temperature: 25 °C
Reaction time: 17 h
Yield: 94 %

Procedure:
Hydrogen chloride was bubbled through a solution of 3-chlorobenzonitrile (25.5 g, 0.185 mol) in ethanol (250 mL) to saturation under ice-cooling and the reaction mixture was stirred at room temperature for 17 hours. The solvent was distilled off under reduced pressure and the residual solid was suspended in diethyl ether (200 mL), then collected by filtration, washed with diethyl ether (200 mL) and dried in vacuo at 60° C. to give 38.3 g (94%) of ethyl 3-chlorobenzimidate hydrochloride as white crystals.
Reaction SMILES: C([O-])([O-])=O.[Cs+].[Cs+].[C:7]1([OH:13])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Br[C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=1[N+:22]([O-:24])=[O:23].O>C1COCC1.C(OCC)(=O)C>[Br:21][C:18]1[CH:19]=[CH:20][C:15]([O:13][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[C:16]([N+:22]([O-:24])=[O:23])[CH:17]=1
Reactant: Oc1ccccc1
Reactant: O=[N+]([O-])c1cc(Br)ccc1Br
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: O=[N+]([O-])c1cc(Br)ccc1Oc1ccccc1
Reaction time: 0.25 h
Yield: 108.8 %

Procedure:
Cs2CO3 (4 g, 12.3 mmol) was added to a solution of phenol (1 g, 10.6 mmol) in 50 mL of THF under N2 atmosphere. After stirring for 15 min. 1,4-dibromo-2-nitrobenzene (2.81 g, 10 mmol) was added. The resulting mixture was heated to reflux and stirred overnight at reflux. Water and ethyl acetate were added, followed by extraction with ethyl acetate (3×). The combined organic layers were washed with water and brine, dried (Na2SO4) and evaporated to give the crude compound (3.2 g, 75%).
Reaction SMILES: [NH2:1][C:2]1[N:3]=[N:4][CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[N:7]=1.CC(C)([O-])C.[K+].[CH3:21][NH:22][C:23]([C:25]1[CH:30]=[C:29](Cl)[CH:28]=[CH:27][N:26]=1)=[O:24].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C(OCC)(=O)C.O>[NH2:1][C:2]1[N:3]=[N:4][CH:5]=[C:6]([C:8]2[CH:9]=[CH:10][C:11]([O:14][C:29]3[CH:28]=[CH:27][N:26]=[C:25]([C:23]([NH:22][CH3:21])=[O:24])[CH:30]=3)=[CH:12][CH:13]=2)[N:7]=1
Reactant: Nc1nncc(-c2ccc(O)cc2)n1
Reactant: CNC(=O)c1cc(Cl)ccn1
Agent: CC(C)(C)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CNC(=O)c1cc(Oc2ccc(-c3cnnc(N)n3)cc2)ccn1
Temperature: 100 °C
Reaction time: 0.25 h

Procedure:
3.71 g (19.73 mmol) of 4-(3-amino-[1,2,4]triazin-5-yl)-phenol can be dissolved in 80 mL of anhydrous DMF under argon atmosphere. 2.44 g (21.71 mmol, 1.1 equivalent) of solid potassium tert-butoxide can be added to the solution. The resulting mixture can be heated to about 100° C. and stirred at that temperature for 15 min. Then a solution of 3.7 g (21.71 mmol, 1.1 equivalent) of 4-chloro-pyridine-2-carboxylic acid methylamide in 10 mL of anhydrous DMF can be added, followed by 3.28 g (23.68 mmol, 1.2 eq.) of anhydrous K2CO3. The reaction mixture can be heated at 140° C. for 30 hrs. The progress of the reaction can be monitored by LC/MS. Then it can be allowed to cool down to ambient temperature. The resulting mixture can be poured into 500 mL of water and 100 mL of ethyl acetate. The aqueous layer can be extracted with a number of solvents, such as ethyl acetate, methylene chloride or ether. The combined extracts can be washed 3 times with 100 mL of water, then with brine and dried over anhydrous sodium sulfate. Solvent can be removed in vacuum to give crude 4-[4-(3-amino-[1,2,4]triazin-5-yl)-phenoxy]-N-methylpyridine-2-carboxamide. The product can be than purified using silica gel column chromatography. Those having ordinary skill in the art can determine which solvent system can be used as an eluents in the chromatographic purification.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([CH2:9][CH:10](OCC)OCC)=[C:4]([NH:17][CH2:18][C:19]2[S:20][CH:21]=[CH:22][CH:23]=2)[N:3]=1.[OH-].[NH4+]>Cl.C(O)C>[NH2:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]2[CH:9]=[CH:10][N:17]([CH2:18][C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)[C:4]=2[N:3]=1
Reactant: CCOC(Cc1c(Cl)nc(N)nc1NCc1cccs1)OCC
Agent: Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: CCO
Product: Nc1nc(Cl)c2ccn(Cc3cccs3)c2n1
Temperature: 25 °C
Reaction time: 24 h
Yield: 77.3 %

Procedure:
A suspension of 2-amino-4-chloro-6-[(2-thienylmethyl) amino]-5-(2,2-diethoxyethyl)pyrimidine (1.0 g, 2.80 mmol) in 65 ml of 0.3N HCl and ethanol (2.25:1) was stirred at 25° C. for 24 hours. The reaction mixture was neutralized with ammonium hydroxide solution and the product collected by filtration. TLC analysis showed that the reaction was not complete, so, the product was resuspended in 50 ml of 0.2N HCl and stirred for 48 hours. The reaction mixture was neutralized with NH4OH solution and concentrated. The residue was taken up in water and then evaporated to dryness to give yellow solid (573 mg) (77.3%). This was used in the next step without further purification.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][C:4](=[O:7])[CH2:3][CH2:2]1.[CH2:8](O)[CH2:9][OH:10].C1(C)C(S(O)(=O)=O)=CC=CC=1>C1C=CC=CC=1>[O:10]1[C:4]2([CH2:5][CH2:6][O:1][CH2:2][CH2:3]2)[O:7][CH2:8][CH2:9]1
Reactant: O=C1CCOCC1
Reactant: OCCO
Agent: Cc1ccccc1S(=O)(=O)O
Solvent: c1ccccc1
Product: C1CC2(CCO1)OCCO2
Temperature: 25 °C
Yield: 80.7 %

Procedure:
A mixture of tetrahydro-4-pyranone (10 g, 99.9 mmol), ethylene glycol (20 mL, 150 mmol) and catalytic toluene sulfonic acid was refluxed in benzene (120 mL) for 5 h. After cooling to room temp, the benzene layer was decanted from the dark oil in the bottom of the flask and was concentrated. The resulting oil was taken up in methylene chloride and shaken in a separatory funnel. The CH2Cl2 layer was decanted from the insoluble oil. The CH2Cl2 layer was concentrated to give the title compound as a pale yellow oil (11.62 g, 81% yield). 1H-NMR (300 MHz, CDCl3) δ: 3.91 (4H, s), 3.71 (4H, t, J=5.5 Hz), 1.68 (4H, t, J=5.7 Hz).
Reaction SMILES: Br[C:2]1[N:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]2=[N:4][C:3]=1[C:11]1[CH:18]=[CH:17][C:14]([CH:15]=[O:16])=[CH:13][CH:12]=1.[F:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1.C([O-])([O-])=O.[K+].[K+].O.C(O)C>C1(C)C=CC=CC=1.O>[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:2]2[N:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]3=[N:4][C:3]=2[C:11]2[CH:18]=[CH:17][C:14]([CH:15]=[O:16])=[CH:13][CH:12]=2)=[CH:22][CH:21]=1
Reactant: O=Cc1ccc(-c2nc3ccccn3c2Br)cc1
Reactant: OB(O)c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: Cc1ccccc1
Solvent: CCO
Product: O=Cc1ccc(-c2nc3ccccn3c2-c2ccc(F)cc2)cc1
Temperature: 90 °C

Procedure:
0.46 g (1.5 mM) 4-(3-bromoimidazo[1,2-a]pyridin-2-yl)benzaldehyde (prepared as described by Sundberg et al.; J. Heterocyclic Chem., 25, 129, 1988) is dissolved in 5 mL of toluene. To this mixture is added 4-fluorphenyl boronic acid (1.5 eq) followed by tetrakis triphenylphosphine palladium (0) 10% by wt, K2CO3 (3 eq) and ethanol water mixture (4 mL). The reaction mixture is heated at 90° C. for 4-6 h. The reaction is cooled to room temperature and 20 mL of water is added and the reaction mixture is extracted with ethyl acetate. The organic layer is dried and concentrated. The crude is purified by flash column chromatography to obtain the desired compound.
Reaction SMILES: C(O)(C(F)(F)F)=O.[SiH](CC)(CC)CC.[CH3:15][C:16]1[C:20]([C:21]2[N:22]([C:35]3[CH:40]=[CH:39][C:38]([OH:41])=[CH:37][CH:36]=3)[C:23]3[C:28]([C:29]=2[CH:30](O)[C:31]([NH2:33])=[O:32])=[CH:27][CH:26]=[CH:25][CH:24]=3)=[C:19]([CH3:42])[O:18][N:17]=1>>[CH3:15][C:16]1[C:20]([C:21]2[N:22]([C:35]3[CH:36]=[CH:37][C:38]([OH:41])=[CH:39][CH:40]=3)[C:23]3[C:28]([C:29]=2[CH2:30][C:31]([NH2:33])=[O:32])=[CH:27][CH:26]=[CH:25][CH:24]=3)=[C:19]([CH3:42])[O:18][N:17]=1
Reactant: Cc1noc(C)c1-c1c(C(O)C(N)=O)c2ccccc2n1-c1ccc(O)cc1
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Product: Cc1noc(C)c1-c1c(CC(N)=O)c2ccccc2n1-c1ccc(O)cc1
Reaction time: 1 h

Procedure:
1 ml TFA and 19 μl Et3SiH were added to 2-(2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1H-indol-3-yl)-2-hydroxyacetamide at 0° C. and the mixture was stirred for 60 min. The solvent was evaporated without heating followed by short silica gel purification (EtOAc/heptane; 1:9 to 8:2) to provide 2-(2-(3,5-dimethylisoxazol-4-yl)-1-(4-hydroxyphenyl)-1H-indol-3-yl)acetamide (E37). ES/MS m/z: 362.3 (M+H); 1H NMR (methanol-d3, 500 MHz): 8.98 m, 1H), 8.46-8.35 (m, 5H), 8.16 (m, 2H), 4.78 (d, 21-1, J=1.9 Hz), 3.54 (s, 3H) and 3.19 (s, 3H).
Reaction SMILES: [NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[O:12][CH2:13][C:14]([NH2:17])([CH3:16])[CH3:15])[N:5]=[C:4]([CH3:18])[C:3]=1[C:19]([O:21][CH2:22][CH3:23])=[O:20].[O:24]1[CH2:29][CH2:28][CH:27]([C:30](O)=[O:31])[CH2:26][CH2:25]1>>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[O:12][CH2:13][C:14]([CH3:16])([NH:17][C:30]([CH:27]2[CH2:28][CH2:29][O:24][CH2:25][CH2:26]2)=[O:31])[CH3:15])[N:5]=[C:4]([CH3:18])[C:3]=1[C:19]([O:21][CH2:22][CH3:23])=[O:20]
Reactant: O=C(O)C1CCOCC1
Reactant: CCOC(=O)c1c(C)nc2cccc(OCC(C)(C)N)c2c1N
Product: CCOC(=O)c1c(C)nc2cccc(OCC(C)(C)NC(=O)C3CCOCC3)c2c1N

Procedure:
Prepared as in Example Da from ethyl 4-amino-5-(2-amino-2-methylpropoxy)-2-methylquinoline-3-carboxylate (Example Db) and tetrahydro-2H-pyran-4-carboxylic acid as a pale-yellow solid (63%). MS 430 (MH+).
Reaction SMILES: [C:1](=O)([O-])[O-].[K+].[K+].IC.[C:9]([C:11]1[C:12]([F:38])=[C:13]([NH:18][C:19]([C:21]2[N:25]([CH3:26])[N:24]=[C:23]([C:27]([F:33])([F:32])[C:28]([F:31])([F:30])[F:29])[C:22]=2[C:34]([F:37])([F:36])[F:35])=[O:20])[CH:14]=[CH:15][C:16]=1[F:17])#[N:10].O>CN(C=O)C>[C:9]([C:11]1[C:12]([F:38])=[C:13]([N:18]([CH3:1])[C:19]([C:21]2[N:25]([CH3:26])[N:24]=[C:23]([C:27]([F:32])([F:33])[C:28]([F:31])([F:30])[F:29])[C:22]=2[C:34]([F:36])([F:37])[F:35])=[O:20])[CH:14]=[CH:15][C:16]=1[F:17])#[N:10]
Reactant: Cn1nc(C(F)(F)C(F)(F)F)c(C(F)(F)F)c1C(=O)Nc1ccc(F)c(C#N)c1F
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Solvent: O
Product: CN(C(=O)c1c(C(F)(F)F)c(C(F)(F)C(F)(F)F)nn1C)c1ccc(F)c(C#N)c1F
Reaction time: 5 h
Yield: 98.5 %

Procedure:
Potassium carbonate (1.28 g, 5.58 mmol, 2.0 eq.) and iodomethane (0.5 ml, 1.2 g, 8.4 mmol, 3.0 eq.) were added to a solution of N-(3-cyano-2,4-difluorophenyl)-1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide (1.25 g, 2.79 mmol) in DMF (4 ml). After 5 h, water was added, the mixture was extracted with ethyl acetate and the extract was washed with sat. aq. sodium chloride solution and dried over MgSO4. Filtration through silica gel gave N-(3-cyano-2,4-difluorophenyl)-N,1-dimethyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide (1.27 g, 98%) as a mixture of rotamers which was reacted further without additional purification.
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]2[CH:22]=[CH:21][C:9]3[C:10]4[N:11]=[C:12]([C:18]([OH:20])=O)[S:13][C:14]=4[CH2:15][CH2:16][O:17][C:8]=3[CH:7]=2)[CH:3]=[N:2]1.[CH3:23][NH:24][CH2:25][CH2:26][CH:27]([CH3:29])[CH3:28]>>[CH3:23][N:24]([CH2:25][CH2:26][CH:27]([CH3:29])[CH3:28])[C:18]([C:12]1[S:13][C:14]2[CH2:15][CH2:16][O:17][C:8]3[CH:7]=[C:6]([C:4]4[CH:3]=[N:2][NH:1][CH:5]=4)[CH:22]=[CH:21][C:9]=3[C:10]=2[N:11]=1)=[O:20]
Reactant: CNCCC(C)C
Reactant: O=C(O)c1nc2c(s1)CCOc1cc(-c3cn[nH]c3)ccc1-2
Product: CC(C)CCN(C)C(=O)c1nc2c(s1)CCOc1cc(-c3cn[nH]c3)ccc1-2

Procedure:
Following Example 216, to a well stirred solution of 8-(1H-Pyrazol-4-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid and N,3-dimethylbutan-1-amine to give 255. MS: (ESI+)=397.1
Reaction SMILES: [CH3:1][C@H:2]1[C@@H:7]2[C@@:8]3([CH3:40])[C@@H:15]([O:16][C:17]([CH3:19])=[O:18])[C@@H:14]([O:20][C:21]([CH3:23])=[O:22])[C@@H:13]4[C@@:24]5([CH3:39])[C@@H:29]([O:30][C:31]([CH3:33])=[O:32])[C@H:28]6[O:34][C@H:27]6[CH2:26][C@@H:25]5[C:35]([C@H:37]([OH:38])[C@H:12]4[C@@H:9]3[C@@H:10]([OH:11])[C@H:6]2[C@@:5]2([CH3:47])[C@@:41]([OH:46])([CH3:45])[C:42]([O:44][C:4]2=[CH:3]1)=[O:43])=[O:36].N1C=CC=CC=1.[C:54](OC(=O)C)(=[O:56])[CH3:55]>>[CH3:1][C@H:2]1[C@@H:7]2[C@@:8]3([CH3:40])[C@@H:15]([O:16][C:17]([CH3:19])=[O:18])[C@@H:14]([O:20][C:21]([CH3:23])=[O:22])[C@@H:13]4[C@@:24]5([CH3:39])[C@@H:29]([O:30][C:31]([CH3:33])=[O:32])[C@H:28]6[O:34][C@H:27]6[CH2:26][C@@H:25]5[C:35]([C@H:37]([OH:38])[C@H:12]4[C@@H:9]3[C@@H:10]([O:11][C:54]([CH3:55])=[O:56])[C@H:6]2[C@@:5]2([CH3:47])[C@@:41]([OH:46])([CH3:45])[C:42]([O:44][C:4]2=[CH:3]1)=[O:43])=[O:36]
Reactant: CC(=O)OC(C)=O
Reactant: CC(=O)O[C@H]1[C@H]2[C@H]([C@@H]3[C@@H](O)[C@@H]4[C@H]([C@H](C)C=C5OC(=O)[C@@](C)(O)[C@@]54C)[C@@]3(C)[C@H]1OC(C)=O)[C@@H](O)C(=O)[C@H]1C[C@@H]3O[C@@H]3[C@H](OC(C)=O)[C@]21C
Solvent: c1ccncc1
Product: CC(=O)O[C@@H]1[C@H]2[C@H]3[C@H]([C@H](OC(C)=O)[C@H](OC(C)=O)[C@]2(C)[C@@H]2[C@@H]1[C@]1(C)C(=C[C@H]2C)OC(=O)[C@@]1(C)O)[C@]1(C)[C@H](C[C@@H]2O[C@@H]2[C@@H]1OC(C)=O)C(=O)[C@@H]3O
Reaction time: 48 h

Procedure:
Taccalonolide B (3 mg) was dissolved in 0.3 mL of acetic anhydride. To this solution, 0.3 mL of anhydrous pyridine was added and was kept at room temperature for 48 h. The reaction solution was dried in miVac and separated using C18 HPLC to yield taccalonolide A and TB-Ac-16.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH2:9][CH2:8]2)(=[O:4])=[O:3]>C(Cl)(Cl)Cl.[O-2].[O-2].[Mn+4]>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[CH:8]2)(=[O:4])=[O:3]
Reactant: CS(=O)(=O)c1ccc2c(c1)CCN2
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClC(Cl)Cl
Product: CS(=O)(=O)c1ccc2[nH]ccc2c1
Temperature: 25 °C
Reaction time: 9 h
Yield: 71.6 %

Procedure:
A solution of 5-(methylsulfonyl)indoline (0.213 g, 1.08 mmol) in chloroform (4 mL) was added with manganese dioxide (0.939 g, 10.8 mmol), and the mixture was stirred at room temperature for 9 hours. The reaction mixture was filtered through Celite, and the resulting filtrate was concentrated to obtain 5-(methylsulfonyl)-1H-indole (0.151 g, 71%).
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][C:10]1[C:11]([CH2:16][CH3:17])=[N:12][NH:13][C:14]=1[NH2:15].O=[C:19]([CH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1)[CH2:20][C:21](OCC)=[O:22]>C(O)(=O)C>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][C:10]1[C:11]([CH2:16][CH3:17])=[N:12][N:13]2[C:21]([OH:22])=[CH:20][C:19]([CH:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)=[N:15][C:14]=12
Reactant: CCOC(=O)CC(=O)C1CCOCC1
Reactant: CCc1n[nH]c(N)c1Cc1cccc(Cl)c1Cl
Solvent: CC(=O)O
Product: CCc1nn2c(O)cc(C3CCOCC3)nc2c1Cc1cccc(Cl)c1Cl
Reaction time: 8 h

Procedure:
To a suspension of 4-[(2,3-dichlorophenyl)methyl]-3-ethyl-1H-pyrazol-5-amine (257 mg, 0.95 mmol) in acetic acid (2 mL) was added ethyl 3-oxo-3-(tetrahydro-2H-pyran-4-yl)propanoate (200, 1.0 mmol). The reaction vessel was sealed, stirred and irradiated (microwave) at 140° C. for 40 minutes. Reaction mixture was cooled and diluted with acetic acid (2 mL). It was stood still overnight. The precipitate was collected, washed with acetic acid (1 mL), then with methanol (2 mL×2) and dried to afford expected compound. (288 mg, 71%); LC/MS: MS (ES+) m/e 406 (MH+); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.06 (t, J=7.45 Hz, 3H) 1.76 (br. s., 4H) 1.91 (s, 3H) 2.45 (q, J=7.41 Hz, 2H) 3.39 (br. s., 2H) 4.07 (s, 2H) 5.56 (s, 1H) 6.87 (s, 1H) 7.25 (s, 1H) 7.51 (s, 1H).
Reaction SMILES: [NH2:1][C:2]1[NH:3][C:4](=[O:22])[C:5]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=3)[CH:9]=[CH:8][C:6]=2[N:7]=1.[C:23](O)(=[O:25])[CH3:24]>C(OC(=O)C)(=O)C>[C:23]([NH:1][C:2]1[NH:3][C:4](=[O:22])[C:5]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=3)[CH:9]=[CH:8][C:6]=2[N:7]=1)(=[O:25])[CH3:24]
Reactant: COc1ccc(-c2ccc3nc(N)[nH]c(=O)c3n2)cc1OC
Reactant: CC(=O)O
Solvent: CC(=O)OC(C)=O
Product: COc1ccc(-c2ccc3nc(NC(C)=O)[nH]c(=O)c3n2)cc1OC
Yield: 77 %

Procedure:
2-amino-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidin-4(3H)-one (2.0 g, 6.70 mmol) was suspended in acetic anhydride (180 ml) and acetic acid (20 ml) and the mixture was refluxed for 16 hours. The hot suspension was filtered and the filtrate was concentrated under reduced pressure until crystallization started. The precipitate was filtered off to give the pure title compound (1.76 g, yield 77%) which was characterized by its mass spectrum as follows: MS (m/z): 341 ([M+H]+, 100).
Reaction SMILES: N#N.[C:3]([O:7][C:8]([NH:10][CH2:11][C:12]([OH:14])=O)=[O:9])([CH3:6])([CH3:5])[CH3:4].C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1.[CH3:40][O:41][C:42](=[O:53])[CH:43]([NH2:52])[CH:44]([OH:51])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>C(Cl)Cl.OS([O-])(=O)=O.[K+]>[CH3:40][O:41][C:42](=[O:53])[CH:43]([NH:52][C:12](=[O:14])[CH2:11][NH:10][C:8]([O:7][C:3]([CH3:4])([CH3:5])[CH3:6])=[O:9])[CH:44]([OH:51])[C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1
Reactant: CC(C)(C)OC(=O)NCC(=O)O
Reactant: COC(=O)C(N)C(O)c1ccccc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: N#N
Agent: O=S(=O)([O-])O
Solvent: ClCCl
Product: COC(=O)C(NC(=O)CNC(=O)OC(C)(C)C)C(O)c1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of tert-butoxycarbonylamino-acetic acid (906 mg, 5.12 mmol) in CH2Cl2 (27.0 mL) was treated at 0° C. with HOBt (777 mg, 5.64 mmol), DCC (1.17 g, 5.64 mmol) N-methylmorpholine (0.85 mL, 7.68 mmol) and 2-amino-3-hydroxy-3-phenyl-propionic acid methyl ester (1.00 g, 5.12 mmol). The resulting mixture was stirred at rt for 2 h, poured in 5% KHSO4 (100 mL), stirred for 15 min, filtered and washed with CH2Cl2. The aqueous phase was extracted with CH2Cl2 and the combined organic phases were washed with sat. aq. NaHCO3, brine, dried over MgSO4, filtered, and the solvent removed under reduced pressure. Purification of the residue by FC(CH2Cl2 to 99:1 CH2Cl2-MeOH) gave the title compound as a white solid. TLC: rf (90:10 CH2Cl2-MeOH)=0.48. LC-MS-conditions 02: tR=0.85 min, [M+H]+=353.05.
Reaction SMILES: Cl[CH2:2][CH:3]([OH:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[O:10][CH3:11].[OH-].[K+]>O1CCOCC1.O>[CH3:11][O:10][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[CH:3]1[CH2:2][O:12]1
Reactant: COc1ccccc1C(O)CCl
Agent: [K+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Product: COc1ccccc1C1CO1
Temperature: 25 °C
Reaction time: 3 h
Yield: 44.4 %

Procedure:
1.4 g of α-chloromethyl-2-methoxybenzylalcohol (crude oil) are dissolved in 12 ml of dioxane, and a solution of 840 mg of potassium hydroxide in 5 ml of water is added thereto. The mixture is stirred at room temperature for 3 hours. Then, the reaction mixture is poured into ice-water, and the aqueous mixture is extracted with benzene. The extract is dried and evaporated to remove solvent. 0.5 g of 2-(2-methoxyphenyl)oxirane are obtained as a crude product.
Reaction SMILES: [CH2:1]([N:5]1[C:12]([NH2:13])=[C:11]([N:14]=O)[C:9](=[O:10])[NH:8][C:6]1=[O:7])[CH2:2][CH2:3][CH3:4].[OH-].[NH4+].S(S([O-])=O)([O-])=O.[Na+].[Na+]>>[CH2:1]([N:5]1[C:12]([NH2:13])=[C:11]([NH2:14])[C:9](=[O:10])[NH:8][C:6]1=[O:7])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCn1c(N)c(N=O)c(=O)[nH]c1=O
Agent: O=S([O-])S(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Product: CCCCn1c(N)c(N)c(=O)[nH]c1=O
Temperature: 80 °C
Reaction time: 0.5 h
Yield: 78.2 %

Procedure:
84.8 g (0.4 mole) of 1-butyl-5-nitroso-6-aminouracil are suspended in 440 ml of a concentrated 50% aqueous solution of ammonium hydroxide. The resulting suspension is heated to 80° C. 88 g (0.48 mole) of sodium dithionite are added in portions with stirring over a period of 30 minutes. Stirring is then continued for 30 minutes at 80° C. and then overnight at room temperature. The product is cooled in ice, the precipitate is filtered and then washed with a little ice water, giving 62 g crystals in the form of a very fine powder.