Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:3]=[C:4]=[S:5])[CH3:2].[C:6]([C:10]1[C:11](=[O:27])[CH2:12][CH:13]([C:17]2[C:22]([CH3:23])=[CH:21][C:20]([CH3:24])=[C:19]([NH2:25])[C:18]=2[CH3:26])[CH2:14][C:15]=1[OH:16])(=[O:9])[CH2:7][CH3:8].C(Cl)Cl>C(O)C>[C:6]([C:10]1[C:11](=[O:27])[CH2:12][CH:13]([C:17]2[C:22]([CH3:23])=[CH:21][C:20]([CH3:24])=[C:19]([NH:25][C:4]([NH:3][CH2:1][CH3:2])=[S:5])[C:18]=2[CH3:26])[CH2:14][C:15]=1[OH:16])(=[O:9])[CH2:7][CH3:8]
Reactant: CCN=C=S
Reactant: CCC(=O)C1=C(O)CC(c2c(C)cc(C)c(N)c2C)CC1=O
Solvent: CCO
Solvent: ClCCl
Product: CCNC(=S)Nc1c(C)cc(C)c(C2CC(=O)C(C(=O)CC)=C(O)C2)c1C
Reaction time: 96 h
Yield: 31 %

Procedure:
Ethylisothiocyanate (0.35 g, 3.98 mmol) was added to a solution of 2-propionyl-3-hydroxy-5-(3-amino-2,4,6-trimethylphenyl)cyclohex-2-en-1-one (1.0 g, 3.32 mmol) in ethanol (5 ml). Stirring was continued at 20° for 4 days. Dilute acid and methylene chloride were added. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated. The crude product was purified by chromatography on silica gel (elution with an increasing gradient of methanol in methylene chloride) to yield 2-propionyl-3-hydroxy-5-(3-ethylthioureido-2,4,6-trimethylphenyl)cyclohex-2-en-1-one as an oil (0.4 g, 33%). The compound was characterized by proton magnetic resonance spectroscopy (CDCl3, δ in ppm): 1.12 (6H,t); 2.18 (3H,s); 2.28 (3H,s); 2.39 (3H,s); 2.4-4.2 (9H,m); 5.4 (1H,brs); 6.29 (1H,s); 8.34 (1H,brs).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=2)[C:17](O)=[O:18])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O:25][C:26](=[O:29])[CH2:27][NH2:28])C>>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=2)[C:17]([NH:28][CH2:27][C:26]([OH:25])=[O:29])=[O:18])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCN(c2cccc(C(=O)O)c2)CC1
Reactant: CCOC(=O)CN
Product: CC(C)(C)OC(=O)N1CCN(c2cccc(C(=O)NCC(=O)O)c2)CC1

Procedure:
The acid 16-3 was coupled with glycine ethyl ester followed by hydrolysis of the resulting ester using previously described chemistry to yield 17-1.
Reaction SMILES: Cl.[O:2]=[C:3]1[CH:8]=[C:7]([CH2:9][N:10]2[C:14]([CH2:15][C:16]3[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=3)=[CH:13][N:12]=[CH:11]2)[CH:6]=[CH:5][N:4]1[C:24]1C=CC=CC=1.ClC1[N:36]=[CH:35][CH:34]=[CH:33][N:32]=1.IC1C=CC=CC=1>>[O:2]=[C:3]1[CH:8]=[C:7]([CH2:9][N:10]2[C:14]([CH2:15][C:16]3[CH:17]=[CH:18][C:19]([C:20]#[N:21])=[CH:22][CH:23]=3)=[CH:13][N:12]=[CH:11]2)[CH:6]=[CH:5][N:4]1[C:24]1[N:36]=[CH:35][CH:34]=[CH:33][N:32]=1
Reactant: Clc1ncccn1
Reactant: N#Cc1ccc(Cc2cncn2Cc2ccn(-c3ccccc3)c(=O)c2)cc1
Agent: Cl
Solvent: Ic1ccccc1
Product: N#Cc1ccc(Cc2cncn2Cc2ccn(-c3ncccn3)c(=O)c2)cc1

Procedure:
4-[3-(2-Oxo-1-pyrimidin-2-yl-1,2-dihydro-pyridin-4-ylmethyl)-3H-imidazol-4-ylmethyl]-benzonitrile was prepared in a manner substantially similar to the procedure described above for 4-[3-(2-oxo-1-phenyl-1,2-dihydropyridin-4-ylmethyl)-3H-imidazol-4-ylmethyl]benzonitrile, hydrochloride, but substituting 2-chloropyrimidine for the iodobenzene in Step 3.
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[Br:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([C:16]1[CH:21]=[CH:20][C:19]([O:22]COC)=[CH:18][CH:17]=1)[C:11]([CH3:26])=[CH:10]2.CN(C)[CH:29]=[O:30]>>[Br:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=1)[C:11]([CH3:26])=[C:10]2[CH:29]=[O:30]
Reactant: COCOc1ccc(-n2c(C)cc3cc(Br)ccc32)cc1
Reactant: CN(C)C=O
Solvent: O=P(Cl)(Cl)Cl
Product: Cc1c(C=O)c2cc(Br)ccc2n1-c1ccc(O)cc1
Yield: 51 %

Procedure:
Phosphorous oxychloride (2.5 mL) was added to anhydrous dimethylformamide (5 mL) and stirred at room temperature for 15 min whereupon a solution of 5-bromo-1-(4-methoxymethyloxyphenyl)-2-methyl-1H -indole (0.65 g, 1.9 mmol) in dimethylformamide (10 mL) was added. The solution was reacted according to the procedure used in Example 2a to afford a tan solid (51%): mp>250° C.; 1H NMR (DMSO-d6): δ 2.50 (3H, s), 6.95-7.02 (3 H, m), 7.21 (1H, dd, J=2.4 Hz, J=8.8 Hz), 7.28 (2H, d, J=8.7 Hz), 8.38 (1H, d, J=2.2 Hz), 9.98 (1H, s), 10.14 (1H, s); MS m/Z (M+H)+ 318/320 (1 Br). Anal. for C16H12BrNO2·0.2H2O: Calc'd: C, 55.99; H, 3.88; N, 4.35. Found: C, 55.69; H, 3.95; N, 4.15.
Reaction SMILES: [S:1]1[C:5]([C:6](=[O:10])[CH:7](Br)[Br:8])=[CH:4][C:3]2[CH:11]=[CH:12][C:13]3[C:18]([C:2]1=2)=[CH:17][CH:16]=[C:15]([C:19](=[O:23])[CH:20](Br)[Br:21])[CH:14]=3.P([O-])(OCC)OCC.C(N(CC)CC)C>C1COCC1>[S:1]1[C:5]([C:6](=[O:10])[CH2:7][Br:8])=[CH:4][C:3]2[CH:11]=[CH:12][C:13]3[C:18]([C:2]1=2)=[CH:17][CH:16]=[C:15]([C:19](=[O:23])[CH2:20][Br:21])[CH:14]=3
Reactant: O=C(c1ccc2c(ccc3cc(C(=O)C(Br)Br)sc32)c1)C(Br)Br
Agent: CCOP([O-])OCC
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C(CBr)c1ccc2c(ccc3cc(C(=O)CBr)sc32)c1
Temperature: 0 °C
Reaction time: 2 h
Yield: 83.3 %

Procedure:
1,1′-(naphtho[1,2-b]thiophene-2,7-diyl)bis(2,2-dibromoethanone) (10b) (180 g, 310 mmol) obtained as above was dissolved in 500 ml of THF and the solution was cooled to 0° C. A mixture of diethyl phosphite (80 ml, 620 mmol) and triethylamine (86 ml, 210 mmol) in 50 ml THF was added dropwise to the solution which was kept on an ice bath. After the addition, the ice bath was removed and the reaction mixture was stirred at room temperature for 2 hr. The volume of THF was reduced by rotary evaporation to obtain a solid residue which was washed with pentane to afford 1,1′-(naphtho[1,2-b]thiophene-2,7-diyl)bis(2-bromoethanone) as a brown solid (10c) (110 g, 84%).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[N:5]=[CH:4][N:3]=1.[CH2:15]([OH:19])[C:16]#[C:17][CH3:18].[H-].[Na+].O>CN(C)C=O>[F:14][C:11]1[CH:12]=[CH:13][C:8]([C:6]2[CH:7]=[C:2]([O:19][CH2:15][C:16]#[C:17][CH3:18])[N:3]=[CH:4][N:5]=2)=[CH:9][CH:10]=1
Reactant: CC#CCO
Reactant: Fc1ccc(-c2cc(Cl)ncn2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CC#CCOc1cc(-c2ccc(F)cc2)ncn1
Temperature: 25 °C
Reaction time: 9 h
Yield: 57.4 %

Procedure:
In 8 ml of N,N-dimethylformamide were dissolved 207 mg of 4-chloro-6-(4-fluorophenyl)pyrimidine and 83 mg of 2-butyn-1-ol, to which 48 mg of sodium hydride (60% in oil) was added, followed by stirring at room temperature for 9 hours. The reaction mixture was then poured into water and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The resulting residue was subjected to silica gel column chromatography to give 138 mg of 4-(4-fluorophenyl)-6-(2-butynyloxy)pyrimidine (the present compound (59)).
Reaction SMILES: [NH2:1][C:2]([NH2:4])=[O:3].N[CH2:6][CH2:7][CH2:8][N:9]1[CH:13]=[CH:12][N:11]=[C:10]1[CH3:14]>>[CH3:14][C:10]1[N:9]([CH2:8][CH2:7][CH2:6][NH:1][C:2]([NH2:4])=[O:3])[CH2:13][CH2:12][N:11]=1
Reactant: NC(N)=O
Reactant: Cc1nccn1CCCN
Product: CC1=NCCN1CCCNC(N)=O
Yield: 95.7 %

Procedure:
60.0 g of urea was added to 139.2 g of 1-(3′-aminopropyl)-2-methylimidazole and reacted at 160° C. for 10 hours, and after the reaction, a volatile component was removed to obtain 176.1 g of a 1-{3′-(2″-methylimidazolinyl)propyl}urea composition. 117.4 g of dipropylene glycol was added thereto to prepare a solution containing 60% of a 1-{3′-(2″-methylimidazolinyl)propyl}urea composition (IZUM), which was subjected to the following foaming test. The composition of the solution is shown in Table 17.
Reaction SMILES: [CH:1]1([CH2:4][N:5]2[C:10](=[O:11])[C:9]([CH2:12][NH:13][CH3:14])=[CH:8][C:7]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([F:23])[CH:16]=3)=[N:6]2)[CH2:3][CH2:2]1.C1(CN2[C:33](=[O:34])C(COS(C)(=O)=O)=CC(C3C=CC(OC)=C(F)C=3)=N2)CC1.NCCO>>[CH:1]1([CH2:4][N:5]2[C:10](=[O:11])[C:9]([CH2:12][NH:13][CH2:14][CH2:33][OH:34])=[CH:8][C:7]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([F:23])[CH:16]=3)=[N:6]2)[CH2:3][CH2:2]1
Reactant: CNCc1cc(-c2ccc(OC)c(F)c2)nn(CC2CC2)c1=O
Reactant: COc1ccc(-c2cc(COS(C)(=O)=O)c(=O)n(CC3CC3)n2)cc1F
Solvent: NCCO
Product: COc1ccc(-c2cc(CNCCO)c(=O)n(CC3CC3)n2)cc1F
Yield: 72.1 %

Procedure:
Following the procedure of Example 9 (4), 2-cyclopropylmethyl-6-(3-fluoro-4-methoxyphenyl)-4-methane-sulfonyloxymethyl-2H-pyridazin-3-one and 2-aminoethanol were reacted to yield the title compound as a yellow oil (yield: 72.1%).
Reaction SMILES: [CH2:1]([SH:3])[CH3:2].C(N(CC)CC)C.[Cl:11][C:12]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:13]=1[O:14][C:15]1[CH:16]=[C:17]([S:24]Cl)[C:18]([N+:21]([O-:23])=[O:22])=[CH:19][CH:20]=1>CCOCC>[CH2:1]([S:3][S:24][C:17]1[C:18]([N+:21]([O-:23])=[O:22])=[CH:19][CH:20]=[C:15]([O:14][C:13]2[CH:26]=[CH:27][C:28]([C:30]([F:31])([F:32])[F:33])=[CH:29][C:12]=2[Cl:11])[CH:16]=1)[CH3:2]
Reactant: CCS
Reactant: O=[N+]([O-])c1ccc(Oc2ccc(C(F)(F)F)cc2Cl)cc1SCl
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: CCSSc1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Reaction time: 2 h
Yield: 98 %

Procedure:
1.62 parts by weight of ethanethiol and 2.6 parts by weight of triethylamine were added simultaneously to a solution of 10 parts by weight of 3-(2'-chloro-4'-trifluoromethylphenoxy)-6-nitrobenzenesulfenyl chloride in 100 parts by volume of absolute ether, and stirring was continued for a further 2 hours at room temperature. The reaction mixture was filtered, and the filtrate was extracted with dilute aqueous hydrochloric acid and water, dried over magnesium sulfate, filtered, and evaporated down under reduced pressure. 8 parts by weight (98% yield) of 3-(2'-chloro-4'-trifluoromethylphenoxy)-6-nitrophenyl ethyl disulfide of refractive index nD25 : 1.6067 were obtained (compound No. 4).
Reaction SMILES: [C:1](Cl)(Cl)=[S:2].[CH3:5][C:6]1[NH:10][N:9]=[C:8]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[NH2:18])[N:7]=1.C(N(CC)CC)C>C(Cl)Cl>[CH3:5][C:6]1[NH:10][N:9]=[C:8]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N:18]=[C:1]=[S:2])[N:7]=1
Reactant: Cc1nc(Cc2ccccc2N)n[nH]1
Reactant: S=C(Cl)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1nc(Cc2ccccc2N=C=S)n[nH]1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 5.41 g of thiophosgene in 30 ml of methylene chloride is added dropwise at 0° a solution of 7.5 g of 5-methyl-3-(o-aminobenzyl)-1,2,4-triazole and 8.07 g of triethylamine in 285 ml of methylene chloride over a period of 45 minutes. The mixture is stirred at room temperature overnight, washed first with 10% aqueous potassium bicarbonate, then with water, dried over magnesium sulfate, decolorized with charcoal and evaporated to dryness to give 5-methyl-3-(o-isothiocyanatobenzyl)-1,2,4-triazole; IR 2080 cm-1.
Reaction SMILES: O1CCC[CH2:2]1.[CH3:6][N:7]1[C:16](=[O:17])[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[N:9]=[C:8]1[S-:18].[K+].CI>CN(C)C=O>[CH3:6][N:7]1[C:16](=[O:17])[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[N:9]=[C:8]1[S:18][CH3:2]
Reactant: Cn1c([S-])nc2c(c1=O)CCCC2
Reactant: C1CCOC1
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: CSc1nc2c(c(=O)n1C)CCCC2
Temperature: 25 °C

Procedure:
To a mixture of 10 ml of tetrahydrofuran and 5 ml of dimethylformamide, 340 mg of potassium 3-methyl-4-oxo-3,4,5,6,7,8-hexahydroquinazoline-2-thiolate was added, followed by addition of 210 mg of methyl iodide and an overnight's stirring at room temperature. The solution was concentrated, to which chloroform was added, followed by washing with saturated brine and drying over anhydrous magnesium sulfate. Distilling the solvent off under reduced pressure, 310 mg (quantitative) of 3-methyl-2-methylthio-5,6,7,8-tetrahydro-3H-quinazolin-4-one was obtained.
Reaction SMILES: ClCCl.[CH3:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][CH:14]2[N:23]([C:24]3[CH:25]=[CH:26][C:27]([Cl:30])=[CH:28][N:29]=3)[C:21](=[O:22])[C:16]3[N:17]=[CH:18][CH:19]=[N:20][C:15]2=3)=[O:12])[CH2:7][CH2:6]1.C(OC(=O)C(C(C(OC(=O)C1C=CC=CC=1)=O)O)O)(=O)C1C=CC=CC=1.C(=O)(O)[O-].[Na+]>O>[CH3:4][N:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C@@H:14]2[N:23]([C:24]3[CH:25]=[CH:26][C:27]([Cl:30])=[CH:28][N:29]=3)[C:21](=[O:22])[C:16]3[N:17]=[CH:18][CH:19]=[N:20][C:15]2=3)=[O:12])[CH2:7][CH2:6]1
Reactant: CN1CCN(C(=O)OC2c3nccnc3C(=O)N2c2ccc(Cl)cn2)CC1
Agent: O=C(OC(=O)C(O)C(O)C(=O)OC(=O)c1ccccc1)c1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: CN1CCN(C(=O)O[C@H]2c3nccnc3C(=O)N2c2ccc(Cl)cn2)CC1
Temperature: 36 °C
Reaction time: 0.75 h

Procedure:
Mixture of dichloromethane 300 ml, 6-(5-chloropyridin-2-yl)-5-(4-methylpiperazin-1-yl)-carbonyloxy-7-oxo-5,6-dihydropyrrolo-[3,4-b]-pyrazine D (+)-O,O′-dibenzoyltartaric acid salt 100 g (Chiral purity 97%) and water 250 ml was warmed to 35-37° C. Sodium bicarbonate (28.1 g) was added to the mixture and maintained at 35-37° C. Reaction mixture was stirred for 30-60 min and cooled to 25-30° C. Organic layer was separated. The organic layer was washed with 200 ml water and then with activated carbon (5 g) for 30 min at 20-25° C. Carbon was filtered over hyflo and washed with 100 ml dichloromethane. The filtrate was concentrated to 150 ml at atmospheric pressure. Cyclohexane (600 ml) was added to residual solution at 25-30° C. in 60 min. The slurry was slowly cooled to 0 to 5° C. and stirred for 60 min at same temperature. The solid was filtered and washed with chilled 50 ml Cyclohexane (10° C.) and then dried at 50-60° C. to obtained 44 g Eszopiclone with chiral purity ˜97%
Reaction SMILES: [CH:1]([C:4]1[C:5](=[O:20])[NH:6][C:7](=[O:19])[NH:8][C:9]=1[S:10][C:11]1[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[CH:12]=1)([CH3:3])[CH3:2].[Si]([O:28][CH2:29][CH:30]1[C:34]([CH2:35]Br)=[CH:33][CH2:32][CH2:31]1)(C(C)(C)C)(C)C>>[OH:28][CH2:29][CH:30]1[C:34]([CH2:35][N:8]2[C:9]([S:10][C:11]3[CH:12]=[C:13]([CH3:18])[CH:14]=[C:15]([CH3:17])[CH:16]=3)=[C:4]([CH:1]([CH3:3])[CH3:2])[C:5](=[O:20])[NH:6][C:7]2=[O:19])=[CH:33][CH2:32][CH2:31]1
Reactant: Cc1cc(C)cc(Sc2[nH]c(=O)[nH]c(=O)c2C(C)C)c1
Reactant: CC(C)(C)[Si](C)(C)OCC1CCC=C1CBr
Product: Cc1cc(C)cc(Sc2c(C(C)C)c(=O)[nH]c(=O)n2CC2=CCCC2CO)c1
Yield: 37.6 %

Procedure:
5-Isopropyl-6-(3,5-dimethylphenylthio)-2,4-pyrimidinedione and (5-t-butyldimethylsilyloxymethylcyclopent-1-en-1-yl)methyl bromide were reacted by the same with the example 10 to obtain the titled compound (83 mg).
Reaction SMILES: [Cl:1][C:2]1[C:6]([C:7]#[N:8])=[C:5]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)[S:4][N:3]=1.[OH-:17].[Na+].OO>C(O)C.O>[Cl:1][C:2]1[C:6]([C:7]([NH2:8])=[O:17])=[C:5]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)[S:4][N:3]=1
Reactant: COc1ccc(-c2snc(Cl)c2C#N)cc1
Reactant: [OH-]
Agent: OO
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: COc1ccc(-c2snc(Cl)c2C(N)=O)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Into a 100-mL round-bottom flask, was placed a solution of 3-chloro-5-(4-methoxyphenyl)-1,2-thiazole-4-carbonitrile (3.4 g, 13.56 mmol, 1.00 equiv) in ethanol/H2O (20/10 mL), sodium hydroxide (1 g, 25.00 mmol, 1.84 equiv), H2O2 (10 g). The resulting solution was stirred overnight at 25° C. The resulting mixture was concentrated under vacuum. The reaction was then quenched by the addition of 50 mL of water. The resulting solution was extracted with 3×80 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate. The solids were filtered out. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:2). This resulted in 680 mg (crude) of 3-chloro-5-(4-methoxyphenyl)-1,2-thiazole-4-carboxamide as a yellow solid. Mass spectrum (ESI, m/z): Calcd. for C11H9ClN2O2S, 269.0 (M+H). found 269.0.
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][C:10]=1[C:16]#[CH:17])([CH3:4])([CH3:3])[CH3:2].Br[C:20]1[CH:21]=[N:22][CH:23]=[CH:24][C:25]=1[CH2:26][CH:27]([CH3:29])[CH3:28]>>[C:1]([O:5][C:6](=[O:18])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][C:10]=1[C:16]#[C:17][C:20]1[CH:21]=[N:22][CH:23]=[CH:24][C:25]=1[CH2:26][CH:27]([CH3:29])[CH3:28])([CH3:4])([CH3:3])[CH3:2]
Reactant: C#Cc1cc(Cl)ccc1OCC(=O)OC(C)(C)C
Reactant: CC(C)Cc1ccncc1Br
Product: CC(C)Cc1ccncc1C#Cc1cc(Cl)ccc1OCC(=O)OC(C)(C)C

Procedure:
Following the general method as outlined in Intermediate 20, starting from (4-chloro-2-ethynyl-phenoxy)-acetic acid tert-butyl ester (Intermediate 3) and 3-bromo-4-isobutylpyridine (Intermediate 52), the title compound was obtained as a dark orange sticky solid after purification by preparative HPLC.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13]2[C:14]([O:21][C@@H:22]3[O:48][C@H:47]([CH2:49][O:50][C:51](=[O:56])[C:52]([CH3:55])([CH3:54])[CH3:53])[C@@H:39]([O:40][C:41](=[O:46])[C:42]([CH3:45])([CH3:44])[CH3:43])[C@H:31]([O:32][C:33](=[O:38])[C:34]([CH3:37])([CH3:36])[CH3:35])[C@H:23]3[O:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])=[N:15][NH:16][C:17]=2[CH:18]([CH3:20])[CH3:19])=[C:8]([O:57][CH:58]2[CH2:63][CH2:62][O:61][CH2:60][CH2:59]2)[CH:7]=1.[NH2:64][C:65]([CH3:70])([CH3:69])[C:66]([NH2:68])=[O:67].C(NCCC(N)=O)C1C=CC=CC=1>>[C:66]([C:65]([NH:64][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13]2[C:14]([O:21][C@@H:22]3[O:48][C@H:47]([CH2:49][O:50][C:51](=[O:56])[C:52]([CH3:55])([CH3:54])[CH3:53])[C@@H:39]([O:40][C:41](=[O:46])[C:42]([CH3:45])([CH3:44])[CH3:43])[C@H:31]([O:32][C:33](=[O:38])[C:34]([CH3:37])([CH3:36])[CH3:35])[C@H:23]3[O:24][C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])=[N:15][NH:16][C:17]=2[CH:18]([CH3:20])[CH3:19])=[C:8]([O:57][CH:58]2[CH2:63][CH2:62][O:61][CH2:60][CH2:59]2)[CH:7]=1)([CH3:70])[CH3:69])(=[O:67])[NH2:68]
Reactant: CC(C)c1[nH]nc(O[C@@H]2O[C@H](COC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@H](OC(=O)C(C)(C)C)[C@H]2OC(=O)C(C)(C)C)c1Cc1ccc(OCCCCl)cc1OC1CCOCC1
Reactant: CC(C)(N)C(N)=O
Agent: NC(=O)CCNCc1ccccc1
Product: CC(C)c1[nH]nc(O[C@@H]2O[C@H](COC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@H](OC(=O)C(C)(C)C)[C@H]2OC(=O)C(C)(C)C)c1Cc1ccc(OCCCNC(C)(C)C(N)=O)cc1OC1CCOCC1

Procedure:
The title compound was prepared in a similar manner to that described in Example 98 using 4-{[4-(3-chloropropoxy)-2-(tetrahydro-4H-pyran-4-yloxy)phenyl]methyl}-5-isopropyl-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-pyrazole and 2-amino-2-methylpropionamide instead of 4-{[4-(3-chloropropoxy)-2-methylphenyl]methyl}-5-isopropyl-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-pyrazole and 3-benzylaminopropionamide, respectively.
Reaction SMILES: [CH3:1][S:2][C:3]1[C:4](Cl)=[N:5][C:6]([Cl:10])=[N:7][C:8]=1[Cl:9].C(O)=O.[S-:15][C:16]#[N:17].[K+]>O>[Cl:10][C:6]1[N:7]=[C:8]([Cl:9])[C:3]([S:2][CH3:1])=[C:4]([S:15][C:16]#[N:17])[N:5]=1
Reactant: N#C[S-]
Reactant: CSc1c(Cl)nc(Cl)nc1Cl
Agent: [K+]
Solvent: O
Solvent: O=CO
Product: CSc1c(Cl)nc(Cl)nc1SC#N
Temperature: 25 °C
Yield: 92.8 %

Procedure:
In a 50-ml four-necked flask equipped with a thermometer, reflux condenser and stirrer, were charged 2.30 g (0.010 mole) of 5-methylthio-2,4,6-trichloropyrimidine and 15 ml of formic acid. While stirring the contents at room temperature, 1.07 g (0.011 mole) of potassium thiocyanate was added. Then, the resulting mixture was heated and was then stirred at 50° C. for 1 hour. After cooling the reaction mixture, it was poured into a great deal of water. The precipitated solid was collected by filtration and dried to obtain 2.34 g of crude crystals (yield: 92.9%). A portion of the crude crystals was recrystallized from ethyl acetate, thereby obtaining a purified product. m.p. 143°-144.5° C.
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5]/[CH:6]=[CH:7]\[CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]([OH:20])=[O:19].C(O)(=[O:39])CCCCCCCCCCCCCCCCC>>[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][C@H:6]1[O:39][C@H:7]1[CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]([OH:20])=[O:19]
Reactant: CCCCCCCCCCCCCCCCCC(=O)O
Reactant: CCCCC/C=C\C/C=C\CCCCCCCC(=O)O
Product: CCCCC[C@H]1O[C@H]1C/C=C\CCCCCCCC(=O)O

Procedure:
Vernolia oil undergoes saponification and acification followed by cold temperature (-20° C.) crystallization to yield a methylated product comprised of vernolic, palmitic, oleic, linoleic and stearic acid. The vernolic acid is isolated and further purified through a series of low temperature recrystalizations. The purified vernolic acid, ##STR1## is then hydrogenated to yield 12,13-epoxystearic acid, having the formula: ##STR2## The 12,13-epoxystearic acid is then oxidized to yield 12-oxododecanoic acid, ##STR3## By reacting the 12-oxododecanoic acid with hydroxylamine, 12-oxododecanoic acid oxime ##STR4## is formed. The Nylon-12 monomer, 12-aminododecanoic acid:
Reaction SMILES: OC1C=CC=C2C=1C(C#N)=CN2.[O:13]1[CH2:28][CH:14]1[CH2:15][O:16][C:17]1[CH:25]=[CH:24][CH:23]=[C:22]2[C:18]=1[C:19]([C:26]#[N:27])=[CH:20][NH:21]2.[CH2:29]([O:32][C:33]1[CH:42]=[CH:41][CH:40]=[CH:39][C:34]=1[O:35][CH2:36][CH2:37][NH2:38])[CH:30]=[CH2:31]>>[OH:13][CH:14]([CH2:28][NH:38][CH2:37][CH2:36][O:35][C:34]1[CH:39]=[CH:40][CH:41]=[CH:42][C:33]=1[O:32][CH2:29][CH:30]=[CH2:31])[CH2:15][O:16][C:17]1[CH:25]=[CH:24][CH:23]=[C:22]2[C:18]=1[C:19]([C:26]#[N:27])=[CH:20][NH:21]2
Reactant: N#Cc1c[nH]c2cccc(OCC3CO3)c12
Reactant: C=CCOc1ccccc1OCCN
Agent: N#Cc1c[nH]c2cccc(O)c12
Product: C=CCOc1ccccc1OCCNCC(O)COc1cccc2[nH]cc(C#N)c12

Procedure:
Compounds of general formula (I) can be further reacted by known methods, for example by saponification and decarboxylation to give 4-hydroxyindole or 4-hydroxy-6-methylindole, or by aminolysis and dehydration to give 4-hydroxy-3-cyanoindole or 4-hydroxy-3-cyano-6-methyl-indole, which, by reaction with epichlorohydrin and alkylamino derivatives, give aminopropanols with useful pharmacological properties (see Federal Republic of Germany Patent Specification Nos. 25 08 251; 27 37 630; 29 05 877 and 30 30 047). However, compounds of general formula (I) can also be reacted to give aminopropanol derivatives directly, whereafter the compounds obtained are subsequently changed. Thus, for example, from 4-hydroxy-3-cyanoindole (see Federal Republic of German Patent Specification No. 30 29 980) there is obtained 4-(2,3-epoxypropoxy)-3-cyanoindole which is reacted with 2-(2-allyloxyphenoxy)-ethylamine to give the pharmacologically effective 4-{2-hydroxy-3-[2-(2-allyloxyphenoxy)-ethylamino]-propoxy}-3-cyanoindole (see Example 3h) of Federal Republic of German Patent Specification No. 30 30 047).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:33]=[CH:32][C:7]2[N:8]([S:18]([C:21]3[CH:26]=[CH:25][C:24]([C:27](O)=[O:28])=[CH:23][C:22]=3[O:30][CH3:31])(=[O:20])=[O:19])[C:9](=[O:17])[N:10]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]3)[C:6]=2[CH:5]=1)[CH3:2].[NH2:34][C:35]([CH3:39])([CH3:38])[CH2:36][OH:37].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH:11]1([N:10]2[C:6]3[CH:5]=[C:4]([O:3][CH2:1][CH3:2])[CH:33]=[CH:32][C:7]=3[N:8]([S:18]([C:21]3[CH:26]=[CH:25][C:24]([C:27](=[O:28])[NH:34][C:35]([CH3:39])([CH3:38])[CH2:36][OH:37])=[CH:23][C:22]=3[O:30][CH3:31])(=[O:19])=[O:20])[C:9]2=[O:17])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1
Reactant: CCOc1ccc2c(c1)n(C1CCCCC1)c(=O)n2S(=O)(=O)c1ccc(C(=O)O)cc1OC
Reactant: CC(C)(N)CO
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCOc1ccc2c(c1)n(C1CCCCC1)c(=O)n2S(=O)(=O)c1ccc(C(=O)NC(C)(C)CO)cc1OC
Yield: 20.9 %

Procedure:
This compound is prepared by the procedure described in EXAMPLE 100 starting from 0.5 g of the compound obtained in EXAMPLE 13, 0.5 g of 2-amino-2- methylpropan-1-ol, 0.6 g of BOP, 1 ml of DIPEA and 20 ml of DCM. It is chromatographed on silica using a DCM/MeOH mixture (99/1; v/v) as the eluent to give 0.12 g of the expected product in the form of white crystals. M.p.=218° C.