Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1([C:6]2[CH:11]=[CH:10][C:9]([S:12](Cl)(=[O:14])=[O:13])=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.[NH2:16][C:17]1[CH:21]=[CH:20][S:19][C:18]=1[C:22]([O:24][CH3:25])=[O:23].N1C=CC=CC=1>ClCCl>[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([S:12]([NH:16][C:17]3[CH:21]=[CH:20][S:19][C:18]=3[C:22]([O:24][CH3:25])=[O:23])(=[O:14])=[O:13])=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1
Reactant: COC(=O)c1sccc1N
Reactant: O=S(=O)(Cl)c1ccc(-n2cccn2)cc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: COC(=O)c1sccc1NS(=O)(=O)c1ccc(-n2cccn2)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 65.4 %

Procedure:
To a solution of 4-(1H-pyrazol-1-yl)benzene-1-sulfonyl chloride (0.5 g; 2.0 mmol) in dichloromethane (4.5 mL) at room temperature, was added methyl 3-aminothiophene-2-carboxylate (0.27 g; 1.7 mmol) followed by pyridine (0.27 g; 3.4 mmol) and then stirred at room temperature under a nitrogen atmosphere for 24 hours. The reaction mixture was concentrated under reduced pressure and then taken up in ethyl acetate (50 mL) and washed with water. The aqueous layer separated and extracted with ethyl acetate (2×50 mL). The combined organic phases were successively washed with water and aqueous saturated sodium chloride, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude residue was recrystallized from ethyl acetate/hexanes (1:9, v/v) to yield the title product as a tan/yellow solid (404 mg).
Reaction SMILES: [C:1]([C:4]1[N:5]=[N:6][C:7]([NH:10][NH2:11])=[CH:8][CH:9]=1)(=[O:3])[NH2:2].[C:12]([CH2:15][C:16](=O)[CH3:17])(=O)[CH3:13]>C(O)C>[C:1]([C:4]1[N:5]=[N:6][C:7]([N:10]2[C:16]([CH3:17])=[CH:15][C:12]([CH3:13])=[N:11]2)=[CH:8][CH:9]=1)(=[O:3])[NH2:2]
Reactant: CC(=O)CC(C)=O
Reactant: NNc1ccc(C(N)=O)nn1
Solvent: CCO
Product: Cc1cc(C)n(-c2ccc(C(N)=O)nn2)n1
Reaction time: 3 h

Procedure:
A mixture of 1.53 g (0.01 moles) of 3-carbamoyl-6-pyridazinyl-hydrazine, 1.1 g (0.011 moles) of acetylacetone and 15 ml ethanol is heated to reflux under stirring for 3 hours. After cooling the separated crystals are filtered, washed with ethanol and dried. Yield: 2.05 g (95%); m.p.: 256°-257° C.
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[CH:12][C:13]3[N:14]([C:16](=[O:19])[NH:17][N:18]=3)[CH:15]=2)=[CH:6][CH:5]=1.[Br:22][CH2:23][CH2:24]Br>CN(C=O)C.O>[Br:22][CH2:23][CH2:24][N:17]1[C:16](=[O:19])[N:14]2[CH:15]=[C:10]([C:7]3[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:20])[F:21])=[CH:9][CH:8]=3)[CH:11]=[CH:12][C:13]2=[N:18]1
Reactant: O=c1[nH]nc2ccc(-c3ccc(OC(F)(F)F)cc3)cn12
Reactant: BrCCBr
Solvent: O
Solvent: CN(C)C=O
Product: O=c1n(CCBr)nc2ccc(-c3ccc(OC(F)(F)F)cc3)cn12
Temperature: 95 °C

Procedure:
6-(4-(trifluoromethoxy)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (synthesized according to Example 1, 500 mg, 1.69 mmol) was dissolved in 5 ml DMF and 1,2 dibromoethane (1.0 mL, 11.8 mmol) was added. The reaction was heated to 95° C. overnight. The reaction was cooled, diluted with water/EtOAC and the layers were separated. The organic layer was washed with NaHCO3. The organics were dried (MgSO4), filtered, concentrated and purified by flash chromatography (Rf=0.46, 1:1 hexanes:EtOAc) to afford 2-(2-bromoethyl)-6-(4-(trifluoromethoxy)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one. To a solution of 2-(2-bromoethyl)-6-(4-(trifluoromethoxy)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (50 mg, 0.124 mmol) in 1 mL DMF was added K2CO3 (51 mg, 0.372 mmol) and 4-phenyl-1H-imidazole (36 mg, 0.249 mmol) and the reaction was heated to 85° C. for 24-72 hours until the SM was consumed. The reaction was concentrated and purified by reverse phase HPLC to afford compound 100 (24 mg, 41%). GS-490257. C24H18F3N5O2, m/z (ESI)=466.2 [M+H]+.
Reaction SMILES: [C:1]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][N:10]1[C:11]([NH:13][C:14](/[C:16]/1=[CH:17]\[CH2:18][C:19](=[O:25])[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])=[O:15])=[O:12])([OH:3])=[O:2].C>CCO.CCOCC>[C:1]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][N:10]1[CH:16]([CH2:17][CH2:18][C:19](=[O:25])[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[C:14](=[O:15])[NH:13][C:11]1=[O:12])([OH:3])=[O:2]
Reactant: CCCCCC(=O)C/C=C1\C(=O)NC(=O)N1CCCCCCC(=O)O
Solvent: CCOCC
Solvent: CCO
Product: CCCCCC(=O)CCC1C(=O)NC(=O)N1CCCCCCC(=O)O

Procedure:
A solution of 1-(6-carboxyhexyl)-5-((E)-3-oxooctylidene)hydantoin (3.06 g) in EtOH (60 ml) was stirred with 10% palladised charcoal (200 mg) under hydrogen at room temperature and pressure, absorption of 1 molecular equivalent of hydrogen occurring in 2 hours. The catalyst was filtered, the filtrate was evaporated in vacuo, and the residual gum was set aside to give a mass of colourless crystals. The crystals were suspended in ether (4 ml) and collected, affording pure 1-(6-carboxyhexyl)-5-(3-oxo-octyl)hydantoin, m.p. 84.5°-86°. A stirred suspension of 0.5 g of this compound in water (15 ml) at 0° C. was treated with NaHCO3 (0.36 g) and then, during 3 minutes, with sodium borohydride (54 mg). After 45 minutes, more sodium borohydride (54 mg) was added and, after a further 11/2 hours, the clear solution was set aside at room temperature for 11/2 hours. The solution was then acidified to Congo Red with hydrochloric acid, the liberated carboxylic acid was extracted into chloroform, and the chloroform solution was washed and dried over magnesium sulphate. Evaporation of the solvent afforded 1-(6-carboxyhexyl)-5-(3-hydroxyoctyl) hydantoin as a mixture of diastereomers which was subjected to HPLC (SiO2, CHCl3 /MeOH/HOAc 97.75:1.25:1.0), affording the individual diastereomers as colourless gums, Rf. 0.44 and 0.40 (relative to 0.64 for a marker of the starting oxo-compound) and SiO2 in CHCl3 /MeOH/HOAc 90:5:5.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=O)=O)=[CH:4][CH:3]=1.[C:19]1([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][C:26](=[O:40])[CH2:27][C:28]2[CH:29]=[C:30]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH:31]=[CH:32][CH:33]=2)[CH:20]=1.[OH-].C([N+](CCCC)(CCCC)CCCC)CCC.O>C(O)(C)(C)C>[C:30]1([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:31]=[CH:32][CH:33]=[C:28]([C:27]2[C:26](=[O:40])[C:25]([C:21]3[CH:20]=[C:19]([C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=4)[CH:24]=[CH:23][CH:22]=3)=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[C:10]=2[C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[CH:29]=1
Reactant: O=C(C(=O)c1ccc(Cl)cc1)c1ccc(Cl)cc1
Reactant: O=C(Cc1cccc(-c2ccccc2)c1)Cc1cccc(-c2ccccc2)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [OH-]
Solvent: O
Solvent: CC(C)(C)O
Product: O=C1C(c2cccc(-c3ccccc3)c2)=C(c2ccc(Cl)cc2)C(c2ccc(Cl)cc2)=C1c1cccc(-c2ccccc2)c1
Temperature: 80 °C
Reaction time: 0.33 h
Yield: 76.6 %

Procedure:
To a degassed solution of 940 mg of 4,4′-dichlorobenzil (3.37 mmol) and 1.22 g of 1,3-di(biphenyl-3-yl)propan-2-one (7, 3.37 mmol) in 20 ml of tert-butanol was added, at 80° C., a methanolic tetrabutylammonium hydroxide solution (1M, 1.7 ml, 1.7 mmol). The reaction solution was stirred at 80° C. for 20 minutes, and the reaction then stopped by adding water. The mixture was extracted three times with dichloromethane and the collected organic phases were washed with saturated sodium chloride solution and dried over magnesium sulfate, before the solvent was distilled off under reduced pressure. The crude product was purified by column chromatography (silica gel, eluent: hexane with 20% DCM) and gave 1.56 g of the tetraarylcyclopentadienone 8b as a pale violet solid (77%, 2.58 mmol). Elemental analysis measured: C 81.3; H 3.3% (calculated for C41H26Cl2O: C, 81.3; H, 4.3%); 1H NMR (700 MHz, d8-THF) δ=7.52 (s, 2H, CH), 7.50 (d, J=7.8 Hz, 2H, CH), 7.42 (d, J=7.2 Hz, 4H, CH), 7.36 (t, J=7.7 Hz, 4H, CH), 7.32 (m, 6H, CH), 7.27 (t, J=7.3 Hz, 2H, CH), 7.23 (d, J=7.8 Hz, 2H, CH), 7.06 (d, J=8.5 Hz, 4H, CH); 13C NMR (175 MHz, d8-THF) δ=199.86, 154.28, 141.91, 141.82, 135.61, 133.14, 132.14, 132.10, 129.98, 129.90, 129.70, 129.69, 129.52, 128.27, 127.78, 127.20, 126.73; MS (MALDI-TOF): m/z (%): 604.6 (100) [M+] (calculated for C41H26Cl2: 604.1); Rf (hexane with 10% ethyl acetate)=0.47.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11]([CH3:13])([CH3:12])[CH2:10][CH2:9][C:8](=[O:14])[N:7]([CH2:15][CH3:16])[C:6]=2[CH:17]=1.Cl[C:19]1[N:24]=[C:23]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[S:32]([N:35]([CH3:37])[CH3:36])(=[O:34])=[O:33])[C:22]([Cl:38])=[CH:21][N:20]=1>>[Cl:38][C:22]1[C:23]([NH:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[S:32]([N:35]([CH3:37])[CH3:36])(=[O:34])=[O:33])=[N:24][C:19]([NH:1][C:2]2[CH:3]=[CH:4][C:5]3[C:11]([CH3:12])([CH3:13])[CH2:10][CH2:9][C:8](=[O:14])[N:7]([CH2:15][CH3:16])[C:6]=3[CH:17]=2)=[N:20][CH:21]=1
Reactant: CCN1C(=O)CCC(C)(C)c2ccc(N)cc21
Reactant: CN(C)S(=O)(=O)c1ccccc1Nc1nc(Cl)ncc1Cl
Product: CCN1C(=O)CCC(C)(C)c2ccc(Nc3ncc(Cl)c(Nc4ccccc4S(=O)(=O)N(C)C)n3)cc21
Yield: 50 %

Procedure:
The title compound was prepared with a procedure analogous to that used to prepare example 381 by combining 8-Amino-1-ethyl-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one and 2-(2,5-Dichloro-pyrimidin-4-ylamino)-N,N-dimethyl-benzenesulfonamide to yield an off-white solid, 2-[5-Chloro-2-(1-ethyl-5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-8-ylamino)-pyrimidin-4-ylamino]-N,N-dimethyl-benzenesulfonamide (50%). LCMS: m/z=543.51 (M+H+), 1H NMR (400 MHz, CDCl3) δ 9.49 (s, 1H), 8.52 (d, 1H, J=8.6 Hz), 8.17 (s, 1H), 7.88 (d, 1H, J=8.1 Hz), 7.68 (s, 1H), 7.50 (m, 1H), 7.28 (m, 4H), 3.68 (m, 2H), 2.76 (s, 6H), 2.34 (m, 2H), 2.05 (m, 2H), 1.35 (s, 2H), 1.16 (m, 3H).
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:10]([F:27])=[C:11]([F:26])[C:12]([NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[Cl:25])=[C:13]([CH:17]=1)[C:14]([OH:16])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)(O)[O-].[K+].[CH2:33](Br)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.O>CN(C=O)C>[CH2:1]([O:8][C:9]1[C:10]([F:27])=[C:11]([F:26])[C:12]([NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[Cl:25])=[C:13]([CH:17]=1)[C:14]([O:16][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:15])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)c1cc(OCc2ccccc2)c(F)c(F)c1Nc1ccccc1Cl
Reactant: BrCc1ccccc1
Agent: O=C([O-])O
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: O=C(OCc1ccccc1)c1cc(OCc2ccccc2)c(F)c(F)c1Nc1ccccc1Cl
Temperature: 25 °C
Reaction time: 5 h
Yield: 94.9 %

Procedure:
To a solution of 5-(benzyloxy)-2-((2-chlorophenyl)amino)-3,4-difluorobenzoic acid (23.80 g, 61.06 mmol) in DMF (200 mL) was added potassium bicarbonate (9.16 g, 91.6 mmol) followed by benzyl bromide (8.0 mL, 67.37 mmol). The mixture was stirred for 5 h at room temperature and water (300 mL) was added. The solution was extracted with ethyl acetate (100 mL×3). The combined organic extracts were washed with water (200 mL×3) and brine (200 mL) sequentially, dried over Na2SO4, filtered and concentrated in vacuo. After purification by column chromatography on silica gel (petroleum ether/ethyl acetate, 50:1, v/v), the corresponding product was obtained as white solid (27.82 g, 95% yield). 1H NMR (400 MHz, CDCl3): δ 8.56 (s, 1H), 7.52 (dd, J=8.5, 2.1 Hz, 1H), 7.40 (m, 11H), 7.15 (m, 1H), 6.88 (m, 1H), 6.74 (m, 1H), 5.34 (s, 2H), 5.16 (s, 2H).
Reaction SMILES: O[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:23])[CH2:9][C:10]([C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=1[N+:20]([O-:22])=[O:21])=[O:11]>Cl.C(O)(=O)C.O>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([C:10]2[O:11][C:4]3[C:3]([C:8](=[O:23])[CH:9]=2)=[CH:2][CH:7]=[CH:6][CH:5]=3)=[C:13]([N+:20]([O-:22])=[O:21])[CH:14]=1
Reactant: COc1ccc(C(=O)CC(=O)c2ccccc2O)c([N+](=O)[O-])c1
Agent: Cl
Solvent: CC(=O)O
Solvent: O
Product: COc1ccc(-c2cc(=O)c3ccccc3o2)c([N+](=O)[O-])c1
Temperature: 100 °C
Yield: 70.3 %

Procedure:
1-(2-Hydroxyphenyl)-3-(4-methoxy-2-nitrophenyl)propane-1,3-dione (5.92 g, 18.77 mmol) was dissolved in a mixture of 48% HCl (2 mL) and acetic acid (35 mL) and heated at 100° C. for 1 h. The reaction mixture was cooled to rt, diluted with water and extracted with ethyl acetate. The organic layer was washed with water, brine, dried and concentrated to give the crude compound, which was purified by column chromatography using 5% ethyl acetate in CH2Cl2 to give 2-(4-methoxy-2-nitrophenyl)-4H-chromen-4-one (3.92 g, 70%).
Reaction SMILES: C(OC([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][C:12]([CH2:18][C:19](=[O:51])[NH:20][CH:21]([B:38]3[O:46]C4C(C)(C5CC(C4)C5(C)C)[O:39]3)[CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([O:31]C(C)(C)C)=[O:30])[C:24]=3OC)=[CH:13][CH:14]=2)[CH2:9]1)=O)(C)(C)C.Cl>>[OH:39][B:38]1[C@@H:21]([NH:20][C:19](=[O:51])[CH2:18][C:12]2[CH:13]=[C:14]3[C:15]([CH2:16][CH2:17][NH:8][CH2:9]3)=[CH:10][CH:11]=2)[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([OH:31])=[O:30])[C:24]=2[O:46]1
Reactant: COc1c(CC(NC(=O)Cc2ccc3c(c2)CN(C(=O)OC(C)(C)C)CC3)B2OC3CC4CC(C4(C)C)C3(C)O2)cccc1C(=O)OC(C)(C)C
Agent: Cl
Product: O=C(Cc1ccc2c(c1)CNCC2)N[C@H]1Cc2cccc(C(=O)O)c2OB1O

Procedure:
Prepared from 7-{[2-(3-tert-Butoxycarbonyl-2-methoxy-phenyl)-1-(2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.02,6]dec-4-yl)-ethylcarbamoyl]-methyl}-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester and HCl following the procedure described in Step 6 of Example 48. The crude product was purified by reverse phase preparative HPLC and dried using lyophilization. ESI-MS m/z 381 (MH)+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[NH:7][C:8](=[O:16])[C:9]([C:14]#[N:15])=[C:10](SC)[N:11]=1.[CH3:20][N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH2:5][C:6]1[NH:7][C:8](=[O:16])[C:9]([C:14]#[N:15])=[C:10]([N:24]2[CH2:25][CH2:26][N:21]([CH3:20])[CH2:22][CH2:23]2)[N:11]=1
Reactant: CN1CCNCC1
Reactant: CSc1nc(Cc2cccc(Cl)c2)[nH]c(=O)c1C#N
Product: CN1CCN(c2nc(Cc3cccc(Cl)c3)[nH]c(=O)c2C#N)CC1

Procedure:
In analogy to the preparation of Example 1, 100 mg (0.34 mmol) of 2-(3-chlorobenzyl)-4-(methyl-sulphanyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile are reacted with 343 mg (3.43 mmol) of N-methylpiperazine to give 101 mg (84% of theory) of the title compound.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:5]([NH:6][C:7](=[S:9])[S-:8])=[CH:4][CH:3]=1.[CH2:12]([NH+](CC)CC)C.C(Br)Br.C(N(CC)CC)C.O>CN(C)C=O.CO>[OH:1][C:2]1[CH:11]=[CH:10][C:5]([N:6]=[C:7]2[S:8][CH2:12][S:9]2)=[CH:4][CH:3]=1
Reactant: Oc1ccc(NC(=S)[S-])cc1
Reactant: CC[NH+](CC)CC
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Oc1ccc(N=C2SCS2)cc1
Reaction time: 8 h
Yield: 24.9 %

Procedure:
A solution of triethylammonium 4-hydroxydithiocarbanilate (28.6 g) in dimethylformamide (100 ml) is added to a mixture of methylene bromide (52.2 g), triethylamine (10.1 g) and dimethylformamide (200 ml) over a 15-minute period while the temperature is being kept below 30° C. The mixture is stirred overnight, poured into water and the aqueous mixture extracted with benzene. The benzene solution is washed, dried, and stripped to yield 12.5 g (63.5% of theory) crude product, as a brown solid. The crude product is dissolved in hot methanol (100 ml) and the solution allowed to stand in the cold one day to yield 4.9 g of a bone-white solid, melting point 162° C to 163° C.
Reaction SMILES: [O:1]1CCOCC1.[CH2:7]([C:14]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:15]=1[CH2:16][CH2:17][CH:18]2[C:23]([OH:25])=[O:24])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[Se](=O)=O.O>C(Cl)(Cl)Cl>[C:7]([C:14]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:15]=1[CH2:16][CH2:17][CH:18]2[C:23]([OH:25])=[O:24])(=[O:1])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: O=C(O)C1CCc2c(Cc3ccccc3)cccc21
Reactant: C1COCCO1
Agent: O=[Se]=O
Solvent: ClC(Cl)Cl
Solvent: O
Product: O=C(c1ccccc1)c1cccc2c1CCC2C(=O)O

Procedure:
To 60 ml. of dioxane are added 6.3 g. of 4-benzylindan-1-carboxylic acid and 2.8 g. of selenium dioxide and the mixture is refluxed for 12 hours. After cooling, water and chloroform are added and the insolubles are filtered off. The filtrate is extracted with chloroform and the chloroform layer is extracted with 5 % aqueous potassium carbonate. The extract is decolorized with activated carbon and rendered acidic with hydrochloride acid. The precipitate is extracted with chloroform and the extract is washed with water and dried. The solvent is distilled off under reduced pressure and the residue is crystallized from a 20:7 solvent mixture of cyclohexane and benzene. The described procedure gives 4-benzoylindan-1-carboxylic acid as crystals melting at 100°-102° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4](I)[C:3]=1[NH2:10].[C:11]1([C:17]#[CH:18])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[Cl:8][C:6]1[CH:5]=[C:4]2[C:3](=[C:2]([Cl:1])[CH:7]=1)[NH:10][C:17]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[CH:18]2
Reactant: C#Cc1ccccc1
Reactant: Nc1c(Cl)cc(Cl)cc1I
Product: Clc1cc(Cl)c2[nH]c(-c3ccccc3)cc2c1
Yield: 85 %

Procedure:
The general procedure was used to convert 2,4-Dichloro-6-iodo-phenylamine and phenylacetylene to the title product. Purification by flash chromatography gave the analytically pure product as a white solid, 85% yield. 1H NMR (300 MHz, DMSO) δ 11.82 (s, 1H), 8.01-7.98 (d, J=8.2, 2H), 7.57 (s, 1H), 7.51-7.46 (t, J=7.15, 2H), 7.40-7.36 (t, J=7.15, 1H), 7.26 (d, J=1.88, 1H), 6.95 (d, J=2.07, 1H). 13C NMR (75 MHz, DMSO) δ 141.99, 133.71, 131.98, 131.86, 129.60, 129.10, 126.98, 124.85, 121.56, 119.11, 117.40, 100.90. Anal. Calcd. for C14H9Cl2N: C, 64.15; H, 3.46; Cl, 27.05; N, 5.34. Found C, 64.09; H, 3.37; Cl, 27.05; N, 5.28. m.p.: 135.5-137.5° C.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].[NH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][CH:22]([OH:24])[CH3:23])=[CH:17][CH:16]=1>>[OH:24][CH:22]([CH3:23])[CH2:21][C:18]1[CH:19]=[CH:20][C:15]([NH:14][C:2]2[N:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][C:3]=2[N+:11]([O-:13])=[O:12])=[CH:16][CH:17]=1
Reactant: CC(O)Cc1ccc(N)cc1
Reactant: CC(=O)c1cnc(Cl)c([N+](=O)[O-])c1
Product: CC(=O)c1cnc(Nc2ccc(CC(C)O)cc2)c([N+](=O)[O-])c1

Procedure:
The title compound was prepared according to the procedure described in step 1 of Example 162 from 1-(6-chloro-5-nitro-3-pyridinyl)ethanone (Paul, B. et al. J. Med. Chem., 1990, 33, 2231–2239.) and 1-(4-aminophenyl)-2-propanol (step 1 of Example 6).
Reaction SMILES: [Na].[CH2:2]([SH:4])[CH3:3].O1CCCC1.[Cl:10][C:11]1[C:12]([NH:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[CH:26][C:25]([CH2:28][CH2:29]Cl)=[CH:24][C:23]=2[CH3:31])=[N:13][CH:14]=[N:15][C:16]=1[CH3:17]>O>[Cl:10][C:11]1[C:12]([NH:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][S:4][CH2:2][CH3:3])=[CH:24][C:23]=2[CH3:31])=[N:13][CH:14]=[N:15][C:16]=1[CH3:17]
Reactant: Cc1cc(CCCl)ccc1OCCNc1ncnc(C)c1Cl
Reactant: CCS
Agent: [Na]
Solvent: O
Solvent: C1CCOC1
Product: CCSCCc1ccc(OCCNc2ncnc(C)c2Cl)c(C)c1

Procedure:
0.5 g of the sodium salt of ethyl mercaptan was added to 30 ml of anhydrous tetrahydrofuran. 1.7 g of 5-chloro-4-{2-[4-(2-chloroethyl)-2-methylphenoxy]ethylamino]-6-methylpyrimidine was added to the mixture, which was then heated for 3 hours whilst stirring. At the end of this time, water was added to the mixture, and the oily product which separated was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous sodium sulfate. The ethyl acetate was removed by distillation under reduced pressure. The oily product obtained was subjected to column chromatography (Wakogen C-200, eluted with a 2:1 by volume mixture of toluene and ethyl acetate), to afford 1.2 g of the title compound as a pale yellow oily liquid, n20.8 =1.5478.
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH:11]=[CH:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(=O)(=O)(O)[OH:14].O.C1C=C(Cl)C=C(C(OO)=O)C=1>CO>[CH2:1]([N:8]1[CH2:12][CH:11]2[O:14][CH:10]2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C1=CCN(Cc2ccccc2)C1
Reactant: O=S(=O)(O)O
Agent: O=C(OO)c1cccc(Cl)c1
Solvent: O
Solvent: CO
Product: c1ccc(CN2CC3OC3C2)cc1
Yield: 96.4 %

Procedure:
To a solution of 15.9 g (0.1 mol) of 1-benzyl-3-pyrroline, 12.0 g (0.12 mol) of 98% sulfuric acid, 15.0 g of water, and 60.0 g of methanol in a round flask reactor, 31.1 g (0.13 mol) of 70% m-CPBA (m-chloroperbenzoic acid produced by Tokyo Chemical Industry Co., Ltd.) was added with stirring and allowed to react for 10 hours at room temperature without irradiation by lamps. After completion, methanol was evaporated under reduced pressure, neutralized by NaOH (aq), and extracted with toluene and water. After the solvent was evaporated under reduced pressure, 16.9 g of 1-benzyl-3,4-epoxypyrrolidine (yield 96.7%) was obtained.
Reaction SMILES: C(OP([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)(=O)OCC)C.C(OP([CH:24](O)[C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=1)(=O)OCC)C>O1CCCC1>[Cl:31][C:28]1[CH:29]=[CH:30][C:25]([CH:24]=[CH:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[CH:26][CH:27]=1
Reactant: CCOP(=O)(Cc1ccccc1)OCC
Reactant: CCOP(=O)(OCC)C(O)c1ccc(Cl)cc1
Solvent: C1CCOC1
Product: Clc1ccc(C=Cc2ccccc2)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 83.8 %

Procedure:
22.8 g (0.1 mol) of benzylphosphonic acid diethyl ester were added dropwise to a solution, cooled to 0° to 5° C., of 22.4 g (0.2 mol) of potassium tert.-butylate in 100 ml of tetrahydrofuran (dried over sodium) in the course of 15 l minutes. The mixture was stirred for one hour; a solution of 28 g (0.1 mol) of α-hydroxy-4-chlorobenzylphosphonic acid diethyl ester in 50 ml of tetrahydrofuran was then added to the mixture, while cooling to 0° to 5° C., and the mixture was stirred at room temperature (about 20° C.) for a further 15 hours. It was then poured into 1 liter of ice-water, filtered off and dried. 18 g (84% of theory) of 1-(4-chlorophenyl)-2-phenyl-ethylene were thus obtained in the form of colorless crystals of melting point 130° C.
Reaction SMILES: [CH:1]([C:3]1[CH:10]=[CH:9][C:6]([CH2:7]Cl)=[CH:5][CH:4]=1)=[CH2:2].[NH:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1>CCCCCC>[CH:1]([C:3]1[CH:10]=[CH:9][C:6]([CH2:7][N:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[CH:5][CH:4]=1)=[CH2:2]
Reactant: C1CCNC1
Reactant: C=Cc1ccc(CCl)cc1
Solvent: CCCCCC
Product: C=Cc1ccc(CN2CCCC2)cc1
Temperature: 0 °C

Procedure:
A 1 L (liter) round bottom flask was charged with hexane (400 mL) and 4-vinylbenzyl chloride (104.4 g, 0.68 moles). The reaction flask was placed into an ice/water bath and stirred with a magnetic stir bar. Two equivalents of pyrrolidine (130 g, 1.37 moles) were added over the course of 1 hour. After completed addition the ice/water bath was removed and the reaction was stirred at room temperature overnight. Solids were removed via vacuum filtration and volatiles were removed under vacuum to render the product in quantitative yield.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([N:11]3[CH2:15][CH2:14][CH2:13][CH2:12]3)[N:10]=2)[CH:7]=1.[C:16]1([C:22]#[CH:23])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>>[C:16]1([C:22]#[C:23][C:2]2[CH:3]=[N:4][C:5]3[N:6]([N:8]=[C:9]([N:11]4[CH2:15][CH2:14][CH2:13][CH2:12]4)[N:10]=3)[CH:7]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: Brc1cnc2nc(N3CCCC3)nn2c1
Reactant: C#Cc1ccccc1
Product: C(#Cc1cnc2nc(N3CCCC3)nn2c1)c1ccccc1

Procedure:
The title compound, a light brown solid, MS: m/e=290.2 (M+H+), can be prepared in accordance with the general method of example 1 from 6-bromo-2-pyrrolidin-1-yl-[1,2,4]triazolo[1,5-a]pyrimidine (example 51, step 1) and phenylacetylene.