Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[CH:9][C:10]2[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][CH:11]=2)=[CH:4][CH:3]=1.Cl.[C:18](OC(=O)C)(=[O:20])[CH3:19].[C:25]([O-])(=[O:27])[CH3:26].[Na+]>O>[C:18]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]=[CH:9][C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:25](=[O:27])[CH3:26])=[CH:14][CH:15]=2)=[CH:6][CH:7]=1)(=[O:20])[CH3:19]
Reactant: CC(=O)OC(C)=O
Reactant: Nc1ccc(C=Cc2ccc(N)cc2)cc1
Reactant: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Product: CC(=O)Nc1ccc(C=Cc2ccc(NC(C)=O)cc2)cc1
Temperature: 90 °C
Reaction time: 0.03 h

Procedure:
4,4'-Diaminostilbene (8.9 grams, 0.0847 --NH2 equivalent) from B above, is ground to a fine powder and added to a beaker containing stirred, 90° C. deionized water (1500 milliliters). After two minutes, aqueous 36.5% hydrochloric acid (8.47 grams, 0.0847 mole) is added to the stirred, 90° C. suspension. The solution which formed within five minutes is cooled to 60° C. Acetic anhydride (10.61 grams, 0.1039 mole) is added to the stirred solution and mixed therein for 30 seconds before addition of an aqueous sodium acetate solution (prepared by dissolution of anhydrous sodium acetate [13.89 grams, 0.1693 mole] in deionized water [41.7 grams]). After thoroughly stirring the white slurry, it is maintained at 4° C. for 16 hours, followed by filtration to remove the precipitated product. The recovered filter cake is washed with two portions (250 milliliters) of deionized water then dried in a vacuum oven at 80° C. and 2 mm Hg to a constant weight of 11.44 grams. The product is recovered as a tan colored crystalline powder. Fourier transform infrared spectrophotometric analysis of a potassium chloride pellet of the product confirms the product structure: disappearance of the absorbances observed for the --NH2 group, appearance of solid state >NH stretching absorbances at 3309 (3396 and 3190 shoulders) cm-1, a solid state amide I carbonyl stretching absorbance at 1669 cm-1, a solid state amide II carbonyl stretching absorbance at 1516 cm-1 (masking the aromatic ring absorbance), an out-of-plane C--H deformation at 959 cm-1 due to the trans substituted ethylene group and a C--H out-of-plane bending vibration at 832 cm-1 due to the para-disubstituted aromatic rings. Proton nuclear magnetic resonance spectroscopy further confirms the product structure.
Reaction SMILES: [N:1](CCO)(CCO)[CH2:2][CH2:3]O.S(Cl)([Cl:13])=O>ClC(Cl)C>[ClH:13].[Cl:13][CH2:3][CH2:2][NH2:1].[Cl:13][CH2:3][CH2:2][NH2:1].[Cl:13][CH2:3][CH2:2][NH2:1]
Reactant: OCCN(CCO)CCO
Reactant: O=S(Cl)Cl
Solvent: CC(Cl)Cl
Product: Cl
Product: NCCCl

Procedure:
Into a 1 L flask, equipped with a refluxing condenser, is added 29.8 g (0.20 mole) of triethanolamine, 300 mL of dichloroethane, then 51.0 mL of thionyl chloride. The mixture is heated to reflux for 4 hrs. The reaction is quenched by adding 20 mL of methanol. Removal of solvent gives a white crystalline mass of tris(2-chloroethylamine) hydrochloride in quantitative yield.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:42])[C@@H:13]([NH:23][C:24]([C:26]2[CH:30]=[C:29]([O:31][CH2:32][C:33]([OH:35])=O)[N:28]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[N:27]=2)=[O:25])[CH2:14][CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:8][CH2:7]1)=[O:5])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[CH2:63]([O:70][C:71](=[O:77])[C@@H:72]1[CH2:76][CH2:75][CH2:74][NH:73]1)[C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1>CN(C=O)C.C(Cl)CCl>[CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:42])[C@@H:13]([NH:23][C:24]([C:26]2[CH:30]=[C:29]([O:31][CH2:32][C:33]([N:73]3[CH2:74][CH2:75][CH2:76][C@H:72]3[C:71]([O:70][CH2:63][C:64]3[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=3)=[O:77])=[O:35])[N:28]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[N:27]=2)=[O:25])[CH2:14][CH2:15][C:16]([O:18][C:19]([CH3:21])([CH3:22])[CH3:20])=[O:17])[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: O=C(OCc1ccccc1)[C@@H]1CCCN1
Reactant: CCOC(=O)N1CCN(C(=O)[C@H](CCC(=O)OC(C)(C)C)NC(=O)c2cc(OCC(=O)O)n(-c3ccccc3)n2)CC1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)N1CCN(C(=O)[C@H](CCC(=O)OC(C)(C)C)NC(=O)c2cc(OCC(=O)N3CCC[C@H]3C(=O)OCc3ccccc3)n(-c3ccccc3)n2)CC1
Temperature: 25 °C

Procedure:
To a solution of 9.5 g 4-{(S)-4-tert-Butoxycarbonyl-2-[(5-carboxymethoxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid ethyl ester in 80 ml DMF were added 2.5 g HOBt, 5.7 ml DIPEA and 3.9 g L-proline benzyl ester hydrochloride at 0° C. At this temperature were added 3.1 g EDC portionwise and the suspension allowed to warm to RT over a period of 12 h. The solvent was evaporated, the residue dissolved in ethyl acetate and subsequently extracted with aqueous LiCl (4 w/w), 0.1 M HCl and aqueous NaHCO3. The organic layer was dried over MgSO4 and the solvent was removed under reduced pressure. The crude product thus obtained was used in the subsequent reaction.
Reaction SMILES: O.Cl.[Cl:3][C:4]1[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[CH:19][C:5]=1[NH:6][C:7]([CH3:18])([CH3:17])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([F:16])[CH:10]=1.CCN(CC)CC>CO.[Fe]>[Cl:3][C:4]1[CH:22]=[C:21]([NH2:23])[CH:20]=[CH:19][C:5]=1[NH:6][C:7]([CH3:18])([CH3:17])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([F:16])[CH:10]=1
Reactant: CC(C)(Cc1ccc(Cl)c(F)c1)Nc1ccc([N+](=O)[O-])cc1Cl
Agent: [Fe]
Agent: Cl
Solvent: O
Solvent: CCN(CC)CC
Solvent: CO
Product: CC(C)(Cc1ccc(Cl)c(F)c1)Nc1ccc(N)cc1Cl
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a mixture of water (20 mL) and iron powder (697 mg, 12.50 mmol) at 65° C. was added concentrated hydrochloric acid (0.2 mL) dropwise and the mixture was stirred for 15 min. The aqueous layer of the mixture was poured out and a solution of 2-chloro-N-(1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl)-4-nitroaniline (446 mg, 1.25 mmol) in MeOH (20 mL) was added to the above processed iron powder. The mixture was adjusted to pH 2-3 and stirred at 65° C. for 20 min. The mixture was then cooled to rt, adjusted to pH 11 with Et3N, and filtered and the filtrate was concentrated in vacuo. The residue was dissolved in EtOAc (100 mL) and the solution was washed with water (30 mL×3) and brine (30 mL×2), dried over anhydrous Na2SO4 (10 g) and concentrated in vacuo to give the crude product, which was used for next step with out further purification. The compound was characterized by the following spectroscopic data:
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[F:10])[CH:5]=O.Cl.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C@H:19]([NH2:22])[CH2:20][CH3:21])=[CH:15][C:14]=1[CH3:23].[NH:24]1[CH2:27][CH:26]([C:28]([OH:30])=[O:29])[CH2:25]1>>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C@H:19]([NH:22][C:2]2[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=2[F:10])[CH2:5][N:24]2[CH2:27][CH:26]([C:28]([OH:30])=[O:29])[CH2:25]2)[CH2:20][CH3:21])=[CH:15][C:14]=1[CH3:23]
Reactant: CC[C@@H](N)c1ccc(Cl)c(C)c1
Reactant: O=Cc1ccc(F)c(Br)c1
Reactant: O=C(O)C1CNC1
Agent: Cl
Product: CC[C@@H](Nc1cc(CN2CC(C(=O)O)C2)ccc1F)c1ccc(Cl)c(C)c1

Procedure:
The title compound was prepared according to Scheme 3 following a procedure analogous to steps 3 to 6 of Example 21 using 3-bromo-4-fluoro-benzaldehyde in step 3, (R)-1-(4-chloro-3-methyl-phenyl)-propylamine hydrochloride in step 4 and azetidine-3-carboxylic acid in step 6.
Reaction SMILES: [Cl:1][C:2]1[C:7]2[N:8]([CH2:11][C:12]([OH:14])=O)[CH:9]=[N:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.Cl.[NH2:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([CH3:28])([CH3:27])[C:25]#[N:26])=[C:20]([F:29])[CH:19]=1.CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Cl:1][C:2]1[C:7]2[N:8]([CH2:11][C:12]([NH:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([C:24]([C:25]#[N:26])([CH3:28])[CH3:27])=[C:20]([F:29])[CH:19]=3)=[O:14])[CH:9]=[N:10][C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C#N)c1ccc(CN)cc1F
Reactant: O=C(O)Cn1cnc2cccc(Cl)c21
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(C)(C#N)c1ccc(CNC(=O)Cn2cnc3cccc(Cl)c32)cc1F

Procedure:
2-(7-Chloro-1H-benzimidazol-1-yl)-N-[4-(1-cyano-1-methylethyl)-3-fluorobenzyl]acetamide is synthesized according to example 14 with (7-chloro-1H-benzimidazol-1-yl)acetic acid (150 mg, 0.712 mmol) prepared according to scheme 1, and 2-[4-(aminomethyl)-2-fluorophenyl]-2-methylpropanenitrile hydrochloride (196 mg, 0.855 mmol) prepared according to scheme 8, Et3N (238 μL, 1.71 mmol) and HATU (325 mg, 0.855 mmol) in DMF (3.0 mL). The product is purified by HPLC: Gilson prep pumps, Flow rate: 30 ml/min, Column: Gemini (50 21.2×50 mm, Mobile phase: A=water (0.075% TFA) B=MeCN (0.075% TFA). Yield=14 mg as TFA salt, 0.035 mmol, 5%); 1H NMR (400 MHz, DMSO-D6) δ ppm 1.67 (s, 6H), 4.30 (d, J=5.86 Hz, 2H), 5.24 (s, 2H), 7.10-7.22 (m, 3H), 7.23-7.28 (m, 1H), 7.38 (t, J=8.40 Hz, 1 H), 7.62 (d, J=7.81 Hz, 1H), 8.31 (s, 1H), 8.81 (s, 1H). MS [M+H], calcd: 385.1. found: 385.0.
Reaction SMILES: [CH2:1]([N:8]([CH:12]1[CH2:14][CH2:13]1)[C:9]([Cl:11])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=C[CH:3]=1.C1(NCC2CCC[O:22]C2)CC1.C(NCC1CC1)C1C=CC=CC=1>C(Cl)Cl.CO>[CH:12]1([N:8]([CH2:1][CH:2]2[CH2:7][CH2:6][CH2:5][O:22][CH2:3]2)[C:9]([Cl:11])=[O:10])[CH2:14][CH2:13]1
Reactant: C1COCC(CNC2CC2)C1
Reactant: O=C(Cl)N(Cc1ccccc1)C1CC1
Agent: c1ccc(CNCC2CC2)cc1
Solvent: CO
Solvent: ClCCl
Product: O=C(Cl)N(CC1CCCOC1)C1CC1

Procedure:
The title compound is prepared analogously as described for benzyl-cyclopropyl-carbamoyl chloride starting from cyclopropyl-(tetrahydro-pyran-3-ylmethyl)-amine (prepared analogously as described for benzyl-cyclopropylmethyl-amine). TLC, Rf (CH2Cl2/MeOH 95:5)=0.9.
Reaction SMILES: [CH3:1][C:2]1([CH3:20])[CH2:3][N:4]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:5]/[C:6]/1=[N:7]\OC.B.C1COCC1>C1COCC1>[NH2:7][CH:6]1[CH2:5][N:4]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:3][C:2]1([CH3:20])[CH3:1]
Reactant: CO/N=C1\CN(C(=O)OCc2ccccc2)CC1(C)C
Agent: B
Solvent: C1CCOC1
Product: CC1(C)CN(C(=O)OCc2ccccc2)CC1N
Temperature: 50 °C
Reaction time: 2 h
Yield: 92.1 %

Procedure:
To a solution of phenylmethyl (4Z)-3,3-dimethyl-4-[(methyloxy)imino]-1-pyrrolidinecarboxylate (0.7126 g, 2.579 mmol) in THF (26 mL) was added borane-THF complex (1.0 M in THF, 5.2 mL, 5.2 mmol). The solution was heated at 50° C. and stirred for 2 h. The solution was then cooled to room temperature and quenched by addition of 6 N aq. NaOH (2 mL). The mixture was diluted with brine and extracted with Et2O (3×100 mL). The combined organic phase was dried over anhydrous MgSO4, filtered, and concentrated in vacuo. To a solution of the residue in MeOH (20 mL) was added 50% aq. NH2OH (5 mL), and the solution was heated at 60° C. and stirred overnight. The solution was then cooled to room temperature and concentrated in vacuo. The residue was partitioned between DCM (200 mL) and 1 N aq. NaOH (50 mL), and the organic phase was dried over anhydrous MgSO4, filtered, and concentrated in vacuo to give racemic phenylmethyl 4-amino-3,3-dimethyl-1-pyrrolidinecarboxylate (0.5899 g, 92% yield) as a colorless oil. LCMS: (M+H)+: 249.1.
Reaction SMILES: [OH-].[Na+].C[O:4][C:5](=[O:25])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]1[O:16][N:15]=[C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[O:23][CH3:24])[CH:13]=1>CO>[CH3:24][O:23][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[C:14]1[CH:13]=[C:12]([CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][C:5]([OH:25])=[O:4])[O:16][N:15]=1
Reactant: COC(=O)CCCCCCc1cc(-c2ccccc2OC)no1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: COc1ccccc1-c1cc(CCCCCCC(=O)O)on1
Reaction time: 3 h
Yield: 99.3 %

Procedure:
Add 2 N sodium hydroxide (15 mL) to a solution of 7-[3-(2-methoxyphenyl)isoxazol-5-yl]heptanoic acid methyl ester (2.89 g, 8 mmol) in methanol (50 mL) at room temperature under nitrogen and stir for 3 hours. Remove the solvent under reduced pressure, dilute the residue with water (100 mL), and wash with methyl tert-butyl ether (100 mL). Acidify the mixture to pH 1 with 1 N HCl and extract with ethyl acetate (3×100 mL). Wash the combined organic extracts with water (100 mL) and brine (100), dry over sodium sulfate, and remove the solvent under reduced pressure to provide 7-[3-(2-methoxyphenyl)isoxazol-5-yl]heptanoic acid (2.41 g, 98%): APCI mass spectrum m/z 302 [C17H21lNO4−H]−.
Reaction SMILES: [NH2:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@@H:11]1[O:16][C@H:15]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C@@H:14]([NH2:22])[C@H:12]1[OH:13].[C:23]([O:27][C:28]([NH:30][CH:31]([C:40](O)=[O:41])[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[Cl:39])=[O:29])([CH3:26])([CH3:25])[CH3:24]>>[NH2:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@@H:11]1[O:16][C@H:15]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C@@H:14]([NH:22][C:40](=[O:41])[CH:31]([CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=2[Cl:39])[NH:30][C:28]([O:27][C:23]([CH3:26])([CH3:24])[CH3:25])=[O:29])[C@H:12]1[OH:13]
Reactant: CC(C)(C)OC(=O)NC(Cc1ccccc1Cl)C(=O)O
Reactant: CCOC(=O)[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1N
Product: CCOC(=O)[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1NC(=O)C(Cc1ccccc1Cl)NC(=O)OC(C)(C)C
Yield: 56.9 %

Procedure:
Ethyl 1-(6amino-9H-purin-9-yl)-1,3-dideoxy-3-[N-tert-butoxycarbonyl-β-(2-chlorophenyl)-D,L-alanylamino]-β-D-ribofuranuronate (320 mg) was prepared by reacting ethyl 1-(6-amino-9H-purin-9-yl)-1,3-dideoxy-3-amino-β-D-ribofuranuronate 294 mg) prepared in Example 63 with N-tert-butoxycarbonyl-β-(2-chlorophenyl)-D,L-alanine (300 mg) according to a similar manner to that of Example 64, mp. 120°-130° C.
Reaction SMILES: Cl[S:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH2:8]2)(=[O:4])=[O:3].[NH3:15]>C(O)C.C(Cl)Cl>[NH2:15][S:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH2:8]2)(=[O:4])=[O:3]
Reactant: O=C1Cc2cc(S(=O)(=O)Cl)ccc2N1
Reactant: N
Solvent: ClCCl
Solvent: CCO
Product: NS(=O)(=O)c1ccc2c(c1)CC(=O)N2
Yield: 843.8 %

Procedure:
A solution of 5-chlorosulphonyloxindole (2 g, 0.86 mmol) in ethanol (30 ml), methylene chloride (150 ml) and 2.8M methanolic ammonia (6.2 ml, 17 mmol) was stirred overnight at ambient temperature. The volatiles were removed by evaporation and the solid residue was purified by column chromatography eluting with methanol/methylene chloride (15/85) to give 5-aminosulphonyloxindole (1.54 g, 84%).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][NH:5][C:6](=[O:11])[CH2:7][C:8]([CH3:10])=[O:9].[CH2:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14][NH:13]1.C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[CH2:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14][N:13]1[CH2:2][CH2:3][CH2:4][NH:5][C:6](=[O:11])[CH2:7][C:8]([CH3:10])=[O:9]
Reactant: c1ccc2c(c1)CCNC2
Reactant: CC(=O)CC(=O)NCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CC(=O)CC(=O)NCCCN1CCc2ccccc2C1
Temperature: 25 °C
Reaction time: 14 h

Procedure:
A suspension of N-(3-bromopropyl)acetoacetamide (4.50 g, 20.3 mmol, 1.00 equiv), 1,2,3,4-tetrahydroisoquinoline (3.30 mL, 26.3 mmol, 1.30 equiv), K2CO3 (3.64 g, 26.3 mmol, 1.30 equiv), and KI (330 mg, 1.99 mmol, 0.10 equiv) in acetone (60 mL) was stirred at ref lux for 14 hours. The mixture was cooled to room temperature, filtered, and concentrated. The residue was purified by flash chromatography (SiO2, MeOH—EtOAc 0:1 to 1:9) to give 1.78 g (43%) of light yellow oil, which was characterized spectroscopically. N-(3-Bromopropyl)acetoacetamide (1.20 g) was also recovered.
Reaction SMILES: [OH-].[Na+].Cl.[CH2:4]([O:6][NH2:7])[CH3:5].[OH:8][C:9]1[CH2:14][CH:13]([C:15]2[CH:20]=[CH:19][C:18]([S:21][CH3:22])=[CH:17][CH:16]=2)[CH2:12][C:11](=[O:23])[C:10]=1[C:24](=O)[CH2:25][CH3:26]>O.C(O)C>[CH2:4]([O:6][N:7]=[C:24]([C:10]1[C:11](=[O:23])[CH2:12][CH:13]([C:15]2[CH:16]=[CH:17][C:18]([S:21][CH3:22])=[CH:19][CH:20]=2)[CH2:14][C:9]=1[OH:8])[CH2:25][CH3:26])[CH3:5]
Reactant: CCON
Reactant: CCC(=O)C1=C(O)CC(c2ccc(SC)cc2)CC1=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CCON=C(CC)C1=C(O)CC(c2ccc(SC)cc2)CC1=O
Temperature: 25 °C
Yield: 82.7 %

Procedure:
A solution of sodium hydroxide (0.15 g) in water (5 ml) and then ethoxyamine hydrochloride (0.37 g) were added to a solution of 3-hydroxy-5-(4-methylthiophenyl)-2-propionylcyclohex-2-en-1-one (1.0 g) in ethanol (40 ml). The mixture was stirred at room temperature and the progress of the reaction was monitored by thin layer chromatography on silica gel (eluant dichloromethane). On completion of the reaction the solvent was removed by distillation under reduced pressure. The residue was treated with dichloromethane and the organic phase was washed with water and dried over anhydrous sodium sulfate. The solvent was evaporated to give 2-[1-(ethoxyimino)propyl]-3-hydroxy-5-(4-methylthiophenyl)cyclohex-2-en-1-one (0.95 g) as a yellow oil.
Reaction SMILES: Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[CH:15]=[C:16]([CH:24]=[CH:25][CH:26]=1)[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].C(N(CC)CC)C.[CH:34]1([C:40]([CH2:42][N:43]2[C:49]3[CH:50]=[CH:51][CH:52]=[CH:53][C:48]=3[N:47]([CH:54]3[CH2:59][CH2:58][CH2:57][CH2:56][CH2:55]3)[CH2:46][CH:45]([NH2:60])[C:44]2=[O:61])=[O:41])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1>O1CCCC1>[CH:34]1([C:40]([CH2:42][N:43]2[C:49]3[CH:50]=[CH:51][CH:52]=[CH:53][C:48]=3[N:47]([CH:54]3[CH2:55][CH2:56][CH2:57][CH2:58][CH2:59]3)[CH2:46][CH:45]([NH:60][C:2]([NH:13][C:14]3[CH:26]=[CH:25][CH:24]=[C:16]([C:17]([O:19][C:20]([CH3:22])([CH3:23])[CH3:21])=[O:18])[CH:15]=3)=[O:4])[C:44]2=[O:61])=[O:41])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1
Reactant: CC(C)(C)OC(=O)c1cccc(N)c1
Reactant: NC1CN(C2CCCCC2)c2ccccc2N(CC(=O)C2CCCCC2)C1=O
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)c1cccc(NC(=O)NC2CN(C3CCCCC3)c3ccccc3N(CC(=O)C3CCCCC3)C2=O)c1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 230 %

Procedure:
Triphosgene (122 mg) was added to a solution of tert-butyl 3-aminobenzoate (213 mg) in anhydrous tetrahydrofuran (30 ml) at 0° C., triethylamine (0.49 ml) was added thereto at 0° C. five times each 98 μl over 15 minutes. After the mixture was stirred at room temperature for 5 minutes, a solution of 1-cyclohexylcarbonylmethyl-2-oxo-3-amino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (395 mg) in anhydrous tetrahydrofuran (10 ml) was added at 0° C., the resultant mixture was stirred at room temperature for one hour. The reaction mixture was concentrated under reduced pressure, and water was added to the residue, extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, diisopropyl ether was added to the residue for crystallization, collected by filtration, to thereby obtain 570 mg of the title compound (Yield: 92%).
Reaction SMILES: C([Li])CCC.[F:6][C:7]([F:15])([F:14])[CH:8]([OH:13])[C:9](F)([F:11])[F:10].Cl[CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][C:18]1=[O:23].Cl.[OH-:25].[Na+]>CCCCCC.O1CCCC1>[F:10][C:9]1([F:11])[C:18]2([OH:23])[CH2:19][CH2:20][CH2:21][CH2:22][CH:17]2[O:13][C:8]1([C:7]([F:15])([F:14])[F:6])[OH:25]
Reactant: OC(C(F)(F)F)C(F)(F)F
Reactant: O=C1CCCCC1Cl
Reactant: [OH-]
Agent: Cl
Agent: [Li]CCCC
Agent: [Na+]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: OC12CCCCC1OC(O)(C(F)(F)F)C2(F)F
Temperature: 5 °C
Reaction time: 1 h
Yield: 63 %

Procedure:
In a nitrogen atmosphere at −5° C., 1000 ml of 2.6M n-butyllithium in hexane was added to a mixture of 224 g of 1,1,1,3,3,3-hexafluoro-2-propanol and 1000 g of tetrahydrofuran, followed by one hour of stirring at 5° C. Then 164 g of 2-chlorocyclohexanone was added at 5° C. The mixture was stirred for 10 hours, after which dilute hydrochloric acid was added to quench the reaction and neutralize the reaction mixture. Then 1200 g of a 10% aqueous solution of sodium hydroxide was added to the reaction mixture, from which an aqueous layer was separated. It was made acidic by adding 560 g of 20% dilute hydrochloric acid and combined with 1000 g of toluene, after which an organic layer was separated. The organic layer thus separated was concentrated and purified by recrystallization from hexane, obtaining 201 g of the product (yield 63%).
Reaction SMILES: C1(C)C=CC(S(O)(=O)=O)=CC=1.[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1.[OH:18][C:19]1[C:24]([OH:25])=[CH:23][CH:22]=[CH:21][C:20]=1[N+:26]([O-:28])=[O:27]>C1C=CC=CC=1>[OH:18][C:19]1[C:24]([O:25][CH:17]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[CH:23][CH:22]=[CH:21][C:20]=1[N+:26]([O-:28])=[O:27]
Reactant: C1=COCCC1
Reactant: O=[N+]([O-])c1cccc(O)c1O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Product: O=[N+]([O-])c1cccc(OC2CCCCO2)c1O
Reaction time: 168 h

Procedure:
0.030 g of p-toluenesulphonic acid and 17.8 g of 3,4-dihydro-2H-pyrane are added to a mixture of 29.8 g of 2,3-dihydroxy-nitrobenzene in 400 ml of absolute benzene and the solution is left to stand for 7 days at 20°. It is filtered through 15 g of a silica gel formulation (Merck silica gel 60; grain size 0.063-0.200 mm) and the silica gel is rinsed with benzene. After distilling off the benzene under reduced pressure, a reddish oil is obtained which, when crystallised from hexane, gives 2-hydroxy-3-(tetrahydropyran2-yloxy)-nitrobenzene in the form of yellow crystals; melting point 72°-73°.
Reaction SMILES: [C:1]1([N:7]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:8]2[CH:13]=[CH:12][C:11]([CH:14]=[CH:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H][H]>O1CCOCC1.[Pd]>[C:1]1([N:7]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:8]2[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][C:16]3[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=3)=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COc1ccc(C=Cc2ccc(N(c3ccccc3)c3ccccc3)cc2)cc1
Reactant: [H][H]
Agent: [Pd]
Solvent: C1COCCO1
Product: COc1ccc(CCc2ccc(N(c3ccccc3)c3ccccc3)cc2)cc1

Procedure:
37.7 g (0.1 mol) of the 4-diphenylamino-4'-methoxystilbene prepared in Synthesis Example 1-1 was dissolved in 250 ml of dioxane. To the thus obtained mixture, 4 g of 5% Pd/C powder and then 2.4 l of hydrogen were added. A solvent was distilled away from the reaction mixture, whereby 1-(4-diphenylaminophenyl)-2-(4-methoxyphenyl)ethane was obtained as an oily transport compound of light yellow in color.
Reaction SMILES: [CH3:1][C:2]1([OH:5])[CH2:4][CH2:3]1.[O:6]=[C:7]1[CH2:11][CH2:10][C:9](=[O:12])[N:8]1[O:13][C:14](=O)[O:15]N1C(=O)CCC1=O.C(N(CC)CC)C>C(#N)C.CCOC(C)=O>[CH3:1][C:2]1([O:5][C:14](=[O:15])[O:13][N:8]2[C:9](=[O:12])[CH2:10][CH2:11][C:7]2=[O:6])[CH2:4][CH2:3]1
Reactant: CC1(O)CC1
Reactant: O=C(ON1C(=O)CCC1=O)ON1C(=O)CCC1=O
Solvent: CCN(CC)CC
Solvent: CC#N
Solvent: CCOC(C)=O
Product: CC1(OC(=O)ON2C(=O)CCC2=O)CC1
Temperature: 25 °C
Reaction time: 21 h
Yield: 19.5 %

Procedure:
To a solution of 1-methyl-cyclopropanol (1.25 g, 17.4 mmol) in acetonitrile (44 mL) was added carbonic acid bis-(2,5-dioxo-pyrrolidin-1-yl) ester (6.68 g, 26.1 mmol) and triethylamine (7.3 mL, 52.3 mmol). The reaction was stirred at room temperature for 21 h. The reaction mixture was diluted with EtOAc and washed with saturated aqueous NaHCO3 (2×) and brine. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by column chromatography on silica (15→50%→100% Hex/EtOAc) to provide carbonic acid 2,5-dioxo-pyrrolidin-1-yl ester 1-methyl-cyclopropyl ester (722.8 mg, 19%): 1H NMR (CDCl3, 300 MHz) δ 2.83 (s, 4H), 1.63 (s, 3H), 1.10 (m, 2H), 0.73 (m, 2H).