Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[NH:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH2:9][CH3:10])[CH:4]=1.Cl>CCOCC>[CH2:9]([C:5]1[CH:4]=[C:3]([CH:8]=[CH:7][CH:6]=1)[NH2:2])[CH3:10]
Reactant: CCc1cccc(NC)c1
Agent: Cl
Solvent: CCOCC
Product: CCc1cccc(N)c1
Yield: 95 %

Procedure:
The N-methyl-3-ethyl aniline obtained in the previous step was dissolved in 250 ml anhydrous ether and to this was added (by annulation) about 400 ml of HCl (1.0M solution in ether) at ambient temperature. The resultant white precipitate was filtered through a Buchner funnel, washed with ether, and dried to afford 39.0 g (95% yield, 76% overall in 3 steps from 3-ethyl aniline) of a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C:9]([OH:11])=O)=[CH:4][CH:3]=1.[NH2:19][CH2:20][CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][CH:26]([C:29]2[CH:30]=[C:31]([NH:36][C:37](=[O:41])[CH:38]([CH3:40])[CH3:39])[CH:32]=[CH:33][C:34]=2[F:35])[CH2:25][CH2:24]1>>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([CH:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[C:9]([NH:19][CH2:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][CH:26]([C:29]3[CH:30]=[C:31]([NH:36][C:37](=[O:41])[CH:38]([CH3:39])[CH3:40])[CH:32]=[CH:33][C:34]=3[F:35])[CH2:25][CH2:24]2)=[O:11])=[CH:13][CH:14]=1
Reactant: O=C(O)C(c1ccc(Cl)cc1)c1ccc(Cl)cc1
Reactant: CC(C)C(=O)Nc1ccc(F)c(C2CCN(CCCN)CC2)c1
Product: CC(C)C(=O)Nc1ccc(F)c(C2CCN(CCCNC(=O)C(c3ccc(Cl)cc3)c3ccc(Cl)cc3)CC2)c1

Procedure:
Example 54 was prepared from bis(4-chlorophenyl)acetic acid and N-{3-[1-(3-aminopropyl)-4-piperidinyl]-4-fluorophenyl}-2-methylpropanamide according to the procedures described in Scheme 10: 1H NMR (400 MHz, CDCl3) δ 7.62–7.57 (m, 3H), 7.27 (s, 8H), 7.23–7.19 (m, 1H), 6.94 (dd, 1H, J=8.8, 10.0 Hz), 4.78 (s, 1H), 3.39 (dd, 2H, J=6.0, 11.6 Hz), 2.93 (d, 2H, J=11.6 Hz), 2.77 (m, 1H), 2.48 (m, 1H), 2.42 (t, 2H, J=6.0 Hz), 1.99 (dt, 2H, J=1.6, 11.6 Hz), 1.77 (d, 2H, J=11.2 Hz), 1.69–1.61 (m, 4H), 1.22 (d, 6H, J=6.8 Hz); ESMS m/e: 584.2 (M+H)+.
Reaction SMILES: [C:1]1([O-:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Na+].C1(O)C=CC=CC=1.[C:16](=[O:18])=[O:17]>O>[OH:7][C:1]1[CH:6]=[CH:5][C:4]([C:16]([OH:18])=[O:17])=[CH:3][CH:2]=1
Reactant: O=C=O
Reactant: [O-]c1ccccc1
Agent: [Na+]
Solvent: O
Solvent: Oc1ccccc1
Product: O=C(O)c1ccc(O)cc1

Procedure:
In a pressure reaction vessel were charged 100 g of sodium phenolate, 35 g of phenol and 400 g of a mixture of hydrogenated triphenyls, and a reaction was allowed to proceed at 250° C. and at a carbon dioxide pressure of 7 kg/cm2 (G) for 20 minutes, with stirring The reaction mixture was cooled and charged into 200 ml of water, followed by separation into the reaction medium layer and the water layer at 60° C. The water layer was extracted with 50 g of xylene, and the phenol was recovered with an aqueous potassium hydroxide solution from the reaction medium and extraction medium layers. After recovery of phenol, the water layer was made acid with dilute sulfuric acid to give 80.8 g of p-hydroxybenzoic acid (having a purity of 100%), with neither salicylic acid nor isophthalic acid being detected as an isomer. The yield based on potassium phenolate was 77.3%, and the recovered phenol was 21.8 g, with the selectivity being 99.7%.
Reaction SMILES: C([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([C:14]=1[CH3:15])=[CH:12][C:11]([O:16][CH3:17])=[C:10]([C:18]([F:21])([F:20])[F:19])[CH:9]=2)=[O:5])C.[OH-].[K+].Cl>C(O)C.O>[CH3:17][O:16][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][C:10]=1[C:18]([F:20])([F:21])[F:19])[NH:7][C:6]([C:4]([OH:5])=[O:3])=[C:14]2[CH3:15]
Reactant: CCOC(=O)c1[nH]c2cc(C(F)(F)F)c(OC)cc2c1C
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: COc1cc2c(C)c(C(=O)O)[nH]c2cc1C(F)(F)F
Yield: 73 %

Procedure:
5-Methoxy-3-methyl-6-trifluoromethyl-1H-indole-2-carboxylic acid ethyl ester (3.0 g, 10 mmol) was dissolved in 10 ml absolute ethanol, and a solution of KOH (1.7 g, 30 mmol) in 7 ml water was added. The reaction mixture was heated to reflux for 2.5 hours, then cooled, acidified slowly with 6 N HCl to pH=2, and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to give 2.0 g, (73%) 5-Methoxy-3-methyl-6-trifluoromethyl-1H-indole-2-carboxylic acid.
Reaction SMILES: [NH2:1][C:2]1[S:10][C:5]2[CH2:6][NH:7][CH2:8][CH2:9][C:4]=2[C:3]=1[C:11](=[O:19])[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1.[N+:20]([C:23]1[CH:28]=[CH:27][C:26]([CH2:29][CH2:30]I)=[CH:25][CH:24]=1)([O-:22])=[O:21]>>[NH2:1][C:2]1[S:10][C:5]2[CH2:6][N:7]([CH2:30][CH2:29][C:26]3[CH:25]=[CH:24][C:23]([N+:20]([O-:22])=[O:21])=[CH:28][CH:27]=3)[CH2:8][CH2:9][C:4]=2[C:3]=1[C:11](=[O:19])[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1
Reactant: Nc1sc2c(c1C(=O)c1ccc(Cl)cc1)CCNC2
Reactant: O=[N+]([O-])c1ccc(CCI)cc1
Product: Nc1sc2c(c1C(=O)c1ccc(Cl)cc1)CCN(CCc1ccc([N+](=O)[O-])cc1)C2
Yield: 72 %

Procedure:
The same procedure as in Example 17 was used except an equivalent amount of 2-amino-3-(4-chloro-benzoyl) 4,5,6,7-tetrahydrothieno[2,3-c]pyridine was used in place of 2-Amino-3-benzoyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine (2 mmol), and an equivalent amount of p-nitrophenylethyl iodide was used in place of methyl iodide (3 mmol). (m.p. 150-152° C.; 72% yield).
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][NH:13][CH2:12][C:11]([CH3:16])([CH3:15])[NH:10]2)=[CH:5][CH:4]=1.[Cl:17][C:18]1[N:23]([CH3:24])[C:22](=[O:25])[CH:21]=[C:20]([C:26]2[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=2)[N:19]=1.C(N(CC)CC)C.Cl.C(OCC)(=O)C>O1CCCC1>[ClH:2].[ClH:17].[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]2[CH2:14][N:13]([C:18]3[N:23]([CH3:24])[C:22](=[O:25])[CH:21]=[C:20]([C:26]4[CH:27]=[CH:28][N:29]=[CH:30][CH:31]=4)[N:19]=3)[CH2:12][C:11]([CH3:16])([CH3:15])[NH:10]2)=[CH:7][CH:8]=1
Reactant: CC1(C)CNCC(c2ccc(Cl)cc2)N1
Reactant: Cn1c(Cl)nc(-c2ccncc2)cc1=O
Agent: Cl
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: Cn1c(N2CC(c3ccc(Cl)cc3)NC(C)(C)C2)nc(-c2ccncc2)cc1=O
Yield: 187.2 %

Procedure:
A solution of 2-(4-chlorophenyl)-6,6-dimethyl-piperazine hydrochloride (155 mg, 0.52 mmol), 2-chloro-3-methyl-6-(4-pyridyl)-pyrimidine-4-one (111 mg, 0.50 mmol) and triethylamine (0.42 mL, 2.50 mmol) in tetrahydrofuran (5 mL) was stirred at room temperature for 6 h. The whole was evaporated in vacuo and the residue was extracted with dichloromethane. The organic layer was washed with water, dried and concentrated in vacuo. The residue was dissolved in methanol (5 mL) and treated with 4M hydrogen chloride in ethyl acetate (0.50 mL, 2.0 mmol) for 20 min. After removing the solvent, filtrating and washing the precipitate with ethanol gave 2-(2-(4-chlorophenyl)-6,6-dimethyl-piperazin-4-yl)-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one dihydrochloride (235 mg, 97%).
Reaction SMILES: [Cl:1][C:2]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[CH:7][C:6]=1[C:11]([N:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16]C[CH2:14]1)=[O:12].CNC1C(C)=CC=CC=1>CCCCCCC.C(OCC)(=O)C>[Cl:1][C:2]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:3]=1[O:4][C:5]1[C:6]([C:11]([N:13]([CH3:14])[C:22]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[CH3:16])=[O:12])=[CH:7][N:8]=[CH:9][CH:10]=1
Reactant: O=C(c1cnccc1Oc1cc(Cl)ccc1Cl)N1CCCc2ccccc21
Agent: CNc1ccccc1C
Solvent: CCCCCCC
Solvent: CCOC(C)=O
Product: Cc1ccccc1N(C)C(=O)c1cnccc1Oc1cc(Cl)ccc1Cl

Procedure:
The title compound was prepared in analogy to Example 1, from 4-(2,5-dichloro-phenoxy)-nicotinic acid (Example 1, intermediate) and N-methyl-o-toluidine (commercially available; CAS RN 611-21-2) and using a gradient of n-heptane:ethyl acetate (100:0 to 40:60). The compound was further purified through a second preparative HPLC chromatography (Phenomenex Gemini column) using a gradient of acetonitrile:water (containing 0.05% formic acid) (10:90 to 98:2). White solid (35%). MS (ESI): m/z=387.066 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][CH:3]=1.[H-].[Na+].[CH2:11]([O:13][C:14](=[O:17])[CH2:15]Br)[CH3:12]>C1COCC1>[CH2:11]([O:13][C:14](=[O:17])[CH2:15][S:8][C:5]1[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=1)[CH3:12]
Reactant: Cc1ccc(S)cc1
Reactant: CCOC(=O)CBr
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)CSc1ccc(C)cc1
Reaction time: 0.5 h
Yield: 99 %

Procedure:
A solution of 4-methylbenzenethiol (5 g, 40.25) in dry THF was added dropwise to a suspension of NaH (60% in mineral oil, 1.98 g, 48.30) in THF at room temperature and stirred for 30 min. under N2 atmosphere. Ethylbromoacetate (4.9 mL, 44.27) was added slowly to this solution and further stirred at room temperature for 3 h. The solvent was removed under vacuum. The residue was dissolved in dil. HCl and extracted by ethylacetate. The combined organic phase was washed successively with saturated NaHCO3 solution, water and brine then dried over Na2SO4. Evaporation of organic phase yielded 8.46 g (99%) colorless oil. 1H NMR (CDCl3): δ 1.22 (t, J=7.2 Hz, 3H), 2.32 (s, 3H), 3.57 (s, 2H), 4.14 (q, J=7.2 Hz, 2H), 7.11 (d, J=8.0 Hz, 2H), 7.33 (d, J=8.0 Hz, 2H). EIMS m/z 210 (M+1), 233 (M+23).
Reaction SMILES: [OH-].[Na+].C([O:5][C:6](=[O:40])[CH2:7][C:8]1[CH:9]=[N:10][C:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([CH2:38][CH3:39])([C:23]3[CH:28]=[CH:27][C:26](/[CH:29]=[CH:30]/[C:31]([CH2:35][CH3:36])([OH:34])[CH2:32][CH3:33])=[C:25]([CH3:37])[CH:24]=3)[CH2:21][CH3:22])=[CH:16][CH:15]=2)=[CH:12][CH:13]=1)C.[Cl-].[NH4+]>CO.O1CCCC1>[CH2:21]([C:20]([C:17]1[CH:18]=[CH:19][C:14]([C:11]2[N:10]=[CH:9][C:8]([CH2:7][C:6]([OH:40])=[O:5])=[CH:13][CH:12]=2)=[CH:15][CH:16]=1)([C:23]1[CH:28]=[CH:27][C:26](/[CH:29]=[CH:30]/[C:31]([CH2:32][CH3:33])([OH:34])[CH2:35][CH3:36])=[C:25]([CH3:37])[CH:24]=1)[CH2:38][CH3:39])[CH3:22]
Reactant: CCOC(=O)Cc1ccc(-c2ccc(C(CC)(CC)c3ccc(/C=C/C(O)(CC)CC)c(C)c3)cc2)nc1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: CCC(O)(/C=C/c1ccc(C(CC)(CC)c2ccc(-c3ccc(CC(=O)O)cn3)cc2)cc1C)CC
Temperature: 25 °C
Reaction time: 8 h
Yield: 52.2 %

Procedure:
A 1 N sodium hydroxide aqueous solution (0.220 mL, 0.220 mmol) was added to a solution of (E)-[6-(4-{1-ethyl-1-[4-(3-ethyl-3-hydroxy-1-pentenyl)-3-methyl-phenyl]-propyl}-phenyl)-pyridin-3-yl]-acetic acid ethyl ester (Example 122-(1); 37.6 mg, 0.073 mmol) in methanol-tetrahydrofuran (1:1, 4 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was then poured into a saturated aqueous ammonium chloride solution, followed by extraction with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (chloroform:methanol=10:1) to give the target compound as a colorless oil (18.5 mg, 52%).
Reaction SMILES: F[C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[CH:4][CH:3]=1.[NH:9]1[CH:13]=[CH:12][CH:11]=[N:10]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1C(=O)CCC1.C(Cl)(Cl)Cl>[N:9]1([C:2]2[N:7]=[CH:6][C:5]([NH2:8])=[CH:4][CH:3]=2)[CH:13]=[CH:12][CH:11]=[N:10]1
Reactant: c1cn[nH]c1
Reactant: Nc1ccc(F)nc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN1CCCC1=O
Solvent: ClC(Cl)Cl
Product: Nc1ccc(-n2cccn2)nc1
Temperature: 120 °C
Yield: 16.8 %

Procedure:
Commercial 6-fluoropyridin-3-amine (500 mg, 4.46 mmol) was dissolved in 20 mL dry NMP. To it were added pyrazole (910 mg, 13.4 mmol) and cesium carbonate (4.4 g, 13.4 mmol). The mixture was stirred in a sealed tube at 120° C. for over the weekend (3 nights). The mixture was diluted with chloroform, washed with brine (3 times), dried, concentrated and subjected to flash column (0 to 30% EtOAc in DCM) to isolate 6-(1H-pyrazol-1-yl)pyridin-3-amine (120 mg, 17% yield).
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[C:10]([CH2:15][CH:16]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:12][CH2:13][CH3:14])=[O:11]>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:9]=[CH:8][C:5](/[CH:6]=[C:15](\[CH3:16])/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1
Reactant: CCOC(=O)CC=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=Cc1ccc(F)cc1
Solvent: Cc1ccccc1
Product: CCOC(=O)/C(C)=C/c1ccc(F)cc1
Yield: 99 %

Procedure:
4-Fluorobenzaldehyde (12 g, 97 mmol) was dissolved in toluene (500 mL). (Carboethoxyethylidene)triphenylphosphorane (42 g, 116 mmol) was added and the mixture was heated to reflux until the starting material was consumed. The solution was cooled, diluted with hexanes, and the solid was filtered. The filtrate was evaporated in vacuo. The remaining residue was dissolved in ether, and filtered through a plug of silica gel using ether as eluent. The solvents were evaporated in vacuo to afford the title compound (20 g, 99% yield) as a yellow solid. 1H NMR (DMSO-d6) δ ppm: 7.64 (s, 1H), 7.38 (dd, J=8.65, 5.59 Hz, 2H), 7.08 (t, J=8.65 Hz, 2H), 4.27 (q, J=7.12 Hz, 2H), 2.10 (d, J=1.36 Hz, 3H), 1.27-1.38 (m, 3H). MS (DCI+) 209 (M+H).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9](=[O:15])[C:10]([O:12][CH2:13][CH3:14])=[O:11].[Br:16]C1C=CC=CC=1CBr.[Mg].C(OCC)(=O)C(OCC)=O>>[Br:16][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9](=[O:15])[C:10]([O:12][CH2:13][CH3:14])=[O:11]
Reactant: CCOC(=O)C(=O)Cc1ccccc1F
Reactant: BrCc1ccccc1Br
Agent: [Mg]
Solvent: CCOC(=O)C(=O)OCC
Product: CCOC(=O)C(=O)Cc1ccccc1Br
Yield: 80 %

Procedure:
The title compound was prepared as described for (B4) using 2-bromobenzyl bromide (1.250 g, 5.00 mmol), magnesium (0.134 g, 5.50 mmol) and diethyl oxalate (1.462 g, 10.00 mmol). The product was isolated in the form of colorless oil in 80% yield and used instantly in next step.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18](OC4C(F)=C(F)C(F)=C(F)C=4F)(=[O:20])=[O:19])=[CH:15][CH:16]=3)[CH:11]=[CH:10][C:9]2=[O:33])=[C:4]([O:34][CH3:35])[CH:3]=1.[O:36]1[CH:40]=[CH:39][C:38]([NH2:41])=[N:37]1.C1COCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([NH:41][C:38]4[CH:39]=[CH:40][O:36][N:37]=4)(=[O:20])=[O:19])=[CH:15][CH:16]=3)[CH:11]=[CH:10][C:9]2=[O:33])=[C:4]([O:34][CH3:35])[CH:3]=1
Reactant: COc1cc(Br)ccc1-n1c(=O)ccc2cc(S(=O)(=O)Oc3c(F)c(F)c(F)c(F)c3F)ccc21
Reactant: Nc1ccon1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COc1cc(Br)ccc1-n1c(=O)ccc2cc(S(=O)(=O)Nc3ccon3)ccc21
Reaction time: 0.17 h
Yield: 98 %

Procedure:
A RBF was charged with perfluorophenyl 1-(4-bromo-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (1.070 g, 1.857 mmol), isoxazol-3-amine (0.158 ml, 2.135 mmol) and THF (12.38 ml) to give a clear solution. The flask was cooled in an ice-water bath for 10 min, then lithium bis(trimethylsilyl)amide (1M in THF) (3.90 ml, 3.90 mmol) was added dropwise. After 10 min, the mixture was diluted with EtOAc and washed with 1N aq. HCl. The aq. layer was washed with EtOAc. The combined organic extracts were dried over sodium sulfate, filtered; and concentrated. The residue was purified by chromatography (50-g SNAP Ultra column, 25-g silica gel loading column, 0-5% MeOH/DCM) to give 1-(4-bromo-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.867 g) as a tan foam that was ca. 90% pure. m/z (ESI) 476.1 (M+H)+.
Reaction SMILES: C1(C2C=CC([CH:8]=[O:9])=CC=2)CC1.Br[C:13]1[CH:18]=[CH:17][C:16]([C:19]2([CH3:22])[CH2:21][CH2:20]2)=[C:15]([Cl:23])[CH:14]=1.[Li]CCCC.CN(C=O)C>>[Cl:23][C:15]1[CH:14]=[C:13]([CH:18]=[CH:17][C:16]=1[C:19]1([CH3:22])[CH2:21][CH2:20]1)[CH:8]=[O:9]
Reactant: CC1(c2ccc(Br)cc2Cl)CC1
Reactant: O=Cc1ccc(C2CC2)cc1
Agent: [Li]CCCC
Solvent: CN(C)C=O
Product: CC1(c2ccc(C=O)cc2Cl)CC1
Yield: 63 %

Procedure:
The title compound was synthesized in analogy to 4-cyclopropyl benzaldehyde (described in example S53) using 4-bromo-2-chloro-1-(1-methylcyclopropyl)-benzene (350 mg, 1.43 mmol), n-BuLi (980 μl, 1.6M solution in hexane, 1.57 mmol) and DMF (443 μl, 5.70 mmol). The isolated residue was purified by flash column chromatography (1:9 ether:pentane) to give 3-chloro-4-(1-methylcyclopropyl)-benzaldehyde (176 mg, 63%) as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ 9.94 (s, 1H), 7.84 (d, J=1.5 Hz, 1H), 7.69 (dd, J=1.5, 8.0 Hz, 1H), 7.52 (d, J=8.0 Hz, 1H), 1.38 (s, 3H), 0.90-0.80(m, 4H).
Reaction SMILES: [CH3:1][C:2]1([C:9]2[CH:10]=[C:11]([CH:15]=[CH:16][CH:17]=2)[C:12]([OH:14])=O)[CH2:7][O:6][CH2:5][C:4](=[O:8])[NH:3]1.[NH2:18][C:19]1[CH:24]=[C:23]([Cl:25])[CH:22]=[CH:21][C:20]=1O>>[Cl:25][C:23]1[CH:22]=[CH:21][C:20]2[O:14][C:12]([C:11]3[CH:10]=[C:9]([C:2]4([CH3:1])[NH:3][C:4](=[O:8])[CH2:5][O:6][CH2:7]4)[CH:17]=[CH:16][CH:15]=3)=[N:18][C:19]=2[CH:24]=1
Reactant: Nc1cc(Cl)ccc1O
Reactant: CC1(c2cccc(C(=O)O)c2)COCC(=O)N1
Product: CC1(c2cccc(-c3nc4cc(Cl)ccc4o3)c2)COCC(=O)N1

Procedure:
The condensation of 3-((RS)-3-methyl-5-oxo-morpholin-3-yl)-benzoic acid (intermediate XXVI-1) and 2-amino-4-chloro-phenol with polyphosphoric acid at 130° C. during 3 hours yielded the title compound.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([N:10]2[C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]#[N:22])[CH:16]=3)=[CH:13][C:12]([C:23]([O:25]CC)=[O:24])=[N:11]2)[CH:6]=[CH:7][C:8]=1[F:9])#[N:2].ClC1C=C(N2C(C3C=C(F)C=C(Cl)C=3)=CC(C(O)=O)=N2)C=CC=1F>>[C:1]([C:3]1[CH:4]=[C:5]([N:10]2[C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]#[N:22])[CH:16]=3)=[CH:13][C:12]([C:23]([OH:25])=[O:24])=[N:11]2)[CH:6]=[CH:7][C:8]=1[F:9])#[N:2]
Reactant: CCOC(=O)c1cc(-c2cccc(C#N)c2)n(-c2ccc(F)c(C#N)c2)n1
Agent: O=C(O)c1cc(-c2cc(F)cc(Cl)c2)n(-c2ccc(F)c(Cl)c2)n1
Product: N#Cc1cccc(-c2cc(C(=O)O)nn2-c2ccc(F)c(C#N)c2)c1
Reaction time: 6 h

Procedure:
The preparation of the title compound takes place starting from the compound of Example 63A in analogy to the synthesis of the compound of Example 71A but with stiffing for 6 hours. 430 mg of the title compound with 43% purity are obtained.
Reaction SMILES: CS(C)=[O:3].[CH3:5][C:6]1[C@@H:22]([O:23][C:24]([C@H:26]([OH:43])[C@@H:27]([NH:34][C:35]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:36])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])[CH2:21][C@:17]2([OH:44])[C:18]([CH3:20])([CH3:19])[C:7]=1[C@@H:8]([O:62][C:63]([CH3:65])=[O:64])[CH2:9][C@@:10]1([CH3:61])[C@H:15]([C@@H:16]2[O:45][C:46]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)=[O:47])[C@:14]2([O:56][C:57]([CH3:59])=[O:58])[CH2:54][O:55][C@@H:13]2[CH2:12][C@@H:11]1[OH:60]>O1CCCC1>[CH3:5][C:6]1[C@@H:22]([O:23][C:24]([C@H:26]([OH:43])[C@@H:27]([NH:34][C:35]([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)=[O:36])[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[O:25])[CH2:21][C@:17]2([OH:44])[C:18]([CH3:19])([CH3:20])[C:7]=1[C@@H:8]([O:62][C:63]([CH3:65])=[O:64])[C:9]([C@@:10]1([CH3:61])[C@H:15]([C@@H:16]2[O:45][C:46]([C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=2)=[O:47])[C@:14]2([O:56][C:57]([CH3:59])=[O:58])[CH2:54][O:55][C@@H:13]2[CH2:12][C@@H:11]1[OH:60])=[O:3]
Reactant: CS(C)=O
Reactant: CC(=O)O[C@H]1C[C@]2(C)[C@@H](O)C[C@H]3OC[C@@]3(OC(C)=O)[C@H]2[C@H](OC(=O)c2ccccc2)[C@]2(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)c3ccccc3)c3ccccc3)C(C)=C1C2(C)C
Solvent: C1CCOC1
Product: CC(=O)O[C@H]1C(=O)[C@@]2(C)[C@H]([C@H](OC(=O)c3ccccc3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)c4ccccc4)c4ccccc4)C(C)=C1C3(C)C)[C@]1(OC(C)=O)CO[C@@H]1C[C@@H]2O
Reaction time: 0.07 h

Procedure:
A coated stent from Example 9 is dipped into a DESMODUR solution (50:50 mixture of dimethylsulfoxide and tetrahydrofuran). The device is then removed and the coating is then partially dried at room temperature for 3 to 5 minutes. The device is then immersed in a beaker of water (room temperature) for 3-5 minutes to cause the polymerization reaction to occur rapidly. An echogenic coating is formed. In addition to 9-deoxotaxol, the following are exemplary compounds that may be used to coat the device: 7-deoxy-9-deoxotaxol and 10-desacetoxy-7-deoxy-9-deoxotaxol.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:19]=[CH:18][C:17]([N:20]4[CH:24]=[N:23][N:22]([CH:25]([CH3:29])[C:26](=O)[CH3:27])[C:21]4=[O:30])=[CH:16][CH:15]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH3:31][C@H:32]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[NH2:33].S1C=CC=C1>C1COCC1.[Pd].CCCCO.CCCCO.CCCCO.CCCCO.[Ti]>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:15]=[CH:16][C:17]([N:20]4[CH:24]=[N:23][N:22]([CH:25]([CH3:29])[CH:26]([NH:33][CH:32]([C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=5)[CH3:31])[CH3:27])[C:21]4=[O:30])=[CH:18][CH:19]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1
Reactant: CC(=O)C(C)n1ncn(-c2ccc(N3CCN(c4ccc(O)cc4)CC3)cc2)c1=O
Reactant: C[C@@H](N)c1ccccc1
Agent: [Pd]
Agent: [Ti]
Solvent: CCCCO
Solvent: C1CCOC1
Solvent: c1ccsc1
Product: CC(NC(C)C(C)n1ncn(-c2ccc(N3CCN(c4ccc(O)cc4)CC3)cc2)c1=O)c1ccccc1
Reaction time: 48 h

Procedure:
A mixture of (±)-2,4-dihydro-4-[4-[4-(4-hydroxyphenyl)-1-piperazinyl]phenyl]-2-(1-methyl-2-oxopropyl)-3H-1,2,4-triazol-3-one (0.05 mol) and (+)-(R)-α-methyl-benzenemethanamine (0.1 mol) in THF (500 ml) was hydrogenated at 50° C. for 48 hours with Pd/C 10% (10 g) as a catalyst in the presence of titanium(IV) n-butoxide (28.4 g) and thiophene solution (10 ml). The catalyst was filtered off. Pd/C 10% (10 g) was added again. Hydrogenation was continued at 50° C. for 48 hours. After uptake of H2, the mixture was cooled, then the catalyst was filtered off and the filtrate was evaporated. The residue was stirred in CH2Cl2 (500 ml) and H2O (50 ml) was added. The mixture was acidified with a concentrated HCl solution, alkalized with a concentrated NH4OH solution and filtered over dicalite. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was triturated in DIPE, filtered off and dried, yielding 23.5 g (91%) of [(R*,R*)(R)+(R*,S*)(R)]-2,4-dihydro-4-[4-[4-(4-hydroxyphenyl)-1-piperazinyl]phenyl]-2-[2-[(1-phenylethyl)amino]-1-methylpropyl]-3H-1,2,4-triazol-3-one (interm. 1).
Reaction SMILES: ClC1C=C(C=C(Cl)C=1)N.[Cl:10][C:11]1[CH:12]=[C:13]([N:18]2[C:22](=[O:23])[CH:21]([CH3:24])[S:20][CH2:19]2)[CH:14]=[C:15]([Cl:17])[CH:16]=1.C(O)(=S)C(C)[OH:27].C1NCSC1=O.ClC1C=C(C=CC=1)C(OO)=O>>[Cl:17][C:15]1[CH:14]=[C:13]([N:18]2[C:22](=[O:23])[CH:21]([CH3:24])[S:20](=[O:27])[CH2:19]2)[CH:12]=[C:11]([Cl:10])[CH:16]=1
Reactant: CC1SCN(c2cc(Cl)cc(Cl)c2)C1=O
Reactant: CC(O)C(O)=S
Agent: Nc1cc(Cl)cc(Cl)c1
Agent: O=C(OO)c1cccc(Cl)c1
Agent: O=C1CNCS1
Product: CC1C(=O)N(c2cc(Cl)cc(Cl)c2)CS1=O

Procedure:
3,5-Dichloroaniline was converted to 3-(3,5-dichlorophenyl)-5-methyl-4-thiazolidinone in accordance with the procedure of Example 4. The only difference was that thiolactic acid was used instead of mercaptoacetic acid. The 3-(3,5-dichlorophenyl)-5-methyl-4-thiazolidinone had a melting point of 80°-88° C. This thiazolidinone (18 g) was oxidized with one equivalent of m-chloroperoxybenzoic acid (14 g) in the same manner as described in Example 2. After removal of the solvent, the reaction product was recrystallized from isopropyl alcohol to yield 3-(3,5-dichlorophenyl)-5-methyl-4-thiazolidinone 1-oxide, m.p. 146°-149° C.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:8]#[C:9][C:10]2[CH:19]=[C:18]3[C:13]([C:14](=[O:29])[CH:15]=[C:16]([C:20]4[N:25]=[CH:24][N:23]5[CH:26]=[CH:27][CH:28]=[C:22]5[CH:21]=4)[O:17]3)=[CH:12][CH:11]=2)[CH:5]=[CH:6][CH:7]=1.Cl.Cl[CH2:32][CH2:33][CH2:34][N:35]([CH3:37])[CH3:36]>>[CH3:36][N:35]([CH3:37])[CH2:34][CH2:33][CH2:32][O:1][C:2]1[CH:3]=[C:4]([C:8]#[C:9][C:10]2[CH:19]=[C:18]3[C:13]([C:14](=[O:29])[CH:15]=[C:16]([C:20]4[N:25]=[CH:24][N:23]5[CH:26]=[CH:27][CH:28]=[C:22]5[CH:21]=4)[O:17]3)=[CH:12][CH:11]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: CN(C)CCCCl
Reactant: O=c1cc(-c2cc3cccn3cn2)oc2cc(C#Cc3cccc(O)c3)ccc12
Agent: Cl
Product: CN(C)CCCOc1cccc(C#Cc2ccc3c(=O)cc(-c4cc5cccn5cn4)oc3c2)c1
Yield: 52 %

Procedure:
7-[3-(3-dimethylamino-propoxy)-phenylethynyl]-2-pyrrolo[1,2-c]pyrimidin-3-yl-chromen-4-one was prepared in 52% yield using the method described in example 42, starting from 7-(3-hydroxy-phenylethynyl)-2-pyrrolo[1,2-c]pyrimidin-3-yl-chromen-4-one (example 120B) and (3-Chloro-propyl)-dimethyl-amine hydrochloride.