Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: COC1C=C(OC)C=CC=1C[N:6]1[CH2:11][CH2:10][CH2:9][CH:8]([F:12])[S:7]1(=[O:14])=[O:13].FC(F)(F)C(O)=O>C(Cl)Cl>[F:12][CH:8]1[S:7](=[O:14])(=[O:13])[NH:6][CH2:11][CH2:10][CH2:9]1
Reactant: COc1ccc(CN2CCCC(F)S2(=O)=O)c(OC)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=S1(=O)NCCCC1F
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 77.3 %

Procedure:
2-(2,4-Dimethoxybenzyl)-6-fluoro-1,2-thiazinane-1,1-dioxide (0.532 g, 1.8 mmol) in methylene chloride (40 mL) was cooled to 0° C. Trifluoroacetic acid (25 mL) was added and the resultant red solution stirred for 1.5 hrs at 0° C., concentrated under reduced pressure. The crude product was purified by silica gel chromatography (20-70% ethyl acetate/hexanes) to give a clear liquid (0.213 g, 79%). 1H NMR (300 MHz, CDCl3) δ 5.35-5.33 (dd, 0.5H, J=5.0, 2.4 Hz), 5.19-5.17 (t, 0.5H, J=3.6 Hz), 4.76 (br s, 1H), 3.52-3.32 (m, 2H), 2.56-2.40 (m, 2H), 1.91-1.81 (m, 1H), 1.59-1.52 (m, 1H).
Reaction SMILES: [C:1]([CH2:7][C:8]#[N:9])(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[Br:10]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[Br:10][CH:7]([C:1](=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3])[C:8]#[N:9]
Reactant: O=C1CCC(=O)N1Br
Reactant: CC(C)(C)C(=O)CC#N
Solvent: ClC(Cl)(Cl)Cl
Product: CC(C)(C)C(=O)C(Br)C#N
Yield: 87.7 %

Procedure:
Pivaloylacetonitrile (1.00 g, 7.99 mmol) was dissolved in carbon tetrachloride (15 mL). N-Bromosuccinimide (1.42 g, 7.99 mmol) was added, and the mixture was refluxed for 15 minutes. After cooling, the insoluble matter was filtered off, and the residue obtained by evaporation of the filtrate under reduced pressure was purified by chromatography on silica gel (n-hexane:ethyl acetate=4:1) to give the title compound (1.43 g, 87.9%) as a yellowish brown oil.
Reaction SMILES: [CH3:1][C:2]1[C:7]2[C:8]3([CH2:13][CH2:14][S:15](=[O:17])(=[O:16])[C:6]=2[C:5]([CH3:18])=[CH:4][C:3]=1[C:19]([OH:21])=[O:20])[O:12][CH2:11][CH2:10][O:9]3.C(Cl)(=O)C(Cl)=O.[CH2:28]([N:30]1[C:34](O)=[CH:33][CH:32]=[N:31]1)[CH3:29].C(N(CC)CC)C>CN(C)C=O.C(Cl)Cl>[CH3:1][C:2]1[C:7]2[C:8]3([CH2:13][CH2:14][S:15](=[O:17])(=[O:16])[C:6]=2[C:5]([CH3:18])=[CH:4][C:3]=1[C:19]([O:21][C:34]1[N:30]([CH2:28][CH3:29])[N:31]=[CH:32][CH:33]=1)=[O:20])[O:9][CH2:10][CH2:11][O:12]3
Reactant: CCn1nccc1O
Reactant: Cc1cc(C(=O)O)c(C)c2c1S(=O)(=O)CCC21OCCO1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCn1nccc1OC(=O)c1cc(C)c2c(c1C)C1(CCS2(=O)=O)OCCO1
Temperature: 0 °C
Reaction time: 8 h
Yield: 15.5 %

Procedure:
1.18 g (3.8 mmol) of the title compound of Step F, 0.99 mL (0.011 mol) of oxalyl chloride (purchased from Janssen), and 2 drops of N,N-dimethylformamide were added to 50 mL of methylene chloride. The mixture was refluxed under nitrogen for 2 h, and was then evaporated to dryness. 50 mL of methylene chloride was added to the residue and the resulting mixture was evaporated to dryness. Another 50 mL of methylene chloride was added to the residue, and the solution was cooled to about 0° C. 0.51 g (4.5 mmol) of 1-ethyl-1H-pyrazol-5-ol was added followed by 1.63 mL (0.012 mol) of triethylamine, and the mixture was stirred overnight while warming to room temperature. The mixture was evaporated to dryness and the crude product was chromatographed eluting with a mixture of ethyl acetate:hexane (6:4) to yield 0.24 g of the title compound of Step G as a semi-solid. 1H NMR (CDCl3): δ1.4 (t,3H), 2.5 (s,3H), 2.6 (m,2H), 2.8 (s,3H), 3.5 (m,2H), 4.1-4.4 (m,6H), 6.26 (s,1H), 7.5-7.7 (2H).
Reaction SMILES: Cl[C:2]([O:4][CH3:5])=[O:3].[NH:6]1[CH2:9][CH:8]([N:10]2[C:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[Cl:25])=[N:17][C:16]3[C:11]2=[N:12][C:13]([CH3:34])=[N:14][C:15]=3[N:26]2[CH2:31][CH2:30][N:29]([CH2:32][CH3:33])[CH2:28][CH2:27]2)[CH2:7]1.N1C=CC=CC=1>ClCCl>[CH3:5][O:4][C:2]([N:6]1[CH2:7][CH:8]([N:10]2[C:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[Cl:25])=[N:17][C:16]3[C:11]2=[N:12][C:13]([CH3:34])=[N:14][C:15]=3[N:26]2[CH2:27][CH2:28][N:29]([CH2:32][CH3:33])[CH2:30][CH2:31]2)[CH2:9]1)=[O:3]
Reactant: CCN1CCN(c2nc(C)nc3c2nc(-c2ccccc2Cl)n3C2CNC2)CC1
Reactant: COC(=O)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CCN1CCN(c2nc(C)nc3c2nc(-c2ccccc2Cl)n3C2CN(C(=O)OC)C2)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Add methyl chloroformate (0.0024 mol, 0.22 g, 2.5 equiv.) to a solution of 9-(azetidin-3-yl)-8-(2-chlorophenyl)-6-(4-ethylpiperazin-1-yl)-2-methyl-9H-purine (0.0009 mol, 0.4 g) and pyridine (2 mL) in dry dichloromethane (2 mL) at 0° C. and stir for 2 hours at room temperature. Quench the reaction mixture with saturated sodium bicarbonate solution and then extract with dichloromethane. Dry the organic layer over anhydrous sodium sulfate, filter and concentrate under reduced pressure to give the residue. Purify the residue by silica gel chromatography eluting with dichloromethane:methanol 98:2 to give the title compound as the freebase (0.155 g). MS (m/z): 470.63 (M+1).
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]([C:8]2[CH:9]=[CH:10][CH:11]=[C:12]3[C:17]=2[N:16]=[CH:15][CH:14]=[CH:13]3)=[CH2:7])[N:3]=[CH:2]1.[H][H]>FC(F)(F)C(O)=O.[Pd]>[NH:1]1[CH:5]=[C:4]([CH:6]([C:8]2[CH:9]=[CH:10][CH:11]=[C:12]3[C:17]=2[N:16]=[CH:15][CH:14]=[CH:13]3)[CH3:7])[N:3]=[CH:2]1
Reactant: C=C(c1c[nH]cn1)c1cccc2cccnc12
Reactant: [H][H]
Agent: [Pd]
Solvent: O=C(O)C(F)(F)F
Product: CC(c1c[nH]cn1)c1cccc2cccnc12
Yield: 86.2 %

Procedure:
The vinyl compound, 8-[1-(1H-imidazol-4-yl)-vinyl]-quinoline (0.23 g) in trifluoroacetic acid: TFA (15 mL) was reduced by the action of 10% Pd/C (58 mg) under 50 psi of hydrogen for 18 h at rt. The mixture was filtered through Celite and basified with NH3-MeOH. The solvent was removed under vacuum. The residue was purified by chromatography on silica gel with 4% NH3-MeOH: CH2Cl2 to give 8-[1-(1H-imidazol-4-yl)-ethyl]-quinoline (Intermediate C2) 0.2 g.
Reaction SMILES: [CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[CH:19]=[CH:18][C:15]([CH:16]=O)=[CH:14][CH:13]=2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[F:20][C:21]([F:30])([F:29])[C:22]1[CH:28]=[CH:27][C:25]([NH2:26])=[CH:24][CH:23]=1>>[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[CH:19]=[CH:18][C:15]([CH2:16][NH:26][C:25]3[CH:27]=[CH:28][C:22]([C:21]([F:20])([F:29])[F:30])=[CH:23][CH:24]=3)=[CH:14][CH:13]=2)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2]
Reactant: CC(C)N1CCN(C(=O)c2ccc(C=O)cc2)CC1
Reactant: Nc1ccc(C(F)(F)F)cc1
Product: CC(C)N1CCN(C(=O)c2ccc(CNc3ccc(C(F)(F)F)cc3)cc2)CC1

Procedure:
Prepared from the product of Example 15 and 4-trifluoromethylaniline.
Reaction SMILES: [O:1]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][C:17]([O:19]CC)=[O:18])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>C1COCC1.CO>[O:1]([CH2:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15][CH2:16][C:17]([OH:19])=[O:18])=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)CCc1ccc(COc2ccccc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)CCc1ccc(COc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of ethyl 3-(4-(phenoxymethyl)phenyl)propanoate (S26, 185 mg, 0.65 mmol) in a THF/MeOH (1/1, 10 mL) was treated with aqueous 4 N NaOH (1 mL) and was stirred overnight at 25° C. The reaction mixture was concentrated, diluted with aqueous 1 N HCl and extracted with CH2Cl2. The organic layer was dried over Na2SO4, filtered and concentrated to afford S27 (115 mg, 0.45 mmol, 69%) as a pale yellow solid: 1H NMR (CDCl3, 500 MHz) 7.39 (d, 2H, J=7.7 Hz), 7.30 (t, 2H, J=7.4 Hz), 7.25 (d, 2H, J=7.7 Hz), 7.00-6.96 (m, 3H), 5.05 (s, 2H), 2.99 (t, 2H, J=7.7 Hz), 2.71 (t, 2H, J=7.7 Hz); 13C NMR (CDCl3, 125 MHz) 178.8, 158.7, 139.9, 135.1, 129.5, 128.5, 127.8, 120.9, 114.7, 69.7, 35.4, 30.2.
Reaction SMILES: [CH:1]1(/[C:6](/[N:10]2[CH:14]=[C:13]([C:15]3[C:16]4[CH:23]=[CH:22][N:21]([CH2:24]OCC[Si](C)(C)C)[C:17]=4[N:18]=[CH:19][N:20]=3)[CH:12]=[N:11]2)=[CH:7]/[C:8]#[N:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:32]1([CH:37]=CC#N)[CH2:36]CC[CH2:33]1.CS(C)=O.[C:45](=[O:48])([O-])[O-:46].[K+].[K+]>>[C:45]([O:46][CH2:24][N:21]1[C:17]2[N:18]=[CH:19][N:20]=[C:15]([C:13]3[CH:12]=[N:11][N:10]([CH:6]([CH:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)[CH2:7][C:8]#[N:9])[CH:14]=3)[C:16]=2[CH:23]=[CH:22]1)(=[O:48])[C:32]([CH3:37])([CH3:36])[CH3:33]
Reactant: C[Si](C)(C)CCOCn1ccc2c(-c3cnn(/C(=C\C#N)C4CCCC4)c3)ncnc21
Reactant: N#CC=CC1CCCC1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: CC(C)(C)C(=O)OCn1ccc2c(-c3cnn(C(CC#N)C4CCCC4)c3)ncnc21
Temperature: 25 °C
Reaction time: 5 h
Yield: 547.3 %

Procedure:
To a stirred suspension of [4-(1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]methyl pivalate (19, 158 mg, 0.50 mmol) and 3-cyclopentylacrylonitrile (8, 122 mg, 1.0 mmol, 2.0 equiv) in dimethyl sulfoxide (DMSO, 1.0 mL, 14 mmol) at room temperature was added powder potassium carbonate (K2CO3, 10.4 mg, 0.075 mmol, 0.15 equiv). The reaction mixture was then stirred at room temperature for 5 h. The reaction mixture became a clear solution in 2 h. When LCMS showed the reaction was deemed complete, the reaction was quenched with water (H2O, 5 mL) and extracted with ethyl acetate (EtOAc, 3×15 mL). The combined organic extracts were washed with saturated aqueous NaCl solution (10 mL), dried over magnesium sulfate (MgSO4), and concentrated under reduced pressure. The residue was then purified by flash chromatography (SiO2, 0-50% EtOAc/hexanes gradient elution) to afford racemic (4-(1-(2-cyano-1-cyclopentylethyl)-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl pivalate (20, 172.6 mg, 210 mg theoretical, 82% yield) as a white solid. For 20: 1H NMR (CDCl3, 400 MHz) δ ppm 8.87 (s, 1H), 8.30 (s, 1H), 8.29 (s, 1H), 7.47 (d, 1H, J=3.9 Hz), 6.75 (d, 1H, J=3.9 Hz), 6.24 (s, 2H), 4.25 (m, 1H), 3.12 (dd, 1H, J=17.0, 8.7 Hz), 2.95 (dd, 1H, J=17.0, 3.9 Hz), 2.58 (m, 1H), 1.95 (m, 1H), 1.72-1.52 (m, 5H), 1.25 (m, 2H), 1.14 (s, 9H); C23H28N6O2 (MW, 420.51), LCMS (EI) m/e 421.4 (M++H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[CH2:9][N:8]([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20](=[O:35])[C:21]1[CH:26]=[C:25]([CH3:27])[CH:24]=[CH:23][C:22]=1[O:28][CH2:29][CH2:30][O:31][CH2:32][CH2:33]O)[CH2:7][CH2:6]2.C(N(S(F)(F)[F:42])CC)C>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[CH2:9][N:8]([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20](=[O:35])[C:21]1[CH:26]=[C:25]([CH3:27])[CH:24]=[CH:23][C:22]=1[O:28][CH2:29][CH2:30][O:31][CH2:32][CH2:33][F:42])[CH2:7][CH2:6]2
Reactant: CCN(CC)S(F)(F)F
Reactant: COc1cc2c(cc1OC)CN(CCCCNC(=O)c1cc(C)ccc1OCCOCCO)CC2
Solvent: ClCCl
Product: COc1cc2c(cc1OC)CN(CCCCNC(=O)c1cc(C)ccc1OCCOCCF)CC2
Reaction time: 8 h
Yield: 34.9 %

Procedure:
To solution of compound 5a (0.20 g, 0.41 mmol) in dichloromethane (60 ml) was added slowly (Diethylamino)sulfur trifluoride (DAST) (0.13 g, 0.81 mmol) at 0° C. The reaction mixture was stirred overnight under an atmosphere of nitrogen and then quenched with water (30 ml). The organic layer was separated and washed with saturated sodium carbonate solution (2×15 ml) and dried over sodium sulfate. Volatile components were removed under reduced pressure. The crude product was purified by silica gel column chromatography using ether:methanol (100:20) as the mobile phase to give 6a (0.07 g; 36% yield) as a viscous colorless oil. 1H NMR spectrum (300 MHz, CDCl3): 1.65-1.69 (m, 4H), 2.32 (s, 3H), 2.50-2.59 (m, 2H), 2.70-2.73 (m, 2H), 2.78-2.82 (m, 2H), 3.45-3.48 (m, 2H), 3.54 (s, 2H), 3.69-3.73 (m, 1H), 3.72-3.82 (m, 7H), 3.87-3.90 (m, 2H), 4.19-4.22 (m, 2H), 4.43-4.47 (m, 1H), 4.59-4.63 (m, 1H), 6.50 (s, 1H), 6.58 (s, 1H), 6.80-6.84 (d, 1H), 7.05-7.20 (m, 1H), 7.97-7.99 (m, 1H), 8.21 (s, 1H). The free base was converted into oxalic acid salt and re-crystallized in methanol and ethyl acetate solvent. Mp 89.2-89.55° C. Elemental Analysis: C27H37FN2O5.H2C2O4.0.5H2O (C, H, N). Calcd: C, 59.27; H, 6.86; N, 4.77; Found: C, 58.95; H, 6.84; N, 4.85.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12].[Li]CCCC.[N:21]1[C:30]2[C:25](=[CH:26][C:27]([CH:31]=[O:32])=[CH:28][CH:29]=2)[N:24]=[CH:23][CH:22]=1>C1COCC1>[F:1][C:2]1[C:7]([CH:31]([OH:32])[C:27]2[CH:26]=[C:25]3[C:30](=[CH:29][CH:28]=2)[N:21]=[CH:22][CH:23]=[N:24]3)=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10](=[O:15])[C:11]([CH3:12])([CH3:14])[CH3:13]
Reactant: CC(C)(C)C(=O)Nc1ccc(F)cc1F
Reactant: O=Cc1ccc2nccnc2c1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC(C)(C)C(=O)Nc1ccc(F)c(C(O)c2ccc3nccnc3c2)c1F
Temperature: -78 °C
Reaction time: 1 h
Yield: 50.6 %

Procedure:
To a solution of N-(2,4-difluorophenyl)pivalamide (740 mg, 3.46 mmol, 1.2 eq.) in THF (10 mL) cooled at −78° C. was added n-BuLi (2.76 mL, 6.9 mmol, 2.4 eq.) dropwise. The resulting mixture was stirred at −78° C. for 1 h, then a solution of quinoxaline-6-carbaldehyde (450 mg, 2.88 mmol, 1.0 eq.) in THF (20 mL) was added dropwise. The mixture was stirred at −78° C. for 1 h, then quenched by the addition of NH4Cl solution. The mixture was extracted with EA (20 mL×3) and the combined organic layers were dried over Na2SO4 and concentrated. The resulting residue was purified via flash column chromatography (PE/EA=2/1, v/v) to afford N-(2,4-difluoro-3-(hydroxy(quinoxalin-6-yl)methyl)phenyl)pivalamide as a yellow foam (541 mg, 50.7%).
Reaction SMILES: [NH:1]([C:3]([C:5]1[NH:6][C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[CH:9][C:8]=2[N:14]([CH3:23])[S:15]([C:18]1[S:19][CH:20]=[CH:21][CH:22]=1)(=[O:17])=[O:16])=[O:4])[NH2:2].Cl[C:25](=[O:32])[CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28].O>CN(C)C(=O)C>[CH3:23][N:14]([S:15]([C:18]1[S:19][CH:20]=[CH:21][CH:22]=1)(=[O:17])=[O:16])[C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:7]=1[NH:6][C:5]([C:3]([NH:1][NH:2][C:25](=[O:32])[CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[O:4])=[CH:13]2
Reactant: CN(c1cccc2cc(C(=O)NN)[nH]c12)S(=O)(=O)c1cccs1
Reactant: CCOC(=O)CC(=O)Cl
Solvent: CC(=O)N(C)C
Solvent: O
Product: CCOC(=O)CC(=O)NNC(=O)c1cc2cccc(N(C)S(=O)(=O)c3cccs3)c2[nH]1
Temperature: 25 °C
Reaction time: 1 h
Yield: 84 %

Procedure:
To a solution of N-[2-(hydrazinocarbonyl)-1H-indol-7-yl]-N-methylthiophene-2-sulfonamide (0.88 g) in N,N-dimethylacetamide (16 mL) was added ethyl 3-chloro-3-oxopropanoate (0.35 mL) at 0° C., and the mixture was stirred at room temperature for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. Diethyl ether was added to the obtained oil, and the resulting crystals were filtrated, washed with diethyl ether, and dried to give the title compound (0.96 g, yield 84%) as colorless crystals. melting point 119-121° C.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C:11](O)([C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(OS([O-])(=O)=O)([O-])(=O)=O.[K+].[K+]>C1C2C(CCCC2)CCC1.O>[CH2:1]([N:8]1[CH2:9][CH:10]=[C:11]([C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)[CH2:12][CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: OC1(c2cccnc2)CCN(Cc2ccccc2)CC1
Agent: O=S(=O)([O-])OS(=O)(=O)[O-]
Agent: [K+]
Solvent: C1CCC2CCCCC2C1
Solvent: O
Product: C1=C(c2cccnc2)CCN(Cc2ccccc2)C1
Temperature: 25 °C
Yield: 95.8 %

Procedure:
A dispersion of 4.52 g (16.8 mmol) of 1'-benzyl-2',3',5',6'-tetrahydro-1'H-[3,4']bipyridinyl-4'-ol and 18 g (71 mmol) of potassium disulphate in 35 ml of decalin was stirred at 190° C. for 30 minutes. After cooling to room temperature the reaction mixure was dissolved in water and extracted twice with 50 ml of toluene each time. Subsequently, the aqueous phase was made alkaline with sodium hydroxide solution and extracted with ethyl acetate. The ethyl acetate phase was thereafter dried over sodium sulphate and evaporated under reduced pressure. For purification, the crude product was chromatographed on silica gel using a 98:2:0.1 mixture of methylene chloride, methanol and ammonia as the eluent. There were obtained 4.03 g (61% of theory) of 1'-benzyl-1',2',3',6'-tetrahydro-3,4'-bipyridine as a yellowish oil; MS: 250 (M)+.
Reaction SMILES: Cl[NH:2][C:3]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]C)=O.N(CC(O)=O)[CH3:15].[OH-].[Na+].[NH:22]1[CH2:28][C:26](=[O:27])N[C:23]1=[O:24]>C(O)(C)(C)C.O>[CH3:15][N:22]1[CH2:28][C:26](=[O:27])[N:2]([CH2:3][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[C:23]1=[O:24]
Reactant: CNCC(=O)O
Reactant: O=C1CNC(=O)N1
Reactant: CCCCCCCCCC(=O)NCl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)(C)O
Solvent: O
Product: CCCCCCCCCN1C(=O)CN(C)C1=O
Yield: 90 %

Procedure:
In accordance with the procedure described in Example 6, 41 g (0.2 mol) capric N-chloramide were reacted with sarcosine, sodium hydroxide in a mixture of tertiary butanol and water and then processed. The hydantoin remained in the aqueous solution was an oil, that was extracted with ether. The ether was removed by distillation to yield 43 g (90% yield) 1-methyl-3-n-nonyl hydantoin of the formula ##STR10## having the following analysis:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11](=[O:18])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.[CH2:19](O)[CH2:20][OH:21].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH3:10][O:9][C:7]1[CH:6]=[C:5]([C:11]2([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[O:21][CH2:20][CH2:19][O:18]2)[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=1
Reactant: CCCCCCC(=O)c1cc(OC)cc(OC)c1
Reactant: OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: CCCCCCC1(c2cc(OC)cc(OC)c2)OCCO1
Yield: 90.4 %

Procedure:
1-(3,5-Dimethoxyphenyl)heptan-1-one (200 mg, 0.80 mmol), ethylene glycol (173 mg, 2.80 mmol) and a catalytic amount of p-toluenesulfonic acid monohydrate were refluxed in toluene (25 mL) overnight in a Dean-Stark apparatus. The reaction mixture was then concentrated and the residue dissolved in chloroform (50 mL) and washed with saturated sodium bicarbonate solution (2×25 mL) then brine (1×25 mL). The organic phase was dried (Na2SO4) and evaporated to give 2-(3,5-dimethoxyphenyl)-2-hexyl-1,3-dioxolane (41) as a light yellow oil (213 mg, 90%). 1H NMR (CDCl3, 300 MHz): δ 0.94, t (6.5 Hz), CH3; 1.31, m, methylene envelope; 1.89, m, CH2; 3.79-3.83, m, 2×OMe, OCH2; 4.04, m, OCH2; 6.46, m, H4′; 6.63, m, H2′,6′. ESI (+ve) MS: m/z 295 (M+H, 62%).
Reaction SMILES: [SiH:1]([Cl:4])([Cl:3])[Cl:2].[CH2:5]([C:8]1[CH:13]=[CH:12][C:11]([N:14]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:15]2[S:19][C:18]([C:20]3[S:21][C:22]([N:25]([C:32]4[CH:37]=[CH:36][C:35]([CH2:38][CH:39]=[CH2:40])=[CH:34][CH:33]=4)[C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[CH:23][CH:24]=3)=[CH:17][CH:16]=2)=[CH:10][CH:9]=1)[CH:6]=[CH2:7]>C1(C)C=CC=CC=1.C1([Pt-](Cl)C2C=CC=C2)C=CC=C1>[Cl:2][Si:1]([CH2:40][CH2:39][CH2:38][C:35]1[CH:34]=[CH:33][C:32]([N:25]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:22]2[S:21][C:20]([C:18]3[S:19][C:15]([N:14]([C:11]4[CH:10]=[CH:9][C:8]([CH2:5][CH2:6][CH2:7][Si:1]([Cl:4])([Cl:3])[Cl:2])=[CH:13][CH:12]=4)[C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=4)=[CH:16][CH:17]=3)=[CH:24][CH:23]=2)=[CH:37][CH:36]=1)([Cl:4])[Cl:3]
Reactant: Cl[SiH](Cl)Cl
Reactant: C=CCc1ccc(N(c2ccccc2)c2ccc(-c3ccc(N(c4ccccc4)c4ccc(CC=C)cc4)s3)s2)cc1
Agent: Cl[Pt-](C1C=CC=C1)C1C=CC=C1
Solvent: Cc1ccccc1
Product: Cl[Si](Cl)(Cl)CCCc1ccc(N(c2ccccc2)c2ccc(-c3ccc(N(c4ccccc4)c4ccc(CCC[Si](Cl)(Cl)Cl)cc4)s3)s2)cc1
Temperature: 60 °C

Procedure:
Excess HSiCl3 (0.09 mL, 8.609×10−4 mol) and a few grains of dicyclopentadienylplatinum(II) chloride (Cp2PtCl2) catalyst were added in a glove box to a solution of Compound 4 (0.050 g, 8.609×10−5 mol) in about 10 mL anhydrous toluene. The solution was transferred to a Schlenk line where it was heated to 60° C. with stirring and left under static N2 to prevent evaporation of the HSiCl3. The reaction progress was monitored by 1H NMR, and cooled to room temperature after 42 h. Toluene and excess HSiCl3 were next removed in vacuo. Upon trituration of the crude product with 15 mL of a dry 1:1 toluene:pentane solution, a solid formed and was removed via cannula filtration.
Reaction SMILES: CO[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[S:9][CH2:10][CH2:11][CH2:12][N:13]([C@H:29]1[CH2:34][CH2:33][C@H:32]([CH3:35])[CH2:31][CH2:30]1)[C:14](=[O:28])[NH:15][C:16]1[S:17][C:18]([S:21][C:22](C)([CH3:26])C(O)=O)=[CH:19][N:20]=1.C1(S)C=CC=CC=1.C([O:45][C:46](=[O:56])CCSC1SC(N)=NC=1)C>>[CH3:35][C@H:32]1[CH2:31][CH2:30][C@H:29]([N:13]([CH2:12][CH2:11][CH2:10][S:9][C:4]2[CH:3]=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:14](=[O:28])[NH:15][C:16]2[S:17][C:18]([S:21][CH2:22][CH2:26][C:46]([OH:56])=[O:45])=[CH:19][N:20]=2)[CH2:34][CH2:33]1
Reactant: CCOC(=O)CCSc1cnc(N)s1
Reactant: COc1ccccc1SCCCN(C(=O)Nc1ncc(SC(C)(C)C(=O)O)s1)[C@H]1CC[C@H](C)CC1
Agent: Sc1ccccc1
Product: C[C@H]1CC[C@H](N(CCCSc2ccccc2)C(=O)Nc2ncc(SCCC(=O)O)s2)CC1

Procedure:
The compound was prepared following an analogous procedure to the one described for the synthesis 2-{2-[3-[3-(2-methoxy-phenylsulfanyl)-propyl]-3-(trans-4-methyl-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-2-methyl-propionic acid using thiophenol and 3-(2-amino-thiazol-5-ylsulfanyl)-propionic acid ethyl ester
Reaction SMILES: [Br:1][C:2]1[N:3]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[CH:10]=2)[C:4](=[O:7])[NH:5][N:6]=1.Cl[CH2:17][C:18]([O:20][CH3:21])=[O:19].C(=O)([O-])[O-].[K+].[K+].Cl>C(#N)C.C(OCC)(=O)C>[CH3:21][O:20][C:18](=[O:19])[CH2:17][N:5]1[C:4](=[O:7])[N:3]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[CH:10]=2)[C:2]([Br:1])=[N:6]1
Reactant: O=c1[nH]nc(Br)n1Cc1cccc(F)c1
Reactant: COC(=O)CCl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CC#N
Product: COC(=O)Cn1nc(Br)n(Cc2cccc(F)c2)c1=O

Procedure:
1.50 g (4.69 mmol) of the compound from Example 137A are stirred under reflux for 4 hrs together with 508 mg (4.69 mmol) of methyl chloroacetate and 1.30 g (9.4 mmol) of potassium carbonate in 33 ml acetonitrile. After cooling, the mixture is neutralized with 1 N hydrochloric acid and diluted with ethyl acetate. The organic phase is separated, washed with saturated sodium chloride solution, dried over sodium sulphate and freed of the volatile components on the rotary evaporator. The residue is dissolved in 20 ml dichloromethane and absorbed onto 3 g of diatomaceous earth. After removal of the solvent on the rotary evaporator the solid is transferred to a silica gel chromatography column and the product purified by elution with cyclohexane/ethyl acetate (gradient 5:1→1:1). 1.36 g (84% of theory) of the title compound are obtained.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.[N:11]1[N:12]=[C:13]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[N:14]2[CH2:19][CH2:18][NH:17][CH2:16][C:15]=12.C(N(C(C)C)CC)(C)C.O>C(#N)C>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([N:17]2[CH2:18][CH2:19][N:14]3[C:13]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[N:12][N:11]=[C:15]3[CH2:16]2)=[N:3][CH:4]=1)([O-:10])=[O:9]
Reactant: CCOC(=O)c1nnc2n1CCNC2
Reactant: O=[N+]([O-])c1ccc(Cl)nc1
Solvent: CC#N
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)c1nnc2n1CCN(c1ccc([N+](=O)[O-])cn1)C2
Temperature: 80 °C
Yield: 73.9 %

Procedure:
2-Chloro-5-nitropyridine (0.97 g, 5.5 mmol), ethyl 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine-3-carboxylate (1.0 g, 5.1 mmol), and diisopropylethylamine (2 mL) were mixed in acetonitrile (5 mL), and heated to 80° C. for one h. The mixture was poured into water, and the precipitate was collected by filtration. The precipitate was washed with water, then by ether, and dried in a vacuum oven overnight to give 1.2 gram of product C-12 (75% yield).