Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [BrH:1].C(=O)=O.[CH3:5]COCC.N[C@H](C(N[C:22]1[CH:30]=[CH:29][C:25]([N+]([O-])=O)=[CH:24][CH:23]=1)=O)CCCNC(=N)N>C(O)(=O)C>[CH2:5]([Br:1])[C:22]1[CH:23]=[CH:24][CH:25]=[CH:29][CH:30]=1.[BrH:1]
Reactant: N=C(N)NCCC[C@H](N)C(=O)Nc1ccc([N+](=O)[O-])cc1
Reactant: CCOCC
Agent: Br
Agent: O=C=O
Solvent: CC(=O)O
Product: BrCc1ccccc1

Procedure:
4.65 g (10 mM) of compound 1a were treated, while stirring, with 40 ml of 2N HBr in glacial acetic acid for 45 min. at 20° in the absence of moisture. The amino acid derivative dissolved with CO2 evolution. The reaction solution was added dropwise with vigorous stirring to 250 ml of absolute ether which resulted in the precipitation of 2HBr.H-Arg-pNA. The ethereal phase was sucked off, whereupon the solid phase was washed 4 times with portions of 100 ml of abs. ether in order to substantially remove benzyl bromide which had formed as a by-product as well as excess HBr and AcOH. The residue was dissolved in 50 ml of MeOH, the pH was adjusted to 4.5 by the addition of Et3N, and the solution was concentrated to dryness in vacuo at 30°. The resulting product was dissolved in 75 ml of MeOH and passed through a column of "Sephadex" LH-20 (cross-linked dextran gel) equilibrated with MeOH. From a fraction of the eluate there was obtained 4.18 g (91.6% of the theory) of amorphous compound 1b which was homogeneous in the SS as shown by TLC. Elementary analysis and calculation from the empirical formula C12H20N6O3Br2 gave the following values: C=31.15% (31.60%), H=4.35% (4.42%), N=18.84% (18.43%) and Br=34.81% (35.03%).
Reaction SMILES: [C:1]([NH:5][S:6]([CH3:9])(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[F:15][C:16]1[CH:25]=[CH:24][C:19]([C:20](OC)=[O:21])=[CH:18][CH:17]=1.C(O)(=O)C>C1COCC1.C(OCC)(=O)C>[C:1]([NH:5][S:6]([CH2:9][C:20]([C:19]1[CH:24]=[CH:25][C:16]([F:15])=[CH:17][CH:18]=1)=[O:21])(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)NS(C)(=O)=O
Reactant: COC(=O)c1ccc(F)cc1
Agent: [Li]CCCC
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)(C)NS(=O)(=O)CC(=O)c1ccc(F)cc1
Temperature: 0 °C
Yield: 36.6 %

Procedure:
N-tert-Butylmethanesulfonamide (1.00 g) was initially charged in THF (10 ml) and cooled to −78° C. n-Butyllithium (1.6 N in hexane, 9.00 ml) was added dropwise. Subsequently, the mixture was warmed up to 0° C. within 5 minutes, stirred for 5 further minutes and cooled again to −78° C. Methyl 4-fluorobenzoate (1.56 g) in THF (10 ml) dissolved and to −78° C. cooled. The solution prepared above was added dropwise at low temperature. After the addition had ended, the mixture was allowed to come to room temperature and stirred for a further 1 hour. After the addition of acetic acid (0.82 ml) and ethyl acetate (50 ml), the mixture was washed with saturated sodium hydrogencarbonate solution (50 ml) and saturated sodium chloride solution (50 ml). The organic phase was dried over magnesium sulfate, filtered and concentrated by rotary evaporation. Purification was effected via normal phase with an n-heptane/ethyl acetate gradient. The fractions of value were combined, concentrated by rotary evaporation and dried under reduced pressure. This gave the product (661 mg) with a molecular weight of 273.3 g/mol (C12H16FNO3S), MS (EST): m/e=296 (M+Na+).
Reaction SMILES: N#N.[SH2:3].[H][H].[CH:6]1([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1>>[CH:7]1[C:6]2[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=3[S:3][C:11]=2[CH:10]=[CH:9][CH:8]=1
Reactant: S
Reactant: [H][H]
Reactant: c1ccc(C2CCCCC2)cc1
Agent: N#N
Product: c1ccc2c(c1)sc1ccccc12
Temperature: 400 °C
Reaction time: 1.5 h

Procedure:
1.5-2 g of the catalysts of Examples 1-4 were placed in a quartz boat which was in turn inserted into a horizontal quartz tube and placed into a Lindberg furnace. The temperature was raised to 370° C. in about one hour with N2 flowing at 50 cc/m, and the flow continued for 1.5 h at 370° C. N2 was switched off and 10% H2S/H2 then added to the reactor at 20 cc/m, the temperature increased to 400° C., and held there for 2 hours. The heat was then shut off and the catalyst cooled in flowing H2S/H2 to 70° C., at which point this flow was discontinued and N2 was added. At room temperature, the quartz tube was removed and the material transferred into a N2 purged glove box. Catalysts were evaluated in a 300 cc modified Carberry batch reactor designed for constant hydrogen flow. The catalyst was pilled and sized to 20/40 mesh and one gram was loaded into a stainless steel basket, sandwiched between a layer of mullite beads. 100 cc of liquid feed, containing 5 wt % Dibenzothiophene in decalin was added to the autoclave. A hydrogen flow of 100 cc/min was passed through the reactor and the pressure was maintained at 3150 kPa using a back pressure regulator. The temperature was raised to 350° C. at 5-6 deg/min and run until either 50% DBT was converted or until 7 hours was reached. A small aliquot of product was removed every 30 minutes and analyzed by GC. Rate constants for the overall conversion as well as the conversion to the reaction products biphenyl (BP) and cyclohexylbenzene (CHB) were calculated as described by M. Daage and R. R. Chianelli [J. Cat. 149, 414-27 (1994)] and are shown in Table 1. As described in that article, high selectivities to cyclohexylbenzene relative to BP during the desulfurization reaction are a good indication of a catalyst with high hydrodenitrogenation activity, whereas high selectivities of BP relative to CHB indicates a catalyst with high hydrodesulfurization activity.
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[S:3][C:4]1[CH:10]=[CH:9][C:7]([NH2:8])=[CH:6][CH:5]=1.[C:13](OCC)(=[O:18])[CH2:14][C:15]([CH3:17])=[O:16]>C1(C)C=CC=CC=1>[F:12][C:2]([F:11])([F:1])[S:3][C:4]1[CH:10]=[CH:9][C:7]([NH:8][C:13](=[O:18])[CH2:14][C:15](=[O:16])[CH3:17])=[CH:6][CH:5]=1
Reactant: CCOC(=O)CC(C)=O
Reactant: Nc1ccc(SC(F)(F)F)cc1
Solvent: Cc1ccccc1
Product: CC(=O)CC(=O)Nc1ccc(SC(F)(F)F)cc1
Yield: 94.5 %

Procedure:
A mixture of 7.72 g (40 mmol of 4-(trifluoromethylthio)aniline and 5.2 g (40 mmol) of ethyl acetoacetate in 80 ml of dry toluene was refluxed for 8 hours using a Dean-Stark trap to remove the ethanol formed during the reaction. The reaction mixture was cooled in an ice-bath to obtain 10.48 g (95%) of N-[4-(trifluoromethylthio)phenyl]-3-oxobutanamide as a white crystalline solid, melting at 120°-2° C.
Reaction SMILES: [H-].[Na+].CO[C:5](=[O:15])[CH2:6][NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[CH:16](OC)=O.Cl.[CH3:21][O:22][C:23](=[NH:25])[NH2:24]>CC(OC)(C)C.CO>[CH3:21][O:22][C:23]1[NH:24][C:5](=[O:15])[C:6]([NH:7][C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9])=[CH:16][N:25]=1
Reactant: COC(=O)CNC(=O)OC(C)(C)C
Reactant: COC=O
Reactant: COC(=N)N
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: COC(C)(C)C
Solvent: CO
Product: COc1ncc(NC(=O)OC(C)(C)C)c(=O)[nH]1
Reaction time: 8 h
Yield: 42.9 %

Procedure:
Under a nitrogen atmosphere, MTBE (3 ml) was added to 60% sodium hydride (0.10 g). Methyl-N-tert-butoxycarbonyl-glycinate (0.39 g, 2.05 mmol) and methyl formate (0.31 g, 5.13 mmol) were dissolved in MTBE (2 ml) in an ice bath and the solution was added dropwise over 1 hr. After overnight stirring at normal temperature, the precipitate was collected by filtration and the crystal and O-methylisourea hydrochloride (0.22 g, 2.05 mmol) were stirred overnight at 40° C. in methanol. The reaction mixture was analyzed by HPLC. As a result, 2-methoxy-6-oxo-5-tert-butoxycarbonylamino-1,6-dihydropyrimidine (0.21 g, 0.88 mmol, yield 43%) was contained.
Reaction SMILES: O[C:2]1([C:14]2[CH:23]=[CH:22][C:17]([O:18][CH2:19][C:20]#[N:21])=[CH:16][CH:15]=2)[CH2:6][CH2:5][CH2:4][CH:3]1[NH:7][S:8]([CH:11]([CH3:13])[CH3:12])(=[O:10])=[O:9].CCN(S(F)(F)[F:30])CC>>[F:30][C:2]1([C:14]2[CH:23]=[CH:22][C:17]([O:18][CH2:19][C:20]#[N:21])=[CH:16][CH:15]=2)[CH2:6][CH2:5][CH2:4][CH:3]1[NH:7][S:8]([CH:11]([CH3:13])[CH3:12])(=[O:10])=[O:9]
Reactant: CC(C)S(=O)(=O)NC1CCCC1(O)c1ccc(OCC#N)cc1
Reactant: CCN(CC)S(F)(F)F
Product: CC(C)S(=O)(=O)NC1CCCC1(F)c1ccc(OCC#N)cc1

Procedure:
The title compound was prepared in a manner analogous to the procedure set forth in example 54 from 2-[4-(1-hydroxy-2-{[(methylethyl)sulfonyl]amino}cyclopentyl)phenoxy]ethanenitrile (90 mg, 0.27 mmol) and DAST (0.01 mL) to yield the title compound (95 mg) as an oil. This material was purified by silica gel chromatography employing the Chromatotron® and using a 1000 micron rotor while eluting with a solvent methylene chloride/ethyl acetate 19:1 to yield the title compound (80 mg, 87%) as an oil. Ion Spray M.S. 339.1 (M*−1) Calculated for C16H21N2O3SF: Theory: C, 56.45; H, 6.22; N, 8.23. Found: C, 56.18; H, 6.06; N, 8.13.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:13]([C:14]3[CH:19]=[CH:18][CH:17]=CN=3)[N:12]=[C:11]([C:20]([OH:22])=[O:21])[CH:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.[ClH:23].Cl.ClC1C=C[N:29]=[CH:28]C=1NN>>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[N:13]([C:14]3[CH:28]=[N:29][C:17]([Cl:23])=[CH:18][CH:19]=3)[N:12]=[C:11]([C:20]([OH:22])=[O:21])[CH:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1
Reactant: Cl
Reactant: NNc1cnccc1Cl
Reactant: O=C(O)c1cc(-c2cc(F)cc(Cl)c2)n(-c2ccccn2)n1
Product: O=C(O)c1cc(-c2cc(F)cc(Cl)c2)n(-c2ccc(Cl)nc2)n1

Procedure:
1.21 g (4.35 mmol) of the compound of Example 1A is reacted analogously to the synthesis of the compound of Example 20A with 1.04 g (4.78 mmol) of 4-chloropyridin-3-yl-hydrazine dihydrochloride. After hydrolysis, 220 mg (14% of theory) of the title compound is obtained.
Reaction SMILES: C([O:8][C:9]1[C:18](=[O:19])[N:17]2[C:12]([CH:13]([CH3:20])[O:14][CH2:15][CH2:16]2)=[N:11][C:10]=1[C:21]([O:23][CH2:24][CH3:25])=[O:22])C1C=CC=CC=1.[H][H]>C(OCC)(=O)C.C(O)C.[Pd]>[OH:8][C:9]1[C:18](=[O:19])[N:17]2[C:12]([CH:13]([CH3:20])[O:14][CH2:15][CH2:16]2)=[N:11][C:10]=1[C:21]([O:23][CH2:24][CH3:25])=[O:22]
Reactant: [H][H]
Reactant: CCOC(=O)c1nc2n(c(=O)c1OCc1ccccc1)CCOC2C
Agent: [Pd]
Solvent: CCO
Solvent: CCOC(C)=O
Product: CCOC(=O)c1nc2n(c(=O)c1O)CCOC2C
Yield: 95.6 %

Procedure:
Hydrogenolysis of intermediate 14, ethyl 3-benzyloxy-9-methyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylate, (0.610 g, 1.77 mmol) in a mixture of ethyl acetate (75 ml) and ethanol (75 ml) at 25° C. over 10% palladium on activated carbon (0.20 g) under 1 atm of hydrogen for 2 h gave 0.430 g (95% yield) of the title ester as white crystals; mp 119-121° C. (ethyl acetate-hexane). 1HNMR 400 MHz (CDCl3) δ ppm: 1.46 (3H, t, J=7.1 Hz, CH3), 1.67 (3H, d, J=6.6 Hz, CH3), 3.90 (2H, m, CH2), 4.13-4.32 (2H, m, CH2), 4.51 (2H, m, OCH2), 4.70 (1H, q, J=6.6 Hz, CH), 10.7 (1H, broad, OH). Anal. Calcd for C11H14N2O5: C, 51.96; H, 5.55; N, 11.01. Found: C, 51.60; H, 5.61; N, 10.70.
Reaction SMILES: [N:1]1([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:31][CH2:30][CH2:29][C@H:2]1[C:3]([NH:5][C@H:6]([C:14]([NH:16][C@H:17]([C:25]([NH:27]N)=[O:26])[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:15])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4].N[CH2:40][C:41]([NH:43][C@H:44]([C:49]([NH:51][C@@H:52]([C:57]([NH2:59])=[O:58])[CH2:53][CH2:54][S:55][CH3:56])=[O:50])[CH2:45][CH:46]([CH3:48])[CH3:47])=[O:42]>>[N:1]1([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:31][CH2:30][CH2:29][C@H:2]1[C:3]([NH:5][C@H:6]([C:14]([NH:16][C@H:17]([C:25]([NH:27][CH2:40][C:41]([NH:43][C@H:44]([C:49]([NH:51][C@@H:52]([C:57]([NH2:59])=[O:58])[CH2:53][CH2:54][S:55][CH3:56])=[O:50])[CH2:45][CH:46]([CH3:48])[CH3:47])=[O:42])=[O:26])[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:15])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4]
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)NN
Reactant: CSCC[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)CN)C(N)=O
Product: CSCC[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H]1CCCN1C(=O)OC(C)(C)C)C(N)=O
Yield: 60 %

Procedure:
Condensation of BocPro-Phe-PheNHNH2 (Example 1, 1.93 g.) and HGly-Leu-DMetNH2 (1.31 g.) by the acyl azide method (Yajima et al., Chem. Pharm. Bull., vol. 19, p. 1900, 1971) gave BocPro-Phe-Phe-Gly-Leu-DMetNH2 in 60% yield. De-t-butoxycarbonylation of BocPro-Phe-Phe-Gly-Leu-DMetNH2 (1.6 g.) using hydrogen chloride in acetic acid gave HPro-Phe-Phe-Gly-Leu-DMetNH2, which was isolated as the amorphous white solid phosphate (1:1) slat sesquihydrate in 72% yield.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4](S(C)(=O)=O)[C:5]2[N:6]([C:8]([NH2:11])=[N:9][N:10]=2)[N:7]=1.[CH3:16][O-:17].[Na+].[CH3:19][OH:20]>>[CH3:16][O:17][C:2]1[CH:3]=[C:4]([O:20][CH3:19])[C:5]2[N:6]([C:8]([NH2:11])=[N:9][N:10]=2)[N:7]=1
Reactant: C[O-]
Reactant: CO
Reactant: CS(=O)(=O)c1cc(Cl)nn2c(N)nnc12
Agent: [Na+]
Product: COc1cc(OC)c2nnc(N)n2n1

Procedure:
6-Chloro-8-methanesulfonyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylamine (W2.126; 100 mg, 0.40 mmol) was dissolved in methanol (10 ml), and sodium methoxide solution (0.75 ml, 4.04 mmol) was added. The mixture was heated to reflux for 3 h, then concentrated, and the residue was dissolved in water and a pH of 6 was established by adding aqueous hydrochloric acid. The mixture was extracted with EA and the combined organic phases were dried and concentrated. The remaining residue was purified by flash chromatography (dichloromethane:MeOH). Yield: 30 mg
Reaction SMILES: O[C:2]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:7]2[CH2:8][CH2:9][CH:3]1[CH2:4][N:5]([C:10]([C:12]1[CH:16]=[C:15]([C:17]3[CH:18]=[N:19][NH:20][CH:21]=3)[S:14][CH:13]=1)=[O:11])[CH2:6]2.C(N(S(F)(F)[F:34])CC)C>C(Cl)Cl>[F:34][C:2]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:7]2[CH2:8][CH2:9][CH:3]1[CH2:4][N:5]([C:10]([C:12]1[CH:16]=[C:15]([C:17]3[CH:18]=[N:19][NH:20][CH:21]=3)[S:14][CH:13]=1)=[O:11])[CH2:6]2
Reactant: CCN(CC)S(F)(F)F
Reactant: O=C(c1csc(-c2cn[nH]c2)c1)N1CC2CCC(C1)C2(O)c1ccccc1
Solvent: ClCCl
Product: O=C(c1csc(-c2cn[nH]c2)c1)N1CC2CCC(C1)C2(F)c1ccccc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
(8-Hydroxy-8-phenyl-3-aza-bicyclo[3.2.1]oct-3-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]methanone (0.05 g, 0.12 mmol) in DCM (2 mL) was cooled to −78° C. under an atmosphere of nitrogen. Diethylaminosulphur trifluoride (0.05 mL) was added and the mixture stirred for 0.25 hour and allowed to warm to room temperature over 1 hour. The mixture was diluted with DCM and washed with water then dried over magnesium sulphate, filtered and the solvent removed by evaporation. The residue was purified by reverse phase HPLC and the fractions containing the desired products were combined and the solvent removed by lyophilisation to give the title compound as a white solid (0.02 g). LCMS m/z 382.1 [M+H]+. RT.=4.25 min (Analytical Method 2).
Reaction SMILES: [Na].[OH:2][CH:3]1[CH2:7][CH2:6][C:5](=[N:8]O)[C:4]1([CH3:11])[CH3:10]>C(O)CC.[Cl-].[Na+].O>[NH2:8][CH:5]1[CH2:6][CH2:7][CH:3]([OH:2])[C:4]1([CH3:11])[CH3:10]
Reactant: CC1(C)C(=NO)CCC1O
Agent: [Cl-]
Agent: [Na+]
Agent: [Na]
Solvent: O
Solvent: CCCO
Product: CC1(C)C(N)CCC1O
Temperature: 25 °C
Yield: 95.6 %

Procedure:
Sodium (2.312 g, 101 mmol) was added in small portions over 30 min to a solution of 3-hydroxy-2,2-dimethylcyclopentanone oxime (3.60 g, 25.1 mmol, from Step 2) in n-propanol (50 mL) at 80° C. The resultant mixture was heated to 100° C. for 2 h, cooled to room temperature, poured into brine (100 mL) and extracted with ethyl acetate (3×200 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated to give crude 3-amino-2,2-dimethylcyclopentanol (3.10 g), which was used in the next reaction without purification.
Reaction SMILES: FC(F)(F)C(O)=O.[CH2:8]([NH:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[C:18]([O:22][CH3:23])[NH:19]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11].C(=O)([O-])[O-].[K+].[K+].Br[CH2:32][CH:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1>CN(C)C=O.C(OCC)(=O)C>[CH2:8]([NH:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[C:18]([O:22][CH3:23])[N:19]2[CH2:32][CH:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11]
Reactant: BrCC1CCOCC1
Reactant: CCCCNc1nc(N)c2nc(OC)[nH]c2n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O=C(O)C(F)(F)F
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCCCNc1nc(N)c2nc(OC)n(CC3CCOCC3)c2n1
Temperature: 60 °C
Reaction time: 1.5 h
Yield: 90 %

Procedure:
To a solution of N2-butyl-8-methoxy-9H-purine-2,6-diamine trifluoroacetic acid salt (500 mg) in dry N,N-dimethylformamide (8 ml) at room temperature and under nitrogen was added potassium carbonate (1.17 g) in one go. The reaction was stirred at 60° C. for 1.5 hours and then cooled to room temperature. 4-(bromomethyl)tetrahydro-2H-pyran (0.3 ml) was added in one go and the reaction heated at 50° C. overnight. The reaction was diluted with ethyl acetate (20 ml) and washed with water (10 ml). The organic layer was separated and concentrated in vacuo. The product was purified by C18 reverse phase chromatography using water (containing 0.1% formic acid)-acetonitrile (containing 0.05% formic acid) as eluant (10-45%) to afford the title compound as a yellow viscous oil (315 mg, 90% clean).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1/[C:9](/[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1)=[CH:10]/[CH:11]=[CH:12]/[C:13]([OH:15])=[O:14].[N+:24]([C:27]1[CH:32]=[CH:31][C:30](O)=[CH:29][CH:28]=1)([O-:26])=[O:25].C1(N=C=NC2CCCCC2)CCCCC1>ClCCl>[N+:24]([C:27]1[CH:32]=[CH:31][C:30]([O:14][C:13](=[O:15])/[CH:12]=[CH:11]/[CH:10]=[C:9](/[C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])\[C:16]2[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=2)=[CH:29][CH:28]=1)([O-:26])=[O:25]
Reactant: COc1ccc(/C(=C\C=C\C(=O)O)c2ccccc2OC)cc1
Reactant: O=[N+]([O-])c1ccc(O)cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: ClCCl
Product: COc1ccc(/C(=C\C=C\C(=O)Oc2ccc([N+](=O)[O-])cc2)c2ccccc2OC)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 63.5 %

Procedure:
As in Example 115, (E,E)-5-(2-methoxyphenyl)-5-(4-methoxyphenyl)-2,4-pentadienoic acid (3.4 g) and 4-nitrophenol (1.8 g) in 25 mL of dichloromethane was treated with 1,3-dicyclohexylcarbodiimide (2.27 g). The mixture was stirred at room temperature for 2 hours. After the usual work up, the ester was crystallized from 2-propanol to yield 3.0 g of (E,E)-5-(2-methoxyphenyl)-5-(4-methoxyphenyl)-2,4-pentadienoic acid 4-nitrophenyl ester, mp 149°-150° C.
Reaction SMILES: [BrH:1].[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH:13]=[C:12]([C:14](=[O:16])[CH3:15])[N:11]=[C:10]2[C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=2[Cl:24])=[CH:5][CH:4]=1.BrBr.C(=O)(O)[O-].[Na+]>C(O)(=O)C>[Br:1][CH2:15][C:14]([C:12]1[N:11]=[C:10]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=2[Cl:24])[N:9]([C:6]2[CH:7]=[CH:8][C:3]([Cl:2])=[CH:4][CH:5]=2)[CH:13]=1)=[O:16]
Reactant: Br
Reactant: CC(=O)c1cn(-c2ccc(Cl)cc2)c(-c2ccc(Cl)cc2Cl)n1
Agent: BrBr
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Product: O=C(CBr)c1cn(-c2ccc(Cl)cc2)c(-c2ccc(Cl)cc2Cl)n1
Temperature: 23 °C
Reaction time: 1 h
Yield: 53 %

Procedure:
Aqueous HBr (0.98 ml of a 48% solution) was added to a solution of 1-[1-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-1H-imidazol-4-yl]-ethanone I-7f (1.60 g, 4.38 mmol) in acetic acid (20 ml). Bromine (0.226 ml, 4.38 mmol) was added next to the reaction mixture in a dropwise manner. The resultant orange solution was stirred at 23° C. for 1 h before warming to 40° C. for 40 min and then cooling to 23° C. for 60 h. The reaction mixture was poured into a mixture of ice and saturated aqueous sodium bicarbonate, and the resultant mixture was extracted with ethyl acetate (2 200-ml portions). The combined organics were washed with saturated aqueous sodium bicarbonate (100 ml) and were dried over anhydrous magnesium sulfate and concentrated to afford 2-bromo-1-[1-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-1H-imidazol-4-yl]-ethanone I-7g (1.03 g, 53%).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:16])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][CH3:14])=[CH:9][C:8]=1[CH3:15])[CH3:2].Cl[CH2:18][C:19]1[S:23][C:22]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=2)=[N:21][C:20]=1[CH3:34].[Na+].[I-].[H-].[Na+]>CN(C=O)C.CCOCC>[CH2:1]([O:3][C:4](=[O:16])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]([CH3:14])[CH2:18][C:19]2[S:23][C:22]([C:24]3[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=3)=[N:21][C:20]=2[CH3:34])=[CH:9][C:8]=1[CH3:15])[CH3:2]
Reactant: Cc1nc(-c2ccc(C(F)(F)F)cc2)sc1CCl
Reactant: CCOC(=O)COc1ccc(NC)cc1C
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: CCOCC
Solvent: CN(C)C=O
Product: CCOC(=O)COc1ccc(N(C)Cc2sc(-c3ccc(C(F)(F)F)cc3)nc2C)cc1C
Temperature: 25 °C
Yield: 113.6 %

Procedure:
To an ice-cooled and stirred solution of (2-methyl-4-methylamino-phenoxy)-acetic acid ethyl ester (0.357 g, 1.6 mmol), 5-chloromethyl-4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole (0.513 g, 1.76 mmol, WO02/28433) and NaI (0.24 g, 1.6 mmol) in DMF (4.8 ml) was added NaH (55% in oil, 0.105 g, 2.4 mmol). The reaction was stirred at RT for 2¾h, diluted with Et2O and extracted with aqueous 10% KHSO4/Et2O (3×). The organic phases were washed with aqueous 10% NaCl, dried (Na2SO4) and evaporated to give 0.87 g (quantitative) of crude (2-methyl-4-{methyl-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethyl]-amino}-phenoxy)-acetic acid ethyl ester as a yellow solid, MS: 479 (MH+).
Reaction SMILES: CN1CCOCC1.[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH:16]1[CH2:28][CH2:29][OH:30])=[O:14])([CH3:11])([CH3:10])[CH3:9]>C(Cl)Cl.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC>[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH:16]1[CH2:28][CH:29]=[O:30])=[O:14])([CH3:11])([CH3:10])[CH3:9]
Reactant: CC(C)(C)OC(=O)N1CCN(C(=O)OC(C)(C)C)C(CCO)C1
Agent: O=[Ru](=O)(=O)[O-]
Agent: CCC[N+](CCC)(CCC)CCC
Solvent: CN1CCOCC1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCN(C(=O)OC(C)(C)C)C(CC=O)C1
Temperature: 25 °C
Reaction time: 17 h

Procedure:
In methylene chloride (150 ml) was dissolved 1,4-bis(tert-butoxycarbonyl)-2-(2-hydroxyethyl)piperazine. Under ice cooling, N-methylmorpholine (2.14 g) and tetra-n-propylammonium perruthenate (0.97 g) were added to the reaction mixture, followed by stirring at room temperature for 17 hours. The reaction mixture was then distilled off under reduced pressure. The residue was subjected to chromatography on a silica gel column (hexane:ethyl acetate=9:1 to 2:1), whereby the title compound (3.11 g) was obtained as colorless powder.