Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4](OS(C(F)(F)F)(=O)=O)[CH:5]=[CH:6][C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([N:14]2[CH2:19][CH2:18][CH:17]([O:20][Si:21]([CH:28]([CH3:30])[CH3:29])([CH:25]([CH3:27])[CH3:26])[CH:22]([CH3:24])[CH3:23])[CH2:16][CH2:15]2)[C:10]1=[O:31].[CH3:40][O:41][C:42]([C:44]1[CH:49]=[CH:48][C:47](B(O)O)=[CH:46][CH:45]=1)=[O:43].C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.O.C(OCC)(=O)C.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>[CH3:40][O:41][C:42]([C:44]1[CH:49]=[CH:48][C:47]([C:4]2[CH:5]=[CH:6][C:7]([CH2:8][C@@H:9]3[CH2:13][CH2:12][N:11]([N:14]4[CH2:19][CH2:18][CH:17]([O:20][Si:21]([CH:25]([CH3:27])[CH3:26])([CH:28]([CH3:30])[CH3:29])[CH:22]([CH3:23])[CH3:24])[CH2:16][CH2:15]4)[C:10]3=[O:31])=[C:2]([Cl:1])[CH:3]=2)=[CH:46][CH:45]=1)=[O:43]
Reactant: COC(=O)c1ccc(B(O)O)cc1
Reactant: CC(C)[Si](OC1CCN(N2CC[C@@H](Cc3ccc(OS(=O)(=O)C(F)(F)F)cc3Cl)C2=O)CC1)(C(C)C)C(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc(-c2ccc(C[C@@H]3CCN(N4CCC(O[Si](C(C)C)(C(C)C)C(C)C)CC4)C3=O)c(Cl)c2)cc1
Temperature: 80 °C
Reaction time: 1 h
Yield: 93.9 %

Procedure:
Bring a mixture of trifluoro-methanesulfonic acid 3-Chloro-4-[(R)-2-oxo-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-3-ylmethyl]-phenyl ester (0.83 g, 1.35 mmol), 4-methoxycarbonylphenylboronic acid (0.29 g, 1.62 mmol), sodium carbonate (0.43 g, 4.06 mmol) in THF (20 mL) and water (6 mL) to 60° C. To the mixture at 60° C., add Pd(PPh3)4 (0.08 g, 0.07 mmol). Raise the reaction temperature to 80° C. and stir for 1 hour. Cool the reaction, dilute with ethyl acetate, and wash with water and brine. Dry the organic layer with Na2SO4, remove the solvent in vacuo, and purify on silica gel column with 0% to 50% ethyl acetate in hexanes gradient to afford 0.76 g (93%) of the titled product. MS (m/z): 599 (M+).
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[C:10]2[C:6]([CH2:7][CH2:8][NH:9]2)=[CH:5][CH:4]=1.[S-:14][C:15]#[N:16].[K+].BrBr>CO>[S:14]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][C:3]=1[C:2]([F:1])([F:12])[F:13])[NH:9][CH2:8][CH2:7]2)[C:15]#[N:16]
Reactant: N#C[S-]
Reactant: FC(F)(F)c1ccc2c(c1)NCC2
Agent: BrBr
Agent: [K+]
Solvent: CO
Product: N#CSc1cc2c(cc1C(F)(F)F)NCC2
Temperature: 25 °C
Reaction time: 8 h
Yield: 71.7 %

Procedure:
A mixture of trifluoromethylindoline (D1) (9.7 g, 52 mmol) and potassium thiocyanate (10.09 g, 104 mmol) in methanol (200 ml) was treated with a solution of bromine (2.82 ml, 55 mmol) in methanol (35 ml) dropwise over 0.5 h at −5-0° C. The reaction mixture was allowed to warm to room temperature and stirred overnight then evaporated to dryness. The residue was partitioned between aqueous K2CO3 (100 ml) and dichloromethane (3×100 ml). The combined extracts were dried (Na2SO4) and evaporated and the residue chromatographed on silica using 2-30% ethyl acetate/petroleum ether as eluant to afford the title compound (9.1 g, 72%) as a yellow solid
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.[N:11]1([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1>CCO>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([N:14]2[CH2:13][CH2:12][N:11]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][CH2:15]2)=[N:3][CH:4]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1ccc(Cl)nc1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Solvent: CCO
Product: CC(C)(C)OC(=O)N1CCN(c2ccc([N+](=O)[O-])cn2)CC1
Reaction time: 16 h
Yield: 127.2 %

Procedure:
To a solution of 2-chloro-5-nitropyridine (LXV) (2.0 g, 12.6 mmol) in EtOH (20 mL) was added tert-butyl piperazine-1-carboxylate (XCVI) (7.05 g, 37.9 mmol). The reaction was headed at 70° C. for 16 h. The reaction was concentrated under vacuum and then dissolved in EtOAc. The EtOAc was washed with 1 M NaOH, brine and then dried over MgSO4 to give tert-butyl 4-(5-nitropyridin-2-yl)piperazine-1-carboxylate (XCVII) as a yellow solid (4.94 g). ESIMS found for C14H20N4O4 m/z 309.0 (M+H).
Reaction SMILES: [Br-].[C:2]([C:5]1[CH:6]=[N+:7]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=2)[CH:8]=[CH:9][C:10]=1[CH2:11][CH:12]1[CH2:21][CH2:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:22][CH3:23])[CH:18]=2)[C:13]1=[O:24])(=[O:4])[CH3:3].C1C(C(N)=O)=CN(CC2C=CC=CC=2)C=C1>>[C:2]([C:5]1[CH:10]([CH2:11][CH:12]2[CH2:21][CH2:20][C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:22][CH3:23])[CH:18]=3)[C:13]2=[O:24])[CH:9]=[CH:8][N:7]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=2)[CH:6]=1)(=[O:4])[CH3:3]
Reactant: COc1ccc2c(c1)CCC(Cc1cc[n+](Cc3cccc(F)c3)cc1C(C)=O)C2=O
Agent: NC(=O)C1=CN(Cc2ccccc2)C=CC1
Agent: [Br-]
Product: COc1ccc2c(c1)CCC(CC1C=CN(Cc3cccc(F)c3)C=C1C(C)=O)C2=O

Procedure:
The title compound 156 is prepared according to the procedure reported in Example 39.1 with compound 128 (70 mg, 0.14 mmol) and BNAH (30 mg, 1 equiv) as reactants. Yellow solid. (Yield 17 mg, 29%).
Reaction SMILES: CC(C)=[O:3].OS(O)(=O)=O.O=[Cr](=O)=O.[C:14]([C:17]1[CH:28]=[CH:27][C:20]2[O:21][CH:22]([CH2:25][OH:26])[CH2:23][O:24][C:19]=2[CH:18]=1)(=[O:16])[CH3:15]>CC(C)=O.C(O)(C)C.O.C(Cl)(Cl)Cl>[C:14]([C:17]1[CH:28]=[CH:27][C:20]2[O:21][CH:22]([C:25]([OH:3])=[O:26])[CH2:23][O:24][C:19]=2[CH:18]=1)(=[O:16])[CH3:15]
Reactant: CC(C)=O
Reactant: CC(=O)c1ccc2c(c1)OCC(CO)O2
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: CC(C)O
Solvent: O
Solvent: ClC(Cl)Cl
Product: CC(=O)c1ccc2c(c1)OCC(C(=O)O)O2
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Jones' reagent (11.6 ml.) was added dropwise to a stirred solution of 6-acetyl-2-hydroxymethyl-1,4-benzodioxan (4.0 g.) in acetone (70 ml.) at 10°-15° C. The reaction was stirred at room temperature for 18 hours then diluted with isopropanol/water/chloroform, the organic layer separated and evaporated in vacuo. The residue was redissolved in chloroform, extracted with saturated sodium carbonate solution (2×30 ml.) then the basic phase washed with chloroform, cooled and acidified to pH 1 with concentrated hydrochloric acid. The acidic solution was extracted with chloroform, the combined extracts washed with saturated brine, dried (Na2SO4) and evaporated in vacuo to give 6-acetyl-1,4-benzodioxan-2-carboxylic acid (1.56 g.), m.p. 159°-162° C. A sample was recrystallized from ethanol/ethyl acetate, m.p. 174°-175° C.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[C:4]([CH3:19])=[CH:5][C:6]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[N:7][C:8]=1[O:9][CH3:10].[Br:20][C:21]1[CH:22]=[C:23]([C:34](O)=[O:35])[C:24]2[C:25]([CH3:33])=[CH:26][N:27]([CH:30]([CH3:32])[CH3:31])[C:28]=2[CH:29]=1.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[Br:20][C:21]1[CH:22]=[C:23]([C:34]([NH:1][CH2:2][C:3]2[C:4]([CH3:19])=[CH:5][C:6]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[N:7][C:8]=2[O:9][CH3:10])=[O:35])[C:24]2[C:25]([CH3:33])=[CH:26][N:27]([CH:30]([CH3:31])[CH3:32])[C:28]=2[CH:29]=1
Reactant: Cc1cn(C(C)C)c2cc(Br)cc(C(=O)O)c12
Reactant: COc1nc(NC(=O)OC(C)(C)C)cc(C)c1CN
Agent: On1nnc2cccnc21
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: COc1nc(NC(=O)OC(C)(C)C)cc(C)c1CNC(=O)c1cc(Br)cc2c1c(C)cn2C(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 99.9 %

Procedure:
To a stirred solution of tert-butyl (5-(aminomethyl)-6-methoxy-4-methylpyridin-2-yl)carbamate (0.40 g, 1.496 mmol), 6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylic acid (0.44 g, 1.486 mmol), and HOAt (0.21 g, 1.543 mmol) in DMF (25 mL) was added EDC free base (0.25 g, 1.610 mmol). The reaction was stirred at RT overnight then evaporated to dryness under vacuum. The remaining was purified by silica gel chromatography (Analogix, SF25-60g, 0 to 30% EtOAc in hexanes) to give the product tert-butyl (5-((6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxamido)methyl)-6-methoxy-4-methylpyridin-2-yl)carbamate (0.81 g, 1.485 mmol, 99% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=9.42 (s, 1H), 8.41 (t, J=4.8 Hz, 1H), 7.77 (d, J=1.5 Hz, 1H), 7.33 (s, 1H), 7.21 (s, 1H), 6.99 (d, J=1.8 Hz, 1H), 4.40 (d, J=5.1 Hz, 2H), 3.81 (s, 3H), 2.35 (s, 3H), 2.10 (d, J=1.0 Hz, 3H), 1.47 (s, 9H), 1.38 (d, J=6.6 Hz, 6H). MS(ES)+ m/e 545.2 [M+H]+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C@:8]2([CH2:32][CH2:33][CH2:34][OH:35])[O:13][C:12](=[O:14])[N:11]([C@H:15]([C:17]3[CH:22]=[CH:21][C:20](B4OC(C)(C)C(C)(C)O4)=[CH:19][CH:18]=3)[CH3:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Br[C:37]1[CH:42]=[C:41]([CH3:43])[N:40]=[C:39]([CH3:44])[N:38]=1>>[CH3:44][C:39]1[N:38]=[C:37]([C:20]2[CH:19]=[CH:18][C:17]([C@@H:15]([N:11]3[CH2:10][CH2:9][C@@:8]([C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)([CH2:32][CH2:33][CH2:34][OH:35])[O:13][C:12]3=[O:14])[CH3:16])=[CH:22][CH:21]=2)[CH:42]=[C:41]([CH3:43])[N:40]=1
Reactant: Cc1cc(Br)nc(C)n1
Reactant: C[C@@H](c1ccc(B2OC(C)(C)C(C)(C)O2)cc1)N1CC[C@](CCCO)(c2ccc(F)cc2)OC1=O
Product: Cc1cc(-c2ccc([C@H](C)N3CC[C@](CCCO)(c4ccc(F)cc4)OC3=O)cc2)nc(C)n1

Procedure:
The title compound was prepared from (R)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one and 4-bromo-2,6-dimethylpyrimidine following a procedure analogous to that described in Example 1 Step 2. LC-MS Method 2 tR=1.073, m/z=464.1; 1H NMR (CD3OD) 1.21 (m, 1H), 1.48 (d, 3H), 1.82 (m, 2H), 2.15 (m, 1H), 2.23 (m, 2H), 2.38 (m, 1H), 2.46 (s, 3H), 2.62 (s, 3H), 3.08 (m, 1H), 3.39 (m, 2H), 5.51 (m, 1H), 6.95-7.08 (m, 4H), 7.21 (m, 2H), 7.51 (s, 1H), 7.83 (d, 2H).
Reaction SMILES: C[Si](C)(C)CCOC[C:7]1([CH:23]([OH:30])[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:11]([S:12]([NH:15][C:16]2[O:20][N:19]=[C:18]([CH3:21])[C:17]=2[CH3:22])(=[O:14])=[O:13])[CH:10]=[CH:9][S:8]1.[F-].[Cs+]>CN(C=O)C>[CH3:21][C:18]1[C:17]([CH3:22])=[C:16]([NH:15][S:12]([C:11]2[CH:10]=[CH:9][S:8][C:7]=2[CH:23]([OH:30])[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)(=[O:14])=[O:13])[O:20][N:19]=1
Reactant: Cc1noc(NS(=O)(=O)C2C=CSC2(COCC[Si](C)(C)C)C(O)c2ccccc2)c1C
Agent: [Cs+]
Agent: [F-]
Solvent: CN(C)C=O
Product: Cc1noc(NS(=O)(=O)c2ccsc2C(O)c2ccccc2)c1C
Temperature: 100 °C
Yield: 51 %

Procedure:
To a solution of 2-[2-(trimethylsilyl)ethoxymethyl]-N-(3,4-dimethyl-5-isoxazolyl)-2-(α-hydroxybenzyl)thiophene-3-sulfonamide (70 mg, 0-14 mmol) in DMF (2 ml) was added cesium fluoride (26 mg, 0.17 mmole) in one portion. The resulting mixture was heated to 100° C. for 10 hours. The solvents were removed by evaporation under vacuum and the remaining residue was extracted into ethyl acetate, washed with water, brine, and dried over MgSO4. The product was then purified by chromatography using 50-70% ethyl acetate/hexanes to give 26.2 mg N-(3,4-dimethyl-5-isoxazolyl)-2-(α-hydroxybenzyl)thiophene-3-sulfonamide as a pale white semisolid (51% yield).
Reaction SMILES: [CH2:1]([O:3][CH2:4][CH:5]1[CH2:10][CH2:9][CH:8]([CH:11]2[CH2:16][CH2:15][CH:14]([CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22](OS(C(F)(F)F)(=O)=O)=[CH:21][CH:20]=3)[CH2:13][CH2:12]2)[CH2:7][CH2:6]1)[CH3:2].OB(O)[C:35]1[CH:40]=[C:39]([F:41])[C:38]([O:42][C:43]([F:46])([F:45])[F:44])=[C:37]([F:47])[CH:36]=1.C(=O)([O-])[O-].[Na+].[Na+]>[Pd].O>[CH2:1]([O:3][CH2:4][CH:5]1[CH2:10][CH2:9][CH:8]([CH:11]2[CH2:16][CH2:15][CH:14]([CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:35]4[CH:40]=[C:39]([F:41])[C:38]([O:42][C:43]([F:46])([F:45])[F:44])=[C:37]([F:47])[CH:36]=4)=[CH:21][CH:20]=3)[CH2:13][CH2:12]2)[CH2:7][CH2:6]1)[CH3:2]
Reactant: CCOCC1CCC(C2CCC(CCc3ccc(OS(=O)(=O)C(F)(F)F)cc3)CC2)CC1
Reactant: OB(O)c1cc(F)c(OC(F)(F)F)c(F)c1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: CCOCC1CCC(C2CCC(CCc3ccc(-c4cc(F)c(OC(F)(F)F)c(F)c4)cc3)CC2)CC1

Procedure:
6.3 g (13 mmol) of 4-(2-(4-(4-ethoxymethylcyclohexyl) cyclohexyl) ethyl) trifluoromethylsulfonyloxybenzene, 4.2 g (17 mmol) of dihydroxy (3,5-difluoro-4-trifluoromethoxyphenyl) borane, 5% palladium on activated charcoal (1.0 g) and 5.7 g (54 mmol) of sodium carbonate were refluxed in toluene/alcohol/water (1/1/1 v/v, 80 ml) under a nitrogen atmosphere for 3 days. After cooling, the reaction solution was added with water (150 ml) and extracted twice with toluene (150 ml). An organic layer was dried over anhydrous magnesium sulfate, filtered and the solvent therein was distilled off under a reduced pressure. The residue thus obtained was purified by column chromatography (silica gel/heptane:toluene=5:1) and recrystallization (heptane-ethanol) to obtain colorless crystals of 4-(4-(2-(4-(4-ethoxymethylcyclohexyl)cyclohexyl)ethyl)phenyl)-2,6-difluorotrifluoromethoxybenzene.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([CH:8]=1)[NH2:7].[NH:12]1[CH:16]=[N:15][CH:14]=[N:13]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[N:12]1([C:2]2[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([CH:8]=2)[NH2:7])[CH:16]=[N:15][CH:14]=[N:13]1
Reactant: Nc1cc(Cl)ccc1[N+](=O)[O-]
Reactant: c1nc[nH]n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Nc1cc(-n2cncn2)ccc1[N+](=O)[O-]
Temperature: 130 °C
Reaction time: 5 h

Procedure:
A 10.0 g portion of 5-chloro-2-nitroaniline, 8.0 g of 1,2,4-triazole and 16.0 g of potassium carbonate were suspended in 50 ml of DMF and stirred for 5hours while heating at 130° C. The reaction solution was poured into ice water, and the thus precipitated crystals were collected by filtration and washed with purified water. By washing the crystals with methanol, 10.0 g (84% in yield) of the title compound was obtained. Its physical property values are shown below.
Reaction SMILES: O.O.[NH2:3][CH:4]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:5]([NH:7][CH:8]1[C:23](=[O:24])[N:10]2[C:11]([C:20]([OH:22])=[O:21])=[C:12]([CH2:15][O:16][C:17](=[O:19])[CH3:18])[CH2:13][S:14][C@H:9]12)=[O:6].[O:31]=[C:32]1[N:36]([C:37](Cl)=[O:38])[C:35]2[CH:40]=[CH:41][CH:42]=[CH:43][C:34]=2[NH:33]1.Cl>C(#N)C>[O:31]=[C:32]1[N:36]([C:37]([NH:3][CH:4]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:5]([NH:7][CH:8]2[C:23](=[O:24])[N:10]3[C:11]([C:20]([OH:22])=[O:21])=[C:12]([CH2:15][O:16][C:17](=[O:19])[CH3:18])[CH2:13][S:14][C@H:9]23)=[O:6])=[O:38])[C:35]2[CH:40]=[CH:41][CH:42]=[CH:43][C:34]=2[NH:33]1
Reactant: CC(=O)OCC1=C(C(=O)O)N2C(=O)C(NC(=O)C(N)c3ccccc3)[C@H]2SC1
Reactant: O=C(Cl)n1c(=O)[nH]c2ccccc21
Agent: Cl
Solvent: O
Solvent: CC#N
Product: CC(=O)OCC1=C(C(=O)O)N2C(=O)C(NC(=O)C(NC(=O)n3c(=O)[nH]c4ccccc43)c3ccccc3)[C@H]2SC1
Temperature: 25 °C
Reaction time: 0.03 h
Yield: 102.6 %

Procedure:
To 15 ml. of dry acetonitrile were added 883 mg. (2 mmoles) of 7-(α-aminophenylacetamido)-3-acetoxymethyl-3-cephem-4-carboxylic acid dihydrate. The mixture was cooled, and 3.13 grams (14.4 mmoles) of N,O-bis-trimethylsilylacetamide were added. Solution was complete within two minutes. The resulting mixture then was stirred at room temperature, and 452 mg. (2.3 mmoles) of 2,3-dihydro-2-oxo-1H-benzimidazol-1-ylcarbonyl chloride were added, the temperature of the mixture rising from 25° C. to 28° C. Analysis of a sample of the reaction mixture after 30 minutes by thin-layer chromatography (TLC) indicated that reaction was complete. After two hours, the reaction mixture was slowly dropped into rapidly stirred ice water, the pH of the resulting suspension being 1.9. The pH was adjusted to 1.7 by addition of hydrochloric acid. The mixture was filtered, and the solid which was collected was washed with dilute hydrochloric acid and air-dried to give 1.16 grams of the title compound as a buff-colored powder.
Reaction SMILES: [OH:1][CH2:2][CH:3]1[CH2:5][N@:4]1[C:6]([C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-])=O)=[C:10]([O:17][CH3:18])[CH:9]=1)=[O:7]>CO.[Pd]>[NH2:14][C:11]1[CH:12]=[CH:13][C:8]([C:6]([N@@:4]2[CH2:5][CH:3]2[CH2:2][OH:1])=[O:7])=[CH:9][C:10]=1[O:17][CH3:18]
Reactant: COc1cc(C(=O)N2CC2CO)ccc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CO
Product: COc1cc(C(=O)N2CC2CO)ccc1N
Temperature: 50 °C
Reaction time: 8 h
Yield: 92 %

Procedure:
To a solution of (R)-(2-(hydroxymethyl)aziridin-1-yl)(3-methoxy-4-nitrophenyl)methanone (1 equiv) in MeOH (0.12 M) was added 10% palladium on charcoal (67 weight %). The reaction mixture was stirred at 50° C. under hydrogen atmosphere (50 psi) overnight and then filtered through celite. The filtrate was concentrated and the residue was purified by silica gel chromatography (0-10% DCM in MeOH) to afford the desired product (92% yield) as a white solid. MS (ESI) m/z 223.2 [M+H]+.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:10]2[N:11]=[C:12]([NH:15][S:16]([C:19]3[CH:24]=[CH:23][C:22]([NH:25]C(=O)C)=[CH:21][CH:20]=3)(=[O:18])=[O:17])[S:13][CH:14]=2)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[OH-].[Na+].C>Cl>[NH2:25][C:22]1[CH:23]=[CH:24][C:19]([S:16]([NH:15][C:12]2[S:13][CH:14]=[C:10]([C:6]3[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[N:11]=2)(=[O:18])=[O:17])=[CH:20][CH:21]=1
Reactant: CC(=O)Nc1ccc(S(=O)(=O)Nc2nc(-c3cccc([N+](=O)[O-])c3)cs2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: Nc1ccc(S(=O)(=O)Nc2nc(-c3cccc([N+](=O)[O-])c3)cs2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 37.8 %

Procedure:
0.47 g of N-{4-[4-(3-nitro-phenyl)-thiazol-2-yl-sulphamoyl]-phenyl}-acetamide was suspended in 10 ml of 6N hydrochloric acid and heated to boiling overnight. The cooled mixture was treated with 35 ml of 2N sodium hydroxide solution. After the addition of 0.4 g of active charcoal the mixture was stirred at room temperature for 30 minutes and subsequently the active charcoal was filtered off. The product separated upon neutralization with concentrated hydrochloric acid. Recrystallization from 50 ml of 40% ethanol yielded 0.16 g of 4-amino-N-[4-(3-nitro-phenyl)-thiazol-2-yl]-benzenesulfonamide as yellowish crystals.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([O:19][C:20]3[CH:25]=[CH:24][C:23]([NH:26][C:27]([NH:29][CH2:30][CH3:31])=[O:28])=[C:22]([Cl:32])[CH:21]=3)=[CH:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[C:33]#[N:34])[C:2]1C=CC=C[CH:3]=1.FC(F)(F)C(O)=[O:38].C1(SC)C=CC=CC=1>>[Cl:32][C:22]1[CH:21]=[C:20]([O:19][C:13]2[C:12]3[C:17](=[CH:18][C:9]([O:8][CH2:1][C@H:2]4[CH2:3][O:38]4)=[C:10]([C:33]#[N:34])[CH:11]=3)[N:16]=[CH:15][CH:14]=2)[CH:25]=[CH:24][C:23]=1[NH:26][C:27]([NH:29][CH2:30][CH3:31])=[O:28]
Reactant: O=C(O)C(F)(F)F
Reactant: CCNC(=O)Nc1ccc(Oc2ccnc3cc(OCc4ccccc4)c(C#N)cc23)cc1Cl
Solvent: CSc1ccccc1
Product: CCNC(=O)Nc1ccc(Oc2ccnc3cc(OC[C@H]4CO4)c(C#N)cc23)cc1Cl

Procedure:
1-(4-(7-Benzyloxy-6-cyanoquinolin-4-yloxy)-2-chloro-phenyl)-3-ethylurea (1 g) was treated with trifluoroacetic acid and thioanisole for deprotection in the same manner as Production Example 21, and the obtained hydroxy compound (0.48 g) was treated in the same manner as Example 543 to obtain the title compound (0.31 g) as a solid.
Reaction SMILES: Cl[CH2:2][C:3]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[N:6]=[N:5][N:4]=1.[CH3:18][C:19]1([CH3:32])[CH2:24][NH:23][CH2:22][CH2:21][N:20]1[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26].C(N(CC)CC)C>C(#N)C>[CH3:18][C:19]1([CH3:32])[CH2:24][N:23]([CH2:2][C:3]2[N:7]([C:8]3[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=3)[N:6]=[N:5][N:4]=2)[CH2:22][CH2:21][N:20]1[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26]
Reactant: CC(C)(C)OC(=O)N1CCNCC1(C)C
Reactant: FC(F)(F)c1cccc(-n2nnnc2CCl)c1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCN(Cc2nnnn2-c2cccc(C(F)(F)F)c2)CC1(C)C
Temperature: 120 °C

Procedure:
To a solution of 5-(chloromethyl)-1-[3-(trifluoromethyl)phenyl]-1H-tetrazole (440 mg, 1.68 mmol, commercially available from Otava, Kiev, Ukraine) in acetonitrile (8 mL) was added 1,1-dimethylethyl 2,2-dimethyl-1-piperazinecarboxylate (359 mg, 1.68 mmol, commercially available, for example from ChemPacific Corp., Baltimore, USA) and triethylamine (0.701 mL, 5.03 mmol). The mixture was then heated to 120° C. for 20 minutes in a microwave reactor.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:11]=[C:10]([CH2:12][CH3:13])[N:9]=[C:8]([S:14]([CH3:17])(=[O:16])=[O:15])[N:7]=1)=[O:5])[CH3:2].[CH2:18](OC(C1C=C(CCC)N=C(SC)N=1)=O)C>>[CH2:1]([O:3][C:4]([C:6]1[CH:11]=[C:10]([CH2:12][CH2:13][CH3:18])[N:9]=[C:8]([S:14]([CH3:17])(=[O:16])=[O:15])[N:7]=1)=[O:5])[CH3:2]
Reactant: CCCc1cc(C(=O)OCC)nc(SC)n1
Reactant: CCOC(=O)c1cc(CC)nc(S(C)(=O)=O)n1
Product: CCCc1cc(C(=O)OCC)nc(S(C)(=O)=O)n1

Procedure:
The title compound is obtained as a yellow solid (107 mg) in analogy to 6-ethyl-2-methanesulfonyl-pyrimidine-4-carboxylic acid ethyl ester starting from 2-methylsulfanyl-6-propyl-pyrimidine-4-carboxylic acid ethyl ester; LC-MS: tR=0.85 min, [M+H]+=272.96.
Reaction SMILES: [NH2:1][C@H:2]([C:7]([C@@H:9]1[C@@H:14]([OH:15])[C@H:13]([OH:16])[C@@H:12]([CH2:17][OH:18])[O:11][C@@:10]1([NH2:53])[N:19]([CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH3:52])[C:20](=[O:38])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]/[CH:28]=[CH:29]\[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5].[C:54]([O:58][C:59]([NH:61][CH2:62][C:63]([NH:65][CH2:66][C:67](O)=[O:68])=[O:64])=[O:60])([CH3:57])([CH3:56])[CH3:55]>O1CCCC1>[C:54]([O:58][C:59]([NH:61][CH2:62][C:63]([NH:65][CH2:66][C:67]([NH:1][C@H:2]([C:7]([C@@H:9]1[C@@H:14]([OH:15])[C@H:13]([OH:16])[C@@H:12]([CH2:17][OH:18])[O:11][C@@:10]1([NH2:53])[N:19]([CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH3:52])[C:20](=[O:38])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]/[CH:28]=[CH:29]\[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])=[O:8])[CH2:3][CH:4]([CH3:5])[CH3:6])=[O:68])=[O:64])=[O:60])([CH3:57])([CH3:56])[CH3:55]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)N(CCCCCCCCCCCCCC)[C@]1(N)O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1C(=O)[C@@H](N)CC(C)C
Reactant: CC(C)(C)OC(=O)NCC(=O)NCC(=O)O
Solvent: C1CCOC1
Product: CCCCCCCC/C=C\CCCCCCCC(=O)N(CCCCCCCCCCCCCC)[C@]1(N)O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1C(=O)[C@H](CC(C)C)NC(=O)CNC(=O)CNC(=O)OC(C)(C)C
Yield: 92 %

Procedure:
from N-(2-L-leucyl-amino-2-deoxy-β-D-glucopyranosyl)-N-tetradecyl-oleamide and N-tert-butyloxycarbonyl-glycyl-glycine. Yield 92%. [α]D =+4.2° (c=0.83, tetrahydrofuran).
Reaction SMILES: [OH:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:3]=1[C:17](=[O:23])[CH2:18]S(C)(=O)=O.C(O)C.C(O)(=O)C>O>[CH3:18][C:17]([C:3]1[N:4]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:5]2[C:10]([C:2]=1[OH:1])=[CH:9][CH:8]=[CH:7][CH:6]=2)=[O:23]
Reactant: CS(=O)(=O)CC(=O)c1c(O)c2ccccc2n1-c1ccccc1
Solvent: CC(=O)O
Solvent: O
Solvent: CCO
Product: CC(=O)c1c(O)c2ccccc2n1-c1ccccc1

Procedure:
In a manner analogous to that of Example 5, the title compound was prepared from 1-(3-hydroxy-1-phenyl-1H-indol-2-yl)-2-(methylsulfonyl)ethanone. The product was obtained as green needles of mpt. 127°-130° from the condensed ethanol-acetic acid filtrate by the addition of warm water, followed by slow cooling.