Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3](=[O:31])[CH2:4][S:5]([CH2:8][C:9]1[C:13]2[CH:14]=[C:15]([N:18]3[C:23](=[O:24])[CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[N:20]([CH3:29])[C:19]3=[O:30])[CH:16]=[CH:17][C:12]=2[S:11][N:10]=1)(=[O:7])=[O:6].Cl>C(O)(=O)C>[CH3:29][N:20]1[C:21]([C:25]([F:28])([F:27])[F:26])=[CH:22][C:23](=[O:24])[N:18]([C:15]2[CH:16]=[CH:17][C:12]3[S:11][N:10]=[C:9]([CH2:8][S:5]([CH2:4][C:3]([OH:31])=[O:2])(=[O:7])=[O:6])[C:13]=3[CH:14]=2)[C:19]1=[O:30]
Reactant: COC(=O)CS(=O)(=O)Cc1nsc2ccc(-n3c(=O)cc(C(F)(F)F)n(C)c3=O)cc12
Agent: Cl
Solvent: CC(=O)O
Product: Cn1c(C(F)(F)F)cc(=O)n(-c2ccc3snc(CS(=O)(=O)CC(=O)O)c3c2)c1=O
Temperature: 60 °C
Reaction time: 8 h
Yield: 78.1 %

Procedure:
A mixture of methyl{{{5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-1,2-benzisothiazol-3-yl}methyl}sulfonyl}acetate (1.00 g, 0.00210 mol), acetic acid and 10% hydrochloric acid (2.00 ml) is stirred overnight at 60° C. Additional hydrochloric acid (37%, 1.20 ml) is added and the mixture is stirred 5 hours at 80° C. The mixture is cooled to room temperature, poured into ice water with stirring, and filtered to give the title compound as a white solid (0.760 g, 78.4%, mp 215° C.) which is identified by NMR spectral analysis.
Reaction SMILES: C([S:4][C:5]1[C:6]([Cl:24])=[CH:7][C:8]([F:23])=[C:9]([C:11]2[C:12](=[O:22])[N:13]([CH3:21])[C:14]([C:17]([F:20])([F:19])[F:18])=[CH:15][CH:16]=2)[CH:10]=1)(=O)C.[OH-].[Na+].O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CO>[Cl:24][C:6]1[C:5]([SH:4])=[CH:10][C:9]([C:11]2[C:12](=[O:22])[N:13]([CH3:21])[C:14]([C:17]([F:20])([F:18])[F:19])=[CH:15][CH:16]=2)=[C:8]([F:23])[CH:7]=1
Reactant: CC(=O)Sc1cc(-c2ccc(C(F)(F)F)n(C)c2=O)c(F)cc1Cl
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: Cn1c(C(F)(F)F)ccc(-c2cc(S)c(Cl)cc2F)c1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 92.3 %

Procedure:
2.8 g (7.7 mmol) of 3-(5-acetylthio-4-chloro-2-fluorophenyl)-1-methyl-6-trifluoromethyl-2(1H)-pyridone was dissolved in 30 ml of methanol, 8.5 ml (8.5 mmol) of a 1N sodium hydroxide aqueous solution was dropwise added thereto under cooling with ice After stirring at room temperature for 1 hour, the mixture was poured into water and acidified with citric acid and extracted with ethyl acetate. After washing with water and a saturated sodium chloride aqueous solution, the organic layer was dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure. Then, the obtained crude crystals were washed with n-hexane to obtain 2.4 g (yield: 93%) of the desired product. Melting point: 141-142° C.
Reaction SMILES: [CH2:1]([CH:9]1[CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14](B(O)O)[CH:15]=2)[O:10]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].C(O)C.Br[C:25]1[CH:26]=[C:27]([C:31]2[N:36]=[CH:35][C:34]([CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46])=[CH:33][N:32]=2)[CH:28]=[CH:29][CH:30]=1.C(=O)([O-])[O-].[Na+].[Na+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1C=CC=CC=1>[CH2:37]([C:34]1[CH:35]=[N:36][C:31]([C:27]2[CH:28]=[CH:29][C:30]([C:14]3[CH:15]=[C:16]4[C:11](=[CH:12][CH:13]=3)[O:10][CH:9]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH2:17]4)=[CH:25][CH:26]=2)=[N:32][CH:33]=1)[CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46]
Reactant: CCCCCCCCC1Cc2cc(B(O)O)ccc2O1
Reactant: CCCCCCCCCCc1cnc(-c2cccc(Br)c2)nc1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: c1ccccc1
Solvent: CCO
Product: CCCCCCCCCCc1cnc(-c2ccc(-c3ccc4c(c3)CC(CCCCCCCC)O4)cc2)nc1
Yield: 66.5 %

Procedure:
Under nitrogen atmosphere, 0.25 g (0.91 mM) of 2-octylcoumaran-5-boronic acid, 0.7 ml of ethanol, 0.30 g (0.80 mM) of 2-(3-bromophenyl)-5-decylpyrimidine and 1.3 ml of benzene were placed in a 20 ml-round-bottomed flask. Under stirring, 0.05 g of tetrakis(triphenylphosphine) palladium (0) and 1.3 ml of a 2M-sodium carbonate aqueous solution were added successively to the mixture, followed by refluxing for 1 hour and 40 minutes. After the reaction, the reaction mixture was left standing at room temperature to precipitate a crystal. The crystal was washed with water and dissolved in toluene. The solution was dried with mirabilite and the solvent was distilled off under reduced pressure to obtain a residue. The residue was purified by silica gel column chromatography and recrystallized from a mixture solvent of toluene and methanol and further recrystallized from acetone to obtain 0.28 g of 5-[4-(5-decylpyrimidine-2-yl)phenyl]-2-octylcoumaran (Ex. Comp. No. I-154) (Yield: 66.5%). The product showed the following phase transition temperatures (°C.). ##STR98##
Reaction SMILES: [CH3:1][C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:19]=[C:18]([CH2:20][O:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH2:28][C:29]([O:31]C)=[O:30])[O:17][N:16]=1.O1CCCC1.[OH-].[Na+].Cl>O.CO>[CH3:1][C:2]1[S:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:19]=[C:18]([CH2:20][O:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH2:28][C:29]([OH:31])=[O:30])[O:17][N:16]=1
Reactant: COC(=O)Cc1ccccc1OCc1cc(OCc2nc(-c3ccccc3)sc2C)no1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: Cc1sc(-c2ccccc2)nc1COc1cc(COc2ccccc2CC(=O)O)on1
Temperature: 50 °C
Reaction time: 1 h
Yield: 93.8 %

Procedure:
To a mixture of methyl 2-[2-[[3-[(5-methyl-2-phenyl-4-thiazolyl)methoxy]-5-isoxazolyl]methoxy]phenyl]acetate (0.44 g), tetrahydrofuran (3 mL) and methanol (3 mL) was added a 1N aqueous sodium hydroxide solution (3 mL) and the mixture was stirred at 50° C. for 1 hr. 1N Hydrochloric acid (3 mL) and water were added to the reaction mixture, and the precipitated crystals were collected by filtration and dried with air to give crystals (0.40 g, 93%) of 2-[2-[[3-[(5-methyl-2-phenyl-4-thiazolyl)methoxy]-5-isoxazolyl]methoxy]phenyl]acetic acid. Recrystallization from ethyl acetate-hexane gave colorless needle crystals. melting point: 147-148° C.
Reaction SMILES: [CH2:1]([O:8][NH:9][C:10]([C:12]1[C:13](Cl)=[N:14][C:15]([Cl:19])=[C:16]([F:18])[CH:17]=1)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH2:23]([N:30]=[C:31]=[O:32])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CC(N(C)C)=O>[CH2:23]([N:30]1[C:13]2[N:14]=[C:15]([Cl:19])[C:16]([F:18])=[CH:17][C:12]=2[C:10](=[O:11])[N:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:31]1=[O:32])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: O=C(NOCc1ccccc1)c1cc(F)c(Cl)nc1Cl
Reactant: O=C=NCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: O=c1c2cc(F)c(Cl)nc2n(Cc2ccccc2)c(=O)n1OCc1ccccc1
Yield: 82.3 %

Procedure:
Using the General Method 5, the reaction of N-benzyloxy-2,6-dichloro-5-fluoro-3-pyridinecarboxamide (Example M-2, 2.00 g, 6.34 mmol) and 60% NaH in oil (300 mg, 7.52 mmol) with benzyl isocyanate (1.17 mL, 9.51 mmol) in DMA afforded crude product. Recrystallization from chloroform provided 2.15 g of the title compound as a solid, mp 209-210° C.
Reaction SMILES: CO[C:3]([CH3:5])=[CH2:4].C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.[F:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1[C@H:31]([NH:38][C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[C@@H:32]([OH:37])[C:33]([O:35][CH3:36])=[O:34]>C1C=CC=CC=1>[C:42]([O:41][C:39]([N:38]1[C@@H:31]([C:25]2[CH:26]=[CH:27][C:28]([F:30])=[CH:29][C:24]=2[F:23])[C@H:32]([C:33]([O:35][CH3:36])=[O:34])[O:37][C:3]1([CH3:5])[CH3:4])=[O:40])([CH3:45])([CH3:44])[CH3:43]
Reactant: C=C(C)OC
Reactant: COC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)c1ccc(F)cc1F
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: c1ccccc1
Product: COC(=O)[C@@H]1OC(C)(C)N(C(=O)OC(C)(C)C)[C@H]1c1ccc(F)cc1F
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
0.3 ml of isopropenyl methyl ether and 39 mg of pyridinium p-toluenesulfonate were added to a solution of 515 mg of methyl (2R,3S)-3-(2,4-difluorophenyl)-3-tert-butoxycarbonylamino-2-hydroxypropionate dissolved in 30 ml of benzene, and the mixture was stirred at room temperature for 30 minutes. The mixture was further stirred at 90° C. for 30 minutes and then returned to room temperature. 0.3 ml of isopropenyl methyl ether was added to the mixture, and the resulting mixture was stirred at 90° C. for 30 minutes. The mixture was cooled again to room temperature, 0.15 ml of isopropenyl methyl ether was added thereto, and the mixture was stirred at 90° C. for 4 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (solvent; toluene:ethyl acetate=50:1) to obtain 428 mg of methyl (4S,5R)-3-tert-butoxycarbonyl-2,2-dimethyl-4-(2,4-difluorophenyl)-5-oxazolidinecarboxylate.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][CH3:10])[CH:5]=[CH:4][C:3]=1[OH:11].[C:12](O)(=O)[C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1.[OH-].[Na+]>>[CH2:8]([C:6]1[CH:5]=[CH:4][C:3]2[O:11][C:12]([C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)=[N:1][C:2]=2[CH:7]=1)[CH2:9][CH3:10]
Reactant: O=C(O)c1ccncc1
Reactant: CCCc1ccc(O)c(N)c1
Agent: [Na+]
Agent: [OH-]
Product: CCCc1ccc2oc(-c3ccncc3)nc2c1
Temperature: 190 °C
Yield: 38.1 %

Procedure:
A mixture of 1.2 g of 2-amino-4-propylphenol, 0.98 g of isonicotinic acid and 32.8 g of polyphosphoric acid was stirred while heating at 190° C. for five hours. The mixture was cooled to room temperature and then poured into an ice-cooled aqueous solution of sodium hydroxide, followed by extraction with ethyl acetate three times. The combined organic layers were washed with water and a saturated sodium chloride solution, and dried over magnesium sulfate. Activated carbon was added thereto, which was filtered through Celite™. The filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 0.72 g of 5-propyl-2-(pyridin-4-yl)-benzoxazole (hereinafter, referred to as “active compound 1”).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]2[N:9]=[C:10]([NH:12][C:13](=[O:23])[C:14]3[CH:19]=[CH:18][C:17]([CH2:20][NH:21][CH3:22])=[CH:16][CH:15]=3)[S:11][C:7]=2[C:6]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[CH:5][CH:4]=1.[CH3:30][O:31][CH2:32][C:33](Cl)=[O:34]>>[CH3:30][O:31][CH2:32][C:33]([N:21]([CH2:20][C:17]1[CH:16]=[CH:15][C:14]([C:13]([NH:12][C:10]2[S:11][C:7]3[C:6]([N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[C:8]=3[N:9]=2)=[O:23])=[CH:19][CH:18]=1)[CH3:22])=[O:34]
Reactant: COCC(=O)Cl
Reactant: CNCc1ccc(C(=O)Nc2nc3c(OC)ccc(N4CCOCC4)c3s2)cc1
Product: COCC(=O)N(C)Cc1ccc(C(=O)Nc2nc3c(OC)ccc(N4CCOCC4)c3s2)cc1

Procedure:
Using N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-4-methylaminomethyl-benzamide and methoxy-acetyl chloride, the title compound was prepared as yellow solid (83% yield). MS: m/e=485(M+H+).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:16][C:17]([F:29])([F:28])[O:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>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.O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:22]2[CH:21]=[CH:20][C:19]([O:18][C:17]([F:16])([F:28])[F:29])=[CH:24][CH:23]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OB(O)c1ccc(OC(F)(F)F)cc1
Reactant: Brc1ccc(OCc2ccccc2)cc1
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: COCCOC
Solvent: O
Product: FC(F)(F)Oc1ccc(-c2ccc(OCc3ccccc3)cc2)cc1
Yield: 35.9 %

Procedure:
A reaction mixture comprising 6.7 g of 4-benzyloxybromobenzene, 5.0 g of 4-(trifluoromethoxy)benzeneboronic acid, 0.3 g of tetrakis(triphenylphosphine)palladium(0), 5.1 g of sodium carbonate, 100 ml of ethylene glycol dimethyl ether and 20 ml of pure water was refluxed for 5 hours. The reaction mixture was extracted with toluene, and the organic layer was dried with anhydrous magnesium sulfate. The solvent was evaporated away, and the resulting residue was purified through silica gel chromatography (elution solvent: heptane/toluene=7/3) and recrystallized from heptane, and 3.0 g of 4-benzyloxy-4′-(trifluoromethoxy)biphenyl was obtained. m.p.: 136-137.2° C.
Reaction SMILES: [OH:1][NH2:2].C(O[C:6](=[O:30])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]([C:20]1[N:21]=[CH:22][C:23]2[C:28]([CH:29]=1)=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1)C>CN(C=O)C.CO>[OH:1][NH:2][C:6](=[O:30])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]([C:20]1[N:21]=[CH:22][C:23]2[C:28]([CH:29]=1)=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1
Reactant: CCOC(=O)CCCCCCN(c1ccccn1)c1cc2ccccc2cn1
Reactant: NO
Solvent: CN(C)C=O
Solvent: CO
Product: O=C(CCCCCCN(c1ccccn1)c1cc2ccccc2cn1)NO
Reaction time: 72 h
Yield: 54 %

Procedure:
HONH2 (50% aqueous, 1 mL) was added to II (40 mg, 0.1 mmol) in DMF (0.5 mL) and MeOH (1 mL) at rt. The reaction mixture was stirred for 72 h, after which the solvents were evaporated under reduced pressure. The resulting residue was dissolved and co-evaporated with toluene (2×2 mL) then was purified by silica gel column chromatography eluting with CH2Cl2/MeOH (100:3 to 100:8) to furnish III as a colourless oil (19 mg, 54%).
Reaction SMILES: [Br:1][CH:2]([C:4]1[N:5]=[C:6]2[S:13][CH:12]=[CH:11][N:7]2[C:8](=[O:10])[CH:9]=1)[CH3:3].[Br:14]N1C(=O)CCC1=O>C(#N)C>[Br:14][C:9]1[C:8](=[O:10])[N:7]2[CH:11]=[CH:12][S:13][C:6]2=[N:5][C:4]=1[CH:2]([Br:1])[CH3:3]
Reactant: O=C1CCC(=O)N1Br
Reactant: CC(Br)c1cc(=O)n2ccsc2n1
Solvent: CC#N
Product: CC(Br)c1nc2sccn2c(=O)c1Br
Temperature: 80 °C
Reaction time: 8 h
Yield: 16.2 %

Procedure:
A mixture of 7-(1-bromoethyl)-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one (17.5 g, 67.5 mmol) and N-bromosuccinimide (14.2 g, 79.8 mmol) in acetonitrile (400 mL) was stirred at 80° C. under N2 overnight. After removal of the solvent under reduced pressure, the resulting solid was dissolved in dichloromethane, washed sequentially with water, saturated aqueous Na2S2O3 and NaHCO3 solution and brine, dried over Na2SO4, and then concentrated to give crude product (3.7 g), which was used in the next step without further purification. LCMS calculated for C8H7Br2N2OS (M+H)+: m/z=336.9. Found: 336.9.
Reaction SMILES: [C:1]1([CH2:7][C:8]([OH:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH:11]1[C:15]2=[N:16][CH:17]=[CH:18][CH:19]=[C:14]2[C:13]([CH:20]=O)=[CH:12]1.C(OC(=O)C)(=O)C.CCN(CC)CC>>[NH:11]1[C:15]2=[N:16][CH:17]=[CH:18][CH:19]=[C:14]2[C:13]([CH:20]=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:8]([OH:10])=[O:9])=[CH:12]1
Reactant: O=C(O)Cc1ccccc1
Reactant: O=Cc1c[nH]c2ncccc12
Solvent: CCN(CC)CC
Solvent: CC(=O)OC(C)=O
Product: O=C(O)C(=Cc1c[nH]c2ncccc12)c1ccccc1
Temperature: 100 °C
Reaction time: 6 h
Yield: 44.3 %

Procedure:
A mixture of phenylacetic acid (0.0376 mol., 5.1 g) and 1H-pyrrolo[2,3-b]pyridine-3-carbaldehyde (0.0376 mol., 5.5 g) in acetic anhydride (0.1881 mol., 17.7 ml) and Et3N (0.0376 mol., 5.2 ml) was stirred at 100° C., for 6 hrs. The obtained solution was cooled to 50° C., quenched with conc. hydrochloric acid (10 ml) and extracted with EtOAc. The organic phase was extracted with 1 N NaOH. 3-(1H-Pyrrolo[2,3-b]pyridin-3-yl) -2-phenyl-2-propenoic acid was then precipitated from the aqueous layer with conc. hydrochloric acid with ice-cooling. Filtration and recrystallization from isopropyl alcohol of the crude product afforded 4,4 g of the desired compound as a white solid (44%), m.p. >230° C.
Reaction SMILES: Br[C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[C:9]([S:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH:10]=[CH:11][CH:12]=3)[C:7](=[O:24])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[N+:25]([C:28]1[CH:34]=[CH:33][C:31]([NH2:32])=[CH:30][CH:29]=1)([O-:27])=[O:26].C(=O)([O-])[O-].[Na+].[Na+].ClC1C=CC=CC=1Cl>O.N1C=CC=CC=1.C1(C)C=CC=CC=1>[N+:25]([C:28]1[CH:34]=[CH:33][C:31]([NH:32][C:2]2[C:15]3[C:14](=[O:16])[C:13]4[C:8](=[C:9]([S:17][C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=5)[CH:10]=[CH:11][CH:12]=4)[C:7](=[O:24])[C:6]=3[CH:5]=[CH:4][CH:3]=2)=[CH:30][CH:29]=1)([O-:27])=[O:26]
Reactant: Nc1ccc([N+](=O)[O-])cc1
Reactant: O=C1c2cccc(Sc3ccccc3)c2C(=O)c2cccc(Br)c21
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Clc1ccccc1Cl
Solvent: O
Solvent: Cc1ccccc1
Product: O=C1c2cccc(Sc3ccccc3)c2C(=O)c2cccc(Nc3ccc([N+](=O)[O-])cc3)c21

Procedure:
A mixture of 9.87 parts of 1-bromo-5-phenylmercaptoanthraquinone (melting point 191°-193°), 4.32 parts of 4-nitroaniline, 2.5 parts of sodium carbonate, 58 parts of o-dichlorobenzene, 6 parts of toluene and a solution of 0.4 part of copper-I iodide in 1.5 parts of pyridine is heated to the boil (160°-165°) for 24 hours, whilst stirring. The water which is liberated in the course of the reaction is separated off by means of a water separator. After stirring for 3 hours at 20°, the reaction product is filtered off, washed in portions with a little o-dichlorobenzene, then with methanol and also with water and finally heated to the boil with 5% strength hydrochloric acid. After filtering, washing and drying, 9.03 parts, that is to say 80% of theory, of 1-(4'-nitrophenylamino)-5-phenylmercaptoanthraquinone with a melting point of 242°-244° are obtained. The properties of this compound are completely identical to those of the colorant obtained according to Example 1.
Reaction SMILES: [F:1][C:2]1[C:3]([CH2:29][CH2:30][C:31]2[S:32][CH:33]=[C:34]([CH:36]([CH3:38])[CH3:37])[N:35]=2)=[CH:4][C:5]2[N:6]([CH:28]=1)[C:7](=[O:27])[C:8](/[CH:18]=[CH:19]/[C:20]([O:22]C(C)(C)C)=[O:21])=[C:9]([N:11]1[CH2:16][CH2:15][CH2:14][CH:13]([OH:17])[CH2:12]1)[N:10]=2>Cl.O1CCOCC1>[F:1][C:2]1[C:3]([CH2:29][CH2:30][C:31]2[S:32][CH:33]=[C:34]([CH:36]([CH3:38])[CH3:37])[N:35]=2)=[CH:4][C:5]2[N:6]([CH:28]=1)[C:7](=[O:27])[C:8](/[CH:18]=[CH:19]/[C:20]([OH:22])=[O:21])=[C:9]([N:11]1[CH2:16][CH2:15][CH2:14][CH:13]([OH:17])[CH2:12]1)[N:10]=2
Reactant: CC(C)c1csc(CCc2cc3nc(N4CCCC(O)C4)c(/C=C/C(=O)OC(C)(C)C)c(=O)n3cc2F)n1
Agent: Cl
Solvent: C1COCCO1
Product: CC(C)c1csc(CCc2cc3nc(N4CCCC(O)C4)c(/C=C/C(=O)O)c(=O)n3cc2F)n1
Temperature: 25 °C
Reaction time: 2 h
Yield: 91.1 %

Procedure:
The tert-butyl (E )-3-{7-fluoro-2-(3-hydroxypiperidino)-8-[2-(4-isopropyl-1,3-thiazol-2-yl)ethyl]-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl}-2-propenoate (43.6 mg, 0.0803 mmol) obtained in (M) was dissolved in 4 N hydrochloric acid/dioxane (3 ml) and stirred at room temperature for 2 hours. The reaction mixture was concentrated and the resulting residue was purified by preparative TLC (chloroform:methanol=10:1) to obtain the title compound (35.6 mg, 91%) as lyophilized product.
Reaction SMILES: Br[C:2]1[C:10]2[N:9]3[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:8]3=[C:7]([CH3:16])[C:6]=2[CH:5]=[C:4]([C:17]#[N:18])[CH:3]=1.[Cl:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][C:21]=1[C:29]([F:32])([F:31])[F:30]>>[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([C:2]2[C:10]3[N:9]4[CH2:11][CH2:12][NH:13][C:14](=[O:15])[C:8]4=[C:7]([CH3:16])[C:6]=3[CH:5]=[C:4]([C:17]#[N:18])[CH:3]=2)=[CH:22][C:21]=1[C:29]([F:30])([F:31])[F:32]
Reactant: OB(O)c1ccc(Cl)c(C(F)(F)F)c1
Reactant: Cc1c2n(c3c(Br)cc(C#N)cc13)CCNC2=O
Product: Cc1c2n(c3c(-c4ccc(Cl)c(C(F)(F)F)c4)cc(C#N)cc13)CCNC2=O

Procedure:
The title compound, light yellow solid (77 mg, 76%), MS (ISP) m/z=404.4 [(M+H)+], mp 278° C., was prepared in accordance with the general method of example 1 from 6-bromo-10-methyl-1-oxo-1,2,3,4-tetrahydro-pyrazino[1,2-a]indole-8-carbonitrile (intermediate 16) (76 mg, 0.25 mmol) and commercially available 4-chloro-3-trifluoromethyl-phenylboronic acid (72.9 mg, 0.325 mmol).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.C(=O)([O-])[O-].[K+].[K+].[CH2:17](Br)[CH:18]=[CH2:19]>CN(C)C=O.C(OCC)(=O)C>[CH2:19]([O:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2)[CH:18]=[CH2:17]
Reactant: C=CCBr
Reactant: Oc1ccc2[nH]ccc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: C=CCOc1ccc2[nH]ccc2c1
Temperature: 60 °C
Reaction time: 0.5 h

Procedure:
5-hydroxyindole (1.00 g, 7.29 mmol) and potassium carbonate (1.38 g, 9.94 mmol) were taken up in 20 mL of dimethylformamide (DMF) and stirred at 60° C. for 0.5 hours. Allyl bromide (0.57 mL, 6.62 mmol) was added and the reaction was stirred for an additional 18 hours then cooled and diluted with ethyl acetate. The organic layer was washed with water, brine, dried over magnesium sulfate, filtered, concentrated in vacuo, and the crude residue was purified by flash chromatography on silica gel (10% ethyl acetate/hexane) to provide the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:26])([CH3:25])[CH2:9][CH:10](I)[Sn:11]([CH2:20][CH2:21][CH2:22][CH3:23])([CH2:16][CH2:17][CH2:18][CH3:19])[CH2:12][CH2:13][CH2:14][CH3:15])=[CH:4][CH:3]=1.O1CCCC1>O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:26])([CH3:25])[CH:9]=[CH:10][Sn:11]([CH2:16][CH2:17][CH2:18][CH3:19])([CH2:12][CH2:13][CH2:14][CH3:15])[CH2:20][CH2:21][CH2:22][CH3:23])=[CH:4][CH:3]=1
Reactant: CCCC[Sn](CCCC)(CCCC)C(I)CC(C)(C)c1ccc(Cl)cc1
Solvent: C1CCOC1
Solvent: O
Product: CCCC[Sn](C=CC(C)(C)c1ccc(Cl)cc1)(CCCC)CCCC
Yield: 75.2 %

Procedure:
Under a nitrogen atmosphere, a stirred solution of 8.7 grams (0.015 mole) of 3-(4-chlorophenyl)-3-methyl-1-iodo-1-tributylstannylbutane and 6.5 mL (0.045 mole) of 1,8-diazabicyclo 5.4.0!undec-7-ene (DBU)in 50 mL of tetrahydrofuran was heated at reflux for about 18 hours. The reaction mixture was cooled and poured into about 225 mL of water. The mixture was then made acidic with aqueous 2N hydrochloric acid and extracted with two 150 mL portions of diethyl ether. The combined extracts were dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel, using 5% methylene chloride in petroleum ether as the eluant. The product-containing fractions were combined and concentrated under reduced pressure, yielding 5.3 grams of 3-(4-chlorophenyl)-3-methyl-1-tributylstannyl-1-butene. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: [CH3:1][C:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=1.C(N(CC)CC)C.[C:23](Cl)(=[O:27])[CH2:24][CH2:25][CH3:26].C1CCCCC1>C(Cl)Cl>[CH3:1][C:2]1[C:7]([NH:8][C:23](=[O:27])[CH2:24][CH2:25][CH3:26])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=1
Reactant: Cc1ccc(-c2cccc(N)c2C)cc1
Reactant: CCCC(=O)Cl
Solvent: C1CCCCC1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCC(=O)Nc1cccc(-c2ccc(C)cc2)c1C
Temperature: 25 °C
Reaction time: 2 h
Yield: 92.1 %

Procedure:
To a solution of 2,4′-dimethyl-1,1′-biphenyl-3-ylamine (20 g, 0.1015 mol) in anhydrous CH2Cl2 (250 ml) at 0° C. under nitrogen was added triethylamine (28.29 ml, 0.203 mol). Butyrylchloride (11.07 ml, 0.1066 mol) was added dropwise over 0.5 h, the rate of addition ensured temperature of reaction mixture was below 10° C. Reaction mixture was then stirred at room temperature for 2 h under nitrogen, diluted with CH2Cl2 (200 ml), washed with water (400 ml), saturated sodium bicarbonate (400 ml) and saturated sodium chloride (400 ml). The organic solution was dried (Na2SO4) and the solvent removed in vacuo to give a cream solid. To the solid was added cyclohexane (400 ml), the mixture stirred for 2 h and filtered. The solid residues were dissolved in CH2Cl2 and the solvents removed in vacuo to afford the title compound as a cream solid (25 g).