Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[CH3:19])[N:10]=[C:9]2[CH:20]([NH:22][C:23]2[N:31]=[CH:30][N:29]=[C:28]3[C:24]=2[N:25]=[CH:26][N:27]3COCC[Si](C)(C)C)[CH3:21])[CH:5]=[CH:6][CH:7]=1.[CH3:40][O:41][C:42]1C=C(N2C(=O)C3C(=CC=CC=3C)N=C2C(NC2N=CN=C3C=2N=CN3COCC[Si](C)(C)C)C)C=C[CH:47]=1.Cl.OC1C=C(N2C(=O)C3C(=CC=CC=3C)N=C2C(NC2N=CN=C3C=2N=CN3)C)C=CC=1>CO>[CH3:40][O:41][CH2:42][CH2:47][O:1][C:2]1[CH:3]=[C:4]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[CH3:19])[N:10]=[C:9]2[CH:20]([NH:22][C:23]2[N:31]=[CH:30][N:29]=[C:28]3[C:24]=2[N:25]=[CH:26][NH:27]3)[CH3:21])[CH:5]=[CH:6][CH:7]=1
Reactant: Cc1cccc2nc(C(C)Nc3ncnc4c3ncn4COCC[Si](C)(C)C)n(-c3cccc(O)c3)c(=O)c12
Reactant: COc1cccc(-n2c(C(C)Nc3ncnc4c3ncn4COCC[Si](C)(C)C)nc3cccc(C)c3c2=O)c1
Agent: Cc1cccc2nc(C(C)Nc3ncnc4[nH]cnc34)n(-c3cccc(O)c3)c(=O)c12
Agent: Cl
Solvent: CO
Product: COCCOc1cccc(-n2c(C(C)Nc3ncnc4[nH]cnc34)nc3cccc(C)c3c2=O)c1

Procedure:
Compound 126 (300 mgs, 0.54 mmol) was treated with toluene 4-sulfonic acid 2-methoxy ethyl ester at 50 C for 42 hrs using the procedure described above for compound 127. The generated intermediate was then treated with 4N HCl in MeOH, using the procedure described for compound 121 (step D). m/z=487 (M+H).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH2:11])(=[O:10])=[O:9])=[CH:4][C:3]=1[S:12]([C:15]([F:18])([F:17])[F:16])(=[O:14])=[O:13].CC[N:21]([CH:25]([CH3:27])[CH3:26])C(C)C.[C:28]([O:31][CH2:32]C)(=[O:30])C>CN(C=O)C>[C:5]1([S:8][CH2:27][C@H:25]([NH:21][C:2]2[CH:7]=[CH:6][C:5]([S:8](=[O:10])(=[O:9])[NH2:11])=[CH:4][C:3]=2[S:12]([C:15]([F:18])([F:17])[F:16])(=[O:14])=[O:13])[CH2:26][C:28]([O:31][CH3:32])=[O:30])[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=1
Reactant: NS(=O)(=O)c1ccc(F)c(S(=O)(=O)C(F)(F)F)c1
Reactant: CCOC(C)=O
Reactant: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COC(=O)C[C@H](CSc1ccccc1)Nc1ccc(S(N)(=O)=O)cc1S(=O)(=O)C(F)(F)F
Temperature: 50 °C
Yield: 56 %

Procedure:
4-Fluoro-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 6, 21.67 g, 71.22 mmol) and DIPEA (129 ml, 738 mmol) were added to a solution of (R)-methyl 3-amino-4-(phenylthio)butanoate, trifluoroacetic acid salt (INTERMEDIATE 7, STEP 2) in DMF (20 ml). The resulting reaction mixture was heated at 50° C. for 1.5 hours, allowed to cool to room temperature, diluted with ethyl acetate (500 ml), and washed with water (250 ml) and brine (250 ml). The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography (ISCO, eluting with 0→30% EtOAc/DCM over 54 minutes) to give the title product (20.5 g, yield: 56%).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:14])[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][CH:3]=1.[C:15]([C:18]1[CH:25]=[CH:24][CH:23]=[CH:22][C:19]=1[CH:20]=[O:21])(O)=[O:16].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[O:16]=[C:15]1[C:18]2[C:19](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([CH:8]([CH3:14])[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:6][CH:7]=2)[O:21]1
Reactant: CCOC(=O)C(C)c1ccc(N)cc1
Reactant: O=Cc1ccccc1C(=O)O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: CCOC(=O)C(C)c1ccc(NC2OC(=O)c3ccccc32)cc1

Procedure:
The mixture of 17.7 g of ethyl α-(4-aminophenyl)-propionate, 15 g of 2-carboxy-benzaldehyde, 50 mg of p-toluenesulfonic acid and 400 ml of toluene is refluxed for two days on a water trap. After collection of the theoretical amount of water (1.9 ml), it is concentrated and the precipitate formed recrystallized from ethanol, to yield the ethyl α-[4-(3-oxo-isobenzofuran-1-ylamino)-phenyl]-propionate, melting at 136°-139°.
Reaction SMILES: [F:1][C:2]([F:24])([F:23])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:22]=[CH:21][C:18](C=O)=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.C1(P(C2C=CC=CC=2)(C2C=CC=CC=2)=[C:32]([CH3:38])[C:33]([O:35][CH2:36][CH3:37])=[O:34])C=CC=CC=1.[C:51]1(C)C=CC=CC=1>>[CH3:51]/[C:32](=[CH:38]\[C:18]1[CH:21]=[CH:22][C:15]([C:12]2[N:13]=[CH:14][N:10]([C:7]3[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:24])[F:23])=[CH:9][CH:8]=3)[N:11]=2)=[CH:16][CH:17]=1)/[C:33]([O:35][CH2:36][CH3:37])=[O:34]
Reactant: CCOC(=O)C(C)=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=Cc1ccc(-c2ncn(-c3ccc(OC(F)(F)F)cc3)n2)cc1
Reactant: Cc1ccccc1
Product: CCOC(=O)/C(C)=C/c1ccc(-c2ncn(-c3ccc(OC(F)(F)F)cc3)n2)cc1
Temperature: 110 °C
Yield: 62 %

Procedure:
4-(1-(4-(Trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzaldehyde (7.56 g, 22.7 mmol) and ethyl 2-(triphenylphosphoranylidene)propanoate (9.87 g, 27.2 mmol) in anhydrous toluene (30 mL) was heated at 110° C. for 16 hours. Additional ethyl 2-(triphenylphosphoranylidene)propanoate (2.40 g, 6.06 mmol) was then added, and the reaction was heated at 110° C. for 4 hours. The reaction was cooled, concentrated under vacuum, and loaded onto silica gel. Purification by flash column chromatography using 0-100% ethyl acetate/hexanes as eluent followed by reverse-phase flash column chromatography using 0-100% acetonitrile/water as eluent afforded the title compound as a white solid (5.92 g, 62%): mp 126-127.5° C.; 1H NMR (400 MHz, CDCl3) δ 8.58 (s, 1H), 8.27-8.17 (m, 2H), 7.84-7.78 (m, 2H), 7.73 (s, 1H), 7.52 (d, J=8.2 Hz, 2H), 7.40 (d, J=8.3 Hz, 2H), 4.29 (q, J=7.1 Hz, 2H), 2.17 (d, J=1.5 Hz, 3H), 1.37 (t, J=7.1 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ −58.02; ESIMS m/z 418 ([M+H]+).
Reaction SMILES: Cl[C:2]1[N:3]=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)=[CH:6][CH:7]=1.[C:15]([NH:19][NH2:20])(=O)[CH2:16][CH3:17]>C(O)CCC>[Cl:14][C:11]1[CH:12]=[CH:13][C:8]([C:5]2[CH:6]=[CH:7][C:2]3[N:3]([C:15]([CH2:16][CH3:17])=[N:19][N:20]=3)[N:4]=2)=[CH:9][CH:10]=1
Reactant: Clc1ccc(-c2ccc(Cl)nn2)cc1
Reactant: CCC(=O)NN
Solvent: CCCCO
Product: CCc1nnc2ccc(-c3ccc(Cl)cc3)nn12

Procedure:
A mixture of 9.0 g. of 3-chloro-6-(p-chlorophenyl)pyridazine (prepared as in Example 16), 7.4 g. of propionic acid hydrazide and 60 ml. of butyl alcohol is stirred at reflux temperature for 48 hours. The mixture is chilled, filtered and the solid is washed with petroleum ether and with water. The material is recrystallized from 50 ml. of ethyl alcohol to afford the product of the example as crystals, m.p. 197°-199° C.
Reaction SMILES: [CH2:1]=[CH:2][CH:3]=[CH2:4]>C1C=CC=CC=1>[CH:2]1[CH2:1][CH2:4][CH:3]=[CH:2][CH2:1][CH2:4][CH:3]=1.[CH:2]1[CH2:1][CH2:4][CH:3]=[CH:2][CH2:1][CH2:4][CH:3]=[CH:2][CH2:1][CH2:4][CH:3]=1
Reactant: C=CC=C
Solvent: c1ccccc1
Product: C1=CCCC=CCC1
Product: C1=CCCC=CCCC=CCC1
Temperature: 120 °C
Reaction time: 1 h

Procedure:
A predried six ounce aerosol compatibility bottle equipped with a magnetic stirring bar was charged in a dry box with 0.17 g (0.20 mmol) of Ni2 (μ-PPh2)2 (PEt3)3, 10 ml of benzene and then capped. The capped bottle was removed from the dry box and 20.65 g (0.382 mol) of 1,3-butadiene was added. The bottle was heated in an oil bath as the contents were magnetically stirred. The temperature was gradually increased. After about one hour at a temperature of about 80° C. the pressure in the bottle was 93 psig. The absence of any observed pressure drop was taken to indicate that no significant reaction had yet ocurred. After heating for about 30 more minutes the temperature was about 118° C. and the pressure in the bottle about 160 psig. After one hour at this temperature, the pressure had fallen to 143 psig. The reaction mixture was then cooled. After being allowed to set at room temperature over the weekend the reaction mixture was heated to about 120° C. After about an hour at this temperature the pressure in the bottle had dropped from 110 psig to 20 psig. The reaction mixture was then cooled and an additional 19.23 g (0.356 mol) of 1,3-butadiene was added. The reaction mixture was then reheated to 120° C. After about 2 more hours at 120° C., the pressure again decreased to about 20 psig. The reaction mixture was then again cooled and a further 29.67 g (0.549 mol) of 1,3-butadiene was added. After heating this mixture for about two more hours at 120° C. the pressure dropped to about 38 psig. The reaction was then terminated although the solution still retained its homogeneous dark green appearance. The mixture was then exposed to air to destroy the catalyst and filtered. The filtrate was distilled to afford 28.7 g of 1,5-cyclooctadiene, 5.7 g of 1,5,9-cyclododecatriene, and other products.
Reaction SMILES: [OH:1][C:2]([CH:7]([F:9])[F:8])([CH3:6])[C:3](O)=[O:4].S(Cl)(Cl)=O.[NH2:14][C:15]1[CH:28]=[CH:27][C:18]([C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:20])=[CH:17][CH:16]=1.Cl.C>CC(N(C)C)=O>[C:21]1([C:19]([C:18]2[CH:17]=[CH:16][C:15]([NH:14][C:3](=[O:4])[C:2]([OH:1])([CH3:6])[CH:7]([F:9])[F:8])=[CH:28][CH:27]=2)=[O:20])[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: CC(O)(C(=O)O)C(F)F
Reactant: Nc1ccc(C(=O)c2ccccc2)cc1
Agent: Cl
Solvent: CC(=O)N(C)C
Solvent: O=S(Cl)Cl
Product: CC(O)(C(=O)Nc1ccc(C(=O)c2ccccc2)cc1)C(F)F
Temperature: -10 °C

Procedure:
A solution of 2-hydroxy-2-difluoromethylpropionic acid (1.07 g, 7.65 mmol) in dry dimethylacetamide.(15 ml) was stirred under a nitrogen atmosphere at -10° C. Thionyl chloride (0.91 g, 7.65 mmol) was added and the resulting mixture was allowed to stir at -10° C. for 1 hour. 4-Aminobenzophenone (1.0 g, 5.1 mmol) was then added and the reaction mixture was stirred at -10° C. for a further 15 mins. The solution was then allowed to warm to room temperature where it was stirred overnight. The reaction mixture was poured into hydrochloric acid solution (1M) and extracted with ethyl acetate. The combined ethyl acetate fractions were washed with water and brine. After drying (Na2SO4) and decolorization (Charcoal) the solution was evaporated in vacuo. A off-white foam was obtained which was triturated with hexane/ethyl acetate. The crude product was filtered through a short silica gel column with chloroform and crystallized from chloroform/hexane to give the title tertiary carbinol (0.89 g, 55%) as shiny, buff-colored crystals; mp=123°-124° C. 1H-NMR (300 MHz, d6 -DMSO): 1.45 (s, 3H, CH3), 6.17 (t, J=55 Hz, 1H, CHF2), 6.77 (s, 1H, OH), 7.56 (t, 2H, ArH), 7.65-7.76 (m, 5H, ArH), 7.96 (d, J=8.7 Hz, 2H, ArH), 10.19 (s, 1H, NH). MS (CI, CH4): 320(M+1, 100). Analysis for C17H15F 2NO3.0.2 H2O: Calculated: C, 63.23; H, 4.81; N, 4.34 Found: C, 63.21; H, 4.74; N, 4.30
Reaction SMILES: [CH2:1]([OH:6])[CH:2]([OH:5])[CH2:3][OH:4].[Br:7][CH2:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=1)=O.CC1C=CC(S(O)(=O)=O)=CC=1.[OH-].[Na+]>O.C1C=CC=CC=1.C(O)CCC>[Br:7][CH2:8][C:9]1([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[O:5][CH:2]([CH2:3][OH:4])[CH2:1][O:6]1
Reactant: OCC(O)CO
Reactant: COc1ccc(C(=O)CBr)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCCCO
Solvent: O
Solvent: c1ccccc1
Product: COc1ccc(C2(CBr)OCC(CO)O2)cc1

Procedure:
A mixture of 69 parts of 1,2,3-propanetriol, 142 parts of 2-bromo-1-(4-methoxyphenyl)-ethanone, 6.3 parts of 4-methylbenzenesulfonic acid, 80 parts of 1-butanol and 450 parts of benzene was stirred and refluxed for 20 hours with water separator. The reaction mixture was cooled and poured into a diluted sodium hydroxide solution. The layers were separated and the aqueous phase was extracted twice with methylbenzene. The combined organic phases were washed with water, dried, filtered and evaporated, yielding 186.5 parts of 2-(bromomethyl)-2-(4-methoxyphenyl)-1,3-dioxolane-4-methanol as a residue (interm. 1).
Reaction SMILES: O.NN.[CH3:4][O:5][C:6]1[C:11]([CH2:12][N:13]2C(=O)C3C(=CC=CC=3)C2=O)=[CH:10][CH:9]=[C:8]([O:24][CH2:25][C:26]([F:29])([F:28])[F:27])[N:7]=1>CO>[CH3:4][O:5][C:6]1[C:11]([CH2:12][NH2:13])=[CH:10][CH:9]=[C:8]([O:24][CH2:25][C:26]([F:29])([F:27])[F:28])[N:7]=1
Reactant: COc1nc(OCC(F)(F)F)ccc1CN1C(=O)c2ccccc2C1=O
Agent: NN
Solvent: CO
Solvent: O
Product: COc1nc(OCC(F)(F)F)ccc1CN
Temperature: 50 °C
Reaction time: 20 h
Yield: 94.9 %

Procedure:
Hydrazine hydrate (0.13 mL) is added to a solution of 2-((2-methoxy-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methyl)isoindoline-1,3-dione (0.67 g, 1.83 mmol) in methanol (20 mL) and stirred for 20 hours at 50° C. After removal of the solvent, the residue is poured into 2N sodium hydroxide (10 mL) and extracted with dichloromethane (30 mL×3) and dried over sodium sulfate, and concentrated in vacuo to give 0.41 g (95% yield) of the title compound as a white solid.
Reaction SMILES: [C:1]1([S:15]([O-:18])(=[O:17])=[O:16])[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([S:11]([O-:14])(=[O:13])=[O:12])[C:5]=2[CH:4]=[CH:3][CH:2]=1.[Na+:19].[Na+:20].[OH-].[Na+]>>[C:1]1([S:15]([O-:18])(=[O:17])=[O:16])[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([S:11]([OH:14])(=[O:13])=[O:12])[C:5]=2[CH:4]=[CH:3][CH:2]=1.[Na+:19].[Na:19][Na:20]
Reactant: O=S(=O)([O-])c1cccc2c(S(=O)(=O)[O-])cccc12
Agent: [Na+]
Agent: [OH-]
Product: O=S(=O)([O-])c1cccc2c(S(=O)(=O)O)cccc12
Product: [Na][Na]
Reaction time: 10 h

Procedure:
The bipolar membrane prepared in this manner was used for the electrodialysis as described in Example 2, the apparatus being shown in FIG. 2. Electrodialysis was carried out for 10 hours at room temperature and at a current density of 2.9 A/cm2. 200 parts of an aqueous 0.25 molar solution of disodium naphthalene-1,5-disulfonate were used in compartment (9), and 100 parts of 0.5% strength sodium hydroxide solution were employed in compartment (8). 1937 parts of a 0.24 molar solution of monosodium naphthalene-1,5-disulfonate (0.02 mole/kg of the disodium salt, current efficiency 50%) were obtained in compartment (9), and about 1000 parts of 2.2% strength Sodium hydroxide solution were obtained in compartment (8).
Reaction SMILES: C(N(CC)CC)C.[OH:8][C:9]1[C:14]2[CH:15]=[CH:16][C:17]([OH:20])=[C:18]([CH3:19])[C:13]=2[O:12][C:11](=[O:21])[CH:10]=1.[C:22]([Si:26]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)Cl)([CH3:25])([CH3:24])[CH3:23].P([O-])([O-])(O)=O.[Na+].[Na+]>O1CCCC1.CO>[CH3:25][C:22]([Si:26]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[O:20][C:17]1[CH:16]=[CH:15][C:14]2[C:9]([OH:8])=[CH:10][C:11](=[O:21])[O:12][C:13]=2[C:18]=1[CH3:19])([CH3:23])[CH3:24]
Reactant: Cc1c(O)ccc2c(O)cc(=O)oc12
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: O=P([O-])([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Solvent: CCN(CC)CC
Product: Cc1c(O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)ccc2c(O)cc(=O)oc12
Reaction time: 20 h

Procedure:
85 ml of triethylamine is agitated in a suspension containing 50 g of 4,7-dihydroxy-8-methyl-2H-1-benzopyran-2-one and 400 ml of tetrahydrofuran. A solution of 76 ml of terbutyldiphenylchlorosilane in 50 ml of tetrahydrofuran is added. The reaction mixture is agitated for 20 hours, then it is poured into a buffer solution of sodium hydrogen phosphate. Extraction is carried out with ethyl acetate, the organic phase is washed with water, dried and brought to dryness. A product is obtained which is taken up in methanol, agitation is carried out for 4 hours, followed by separating, washing and drying. 84,5 g of sought product is obtained.
Reaction SMILES: C(OC(N1C2CCC1C(NC1C=CC=C(C(F)(F)F)N=1)C2)=O)(C)(C)C.[Cl:26][C:27]1[CH:28]=[CH:29][C:30]2[O:34][C:33]([NH:35][CH:36]3[CH2:41][CH:40]4[N:42](C(OC(C)(C)C)=O)[CH:37]3[CH2:38][CH2:39]4)=[N:32][C:31]=2[CH:50]=1>>[ClH:26].[CH:37]12[NH:42][CH:40]([CH2:39][CH2:38]1)[CH2:41][CH:36]2[NH:35][C:33]1[O:34][C:30]2[CH:29]=[CH:28][C:27]([Cl:26])=[CH:50][C:31]=2[N:32]=1
Reactant: CC(C)(C)OC(=O)N1C2CCC1C(Nc1nc3cc(Cl)ccc3o1)C2
Agent: CC(C)(C)OC(=O)N1C2CCC1C(Nc1cccc(C(F)(F)F)n1)C2
Product: Cl
Product: Clc1ccc2oc(NC3CC4CCC3N4)nc2c1

Procedure:
Prepared analogous to Example 209 substituting (±)-tert-butyl-2-((6-(trifluoromethyl)pyridin-2-yl)amino)-7-azabicyclo[2.2.1]heptane-7-carboxylate with the title compound of step A. MS (ESI) mass calcd. for C13H14ClN3O, 263.1; m/z found 264.0 [M+H]+.
Reaction SMILES: [C:1]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21]O)[CH:16]=2)[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH2:23]([N:30]1[CH2:35][CH2:34][O:33][CH:32]([CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([CH3:43])[C:38]=2[F:44])[C:31]1=O)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+].C(OCC)(=O)C>O1CCCC1>[C:1]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH:21]=[CH:38][C:37]3[CH:42]=[N:30][CH:31]=[CH:32][CH:36]=3)[CH:16]=2)[CH2:9]1)([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2].[CH2:23]([N:30]1[CH2:35][CH2:34][O:33][CH:32]([CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([CH3:43])[C:38]=2[F:44])[CH2:31]1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: CC(C)(C)OC(=O)N1CCO[C@H](Cc2cccc(CO)c2)C1
Reactant: Cc1cccc(CC2OCCN(Cc3ccccc3)C2=O)c1F
Agent: O=C([O-])[C@H](O)[C@@H](O)C(=O)[O-]
Agent: [K+]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCO[C@H](Cc2cccc(C=Cc3cccnc3)c2)C1
Product: Cc1cccc(CC2CN(Cc3ccccc3)CCO2)c1F
Temperature: 23 °C
Reaction time: 1 h

Procedure:
To a solution of intermediate (b), N-benzyl-2-(2-Fluoro-3-methyl-benzyl)-morpholin-3-one (275 mg, 0.876 mmol) in tetrahydrofuran (10 mL) at 0° C. was added BH3 (1M in tetrahydrofuran, 2.63 mL, 2.63 mmol). The mixture was stirred at 23° C. for 1 h then heated to reflux for 18 h, cooled to 23° C. and stirred vigorously with Rochelle's salt solution (15 mL) for 1.5 h. Ethyl acetate (30 mL) was added and stirring continued for 1.5 h. The organic phase was separated, dried (Na2SO4) and concentrated affording intermediate (a), N-benzyl-2-(2-fluoro-3-methyl-benzyl)-morpholine, as a pale yellow oil (190 mg, 73%).
Reaction SMILES: C[O:2][CH:3](OC)[CH2:4][NH:5][C:6](=[O:21])[C:7]([NH:10][C:11](=[O:20])[O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([CH3:9])[CH3:8].Cl.C(OCC)(=O)C>C1COCC1>[CH3:9][C:7]([NH:10][C:11](=[O:20])[O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([CH3:8])[C:6](=[O:21])[NH:5][CH2:4][CH:3]=[O:2]
Reactant: COC(CNC(=O)C(C)(C)NC(=O)OCc1ccccc1)OC
Agent: Cl
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)(NC(=O)OCc1ccccc1)C(=O)NCC=O
Temperature: 25 °C
Yield: 99.9 %

Procedure:
To a solution of benzyl 1-(2,2-dimethoxyethylamino)-2-methyl-1-oxopropan-2-ylcarbamate (0.52 g, 1.6 mmol) in THF (20 mL) was added 5 M hydrochloric acid (10 mL) and the mixture was stirred at room temperature until TLC showed the reaction was completed. Ethyl acetate (50 mL) was added and the phases were separated. The organic layer was washed with brine (4×30 mL) to pH=6-7, dried over anhydrous sodium sulfate and concentrated to yield product (0.445 g, 100%) as yellow oil, which was used directly in the next step without purification; MS: m/e 279.1 [M+H]+.
Reaction SMILES: [CH2:1]([N:13]1[CH:17]=[CH:16][N:15]=[C:14]1[CH2:18][CH3:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[CH2:20]([Br:32])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31]>C(O)C>[Br-:32].[CH2:1]([N:13]1[CH:17]=[CH:16][N:15]([CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH3:20])[CH:14]1[CH2:18][CH3:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCCCn1ccnc1CC
Reactant: CCCCCCCCCCCCBr
Solvent: CCO
Product: CCCCCCCCCCCCN1C=CN(CCCCCCCCCCCC)C1CC
Product: [Br-]

Procedure:
0.38 mole of 1-n-dodecyl-2-ethylimidazole and 0.42 mole of n-dodecyl bromide are dissolved in 250 ml of ethanol and boiled with reflux for 5 hours. The solvent then is separated and the residue is washed with ether.
Reaction SMILES: [CH3:1][N:2]1[CH2:6][C@@H:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[N:4]([C:14](=[O:28])[C@H:15](OS(C2C=CC(C)=CC=2)(=O)=O)[CH3:16])[C:3]1=[O:29].[NH2:30][C@@H:31]([CH2:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33]>>[CH3:1][N:2]1[CH2:6][C@@H:5]([C:7]([O:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:8])[N:4]([C:14](=[O:28])[C@@H:15]([NH:30][C@H:31]([C:32]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[O:33])[CH2:42][CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH3:16])[C:3]1=[O:29]
Reactant: N[C@@H](CCc1ccccc1)C(=O)OCc1ccccc1
Reactant: Cc1ccc(S(=O)(=O)O[C@H](C)C(=O)N2C(=O)N(C)C[C@H]2C(=O)OC(C)(C)C)cc1
Product: C[C@H](N[C@@H](CCc1ccccc1)C(=O)OCc1ccccc1)C(=O)N1C(=O)N(C)C[C@H]1C(=O)OC(C)(C)C
Yield: 82.3 %

Procedure:
t-Butyl (4S)-1-methyl-3-[(2R)-2-(p-toluenesulfonyloxy)propionyl]-2-oxoimidazolidine-4-carboxylate (1 g) obtained in Example 1 - (1) and benzyl (2S)-2-amino-4-phenylbutyrate (1.55 g) were treated similarly as in Example 1 - (2) to give t-butyl (4S)-1-methyl-3-{(2S)-2-[N-((1S)-1-benzyloxycarbonyl-3-phenyl-propyl)amino]propionyl}-2-oxoimidazolidine-4-carboxylate (1.01 g) as colorless syrup. Yield: 82.3%.
Reaction SMILES: [O:1]=[C:2]1[NH:7][CH2:6][C:5]([C:8]2[CH:20]=[CH:19][C:11]([O:12][CH2:13][C:14]([O:16]CC)=[O:15])=[CH:10][CH:9]=2)=[N:4][NH:3]1.[N:21]1([CH2:27][CH2:28][NH2:29])[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1>C(O)C>[OH2:1].[N:21]1([CH2:27][CH2:28][NH:29][C:14](=[O:16])[CH2:13][O:12][C:11]2[CH:10]=[CH:9][C:8]([C:5]3[CH2:6][NH:7][C:2](=[O:1])[NH:3][N:4]=3)=[CH:20][CH:19]=2)[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.[N:21]1([CH2:27][CH2:28][NH:29][C:14](=[O:15])[CH2:13][O:12][C:11]2[CH:10]=[CH:9][C:8]([C:5]3[CH2:6][NH:7][C:2](=[O:1])[NH:3][N:4]=3)=[CH:20][CH:19]=2)[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1
Reactant: CCOC(=O)COc1ccc(C2=NNC(=O)NC2)cc1
Reactant: NCCN1CCNCC1
Solvent: CCO
Product: O
Product: O=C(COc1ccc(C2=NNC(=O)NC2)cc1)NCCN1CCNCC1
Yield: 110.7 %

Procedure:
A solution of 3.05 g of ethyl α-[4-(2,3,4,5-tetrahydro-3-oxo-1,2,4-triazin-6-yl)phenoxy]acetate [prepared as described in Example 15(b) or (c) above] and 2.13 g of 2-(1-piperazinyl)ethylamine dissolved in 50 ml of ethanol was heated under reflux for 24 hours, whilst stirring. At the end of this time, the crystals which precipitated were collected by filtration and recrystallized from ethanol, to give 3 g of the title compound as colorless fine crystals melting at 177°-180° C.
Reaction SMILES: [C:1]([CH:5]1[CH2:10][CH2:9][CH2:8][CH:7]([CH2:11][CH2:12][CH:13]2OCC[O:14]2)[CH2:6]1)([CH3:4])([CH3:3])[CH3:2]>O.O.O.O.O.O.[Fe](Cl)(Cl)Cl.ClCCl.CC(C)=O>[C:1]([CH:5]1[CH2:10][CH2:9][CH2:8][CH:7]([CH2:11][CH2:12][CH:13]=[O:14])[CH2:6]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)C1CCCC(CCC2OCCO2)C1
Agent: Cl[Fe](Cl)Cl
Solvent: ClCCl
Solvent: CC(C)=O
Solvent: O
Product: CC(C)(C)C1CCCC(CCC=O)C1
Temperature: 25 °C
Reaction time: 4 h
Yield: 41.2 %

Procedure:
2-[2-(3-tert-butylcyclohexyl)ethyl]-1,3-dioxolane (62 g, 0.22 mol, gc purity of 87%) and dichloromethane/acetone in a 4:1 ratio (3.7 L) were charged into a 5 L three-necked round-bottom flask equipped with a reflux condenser and a mechanical stirrer. Iron (III) chloride hexahydrate (212.3 g, 0.78 mol, 3.5 eq) was added to the reaction at ambient temperature. The reaction mixture was then stirred at ambient temperature for 4 h and subsequently quenched, at 5-10° C., with the addition of a saturated aqueous NaHCO3 (500 mL). The organic phase was then washed with brine (500 mL), dried over magnesium sulphate and concentrated. The resulting crude product was distilled via a Vigreux column (0.5 mBar, 82-85° C.), to give colourless oil (34.7 g, gc purity 79%). The oil was chromatographed on a silica gel column with 2% EtOAc in hexane as elution agent giving 3-(3-tert-butylcyclohexyl)propanal (17.8 g, gc purity>98%, ratio cis:trans 75:25; yield 40%).