Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH3:15])[C:10]([OH:12])=O)[N:8]=1)=[O:2].[NH2:16][CH:17]1[C:50](=[O:51])[N:19]2[C:20]([C:34]([O:36][CH:37]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)=[O:35])=[C:21]([CH2:24][S:25]/[CH:26]=[CH:27]\[C:28]3[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=3)[CH2:22][S:23][C@H:18]12.C[Si](NC(=O)N[Si](C)(C)C)(C)C.C(OCC)(=O)C>O1CCCC1.O>[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH3:15])[C:10]([NH:16][CH:17]2[C:50](=[O:51])[N:19]3[C:20]([C:34]([O:36][CH:37]([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)[C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=4)=[O:35])=[C:21]([CH2:24][S:25]/[CH:26]=[CH:27]\[C:28]4[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=4)[CH2:22][S:23][C@H:18]23)=[O:12])[N:8]=1)=[O:2]
Reactant: CON=C(C(=O)O)c1csc(NC=O)n1
Reactant: NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(CS/C=C\c3cccnc3)CS[C@H]12
Agent: C[Si](C)(C)NC(=O)N[Si](C)(C)C
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1CCOC1
Product: CON=C(C(=O)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(CS/C=C\c3cccnc3)CS[C@H]12)c1csc(NC=O)n1
Temperature: -20 °C
Reaction time: 0.5 h
Yield: 37.6 %

Procedure:
2-(2-Formamidothiazol-4-yl)-2-methoxyiminoacetic acid (syn isomer) (1.06 g) was added to the mixture at 0° C. The mixture was stirred for 30 minutes at the same temperature to give an activated acid solution. On the other hand, to the suspension of benzhydryl 7-amino-3-[(Z)-2-(3-pyridyl)vinylthiomethyl]-3-cephem-4-carboxylate (2.38 g) in tetrahydrofuran (30 ml) was added bis(trimethylsilyl)urea (2.8 g) at ambient temperature. The mixture was stirred at 48° C. for 30 minutes to give a clear solution. The solution was cooled to -20° C. To this solution was added the activated acid solution obtained above at once at -20° C. The mixture was stirred at -20°~-12° C. for 40 minutes. To this mixture was added a mixture of ethyl acetate (150 ml) and water. The separated organic layer was washed with an aqueous solution of sodium bicarbonate, dried over magnesium sulfate and concentrated in vacuo to give a solid. The solid was recrystallized from ethyl acetate to give benzhydryl 7-[2-(2-formamidothiazol-4-yl)-2-methoxyiminoacetamido]-3-[(Z)-2-(3-pyridyl)vinylthiomethyl]-3-cephem-4-carboxylate (syn isomer) (1.26 g).
Reaction SMILES: [F:1][C:2]1[C:3]([O:20]CC2C=CC=CC=2)=[C:4]([C:17](=[O:19])[CH3:18])[CH:5]=[C:6]([F:16])[C:7]=1[O:8]CC1C=CC=CC=1>CCOC(C)=O>[F:1][C:2]1[C:3]([OH:20])=[C:4]([C:17](=[O:19])[CH3:18])[CH:5]=[C:6]([F:16])[C:7]=1[OH:8]
Reactant: CC(=O)c1cc(F)c(OCc2ccccc2)c(F)c1OCc1ccccc1
Solvent: CCOC(C)=O
Product: CC(=O)c1cc(F)c(O)c(F)c1O

Procedure:
A 0.4M solution of Compound 25 over 10% Pd/C (10% wt. to Compound 25) in EtOAc is hydrogenated at 40 psi for 24 hours. The reaction is filtered and concentrated in vacuo followed by sublimation to yield Compound 26.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[CH3:22])[C:5]([C:7]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([F:18])[CH:14]=2)[NH:9][CH:8]=1)=[O:6].C[Si](C)(C)[N-][Si](C)(C)C.[K+].[Br:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([CH2:40]Br)[N:35]=1>O1CCCC1>[Br:33][C:34]1[N:35]=[C:36]([CH2:40][N:9]2[C:10]3[C:15](=[CH:14][C:13]([F:18])=[CH:12][CH:11]=3)[C:16](=[O:17])[C:7]([C:5](=[O:6])[C:4]3[CH:19]=[CH:20][C:21]([CH3:22])=[C:2]([CH3:1])[CH:3]=3)=[CH:8]2)[CH:37]=[CH:38][CH:39]=1
Reactant: Cc1ccc(C(=O)c2c[nH]c3ccc(F)cc3c2=O)cc1C
Reactant: BrCc1cccc(Br)n1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: C1CCOC1
Product: Cc1ccc(C(=O)c2cn(Cc3cccc(Br)n3)c3ccc(F)cc3c2=O)cc1C
Reaction time: 0.08 h
Yield: 73.8 %

Procedure:
To a solution of 0.050 g (0.169 mmol) of 3-(3,4-dimethyl-benzoyl)-6-fluoro-1H-quinolin-4-one 4tt in 1.0 mL of tetrahydrofuran was added 0.4 mL (0.5 M in toluene, 0.203 mmol) of potassium hexamethyldisilazide and the reaction solution was stirred for 5 min, followed by the addition of 50.9 mg (0.203 mmol) of 2-bromo-6-bromomethyl-pyridine in 0.5 ml of tetrahydrofuran. The resultant solution was stirred at 60° C. for 3 h. The reaction solution was quenched by the addition of water and the aqueous phase was extracted with 3×5 mL of ether. The combined organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to yield 58 mg of 1-(6-Bromo-pyridin-2-ylmethyl)-3-(3,4-dimethyl-benzoyl)-6-fluoro-1H-quinolin-4-one 4tt as a yellow solid: LC-MSD, m/z for C24H18BrFN2O2, [M+H]=465.4, 466.5, 467.4, 468.4; Reverse phase HPLC gradient, 20-95% acetonitrile with 0.1% TFA in 4 minutes, retention time=2.8 min; 1H NMR (400 MHz, CDCl3): δ 8.27 (1H, s), 8.12 (1H, m), 7.64 (1H, s), 7.56 (1H, m), 7.51 (1H, m), 7.47 (1H, m), 7.40-7.34 (2H, m), 7.19 (1H, m), 7.00 (1H, m), 5.46 (2H, s), 2.32 (3H, s), 2.31 (3H, s).
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.BrC1C=CC(OC)=C([N+]([O-])=O)C=1.[CH3:29][O:30][C:31]1[C:36]2[N:37]=[C:38]([NH:40][C:41]([C:43]3[S:44][C:45]([CH3:48])=[CH:46][CH:47]=3)=[O:42])[S:39][C:35]=2[C:34](N2CCOCC2)=[CH:33][CH:32]=1>>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:34]2[C:35]3[S:39][C:38]([NH:40][C:41]([C:43]4[S:44][C:45]([CH3:48])=[CH:46][CH:47]=4)=[O:42])=[N:37][C:36]=3[C:31]([O:30][CH3:29])=[CH:32][CH:33]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1ccc(N2CCOCC2)c2sc(NC(=O)c3ccc(C)s3)nc12
Reactant: O=C(OCc1ccccc1)N1CCNCC1
Agent: COc1ccc(Br)cc1[N+](=O)[O-]
Product: COc1ccc(N2CCN(C(=O)OCc3ccccc3)CC2)c2sc(NC(=O)c3ccc(C)s3)nc12

Procedure:
The title compound was synthesized starting from N-benzyloxycarbonylpiperazine and 4-bromo-2-nitroanisole as described for 5-methyl-thiophene-2-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide and obtained as a white solid in 12% overall yield, MS: m/e=523 (M+H+).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:12]([NH2:13])=[CH:11][C:10]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)=[CH:9][N:8]=2)[CH2:3][CH2:2]1.Cl[C:21]1[C:30]2[C:25](=[CH:26][C:27]([F:31])=[CH:28][CH:29]=2)[N:24]=[C:23]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=2)[C:22]=1[CH3:38].Cl.O1CCOCC1.CN1C(=O)CCC1>>[N:4]1([C:7]2[C:12]([NH:13][C:21]3[C:30]4[C:25](=[CH:26][C:27]([F:31])=[CH:28][CH:29]=4)[N:24]=[C:23]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=4)[C:22]=3[CH3:38])=[CH:11][C:10]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)=[CH:9][N:8]=2)[CH2:5][CH2:6][O:1][CH2:2][CH2:3]1
Reactant: Cc1c(-c2ccccn2)nc2cc(F)ccc2c1Cl
Reactant: Nc1cc(N2CCOCC2)cnc1N1CCOCC1
Agent: Cl
Solvent: C1COCCO1
Solvent: CN1CCCC1=O
Product: Cc1c(-c2ccccn2)nc2cc(F)ccc2c1Nc1cc(N2CCOCC2)cnc1N1CCOCC1
Temperature: 160 °C

Procedure:
Prepared according to Procedure K, method 2 using 2,5-dimorpholinopyridin-3-amine (143 mg, 0.543 mmol; described herein), 4-chloro-7-fluoro-3-methyl-2-(pyridin-2-yl)quinoline (148 mg, 0.54 mmol; described herein), 4.0M hydrochloric acid in 1,4-dioxane (140 μL, 0.54 mmol), and NMP (780 μL, 8.1 mmol). The reaction was heated in a microwave at 160° C. for three h. Purification afforded N-(2,5-di-4-morpholinyl-3-pyridinyl)-7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine as a yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 8.75 (1H, dd, J=4.3, 0.8 Hz), 7.93 (3H, d, J=5.5 Hz), 7.86 (1H, br. s.), 7.60-7.69 (1H, m), 7.38-7.46 (1H, m), 7.29-7.36 (2H, m), 6.31 (1H, br. s.), 3.91 (4H, br. s.), 3.68-3.81 (4H, m), 3.25 (4H, br. s.), 2.95 (4H, br. s.), 2.38 (3H, s). Mass Spectrum (ESI) m/e=501.2 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][NH:13][C:14](=[O:22])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1I.[NH:23]1[CH:27]=[CH:26][CH:25]=[N:24]1.C(=O)([O-])[O-].[K+].[K+]>CC(O)C.[Cu]I>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][NH:13][C:14](=[O:22])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[N:23]1[CH:27]=[CH:26][CH:25]=[N:24]1
Reactant: c1cn[nH]c1
Reactant: O=C(NCCc1c[nH]c2ccc(Cl)cc12)c1ccccc1I
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)O
Product: O=C(NCCc1c[nH]c2ccc(Cl)cc12)c1ccccc1-n1cccn1
Yield: 40.8 %

Procedure:
A mixture of N-(2-(5-chloro-1H-indol-3-yl)ethyl)-2-iodobenzamide (0.080 g; 0.188 mmol), 1H-pyrazole (0.065 g; 0.942 mmol), copper (I) iodide (0.0036 g; 0.002 mmol), and potassium carbonate (0.032 g; 0.226 mmol) in 2-propanol (3 ml) was irradiated in a microwave oven microwave for 20 minutes at 150° C. The volatiles were removed under reduced pressure and the residue was partitioned between water and ethyl acetate. The aqueous layer was then extracted several times with ethyl acetate. The combined organic layers were evaporated to dryness and the residue was purified by flash chromatography on silica gel (eluent 1 to 10% methanol in dichloromethane) to afford 0.028 g (41%) of N-(2-(5-Chloro-1H-indol-3-yl)ethyl)-2-(1H-pyrazol-1-yl)benzamide as a white solid.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH3:11][O:12][C:13]1[CH:14]=[C:15]([CH:43]=[CH:44][C:45]=1[O:46][CH3:47])[CH2:16][C:17]1[NH:22][C:21](=[O:23])[C:20]([CH:24]([NH:27][C:28](=[O:42])[CH:29]([CH:39]([OH:41])[CH3:40])[CH2:30][CH2:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:25][CH3:26])=[N:19][N:18]=1.C(N(CC)CC)C>>[C:39]([CH:29]([CH2:30][CH2:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:28]([NH:27][CH:24]([C:20]1[C:21](=[O:23])[NH:22][C:17]([CH2:16][C:15]2[CH:43]=[CH:44][C:45]([O:46][CH3:47])=[C:13]([O:12][CH3:11])[CH:14]=2)=[N:18][N:19]=1)[CH2:25][CH3:26])=[O:42])(=[O:41])[CH3:40]
Reactant: CCC(NC(=O)C(CCCc1ccccc1)C(C)O)c1nnc(Cc2ccc(OC)c(OC)c2)[nH]c1=O
Agent: O=C(Cl)C(=O)Cl
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Product: CCC(NC(=O)C(CCCc1ccccc1)C(C)=O)c1nnc(Cc2ccc(OC)c(OC)c2)[nH]c1=O

Procedure:
Analogously to Example 40A, 440 mg (305 mmol) of oxalyl chloride, 550 mg (7.00 mmol) of dimethyl sulphoxide, 920 mg (1.82 mmol) of N-{1-[3-(3,4-dimethoxybenzyl)-5-oxo-4,5-dihydro-1,2,4-triazin-6-yl]propyl}-2-(1-hydroxyethyl)-5-phenyl-pentanamide and 1.82 g (18 mmol) of triethylamine are reacted to give 2-acetyl-N-{1-[3-(3,4-dimethoxybenzyl)-5-oxo-4,5-dihydro-1,2,4-triazin-6-yl]propyl}-5-phenylpentanamide.
Reaction SMILES: [CH2:1]([O:5][C:6]1[C:11]2[C:12]([O:15][CH2:16][CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[N:13][O:14][C:10]=2[CH:9]=[CH:8][CH:7]=1)[CH:2]([CH3:4])[CH3:3].[CH3:23][C:24]([CH3:31])([CH:29]=O)[C:25]([O:27][CH3:28])=[O:26].C(C1(C(OC)=O)CCC1)=O>>[CH2:1]([O:5][C:6]1[C:11]2[C:12]([O:15][CH2:16][CH:17]3[CH2:22][CH2:21][N:20]([CH2:23][C:24]([CH3:31])([CH3:29])[C:25]([O:27][CH3:28])=[O:26])[CH2:19][CH2:18]3)=[N:13][O:14][C:10]=2[CH:9]=[CH:8][CH:7]=1)[CH:2]([CH3:4])[CH3:3]
Reactant: COC(=O)C(C)(C)C=O
Reactant: CC(C)COc1cccc2onc(OCC3CCNCC3)c12
Agent: COC(=O)C1(C=O)CCC1
Product: COC(=O)C(C)(C)CN1CCC(COc2noc3cccc(OCC(C)C)c23)CC1

Procedure:
The title compound was prepared according to the procedure described in Step 3 of EXAMPLE 2 using 4-isobutoxy-3-(piperidin-4-ylmethoxy)-1,2-benzisoxazole (EXAMPLE 10, Step 1) and methyl 2,2-dimethyl-3-oxopropanoate (0.96 mg, 0.74 mmol, Tetrahedron Asymmetry 2003, 14, 3371-3378) instead of 3-(piperidin-4-ylmethoxy)-4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazole and methyl 1-formylcyclobutanecarboxylate.
Reaction SMILES: P([O:4][C@H:5]([CH2:39][O:40][C:41](=[O:43])[CH3:42])[C@@H:6]([O:35][C:36](=[O:38])[CH3:37])[C@H:7]([O:31][C:32](=[O:34])[CH3:33])[C@@H:8]([O:27][C:28](=[O:30])[CH3:29])[C:9]([P:11]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:12])=[O:10])(O)O.OO>C1COCC1.CCOCC>[CH2:13]([P:11]([C:9]([C@@H:8]([C@H:7]([C@@H:6]([C@@H:5]([CH2:39][O:40][C:41](=[O:43])[CH3:42])[OH:4])[O:35][C:36](=[O:38])[CH3:37])[O:31][C:32](=[O:34])[CH3:33])[O:27][C:28](=[O:30])[CH3:29])=[O:10])([CH2:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)=[O:12])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: CC(=O)OC[C@@H](OP(O)O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](OC(C)=O)C(=O)P(=O)(Cc1ccccc1)Cc1ccccc1
Agent: OO
Solvent: C1CCOC1
Solvent: CCOCC
Product: CC(=O)OC[C@@H](O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](OC(C)=O)C(=O)P(=O)(Cc1ccccc1)Cc1ccccc1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
To a solution of Compound 78 (1.2 g, 2.2 mmol) in THF (50 mL) cooled to −78° C. with a dry ice-acetone bath was added dropwise 30 percent H2O2 (10 mL), and the mixture was allowed to warm up to room temperature, and stirred for 1.5 hours at room temperature. The mixture was diluted with ether and successively washed with ice-cold saturated Na2S2O3, saturated NaHCO3, saturated NaCl, and water. The organic phase was dried over anhydrous Na2SO4 and concentrated to give a α:β (1:4) mixture of Compound 85 (1.36 g, 98 percent) as judged by 1H-NMR (CDCl3). This product was used for the next step without further purification.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[F:7][C:8]1[CH:9]=[C:10]([C:15]#[C:16][Si](C)(C)C)[CH:11]=[CH:12][C:13]=1[F:14].Cl>C(O)C>[C:15]([C:10]1[CH:11]=[CH:12][C:13]([F:14])=[C:8]([F:7])[CH:9]=1)#[CH:16]
Reactant: C[Si](C)(C)C#Cc1ccc(F)c(F)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: C#Cc1ccc(F)c(F)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 76.6 %

Procedure:
Add potassium carbonate (719 mg, 5.2 mmol) to a solution of (3,4-difluorophenylethynyl)-trimethylsilane (2.20 g, 10.4 mmol) in ethanol (30 mL). Stir at room temperature for 16 h. Neutralize with 10% aqueous hydrochloric acid. Add water and extract the product with hexanes. Concentrate hexanes slowly in a cooled water bath (˜10° C.) to give the title compound (1.10 g, 76%).
Reaction SMILES: [CH2:1]([N:3]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[F:22])[C:4](=[O:14])[CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)[CH3:2].Br[CH2:24][C:25]1[CH:34]=[CH:33][CH:32]=[CH:31][C:26]=1[C:27]([O:29][CH3:30])=[O:28].C(=O)([O-])[O-].[K+].[K+].C(O)C(N)(CO)CO>C(#N)C>[CH2:1]([N:3]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[F:22])[C:4](=[O:14])[CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:24][C:25]2[CH:34]=[CH:33][CH:32]=[CH:31][C:26]=2[C:27]([O:29][CH3:30])=[O:28])=[CH:9][CH:8]=1)[CH3:2]
Reactant: COC(=O)c1ccccc1CBr
Reactant: CCN(Cc1ccccc1F)C(=O)CCc1ccc(O)cc1
Agent: NC(CO)(CO)CO
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCN(Cc1ccccc1F)C(=O)CCc1ccc(OCc2ccccc2C(=O)OC)cc1
Temperature: 65 °C
Reaction time: 3 h
Yield: 76.1 %

Procedure:
N-Ethyl-N-(2-fluorobenzyl)-3-(4-hydroxyphenyl)propanamide (0.400 g, 1.327 mmol) and methyl 2-(bromomethyl)benzoate (0.334 g, 1.460 mmol) were dissolved in acetonitrile (10 ml) and potassium carbonate (0.367 g, 2.654 mmol) was added. The mixture was stirred at 65° C. for three hours. When N-ethyl-N-(2-fluorobenzyl)-2-(4-hydroxyphenyl)acetamide was consumed, PS-trisamine (0.3 eqv) was added and the solution was stirred overnight at room temperature. The polymer was filtered off and acetonitrile was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two portions of water, dried (MgSO4) and the solvent was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two portions on water, dried (MgSO4) and the solvent was removed by evaporation. The crude was purified by preparative HPLC (starting with isocratic acetonitrile/buffer 60/40 and then the acetonitrile concentration was increased to 100%, the buffer was a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min). The product-containing fractions were pooled and the acetonitrile was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two portions of brine and dried (MgSO4). The solvent was removed by evaporation. to give 0.454 g of methyl 2-[(4-{3-[ethyl(2-fluorobenzyl)amino]-3-oxopropyl}phenoxy)methyl]-benzoate (yield 76.1%).
Reaction SMILES: [C:1]1([CH:7]2[N:21]3[C:22]4[C:14]([C:15]5[C:20]3=[CH:19][CH:18]=[CH:17][C:16]=5[OH:23])=[CH:13][CH:12]=[CH:11][C:10]=4[O:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+].Cl.[CH2:31]([N:33]([CH2:36][CH2:37]Cl)[CH2:34][CH3:35])[CH3:32].[I-].[Na+].Cl.[Cl-]>CN(C=O)C>[CH2:31]([N:33]([CH2:36][CH3:37])[CH2:34][CH2:35][O:23][C:16]1[C:15]2[C:14]3[C:22]4=[C:10]([O:9][CH2:8][CH:7]([C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)[N:21]4[C:20]=2[CH:19]=[CH:18][CH:17]=1)[CH:11]=[CH:12][CH:13]=3)[CH3:32]
Reactant: Oc1cccc2c1c1cccc3c1n2C(c1ccccc1)CO3
Reactant: CCN(CC)CCCl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cl-]
Solvent: CN(C)C=O
Product: CCN(CC)CCOc1cccc2c1c1cccc3c1n2C(c1ccccc1)CO3
Temperature: 25 °C
Reaction time: 5.5 h
Yield: 62.8 %

Procedure:
To a mixture of 1-phenyl-1,2-dihydro[1,4]oxazino[2,3,4-jk]carbazol-7-ol (0.048 g, 0.159 mmol), potassium carbonate (0.044 g, 0.318 mmol), and DMF (1.0 mL) at 100° C. is added diethylaminoethyl chloride hydrochloride (0.033 g, 0.191 mmol) in aliquots over 1 h. After 5.5 h, an additional 0.011 g of diethylaminoethyl chloride hydrochloride is added, and one hour later, a few crystals of sodium iodide are added. After heating for ten hours, the mixture is allowed to stir at room temperature for the remainder of the night. Additional potassium carbonate (0.022 g) and diethylarminoethyl chloride hydrochloride (0.017 g) are added and the mixture is stirred at 100° C. for 1.5 h. The major portion of the DMF is distilled off and the residue is partitioned between dichloromethane and water. The organic layers are dried over sodium sulfate and concentrated. The residue is chromatographed on silica gel (17 mL) using EtOAc/dichloromethane (30/70 to 60/40) to give 0.040 g of N,N-diethyl-2-[(1-phenyl-1,2-dihydro[1,4]oxazino[2,3,4-jk]carbazol-7-yl)oxy]-1-ethanamine.
Reaction SMILES: [N:1]1([C:6]2[CH:11]=[C:10]([N+:12]([O-])=O)[C:9]([NH2:15])=[C:8]([CH3:16])[CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1>[Pd].O>[N:1]1([C:6]2[CH:11]=[C:10]([NH2:12])[C:9]([NH2:15])=[C:8]([CH3:16])[CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: Cc1cc(-n2ccnc2)cc([N+](=O)[O-])c1N
Agent: [Pd]
Solvent: O
Product: Cc1cc(-n2ccnc2)cc(N)c1N
Temperature: 25 °C
Reaction time: 14 h
Yield: 90.7 %

Procedure:
To 4-imidazol-1-yl-2-methyl-6-nitro-phenylamine (350 mg, 1.61 mmol) and 10% Palladium on carbon (40 mg) were added degassed methanol (5 mL) and TFA (5 drops). The reaction mixture was flushed and evacuated with hydrogen/vacuum line, stirred at room temperature for 14 h under hydrogen atmosphere (hydrogen balloon). The dark reaction mixture was filtered through a pad of celite and rinsed with methanol. Concentration of the filtrate gave the residue, which was diluted with water, extracted with ethyl acetate. The combined organic layers were washed with saturated NaHCO3, brine, dried over Na2SO4. Concentration to dryness gave the title compound (275 mg, 91%) as a solid. 1H NMR (300 MHz, CD3OD) δ 7.87 (1H, s), 7.34 (1H, s), 7.05 (1H, s), 6.72 (1H, d, J=2.4 Hz), 6.65 (1H, d, J=2.4 Hz) 2.21 (3H, s). LCMS (M+H)+ m/z 189 (t=0.23 min.).
Reaction SMILES: [OH:1][CH2:2][C@@H:3]1[CH2:7][CH2:6][CH2:5][N:4]1/[N+:8](/[O-:11])=[N:9]/[O-:10].[Na+].Br[CH2:14][CH2:15][CH2:16][CH3:17]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[CH2:14]([O:10]/[N:9]=[N+:8](/[N:4]1[CH2:5][CH2:6][CH2:7][C@H:3]1[CH2:2][OH:1])\[O-:11])[CH2:15][CH2:16][CH3:17]
Reactant: [O-]/N=[N+](\[O-])N1CCC[C@H]1CO
Reactant: CCCCBr
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCO/N=[N+](\[O-])N1CCC[C@H]1CO
Temperature: 65 °C

Procedure:
To a suspension of sodium (2S)-2-(hydroxymethyl)-1-[(Z)-oxido-NNO-azoxy]pyrrolidine (447 mg, 2.44 mmol) and tetrabutylammonium iodide (90 mg, 0.24 mmol) in DMF (10 mL) was added 1-bromobutane (315 μL, 2.93 mmol). The resulting suspension was allowed to stir at 65° C. over night. After cooling to rt, the mixture was partitioned between Et2O (50 mL) and brine (50 mL). The organic layer was separated and washed with brine (2×50 mL), dried over MgSO4 and concentrated. The residue was purified by flash chromatography (Biotage 40+M) using 35-50% ethyl acetate in hexanes gradient, affording the title product: 1H NMR (500 MHz, CDCl3) δ 4.21 (t, J=6.7 Hz, 2H), 4.07-4.02 (m, 1H), 3.75 (dd, J=3.6, 11.3 Hz, 1H), 3.63-3.54 (m, 3H), 3.06 (br. s, 1H), 2.12-2.04 (m, 1H), 1.98-1.91 (m, 2H), 1.81-1.71 (m, 3H), 1.47-1.39 (m, 2H), 0.95 (t, J=7.4 Hz, 3H).
Reaction SMILES: [CH2:1]([C:8]1[C:9](=[O:19])[O:10][C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:20]1[CH2:25][CH2:24][N:23]([CH2:26][CH2:27]Cl)[CH2:22][CH2:21]1>>[CH2:1]([C:8]1[C:9](=[O:19])[O:10][C:11]2[C:16]([C:17]=1[O:18][CH2:27][CH2:26][N:23]1[CH2:24][CH2:25][O:20][CH2:21][CH2:22]1)=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=c1oc2ccccc2c(O)c1Cc1ccccc1
Reactant: ClCCN1CCOCC1
Product: O=c1oc2ccccc2c(OCCN2CCOCC2)c1Cc1ccccc1
Yield: 88.5 %

Procedure:
Prepared as indicated in Example 8, from 13.7 g. (0.54 mol) of 3-benzyl-4-hydroxy-coumarin and 10.6 g. (0.071 mol) of 2-morpholino-1-chlorethane. After evaporation of the chloroform, there are obtained 17 g. of an oil which cannot be crystallised. Yield 88.5% (theoretical yield 19.2 g.).
Reaction SMILES: [C:1]1([N:7]2[C:22]([OH:23])=[C:10]3[N:11]=[CH:12][N:13]=[C:14]([S:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:9]3=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37].Cl>CN(C=O)C>[C:1]1([N:7]2[C:22]([O:23][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])=[C:10]3[N:11]=[CH:12][N:13]=[C:14]([S:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:9]3=[N:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCOC(=O)CSc1ncnc2c(O)n(-c3ccccc3)nc12
Reactant: CCCCCCCBr
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCCCCCOc1c2ncnc(SCC(=O)OCC)c2nn1-c1ccccc1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
1 g of 2-phenyl-3-hydroxy-7-ethoxycarbonylmethylthio-pyrazolo[4,3-d]pyrimidine was dissolved in 10 ml of DMF, and 0.5 g of anhydrous potassium carbonate and 0.65 g of bromoheptane were added thereto. The mixture was stirred at room temperature for 48 hours. Then, after confirming the completion of the reaction by means of TLC, an aqueous hydrochloric acid solution was added. The reaction mixture was extracted with chloroform. The chloroform layer was washed with an aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and then chloroform was distilled off. The residue was purified by silica gel chromatography (60% chloroform-hexane), whereby the desired product was obtained.
Reaction SMILES: N1C=CN=C1.[CH3:6][C:7]([Si:10](Cl)([CH3:12])[CH3:11])([CH3:9])[CH3:8].[OH:14][C@H:15]1[CH2:19][CH2:18][NH:17][C:16]1=[O:20]>CN(C)C1C=CN=CC=1.C(Cl)Cl.O>[Si:10]([O:14][C@H:15]1[CH2:19][CH2:18][NH:17][C:16]1=[O:20])([C:7]([CH3:9])([CH3:8])[CH3:6])([CH3:12])[CH3:11]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: O=C1NCC[C@@H]1O
Agent: CN(C)c1ccncc1
Agent: c1c[nH]cn1
Solvent: ClCCl
Solvent: O
Product: CC(C)(C)[Si](C)(C)O[C@H]1CCNC1=O
Reaction time: 24 h
Yield: 97.6 %

Procedure:
4-Dimethylaminopyridine (0.199 g, 1.63 mmol), imidazole (6.73 g, 99 mmol) and TBDMS-Cl (20.6 ml, 59.3 mmol) was added to a stirred solution of (S)-3-hydroxypyrrolidin-2-one (5.0 g, 49.5 mmol) in DCM (198 ml) at RT. The reaction mixture was stirred for 24 h and then diluted with water. The mixture was extracted with DCM. The combined organic layers were washed with saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified using silica gel column chromatography (50-80% EtOAc/hexanes) to afford (S)-3-((tert-butyldimethylsilyl)oxy)pyrrolidin-2-one (10.4 g, 97% yield) as a white solid: 1H NMR (500 MHz, chloroform-d) δ 6.15 (br. s., 1H), 4.28 (t, J=7.6 Hz, 1H), 3.40 (dddd, J=9.7, 8.5, 3.1, 1.2 Hz, 1H), 3.28 (dt, J=9.6, 7.4 Hz, 1H), 2.39 (dtd, J=12.7, 7.3, 3.1 Hz, 1H), 2.10-2.02 (m, 1H), 0.97-0.92 (m, 9H), 0.20-0.14 (m, 6H).