Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[S:6][C:5]2=[C:7](C(OCC)=O)[N:8]=[CH:9][N:4]2[CH:3]=1.O.S(=O)(=O)(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C(O)(=O)C>[Br:1][C:2]1[S:6][C:5]2=[CH:7][N:8]=[CH:9][N:4]2[CH:3]=1
Reactant: CCOC(=O)c1ncn2cc(Br)sc12
Agent: O=C([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: Brc1cn2cncc2s1
Temperature: 105 °C
Reaction time: 30 h
Yield: 68.8 %

Procedure:
Ethyl 2-bromoimidazo[5,1-b]thiazole-7-carboxylate (2.00 g, 7.3 mmol) was suspended in a mixed solvent composed of water (16 ml) and acetic acid (24 ml), concentrated sulfuric acid (7.84 g, 80.0 mmol) was added to the suspension at room temperature, and the mixture was stirred at 105° C. for about 30 hr. After the completion of the reaction, sodium carbonate (9.32 g, 88.0 mmol) was added to the reaction solution, and acetic acid was removed by distillation under the reduced pressure. Further, water (10 ml) was again added to the concentrate, and the solvent was removed by distillation under the reduced pressure. Water (10 ml) and ethyl acetate (20 ml) were added to the residue, and the mixture was adjusted to pH 7 by the addition of a 25 wt % aqueous solution of sodium hydroxide with stirring. The insolubles were removed by filtration, followed by separation. The aqueous layer was then extracted twice with ethyl acetate (20 ml, 20 ml). The organic layer was washed with 15 wt % brine (20 ml). After washing, while concentrating the organic layer, the solvent was replaced with n-hexane to crystallize 2-bromoimidazo[5,1-b]thiazole. Subsequently, the suspension was cooled to 5° C. or below and was stirred overnight. The crystals were collected by filtration, were washed with n-hexane (20 ml) and were dried under the reduced pressure to give 2-bromoimidazo[5,1-b]thiazole (1.02 g, yield 68.5%) as a white solid.
Reaction SMILES: C(OC(N[C@:7]([CH2:35]CC)([C:15]([N:17]1[CH2:34][CH2:33][CH2:32][C@H:18]1[C:19]([NH:21][C@H:22]([CH:30]=[O:31])[CH2:23][CH2:24][CH2:25][NH:26][C:27](=[NH:29])[NH2:28])=[O:20])=O)CC1C=CC=CC=1)=O)C.[ClH:38].[CH2:39]([O:41][C:42]([NH:44][C@:45](CCC)([C:53](N1CCC[C@H]1C(OCC1C=CC=CC=1)=O)=[O:54])[CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:43])[CH3:40]>>[ClH:38].[CH2:39]([O:41][C:42]([NH:44][C@H:45]([C:53]([C@@:18]1([C:19]([NH:21][C@H:22]([CH:30]=[O:31])[CH2:23][CH2:24][CH2:25][NH:26][C:27](=[NH:29])[NH2:28])=[O:20])[CH2:32][CH2:33][CH2:34][N:17]1[CH2:15][CH2:7][CH3:35])=[O:54])[CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:43])[CH3:40]
Reactant: CCC[C@@](Cc1ccccc1)(NC(=O)OCC)C(=O)N1CCC[C@H]1C(=O)N[C@H](C=O)CCCNC(=N)N
Reactant: CCC[C@@](Cc1ccccc1)(NC(=O)OCC)C(=O)N1CCC[C@H]1C(=O)OCc1ccccc1
Agent: Cl
Product: CCCN1CCC[C@]1(C(=O)N[C@H](C=O)CCCNC(=N)N)C(=O)[C@H](Cc1ccccc1)NC(=O)OCC

Procedure:
By methods substantially equivalent to those described in Example 15, 0.34 g of EtOCO-Phe(αn-Pr)-Pro-Arg-H·HCl was prepared from EtOCO-Phe(αn-Pr)-Pro-OBzl (TLC Rf =0.67, 50% ethyl acetate:hexanes). EtOCO-Phe(αn-Pr)-Pro-Arg-H·HCl was purified by RPHPLC (98/2 (A/B), 60 min; to 80/20 (A/B), 300 min).
Reaction SMILES: [CH3:1][C:2]1[C:8](=[O:9])[C:7]2[N:10]3[C@@:14]([O:21][CH3:22])([C@H:15]([CH2:16][O:17][C:18]([NH2:20])=[O:19])[C:6]=2[C:4](=[O:5])[C:3]=1OC)[C@H:13]1[N:23]([CH3:24])[C@H:12]1[CH2:11]3.[CH3:27][OH:28]>C(N)C1OC=CC=1>[C:18](=[O:17])([OH:19])[NH2:20].[OH:17][CH2:16][CH:15]1[C:6]2[C:4](=[O:5])[C:3]([NH:10][CH2:7][C:6]3[O:28][CH:27]=[CH:3][CH:4]=3)=[C:2]([CH3:1])[C:8](=[O:9])[C:7]=2[N:10]2[CH2:11][CH:12]3[N:23]([CH3:24])[CH:13]3[C:14]12[O:21][CH3:22]
Reactant: COC1=C(C)C(=O)C2=C(C1=O)[C@@H](COC(N)=O)[C@@]1(OC)[C@@H]3[C@H](CN21)N3C
Reactant: CO
Agent: NCc1ccco1
Product: COC12C(CO)C3=C(C(=O)C(C)=C(NCc4ccco4)C3=O)N1CC1C2N1C
Product: NC(=O)O
Yield: 55.7 %

Procedure:
To a solution of 50 mg (0.13 mmol) of N-methylmitomycin A in 6 ml of anhydrous methanol, 0.5 ml of furfurylamine was added with stirring. The solvent was removed by evaporation under reduced pressure and the residue was chromatographed using silica-gel as adsorbent. The fraction obtained by eluting the column with a mixture of chloroform and ethyl acetate (1:1 by volume) was evaporated under reduced pressure. Recrystallization from a mixture of chloroform and hexane gave 31 mg (55.7% yield) of the desired product as purple colored crystals having a melting point of 140°-141° (decomposing) and providing the following analyses:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:17]([C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=2)=[C:11]2[N:12]=[CH:13][N:14]=[C:15]([OH:16])[C:10]2=[N:9]1.C([O-])([O-])=O.[Cs+].[Cs+].CS(C)=O.FC(F)(F)S(O[CH2:44][C:45]([F:48])([F:47])[F:46])(=O)=O>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:17]([C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:25])[F:26])=[CH:20][CH:19]=2)=[C:11]2[N:12]=[CH:13][N:14]([CH2:44][C:45]([F:48])([F:47])[F:46])[C:15](=[O:16])[C:10]2=[N:9]1
Reactant: O=S(=O)(OCC(F)(F)F)C(F)(F)F
Reactant: Oc1ncnc2c(-c3ccc(C(F)(F)F)cc3)n(-c3ccccc3Cl)nc12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CS(C)=O
Product: O=c1c2nn(-c3ccccc3Cl)c(-c3ccc(C(F)(F)F)cc3)c2ncn1CC(F)(F)F
Reaction time: 8 h

Procedure:
To a stirred mixture of 2-(2-chlorophenyl)-3-(4-(trifluoromethyl)phenyl)-2H-pyrazolo[4,3-d]pyrimidin-7-ol (I-2A-2b: 100 mg, 0.26 mmol) and Cs2CO3(85 mg, 0.26 mmol) in DMF (1.5 ml) was added a DMSO solution (0.1 ml) of 2,2,2-trifluoroethyl trifluoromethanesulfonate (60 mg, 0.26 mmol). After stirring overnight, the reaction mixture was extracted from water with ethyl acetate. The organic solution was washed with half saturated aqueous NaCl and then concentrated in vacuo. The crude residue was purified on a Biotage™ Flash 12S column using 20% ethyl acetate in hexanes as eluant to give the title compound 2A-2 (65 mg, 53%) as a solid: +ES MS (M+1) 473.4; 1H NMR (CD3OD) δ 8.17 (s, 1H), 7.73–7.52 (m, 8H), 4.83 (q, J=9.1 Hz, 2H).
Reaction SMILES: IC.[CH3:3][O:4][C:5](=[O:38])[CH2:6][C@H:7]1[C:11]2[CH:12]=[CH:13][C:14]([O:16][C@H:17]3[C:25]4[C:20](=[C:21]([CH2:30][C:31]5[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][CH:32]=5)[C:22]([C:26]([F:29])([F:28])[F:27])=[CH:23][CH:24]=4)[CH2:19][CH2:18]3)=[CH:15][C:10]=2[O:9][CH2:8]1.[C:39]([O-])([O-])=O.[K+].[K+]>CN(C)C=O>[CH3:3][O:4][C:5](=[O:38])[CH2:6][C@H:7]1[C:11]2[CH:12]=[CH:13][C:14]([O:16][C@H:17]3[C:25]4[C:20](=[C:21]([CH2:30][C:31]5[CH:36]=[CH:35][C:34]([O:37][CH3:39])=[CH:33][CH:32]=5)[C:22]([C:26]([F:27])([F:28])[F:29])=[CH:23][CH:24]=4)[CH2:19][CH2:18]3)=[CH:15][C:10]=2[O:9][CH2:8]1
Reactant: O=C([O-])[O-]
Reactant: COC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c3ccc(C(F)(F)F)c4Cc3ccc(O)cc3)ccc21
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: COC(=O)C[C@@H]1COc2cc(O[C@@H]3CCc4c3ccc(C(F)(F)F)c4Cc3ccc(OC)cc3)ccc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Iodomethane (8 μL) is added to a mixture of {(S)-6-[(R)-4-(4-hydroxy-benzyl)-5-trifluoromethyl-indan-1-yloxy]-2,3-dihydro-benzofuran-3-yl}-acetic acid methyl ester (30 mg), K2CO3 (15 mg), and N,N-dimethylformamide (1 mL) at room temperature. The mixture is stirred at room temperature overnight. The mixture is filtered and then chromatographed (HPLC; acetonitrile/water) to give the title compound. LC (method 6): tR=1.26 min; Mass spectrum (ESI+): m/z=535 [M+Na]+.
Reaction SMILES: I[CH2:2]CI.ICI.[Cl:8][C:9]1[CH:25]=[CH:24][C:12]([CH2:13][CH:14]2[C:18](=[O:19])[CH:17]([C:20]([F:23])([F:22])[F:21])[CH2:16][CH2:15]2)=[CH:11][CH:10]=1.[OH-].[Na+].Cl>C1COCC1>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:13][CH:14]2[C:18]3([O:19][CH2:2]3)[CH:17]([C:20]([F:21])([F:22])[F:23])[CH2:16][CH2:15]2)=[CH:24][CH:25]=1
Reactant: O=C1C(Cc2ccc(Cl)cc2)CCC1C(F)(F)F
Reactant: ICCI
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ICI
Solvent: C1CCOC1
Product: FC(F)(F)C1CCC(Cc2ccc(Cl)cc2)C12CO2
Reaction time: 2 h

Procedure:
Under nitrogen flow, anhydrous THF (1 ml) was combined with Sm (705 mg, 4.7 mmol), and a solution of 1,2-diiodoethane (662 mg, 2.3 mmol) dissolved in anhydrous THF (2 ml) was added dropwise with stirring. The reaction solution was stirred for 30 minutes at room temperature. Thereafter, while cooling with ice, a solution of diiodomethane (723 mg, 2.7 mmol) and 5-(4-chlorobenzyl)-2-trifluoromethylcyclopentanone (Compound (V), (Ra)Xana=H, (Rb)Xbnb=CF3, Ym=4-Cl) (432 mg, 1.6 mmol) dissolved in anhydrous THF (2 ml) was added dropwise, and stirring was continued for 2 hours at room temperature. The reaction solution was poured into a solution mixture of an aqueous solution of NaOH (NaOH (1.1 g) dissolved in 10 ml of water) and THF (10 ml), and stirring was continued for 30 minutes at room temperature. This reaction solution was combined with ice, neutralized with a 1N aqueous solution of hydrochloric acid, and then extracted with hexane. The organic layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure. Silica gel chromatography (eluent; hexane:ethyl acetate=70:1) was conducted for purification to obtain the desired substance.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([O:10][CH3:11])[C:3]=1[C:12](=[O:14])[CH3:13].[CH3:15][O:16][C:17]1[CH:18]=[CH:19][C:20]([CH:23]=O)=[CH:21][CH:22]=1.[OH-].[K+].O>C(O)C>[OH:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([O:10][CH3:11])[C:3]=1[C:12](=[O:14])[CH:13]=[CH:23][C:20]1[CH:19]=[CH:18][C:17]([O:16][CH3:15])=[CH:22][CH:21]=1
Reactant: COc1ccc(C=O)cc1
Reactant: COc1cc(O)c(C(C)=O)c(OC)c1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: COc1ccc(C=CC(=O)c2c(O)cc(OC)cc2OC)cc1
Temperature: 25 °C
Reaction time: 72 h
Yield: 58 %

Procedure:
To a stirred solution containing 196 mg of 2'-hydroxy-4',6'-dimethoxyacetophenone and 150 mg of anisaldehyde in 3 ml of ethanol was added 50% aqueous potassium hydroxide (3 ml). After being stirred at room temperature for 3 days, the mixture was poured into 30 ml of cold water. The mixture was then extracted with three 30 ml portions of ethyl acetate. The combined ethyl acetate extracts were washed with water, dried over anhydrous sodium sulfate and then evaporated under reduced pressure to give a crystalline residue. Recrystallization of the residue from methanol gave 182 mg (50% yield) of 2'-hydroxy-4,4',6'-trimethoxychalcone as yellow needles: m.p. 110.7° C.
Reaction SMILES: [N+:1]([C:4]1[CH:20]=[CH:19][C:7]([CH:8]2[CH2:17][C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[O:9]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].C=O.Cl.[CH3:24]NC.Cl>C(OCC)(=O)C.CC(C)=O.CC(O)C>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH:8]2[C:17](=[CH2:24])[C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[O:9]2)=[CH:19][CH:20]=1)([O-:3])=[O:2]
Reactant: O=C1CC(c2ccc([N+](=O)[O-])cc2)Oc2ccccc21
Reactant: CNC
Agent: C=O
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CC(C)O
Solvent: CC(C)=O
Product: C=C1C(=O)c2ccccc2OC1c1ccc([N+](=O)[O-])cc1
Yield: 4.3 %

Procedure:
A mixture of 18.1 g (67 mmol) of 4'-nitro flavanone, prepared as described in J. Chem. Soc. Japan, Pure Chem. Sect. 74, 827 (1953), 4.04 g (134 mmol) of paraformaldehyde, 10.97 g (134 mmol) of dimethylamine hydrochloride, 1 ml of concentrated HCl, and 200 ml of 2-propanol was refluxed for three hours. When cool, the solvent was removed under reduced pressure and the residue partitioned between CHCl3 and 5 percent aqueous HCl. The layers were separated and the organic layer was washed with 3-100 ml portions of 5 percent HCl. The combined aqueous extracts were neutralized with solid Na2CO3 and extracted with ether. The ether was dried over anhydrous Na2SO4, filtered, and concentrated. The oily residue was dissolved in ethyl acetate and treated with 1 ml of ethanol and 1.5 ml of acetyl chloride. The solvent was then evaporated to give a glassy residue. This was taken up in 500 ml of hot ethyl acetate containing 20 ml of acetone and cooled. A precipitate formed that was recrystallized from methanol to give 810 mg of 4'-nitro-3-methylene flavanone as a solid, m.p. 135°-136° C.
Reaction SMILES: [C:1]1([CH3:21])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]1[O:9][C:10]2[CH:16]=[C:15]([CH2:17][C:18](O)=[O:19])[CH:14]=[CH:13][C:11]=2[N:12]=1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[CH2:55]([O:57][C:58](=[O:77])[CH2:59][CH:60]([C:67]1[CH:76]=[C:75]2[C:70]([CH2:71][CH2:72][NH:73][CH2:74]2)=[CH:69][CH:68]=1)[C:61]1[CH:66]=[CH:65][N:64]=[CH:63][CH:62]=1)[CH3:56]>CN(C)C=O>[CH2:55]([O:57][C:58](=[O:77])[CH2:59][CH:60]([C:61]1[CH:62]=[CH:63][N:64]=[CH:65][CH:66]=1)[C:67]1[CH:76]=[C:75]2[C:70]([CH2:71][CH2:72][NH:73][CH:74]2[C:18](=[O:19])[CH2:17][C:15]2[CH:14]=[CH:13][C:11]3[N:12]=[C:8]([NH:7][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=4[CH3:21])[O:9][C:10]=3[CH:16]=2)=[CH:69][CH:68]=1)[CH3:56]
Reactant: Cc1ccccc1Nc1nc2ccc(CC(=O)O)cc2o1
Reactant: CCOC(=O)CC(c1ccncc1)c1ccc2c(c1)CNCC2
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)CC(c1ccncc1)c1ccc2c(c1)C(C(=O)Cc1ccc3nc(Nc4ccccc4C)oc3c1)NCC2
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
A solution of 2-o-tolylaminobenzoxazole-6-acetic acid (0.124 g) and diisopropylethylamine (0.17 g) in dimethylformamide (2 mL) was treated with a solution of O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (0.183 g) in dimethylformamide. After 10 minutes at room temperature this yellow solution was added dropwise to a rapidly stirred solution of 3-(1,2,3,4-tetrahydro-isoquinolin-7-yl)-3-(pyrid-4-yl)-propionic acid ethyl ester, enantiomer A {0.219 mmoles, Reference Example 17(a)} in dimethylformamide. After stirring at room temperature for 2.5 hours the reaction mixture was evaporated. The residual oil was dissolved in a mixture of acetonitrile, water and trifluoroacetic acid (25:75:0.1) and treated with dimethylformamide and trifluoroacetic acid to bring to pH2. This mixture was subjected to preparative HPLC {Hypersil Elite C18 column, 10 cm×2.1 cm, using a mixture of acetonitrile, water and trifluoroacetic acid (25:75:0.1) as the mobile phase followed by a 1% acetonitrile/minute gradient) to give the title compound. LC-MS:MS (ES)=575 (M+H)+, 573 (M−H)−.
Reaction SMILES: C[CH:2]([O:4][C:5]([CH2:7][CH2:8][CH2:9]/[CH:10]=[CH:11]\[CH2:12][C@@H:13]1[C@@H:17]([CH2:18][CH2:19][C@@H:20]([OH:29])[CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C@H:16]([OH:30])[CH2:15][C@@H:14]1[OH:31])=[O:6])C>CO.CC(O)=O>[OH:30][C@@H:16]1[CH2:15][C@H:14]([OH:31])[C@H:13]([CH2:12]/[CH:11]=[CH:10]\[CH2:9][CH2:8][CH2:7][C:5]([O:4][CH3:2])=[O:6])[C@H:17]1[CH2:18][CH2:19][C@@H:20]([OH:29])[CH2:21][CH2:22][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: CC(C)OC(=O)CCC/C=C\C[C@@H]1[C@@H](CC[C@@H](O)CCc2ccccc2)[C@H](O)C[C@@H]1O
Solvent: CO
Solvent: CC(=O)O
Product: COC(=O)CCC/C=C\C[C@@H]1[C@@H](CC[C@@H](O)CCc2ccccc2)[C@H](O)C[C@@H]1O

Procedure:
To Latanoprost free acid in MeOH at 0° C. was added TMS-CH2N2 until the solution persisted a yellow color. AcOH (2 drops) were added to quench excess TMS-CH2N2 and the solvents were evaporated. Column chromatography 70%-100% EtOAc/Hexanes gave pure (Z) -methyl 7-((1R,2R,3R,5S)-3,5-dihydroxy-2-((R)-3-hydroxy -5-phenylpentyl)cyclopentyl)hept-5-enoate (2).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[Cl:18])[O:5][CH:6]1[CH2:11][CH2:10][N:9]([CH2:12][CH2:13][NH2:14])[CH2:8][CH2:7]1.[CH3:19][S:20]([C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=1)[C:26](O)=[O:27])(=[O:22])=[O:21].C(N(CC)CC)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[Cl:18])[O:5][CH:6]1[CH2:7][CH2:8][N:9]([CH2:12][CH2:13][NH:14][C:26](=[O:27])[C:25]2[CH:29]=[CH:30][CH:31]=[C:23]([S:20]([CH3:19])(=[O:22])=[O:21])[CH:24]=2)[CH2:10][CH2:11]1
Reactant: NCCN1CCC(Oc2ccc(Cl)c(Cl)c2)CC1
Reactant: CS(=O)(=O)c1cccc(C(=O)O)c1
Agent: Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CS(=O)(=O)c1cccc(C(=O)NCCN2CCC(Oc3ccc(Cl)c(Cl)c3)CC2)c1
Product: Cl
Yield: 47.8 %

Procedure:
The product of Step b (0.200 g) was dissolved in DMF (5 ml). 3-Methylsulphonyl-benzoic acid (0.132 g), triethylamine (0.250 ml) and PyBrop® (0.420 g) were added. After 24 hours at room temperature the solvents were evaporated and the residue redissolved in ethyl acetate. The organics were washed with H2O, dried with MgSO4 and concentrated. Purification by reverse phase HPLC (with a gradient eluent system (25% MeCN/NH4OAcaq (0.1%) to 95% MeCN//NH4OAcaq (0.1%)) (any excess NH4OAc was removed by dissolving the compound in ethyl acetate and washing with aqueous saturated NaHCO3 followed by drying of the organics with MgSO4 and evaporation of solvent) and formation of the hydrochloride salt by addition of HCl dissolved in ether and evaporation of solvent gave the title compound (0.084 g).
Reaction SMILES: [CH2:1]([O:11][C:12]1[CH:13]=[C:14]([N:29]2[CH2:34][C:33](=[O:35])[O:32][C:31](=[O:36])[CH2:30]2)[CH:15]=[C:16]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[CH:17]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[CH2:37]([N:39]([CH2:43][CH3:44])[CH2:40][CH2:41][OH:42])[CH3:38].C(Cl)[Cl:46]>>[ClH:46].[CH2:37]([N:39]([CH2:43][CH3:44])[CH2:40][CH2:41][O:42][C:33](=[O:35])[CH2:34][N:29]([C:14]1[CH:15]=[C:16]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[CH:17]=[C:12]([O:11][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])[CH:13]=1)[CH2:30][C:31]([OH:36])=[O:32])[CH3:38]
Reactant: CCN(CC)CCO
Reactant: ClCCl
Reactant: CCCCCCCCCCOc1cc(OCCCCCCCCCC)cc(N2CC(=O)OC(=O)C2)c1
Product: CCCCCCCCCCOc1cc(OCCCCCCCCCC)cc(N(CC(=O)O)CC(=O)OCCN(CC)CC)c1
Product: Cl
Yield: 82 %

Procedure:
A solution of 0.43 g (0.85 mmol) of 4-[3,5-bis(decyloxy)phenyl]2,6-morpholinedione and 0.23 ml (1.71 mmol) of N,N-diethylethanolamine in 40 ml of methylene chloride was kept at room temperature for 3.5 days. The solvent was removed at reduced pressure and the residue was dissolved in ethyl acetate. The extract was washed with water and then with 0.5N HCl, dried and concentrated at reduced pressure to a yellow foam which was dissolved in ether and cooled. Filtration gave 0.46 g (82% yield, mp 89°-91°) of N-(2-diethylaminoethoxy-2-oxoethyl)-N-[3,5-bis(decyloxy)phenyl]glycine monohydrochloride salt
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]([CH3:10])[C:8]3=[N:11][C:12]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[C:13]([CH2:14][C:15]([OH:17])=O)[N:7]3[C:6]=2[CH:24]=1.[NH3:25]>O1CCCC1>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]([CH3:10])[C:8]3=[N:11][C:12]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[C:13]([CH2:14][C:15]([NH2:25])=[O:17])[N:7]3[C:6]=2[CH:24]=1
Reactant: Cc1ccc2c(c1)n1c(CC(=O)O)c(-c3ccccc3)nc1n2C
Reactant: N
Solvent: C1CCOC1
Product: Cc1ccc2c(c1)n1c(CC(N)=O)c(-c3ccccc3)nc1n2C
Reaction time: 2 h

Procedure:
A suspension of 1.5 g (0.0047 mol) of 6,9-dimethyl-2-phenyl-9H-imidazo[1,2-a]benzimidazole-3-acetic acid is prepared in 50 ml of dry tetrahydrofuran. 1.22 g (0.0075 mol) of N,N'-carbonyldiimidazole are added thereto and the mixture is stirred for 2 h at 40°-45° C. The solution obtained is then treated with an excess of dry ammonia and stirred for 2 h. The solvent is evaporated under reduced pressure. The residue is washed with water and dried. The product obtained is purified by silica gel column chromatography, eluting with a chloroform/acetone 95/5 mixture and 0.71 g of product is isolated. Melting point: 247°-249° C. (decomposition).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:21])[C:7]=1[CH2:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:19][CH3:20])=[CH:16][CH:17]=2)[CH2:12][NH:11][N:10]=1.[CH2:22](N(CC)CC)C.[CH2:29]1C[O:32][CH2:31][CH2:30]1>>[C:2]([Cl:1])(=[O:32])[CH:7]([CH3:8])[CH3:6].[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:21])[C:7]=1[CH2:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:19][CH3:20])=[CH:16][CH:17]=2)[CH2:12][N:11]([C:31](=[O:32])[CH:30]([CH3:29])[CH3:22])[N:10]=1
Reactant: CCN(CC)CC
Reactant: COc1ccc2c(c1)CNN=C2Cc1c(Cl)cncc1Cl
Reactant: C1CCOC1
Product: CC(C)C(=O)Cl
Product: COc1ccc2c(c1)CN(C(=O)C(C)C)N=C2Cc1c(Cl)cncc1Cl

Procedure:
Operating substantially as described in example 25 starting from 4-(3,5-dichloro-pyridin-4-ylmethyl)-7-methoxy-1,2-dihydro-phthalazine (1 g, 3.1 mmoles), prepared as described in example 22, in dry THF (35 ml), triethylamine (1.08 ml, 7.76 mmoles) and isobutanoyl chloride (0.39 ml, 3.72 mmoles), 1 g of the title compound was obtained (yield: 83%). m.p.: 210-212° C.
Reaction SMILES: [CH2:1]([C:5]1[C:6](Cl)=[N:7][C:8]([Cl:12])=[N:9][C:10]=1[CH3:11])[CH2:2][CH2:3][CH3:4].[C:14]1(B(O)O)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O.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>[CH2:1]([C:5]1[C:10]([CH3:11])=[N:9][C:8]([Cl:12])=[N:7][C:6]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:2][CH2:3][CH3:4]
Reactant: OB(O)c1ccccc1
Reactant: CCCCc1c(C)nc(Cl)nc1Cl
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: CCO
Solvent: O
Solvent: Cc1ccccc1
Product: CCCCc1c(C)nc(Cl)nc1-c1ccccc1
Reaction time: 6 h

Procedure:
A mixture of 5-butyl-2,4-dichloro-6-methyl-pyrimidine (711 mg, 3.24 mmol), phenylboronic acid (475 mg, 3.89 mmol), Na2CO3 (1.03 g, 9.73 mmol), and Pd(PPh3)4 (187 mg, 0.162 mmol) in toluene-EtOH—H2O (4 ml-0.5 ml-2 mL) is stirred at relux for 6 hours. After cooling, the reaction mixture is diluted with H2O and extracted with EtOAc. The extract is then washed with brine, dried over Na2SO4, and concentrated. The residue is purified by flash chromatography on silica gel. Elution with 8:1 hexanes-EtOAc followed by 7:1 hexanes-EtOAc affords 5-butyl-2-chloro-4-methyl-6-phenyl-pyrimidine as a colorless oil. 1H NMR (CDCl3, 300 MHz) δ 7.45 (m, 5H), 2.65–2.62 (m, 2H), 2.60 (s, 3H), 1.46–1.36 (m, 2H), 1.25 (sext, J=7.2 Hz, 2H), 0.81 (t, J=7.2 Hz, 3H) ppm.
Reaction SMILES: [C:1]1(C(O)=O)[C:14]2[C:15]3=[C:16]4[C:11](=[CH:12][CH:13]=2)[CH:10]=[CH:9][CH:8]=[C:7]4[CH:6]=[CH:5][C:4]3=[CH:3][CH:2]=1>C(O)C>[CH:8]1[C:7]2[C:16]3=[C:15]4[C:4](=[CH:5][CH:6]=2)[CH:3]=[CH:2][CH:1]=[C:14]4[CH:13]=[CH:12][C:11]3=[CH:10][CH:9]=1.[C:1]
Reactant: O=C(O)c1ccc2ccc3cccc4ccc1c2c34
Solvent: CCO
Product: [C]
Product: c1cc2ccc3cccc4ccc(c1)c2c34
Reaction time: 6 h

Procedure:
1-Pyrenecarboxylic acid (1-PCA, 250 mg) was stirred in ethanol (400 mL) for 30 minutes. Herringbone-type carbon nanofiber (CNF, 500 mg) was added to the 1-PCA solution and stirred for 6 hours. Then, CNF doped with 1-PCA was recovered through filtration under reduced pressure. 1-PCA was introduced to CNF in order to form π-π interaction between pyrene and graphene of CNF. The 1-PCA-doped CNF has a hydrophilic surface and allows easy supporting of platinum. The 1-PCA-doped CNF (140 mg) was added to ethylene glycol (25 mL) and stirred for 10 minutes. Then, after adding NaOH (100 mg), the mixture was further stirred for 10 minutes. The concentration of NaOH was 0.1 M. NaOH serves to adjust pH for control of the platinum particle size. Subsequently, after adding PtCl4 (150 mg) and stirring for about 10 minutes, the mixture was refluxed at 160° C. for 3 hours. Then, platinum ions are reduced and adsorbed on the surface of CNF. In order to further increase the supporting ratio, after stirring at room temperature for 12 hours, the solution was further stirred for 24 hours after lowering pH to 1-2. The resulting solution was filtered under reduced pressure and washed several times with ultrapure water. The recovered catalyst was dried at 160° C. for 1 hour to remove impurities.