Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]([CH3:22])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:18]=[C:17]([C:19]([OH:21])=O)[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=2)=[CH:5][CH:4]=1.Cl.[CH3:24][O:25][C:26]1[C:35]([O:36][CH3:37])=[CH:34][CH:33]=[C:32]2[C:27]=1[CH2:28][CH2:29][NH:30][CH2:31]2>>[CH3:1][N:2]([CH3:22])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:18]=[C:17]([C:19]([N:30]3[CH2:29][CH2:28][C:27]4[C:32](=[CH:33][CH:34]=[C:35]([O:36][CH3:37])[C:26]=4[O:25][CH3:24])[CH2:31]3)=[O:21])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=2)=[CH:5][CH:4]=1
Reactant: COc1ccc2c(c1OC)CCNC2
Reactant: CN(C)c1ccc(-c2nc(C(=O)O)c3ccccc3n2)cc1
Agent: Cl
Product: COc1ccc2c(c1OC)CCN(C(=O)c1nc(-c3ccc(N(C)C)cc3)nc3ccccc13)C2
Yield: 11 %

Procedure:
Reaction of 2-(4-(dimethylamino)phenyl)quinazoline-4-carboxylic acid with 5,6-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride gave compound 34 (11% yield) as a brown solid, 1H NMR (300 MHz, DMSO-d6) δ 2.73 and 2.97 (2t, 2H), 3.03 (s, 6H), 3.47 and 4.02 (2t, 2H), 3.69-3.81 (4s, 6H), 4.40 and 4.92 (2s, 2H), 6.63 and 7.01 (2d, 1H), 6.80 and 7.07 (2d, 1H), 6.83-6.86 (m, 2H), 7.55-7.65 (m, 1H), 7.77-7.88 (2d, 1H), 7.96-8.02 (m, 2H), 8.32-8.38 (m, 2H); MS (ESI) m/z 469 ([M+H]+).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[NH:11][C:12]1[N:17]=[C:16]([C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)[C:15](C(OCC)=O)=[CH:14][N:13]=1.C(=O)([O-])[O-].[K+].[K+].O>C(O)C>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[NH:11][C:12]1[N:17]=[C:16]([C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)[CH:15]=[CH:14][N:13]=1
Reactant: CCOC(=O)c1cnc(Nc2cc([N+](=O)[O-])ccc2C)nc1-c1cccnc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: O
Product: Cc1ccc([N+](=O)[O-])cc1Nc1nccc(-c2cccnc2)n1
Temperature: 80 °C
Yield: 80 %

Procedure:
140 g ethyl 2-[(2-methyl-5-nitrophenyl)amino]-4-(3-pyridinyl)pyrimidine-5-carboxylate and 109 g potassium carbonate is suspended in a mixture composed by 1050 mL water and 560 mL ethanol. The mixture is refluxed for 1 hour, then 700 mL solvent are slowly distilled. Once completed the conversion, the mixture is cooled to 80° C. and it is adjusted to pH a 7 with 95 mL acetic acid. 560 mL N-methylpyrrolidone and 0.9 g CuO is added. The water present is distilled under reduced pressure, and the mixture is heated to 175-180° C. for 2 hours. Once completed the conversion, the mixture is cooled to 80-90° C., 1000 mL water and 5 g EDTA is slowly added, the mixture is stirred at room temperature, the product is filtrated and washed with water. Upon drying, 108 g of product with HPLC purity of 95% (A %) is achieved. This can be recrystallized from 10 volumes of 95:5 xylene/N-methylpyrrolidone to yield a product with 98% purity (A %) in a 80% yield.
Reaction SMILES: Cl[CH2:2][CH2:3][CH:4]1[CH2:8][CH2:7][CH2:6][N:5]1[CH3:9].[Cl:10][C:11]1[CH:12]=[C:13]([SH:18])[CH:14]=[CH:15][C:16]=1[Cl:17].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:10][C:11]1[CH:12]=[C:13]([S:18][CH2:2][CH2:3][CH:4]2[CH2:8][CH2:7][CH2:6][N:5]2[CH3:9])[CH:14]=[CH:15][C:16]=1[Cl:17]
Reactant: CN1CCCC1CCCl
Reactant: Sc1ccc(Cl)c(Cl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CN1CCCC1CCSc1ccc(Cl)c(Cl)c1
Yield: 43 %

Procedure:
2-(2-Chloroethyl)-1-methylpyrrolidine (1.50 g, 10.26 mmole), 3,4-dichlorobenzenethiol (1.82 g, 10.1 mmole), potassium carbonate (14.03 g, 101.6 mmole) and DMF (20 mL) were combined, yielding 0.46 g (4.34 mmole, 43%) of the desired compound.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:8]([CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[C:9]([C:11]2[CH:30]=[CH:29][C:14]3[N:15]([CH3:28])[C:16]([CH2:18][NH:19][C:20]4[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][CH:21]=4)=[N:17][C:13]=3[CH:12]=2)=[O:10])[CH:5]=[CH:6][CH:7]=1.[ClH:38].C(O)C.C(=O)([O-])[O-].[NH4+:46].[NH4+]>ClCCl.CO>[ClH:38].[F:1][C:2]1[CH:3]=[C:4]([N:8]([CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[C:9]([C:11]2[CH:30]=[CH:29][C:14]3[N:15]([CH3:28])[C:16]([CH2:18][NH:19][C:20]4[CH:25]=[CH:24][C:23]([C:26](=[NH:46])[NH2:27])=[CH:22][CH:21]=4)=[N:17][C:13]=3[CH:12]=2)=[O:10])[CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)CCN(C(=O)c1ccc2c(c1)nc(CNc1ccc(C#N)cc1)n2C)c1cccc(F)c1
Reactant: [NH4+]
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: ClCCl
Solvent: CCO
Solvent: CO
Product: CCOC(=O)CCN(C(=O)c1ccc2c(c1)nc(CNc1ccc(C(=N)N)cc1)n2C)c1cccc(F)c1
Yield: 42 %

Procedure:
Prepared analogously to Example 25d from 1-methyl-2-[N-(4-cyanophenyl)aminomethyl]benzimidazol-5-yl-carboxylic acid-N-(3-fluorophenyl)-N-(2-ethoxycarbonylethyl)amide and ethanolic hydrochloric acid, ethanol, and ammonium carbonate. Yield: 42% of theory, C28H29FN6O3 (516.6); Rf value: 0.31 (silica gel; dichloromethane/methanol 5:1); EKA mass spectrum: (M+H)+=517; (M+H+Na)++=270.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([CH:6]=[O:7])=[CH:2]1.[CH3:8][Si:9](C#N)([CH3:11])[CH3:10].[CH2:14]([N:16](CC)CC)C>C(Cl)Cl>[S:1]1[CH:5]=[CH:4][C:3]([CH:6]([O:7][Si:9]([CH3:11])([CH3:10])[CH3:8])[C:14]#[N:16])=[CH:2]1
Reactant: C[Si](C)(C)C#N
Reactant: CCN(CC)CC
Reactant: O=Cc1ccsc1
Solvent: ClCCl
Product: C[Si](C)(C)OC(C#N)c1ccsc1
Reaction time: 4 h

Procedure:
3-Thiophene carboxaldehyde (0.438 mL, 5.000 mmol) was dissolved into dry CH2Cl2 and placed under argon. To this was added trimethylsilyl cyanide (0.933 mL, 7.000 mmol) and triethylamine (0.070 mL, 0.500 mmol). The reaction mixture was allowed to stir for 4 h. The mixture was concentrated on a rotary evaporator to dryness to give thiophen-3-yl-trimethylsilanyloxy-acetonitrile as a clear oil.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10]N(C)C)=[CH:2]1.[C-:14]#[N:15].[Na+]>CS(C)=O.C(OCC)(=O)C>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:14]#[N:15])=[CH:2]1
Reactant: [C-]#N
Reactant: CN(C)Cc1c[nH]c2ccccc12
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: N#CCc1c[nH]c2ccccc12
Temperature: 80 °C
Yield: 153.7 %

Procedure:
Dissolve a mixture of the (1H-Indol-3-ylmethyl)-dimethylamine (3.54 mmol), sodium cyanide (0.500 g, 10.62 mmol), and ethyl acetate (1.7 mL, 17.7 mmol) in dry dimethyl sulfoxide (12 mL) and heat to 80° C. under nitrogen for 3 h. Cool the reaction mixture to room temperature, dilute with ethyl acetate (150 mL), and wash with water (50 mL), Dry the organic layer over anhydrous magnesium sulfate, and remove the solvent in vacuo to yield (1H-indol-3-yl)-acetonitrile 0.850 g (96%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:14]=[CH:15][C:16]=1[O:17][CH3:18])[CH2:6][CH:7]([CH2:10][CH2:11][CH2:12][CH3:13])[CH2:8]O.C(Br)(Br)(Br)[Br:20].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Br:20][CH2:8][CH:7]([CH2:6][C:5]1[CH:14]=[CH:15][C:16]([O:17][CH3:18])=[C:3]([O:2][CH3:1])[CH:4]=1)[CH2:10][CH2:11][CH2:12][CH3:13]
Reactant: CCCCC(CO)Cc1ccc(OC)c(OC)c1
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CCCCC(CBr)Cc1ccc(OC)c(OC)c1
Temperature: 0 °C
Reaction time: 14 h

Procedure:
Part E. The alcohol compound from Part D above (3.39 g, 13.4 mmol) and carbon tetrabromide (5.78 g, 17.4 mmol) were dissolved in methylene chloride (30 mL). This solution was cooled to 0° C. and treated with a 20 mL methylene chloride solution of triphenylphosphine (4.57 g, 17.4 mmol). The solution was allowed to stir for 14 hours, then evaporated. The residual oil was separated by flash chromatography (1:9 ethyl acetate-hexane) to afford the product, 1-bromo-2-(3,4-dimethoxybenzyl)hexane, as an oil (4.01 g, 12.7 mmol, 95%). 1H NMR (CDCl3): δ 6.81-6.71 (3H, m); 3.88 (3H, s); 3.87 (3H, s); 3.41 (1H, dd, J=9.9, 4,4 Hz); 3.33 (1H, dd, J=9.9, 4.0 Hz); 2.64 (1H, dd, J=13.5, 6.2 Hz); 2.58 (1H, dd, J=13.5, 8.0 Hz); 1.90-1.80 (1H, m); 1.48-1.24 (6H, m); 0.91 (3H, t, J=6.8 Hz). Mass spectrum (NH3 -CI/DDIP): m/z 334 (98%); 332 (100%); 317 (33%); 315 (34%); 252 (3%).
Reaction SMILES: Cl[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][CH:6]=1)=[CH2:4].[F-:14].[K+].[Br-]>O>[F:14][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][CH:6]=1)=[CH2:4]
Reactant: C=C(CCl)c1ccc([N+](=O)[O-])cc1
Reactant: [F-]
Agent: [Br-]
Agent: [K+]
Solvent: O
Product: C=C(CF)c1ccc([N+](=O)[O-])cc1
Reaction time: 5 h

Procedure:
Under a N2 blanket is stirred a mixture of 296.5 g (1.5 Mol) 4(1-chloromethyl-ethenyl)-nitrobenzene, 430 g (7.4 Mol) KF, 78 g (0.15 Mol) hexadecyltributylphosphonimine bromide and 800 ml H2O, during 5 hours at 110°-112°.
Reaction SMILES: C([NH:9][C:10]1[N:18]=[CH:17][N:16]=[C:15]2[C:11]=1[N:12]=[CH:13][N:14]2[C@@H:19]1[O:24][C@H:23]([C:25]([OH:27])=[O:26])[C@@H:22]([NH:28][C:29](=[O:57])[C@H:30]([CH2:42][C:43]2[CH:48]=[CH:47][C:46]([O:49][CH2:50][C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)=[CH:45][CH:44]=2)[NH:31][C:32]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[O:33])[C@H:20]1[OH:21])(=O)C1C=CC=CC=1.C(N)CCC>>[NH2:9][C:10]1[N:18]=[CH:17][N:16]=[C:15]2[C:11]=1[N:12]=[CH:13][N:14]2[C@@H:19]1[O:24][C@H:23]([C:25]([OH:27])=[O:26])[C@@H:22]([NH:28][C:29](=[O:57])[C@H:30]([CH2:42][C:43]2[CH:44]=[CH:45][C:46]([O:49][CH2:50][C:51]3[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=3)=[CH:47][CH:48]=2)[NH:31][C:32]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[O:33])[C@H:20]1[OH:21]
Reactant: O=C(N[C@@H](Cc1ccc(OCc2ccccc2)cc1)C(=O)N[C@H]1[C@@H](O)[C@H](n2cnc3c(NC(=O)c4ccccc4)ncnc32)O[C@@H]1C(=O)O)OCc1ccccc1
Solvent: CCCCN
Product: Nc1ncnc2c1ncn2[C@@H]1O[C@H](C(=O)O)[C@@H](NC(=O)[C@H](Cc2ccc(OCc3ccccc3)cc2)NC(=O)OCc2ccccc2)[C@H]1O
Yield: 79.1 %

Procedure:
1-(6-Amino-9H-purin-9-yl)-3-(N-benzyloxycarbonyl-O-benzyl-L-tyrosylamino)-1,3-dideoxy-β-D-ribofuranuronic acid (130 mg) was prepared by reacting 1-(6-benzoylamino-9H-purin-9-yl)-3-(N-benzyloxycarbonyl-O-benzyl-L-tyrosylamino)-1,3-dideoxy-β-D-ribofuranuronic acid (190 mg) prepared in Example 12 with n-butylamine (1.5 ml) according to a similar manner to that of Example 23, mp. 173°-176° C. (dec.).
Reaction SMILES: [Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[CH3:13][O:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH:16]1[N:21]1[C:26](=[O:27])[C:25]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([C:35]3[C:36]([C:41]#[N:42])=[CH:37][CH:38]=[CH:39][CH:40]=3)=[CH:31][CH:30]=2)=[C:24]([CH2:43][CH2:44][CH3:45])[N:23]2[N:46]=[C:47]([CH3:49])[N:48]=[C:22]12>C(OCC)(=O)C>[CH3:13][O:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH:16]1[N:21]1[C:26](=[O:27])[C:25]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[C:41]3[NH:3][C:4](=[O:7])[O:5][N:42]=3)=[CH:31][CH:30]=2)=[C:24]([CH2:43][CH2:44][CH3:45])[N:23]2[N:46]=[C:47]([CH3:49])[N:48]=[C:22]12
Reactant: O=C([O-])O
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n(C2CCCCC2OC)c2nc(C)nn12
Reactant: [NH3+]O
Agent: [Cl-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CCCc1c(Cc2ccc(-c3ccccc3-c3noc(=O)[nH]3)cc2)c(=O)n(C2CCCCC2OC)c2nc(C)nn12
Temperature: 40 °C
Reaction time: 0.5 h
Yield: 53 %

Procedure:
A mixture of hydroxylammonium chloride (0.59 g), sodium hydrogen carbonate (0.92 g) and dimethyl sulfoxide (10 mL) was stirred at 40° C. for 30 min, 4′-{[4-(2-methoxycyclohexyl)-2-methyl-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (0.27 g) was added, and the mixture was stirred at 90° C. for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (10 mL). N,N′-Carbonyldiimidazole (0.11 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.09 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium hydrogensulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as colorless crystals (0.16 g, 53%).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1.[CH2:15]([NH:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)C.C(#N)C>>[CH3:15][N:17]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1
Reactant: CCNc1ccccc1
Reactant: Oc1ccc(OCCCCCBr)cc1
Solvent: CC#N
Product: CN(CCCCCOc1ccc(O)cc1)c1ccccc1
Temperature: 60 °C
Reaction time: 12 h
Yield: 12.3 %

Procedure:
To a solution of compound 14a (150 mg, 0.57 mmol) and N-ethylaniline (0.07 mL, 0.63 mmol) in acetonitrile (5.0 mL) diisopropylethylamine (0.24 mL, 1.73 mmol) was added dropwise. After the addition was complete the reaction was stirred at 60° C. for 12 hours. The reaction mixture was concentrated, purified by column chromatography to isolate the required compound 14 as a colorless oil (20 mg, 0.07 mmol, 12% yield). MS (ESI, positive) m/z calcd. for C18H24NO2 [M+H]+: 286.18, found: 285.95. 1H NMR (CDCl3, 400 MHz) δ 7.28 (t, J=8.8 Hz, 2H), 6.70-6.85 (m, 7H), 4.72 (s, 1H), 3.93 (t, J=6.4 Hz, 2H), 3.36 (t, J=7.6 Hz, 2H), 2.95 (s, 3H), 1.85-1.78 (m, 2H), 1.65-1.71 (m, 2H), 1.47-1.55 (m, 2H).
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][C:9]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)=O)[CH:5]=[CH:4][N:3]=[CH:2]1.[ClH:21].Cl.[NH2:23][CH2:24][CH2:25][O:26][NH2:27].N1C=CC=CC=1>C(O)C>[ClH:21].[ClH:21].[NH2:23][CH2:24][CH2:25][O:26][N:27]=[C:9]([C:11]1[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=1)[CH2:8][CH2:7][CH2:6][N:1]1[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: NCCON
Reactant: O=C(CCCn1ccnc1)c1ccc(C(F)(F)F)cc1
Agent: Cl
Solvent: CCO
Solvent: c1ccncc1
Product: NCCON=C(CCCn1ccnc1)c1ccc(C(F)(F)F)cc1
Reaction time: 2 h
Yield: 70.5 %

Procedure:
A mixture of 4-(1-(1H)-imidazolyl)-1-(4-trifluoromethylphenyl)-1-butanone (5.00 g), O-(2-aminoethyl)hydroxylamine dihydrochloride (3.17 g), 3 equivalents of pyridine, and absolute ethanol (75 ml) was heated under reflux, under nitrogen, with stirring, for two hrs. The reaction mixture was evaporated, toluene was added and evaporated. The residue was partitioned between 10% sodium hydroxide solution and ethyl acetate. The layers were separated and the aqueous phase extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated. The residue was purified by flash chromatography (180:19:1 dichloromethane/methanol/ammonium hydroxide). The appropriate fractions were collected and concentrated. The residue was dissolved in absolute ethanol and treated with ethereal hydrogen chloride. Diethyl ether was added. The precipitate was collected and recrystallized twice from absolute ethanol/ether to give 3.1 g (42%) of product, mp 207°-208° C. (dec).
Reaction SMILES: [CH:1]1([NH2:6])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:7]([O:9][C:10]([C:12]1[C:13](Cl)=[N:14][C:15]([S:18][CH3:19])=[N:16][CH:17]=1)=[O:11])[CH3:8]>C(Cl)Cl>[CH2:7]([O:9][C:10]([C:12]1[C:17]([NH:6][CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)=[N:16][C:15]([S:18][CH3:19])=[N:14][CH:13]=1)=[O:11])[CH3:8]
Reactant: NC1CCCC1
Reactant: CCOC(=O)c1cnc(SC)nc1Cl
Solvent: ClCCl
Product: CCOC(=O)c1cnc(SC)nc1NC1CCCC1
Reaction time: 72 h
Yield: 105.5 %

Procedure:
Cyclopentylamine (12.7 mL, 129.3 mmol) was added to solution of 4-chloro-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester (10 g, 43.10 mmol) in DCM (250 mL) at RT and the resulting mixture was stirred for 3 days. The reaction mixture was washed 3 times with water; the aqueous extracts were combined and extracted twice with DCM. The combined organic extracts were dried over Na2SO4, filtered, and evaporated under reduced pressure to give 12.8 g of 4-cyclopentylamino-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester as a crude oil without further purifications.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[O:6].S(C1C=CC(C)=CC=1)(OO[CH2:15][CH2:16][C:17]([F:20])([F:19])[F:18])(=O)=O.C(=O)([O-])[O-].[K+].[K+]>C(O)C>[F:18][C:17]([F:20])([F:19])[CH2:16][CH2:15][O:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[O:6]
Reactant: O=Cc1cccc(O)c1
Reactant: Cc1ccc(S(=O)(=O)OOCCC(F)(F)F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: O=Cc1cccc(OCCC(F)(F)F)c1
Yield: 47.7 %

Procedure:
Combine 3-hydroxybenzaldehyde (130.2 g, 1.066 mol), 3,3,3-trifluoropropoxy tosylate (143 g, 0.533 mol), potassium carbonate (147.35 g, 1,066 mol) and absolute ethanol (1430 mL) in a three-necked round-bottomed flask equipped with a reflux condenser and a magnetic stirred and reflux for 4 h under argon atmosphere. Concentrate the reaction mixture under reduced pressure. Pour the concentrated mixture over 1N sodium hydroxide (2145 mL), stir for 30 min and extract with dichloromethane (2145 mL). Decant the organic layer wash with 1N sodium hydroxide (2145 mL). After separation, wash the organic layer successively twice by 1 L water (pH aqueous phase=7), dry over 30 g magnesium sulfate, evaporate the dichloromethane organic layer to dryness under reduced pressure to yield 55.4 g of the title compound (0.254 mol, 47.6% yield) as a slightly yellow oily material.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH:12]([C:13]([OH:15])=O)[CH2:11][S:10][CH:9]1[C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:23][O:24][C:25](=[O:32])[C@H:26]([CH2:28][CH:29]([CH3:31])[CH3:30])[NH2:27].ON1C2C=CC=CC=2N=N1.CN1CCOCC1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1>[CH3:23][O:24][C:25](=[O:32])[C@H:26]([CH2:28][CH:29]([CH3:31])[CH3:30])[NH:27][C:13]([CH:12]1[CH2:11][S:10][CH:9]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[O:15]
Reactant: CC(C)(C)OC(=O)N1C(C(=O)O)CSC1c1cccnc1
Reactant: COC(=O)[C@@H](N)CC(C)C
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: C1CCOC1
Solvent: CN1CCOCC1
Product: COC(=O)[C@H](CC(C)C)NC(=O)C1CSC(c2cccnc2)N1C(=O)OC(C)(C)C
Yield: 98.5 %

Procedure:
To a solution of 600 mg of N-tert-butoxycarbonyl-2-(3-pyridyl)thiazolidine-4 carboxylic acid in 5 ml of tetrahydrofuran, there were added, at 4° C. or below, 350 mg of L-leucine methyl ester hydrochloride, 390 mg of 1-hydroxybenzotriazole, 190 mg of N-methylmorpholine and 440 mg of dicyclohexylcarbodiimide, in that order, and the mixture was stirred overnight in an icehouse. The resultant precipitate was filtered off, the filtrate was concentrated under reduced pressure, 50 ml of ethyl acetate was added, the insoluble matter was filtered off, and the filtrate was washed in sequence with 0.5M aqueous citric acid, water, saturated aqueous solution of sodium hydrogen carbonate and water, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 830 mg of oily [N-tert-butoxycarbonyl-2-(3-pyridyl)thiazolidine-4-carbonyl]-L-leucine methyl ester. Trifluoroacetic acid (3 ml) was added to 800 mg of the thus obtained compound with ice cooling, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, 10 ml of ethyl acetate was added and the solution was again concentrated under reduced pressure. The residue was dissolved in 10 ml of ethyl acetate, 3 ml of 2.2N hydrogen chloride solution in dioxane was added with ice colling, and the mixture was allowed to stand overnight in an icehouse. The resultant crystals were collected by filtration, washed with ethyl acetate and dried to give 510 mg of [2-(3-pyridyl)thiazolidine-4-carbonyl]-L-leucine methyl ester dihydrochloride. Melting point 97°-100° C.
Reaction SMILES: O=C=[N:3]C1CC(C)(C)CC(C)(CN=C=O)C1.[C:17]([O:21]CC(CC)CCCC)(=[O:20])[CH:18]=[CH2:19].[C:30]([O:34][CH2:35][CH2:36]O)(=[O:33])C=C>C([O-])(=O)CCCCCCCCCCC.C([O-])(=O)CCCCCCCCCCC.C([Sn+2]CCCC)CCC>[C:17]([OH:21])(=[O:20])[CH:18]=[CH2:19].[NH2:3][C:30]([O:34][CH2:35][CH3:36])=[O:33]
Reactant: CC1(C)CC(N=C=O)CC(C)(CN=C=O)C1
Reactant: C=CC(=O)OCC(CC)CCCC
Reactant: C=CC(=O)OCCO
Agent: CCCCCCCCCCCC(=O)[O-]
Agent: CCCC[Sn+2]CCCC
Product: C=CC(=O)O
Product: CCOC(N)=O
Reaction time: 2 h

Procedure:
A four-neck flask fitted with a stirrer, a dropping funnel, a nitrogen inlet tube and a thermometer was charged with 1,000 g of the polyoxyalkylene polyol (a1-1), 166 g of isophorone diisocyanate (IPDI), 700 g of 2-ethylhexyl acrylate as a diluent, and 0.1 g of dibutyltin dilaurate as a catalyst, and these components were reacted for 4 hours at a temperature of 100° C. Subsequently, 57 g of hydroxyethyl acrylate (HEA) was added to the reaction mixture, and reaction was continued for a further 2 hours at a temperature of 100° C. The infrared absorption spectrum of the thus obtained reaction mixture was then measured, confirming that the isocyanate group absorption (2250 cm−1) had disappeared.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:12])[O:9]2)=[CH:4][CH:3]=1.Cl[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][OH:20].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[OH:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][O:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:6]=[CH:7][C:8](=[O:12])[O:9][C:10]=2[CH:11]=1
Reactant: OCCCCCCCl
Reactant: O=c1ccc2ccc(O)cc2o1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: O=c1ccc2ccc(OCCCCCCO)cc2o1
Temperature: 100 °C
Reaction time: 8 h
Yield: 89 %

Procedure:
4.87 g (30 mmol) of 7-hydroxy-coumarin, 6.17 g (45.2 mmol) of 6-chlorohexanol and 6.56 g (47.5 mmol) of potassium carbonate were treated with 50 ml of absolute N,N-dimethylformamide and stirred at 100° C. overnight. Subsequently, the batch was poured into water. The white precipitate which separated was filtered off and rinsed with water. The mother liquor was evaporated to dryness in a vacuum, taken up in a small amount of water and extracted several times with ethyl acetate. The precipitate and the ethyl acetate phases were combined, dried over sodium sulphate, evaporated and, for purification, chromatographed on silica gel with an eluent mixture of ethyl acetate and cyclohexane in the ratio 1:1. Therefrom there resulted 7 g of 7-(6-hydroxy-hexyloxy)-2H-1-benzopyran-2-one as white crystals.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](O)=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:8](=[O:12])[NH:9]2)=[CH:4][CH:3]=1.[CH2:20]([NH2:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>>[CH2:20]([NH:27][C:6]1[C:5]2[C:10](=[CH:11][C:2]([Cl:1])=[CH:3][CH:4]=2)[NH:9][C:8](=[O:12])[C:7]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: O=c1[nH]c2cc(Cl)ccc2c(O)c1-c1ccccc1
Reactant: NCc1ccccc1
Product: O=c1[nH]c2cc(Cl)ccc2c(NCc2ccccc2)c1-c1ccccc1

Procedure:
7-Chloro-4-hydroxy-3-phenyl-2(1H)-quinolone (0.5 g) and benzylamine (20 ml) was heated under reflux for 24 h. The reaction was concentrated under high vacuum and the residue was triturated with diethyl ether and filtered. The filtrate was evaporated and purified by chromatography (25% ethyl acetate-dichloromethane eluent) to give the title compound as a white solid (0.045 g); mp 179° C. (diethyl ether). Found: C, 72.63; H, 4.45; N, 7.65. C22H17ClN2O.0.1H2O requires C, 72.87; H, 4.78; o N, 7.72%; δ (360 MHz, DMSO-d6) 3.81 (2H, d, J=4.8 Hz, PhCH2NH), 8.67 (1H, t, J=4.8 Hz, PhCH2NH), 6.85 (2H, d, J=6.5 Hz, ortho aromatics), 7.10-7.33 (11H, m, aromatics), 8.16 (1H, d, J=8.8 Hz, 5-H), 11.23 (1H, br s, NH); m/z (EI) 360 (M+).