Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:3]2[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:4]=2[N:5]([CH3:21])[C:6](=[O:20])[CH:7]([CH2:9][C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=2)[N:8]=1.[OH:27][CH:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1.C(=O)([O-])[O-].[Na+].[Na+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:26][C:24]1[CH:23]=[CH:22][C:4]2[N:5]([CH3:21])[C:6](=[O:20])[CH:7]([CH2:9][C:10]3[CH:19]=[CH:18][C:17]4[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=4)[CH:11]=3)[N:8]=[C:2]([N:31]3[CH2:32][CH2:33][CH:28]([OH:27])[CH2:29][CH2:30]3)[C:3]=2[CH:25]=1
Reactant: OC1CCNCC1
Reactant: CN1C(=O)C(Cc2ccc3ccccc3c2)N=C(Cl)c2cc(Cl)ccc21
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: CN1C(=O)C(Cc2ccc3ccccc3c2)N=C(N2CCC(O)CC2)c2cc(Cl)ccc21
Temperature: 100 °C
Yield: 8 %

Procedure:
5,7-Dichloro-1-methyl-3-(naphthalen-2-ylmethyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (0.36 g, 0.94 mmol), 4-hydroxypiperidine (0.38 g, 3.8 mmol), sodium carbonate (0.40 g, 3.8 mmol), and tetrabutylammonium iodide (0.09 g, 0.24 mmol) were combined in toluene (5 mL) and heated to 100° C. for 24 hours. The solution was cooled, diluted with ethyl acetate, washed with water, brine, dried with magnesium sulfate, filtered and concentrated in vacuo. Column chromatography eluting with a gradient of 25-100% ethyl acetate in hexanes provided 7-chloro-5-(4-hydroxypiperidin-1-yl)-1-methyl-3-(naphthalen-2-ylmethyl)-1H-benzo[e][1,4]diazepin-2(3H)-one. (35 mg, 8% yield) ESI m/z measured 448.1794 [M+H]+. calculated 448.1792.
Reaction SMILES: ClCCCC(OC(=O)C)CCCCC.ClCCCC(OC(=O)C)CCCC(C)(C)C.C([O:34][CH:35]([CH2:55][CH2:56][CH2:57][C:58](C)(C)[CH3:59])[CH2:36][CH2:37][CH2:38][N:39]([CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][C:50]([O:52]CC)=[O:51])[S:40]([CH3:43])(=[O:42])=[O:41])(=O)C>>[OH:34][C@H:35]([CH2:55][CH2:56][CH2:57][CH2:58][CH3:59])[C:36]#[C:37][CH2:38][N:39]([CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][C:50]([OH:52])=[O:51])[S:40]([CH3:43])(=[O:41])=[O:42]
Reactant: CCOC(=O)CCCCCCN(CCCC(CCCC(C)(C)C)OC(C)=O)S(C)(=O)=O
Agent: CC(=O)OC(CCCCl)CCCC(C)(C)C
Agent: CCCCCC(CCCCl)OC(C)=O
Product: CCCCC[C@@H](O)C#CCN(CCCCCCC(=O)O)S(C)(=O)=O

Procedure:
The synthesis of this compound is carried out as described in Example 1 except that, in Step A, the 1-chloro-4-acetoxynonane is replaced by an equimolar amount of 1-chloro-4-acetoxy-8,8-dimethylnonane (Example D). The product of Step A is thus ethyl 7-[N-(4-acetoxy-8,8-dimethylnonyl)methanesulfonamido]heptanoate. The subsequent step yields 7-[N-(4-hydroxy-8,8-dimethylnonyl)methanesulfonamido]heptanoic acid (B).
Reaction SMILES: [C:1]1([CH:7]([CH2:11][CH3:12])[C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:13][NH:14][C@H:15]1[CH2:34][N:19]2[C:20]3[C:25]([C:26]([CH2:27][C:28]([O:30]CCC)=[O:29])=[C:18]2[CH2:17][CH2:16]1)=[CH:24][CH:23]=[CH:22][CH:21]=3>>[C:1]1([CH:7]([C:11]2[CH:12]=[CH:3][CH:2]=[CH:1][CH:6]=2)[C:8]([N:14]([CH3:13])[C@H:15]2[CH2:34][N:19]3[C:20]4[C:25]([C:26]([CH2:27][C:28]([OH:30])=[O:29])=[C:18]3[CH2:17][CH2:16]2)=[CH:24][CH:23]=[CH:22][CH:21]=4)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCC(C(=O)Cl)c1ccccc1
Reactant: CCCOC(=O)Cc1c2n(c3ccccc13)C[C@H](NC)CC2
Product: CN(C(=O)C(c1ccccc1)c1ccccc1)[C@@H]1CCc2c(CC(=O)O)c3ccccc3n2C1

Procedure:
The title compound was prepared using analogous procedures described in Example 2 (Method B) from 2-phenylbutanoyl chloride and propyl [(7R)-7-(methylamino)-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]acetate. MS (+ESI) m/z: 405.
Reaction SMILES: [Cl:1][C:2]1[C:3]([NH2:9])=[N:4][C:5]([Cl:8])=[CH:6][CH:7]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:16](Cl)(Cl)=[S:17]>C(Cl)Cl>[Cl:1][C:2]1[C:3]([N:9]=[C:16]=[S:17])=[N:4][C:5]([Cl:8])=[CH:6][CH:7]=1
Reactant: S=C(Cl)Cl
Reactant: Nc1nc(Cl)ccc1Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: S=C=Nc1nc(Cl)ccc1Cl
Temperature: 55 °C

Procedure:
A mixture of 3,6-dichloropyridin-2-amine (0.772 g, 4.74 mmol), sodium carbonate (2.01 g, 18.9 mmol), and thiophosgene (0.726 mL, 9.47 mmol) in 6 mL DCM was heated to 55° C. in a sealed tube for 36 h. The reaction was filtered through a frit, rinsing with DCM, and the material was adsorbed onto 6 g silica gel and dried. The material was purified by silica gel chromatography, 40 g, 0-100% EA/hexanes to give 3,6-dichloro-2-isothiocyanatopyridine. 1H NMR (400 MHz, DMSO-d6) 8 ppm 8.19 (d, J=8.5 Hz, 1 H), 7.59 (d, J=9.5 Hz, 1 H).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[C:7]([O:12]C)[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([CH3:14])[C:3]=1[CH3:15].B(Br)(Br)Br>ClCCl>[Cl:1][C:2]1[C:11]2[C:6](=[C:7]([OH:12])[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([CH3:14])[C:3]=1[CH3:15]
Reactant: COc1cccc2c(Cl)c(C)c(C)nc12
Agent: BrB(Br)Br
Solvent: ClCCl
Product: Cc1nc2c(O)cccc2c(Cl)c1C
Reaction time: 3 h
Yield: 64.1 %

Procedure:
To a solution of 4-chloro-2,3-dimethyl-8-methoxyquinoline (2.5 g) in dichloromethane (5 ml) was added boron tribromide (22.6 ml) under ice-cooling, and the mixture was stirred for 3 hours. The reaction mixture was extracted with 10% solution of methanol in chloroform, and the organic layer was dried over magnesium sulfate and concentrated. The residue was dissolved in acetonitrile under heating, and the mixture was allowed to cool. The resulting precipitates were collected by filtration to give 4-chloro-2,3-dimethyl-8-hydroxyquinoline (1.50 g).
Reaction SMILES: COC1C=C(OC)C=CC=1C[N:6]([C:41]1[S:45][N:44]=[CH:43][N:42]=1)[S:7]([C:10]1[C:39]([F:40])=[CH:38][C:13]2[N:14]([C@@H:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]3([F:37])[CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27]3)[CH3:19])[C:15](=[O:17])[O:16][C:12]=2[CH:11]=1)(=[O:9])=[O:8].C(Cl)Cl.C(O)(C(F)(F)F)=O>CO>[F:40][C:39]1[C:10]([S:7]([NH:6][C:41]2[S:45][N:44]=[CH:43][N:42]=2)(=[O:9])=[O:8])=[CH:11][C:12]2[O:16][C:15](=[O:17])[N:14]([C@@H:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]3([F:37])[CH2:27][NH:28][CH2:29]3)[CH3:19])[C:13]=2[CH:38]=1
Reactant: COc1ccc(CN(c2ncns2)S(=O)(=O)c2cc3oc(=O)n([C@H](C)c4ccccc4C4(F)CN(C(=O)OC(C)(C)C)C4)c3cc2F)c(OC)c1
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: C[C@H](c1ccccc1C1(F)CNC1)n1c(=O)oc2cc(S(=O)(=O)Nc3ncns3)c(F)cc21
Reaction time: 0.25 h

Procedure:
In a 1 dram vial, added crude (R)-tert-butyl 3-(2-(1-(6-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-5-fluoro-2-oxobenzo[d]oxazol-3(2H)-yl)ethyl)phenyl)-3-fluoroazetidine-1-carboxylate (32-5, 25.8 mg, 0.035 mmol) to DCM (277 μl) and TFA (69.4 μl). After 15 min, diluted with 1 mL MeOH, filtered through Celite and concentrated in vacuo. Dissolved in 2 mL DMSO and purified by reverse-phase HPLC (C18 column, 5-60% 0.1% TFA/CH3CN:0.1% TFA/H2O) to give 32-6 as a white solid. 1H NMR δ (ppm) (CH3OH-d4): 8.22 (1H, s), 7.80 (1H, d, J=7.86 Hz), 7.75 (1H, d, J=5.61 Hz), 7.62 (1H, t, J=7.61 Hz), 7.56-7.44 (2H, m), 7.06 (1H, d, J=9.97 Hz), 5.49 (1H, d, J=6.64 Hz), 5.12-4.90 (2H, m), 4.81-4.61 (2H, m), 1.95 (3H, d, J=7.03 Hz). HRMS C20H18F2N5O4S2 [M+H] calc: 494.0763, obs: 494.0754.
Reaction SMILES: S(=O)(=O)(O)O.O[C:7]([C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][C:25]2[CH:26]=[C:27]([OH:32])[CH:28]=[C:29]([OH:31])[CH:30]=2)[CH:20]=[CH:21][CH:22]=1)([CH3:16])[CH2:8][CH2:9][CH2:10][CH2:11][C:12]([OH:15])([CH3:14])[CH3:13]>C1COCC1>[OH:15][C:12]([CH3:14])([CH3:13])[CH2:11][CH2:10][CH2:9][CH:8]=[C:7]([C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][C:25]2[CH:30]=[C:29]([OH:31])[CH:28]=[C:27]([OH:32])[CH:26]=2)[CH:20]=[CH:21][CH:22]=1)[CH3:16]
Reactant: CC(C)(O)CCCCC(C)(O)c1cccc(C=Cc2cc(O)cc(O)c2)c1
Agent: O=S(=O)(O)O
Solvent: C1CCOC1
Product: CC(=CCCCC(C)(C)O)c1cccc(C=Cc2cc(O)cc(O)c2)c1

Procedure:
In a manner similar to Example 1(j), by reacting 0.09 ml of concentrated sulphuric acid in 3 ml of THF with 152 mg (0.41 mmol) of 5-{2-[3-(1,6-dihydroxy-1,6-dimethylheptyl)phenyl]vinyl}benzene-1,3-diol in 1.5 ml of THF, after purification on a silica column (ethyl acetate 50-heptane 50), a yellow powder (m=65 mg; Y=45%) is obtained. m.p.=55-60° C.
Reaction SMILES: [OH:1][CH2:2][CH:3]([N:8]([S:20]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=1)(=[O:22])=[O:21])[CH2:9][C:10]1[CH:15]=[C:14]([CH3:16])[CH:13]=[CH:12][C:11]=1[N+:17]([O-])=O)[C:4]([O:6][CH3:7])=[O:5].[H][H]>C(O)C.C(OCC)(=O)C.[Pd]>[OH:1][CH2:2][CH:3]([N:8]([S:20]([C:23]1[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=1)(=[O:22])=[O:21])[CH2:9][C:10]1[CH:15]=[C:14]([CH3:16])[CH:13]=[CH:12][C:11]=1[NH2:17])[C:4]([O:6][CH3:7])=[O:5]
Reactant: [H][H]
Reactant: COC(=O)C(CO)N(Cc1cc(C)ccc1[N+](=O)[O-])S(=O)(=O)c1ccc(OC)cc1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCO
Product: COC(=O)C(CO)N(Cc1cc(C)ccc1N)S(=O)(=O)c1ccc(OC)cc1
Yield: 90.3 %

Procedure:
To a solution of 3.4 g of methyl 3-hydroxy-2-[(4-methoxybenzenesulfonyl)-(5-methyl-2-nitrobenzyl)-amino]propionate in 200 ml of ethanol-ethyl acetate (1:1) was added 0.34 g of 10% palladium on carbon (wet −50% H2O). The mixture was then shaken in a Parr hydrogenator under 35 psi of hydrogen for 2.5 hours. The mixture was filtered through diatomaceous earth and the filtrate concentrated under vacuum to give 2.86 g of a brown oil. Anal. for C19H24N2O6S: Calc'd: C, 55.9; H, 5.9; N, 6.9; Found: C, 55.6; H, 5.9; N, 6.4.
Reaction SMILES: [H-].[Na+].[C:3](=[O:10])([O:7][CH2:8][CH3:9])OCC.[CH3:11][C:12]([C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)=[O:13].O>CCCCC.C(OCC)C.C(O)C>[F:20][C:17]1[CH:18]=[CH:19][C:14]([C:12](=[O:13])[CH2:11][C:3]([O:7][CH2:8][CH3:9])=[O:10])=[CH:15][CH:16]=1
Reactant: CCOC(=O)OCC
Reactant: CC(=O)c1ccc(F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CCOCC
Solvent: O
Solvent: CCCCC
Product: CCOC(=O)CC(=O)c1ccc(F)cc1
Temperature: 0 °C
Yield: 77.4 %

Procedure:
57.92 g. (1.448 moles) of 60% sodium hydride/mineral oil is washed twice with pentane, the pentane is decanted, the sodium hydride is dried in a stream of nitrogen, 171 g. (1.448 moles) of diethyl carbonate is added neat at 20°-25° C., and the dropwise addition of a solution of 100 g. (0.724 mole) of 4-fluoroacetophenone in 100 ml of dry diethyl ether is commenced, the reaction mixture being stirred at 20°-25° C. under nitrogen throughout. After about 10% of the diethyl ether solution is added, 10 drops of ethanol is added (gas evolution commences immediately), and the balance of the solution is added dropwise over a period 1 hour at a rate such that the reaction mixture refluxes, the reaction mixture being stirred under nitrogen throughout. 1 kg. of dry diethyl ether is added to facilitate stirring, and the reaction mixture is refluxed under nitrogen for 3 hours and cooled to 0° C., water is carefully added (to destroy the excess sodium hydride) until all solids dissolve (the addition being exothermic), the diethyl ether phase is separated, the aqueous phase is acidified to pH 1 with concentrated hydrochloric acid and extracted twice with diethyl ether, and the three diethyl ether phases are combined, washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and evaporated at reduced pressure to obtain an orange oil. The orange oil is fractionally distilled at about 1 mm. Hg. to obtain the product as a colorless liquid (117.8 g. (77%)). B.p. 117°-125° C.λ1 mm. Hg.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].C(Cl)Cl.[F:8][C:9]1[CH:17]=[CH:16][C:15]2[N:14]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[C:13]3[CH2:25][N:26]([CH2:28][CH2:29][CH2:30][CH:31]([C:33]4[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=4)[OH:32])[CH2:27][C:12]=3[C:11]=2[CH:10]=1>N1C=CC=CC=1>[F:8][C:9]1[CH:17]=[CH:16][C:15]2[N:14]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[C:13]3[CH2:25][N:26]([CH2:28][CH2:29][CH2:30][CH:31]([C:33]4[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=4)[O:32][C:1](=[O:3])[CH3:2])[CH2:27][C:12]=3[C:11]=2[CH:10]=1
Reactant: OC(CCCN1Cc2c(n(-c3ccc(F)cc3)c3ccc(F)cc23)C1)c1ccc(F)cc1
Reactant: CC(=O)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(=O)OC(CCCN1Cc2c(n(-c3ccc(F)cc3)c3ccc(F)cc23)C1)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Acetyl chloride (260 mg., 3.3 m moles) in 10 ml. of methylene chloride is added dropwise to a cold solution of 959 mg. (2.2m moles) of 7-fluoro-4-(p-fluorophenyl)-2-[4-(p-fluorophenyl)-4-hydroxybutyl]-1,2,3,4-tetrahydropyrrolo[3,4-b]indole in 30 ml. of methylene chloride containing 350 mg. (4.4 m mols) of pyridine. Following the addition, the reaction mixture is allowed to warm to room temperature and stir overnight. The mixture is decanted into a cold saturated aqueous sodium bicarbonate solution, and the crude product is extracted (3 × 50 ml.) with methylene chloride. The combined organic extracts are dried over magnesium sulfate and concentrated to an oil, which on chromatographing on a silica gel column, using 1:1 benzene-ethyl acetate as an eluate, provides the purified product.
Reaction SMILES: [CH2:1]([C:13]1[CH:18]=[CH:17][C:16]([S:19](Cl)(=[O:21])=[O:20])=[CH:15][CH:14]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[NH2:23][C:24]1[S:28][C:27]([C:29]([O:31][CH2:32][CH3:33])=[O:30])=[N:26][N:25]=1.Cl>N1C=CC=CC=1>[CH2:1]([C:13]1[CH:18]=[CH:17][C:16]([S:19]([NH:23][C:24]2[S:28][C:27]([C:29]([O:31][CH2:32][CH3:33])=[O:30])=[N:26][N:25]=2)(=[O:21])=[O:20])=[CH:15][CH:14]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCCCc1ccc(S(=O)(=O)Cl)cc1
Reactant: CCOC(=O)c1nnc(N)s1
Agent: Cl
Solvent: c1ccncc1
Product: CCCCCCCCCCCCc1ccc(S(=O)(=O)Nc2nnc(C(=O)OCC)s2)cc1
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 34 %

Procedure:
To a solution of p-dodecylbenzenesulfonyl chloride (260 mg, 0.75 mmol) in pyridine (3 mL) was added ethyl 5-amino-1,3,4-thiadiazole-2-carboxylate (100 mg, 0.58 mmol). The reaction mixture was stirred at room temperature for 4.5 h, then 2 M HCl was added to quench the reaction. The mixture was extracted with ethyl acetate (3×40 mL). The organic extracts were washed with water (20 mL), brine (20 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by chromatography over silica gel (70-230 mesh) eluted with CH2Cl2:methanol 49:1 to give the product as a solid, mp 96-97° C., in 34% yield (95 mg, 0.20 mmol); 1H NMR (300 MHz, CDCl3) δ 0.85 (t, 3H, J=6.6 Hz), 1.20-1.35 (m, 21H), 1.57 (m, 2H), 2.60 (t, 2H, J=7.0 Hz), 4.43 (q, 2H, J=7.2 Hz), 7.26 (d, 2H, J=8.0 Hz), 7.77 (d, 2H, J=7.7 Hz); 13C NMR (300 MHz, CDCl3) δ 14.1, 22.7, 29.3, 29.4, 29.6, 29.6, 31.1, 31.9, 35.9, 63.4, 126.6, 128.9, 136.9, 145.8, 159.9, 163.7, 167.9; MS (LCQ, ESI+) Calcd for C23H36N3O4S2 482.2. found 482.1 (M+H)+. HRMS (ESI+, m/z) Calcd for C23H36N3O4S2 482.2140. found 482.2134 (M+H)+.
Reaction SMILES: [C:1]([CH:6]1[C:11](=[O:12])[CH:10]([CH3:13])[CH:9]([CH2:14][CH:15]([S:17][CH2:18][CH3:19])[CH3:16])[CH2:8][C:7]1=[O:20])(=O)[CH2:2][CH2:3][CH3:4].[CH2:21]([O:23][NH2:24])[CH3:22]>C(O)C>[CH2:21]([O:23][NH:24][C:1](=[C:6]1[C:11](=[O:12])[CH:10]([CH3:13])[CH:9]([CH2:14][CH:15]([S:17][CH2:18][CH3:19])[CH3:16])[CH2:8][C:7]1=[O:20])[CH2:2][CH2:3][CH3:4])[CH3:22]
Reactant: CCCC(=O)C1C(=O)CC(CC(C)SCC)C(C)C1=O
Reactant: CCON
Solvent: CCO
Product: CCCC(NOCC)=C1C(=O)CC(CC(C)SCC)C(C)C1=O
Temperature: 0 °C
Reaction time: 3 h
Yield: 88.3 %

Procedure:
Into 10 ml of ethanol, 2.97 g of 2-butyryl-5-(2-ethylthiopropyl)-4-methylcyclohexane-1,3-dione was dissolved and 0.81 g of ethoxyamine was dropped thereto at 0° C. and the resulting solution was stirred at room temperature for 3 hours. After pouring the reaction solution into ice-cold water, the mixture was extracted with chloroform. The chloroform solution was washed with water and extracted with 1N-sodium hydroxide solution. The sodium hydroxide solution was acidified with 1N-hydrochloric acid and the acidified mixture was extracted with chloroform. The chloroform solution was washed with water and dried over anhydrous magnesium sulfate. The removal of chloroform from said chloroform solution by distillation under reduced pressure gave 3.0 g of the desired product as yellow oily material.
Reaction SMILES: C1C2C(CO[C:16]([NH:18][C@H:19]([C:36]([O:38][CH3:39])=[O:37])[CH2:20][S:21][CH2:22][CH:23]([C:28](=[O:35])[C:29]3[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=3)[CH2:24][C:25]([OH:27])=[O:26])=[O:17])C3C(=CC=CC=3)C=2C=CC=1.[F:40][C:41]1[CH:46]=[CH:45][C:44]([N:47]=C=O)=[CH:43][CH:42]=1>>[F:40][C:41]1[CH:46]=[CH:45][C:44]([NH:47][C:16]([NH:18][C@H:19]([C:36]([O:38][CH3:39])=[O:37])[CH2:20][S:21][CH2:22][CH:23]([C:28](=[O:35])[C:29]2[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=2)[CH2:24][C:25]([OH:27])=[O:26])=[O:17])=[CH:43][CH:42]=1
Reactant: COC(=O)[C@H](CSCC(CC(=O)O)C(=O)c1cccnc1)NC(=O)OCC1c2ccccc2-c2ccccc21
Reactant: O=C=Nc1ccc(F)cc1
Product: COC(=O)[C@H](CSCC(CC(=O)O)C(=O)c1cccnc1)NC(=O)Nc1ccc(F)cc1
Yield: 5 %

Procedure:
The title compound was prepared from 3-({(2R)-2-[(fluoren-9-ylmethoxy)carbonylamino]-2-(methoxycarbonyl)ethylthio}methyl)-4-oxo-4-(3-pyridyl)butanoic acid and 4-fluorophenyl isocyanate as described in Example 16 in a 5% yield; ESMS, (M+1)+464.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][CH:3]=1.Cl[C:10]1[S:14][C:13]([C:15](=[O:17])[CH3:16])=[CH:12][C:11]=1[N+:18]([O-:20])=[O:19]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:10]2[S:14][C:13]([C:15](=[O:17])[CH3:16])=[CH:12][C:11]=2[N+:18]([O-:20])=[O:19])=[CH:4][CH:3]=1
Reactant: Sc1ccc(Br)cc1
Reactant: CC(=O)c1cc([N+](=O)[O-])c(Cl)s1
Product: CC(=O)c1cc([N+](=O)[O-])c(Sc2ccc(Br)cc2)s1

Procedure:
Prepared according to the procedure described as in Step B for example 1 from 4-Bromobenzenethiol (1.03 g, 5.5 mmol) and 1-(5-chloro-4-nitro-2-thienyl)ethanone (1.14 g, 5.5 mmol). The title compound was obtained as an orange solid (1.15 g, 58% yield). 1H NMR (300 MHz, CDCl3) δ: 8.07 (1H, s) 7.68 (2H, d, J=8.69 Hz), 7.53 (2H, d, J=8.69 Hz), 2.49 (3H, s).
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH2:12]([S:14][C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]2=[N:25][N:26]=[C:27]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[N:17]2[N:16]=1)[CH3:13]>C(Cl)Cl>[CH2:12]([S:14]([C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]2=[N:25][N:26]=[C:27]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[N:17]2[N:16]=1)=[O:9])[CH3:13]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCSc1nn2c(-c3ccccc3)nnc2c2ccccc12
Solvent: ClCCl
Product: CCS(=O)c1nn2c(-c3ccccc3)nnc2c2ccccc12
Temperature: 25 °C
Reaction time: 5 h

Procedure:
m-Chloroperbenzoic acid (3.1 g) is added to a solution of the compound of example 109 (4.6 g) in methylene chloride (50 ml) and the reaction mixture is stirred at room temperature for five hours. The mixture is washed first with diluted sodium metabisulfite and then with aqueous sodium bicarbonate.
Reaction SMILES: [CH:1]([N:3]([CH2:12][C@@H:13]([CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[C:14]([N:16]1[C@H:20]([C:21](O)=[O:22])[CH2:19][CH:18]=[N:17]1)=[O:15])[O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:2].[F:29][C:30]1[CH:31]=[CH:32][C:33]([NH2:36])=[N:34][CH:35]=1.CN1CCOCC1.ClC1N=C(OC)N=C(OC)N=1>C(#N)C>[F:29][C:30]1[CH:31]=[CH:32][C:33]([NH:36][C:21]([C@H:20]2[N:16]([C:14](=[O:15])[C@@H:13]([CH2:12][N:3]([CH:1]=[O:2])[O:4][CH2:5][C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=3)[CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[N:17]=[CH:18][CH2:19]2)=[O:22])=[N:34][CH:35]=1
Reactant: CCCCC[C@H](CN(C=O)OCc1ccccc1)C(=O)N1N=CC[C@H]1C(=O)O
Reactant: Nc1ccc(F)cn1
Agent: COc1nc(Cl)nc(OC)n1
Solvent: CN1CCOCC1
Solvent: CC#N
Product: CCCCC[C@H](CN(C=O)OCc1ccccc1)C(=O)N1N=CC[C@H]1C(=O)Nc1ccc(F)cn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 85.9 %

Procedure:
To a solution of (5S)-1-[(2R)-2-({formyl[(phenylmethyl)oxy]amino}methyl)heptanoyl]-4,5-dihydro-1H-pyrazole-5-carboxylic acid (100 mg, 0.26 mmol) and 5-fluoro-2-pyridinamine (37 mg, 0.33 mmol) in acetonitrile (10 mL) was added 4-methylmorpholine (39 mg, 0.39 mmol) and 2-chloro-4,6-bis(methyloxy)-1,3,5-triazine (49.5 mg, 0.28 mmol). The mixture was stirred at rt overnight. LCMS showed that the reaction was complete. The solvent was removed under vacuum and ethyl acetate was added. The mixture was washed with 10% KHSO4, sat. NaHCO3, brine, dried and concentrated. The residue was purified by flash column chromatography eluting with petroleum ether/ethyl acetate (3:1 to 1:1) to provide the titled compound (108 mg, 85%) as a yellow oil.
Reaction SMILES: [H-].[Na+].[O:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[NH:5][C:4]1=[O:12].IC[CH2:15][CH2:16][C:17]([CH3:22])([N+:19]([O-:21])=[O:20])[CH3:18]>CN(C=O)C>[CH3:18][C:17]([N+:19]([O-:21])=[O:20])([CH3:22])[CH2:16][CH2:15][N:5]1[C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[O:3][C:4]1=[O:12]
Reactant: CC(C)(CCCI)[N+](=O)[O-]
Reactant: O=c1[nH]c2ccccc2o1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(CCn1c(=O)oc2ccccc21)[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 8 h
Yield: 132 %

Procedure:
1.70 g (42.5 mmol) sodium hydride (60%) are added batchwise to a solution of 4.50 g (33.3 mmol) benzoxazol-2-one in 50 mL DMF, while the temperature is kept below 0° C. by cooling. After one hour's stirring a solution of 9.61 g (37.4 mmol) 1-iodo-4-methyl-4-nitro-pentane in 20 mL DMF is added dropwise so that the temperature does not exceed 5° C. The mixture is stirred overnight at ambient temperature and the solvent is distilled off. The residue is taken up in ethyl acetate and washed successively with water and sodium chloride solution, dried with sodium sulphate and evaporated down. 11.0 g oil are obtained. Mass spectroscopy: [M+H]+=265.
Reaction SMILES: FC(F)(F)S(O[C:7]1[N:12]=[N:11][C:10]2[O:13][CH2:14][CH2:15][CH2:16][C:9]=2[CH:8]=1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].O.[CH:26](B1OB(C=C)OB(C=C)O1)=[CH2:27]>COCCOC.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>[CH:26]([C:7]1[N:12]=[N:11][C:10]2[O:13][CH2:14][CH2:15][CH2:16][C:9]=2[CH:8]=1)=[CH2:27]
Reactant: O=S(=O)(Oc1cc2c(nn1)OCCC2)C(F)(F)F
Reactant: C=CB1OB(C=C)OB(C=C)O1
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: [K+]
Solvent: COCCOC
Solvent: O
Product: C=Cc1cc2c(nn1)OCCC2
Reaction time: 0.33 h
Yield: 77 %

Procedure:
Argon was bubbled for 15 minutes through a solution of 6,7-dihydro-5H-pyrano[2,3-c]pyridazin-3-yl trifluoromethanesulfonate (228 mg, 0.8 mmol) in 1,2-dimethoxyethane (6.5 ml). Tetrakis(triphenylphosphine)palladium(0) (50 mg, 0.0435 mmol) was added and the solution stirred for 20 minutes under argon. The mixture was then treated with potassium carbonate (111 mg, 0.8 mmol), water (1.9 ml) and 2,4,6-trivinylcyclotriboroxane:pyridine complex (180 mg, 0.75 mmol) (for a preparation of this reagent see F. Kerins and D. F. O'Shea, J. Org. Chem. 2002, 67, 4968-4971). After stirring for 2 hours at 80° C., the mixture was cooled and partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution. The layers were separated and the aqueous fraction was extracted twice with 20% methanol/dichloromethane. The combined organic solution was dried, evaporated and the residue chromatographed on silica gel, eluting with ethyl acetate to give product as a white solid (100 mg, 77%).