Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CS[C:3]1[N:8]=[C:7]([C:9]2[CH:10]=[C:11]([C:26]#[N:27])[C:12](=[O:25])[NH:13][C:14]=2[C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)[CH:6]=[CH:5][N:4]=1.O[O:29][S:30]([O-:32])=O.[K+].[CH3:34]C(C)=O>CO.O>[CH3:34][S:30]([C:3]1[N:8]=[C:7]([C:9]2[CH:10]=[C:11]([C:26]#[N:27])[C:12](=[O:25])[NH:13][C:14]=2[C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)[CH:6]=[CH:5][N:4]=1)(=[O:32])=[O:29]
Reactant: CSc1nccc(-c2cc(C#N)c(=O)[nH]c2-c2cccc(C(F)(F)F)c2)n1
Reactant: CC(C)=O
Reactant: O=S([O-])OO
Agent: [K+]
Solvent: CO
Solvent: O
Product: CS(=O)(=O)c1nccc(-c2cc(C#N)c(=O)[nH]c2-c2cccc(C(F)(F)F)c2)n1
Reaction time: 0.5 h
Yield: 57 %

Procedure:
To a solution of 5-(2-methylsulfanylpyrimidin-4-yl)-2-oxo-6-(3-trifluoromethylphenyl)-1,2-dihydropyridine-3-carbonitrile (0.40 gm, 0.00104 mole) in methanol (40 mL) was slowly added a solution of Oxone (1.90 gm, 0.0030 mole) in water (40 mL). The mixture was allowed to stir for 30 minutes and then acetone (20 mL) added. The reaction was then stirred for 48 hrs, and then concentrated to remove the acetone and methanol. The resulting mixture was dissolved in ethyl acetate and water and the pH adjusted to 7.0 with 10% aqueous sodium hydrogen sulfate. The ethyl acetate layer was removed and aqueous layer washed with ethyl acetate. The ethyl acetate extracts were dried over sodium sulfate and concentrated to give 0.25 gm (57%) of the title compound.
Reaction SMILES: C1(SC2C3C=CC=CC=3SC=2I)C=CC=CC=1.[N+:18]([C:21]1[CH:26]=[CH:25][C:24]([S:27][C:28]2[C:29]3[CH:37]=[CH:36][CH:35]=[CH:34][C:30]=3[S:31][C:32]=2I)=[CH:23][CH:22]=1)([O-:20])=[O:19]>>[N+:18]([C:21]1[CH:26]=[CH:25][C:24]2[S:27][C:28]3[C:29]4[CH:37]=[CH:36][CH:35]=[CH:34][C:30]=4[S:31][C:32]=3[C:23]=2[CH:22]=1)([O-:20])=[O:19]
Reactant: O=[N+]([O-])c1ccc(Sc2c(I)sc3ccccc23)cc1
Agent: Ic1sc2ccccc2c1Sc1ccccc1
Product: O=[N+]([O-])c1ccc2sc3c4ccccc4sc3c2c1
Yield: 81 %

Procedure:
Except that 3-(phenylsulfenyl)-2-iodobenzo[b]thiophene was replaced with 3-((p-nitrophenyl)sulfenyl)-2-iodobenzo[b]thiophene, the reaction was implemented in the same way as in Example 3. Purification was implemented by column chromatography (silica gel, CHCl3, Rf: 0.9), so that a yellow solid was produced (yield: 81%).
Reaction SMILES: Cl[C:2]([C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=1)([C:25]1[N:26]([CH3:30])[CH:27]=[N:28][CH:29]=1)[C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:13][CH:14]1[CH2:16][CH2:15]1)[C:8](=[O:17])[CH:7]=[C:6]2[C:18]1[CH:23]=[CH:22][CH:21]=[C:20](Cl)[CH:19]=1.[ClH:38].[NH4+:39]>C1COCC1>[NH2:39][C:2]([C:31]1[CH:32]=[CH:33][C:34]([Cl:37])=[CH:35][CH:36]=1)([C:25]1[N:26]([CH3:30])[CH:27]=[N:28][CH:29]=1)[C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:13][CH:14]1[CH2:16][CH2:15]1)[C:8](=[O:17])[CH:7]=[C:6]2[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([Cl:38])[CH:19]=1
Reactant: Cn1cncc1C(Cl)(c1ccc(Cl)cc1)c1ccc2c(c1)c(-c1cccc(Cl)c1)cc(=O)n2CC1CC1
Reactant: [NH4+]
Reactant: Cl
Solvent: C1CCOC1
Product: Cn1cncc1C(N)(c1ccc(Cl)cc1)c1ccc2c(c1)c(-c1cccc(Cl)c1)cc(=O)n2CC1CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 79 %

Procedure:
A solution of 6-[Chloro-(4-chloro-phenyl)-(3-methyl-3H-imidazol-4-yl)-methyl]-4-(3-chloro-phenyl)-1-cyclopropylmethyl-1H-quinolin-2-one; hydrochloride (2.15 g, 3.7 mmol) in THF (40 mL) was treated with ammonium, stirred at ambient temperature for 2 hours, and concentrated in vacuo. The reaction mixture was diluted with ethyl acetate/H2O (1:1, 200 mL) and extracted with ethyl acetate (3×100 mL). The combined organic extracts were washed with brine (200 mL), dried (MgSO4), filtered, and concentrated in vacuo to give a crude yellow foam. Purification by flash column chromatography (silica, EtOAc:MeOH:NEt3 9:1:.01) gave 6-[Amino-(4-chloro-phenyl)-(3-methyl-3H-imidazol-4-yl)-methyl]-4-(3-chloro-phenyl)-1-cyclopropylmethyl-1H-quinolin-2-one (1.54 g, 79%) as a yellow foam.
Reaction SMILES: [H-].[Na+].[CH2:3]([O:19][C:20](=[O:57])[CH:21]([CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])[C:22]([O:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])=[O:23])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].I[CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH3:74].Cl>O1CCCC1.CN(C)C=O.O>[CH2:3]([O:19][C:20](=[O:57])[C:21]([CH2:74][CH2:73][CH2:72][CH2:71][CH2:70][CH2:69][CH2:68][CH2:67][CH2:66][CH2:65][CH2:64][CH2:63][CH2:62][CH2:61][CH2:60][CH3:59])([CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])[C:22]([O:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])=[O:23])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCCCCCCCCCCI
Reactant: CCCCCCCCCCCCCCCCOC(=O)C(CCCCCCCCCCCCCCCC)C(=O)OCCCCCCCCCCCCCCCC
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Solvent: O
Product: CCCCCCCCCCCCCCCCOC(=O)C(CCCCCCCCCCCCCCCC)(CCCCCCCCCCCCCCCC)C(=O)OCCCCCCCCCCCCCCCC
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 66 %

Procedure:
Sodium hydride (72 mg, 3 mmol) was added in portions to a cooled (ice/water) solution of 2-hexadecylmalonic acid dihexadecyl ester (2.33 g, 3 mmol) in tetrahydrofuran (45 ml) under an argon atmosphere and the resulting mixture was stirred at ambient temperature for 30 minutes. The solvent was evaporated and the solid residue was redissolved in N,N-dimethylformamide (45 ml). A solution of 1-iodohexadecane (1.06 g, 3 mmol) in N,N-dimethylformamide (20 ml) was added and stirring was continued at room temperature for 24 hours. Water (75 ml) was added to the reaction mixture after the pH had been adjusted to about 5 with 2N HCl. The mixture was extracted with chloroform (3×75 ml) and the chloroform phase was washed with water (3×75 ml). The organic phase was dried with magnesium sulphate and the solvent was removed at reduced pressure. The residue was purified by flash chromatography (silicagel 60, chloroform/hexane). Yield: 66%. 1H-NMR (300 MHz, CDCl3): δ 0.88(t,12H), 1.26(m,108H), 1.60(m,4H), 1.85(m,4H), 4.09(t,4H). FAB-MS: 1024 (M+Na).
Reaction SMILES: C(OC(=O)[N:7]([S:13]([C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]2[CH:24]=[N:25][C:26](Cl)=[CH:27][C:28]=2[C:29]2[CH:30]=[N:31][CH:32]=[N:33][CH:34]=2)=[C:18]([C:36]#[N:37])[CH:17]=1)(=[O:15])=[O:14])[C:8]1[N:9]=[CH:10][S:11][CH:12]=1)(C)(C)C.[F:39][C:40]1[CH:41]=[C:42](B(O)O)[CH:43]=[CH:44][CH:45]=1.C([O-])([O-])=O.[Na+].[Na+].O>CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:36]([C:18]1[CH:17]=[C:16]([S:13]([NH:7][C:8]2[N:9]=[CH:10][S:11][CH:12]=2)(=[O:14])=[O:15])[CH:21]=[CH:20][C:19]=1[O:22][C:23]1[CH:24]=[N:25][C:26]([C:44]2[CH:43]=[CH:42][CH:41]=[C:40]([F:39])[CH:45]=2)=[CH:27][C:28]=1[C:29]1[CH:34]=[N:33][CH:32]=[N:31][CH:30]=1)#[N:37]
Reactant: CC(C)(C)OC(=O)N(c1cscn1)S(=O)(=O)c1ccc(Oc2cnc(Cl)cc2-c2cncnc2)c(C#N)c1
Reactant: OB(O)c1cccc(F)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: N#Cc1cc(S(=O)(=O)Nc2cscn2)ccc1Oc1cnc(-c2cccc(F)c2)cc1-c1cncnc1
Reaction time: 0.17 h
Yield: 753.9 %

Procedure:
10 mg (0.02 mmol) of tert-butyl((4-((6-chloro-4-(pyrimidin-5-yl)pyridin-3-yl)oxy)-3-cyanophenyl)sulfonyl)(thiazol-4-yl)carbamate was dissolved in 3 mL of N,N-dimethylformamide, and 3.7 mg (0.03 mmol) of (3-fluorophenyl)boronic acid was added thereto, and then 2 mg (10 mol %) of Pd(PPh3)4, 5.5 mg (0.05 mmol) of Na2CO3, and 1 mL of H2O were added thereto. After reacting with microwave reactor at 120° C. for 10 minutes, the solvent was removed, and the remaining material was diluted with ethyl acetate and the organic layer was separated, and washed with saturated sodium chloride. The organic layer was collected, dried with magnesium sulfate to remove water, and concentrated under reduced pressure, and the residue was purified by column chromatography (developing solvent, hexane:ethyl acetate=3:1) to obtain 80 mg (70% yield) of the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH2:5][CH2:6][C:7]2=O.[NH2:13][OH:14].Cl.C([O-])(=O)C.[Na+]>CO>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH2:5][CH2:6][C:7]2=[N:13][OH:14]
Reactant: COc1cccc2c1CCC2=O
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: COc1cccc2c1CCC2=NO
Temperature: 25 °C
Reaction time: 8 h
Yield: 98.8 %

Procedure:
To a solution of 4-methoxy-2,3-dihydro-1H-inden-1-one (1.0 g, 1.0 eq.) in 25 ml MeOH was added NH2OH.HCl (0.493 g, 1.15 eq.) and sodium acetate (0.597 g, 1.18 eq.). The resulting mixture was stirred at room temperature overnight. The reaction mixture was diluted with 100 ml ice-water. The white precipitate was collected by filtration, washed with 3×20 ml water and dried in vacuo to afford 1.08 g (yield 99%) 4-methoxy-2,3-dihydro-1H-inden-1-one oxime which was used to next step without further purification.
Reaction SMILES: [CH:1]1[CH:13]=[CH:12][C:11]2[C:14](=[O:17])[CH2:15][CH2:16][N:9]3[C:10]=2[C:2]=1[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:8]=13.C([Li])CCC.[CH:23](=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[Cl-].[NH4+]>O1CCCC1>[C:23]([C:15]1[C:14](=[O:17])[C:11]2[CH:12]=[CH:13][CH:1]=[C:2]3[C:10]=2[N:9]([CH:16]=1)[C:8]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]3=1)(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: O=C1CCn2c3ccccc3c3cccc1c32
Reactant: O=Cc1ccccc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Product: O=C(c1ccccc1)c1cn2c3ccccc3c3cccc(c1=O)c32
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 14 %

Procedure:
5,6-dihydro-4H-pyrido[3,2,1-jk]carbazole-4-one (4 g) prepared by the procedure described in J.O.C., 24, 324 (1959) was dissolved in anhydrous tetrahydrofuran (160 ml). n-butyl lithium (solution in hexane, 15 ml) was added dropwise to the solution cooled in an acetone-dry ice bath, and the mixture was stirred for 30 minutes. Benzaldehyde (2 ml) dissolved in anhydrous tetrahydrofuran (80 ml) was gradually added dropwise to the solution cooled in an acetone-dry ice bath, and the mixture was stirred for 90 minutes. Saturated aqueous solution of ammonium chloride of an adequate amount was added to the reaction mixture, and the mixture was heated to room temperature, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel flash column chromatography (eluent: hexane/ethyl acetate=5:1) to obtain the title compound (852 mg, 14%).
Reaction SMILES: C(N(C(C)C)C(C)C)C.[F:10][C@H:11]1[CH2:28][C@@:26]2([CH3:27])[C@@H:22]([CH2:23][CH2:24][C@@H:25]2[OH:29])[C@H:21]2[C@H:12]1[C:13]1[CH:14]=[CH:15][C:16]([OH:56])=[CH:17][C:18]=1[CH2:19][C@H:20]2[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][N:35]([CH3:55])[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][C:42]([F:54])([F:53])[C:43]([F:52])([F:51])[C:44]([F:50])([F:49])[C:45]([F:48])([F:47])[F:46]>CS(C)=O.C(OCC)(=O)C>[F:10][C@H:11]1[CH2:28][C@@:26]2([CH3:27])[C@@H:22]([CH2:23][CH2:24][C:25]2=[O:29])[C@H:21]2[C@H:12]1[C:13]1[CH:14]=[CH:15][C:16]([OH:56])=[CH:17][C:18]=1[CH2:19][C@H:20]2[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][N:35]([CH3:55])[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][C:42]([F:53])([F:54])[C:43]([F:51])([F:52])[C:44]([F:49])([F:50])[C:45]([F:46])([F:47])[F:48]
Reactant: CN(CCCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)F)CCCCC[C@@H]1Cc2cc(O)ccc2[C@@H]2[C@@H]1[C@@H]1CC[C@H](O)[C@@]1(C)C[C@@H]2F
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Product: CN(CCCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)F)CCCCC[C@@H]1Cc2cc(O)ccc2[C@@H]2[C@@H]1[C@@H]1CCC(=O)[C@@]1(C)C[C@@H]2F
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
1.5 ml of ethyldiisopropylamine is added in drops at 10° C. to a solution of 1.23 g of pyridine sulfur trioxide complex in 10 ml of dried dimethyl sulfoxide. Then, 1.72 g of 11β-fluoro-7α-{5-[methyl(7,7,8,8,9,9,10,10,10-nonafluorodecyl)amino]pentyl}-estra-1,3,5(10)-triene-3,17β-diol (compound No. Z9) as well as another 10 ml of dried dimethyl sulfoxide are added and stirred for 30 minutes at room temperature. Then, it is diluted with ethyl acetate, washed with saturated sodium bicarbonate solution, water and sodium chloride solution, dried on sodium sulfate, evaporated to the dry state in a vacuum and chromatographed on silica gel with dichloromethane/methanol. 11β-Fluoro-7α-{5-[methyl(7,7,8,8,9,9,10,10,10-nonafluorodecyl)amino]pentyl}estra-1,3,5(10)-trien-3-ol-17-one, [α]D=+58.2°, in chloroform, is obtained.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]2[C:8]3([CH2:18][O:19][C:4]=2[CH:3]=1)[C:16]1[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=1)[NH:10][C:9]3=[O:17].N1C=CN=C1.[CH:25]([Si:28](Cl)([CH:32]([CH3:34])[CH3:33])[CH:29]([CH3:31])[CH3:30])([CH3:27])[CH3:26]>CN(C)C=O>[CH3:26][CH:25]([Si:28]([CH:32]([CH3:34])[CH3:33])([CH:29]([CH3:31])[CH3:30])[O:1][C:2]1[CH:7]=[CH:6][C:5]2[C:8]3([CH2:18][O:19][C:4]=2[CH:3]=1)[C:16]1[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=1)[NH:10][C:9]3=[O:17])[CH3:27]
Reactant: O=C1Nc2ccccc2C12COc1cc(O)ccc12
Reactant: CC(C)[Si](Cl)(C(C)C)C(C)C
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(C)[Si](Oc1ccc2c(c1)OCC21C(=O)Nc2ccccc21)(C(C)C)C(C)C
Temperature: 25 °C
Reaction time: 16 h
Yield: 55.4 %

Procedure:
To a solution of 6-hydroxyspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one (3.0 g, 11.8 mmol) in anhydrous N,N-dimethylformamide (30 mL) under nitrogen were added imidazole (1.97 g, 28.9 mmol) and triisopropylsilyl chloride (6.03 mL, 28.5 mmol). The reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was concentrated in vacuo to dryness. The residue was extracted twice with ethyl acetate (50 mL), the combined organic phases were dried over sodium sulfate, and the filtrate was concentrated and purified by flash chromatography with 30% ethyl acetate in hexanes to give 6-{[tris(1-methylethyl)silyl]oxy}spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one (2.68 g, 69% yield) as colorless solid: 1H NMR (300 MHz, CDCl3) δ 8.48-8.08 (br, 1H), 7.29-6.90 (m, 4H), 6.10 (d, J=8.1 Hz, 1H), 6.50 (d, J=2.1 Hz, 1H), 6.35 (dd, J=8.1, 2.1 Hz, 1H), 4.96 (d, J=9.0 Hz, 1H), 4.69 (d, J=9.0 Hz, 1H), 1.34-0.98 (m, 21H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:11][C:12]#[N:13])(=[O:10])=[O:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[C:20]([C:22]1[CH:23]=[C:24]([N:28]=[C:29]=[S:30])[CH:25]=[CH:26][CH:27]=1)#[N:21].[CH3:31]I>CC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([C:11](=[C:29]([NH:28][C:24]2[CH:25]=[CH:26][CH:27]=[C:22]([C:20]#[N:21])[CH:23]=2)[S:30][CH3:31])[C:12]#[N:13])(=[O:9])=[O:10])=[CH:6][CH:7]=1
Reactant: N#Cc1cccc(N=C=S)c1
Reactant: N#CCS(=O)(=O)c1ccc(Cl)cc1
Reactant: CI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CSC(Nc1cccc(C#N)c1)=C(C#N)S(=O)(=O)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 96.2 %

Procedure:
A solution of 4-chlorophenylsulfonylacetonitrile (1.0 g, 4.64 mmol) in dry acetone (10 ml) was stirred while dry potassium carbonate (1.28 g, 9.28 mmol) and 3-cyanophenyl isothiocyanate (0.78 g, 4.87 mmol) were added. The resulting mixture was stirred at room temperature under nitrogen for 20 h. Excess of potassium carbonate was filtered off, methyl iodide (0.859 ml, 13.9 mmol) was added to the filtrate, and stirring was continued for 3 h. The mixture was evaporated and the residue was dissolved in dichloromethane and extracted with water and brine. The organic phase was dried over magnesium sulphate, filtered and evaporated to afford 1.74 g (96%) of the title compound as golden brown crystals. Mp 168-170° C. 1H NMR (200 MHz, CDCl3): δ=2.22 (s, 3H), 7.50-7.68 (m, 6H), 7.84-7.93(m, 2H), 9.89 (br s, 1H).
Reaction SMILES: [C:1]([O:7][CH:8]([C:16]1[S:17][CH:18]=[CH:19][CH:20]=1)[CH2:9][N:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1)(=[O:6])[CH2:2][C:3]([CH3:5])=O.[N+:21]([C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)[CH:27]=O)([O-:23])=[O:22].[NH2:32]/[C:33](/[CH3:39])=[CH:34]\[C:35]([O:37][CH3:38])=[O:36]>C(O)(C)C>[S:17]1[CH:18]=[CH:19][CH:20]=[C:16]1[CH:8]([O:7][C:1]([C:2]1[CH:27]([C:26]2[CH:29]=[CH:30][CH:31]=[C:24]([N+:21]([O-:23])=[O:22])[CH:25]=2)[C:34]([C:35]([O:37][CH3:38])=[O:36])=[C:33]([CH3:39])[NH:32][C:3]=1[CH3:5])=[O:6])[CH2:9][N:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1
Reactant: CC(=O)CC(=O)OC(CN1CCCCC1)c1cccs1
Reactant: O=Cc1cccc([N+](=O)[O-])c1
Reactant: COC(=O)/C=C(/C)N
Solvent: CC(C)O
Product: COC(=O)C1=C(C)NC(C)=C(C(=O)OC(CN2CCCCC2)c2cccs2)C1c1cccc([N+](=O)[O-])c1

Procedure:
In 350 ml of isopropanol are dissolved 30.9 g of 1-(2-thienyl)-2-piperidinoethyl acetoacetate, 15.4 g of m-nitrobenzaldehyde and 11.7 g of methyl β-aminocrotonate, and the mixture is refluxed under heating for 20 hours. The reaction mixture is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel (eluent:chloroform:methanol=10:1.2 (by volume)). The firstly eluted solution is concentrated and recrystallized from ethanol to give 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid-3-methylester-5-[1-(2-thienyl)-2-piperidinoethyl]ester as crystals melting at 179° C.-181° C. This is α-diastereoisomer and the hydrochloride therefore melts at 215° C.-218° C. (decomposition). The lastly eluted solution is concentrated and recrystallized from ethanol as crystals melting at 128° C.-134° C. The hydrochloride thereof melts at 188° C.-190° C. (decomposition).
Reaction SMILES: [CH:1](/[C@H:6]1[CH2:11][CH2:10][C@H:9]([C:12]([OH:14])=[O:13])[CH2:8][CH2:7]1)=[CH:2]\[CH2:3][CH2:4][CH3:5].[CH2:15]([O:17][C:18]1[CH:23]=[CH:22][C:21](O)=[CH:20][CH:19]=1)[CH3:16].C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C1C=CN=CC=1.C(Cl)Cl.C(OCC)C>[CH2:15]([O:17][C:18]1[CH:23]=[CH:22][C:21]([O:13][C:12]([C@H:9]2[CH2:8][CH2:7][C@H:6](/[CH:1]=[CH:2]/[CH2:3][CH2:4][CH3:5])[CH2:11][CH2:10]2)=[O:14])=[CH:20][CH:19]=1)[CH3:16]
Reactant: CCOc1ccc(O)cc1
Reactant: CCC/C=C/[C@H]1CC[C@H](C(=O)O)CC1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: CCOCC
Solvent: ClCCl
Product: CCC/C=C/[C@H]1CC[C@H](C(=O)Oc2ccc(OCC)cc2)CC1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
A mixture of 800 mg of trans-4-(trans-1-pentenyl)cyclohexanecarboxylic acid, 675.64 mg of p-ethoxyphenol, 1.01 g of dicyclohexylcarbodiimide and 49.79 mg of 4-(dimethylamino)pyridine was suspended in 14.5 ml of methylene chloride and stirred at room temperature for 20 hours. The mixture was subsequently diluted with diethyl ether, the precipitated urea was filtered off and the filtrate was concentrated. The residue was taken up in hexane and washed with dilute hydrochloric acid, sodium hydrogen carbonate solution and water. The aqueous phases were back-extracted twice with hexane. The organic phases were dried over magnesium sulphate and evaporated. Low-pressure chromatography of the resulting residue on silica gel with ethyl acetate/petroleum ether (vol. 3:97) gave 1.080 g (83.8%) of trans-4-(trans-1-pentenyl)cyclohexanecarboxylic acid p-ethoxyphenyl ester. After recrystallization from 40 ml of hexane, there were finally obtained 880 mg of product in the form of transparent crystals; m.p. (C-N) 57.2° C., cl.p. (N-I) 93.1° C.
Reaction SMILES: [H-].[Na+].[O:3]=[C:4]1[NH:13][CH:12]([C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][C:15]=2[CH3:22])[C:11]2[C:10](=[O:23])[CH2:9][CH2:8][CH2:7][C:6]=2[N:5]1[C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=1.[C:34](#N)C>CN(C)C=O>[CH3:22][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][C:14]=1[CH:12]1[C:11]2[C:10](=[O:23])[CH2:9][CH2:8][CH2:7][C:6]=2[N:5]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:31])[F:32])[CH:25]=2)[C:4](=[O:3])[N:13]1[CH3:34])[C:18]#[N:19]
Reactant: Cc1cc(C#N)ccc1C1NC(=O)N(c2cccc(C(F)(F)F)c2)C2=C1C(=O)CCC2
Reactant: CC#N
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1cc(C#N)ccc1C1C2=C(CCCC2=O)N(c2cccc(C(F)(F)F)c2)C(=O)N1C
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
Sodium hydride (60% in mineral oil, 6 mg, 0.16 mmol) is added to a solution of 4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-3-methylbenzonitrile (example 55, 60 mg, 0.13 mmol) in acetonitrile (3 mL), and the mixture is stirred at room temperature for 20 min. Methyl idodide (16 μL, 0.26 mmol) is added, and the mixture is stirred over night, diluted with N,N-dimethylformamide (1 mL) and purified by preparative HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 13 mg; ESI mass spectrum [M+H]+=440; Retention time HPLC: 0.65 min (X012_S01).
Reaction SMILES: [CH:1]1[C:9]2[C:8]3[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=3[S:6][C:5]=2[C:4]([C:14]2[CH:19]=[C:18]([CH3:20])[CH:17]=[C:16]([C:21]3[C:26]4[S:27][C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=5[C:25]=4[CH:24]=[CH:23][CH:22]=3)[C:15]=2[OH:34])=[CH:3][CH:2]=1.C(Cl)Cl.C(N(CC)CC)C.[C:45](Cl)(=[O:48])[CH:46]=[CH2:47]>O>[C:45]([O:34][C:15]1[C:16]([C:21]2[C:26]3[S:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[C:25]=3[CH:24]=[CH:23][CH:22]=2)=[CH:17][C:18]([CH3:20])=[CH:19][C:14]=1[C:4]1[C:5]2[S:6][C:7]3[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=3[C:9]=2[CH:1]=[CH:2][CH:3]=1)(=[O:48])[CH:46]=[CH2:47]
Reactant: C=CC(=O)Cl
Reactant: Cc1cc(-c2cccc3c2sc2ccccc23)c(O)c(-c2cccc3c2sc2ccccc23)c1
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: C=CC(=O)Oc1c(-c2cccc3c2sc2ccccc23)cc(C)cc1-c1cccc2c1sc1ccccc12
Reaction time: 0.5 h
Yield: 57 %

Procedure:
1.35 g of the thus obtained 2,6-bis(4-dibenzothiophenyl)-4-methylphenol is placed in a round bottom flask; 20 mL of methylene chloride is added; after ice cooling the flask, 0.33 g of triethylamine is added; 0.30 g of acryloyl chloride is then added dropwise; after adding the whole, the temperature is returned to room temperature; and the mixture is stirred for 30 minutes. 10 mL of water is added; the mixture is vigorously stirred; an aqueous layer is then removed; the aqueous layer is washed with methylene chloride and then gathered with the original methylene chloride solution; and the mixture is dried upon application of magnesium sulfate. The resulting mixture is concentrated by filtration with a filter paper; and the concentrate is separated by a silica gel column (eluate: hexane/ethyl acetate=80/20 (volume ratio)) to concentrate a component having an Rf of 0.42, thereby obtaining 0.85 g (yield: 57%) of the foregoing white solid. 1H NMR (CDCl3, 400 MHz): δ (ppm) 2.57 (s, 3H), 5.41 (dd=1.2 & 10.4 Hz, 1H), 5.64 (dd=10.4 & 17.2 Hz, 1H), 5.97 (dd=1.2 & 17.2 Hz, 1H), 7.49 to 7.59 (m, 10H), 7.90 (m, 2H), 8.16 to 8.21 (m, 4H)