Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [S:1]([NH2:5])([NH2:4])(=[O:3])=[O:2].N[CH2:7][C:8](N)([CH3:10])[CH3:9]>N1C=CC=CC=1>[CH3:7][C:8]1([CH3:10])[CH2:9][NH:5][S:1](=[O:3])(=[O:2])[NH:4]1
Reactant: NS(N)(=O)=O
Reactant: CC(C)(N)CN
Solvent: c1ccncc1
Product: CC1(C)CNS(=O)(=O)N1
Yield: 84.9 %

Procedure:
To a refluxing solution of sulfamide (27.25 g, 283 mmol) in anhydrous pyridine (300 ml) was added dropwise 1,2-diamino-2-methylpropane (25 g, 283 mmol) over 2 hours. The resulting mixture was refluxed for further 16 hours under nitrogen before the solvent was removed under vacuum. The residue was triturated with hexane and the solid was collected by filtration and purified by flash chromatography (silica gel, dichloromethane-methanol 96:4) to give 36.1 g (85%) of the title compound as a white solid; mp 80°-83° C.; δH (360 MHz, DMSO-d6) 7.08 (1H, br t, --NH--), 6.77 (1H, s, --NH--), 3.04 (2H, d, J=6.9 Hz, --CH2 --), 1.24 (6H, s, --CMe2); m/z (EI) 151 (M+ +1).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][OH:5].[Cl:6][C:7]1[CH:12]=[C:11]([O:13][CH2:14][CH:15]=[C:16]([Cl:18])[Cl:17])[CH:10]=[C:9]([Cl:19])[C:8]=1[OH:20].[OH-].[Na+].S(=O)(=O)(O)O>[Cl-].C([N+]1C=CC=CC=1)CCCCCCCCCCC.C1(C)C=CC=CC=1.O>[Cl:6][C:7]1[CH:12]=[C:11]([O:13][CH2:14][CH:15]=[C:16]([Cl:18])[Cl:17])[CH:10]=[C:9]([Cl:19])[C:8]=1[O:20][CH2:2][CH2:3][CH2:4][OH:5]
Reactant: OCCCBr
Reactant: Oc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Agent: CCCCCCCCCCCC[n+]1ccccc1
Agent: O=S(=O)(O)O
Agent: [Cl-]
Solvent: O
Solvent: Cc1ccccc1
Product: OCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Temperature: 60 °C
Reaction time: 6 h
Yield: 108.2 %

Procedure:
A mixture of 0.53 g of 3-bromopropanol, 5.0 g of toluene and 0.05 g of n-dodecylpyridinium chloride was heated to 60° C. Thereto was added dropwise a mixed solution of 1.0 g of 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenol, 5.0 g of water and 0.54 g of a 27% aqueous sodium hydroxide solution with stirring over 6 hours. After completion of the addition, the mixture was further stirred at 60° C. for 11 hours. In this period, 0.10 g of 3-bromopropanol and 0.10 g of a 27% aqueous sodium hydroxide solution were further added thereto at each time point of 4 and 7 hours. Then, the reaction mixture was cooled to 20° C. After 2.0 g of a 20% aqueous sulfuric acid solution and 5.0 g of toluene were added thereto, the mixture was stirred and then separated. The obtained organic layer was washed with 5.0 g of water and concentrated under reduced pressure to give 1.3 g of 3-(2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)-1-propyl alcohol (purity: 85%, yield: 89%).
Reaction SMILES: [CH2:1]1[CH:6]2[CH2:7][C:8]3([NH2:11])[CH2:10][CH:4]([CH2:5]2)[CH2:3][CH:2]1[CH2:9]3.C(OC([NH:19][C:20](=[N:23]C(OC(C)(C)C)=O)SC)=O)(C)(C)C.O>CN(C=O)C.Cl[Hg]Cl>[C:8]12([NH:11][C:20]([NH2:23])=[NH:19])[CH2:10][CH:4]3[CH2:5][CH:6]([CH2:1][CH:2]([CH2:3]3)[CH2:9]1)[CH2:7]2
Reactant: CSC(=NC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C
Reactant: NC12CC3CC(CC(C3)C1)C2
Agent: Cl[Hg]Cl
Solvent: CN(C)C=O
Solvent: O
Product: N=C(N)NC12CC3CC(CC(C3)C1)C2

Procedure:
Amantadine (0.30 g, 2 mmol), HgCl2 (0.54 g, 2 mmol), and 1,3-bis(tert-butoxycarbonyl)-2-methyl-2-thiopseudourea (0.58 g, 2 mmol) were stirred in DMF (10 mL) under a N2 atmosphere for 24 h. H2O was added to the reaction mixture, and the white precipitate was removed by filtration. The precipitate was washed with CH2Cl2 twice, and the combined filtrate was extracted with CH2Cl2, washed with brine and dried over MgSO4, concentrated in vacuo, and purified by flash chromatography. The Boc protecting group was removed by 50% TFA/CH2Cl2 for 2 h at RT. Excess TFA was removed by passing N2 through the solution to give a yellow solid which was subsequently purified by flash chromatography (0.41 g, 74% over two steps). 1H-NMR (360 MHz, CD3OD) δ 2.13 (br s, 3H), 1.97 (br s, 6H), 1.76 (br s, 6H); 13C-NMR (90 MHz, CD3OD) δ 160.35, 53.83, 42.45, 36.86, 31.03; ESI-MS: Calculated for C11H19N3 (M+H)+ 194.2. Found: 194.7.
Reaction SMILES: [C:1]([C:4]1[C:5]([CH3:20])=[C:6]2[C:11](=[CH:12][CH:13]=1)[S:10](=[O:15])(=[O:14])[CH2:9][CH2:8][C:7]12OCC[O:16]1)([OH:3])=[O:2].Cl>CC(C)=O.O>[C:1]([C:4]1[C:5]([CH3:20])=[C:6]2[C:11](=[CH:12][CH:13]=1)[S:10](=[O:15])(=[O:14])[CH2:9][CH2:8][C:7]2=[O:16])([OH:3])=[O:2]
Reactant: Cc1c(C(=O)O)ccc2c1C1(CCS2(=O)=O)OCCO1
Agent: Cl
Solvent: CC(C)=O
Solvent: O
Product: Cc1c(C(=O)O)ccc2c1C(=O)CCS2(=O)=O
Temperature: 25 °C
Reaction time: 48 h
Yield: 99.8 %

Procedure:
16.0 Grams (54 mmol) of 6-carboxy-4,4-ethylenedioxy-5-methylthiochroman-1,1-dioxide was dissolved in 90 ml of acetone and 30 ml of water, and 10 ml of a 12N hydrochloric acid aqueous solution was added. The mixture was stirred at room temperature for 2 days. After the completion of the reaction, the reaction mixture was concentrated, and extracted with ethyl acetate. An organic layer was washed with a saturated sodium chloride aqueous solution and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to give 13.7 g (yield: quantitative) of the titled compound.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]3[C:14](=[CH:15][CH:16]=2)[CH2:13][C@@H:12]([NH:17][C:18](=[O:32])[C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][C@@H:27]4[CH2:31][CH2:30][CH2:29][O:28]4)=[CH:21][CH:20]=2)[CH2:11][CH2:10]3)[CH:2]=1>[Pt](=O)=O.C(O)(=O)C>[NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([C:7]2[CH:8]=[C:9]3[C:14](=[CH:15][CH:16]=2)[CH2:13][C@@H:12]([NH:17][C:18](=[O:32])[C:19]2[CH:20]=[CH:21][C:22]([O:25][CH2:26][C@@H:27]4[CH2:31][CH2:30][CH2:29][O:28]4)=[CH:23][CH:24]=2)[CH2:11][CH2:10]3)[CH2:2]1
Reactant: O=C(N[C@H]1CCc2cc(-c3cccnc3)ccc2C1)c1ccc(OC[C@@H]2CCCO2)cc1
Agent: O=[Pt]=O
Solvent: CC(=O)O
Product: O=C(N[C@H]1CCc2cc(C3CCCNC3)ccc2C1)c1ccc(OC[C@@H]2CCCO2)cc1
Reaction time: 12 h

Procedure:
A mixture of N-((S)-6-pyridin-3-yl-1,2,3,4-tetrahydronaphthalen-2-yl)-4-[(S)-1-(tetrahydrofuran-2-yl)methoxy]benzamide (0.60 g), glacial acetic acid (30 ml) and platinum(IV) oxide (0.10 g) was stirred vigorously under a hydrogen atmosphere (balloon) for 12 hours. The catalyst was filtered off with suction and the filtrate was concentrated. The product was thus obtained with the molecular weight of 434.58 (C27H34N2O3); MS (ESI): 435 (M+H+).
Reaction SMILES: C(Cl)(=O)C(Cl)=O.C(Cl)(Cl)Cl.C(=O)=O.[Si:14]([O:31][C:32]1[CH:49]=[CH:48][C:47]2[C@@H:46]3[C@H:37]([C@H:38]4[C@@:42]([CH2:44][CH:45]3[OH:50])([CH3:43])[CH:41]3[O:51][CH2:52][CH2:53][O:54][CH:40]3[CH2:39]4)[CH2:36][CH2:35][C:34]=2[CH:33]=1)([C:27]([CH3:30])([CH3:29])[CH3:28])([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(N(CC)CC)C>ClCCl>[Si:14]([O:31][C:32]1[CH:49]=[CH:48][C:47]2[C@@H:46]3[C@H:37]([C@H:38]4[C@@:42]([CH2:44][C:45]3=[O:50])([CH3:43])[CH:41]3[O:51][CH2:52][CH2:53][O:54][CH:40]3[CH2:39]4)[CH2:36][CH2:35][C:34]=2[CH:33]=1)([C:27]([CH3:30])([CH3:29])[CH3:28])([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: CC(C)(C)[Si](Oc1ccc2c(c1)CC[C@@H]1[C@@H]2C(O)C[C@]2(C)C3OCCOC3C[C@@H]12)(c1ccccc1)c1ccccc1
Agent: O=C(Cl)C(=O)Cl
Agent: O=C=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: CC(C)(C)[Si](Oc1ccc2c(c1)CC[C@@H]1[C@@H]2C(=O)C[C@]2(C)C3OCCOC3C[C@@H]12)(c1ccccc1)c1ccccc1
Reaction time: 0.17 h
Yield: 83.8 %

Procedure:
To a stirred solution of 1.5 mL (16.5 mmol) of oxalyl chloride in 15 mL of freshly distilled dichloromethane was added dropwise 2.35 mL (33.0 mmol) of dimethyl sufoxide at −65° C. (chloroform/dry ice bath) under argon atmosphere. After 10 minutes, a solution of 6.2 gm (10.9 mmol) of 3-tert-butyldiphenylsilyloxy-17-ethylenedioxyestra-1,3,5(10)-11-ol 38 in 15 mL of dichloromethane was added dropwise, and the reaction mixture was stirred for 40 minutes at the same temperature. Then, a 12 mL (87.3 mmol) of triethylamine was added at −65° C., slowly allowed to attain room temperature, washed with saturated NH4Cl solution, water, brine, and dried (Na2SO4). Evaporation of the solvent furnished a gum, which was chromatographed (15% ethyl acetate/hexanes) to afford 5.18 g (84%) the product 39.
Reaction SMILES: O[CH2:2][CH2:3][CH2:4][CH2:5][NH:6][C:7](=[O:16])[CH:8]=[CH:9][C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH:36](=[C:43]1[S:47][C:46](=[O:48])[NH:45][C:44]1=[O:49])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C(OC(N=NC(OCC)=O)=O)C>C1COCC1>[CH:36](=[C:43]1[S:47][C:46](=[O:48])[N:45]([CH2:2][CH2:3][CH2:4][CH2:5][NH:6][C:7](=[O:16])[CH:8]=[CH:9][C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[C:44]1=[O:49])[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1
Reactant: O=C(C=Cc1cccnc1)NCCCCO
Reactant: O=C1NC(=O)C(=Cc2ccccc2)S1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: O=C(C=Cc1cccnc1)NCCCCN1C(=O)SC(=Cc2ccccc2)C1=O

Procedure:
Batch size: 13.5 g (61.3 mmol) N-(4-hydroxybutyl)-3-pyridin-3-yl-acrylamide, 16.1 g (61.3 mmol) triphenylphosphine, 12.6 g (61.3 mmol) 5-benzyliden-thiazolidin-2,4-dione and 9.7 ml (61.3 mmol) azodicarboxylic acid diethyl ester in 250 ml THF.
Reaction SMILES: [ClH:1].FC(F)(F)[C:4]1[CH:15]=[CH:14][CH:13]=[CH:12][C:5]=1[O:6][C@H:7]1[CH2:11][CH2:10][NH:9][CH2:8]1.O[C@@H]1CCN(C(OC(C)(C)C)=O)C1.[Br:31]C1C=CC=CC=1O>>[ClH:1].[Br:31][C:4]1[CH:15]=[CH:14][CH:13]=[CH:12][C:5]=1[O:6][C@H:7]1[CH2:11][CH2:10][NH:9][CH2:8]1
Reactant: Oc1ccccc1Br
Reactant: FC(F)(F)c1ccccc1O[C@H]1CCNC1
Agent: CC(C)(C)OC(=O)N1CC[C@@H](O)C1
Agent: Cl
Product: Brc1ccccc1O[C@H]1CCNC1

Procedure:
The title compound was prepared in the same manner as described for (3S)-3-[2-(trifluoromethyl)phenoxy]pyrrolidine hydrochloride from tert-butyl (3R)-3-hydroxypyrrolidine-1-carboxylate and 2-bromophenol. 1H NMR (300 MHz, DMSO-d6): δ 7.60 (m, 1H), 7.35 (m, 1H), 7.18 (m, 1H), 6.94 (m, 1H), 5.18 (s, 1H), 3.53 (d, 1H), 3.32 (m, 3H), 2.14 (m, 2H).
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])[NH:9][CH:8]([CH3:15])[CH2:7][C:6]2=[O:16].N1C=CC=CC=1.Cl[C:24]([O:26][CH2:27][CH2:28][CH2:29][CH3:30])=[O:25]>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]([C:24]([O:26][CH2:27][CH2:28][CH2:29][CH3:30])=[O:25])[CH:8]([CH3:15])[CH2:7][C:6]2=[O:16]
Reactant: COc1cc2c(cc1OC)C(=O)CC(C)N2
Reactant: CCCCOC(=O)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCCCOC(=O)N1c2cc(OC)c(OC)cc2C(=O)CC1C
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
To a cooled mixture of 1.15 g. (5.17 mmol) of the quinoline product of Example 4, 751 mg. (10.15 mmol) of dry pyridine and 5.5 ml. of methylene chloride stirred under a nitrogen atmosphere was added dropwise 1.03 g. (7.60 mmol) of butyl chloroformate in 1 ml. methylene chloride over 10 min. at a rate to maintain a 10°-15° temperature. After the addition was complete the bath was removed, the reaction stirred at room temperature for 45 min., and poured onto 25 ml. saturated sodium bicarbonate solution. The organic phase was collected and washed with 25 ml. of saturated sodium bicarbonate solution, 50 ml. saturated sodium chloride solution, dried over magnesium sulfate, then gravity filtered and evaporated to a viscous amber oil. Evaporative distillation at 110° C (0.05 mm) gave 1.4 g. of a very viscous amber oil.
Reaction SMILES: CO[C:3]([C:5]1[C:6]([OH:23])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10](=[O:22])[CH:9]=[CH:8]2)=[O:4].[NH2:24][CH2:25][C:26]([O-:28])=[O:27].[Na+]>COCCO>[CH2:15]([N:11]1[C:12]2[C:7](=[C:6]([OH:23])[C:5]([C:3]([NH:24][CH2:25][C:26]([OH:28])=[O:27])=[O:4])=[N:14][CH:13]=2)[CH:8]=[CH:9][C:10]1=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: NCC(=O)[O-]
Reactant: COC(=O)c1ncc2c(ccc(=O)n2Cc2ccccc2)c1O
Agent: [Na+]
Solvent: COCCO
Product: O=C(O)CNC(=O)c1ncc2c(ccc(=O)n2Cc2ccccc2)c1O
Yield: 74.3 %

Procedure:
A mixture of 1-benzyl-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (100 mg, 0.32 mmol) and sodium glycinate (626 mg, 6.45 mmol) in 2-methoxyethanol (10 mL) was refluxed for 2 h. The solvent was evaporated in vacuo, and the residue was dissolved in saturated NaHCO3. The aqueous phase was washed with ether, and then acidified to pH about 2 with 4M HCl. The resulting suspension was extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated to give 84 mg of the title compound as a pale yellow solid. MS: (+) m/z 354.02 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:33])[CH:4]([N:13]1[C:19](=[O:20])[CH2:18][CH2:17][N:16]([C:21](=[O:32])/[CH:22]=[CH:23]/[C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([Cl:31])[CH:25]=2)[CH2:15][CH2:14]1)[CH2:5][C:6]([O:8]C(C)(C)C)=[O:7].Cl>O1CCOCC1.O>[CH3:1][O:2][C:3](=[O:33])[CH:4]([N:13]1[C:19](=[O:20])[CH2:18][CH2:17][N:16]([C:21](=[O:32])/[CH:22]=[CH:23]/[C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([Cl:31])[CH:25]=2)[CH2:15][CH2:14]1)[CH2:5][C:6]([OH:8])=[O:7]
Reactant: COC(=O)C(CC(=O)OC(C)(C)C)N1CCN(C(=O)/C=C/c2ccc(Cl)c(Cl)c2)CCC1=O
Agent: Cl
Solvent: O
Solvent: C1COCCO1
Product: COC(=O)C(CC(=O)O)N1CCN(C(=O)/C=C/c2ccc(Cl)c(Cl)c2)CCC1=O
Reaction time: 8 h

Procedure:
A solution of 0.30 g (0.60 mmol) of) 2-{4-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-succinic acid 4-tert-butyl ester 1-methyl ester in 1.2 ml of dioxane was cooled down to ˜6° C. and 1.50 ml (6.01 mmol) of hydrochloric acid 4M in dioxane, then 1 drop of water were added and stirring was continued overnight at RT. The solution was evaporated, dissolved in acetonitrile and evaporated (2×) to give the titled compound in quant. yield as yellow oil. MS: 441.2 (M−H−, 2Cl).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([N:9]([CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][N:26]=2)[C:10]([C@@H:12]([O:19]C(=O)C)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:11])[CH:5]=[CH:6][C:7]=1[CH3:8].O.[OH-].[Li+]>O1CCCC1.O>[CH3:1][C:2]1[CH:3]=[C:4]([N:9]([CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:33])([F:34])[F:32])=[CH:27][N:26]=2)[C:10](=[O:11])[C@@H:12]([OH:19])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:5]=[CH:6][C:7]=1[CH3:8]
Reactant: CC(=O)O[C@H](C(=O)N(CCc1ccc(C(F)(F)F)cn1)c1ccc(C)c(C)c1)c1ccccc1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: Cc1ccc(N(CCc2ccc(C(F)(F)F)cn2)C(=O)[C@@H](O)c2ccccc2)cc1C
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.5 %

Procedure:
To a solution of 116 mg (0.25 mmol) acetic acid (S)-{(3,4-dimethyl-phenyl)-[2-(5-trifluoromethyl-pyridin-2-yl)-ethyl]-carbamoyl}-phenyl-methyl ester in 1.2 mL tetrahydrofuran were added 0.6 mL water and 11.4 mg (0.27 mmol) lithium hydroxide monohydrate. The mixture was stirred at room temperature overnight. The mixture was diluted with water and extracted 3 times with ethyl acetate. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude oil was purified with flash column chromatography on silica eluting with a gradient formed from heptane and ethylacetate to provide 0.098 g (93%) of the title compound as a colorless oil. MS(m/e): 429.2 [M+H]+.
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[C:23]3[C:18](=[CH:19][C:20]([C:24]4[C:29]5[S:30][C:31]6[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=6[C:28]=5[CH:27]=[CH:26][CH:25]=4)=[CH:21][CH:22]=3)[CH:17]=[CH:16][C:15]=2[OH:37])=[CH:3][CH:2]=1.[CH2:38]1C[O:41][CH2:40][CH2:39]1.C(N(CC)CC)C.C(Cl)(=O)C=C>O.C(OCC)(=O)C>[C:40]([O:37][C:15]1[CH:16]=[CH:17][C:18]2[C:23](=[CH:22][CH:21]=[C:20]([C:24]3[C:29]4[S:30][C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=5[C:28]=4[CH:27]=[CH:26][CH:25]=3)[CH:19]=2)[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:41])[CH:39]=[CH2:38]
Reactant: C1CCOC1
Reactant: Oc1ccc2cc(-c3cccc4c3sc3ccccc34)ccc2c1-c1cccc2c1sc1ccccc12
Agent: C=CC(=O)Cl
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: O
Product: C=CC(=O)Oc1ccc2cc(-c3cccc4c3sc3ccccc34)ccc2c1-c1cccc2c1sc1ccccc12
Reaction time: 0.5 h
Yield: 90 %

Procedure:
1.8 g of the thus obtained 1,6-bis(4-dibenzothiophenyl)-2-naphthol is placed in a round bottom flask; 30 mL of THF is added to form a transparent solution; after ice cooling the flask, 0.58 g of triethylamine is added; 0.48 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. 15 mL of water is added; the mixture is vigorously stirred; and 30 mL of ethyl acetate and 15 mL of saturated salt water are then added, thereby separating an aqueous solution. An organic phase is washed with saturated salt water and dried upon application of magnesium sulfate. The resulting mixture is concentrated by filtration with a filter paper; and a major product is separated by a silica gel column (eluate: hexane/dichloromethane mixture), thereby obtaining 1.8 g (yield: 90%) of the foregoing white solid. 1H NMR (CDCl3, 400 MHz): δ (ppm) 5.66 (dd=1.2 & 10.4 Hz, 1H), 5.94 (dd=10.4 & 17.2 Hz, 1H), 6.18 (dd=1.2 & 17.2 Hz, 1H), 7.37 to 7.60 (m, 10H), 7.67 to 7.74 (m, 2H), 7.77 to 7.82 (m, 1H), 8.07 (d=8.8 Hz, 1H), 8.10 to 8.24 (m, 4H), 8.15 (d=1.6 Hz, 1H)
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([NH2:9])=[C:4]([NH2:10])[CH:3]=1.[C:11]([C:19](O)=[O:20])(=O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:6][C:7]=1[Cl:8])[NH:9][C:19](=[O:20])[C:11]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[N:10]2
Reactant: O=C(O)C(=O)c1ccccc1
Reactant: Nc1cc(Cl)c(Cl)cc1N
Solvent: CCO
Product: O=c1[nH]c2cc(Cl)c(Cl)cc2nc1-c1ccccc1
Yield: 87.6 %

Procedure:
A mixture of 528 mg (2.98 mmol) of 4,5-dichloro-1,2-phenylenediamine and 448 mg (2.98 mmol) of benzoylformic acid in 8 mL of ethanol was refluxed overnight. It was filtered, washed by water, and dried to leave 760 mg (87%) of solid. 1H NMR (DMSO-d6), 7.465-7.536 (m, 4), 8.088 (s, 1), 8.256-8.282 (m, 2) 12.683 (s, 1).
Reaction SMILES: [C:1]1([CH3:26])[CH:6]=[CH:5][C:4]([N:7]2[C:19]3[CH:18]=[CH:17][C:16]([CH:20]=[C:21]([C:24]#[N:25])[C:22]#[N:23])=[CH:15][C:14]=3[C:13]3[C:8]2=[CH:9][CH:10]=[CH:11][CH:12]=3)=[CH:3][CH:2]=1.[C-:27]#[N:28].[Na+].C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Pb+4]>CN(C)C=O.O.C(Cl)(Cl)Cl>[C:1]1([CH3:26])[CH:2]=[CH:3][C:4]([N:7]2[C:19]3[CH:18]=[CH:17][C:16]([C:20]([C:27]#[N:28])=[C:21]([C:24]#[N:25])[C:22]#[N:23])=[CH:15][C:14]=3[C:13]3[C:8]2=[CH:9][CH:10]=[CH:11][CH:12]=3)=[CH:5][CH:6]=1
Reactant: [C-]#N
Reactant: Cc1ccc(-n2c3ccccc3c3cc(C=C(C#N)C#N)ccc32)cc1
Agent: CC(=O)[O-]
Agent: [Na+]
Agent: [Pb+4]
Solvent: ClC(Cl)Cl
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ccc(-n2c3ccccc3c3cc(C(C#N)=C(C#N)C#N)ccc32)cc1
Reaction time: 0.17 h
Yield: 21.5 %

Procedure:
6.50 g (19.5 mmol) of N-(p-tolyl)-3-(dicyanovinyl)carbazole and 60 ml of N,N-dimethylformamide as solvent were placed in a 500 ml four-necked flask with a mechanical stirrer and bulb-shaped cooler. To this was added an aqueous solution prepared from 1.05 g (21.4 mmol) of sodium cyanide and 5.0 ml of water, which was stirred for 10 minutes. Further, 8.64 g (19.5 mmol) of lead tetraacetate was added. The resultant product was subjected to the reaction for 30 minutes. After the reaction was completed, 300 ml of chloroform was added. To the resultant solution was added 300 ml of water. The resultant liquid was washed in a separatory funnel. To the washed liquid was added sodium sulfate, which was left to stand for 30 minutes and dehydrated. The dehydrated solution was concentrated in an evaporator and dried under vacuum to obtain a red solid. The resultant solid was recrystallized in the presence of benzene to obtain 1.50 g of a red crystal.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([CH:11]=O)[CH:2]=1.N1(C2C=C[C:21]([CH:22]=[O:23])=CC=2)C=CC=N1>>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([CH:11]=[CH:21][CH:22]=[O:23])[CH:2]=1
Reactant: O=Cc1ccc(-n2cccn2)cc1
Reactant: O=Cc1cnc2ccccc2c1
Product: O=CC=Cc1cnc2ccccc2c1

Procedure:
The title compound was prepared by a procedure analogous to Reference Example 30 by substituting 3-quinolinecarboxaldehyde for the 4-(1H-pyrazol-1-yl)-benzaldehyde of Reference Example 30. MS 184 (M+H)+.
Reaction SMILES: C([NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]3[N:26]=[C:25]([C:27]4[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[CH:29][CH:28]=4)[CH:24]=[C:23]([CH3:35])[N:22]=3)[N:16]=2)[CH:10]=1)(=[O:8])=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O>>[C:33]([C:30]1[CH:29]=[CH:28][C:27]([C:25]2[CH:24]=[C:23]([CH3:35])[N:22]=[C:21]([C:17]3[N:16]=[C:15]([C:11]4[CH:10]=[C:9]([S:6]([NH2:5])(=[O:7])=[O:8])[CH:14]=[CH:13][CH:12]=4)[CH:20]=[CH:19][CH:18]=3)[N:26]=2)=[CH:32][CH:31]=1)#[N:34]
Reactant: Cc1cc(-c2ccc(C#N)cc2)nc(-c2cccc(-c3cccc(S(=O)(=O)NC(C)(C)C)c3)n2)n1
Solvent: O=C(O)C(F)(F)F
Product: Cc1cc(-c2ccc(C#N)cc2)nc(-c2cccc(-c3cccc(S(N)(=O)=O)c3)n2)n1
Temperature: 23 °C
Reaction time: 3 h
Yield: 66.6 %

Procedure:
To N-tert-butyl-3-{6-[4-(4-cyano-phenyl)-6-methyl-pyrimidin-2-yl]-pyridin-2-yl}-benzenesulfonamide (Example 441) (0.080 g, 0.165 mmol) was added TFA (2 mL) and the reaction mixture was stirred at 23° C. for 3 h. The mixture was partitioned between EtOAc and saturated NaHCO3 solution, the organic layer was dried over Na2SO4. Removal of the solvent in vacuum left a crude product which was triturated with diethyl ether to give the title compound as a light brown solid (0.047 g, 67%). MS (ISP) 428.1 [(M+H)+]; mp 255° C.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].C[Si]([C:11]#[C:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2([NH2:22])[CH2:21][CH2:20]2)=[CH:15][CH:14]=1)(C)C>CO>[C:12]([C:13]1[CH:18]=[CH:17][C:16]([C:19]2([NH2:22])[CH2:20][CH2:21]2)=[CH:15][CH:14]=1)#[CH:11]
Reactant: C[Si](C)(C)C#Cc1ccc(C2(N)CC2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: C#Cc1ccc(C2(N)CC2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 74.9 %

Procedure:
Potassium carbonate (0.33 g) was added to a methanol (10 mL) solution of 1-{4-[(trimethylsilyl)ethynyl]phenyl}cyclopropylamine (0.37 g) as obtained in Example 21-(2), and the mixture was stirred for 1 hour at room temperature. After the potassium carbonate was filtered out and washed with chloroform, the solvent was distilled off under reduced pressure. The resulting residue was purified by OH type silica gel chromatography (gradient elution with hexane/AcOEt=70/30→30/70) to obtain 1-(4-ethynylphenyl)cyclopropylamine (Compound 404, yellow solid) (0.19 g, 76%).
Reaction SMILES: [C:1]1([CH2:7][CH:8]=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:11][CH:12]=[CH2:13].Cl[Sn]Cl.O.CC(=O)OCC>O>[C:1]1([CH2:7][CH:8]([OH:9])[CH2:13][CH:12]=[CH2:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C=CCBr
Reactant: O=CCc1ccccc1
Agent: Cl[Sn]Cl
Solvent: O
Solvent: CCOC(C)=O
Product: C=CCC(O)Cc1ccccc1
Yield: 54.3 %

Procedure:
To a mixture of phenylacetaldehyde 30a (7.84 g, 65.3 mmol) and 3-bromoprop-1-ene (11.1 g, 91.5 mmol) in water (50 mL), KI (3.25 g, 19.6 mmol) and NiCl2.6H2O (3.1 g, 13 mmol) were added. After the mixture was stirred for several minutes, SnCl2.H2O (29.5 g, 13 mmol) was added. The mixture was vigorously stirred at rt overnight and then extracted with EA. The combined organic layer was washed by brine, dried over anhydrous sodium sulfate, evaporated in vacuo. The residue was purified by CC using PE:EA=5:1 as mobile phase to give the desired product (5.75 g, 54% yield).
Reaction SMILES: [NH2:1]/[C:2](/[CH3:11])=[CH:3]\[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5].[C:12]([N:20]=[C:21]=[S:22])(=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C(OCC)C>[NH2:1]/[C:2](/[CH3:11])=[C:3](/[C:21](=[S:22])[NH:20][C:12](=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)\[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5]
Reactant: O=C(N=C=S)c1ccccc1
Reactant: C/C(N)=C/C(=O)OC(C)(C)C
Solvent: CCOCC
Product: C/C(N)=C(/C(=O)OC(C)(C)C)C(=S)NC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 43.7 %

Procedure:
A mixture of t-butyl 3-aminocrotonate (65.3 g, 0.4 mol), benzoyl isothiocyanate (62.9 g, 0.4 mol), and diethyl ether (300 ml) was stirred at ambient temperature for 3 hours. The solid product was collected on a filter, washed with ether and dried to give 56 g (43.7 percent yield) of material melting at 107° to 110° C.