Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]#[C:16][C:17]([O:19]CC)=O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[OH:23][NH2:24].CO.[OH-].[K+].Cl>CO.O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:23][N:24]=[C:17]([OH:19])[CH:16]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)C#Cc1ccc(OCc2ccccc2)cc1
Reactant: NO
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: Oc1cc(-c2ccc(OCc3ccccc3)cc2)on1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of ethyl 3-(4-(benzyloxy)phenyl)-2-propinoate (1.46 g) in methanol (30 ml), 1.45 g of hydroxyamine hydrochloride and 6.25 ml of 5M potassium hydroxide methanol were added, and the reaction solution was stirred overnight at room temperature. The solvent was distilled off under reduced pressure, the residue obtained was suspended in water, and the suspension was adjusted to pH 2-3 with a 2N aqueous hydrochloric acid solution. The resultant solid was obtained by filtration to afford the title compound as a light brown solid.
Reaction SMILES: [C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13](=[O:15])[CH3:14])=[CH:10][CH:11]=2)[CH2:6][C:5]1=[O:16])(=[O:3])[CH3:2].[C:17](O)(=[O:22])[CH2:18][CH:19]([CH3:21])[CH3:20]>>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13](=[O:15])[CH3:14])=[CH:10][CH:11]=2)[C:6](=[C:17]([OH:22])[CH2:18][CH:19]([CH3:21])[CH3:20])[C:5]1=[O:16])(=[O:3])[CH3:2]
Reactant: CC(C)CC(=O)O
Reactant: CC(=O)c1ccc2c(c1)CC(=O)N2C(C)=O
Product: CC(=O)c1ccc2c(c1)C(=C(O)CC(C)C)C(=O)N2C(C)=O

Procedure:
Prepared from 1,5-diacetyl-2-indolinone and isovaleric acid
Reaction SMILES: C(O[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13](OCCCC)=[C:12](F)[CH:11]=2)=[CH:6][C:5]=1F)C.C([Li])CCC.[C:28](=[O:33])(OC)OC.Cl>CCCCCC.O1CCCC1>[C:28]1(=[O:33])[C:6]2[C:7]([C:10]3[C:11]([CH:5]=2)=[CH:12][CH:13]=[CH:14][CH:15]=3)=[CH:8][CH:9]=[CH:4]1
Reactant: CCCCOc1ccc(-c2ccc(OCC)c(F)c2)cc1F
Reactant: COC(=O)OC
Agent: Cl
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: O=C1C=CC=C2C1=Cc1ccccc12
Temperature: -70 °C
Reaction time: 2 h

Procedure:
60 mmol of 4-ethoxy-3,3′-difluoro-4′-butoxybiphenyl (5) are introduced into 200 ml of tetrahydrofuran, and the mixture is cooled to −70° C. 120 mmol of a 1.6 M solution of n-butyllithium in hexane are added dropwise, and the mixture is stirred at this temperature for 2 hours. 60 mmol of dimethyl carbonate are subsequently added rapidly with vigorous stirring, the mixture is stirred at −70° C. for a further hour, allowed to warm to 0° C., hydrolysed with dilute hydrochloric acid and subjected to conventional work-up.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:8][C:9](=[O:13])[NH:10]2)=[CH:5][CH:4]=1.[H-].[Na+].[CH3:22]I.O>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:8][C:9](=[O:13])[N:10]2[CH3:22])=[CH:5][CH:4]=1
Reactant: CI
Reactant: COc1ccc2c(-c3ccccc3)cc(=O)[nH]c2c1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc2c(-c3ccccc3)cc(=O)n(C)c2c1
Temperature: 50 °C
Reaction time: 0.75 h

Procedure:
A solution of 7-methoxy-4-phenyl-2-quinolinone from Example 1, Step 2 (1.62 g) in DMF (30 mL) was treated with NaH (60% in mineral oil; 310 mg). After stirring at 50° C. for 45 min., the mixture was cooled to r.t. and methyl iodide (0.6 mL) was added. After 30 min., H2O (100 mL) was added and the resulting solution extracted with EtOAc (3×). The organics were washed with H2O (2×), brine, dried (MgSO4) and the solvents evaporated. Flash chromatography of the residue (silica gel; CHCl3 /EtOAc (4:1)) provided the title compound as a foam.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH:6]=[C:5]2[Cl:13].[N:14]([O-])=O.[Na+].O.O.Cl[Sn]Cl.NN>Cl.O>[Cl:13][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([NH:1][NH2:14])[CH:3]=2)[NH:8][C:7](=[O:12])[CH:6]=1
Reactant: Nc1ccc2[nH]c(=O)cc(Cl)c2c1
Reactant: O=N[O-]
Agent: Cl
Agent: Cl[Sn]Cl
Agent: NN
Solvent: O
Product: NNc1ccc2[nH]c(=O)cc(Cl)c2c1
Temperature: -1 °C
Reaction time: 2 h

Procedure:
In a 250 mL round bottomed flask a suspension of 6-amino-4-chloroquinolin-2(1H)-one (structure 1 of Scheme I, where RA=chloro) (1.94 g, 10 mmol) in 10 mL conc. HCl was cooled to −1° C. and a solution of NaNO2 (0.40 g, 12 mmol) in water (5 mL) was added dropwise over 20 min. The resulting dark yellow suspension was stirred at −1° C. for 2 hours and then a solution of SnCl2.2H2O (5.2 g, 15 mmol) in concentrated HCl (10 mL) was added dropwise over 10 minutes. The resulting light yellow suspension of the hydrazine was stirred at −1° C. for 2 hours and then used directly or stored in a refrigerator at −1° C. until it was used (the crude compound can be stored for at least one month without decomposition).
Reaction SMILES: C[N:2](C)[S:3](=[O:27])(=[O:26])[O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[C:15]([CH2:17][N:18]3[CH:22]=[N:21][CH:20]=[N:19]3)[CH:14]=[CH:13][C:12]=2[C:23]#[N:24])=[CH:7][C:6]=1[Cl:25].CN(C)S(=O)(=O)OC1C=CC(C2C=C(CN3C=NC=N3)C=CC=2C#N)=CC=1>>[S:3](=[O:26])(=[O:27])([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[C:15]([CH2:17][N:18]3[CH:22]=[N:21][CH:20]=[N:19]3)[CH:14]=[CH:13][C:12]=2[C:23]#[N:24])=[CH:7][C:6]=1[Cl:25])[NH2:2]
Reactant: CN(C)S(=O)(=O)Oc1ccc(-c2cc(Cn3cncn3)ccc2C#N)cc1Cl
Agent: CN(C)S(=O)(=O)Oc1ccc(-c2cc(Cn3cncn3)ccc2C#N)cc1
Product: N#Cc1ccc(Cn2cncn2)cc1-c1ccc(OS(N)(=O)=O)c(Cl)c1

Procedure:
5′-((1H-1,2,4-triazol-1-yl)methyl)-3-chloro-2′-cyanobiphenyl-4-yl dimethylsulfamate 24, The title compound was prepared from 22 using similar conditions to those described for the synthesis of 21. Chromatography (CH2Cl2/acetone 75:25) eluted 24 as a white solid (0.189 g, 60%), mp 119-120° C.; 1H NMR δH (270 MHz, CDCl3) 3.07 (s, 6H), 5.45 (s, 2H), 7.30-7.33 (m, 2H), 7.43 (dd, J=2.2 Hz, 8.4 Hz, 1H), 7.58 (d, J=2.2 Hz, 1H), 7.62 (d, J=10.9 Hz, 1H), 7.77 (d, J=8.7 Hz, 1H), 8.01 (s, 1H) and 8.18 (s, 1H); LCMS (APCI), m/z 418 (40, [37CIM+H]−), 416 (100, [35CIM−-H]−); HRMS (ES+) m/z calcd. for C18H17ClN5O3S [M+H]+: 418.0735, found 418.0725; Anal. (C18H16ClN5O3S) C, H, N.
Reaction SMILES: [C:1]1([S:7][CH2:8][CH2:9][OH:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[N+:12]([CH2:15][C:16]([O-])=[O:17])([O-:14])=[O:13]>ClCCl>[N+:12]([CH2:15][C:16]([O:10][CH2:9][CH2:8][S:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:17])([O-:14])=[O:13]
Reactant: O=C([O-])C[N+](=O)[O-]
Reactant: OCCSc1ccccc1
Agent: Cl
Solvent: ClCCl
Product: O=C(C[N+](=O)[O-])OCCSc1ccccc1

Procedure:
This compound was prepared according to a known process (British Pat. No. 835,521 Spec.). Namely, a solution of β-phenylthioethylalcohol (50g) in dichloromethane (15ml) was saturated with dry hydrogen chloride at 0° C. and to the resulting solution was added, in three portions, dipottassium nitroacetate (27.5g). During the addition, hydrogen chloride was passed into the well stirred mixture while the temperature was allowed to rise to 10° C. Then the gas supply was stopped and the reaction mixture was stirred for 4 hours at less than 10° C. After stirring for 20 hours at 0° C., excess β-phenylthioethyl-alcohol was removed under reduced pressure and the remaining solution was kept to cool, the crystals precipitated was washed with water and then with n-hexane, giving β-phenylthioethyl nitroacetate (11.1g), m.p. 22.0°-24.0° C..
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:8]2[N:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[N:11]=[C:10]([C:20]([F:26])([F:25])[C:21]([F:24])([F:23])[F:22])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[C:27]([N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[C:27]([N:34]1[CH2:35][CH2:36][N:37]([C:2]2[CH:3]=[C:4]([CH:8]3[N:12]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=4[Cl:19])[N:11]=[C:10]([C:20]([F:26])([F:25])[C:21]([F:24])([F:23])[F:22])[CH2:9]3)[CH:5]=[CH:6][CH:7]=2)[CH2:38][CH2:39]1)([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: FC(F)(F)C(F)(F)C1=NN(c2ccccc2Cl)C(c2cccc(Br)c2)C1
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1CCN(c2cccc(C3CC(C(F)(F)C(F)(F)F)=NN3c3ccccc3Cl)c2)CC1
Temperature: 100 °C
Reaction time: 12 h
Yield: 76.7 %

Procedure:
5-(3-Bromo-phenyl)-1-(2-chloro-phenyl)-3-pentafluoroethyl-4,5-dihydro-1H-pyrazole (650.0 mg, 1.4 mmol) prepared in Step 1 of Preparation 6, 1-BOC-piperazine (402.0 mg, 2.2 mmol), Pd2(dba)3 (66.0 mg, cat.), BINAP (90.0 mg, cat.) and sodium t-butoxide (250.0 mg, 2.6 mmol) were added to toluene (10.0 mL). The reaction mixture was stirred at 100° C. for 12 hours and then filtered through celite pad. A saturated solution of ammonium chloride was added to the filtrate, which was then extracted with ethyl acetate three times. The combined extract was washed with brine, dried on anhydrous magnesium sulfate, and then concentrated under reduced pressure to give a yellow liquid residue. The resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/6) to give 600.0 mg of the titled compound as a yellow liquid.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][CH:12]1[CH2:17][CH2:16][N:15]([C:18]2([CH3:31])[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[CH2:14][CH2:13]1.C(N(CC)CC)C>ClCCl>[CH3:31][C:18]1([N:15]2[CH2:14][CH2:13][C:12](=[O:11])[CH2:17][CH2:16]2)[CH2:19][CH2:20][N:21]([C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])[CH2:22][CH2:23]1
Reactant: CC(C)(C)OC(=O)N1CCC(C)(N2CCC(O)CC2)CC1
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(C)(N2CCC(=O)CC2)CC1
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 94.1 %

Procedure:
A solution of oxalyl chloride in dichloromethane (2M, 13.67 mL, 27.33 mmol) was cooled to −78° C. under nitrogen atmosphere and was added to a solution of dimethylsulfoxide (3.87 mL, 54.0 mmol) in dichloromethane (40 mL) at −78° C. under nitrogen atmosphere via cannula. After 10 minutes, a solution of tert-butyl 4-(4-hydroxy-1-piperidyl)-4-methyl-piperidine-1-carboxylate (18.0 mmol) in dichloromethane (20 mL) was added at −78° C. under nitrogen atmosphere to the reaction mixture via cannula. The mixture was stirred at −78° C. for 10 minutes and then triethylamine (10.07 mL, 72.0 mmol) was added dropwise. The reaction was stirred at −78° C. under nitrogen atmosphere for another 20 minutes, then allowed to warm up to 0° C. over 1 hour. The reaction was quenched with water (50 mL) and diluted with dichloromethane (100 mL). The phases were separated and the aqueous layer was extracted with dichloromethane (2×50 mL). The combined organic phases were washed with saturated aqueous ammonium chloride, brine, dried over Na2SO4 and concentrated in vacuo to afford the title compound as yellow oil (5.02 g, 94%), which was used for the subsequent step without further purification. MS (M+1): 297.24.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][CH2:11][C:10](=[CH2:13])[C:9]2=[O:14])=[CH:4][CH:3]=1.[CH3:15][O:16][CH2:17][CH2:18][N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.COCCOC>O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][CH2:11][CH:10]([CH2:13][N:22]3[CH2:23][CH2:24][N:19]([CH2:18][CH2:17][O:16][CH3:15])[CH2:20][CH2:21]3)[C:9]2=[O:14])=[CH:4][CH:3]=1
Reactant: C=C1CCN(c2ccc(Br)cc2)C1=O
Reactant: COCCN1CCNCC1
Solvent: COCCOC
Solvent: O
Product: COCCN1CCN(CC2CCN(c3ccc(Br)cc3)C2=O)CC1
Yield: 92.7 %

Procedure:
1.31 g of 1-(4-bromophenyl)-3-methylene-2-pyrrolidinone and 1.00 g of 4-(2-methoxyethyl)piperazine were mixed with 5 ml of ethylene glycol dimethyl ether. The mixture was refluxed for 6.5 hours and then cooled. Thereto was added water. The mixture was subjected to extraction with ethyl acetate twice. The organic layer was dried over anhydrous magnesium sulfate and then concentrated to obtain 1.91 g of 1-(4-bromophenyl)-3-[4-(2-methoxyethyl)piperazine-1-yl]methyl-2-pyrrolidinone.
Reaction SMILES: [Mg].II.Br[C:5]1[CH:6]=[C:7]([CH:13]2[O:18][CH2:17][C:16]([CH3:20])([CH3:19])[CH2:15][O:14]2)[CH:8]=[CH:9][C:10]=1[O:11][CH3:12].[Na].[Cl:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[NH:28][C:27](=[O:32])[C:26]2=[O:33].ClC1C=C2C(=CC=1)NC(=O)C2=O.[H-].[Na+].[Cl-].[NH4+]>C1COCC1>[Cl:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[NH:28][C:27](=[O:32])[C:26]2([C:5]1[CH:6]=[C:7]([CH:13]2[O:18][CH2:17][C:16]([CH3:20])([CH3:19])[CH2:15][O:14]2)[CH:8]=[CH:9][C:10]=1[O:11][CH3:12])[OH:33]
Reactant: COc1ccc(C2OCC(C)(C)CO2)cc1Br
Reactant: O=C1Nc2ccc(Cl)cc2C1=O
Agent: II
Agent: [Cl-]
Agent: [H-]
Solvent: C1CCOC1
Product: COc1ccc(C2OCC(C)(C)CO2)cc1C1(O)C(=O)Nc2ccc(Cl)cc21
Temperature: 25 °C

Procedure:
Magnesium shavings (2.2 g, 89 mmol) were placed in THF (30 mL) and etched with several iodine crystals. A solution of 2-(3-bromo-4-methoxyphenyl)-5,5-dimethyl[1,3]dioxane (26.0 g, 86 mmol) in THF (80 mL) was added thereto, with stirring. After initiation of the reaction (identifiable by the exothermic evolution of heat), the rate of dropwise addition was decreased so that the reaction mixture was just at the boiling point. The reaction mixture was stirred for an additional 20 min and then was cooled to room temperature. The Grignard solution thus obtained was pumped into an ice-cold solution of the 5-chlorisatin sodium salt (prepared by treating a solution of 5-chlorisatin (13.1 g, 72 mmol) in THF (400 mL) with one equivalent of sodium hydride for one hour at 0° C.), and was then stirred for 5 hours at room temperature. The reaction solution was combined with aqueous ammonium chloride solution, with stirring, and the batch was extracted twice with ethyl acetate. The combined organic phase was washed with water and saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure. Treatment of the residue with diethyl ether resulted in crystallization of the desired product. Yield: 19.2 g (66%) of a white solid. MS (API-ES, pos) m/z=386 [M+H—H2O]+.
Reaction SMILES: CS(C)=O.[CH3:5][O:6][C:7](=[O:38])[CH2:8][CH2:9][CH2:10]/[CH:11]=[CH:12]\[CH2:13][C@@H:14]1[C@@H:18]([C@@H:19]([O:29][CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][O:31]2)/[CH:20]=[CH:21]/[C:22]([CH3:28])([CH3:27])[CH2:23][CH2:24][CH2:25][CH3:26])[C@H:17]([CH3:36])[CH2:16][CH:15]1[OH:37].C(N(CC)CC)C>[Cl-].[Na+].O>[CH3:5][O:6][C:7](=[O:38])[CH2:8][CH2:9][CH2:10]/[CH:11]=[CH:12]\[CH2:13][C@@H:14]1[C@@H:18]([C@@H:19]([O:29][CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][O:31]2)/[CH:20]=[CH:21]/[C:22]([CH3:27])([CH3:28])[CH2:23][CH2:24][CH2:25][CH3:26])[C@H:17]([CH3:36])[CH2:16][C:15]1=[O:37]
Reactant: CCCCC(C)(C)/C=C/[C@H](OC1CCCCO1)[C@H]1[C@H](C)CC(O)[C@@H]1C/C=C\CCCC(=O)OC
Agent: [Cl-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Solvent: O
Product: CCCCC(C)(C)/C=C/[C@H](OC1CCCCO1)[C@H]1[C@H](C)CC(=O)[C@@H]1C/C=C\CCCC(=O)OC

Procedure:
A DMSO (60 mL) solution of the crude optically active (5Z,11alpha,13S,14E)-13-(2-tetrahydropyranyloxy)-11,16,16-trimethyl-9-hydroxyprosta-5,14-dien-1-oic acid methyl ester (11.1 g) was treated with triethylamine (22 mL) and then dropwise with a DMSO (60 mL) solution of sulfur trioxide pyridine complex (11.1 g) during 30 minutes while stirring. After 31/2 hours, the reaction mixture was poured into a slush of ice and brine (600 mL) and extracted with hexane (3×150 mL). The combined extracts were washed with 2 N HCL, water, NaHCO3 solution, and brine, then dried over sodium sulfate and stripped of solvent. The crude optically active (5Z,11alpha,13S,14E)-13-(2-tetrahydropyranyloxy)-11,16,16-Trimethyl-9-oxoprosta-5,14-dien-1-oic acid methyl ester was obtained as a yellow oil weighing 10.55 g (95.4%).
Reaction SMILES: [F:1][C:2]([F:17])([F:16])[C:3]([NH:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[CH:11][CH:10]=[CH:9]2)=[O:4]>C(O)(=O)C.[Pt]=O>[F:17][C:2]([F:1])([F:16])[C:3]([NH:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH2:11][CH2:10][CH2:9]2)=[O:4]
Reactant: O=C(Nc1ccc2ncccc2c1)C(F)(F)F
Agent: O=[Pt]
Solvent: CC(=O)O
Product: O=C(Nc1ccc2c(c1)CCCN2)C(F)(F)F

Procedure:
2,4 g (0.01 mol) of 6-trifluoroacetylamino-quinoline are dissolved in 20 ml glacial acetic acid and hydrogenated for I hour with 0.6 g platinum oxide at 3 bar. Then the catalyst is suction filtered and the solution is concentrated by evaporation. The residue is washed with a little sodium hydrogen carbonate solution and dried.
Reaction SMILES: C([NH:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12](Cl)[CH:13]=2)[N:8]=[C:7]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=2[O:25][CH3:26])[CH:6]=1)C=C.[CH3:27][O:28][C:29]1[CH:36]=[CH:35][CH:34]=[CH:33][C:30]=1[CH2:31][NH2:32]>>[F:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][NH:16][C:7]2[CH:6]=[C:5]([NH2:4])[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([NH:32][CH2:31][C:30]4[CH:33]=[CH:34][CH:35]=[CH:36][C:29]=4[O:28][CH3:27])[CH:13]=3)[N:8]=2)=[C:19]([O:25][CH3:26])[CH:20]=1
Reactant: C=CCNc1cc(NCc2ccc(F)cc2OC)nc2ccc(Cl)cc12
Reactant: COc1ccccc1CN
Product: COc1ccccc1CNc1ccc2nc(NCc3ccc(F)cc3OC)cc(N)c2c1

Procedure:
The title compound, MS: m/e=433.2 (M+H+), was prepared in accordance with the general method of example 44 from N4-allyl-6-chloro-N2-(4-fluoro-2-methoxy-benzyl)-quinoline-2,4-diamine and 2-methoxybenzylamine
Reaction SMILES: [CH2:1]([C:9]1[S:13][C:12]([C:14]([OH:16])=[O:15])=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[CH2:17]([Si:21]([CH3:34])([CH3:33])[CH2:22][CH2:23][CH2:24][O:25][C:26]1[CH:31]=[CH:30][C:29](O)=[CH:28][CH:27]=1)[CH2:18][CH2:19][CH3:20].C1(N=C=NC2CCCCC2)CCCCC1.N1(C2C=CN=CC=2)CCCC1>ClCCl>[CH2:1]([C:9]1[S:13][C:12]([C:14]([O:16][C:29]2[CH:30]=[CH:31][C:26]([O:25][CH2:24][CH2:23][CH2:22][Si:21]([CH2:17][CH2:18][CH2:19][CH3:20])([CH3:34])[CH3:33])=[CH:27][CH:28]=2)=[O:15])=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCCCCc1ccc(C(=O)O)s1
Reactant: CCCC[Si](C)(C)CCCOc1ccc(O)cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: c1cc(N2CCCC2)ccn1
Solvent: ClCCl
Product: CCCCCCCCc1ccc(C(=O)Oc2ccc(OCCC[Si](C)(C)CCCC)cc2)s1
Temperature: 25 °C
Reaction time: 5 h
Yield: 58.4 %

Procedure:
15 ml of dichloromethane was added to 0.38 g (1.58 mM) of 5-octylthiophene-2-carboxylic acid and 0.42 g (1.58 mM) of 4-[3-(butyldimethylsilyl)propoxy]phenol, followed by stirring at room temperature to the mixture, 0.31 g (1.50 mM) of N,N'-dicyclohexylcarbodiimide (DCC) and 0.02 g of 4-pyrrolidinopyridine were added, followed by stirring for 5 hours at room temperature. The resultant dicyclohexylurea was recovered by filtration, followed by washing with dichloromethane to be added to the filtrate. The resultant dichloromethane solution was condensed into a solid under reduced pressure, followed by purification by silica gel column chromatography (eluent: toluene) and recrystallization from ethanol to obtain 0.45 g of 4-[3-(butyldimethylsilyl)propoxy]phenyl 5-octylthiophene-2-carboxylate (Yield: 61.4 %). ##STR71##
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[CH:4][C:3]=1/[CH:11]=[CH:12]/[C:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[CH2:49]([CH2:51][NH2:52])[OH:50]>[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[OH:50][CH2:49][CH2:51][NH:52][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[CH:4][C:3]=1/[CH:11]=[CH:12]/[C:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=1
Reactant: NC(=O)c1ccc(Br)c(/C=C/c2ccc(OC(F)(F)F)cc2)c1
Reactant: NCCO
Agent: [Pd]
Agent: O=C(C=Cc1ccccc1)C=Cc1ccccc1
Agent: c1ccc(-c2ccccc2P(C2CCCCC2)C2CCCCC2)cc1
Product: NC(=O)c1ccc(NCCO)c(/C=C/c2ccc(OC(F)(F)F)cc2)c1
Temperature: 65 °C
Reaction time: 3.5 h

Procedure:
The interior of a container containing 4-bromo-3-[(E)-2-(4-trifluoromethoxy-phenyl)-vinyl]-benzamide (50.2 mg) obtained in Example 2-5-1, 2.8 mg of tris(dibenzylideneacetone) dipalladium(0), 10 μL of ethanolamine, and 2.6 mg of 2-(dicyclohexylphosphino)biphenyl was purged with argon. A 1.0M tetrahydrofuran solution (1 mL) of lithium bis(trimethylsilyl)amide was added into the container, and the mixture was stirred for 3.5 hours at 65° C. Then, 2.0 mg of tris(dibenzylideneacetone) dipalladium(0), and 10 μL of ethanolamine were further added, the interior of the container was purged with argon, and the mixture was stirred for 13.5 hours at 65° C. The reaction mixture was cooled to room temperature, and 2 mL of 1N hydrochloric acid was added for neutralization, followed by extracting the aqueous layer with ethyl acetate 4 times. After the respective organic layers were combined, the combined organic layer was filtered through Presep Dehydration Column (produced by Wako Pure Chemical Industries), and the filtrate was concentrated under reduced pressure. The resulting residue was subjected to 11 g silica gel column chromatography to obtain 5.6 mg of 4-(2-hydroxy-ethylamino)-3-[(E)-2-(4-trifluoromethoxy-phenyl)-vinyl]-benzamide with the use of an eluant (dichloromethane and methanol, 15:1).
Reaction SMILES: [CH2:1]([NH:3][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH3:10])[CH:5]=1)[CH3:2].[C:11]([O:15][CH:16]([CH3:18])[CH3:17])(=[O:14])[CH:12]=[CH2:13].C(O)(=O)C>CCOCC>[CH2:1]([N:3]([CH2:13][CH2:12][C:11]([O:15][CH:16]([CH3:18])[CH3:17])=[O:14])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH3:10])[CH:5]=1)[CH3:2]
Reactant: C=CC(=O)OC(C)C
Reactant: CCNc1cccc(C)c1
Solvent: CCOCC
Solvent: CC(=O)O
Product: CCN(CCC(=O)OC(C)C)c1cccc(C)c1
Yield: 88.2 %

Procedure:
A mixture of 13.5 g (0.1 mole) N-ethyl-m-toluidine, 11.4 g (0.1 mole) isopropyl acrylate and 2 ml glacial acetic acid was heated over the steam bath for 16 hours. The mixture was cooled and diluted with ether. The ether solution was washed with 10 ml water, twice with 10 ml portions of 5% sodium carbonate solution, once with 10 ml of water and then dried over sodium sulfate. Removal of the ether with a rotary evaporator at 50° C. and reduced pressure gave 22.0 g (86%) of oil, which was pure by thin layer chromatography and was used as isolated.
Reaction SMILES: [O:1]=[CH:2][C:3]1[CH:11]=[CH:10][C:8]([OH:9])=[C:5]([O:6][CH3:7])[CH:4]=1.C([O-])([O-])=O.[K+].[K+].[CH2:18]([O:20][C:21](=[O:24])[CH2:22]Br)[CH3:19].C(O)C>CC(C)=O>[CH:2]([C:3]1[CH:11]=[CH:10][C:8]([O:9][CH2:22][C:21]([O:20][CH2:18][CH3:19])=[O:24])=[C:5]([O:6][CH3:7])[CH:4]=1)=[O:1]
Reactant: COc1cc(C=O)ccc1O
Reactant: CCOC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CCO
Product: CCOC(=O)COc1ccc(C=O)cc1OC
Yield: 77.6 %

Procedure:
The compound was prepared according to general procedure E with vanillin (5.3 mmol) in dry acetone (20 ml), anhydrous K2CO3 (6.8 mmol), and ethylbromoacetate (6.3 mmol) at reflux for 1 h. Ethanol was added and evaporated by azeotropic distillation with ethylbromoacetate. 980 mg of pure compound were obtained (78% yield). 1H NMR (250 MHz, CDCl3): δ 1.23 (m, 3H), 3.88 (s, 3H), 4.21 (m, 2H), 4.78 (s, 2H), 6.90 (m, 1H), 7.38 (m 2H), 9.80 (s, 1H) 13C NMR (63 MHz, CDCl3): δ 13.9, 55.7, 61.2, 65.6, 109.8, 112.3, 125.7, 130.8, 149.7, 152.4, 167.9, 190.6 MS (ESI): m/z 253.0 [M+H]+.