Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([NH2:4])([CH3:3])[CH3:2].[N+:5]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][C:17]([S:20](Cl)(=[O:22])=[O:21])=[CH:16][CH:15]=2)=[CH:10][CH:9]=1)([O-:7])=[O:6].O>CN(C=O)C>[CH:1]([NH:4][S:20]([C:17]1[CH:18]=[CH:19][C:14]([C:11]2[CH:12]=[CH:13][C:8]([N+:5]([O-:7])=[O:6])=[CH:9][CH:10]=2)=[CH:15][CH:16]=1)(=[O:21])=[O:22])([CH3:3])[CH3:2]
Reactant: O=[N+]([O-])c1ccc(-c2ccc(S(=O)(=O)Cl)cc2)cc1
Reactant: CC(C)N
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)NS(=O)(=O)c1ccc(-c2ccc([N+](=O)[O-])cc2)cc1
Reaction time: 18 h

Procedure:
0.22 ml (2.52 mmol) of isopropylamine is added to a solution of 150 mg (0.50 mmol) of 4′-nitrobiphenyl-4-sulfonyl chloride in 2.0 ml of DMF. After 18 h at room temperature, 2.5 ml of water are added to the reaction mixture. The resulting precipitate is filtered off with suction and dried under high vacuum. 126 mg (64.4% of theory) of the title compound are obtained and reacted further without further purification.
Reaction SMILES: [NH2:1][C:2]1[NH:6][N:5]=[N:4][CH:3]=1.[C:7]([C:10](=[CH:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[F:24])[C:11]([O:13][CH:14]([CH3:16])[CH3:15])=[O:12])(=O)[CH3:8]>C(#N)C>[F:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[CH:17]1[N:6]2[N:5]=[N:4][CH:3]=[C:2]2[NH:1][C:7]([CH3:8])=[C:10]1[C:11]([O:13][CH:14]([CH3:16])[CH3:15])=[O:12]
Reactant: CC(=O)C(=Cc1ccccc1F)C(=O)OC(C)C
Reactant: Nc1cnn[nH]1
Solvent: CC#N
Product: CC1=C(C(=O)OC(C)C)C(c2ccccc2F)n2nncc2N1
Yield: 23.7 %

Procedure:
A mixture of 0.34 g of 5-amino-1,2,3-triazole and 1.0 g of isopropyl α-acetyl-2-fluorocinnamate in 10 ml of acetonitrile is refluxed under heating for 4 hours. The solvent is distilled off under reduced pressure and the residue is crystallized from a mixture of diisopropyl ether and dichloromethane. The resulting crystals are recrystallized from a mixture of methanol, diisopropyl ether and hexane to give 0.3 g of 7-(2-fluorophenyl)-6-isopropoxycarbonyl-5-methyl-4,7-dihydro-1,2,3-triazolo[1,5-a]pyrimidine, melting at 137°-139° C., as colorless crystals.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[C:13]([CH2:14][OH:15])=[C:12]([CH:16]([CH3:18])[CH3:17])[CH:11]=[N:10]1.F[C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[C:22]([CH3:28])[CH:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[N:9]1[C:13]([CH2:14][O:15][C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[C:22]([CH3:28])[CH:21]=2)=[C:12]([CH:16]([CH3:18])[CH3:17])[CH:11]=[N:10]1
Reactant: Cc1cc(F)ccc1C#N
Reactant: CC(C)c1cnn(-c2c(Cl)cccc2Cl)c1CO
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: Cc1cc(OCc2c(C(C)C)cnn2-c2c(Cl)cccc2Cl)ccc1C#N
Temperature: 80 °C
Yield: 60.7 %

Procedure:
To an ambient temperature solution of [2-(2,6-Dichloro-phenyl)-4-isopropyl-2H-pyrazol-3-yl]-methanol (2.50 g, 8.76 mmol) in DMF (15 mL) is added 4-Fluoro-2-methyl-benzonitrile 1.18 g, 8.76 mmol), cesium carbonate (5.71 g, 17.53 mmol). The reaction mixture is heated to 80° C. overnight. The reaction mixture is concentrated and the residue is partitioned between Et2O and water. The aqueous layer is extracted with Et2O and the combined organic layers are washed with brine, dried (MgSO4), filtered, concentrated, and chromatographed (0% to 20% EtOAc/Hex) to yield the title compound (2.13 g, 61%). 1H NMR (400 MHz, CDCl3) δ 7.72 (s, 1H), 7.46-7.40 (m, 3H), 7.32 (dd, 1H, J=9.0, 7.3 Hz), 6.68-6.62 (m, 2H), 4.85 (s, 2H), 2.99 (sept, 1H, J=7.0 Hz), 2.46 (s, 3H), 1.31 (d, 6H, J=7.0 Hz).
Reaction SMILES: [Cl:1][C:2]1[C:3]([Cl:9])=[C:4](Cl)[CH:5]=[CH:6][CH:7]=1.[CH3:10][O-:11].[Na+]>CC(N(C)C)=O.CO>[Cl:9][C:3]1[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=1[O:11][CH3:10]
Reactant: C[O-]
Reactant: Clc1cccc(Cl)c1Cl
Agent: [Na+]
Solvent: CC(=O)N(C)C
Solvent: CO
Product: COc1cccc(Cl)c1Cl
Reaction time: 0.5 h

Procedure:
Trichlorobenzene (363 g, 2 moles) was dissolved in 600 ml of dimethyl acetamide and 650 ml of 25% sodium methoxide in methanol solution added all at once. The solution was stirred and heated to 166° as the methanol slowly distilled out. The solution was held at 166° for 30 minutes, * cooled and quenched with 5 times its volume of water and extracted with toluene (2 × 1000 ml). The toluene extracts were washed with water (1 L) and dried over sodium sulfate. The toluene was removed by distillation under reduced pressure and the residue fractionated to yield the pure 2,3-dichloroanisole, bp 140°/28 mm. Yield 212 g (60%). Considerable material remains in the aqueous DMAC layer and can be recovered by repeated extractions with methylene chloride.
Reaction SMILES: [CH:1]1[C:6]([OH:7])=[CH:5][CH:4]=[CH:3][C:2]=1[CH3:8].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[C@@H:29]([CH3:34])[C:30]([O:32][CH3:33])=[O:31].CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1.C(OCC)(=O)C>[C:2]1([CH3:8])[CH:3]=[CH:4][CH:5]=[C:6]([O:7][C@H:29]([CH3:34])[C:30]([O:32][CH3:33])=[O:31])[CH:1]=1
Reactant: Cc1cccc(O)c1
Reactant: COC(=O)[C@H](C)O
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COC(=O)[C@@H](C)Oc1cccc(C)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 45.9 %

Procedure:
To a solution of the m-cresol (1.0 g, 9.2 mmol) in anhydrous THF (15 mL) at 0° C. under argon protection was added triphenylphosphine (2.55 g, 9.7 mmol), followed by addition of the (S)-methyl 2-hydroxypropanoate (926 μL, 9.7 mmol). Then diisopropylazodicarboxylate (DIAD) (2.85 mL, 13.8 mmol) was added dropwise at 0° C. The reaction mixture was stirred at room temperature overnight. The resulting mixture was diluted by ethyl acetate, washed with a 0.5 N HCl solution, a saturated solution of NaHCO3, and brine, dried on MgSO4, and concentrated. The obtained oil was purified by flash chromatography (Hexane/Ethyl acetate 0˜50%) to afford a colorless oil (820 mg, 46%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[CH:18]=[CH:17][N:16]=[C:15]([C:19]([OH:21])=[O:20])[CH:14]=2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].Cl.[CH2:23](N=C=NCCCN(C)C)C>CO.ClCCl>[CH3:12][O:11][C:7]1[CH:6]=[C:5]([C:13]2[CH:18]=[CH:17][N:16]=[C:15]([C:19]([O:21][CH3:23])=[O:20])[CH:14]=2)[CH:4]=[C:3]([O:2][CH3:1])[C:8]=1[O:9][CH3:10]
Reactant: CCN=C=NCCCN(C)C
Reactant: COc1cc(-c2ccnc(C(=O)O)c2)cc(OC)c1OC
Agent: Cl
Solvent: ClCCl
Solvent: CO
Product: COC(=O)c1cc(-c2cc(OC)c(OC)c(OC)c2)ccn1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
4-(3,4,5-Trimethoxyphenyl)pyridine-2-carboxylic acid (587 mg) was dissolved in methanol (2 mL) and dichloromethane (8 mL), and to the solution 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (583 mg) was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with ethyl acetate. After the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure, the residue was purified by column chromatography on silica gel (chloroform:methanol=40:1) to obtain the title compound.
Reaction SMILES: [OH:1][C@@H:2]([C:5]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)[N:8]=[C:7]([C:25]([O:27]C)=[O:26])[CH:6]=1)[CH2:3][OH:4].C1COCC1.O[Li].O>O>[OH:1][C@@H:2]([C:5]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)[N:8]=[C:7]([C:25]([OH:27])=[O:26])[CH:6]=1)[CH2:3][OH:4]
Reactant: COC(=O)c1cc([C@H](O)CO)cc(-c2ccc(Oc3ccc(F)cc3)cc2)n1
Agent: [Li]O
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)c1cc([C@H](O)CO)cc(-c2ccc(Oc3ccc(F)cc3)cc2)n1
Reaction time: 8 h

Procedure:
To the crude (S)-methyl 4-(1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)picolinate (assume 0.884 mmol) in 5 mL of a 5:1 mixture of THF and water was added LiOH.H2O (0.084 g, 2.00 mmol). The reaction was stirred overnight then evaporated in vacuo. The residue was dissolved in 5 mL water, filtered and acidified with 2.00 mL 1N HCl. The mixture was evaporated in vacuo to give the product (S)-4-(1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)picolinic acid mixed with lithium chloride (LC/MS: m/z=370.2 [M+H]+).
Reaction SMILES: [NH:1]([C:5]1[S:6][CH:7]=[C:8]([C:10]2[CH:11]=[C:12]([NH:16][C:17](SC)=[CH:18][N+:19]([O-:21])=[O:20])[CH:13]=[CH:14][CH:15]=2)[N:9]=1)[C:2]([NH2:4])=[NH:3].[CH3:24][N:25]([CH2:27][C:28]1[O:32][C:31]([CH2:33][S:34][CH2:35][CH2:36][NH2:37])=[CH:30][CH:29]=1)[CH3:26]>>[NH:1]([C:5]1[S:6][CH:7]=[C:8]([C:10]2[CH:11]=[C:12]([NH:16][C:17]([NH:37][CH2:36][CH2:35][S:34][CH2:33][C:31]3[O:32][C:28]([CH2:27][N:25]([CH3:26])[CH3:24])=[CH:29][CH:30]=3)=[CH:18][N+:19]([O-:21])=[O:20])[CH:13]=[CH:14][CH:15]=2)[N:9]=1)[C:2]([NH2:4])=[NH:3]
Reactant: CN(C)Cc1ccc(CSCCN)o1
Reactant: CSC(=C[N+](=O)[O-])Nc1cccc(-c2csc(NC(=N)N)n2)c1
Product: CN(C)Cc1ccc(CSCCNC(=C[N+](=O)[O-])Nc2cccc(-c3csc(NC(=N)N)n3)c2)o1
Temperature: 100 °C

Procedure:
A mixture of 1-[3-(2-guanidinothiazol-4-yl)phenylamino]-1-methylthio-2-nitroethylene (0.16 g.) and 2-[(5-dimethylaminomethylfuran-2-yl)methylthio]ethylamine (1 g.) was heated at 100° C. for 2 hours. The product was extracted 10 times with 5 ml. portions of diethyl ether and the residual gum was applied to Merck 60 F254 preparative plates and eluted with ethyl acetate/methanol/concentrated aqueous ammonia 6:1:1 v/v/v. The solid obtained (0.05 g.) was crystallised twice from acetonitrile to give 1-[3-(2-guanidinothiazol-4-yl)phenylamino]-1-[2-[(5-dimethylaminomethylfuran-2-yl)methylthio]ethylamino]-2-nitroethylene, m.p. 175°-180° C. (decomp.).
Reaction SMILES: [Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[C@H:10]([O:12][C:13]1[C:14]([NH2:28])=[N:15][CH:16]=[C:17](B2OC(C)(C)C(C)(C)O2)[CH:18]=1)[CH3:11].Br[C:30]1[CH:31]=[N:32][N:33]([CH:35]2[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]2)[CH:34]=1>>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[C@H:10]([O:12][C:13]1[C:14]([NH2:28])=[N:15][CH:16]=[C:17]([C:30]2[CH:31]=[N:32][N:33]([CH:35]3[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]3)[CH:34]=2)[CH:18]=1)[CH3:11]
Reactant: CN1CCC(n2cc(Br)cn2)CC1
Reactant: C[C@@H](Oc1cc(B2OC(C)(C)C(C)(C)O2)cnc1N)c1c(Cl)ccc(F)c1Cl
Product: C[C@@H](Oc1cc(-c2cnn(C3CCN(C)CC3)c2)cnc1N)c1c(Cl)ccc(F)c1Cl

Procedure:
The title compound was prepared according to procedure 62 using 3-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-ylamine and 4-(4-bromo-pyrazol-1-yl)-1-methyl-piperidine (prepared according to general procedure 11. 1H NMR (400 MHz, CDCl3) δ 7.65 (s, 1H), 7.55 (s, 1H), 7.50 (s, 1H), 7.31 (m, 1H), 7.06 (m, 1H), 6.87 (s, 1H), 6.08 (m, 1H), 5.50 (bs, 2H), 4.18 (m, 1H), 3.11 (m, 2H), 2.40 (s, 3H), 2.30 (m, 2H), 2.20 (m, 4H), 2.07 (s, 3H), 1.86 (d, J 8 Hz, 3H); LCMS: 464 [M+1]; c-Met Ki: 0.01 μM.
Reaction SMILES: [OH:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1I)=[O:4].[F:12][C:13]1[CH:18]=[CH:17][C:16](/[CH:19]=[CH:20]/[C:21]2[CH:26]=[CH:25][C:24]([S:27]([O-:29])=[O:28])=[CH:23][CH:22]=2)=[CH:15][CH:14]=1.[Na+]>>[F:12][C:13]1[CH:14]=[CH:15][C:16](/[CH:19]=[CH:20]/[C:21]2[CH:26]=[CH:25][C:24]([S:27]([C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=3[C:3](=[O:4])[CH2:2][OH:1])(=[O:29])=[O:28])=[CH:23][CH:22]=2)=[CH:17][CH:18]=1
Reactant: O=C(CO)c1ccccc1I
Reactant: O=S([O-])c1ccc(/C=C/c2ccc(F)cc2)cc1
Agent: [Na+]
Product: O=C(CO)c1ccccc1S(=O)(=O)c1ccc(/C=C/c2ccc(F)cc2)cc1

Procedure:
The title compound was prepared from 2-hydroxy-1-(2-iodophenyl)ethanone (Step 1) and sodium 4-[(E)-2-(4-fluorophenyl)vinyl]benzenesulfinate according to the method of Example 135 Step 2. δH (500 MHz, d6 DMSO): 8.07 (1H, d, J=7.8 Hz), 7.88 (2H, d, J=8.4 Hz), 7.80 (2H, d, J=8.4 Hz), 7.76-7.66 (4H, m), 7.54 (1H, d, J=7.4 Hz), 7.45 (1H, d, J=16.4 Hz), 7.28 (1H, d, J=16.4 Hz), 7.23 (2H, t, J=8.7 Hz), 5.47 (1H, t, J=5.9 Hz), 4.54 (2H, d, J=5.9 Hz).
Reaction SMILES: [CH2:1]([C@@H:7]([CH2:11][C:12]#[CH:13])[C:8]([OH:10])=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]>C(=O)([O-])[O-].[Ca+2].[Pd+2].C(=O)([O-])[O-].C(O)C>[CH2:1]([C@H:7]1[CH2:11][C:12](=[CH2:13])[O:9][C:8]1=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: C#CC[C@H](CCCCCC)C(=O)O
Agent: [Pd+2]
Agent: O=C([O-])[O-]
Agent: [Ca+2]
Solvent: CCO
Product: C=C1C[C@H](CCCCCC)C(=O)O1

Procedure:
Under an atmosphere of argon, ethanol solution of (2S)-2-hexylpent-4-ynoic acid was reacted in the presence of palladium-calcium carbonate to give (3S)-3-hexyl-5-methylidenedihydrofuran-2-(3H)-one. The obtained compound was reacted in the presence of 5% palladium-carbon, under an atmosphere of hydrogen gas, to give the compound of the present invention having the following physical data.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([Cl:9])[C:3]=1[N:10]1[C:14](=[O:15])[CH:13](Br)[C:12]([NH:17][C:18](=[O:39])[CH:19]([O:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]([CH2:32][CH3:33])([CH3:31])[CH3:30])=[CH:25][C:24]=2[C:34]([CH2:37][CH3:38])([CH3:36])[CH3:35])[CH2:20][CH3:21])=[N:11]1.[NH:40]1[CH:44]=[CH:43][N:42]=[CH:41]1.CO>C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([Cl:9])[C:3]=1[N:10]1[C:14](=[O:15])[CH:13]([N:40]2[CH:44]=[CH:43][N:42]=[CH:41]2)[C:12]([NH:17][C:18](=[O:39])[CH:19]([O:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]([CH2:32][CH3:33])([CH3:31])[CH3:30])=[CH:25][C:24]=2[C:34]([CH2:37][CH3:38])([CH3:36])[CH3:35])[CH2:20][CH3:21])=[N:11]1
Reactant: CCC(Oc1ccc(C(C)(C)CC)cc1C(C)(C)CC)C(=O)NC1=NN(c2c(Cl)cc(Cl)cc2Cl)C(=O)C1Br
Reactant: c1c[nH]cn1
Solvent: CCOC(C)=O
Solvent: CO
Product: CCC(Oc1ccc(C(C)(C)CC)cc1C(C)(C)CC)C(=O)NC1=NN(c2c(Cl)cc(Cl)cc2Cl)C(=O)C1n1ccnc1
Temperature: 100 °C
Reaction time: 2 h

Procedure:
66 g (0.1 mol) of 1-(2,4,6-trichlorophenyl)-3-[α-(2,4-di-tert-amylphenoxy)butyramido]-4-bromo-5-oxo-2-pyrazoline and 27.2 g (0.4 mol) of imidazole were well mixed with each other in a mortar, then stirred for 2 hours under heating to 100° C. To the reaction mixture was added 200 ml of methanol to prepare a solution. Then 1 liter of ethyl acetate was added thereto, followed by washing several times with water. The ethyl acetate layer was dried with anhydrous sodium sulfate, and concentrated. Upon crystallization of the residue from acetonitrile-ethyl acetate (volume ratio:20.1), 48 g of pure Coupler (1) was obtained. The melting point of the coupler was 185°-187° C.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH:6]=O.[NH:8]1[CH2:14][C:12](=[O:13])[NH:11][C:9]1=[O:10]>>[C:2]1([CH:6]=[C:14]2[NH:8][C:9](=[O:10])[NH:11][C:12]2=[O:13])[S:1][CH:5]=[CH:4][CH:3]=1
Reactant: O=C1CNC(=O)N1
Reactant: O=Cc1cccs1
Product: O=C1NC(=O)C(=Cc2cccs2)N1
Yield: 75 %

Procedure:
It known that the condensation of thiophene-2-carbaldehyde with hydantoin gives 5-(2-thenylidene) hydantoin, which can then be reduced either into 5-(2-thenyl) hydantoin, with a yield of 75% by sodium amalgam in a petroleum ether (G. BARGER and A. EASSON, J. Chem. Soc. 1938, 2100), or directly into β 2-thienyl alanine, with a yield of 72% by using ammonium sulphide (V. du VIGNEAUD et al, J. Biol. Chem., 159, 385-94, 1945).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[CH:12][C:11](Br)=[CH:10][N:9]=2)=[CH:4][CH:3]=1.[CH:15]#[C:16][CH2:17][CH2:18][CH3:19].FC1C(F)=C(OCCCCCCCC)C=CC=1C1N=CC(C#CCCCCCCC)=CN=1>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.[Cu]I.C(NC(C)C)(C)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[CH:12][C:11]([C:15]#[C:16][CH2:17][CH2:18][CH3:19])=[CH:10][N:9]=2)=[CH:4][CH:3]=1
Reactant: C#CCCC
Reactant: Fc1ccc(-c2ncc(Br)cn2)cc1
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CCCCCCCC#Cc1cnc(-c2ccc(OCCCCCCCC)c(F)c2F)nc1
Solvent: CC(C)NC(C)C
Product: CCCC#Cc1cnc(-c2ccc(F)cc2)nc1
Yield: 87 %

Procedure:
--Quantities: 2-(4'-fluorophenyl)-5-bromo-pyrimidine 20 (1.48 g, 4.88 mmol), pent-1-yne (0.98 ml, 10 mmol), tetrakis(triphenylphosphine)palladium (350 mg, 0.30 mmol), copper(I) iodide (57 mg, 0.30 mmol), diisopropylamine (20 ml). The experimental procedure was as described for compound 38. The crude product was purified by flash chromatography (8% ethyl acetate-light petroleum) to give the fluorophenylpyrimidine 42 (1.02 g, 85%), m.p. 51° C.; νmax /cm-1 (KBr) 2960, 2870, 2220, 1600, 1510, 1430, 1220, 1150 and 855; δ 1.07 (3H, t, Me), 1.68 (2H, sext, CH2CH3), 2.47 (2H, t, CH2C≡C), 7.18 (2H, t, 3'- and 5'-H), 8.44 (2H, dd, 2'- and 6'-H) and 8.75 (2H, s, 4- and 6-H); m/z 240 (M+), 225, 212, 198, 184, 171 and 118.
Reaction SMILES: [CH:1]([C:3]1[CH:12]=[CH:11][C:6]2[C:7](=[O:10])[O:8][CH2:9][C:5]=2[C:4]=1[CH2:13][CH2:14][OH:15])=[CH2:2].C1C=C(Cl)C=C(C(OO)=[O:24])C=1>ClCCl>[OH:24][CH2:2][CH:1]1[C:3]2[C:4](=[C:5]3[CH2:9][O:8][C:7](=[O:10])[C:6]3=[CH:11][CH:12]=2)[CH2:13][CH2:14][O:15]1
Reactant: C=Cc1ccc2c(c1CCO)COC2=O
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: O=C1OCc2c1ccc1c2CCOC1CO
Temperature: 25 °C
Reaction time: 8 h

Procedure:
5-Ethenyl-4-(2-hydroxyethyl)-2-benzofuran-1(3H)-one (1.2 g, 5.9 mmol) was added to a flask containing a stir bar. To the flask was then added dichloromethane (20 mL). The flask was placed in a cool bath of 0° C.; to the flask was poured mCPBA (1.5 g, 8.8 mmol) and the resulting mixture was stirred at room temperature for overnight; LC as well as TLC (hexanes/EtOAc=1/1) indicated that reaction had gone to completion. The solution was treated with dichloromethane and washed with NaHCO3, Na2S2O3, and water, the organic layer was then dried over Na2SO4, filtered and concentrated to dryness, it was then treated with AcOH (20 mL) and stirred overnight; LC indicated formation of cyclized product. The solvent was removed and the resulting residue was absorbed into silica gel and 6-(hydroxymethyl)-8,9-dihydro-1H-furo[3,4-f]isochromen-3(6H)-one was isolated with the solvent systems of hexanes/EtOAc (1/1). 1H-NMR (400 MHz, CDCl3) δ ppm 7.807 (d, J=8 Hz, 1H), 7.337 (d, J=8 Hz, 1H), 5.279 (s, 2H), 4.985 (s, 1H), 4.302-4.302 (m, 1H), 4.183-4.084 (m, 2H), 3.954-3.912 (m, 2H), 3.006-2.944 (m, 1H), 2.717-2.686 (m, 1H), 2.179-2.172 (m, 2H)
Reaction SMILES: [C-:1]#[N:2].[Na+].[CH3:4][O:5][C:6]1[CH:7]=[C:8]([CH2:12][CH2:13][CH2:14]I)[CH:9]=[CH:10][CH:11]=1.C(OCC)C>CS(C)=O>[CH3:4][O:5][C:6]1[CH:7]=[C:8]([CH2:12][CH2:13][CH2:14][C:1]#[N:2])[CH:9]=[CH:10][CH:11]=1
Reactant: COc1cccc(CCCI)c1
Reactant: [C-]#N
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCOCC
Product: COc1cccc(CCCC#N)c1
Temperature: 90 °C

Procedure:
A magnetically stirred suspension of sodium cyanide (13.65 g, 265 mmol) in anhydrous methyl sulfoxide (65 mL) was treated dropwise with 3-(3-methoxyphenyl)propyl iodide (66.25 g, 240 mmol) at a rate sufficient to keep the temperature below 45° C. The suspension was heated at 90° C. for 1 h, cooled to room temperature, poured over ice (1000 g), treated with diethyl ether (500 mL), the layers separated, and the aqueous portion back-extracted with diethyl ether (2×300 mL). The combined organic extracts were washed with water (3×500 mL), 6N HCl (500 mL), brine (500 mL), dried (MgSO4), filtered, and concentrated in vacuo to a clear liquid. Kugelrohr distillation (0.1 torr, 120° C.) provided the desired product as a dear liquid (37.62 g, 89%): 1H NMR (CDCl3) δ7.25 (t, J=8 Hz, 1H), 6.78-6.69 (m, 3 H), 3.80 (s, 3 H), 2.75 (t, J=8 Hz, 2 H), 2.31 (t, J=8 Hz, 2 H), 1.98 (quint, J=8 Hz, 2 H). 4-(3-Methoxyphenyl)butylamine: To a Parr bottle flushed with nitrogen was added -1.0 g of Raney Nickel (50% suspension in H2O), ethanol (125 mL), ammonium hydroxide (30 mL), and a solution of 4-(3-methoxyphenyl)butyronitrile (8.49 g, 48.4 mmol) in ethanol (150 mL). The bottle was charged with hydrogen (60 psi) and rocked 3 d. The suspension was filtered through Celite, the cake rinsed with fresh ethanol (400 mL), and the combined filtrate concentrated in vacuo. The resulting suspension was treated with dichloromethane (200 mL) and water (200 mL), the layers separated, and the aqueous portion back-extracted with fresh dichloromethane (2×150 mL). The combined organic portions were washed with saturated sodium chloride solution (300 mL), dried (K2CO3), filtered, and concentrated in vacuo. Kugelrohr distillation (0.1 torr, 120° C.) provided the desired product as a dear liquid (6.77 g, 78%) which was identical spectroscopically to that previously reported. Venit, J. J.; DiPierro, M.; Magnus, P. J. Org. Chem. 1989, 54, 4298-4301. 1H NMR (CDCl3) δ 7.20 (t, J=8 Hz, 1 H), 6.79-6.70 (m, 3 H), 3.80 (s, 3 H), 2.75-2.68 (m, 2 H), 2.61 (t, J=8 Hz, 2 H), 1.82-1.45 (m, 6 H).
Reaction SMILES: C(N(CC)CC)C.[C:8]([OH:31])(=O)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29].C(Cl)(=O)OCC.[C:38](O)(=[O:46])[C:39]1[C:40](=[CH:42][CH:43]=[CH:44][CH:45]=1)[NH2:41]>C(Cl)Cl>[CH2:9]([C:8]1[O:31][C:38](=[O:46])[C:39]2[CH:45]=[CH:44][CH:43]=[CH:42][C:40]=2[N:41]=1)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]
Reactant: CCCCCCCCCCCCCCCCCCCCCC(=O)O
Reactant: Nc1ccccc1C(=O)O
Agent: CCOC(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCCCCCCCCCCCCCCCCCCc1nc2ccccc2c(=O)o1
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 74.5 %

Procedure:
Triethylamine (1.58 ml) was added to a suspension of behenic acid (3.51 g) in methylene chloride (35 ml). Then, ethyl chlorocarbonate (1.08 ml) was dropwise added to the mixture while being cooled with ice. After being stirred for 1.5 hours at 0° C., the mixture, with a mixed solution of anthranilic acid (1.42 g) and triethylamine (1.44 ml) in methylene chloride (7 ml) dropwise added thereto, was stirred for 3 hour at 0° C. and for 15 hours at room temperature successively, and then cooled with ice. The reaction mixture, with triethylamine (1.58 ml) and ethyl chlorocarbonate (1.08 ml) dropwise added thereto, was stirred for 1 hour at 0° C. and for 2.5 hours at room temperature successively, and then concentrated. The residue, with chloroform added thereto, was washed with water and saturated brine successively. The organic layer was dried over sodium sulfate anhydride, and then concentrated. The residue was purified by silica gel column chromatography (silica gel 100 g, hexane-chloroform), thereby yielding 3.39 g of the aimed compound as colorless solid.
Reaction SMILES: NC1C=C(C(C2C=CC(OC)=C(OCC)C=2)=CC#N)C=CC=1OC.[CH3:25][O:26][C:27]1[CH:28]=[C:29]([C:36]([C:40]2[CH:45]=[C:44]([O:46][CH3:47])[CH:43]=[C:42]([O:48][CH3:49])[CH:41]=2)=[CH:37][C:38]#[N:39])[CH:30]=[CH:31][C:32]=1[N+:33]([O-])=O.O.O.[Sn](Cl)(Cl)(Cl)Cl>>[NH2:33][C:32]1[CH:31]=[CH:30][C:29]([C:36]([C:40]2[CH:45]=[C:44]([O:46][CH3:47])[CH:43]=[C:42]([O:48][CH3:49])[CH:41]=2)=[CH:37][C:38]#[N:39])=[CH:28][C:27]=1[O:26][CH3:25]
Reactant: COc1cc(OC)cc(C(=CC#N)c2ccc([N+](=O)[O-])c(OC)c2)c1
Agent: CCOc1cc(C(=CC#N)c2ccc(OC)c(N)c2)ccc1OC
Agent: Cl[Sn](Cl)(Cl)Cl
Solvent: O
Product: COc1cc(OC)cc(C(=CC#N)c2ccc(N)c(OC)c2)c1
Yield: 86.9 %

Procedure:
3-(4-Amino-3-methoxy-phenyl)-3-(3,5-dimethoxy-phenyl)-acrylonitrile was prepared analogously to 3-(3-amino-4-methoxy-phenyl)-3-(3-ethoxy-4-methoxy-phenyl)-acrylonitrile using 3-(3-methoxy-4-nitro-phenyl)-3-(3,5-dimethoxy-phenyl)-acrylonitrile (3.9 g, 11.5 mmol) and tin chloride dihydrate (12.8 g, 58.0 mmol) to afford mixture isomers of 3-(4-amino-3-methoxy-phenyl)-3-(3,5-dimethoxy-phenyl)-acrylonitrile (3.1 g, 84%) as a yellow solid: mp 114-116° c; 1H NMR (CDCl3) δ 7.04-6.45 (m, 6H), 5.60(5.46) (s, 1H), 3.86-3.70(m, 11H); 13CNMR(CDCl3)δ 163.18, 162.98, 160.57, 146.32, 142.06, 139.34, 139.07, 138.57, 128.03, 126.37, 124.00, 122.74, 107.15, 102.02, 101.95, 91.86, 90.98, 55.69, 55.55; Anal Calcd for C18H18N2O3: C, 69.66; H, 5.85; N, 9.03. Found: C, 69.33; H, 5.67; 8.85.