Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[CH:2]1[C:13]2[C:12](=[CH:14][CH2:15][CH2:16][N:17]3[CH2:21][CH2:20][CH:19]([CH2:22][C:23]([OH:25])=[O:24])[CH2:18]3)[C:11]3[CH:26]=[CH:27][CH:28]=[CH:29][C:10]=3[O:9][CH2:8][O:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.Br[CH2:31]CC=C1C2C=CC=CC=2OCOC2C=CC=CC1=2.C(O)(=O)C.N1CCC(CC(OC)=O)C1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CC(=O)CC.CCOCC.O>[CH3:31][O:24][C:23](=[O:25])[CH2:22][CH:19]1[CH2:20][CH2:21][N:17]([CH2:16][CH2:15][CH:14]=[C:12]2[C:11]3[CH:26]=[CH:27][CH:28]=[CH:29][C:10]=3[O:9][CH2:8][O:7][C:6]3[CH:5]=[CH:4][CH:3]=[CH:2][C:13]2=3)[CH2:18]1
Reactant: BrCCC=C1c2ccccc2OCOc2ccccc21
Reactant: O=C(O)CC1CCN(CCC=C2c3ccccc3OCOc3ccccc32)C1
Agent: COC(=O)CC1CCNC1
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CCC(C)=O
Solvent: CCOCC
Solvent: O
Product: COC(=O)CC1CCN(CCC=C2c3ccccc3OCOc3ccccc32)C1
Reaction time: 0.08 h

Procedure:
1-(3-(12H-Dibenzo[d,g][1,3]dioxocin-12-ylidene)-1-propyl)-3-pyrrolidineacetic acid hydrochloride ##STR8## A mixture of 12-(3-bromo-1-propylidene)-12H-dibenzo[d,g][1,3]dioxocine (500 g, 15 mmol, prepared as described in example 1), methyl 3-pyrrolidineacetate acetate (3.04 g, 15 mmol), potassium carbonate (6.2 g, 45 mmol) and potassium iodide (2.23 g, 13 mmol) in 2-butanone (70 ml) was heated at reflux temperature for 5 h. The readon mixture was cooled and water (140 ml) and ether (140 ml) were added. The mixture was vigorously stirred for 5 minutes, the organic layer was separated, washed with water (2×50 ml) and dried over MgSO4. The solvent was evaporated in vacuo and the residue (4.34 g) was submitted to column chromatography on silica gel (100 g) using a mixture of dichloro-methane and methanol (10:1) as eluent. This afforded l.05 g of 1-(3-(12H-dibenzo[d,g]-[1,3]dioxocin-12-ylidene)-1-propyl)-3-pyrrolidineacetic acid methyl ester.
Reaction SMILES: C([O:3][P:4]([C:9]1[S:13][C:12]2[CH:14]=[CH:15][C:16]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([CH2:25][CH3:26])=[CH:21][CH:20]=3)=[CH:17][C:11]=2[CH:10]=1)(=[O:8])[O:5]CC)C.Br[Si](C)(C)C.CO>ClCCl>[CH2:25]([C:22]1[CH:23]=[CH:24][C:19]([CH2:18][C:16]2[CH:15]=[CH:14][C:12]3[S:13][C:9]([P:4]([OH:5])(=[O:3])[OH:8])=[CH:10][C:11]=3[CH:17]=2)=[CH:20][CH:21]=1)[CH3:26]
Reactant: CCOP(=O)(OCC)c1cc2cc(Cc3ccc(CC)cc3)ccc2s1
Agent: C[Si](C)(C)Br
Solvent: ClCCl
Solvent: CO
Product: CCc1ccc(Cc2ccc3sc(P(=O)(O)O)cc3c2)cc1
Temperature: 25 °C
Reaction time: 19 h
Yield: 84.2 %

Procedure:
To a solution of [5-(4-ethylbenzyl)benzo[b]thiophen-2-phosphonic acid diethylester (1.00 g) in dichloromethane (17.0 mL) was added bromotrimethylsilane (1.7 mL) at 0° C., and the reaction mixture was stirred for 19 hr at room temperature. Methanol (4.5 mL) was added to the reaction mixture, and the mixture was stirred for 10 min at room temperature. After evaporation, the residue was crystallized from ethyl acetate-n-hexane to give the title compound (0.72 g) as a colorless crystal.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([CH2:8]O)[CH:5]=[C:4]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[N:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[CH:32]([C:35]1[C:40](=[O:41])[NH:39][C:38](=[O:42])[NH:37][C:36]=1[C:43]([C:45]1[CH:46]=[C:47]([CH:51]=[CH:52][C:53]#[N:54])[CH:48]=[CH:49][CH:50]=1)=[O:44])([CH3:34])[CH3:33].C(=O)([O-])[O-].[K+].[K+].[I-].[Li+]>C(Cl)(Cl)Cl.ClCCl.CN(C=O)C>[F:1][C:2]1[CH:7]=[C:6]([CH2:8][N:37]2[C:36]([C:43]([C:45]3[CH:46]=[C:47]([CH:51]=[CH:52][C:53]#[N:54])[CH:48]=[CH:49][CH:50]=3)=[O:44])=[C:35]([CH:32]([CH3:33])[CH3:34])[C:40](=[O:41])[NH:39][C:38]2=[O:42])[CH:5]=[C:4]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[N:3]=1
Reactant: CC(C)c1c(C(=O)c2cccc(C=CC#N)c2)[nH]c(=O)[nH]c1=O
Reactant: COc1ccc(CNc2cc(CO)cc(F)n2)cc1
Agent: CS(=O)(=O)Cl
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: ClCCl
Product: COc1ccc(CNc2cc(Cn3c(C(=O)c4cccc(C=CC#N)c4)c(C(C)C)c(=O)[nH]c3=O)cc(F)n2)cc1
Reaction time: 1.5 h
Yield: 46.2 %

Procedure:
To a stirred solution of 2-fluoro-6-(p-methoxybenzylamino)-4-pyridine-methanol (186 mg, 0.712 mmol) in chloroform (7 ml) at 0° C. (ice bath), was added triethylamine (150 μl, 1.07 mmol) followed by methanesulfonyl chloride (64 μl, 0.85 mmol). After stirring for 1.5 hr., the mixture was diluted with dichloromethane, washed with aqueous saturated sodium bicarbonate solution, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was further dried in high vacuo and mixed with 3-[3-(5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-phenyl]-acrylonitrile (309 mg, 0.712 mmol), anhydrous powdered potassium carbonate (110 mg, 0.8 mmol), lithium iodide (107 mg, 0.8 mmol). Anhydrous DMF (5 ml) was then added into the mixture and stirred for overnight at room temperature. The mixture was evaporated in vacuo. The residue was dissolved in methanol-dichloromethane (1:9), filtered through celite pad, and evaporated in vacuo to give a pale yellow foam. The crude product was purified by silica gel column chromatography (eluent, EA:hexanes (1:2); The fraction of Rf=0.14 was collected.) to afford 182 mg (46%) of a pale yellow syrup.
Reaction SMILES: [N:1]([CH2:4][C:5]([C:7]1[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=1)=[O:6])=[N+]=[N-].[CH3:15][C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][C:17]=1[N:25]=[C:26]=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1>[CH3:15][C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][C:17]=1[NH:25][C:26]1[O:6][C:5]([C:7]2[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=2)=[CH:4][N:1]=1
Reactant: N#Cc1ccc(C(=O)CN=[N+]=[N-])cc1
Reactant: Cc1ccc([N+](=O)[O-])cc1N=C=O
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Product: Cc1ccc([N+](=O)[O-])cc1Nc1ncc(-c2ccc(C#N)cc2)o1
Reaction time: 0.5 h
Yield: 44.9 %

Procedure:
To a solution of 4-Azidoacetyl-benzonitrile (1.5 g, 8.06 mmol) in dioxane 25 mL was added 2-methyl-5-nitrophenyl isocyanate (1.43 mg, 8.06 mmol) (commercially available), and triphenylphosphine (2.11 g, 8.06 mmol). The reaction mixture was placed in an oil bath preheated to 100° C. and stirred for 30 min. After evaporation of the solvent under reduced pressure, the solid residue was recrystallized from ethanol to give the title compound as yellow micro crystals (1.16 g, 45%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](=[O:13])[C:11](=[CH:14]O)[C:10]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[N+:22]([O-])=O)=[N:9]2)=[CH:4][CH:3]=1>O1CCCC1.[Pt]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](=[O:13])[C:11]3=[CH:14][NH:22][C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=4[C:10]3=[N:9]2)=[CH:4][CH:3]=1
Reactant: O=C1C(=CO)C(c2ccccc2[N+](=O)[O-])=NN1c1ccc(Cl)cc1
Agent: [Pt]
Solvent: C1CCOC1
Product: O=c1c2c[nH]c3ccccc3c-2nn1-c1ccc(Cl)cc1
Reaction time: 0.5 h

Procedure:
The solution of 308 mg of 1-(p-chlorophenyl)-4-hydroxymethylene-3-(o-nitrophenyl)-4,5-dihydropyrazol-5-one in 80 ml of tetrahydrofuran is hydrogenated over 50 mg of 5% platinum on charcoal at room temperature and 3 atmospheres for 0.5 hour. The mixture is filtered, the filtrate evaporated and the residue taken up in 150 ml of toluene. To the solution, 0.1 ml of conc. hydrochloric acid is added, and the mixture refluxed at a water separator for 18 hours. It is cooled, the precipitate formed filtered off and purified by preparative thin layer chromotography, using ethyl acetate:ethanol:conc. ammonium hydroxide (17:3:3) as developing solvent on silica gel, to yield the 2-(p-chlorophenyl)-pyrazolo[4, 3-c]quinolin-3(5H)-one melting at 327°, it is identical with that of Example 1.
Reaction SMILES: [CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[C:14]([Cl:15])=[CH:13][N:12]=[CH:11][C:10]=3[Cl:16])[C:5]=2[C:17]([O:19]CC)=[O:18])[CH2:3][CH2:2]1.O1CCCC1.[OH-].[Na+].Cl>CO>[CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[C:14]([Cl:15])=[CH:13][N:12]=[CH:11][C:10]=3[Cl:16])[C:5]=2[C:17]([OH:19])=[O:18])[CH2:2][CH2:3]1
Reactant: CCOC(=O)c1c(-c2c(Cl)cncc2Cl)noc1C1CC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)c1c(-c2c(Cl)cncc2Cl)noc1C1CC1
Temperature: 120 °C
Yield: 82.3 %

Procedure:
To a solution of ethyl 5-cyclopropyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolecarboxylate (210 mg, 0.642 mmol) in 2:1 tetrahydrofuran:methanol (3 mL) was added 1 N sodium hydroxide (0.963 mL, 0.963 mmol). The solution was heated in a microwave reactor to 120° C. for 500 seconds. Then 1 N hydrochloric acid (0.963 mL, 0.963 mmol) was added and the solution was concentrated. The residue was taken up with water and extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate and concentrated to afford 5-cyclopropyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolecarboxylic acid (158 mg, 82%). 1H-NMR (400 MHz, DMSO-d6) δ 13.35 (s, 1H), 8.81 (s, 2H), 2.91-2.84 (m, 1H), 1.34-1.24 (m, 4H).
Reaction SMILES: [NH:1]=[C:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH3:7].[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]=[C:16]=[O:17])=[CH:11][CH:10]=1>C1C=CC=CC=1>[CH3:7][N:3]1[CH2:4][CH2:5][CH2:6][C:2]1=[N:1][C:16]([NH:15][C:12]1[CH:13]=[CH:14][C:9]([Cl:8])=[CH:10][CH:11]=1)=[O:17]
Reactant: CN1CCCC1=N
Reactant: O=C=Nc1ccc(Cl)cc1
Solvent: c1ccccc1
Product: CN1CCCC1=NC(=O)Nc1ccc(Cl)cc1
Reaction time: 0.21 h

Procedure:
After dissolving 14.2 g. (0.1445 mole) of 2 -imino-1 -methylpyrrolidine in anhydrous benezene, 22.2 g. (0.1445 mole) of p- chlorophenylisocyanate dissolved in anhydrous benzene is added slowly with stirring and ice-bath cooling to the above solution. Solid material forms after 10 to 15 mins. The reaction mixture is stirred at room temperature overnight. The solid is collected (m.p. = 138-141° C.) and titurated with hot CH2Cl2. The material which does not dissolve is filtered off. Removal of the methylene chloride and recrystallizations from methanol of the subsequent solid product, 1 -(1 -methyl-2 -pyrrolidylidene)-3 -p-chlorophenylurea, yields the pure material, m.p. = 142-144° C.
Reaction SMILES: [O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][CH:2]1[CH2:11][NH2:12].[Cl:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]([NH:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=1)=[O:19].C(=O)(O)[O-].[Na+].[I-].[K+].Cl>CN(C)C=O.C(O)C>[ClH:13].[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][CH:2]1[CH2:11][NH:12][CH2:14][CH2:15][CH2:16][CH2:17][C:18]([NH:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]([F:28])([F:29])[F:30])=[CH:25][CH:26]=1)=[O:19]
Reactant: NCC1COc2ccccc2O1
Reactant: O=C(CCCCCl)Nc1ccc(C(F)(F)F)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [I-]
Solvent: CN(C)C=O
Solvent: CCO
Product: O=C(CCCCNCC1COc2ccccc2O1)Nc1ccc(C(F)(F)F)cc1
Reaction time: 60 h
Yield: 12.4 %

Procedure:
2,3-Dihydro-1,4-benzodioxin-2-methanamine (350 mg) and 5-chloro-N-[4-(trifluoromethyl)phenyl]-pentanamide (593 mg) were stirred in dimethylformamide (7.0 mL) under a nitrogen atmosphere. Sodium bicarbonate (395 mg) and potassium iodide (40 mg) were added and mixture was stirred for 60 hours at 70°-75° C. Saturated sodium bicarbonate solution (50 mL) was added to the cooled reaction and the mixture extracted with diethyl ether (3×30 mL). The combined extracts were dried (MgSO4), filtered, and concentrated in vacuo. The resulting oil was chromatographed eluting with 40:60 ethyl acetate:hexane, then 10:90 ethanol:ethyl acetate to give a yellow-white solid with an Rf of 0.15 in 50:50 ethyl acetate:ethanol. This solid was dissolved in ethanol (20 mL) and treated with 1.0M aqueous HCl (1.0 mL). The solution was concentrated in vacuo to a white solid which after recrystallization from ethanol:ethyl acetate afforded the title compound as a white powder (117 mg).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:22])[CH:5]([O:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=1)[C:6](=O)[CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[CH3:2].S(=O)(=O)(O)O>>[CH2:1]([O:3][C:4]([C:5]1[O:13][C:14]2[CH:15]=[C:16]([O:20][CH3:21])[CH:17]=[CH:18][C:19]=2[C:6]=1[CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])=[O:22])[CH3:2]
Reactant: CCCCCC(=O)C(Oc1cccc(OC)c1)C(=O)OCC
Agent: O=S(=O)(O)O
Product: CCCCCc1c(C(=O)OCC)oc2cc(OC)ccc12
Temperature: 0 °C
Reaction time: 1 h
Yield: 53.6 %

Procedure:
A mixture of 2-chloro-3-oxooctanoic acid (51.5 g) and sodium 3-methoxyphenolate (35 g) was refluxed with stirring in benzene (250 mL) for 7 hours, then stirred at room temperature overnight. The cooled reaction was washed with water (2×250 mL) and the dried (MgSO4) organic layer was evaporated to give 70 g of a brown oil. The crude product was purified by HPLC (diethyl ether-hexane; 1:19) to give 30.45 g of 3-oxo-2-(3-methoxyphenoxy)octanoic acid ethyl ester as a colorless oil. 3-Oxo-2-(3-methoxyphenoxy)octanoic acid ethyl ester (21.5 g) was added over 1 hour with stirring to sulfuric acid (22 mL) at -10° C. After 1 hour at -10° C., the reaction was diluted carefully with ice (400 g) and then extracted with diethyl ether (2×400 mL). The organic extracts were washed in turn with saturated sodium bicarbonate solution and with brine, then were combined, dried (MgSO4) and evaporated. The crude reaction product was crystallized from hexane to give 10.86 g of 6-methoxy-3-pentyl-2-benzofuranecarboxylic acid ethyl ester, mp 38°-41° C.
Reaction SMILES: [CH2:1]([O:15][C:16]1[C:17]2[C:25]([CH:26]=[C:27]3[CH:31]=[CH:30][S:29][C:28]=13)=[C:24]([O:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46])[C:20]1[S:21][CH:22]=[CH:23][C:19]=1[CH:18]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].C([Li])CCC.[CH3:52][Sn:53](Cl)([CH3:55])[CH3:54].O>C1COCC1>[CH3:52][Sn:53]([CH3:55])([CH3:54])[C:22]1[S:21][C:20]2[C:24]([O:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH3:46])=[C:25]3[C:17](=[CH:18][C:19]=2[CH:23]=1)[C:16]([O:15][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])=[C:28]1[S:29][C:30]([Sn:53]([CH3:55])([CH3:54])[CH3:52])=[CH:31][C:27]1=[CH:26]3
Reactant: CCCCCCCCCCCCCCOc1c2cc3ccsc3c(OCCCCCCCCCCCCCC)c2cc2ccsc12
Reactant: C[Sn](C)(C)Cl
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Product: CCCCCCCCCCCCCCOc1c2cc3cc([Sn](C)(C)C)sc3c(OCCCCCCCCCCCCCC)c2cc2cc([Sn](C)(C)C)sc12
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 86 %

Procedure:
Compound (4b) (0.500 g, 0.752 mmol) was solubilized in anhydrous THF (40 mL) and cooled at −78° C. under N2. n-Butyllithium (0.75 mL, 2.5M) was then added and the stirring was continued for 30 minutes at this temperature and then 30 minutes at room temperature. The reaction mixture was cooled to −78° C. again before adding trimethylstannyl chloride (1.9 mL, 1.0 M). The reaction was warmed up to room temperature and stirred overnight. The reaction was stopped by adding water, and the mixture was extracted with diethyl ether, dried over MgSO4, filtered, and concentrated in vacuo. The crude monomer was solubilized in 5 mL of THF and then dropped in methanol (200 mL). The product was allowed to precipitate in the freezer overnight before filtering and washing with cold methanol to afford a yellow fluffy powder as the title compound (0.650 g, 86%). 1H NMR (500 MHz, CDCl3, 298 K): 8.45 (s, 2H); 7.53 (s, 2H); 4.38 (t, J=6.6 Hz, 4H); 2.01 (quintet, J=7.9 Hz, 4H); 1.65 (quintet, J=7.7 Hz, 4H); 1.39 (m, 40H); 0.89 (t, J=7.0 Hz 6H); 0.47 (s, 18H) ppm. 13C NMR (125 MHz, CDCl3, 298 K): 149.07; 142.85; 141.22; 132.66; 130.48; 124.58; 109.85; 73.20; 31.96; 30.65; 29.76; 29.73; 29.70; 29.57; 29.41; 26.17; 22.73; 14.17; 8.38 ppm. HRMS (ESI-TOF-MS): m/z calcd for C48H80O2S2Sn2 990.3638. found 990.3670.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=O)[CH2:9][CH2:10][CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][CH:16]([C:19]2[CH:20]=[C:21]([NH:25][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[CH:22]=[CH:23][CH:24]=2)[CH2:15][CH2:14]1.[CH3:32][N:33]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)N>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:33]([CH3:32])[C:35]2[C:40]([C:9]=1[CH2:10][CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][CH:16]([C:19]3[CH:20]=[C:21]([NH:25][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[CH:22]=[CH:23][CH:24]=3)[CH2:15][CH2:14]1)=[CH:39][CH:38]=[CH:37][CH:36]=2
Reactant: CN(N)c1ccccc1
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CCCCC(=O)c3ccccc3Cl)CC2)c1
Product: CC(C)C(=O)Nc1cccc(C2CCN(CCCc3c(-c4ccccc4Cl)n(C)c4ccccc34)CC2)c1

Procedure:
Prepared by Procedure E and Scheme M using N-(3-{1-[5-(2-chlorophenyl)-5-oxopentyl]-4-piperidinyl}phenyl)-2-methylpropanamide and 1-methyl-1-phenylhydrazine: ESMS m/e: 528.2 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:27][C:28]([O:30][CH3:31])=[O:29])[CH:5]=[CH:6][C:7]=1[S:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19](=O)[CH2:20][CH3:21])=[C:15]([OH:23])[C:14]=1[CH2:24][CH2:25][CH3:26].Cl.[NH2:33][OH:34].C([O-])(=O)C.[Na+]>CO>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:27][C:28]([O:30][CH3:31])=[O:29])[CH:5]=[CH:6][C:7]=1[S:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19](=[N:33][OH:34])[CH2:20][CH3:21])=[C:15]([OH:23])[C:14]=1[CH2:24][CH2:25][CH3:26]
Reactant: NO
Reactant: CCCc1c(OCCCSc2ccc(CC(=O)OC)cc2Cl)ccc(C(=O)CC)c1O
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: CCCc1c(OCCCSc2ccc(CC(=O)OC)cc2Cl)ccc(C(CC)=NO)c1O

Procedure:
A solution of methyl 3-chloro-4-(3-(2-propyl-3-hydroxy-4-propionylphenoxy)propylthio)phenylacetate (Step B; 25.655 grams) in dry methanol (260 mL) was treated with hydroxylamine hydrochloride (3.833 grams). Anhydrous sodium acetate (4.524 grams) was added and the mixture refluxed for 4 hours. The reaction mixture was partitioned between isopropyl acetate and pH 7 buffer. The organic phase was washed once with water and dried over magnesium sulfate, filtered and evaporated to an oil. The title compound was used without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:23][CH3:24])=[C:18]([O:21][CH3:22])[CH:19]=3)[N:14]=[CH:13][CH:12]=2)=[C:6]([CH:9]=1)[CH:7]=[O:8].[CH2:25]([Mg]Br)[CH3:26].O>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:23][CH3:24])=[C:18]([O:21][CH3:22])[CH:19]=3)[N:14]=[CH:13][CH:12]=2)=[C:6]([CH:7]([OH:8])[CH2:25][CH3:26])[CH:9]=1
Reactant: CC[Mg]Br
Reactant: COc1cc2nccc(Oc3ccc(Cl)cc3C=O)c2cc1OC
Solvent: C1CCOC1
Solvent: O
Product: CCC(O)c1cc(Cl)ccc1Oc1ccnc2cc(OC)c(OC)cc12
Temperature: 0 °C
Reaction time: 1 h

Procedure:
5-Chloro-2-[(6,7-dimethoxy-4-quinolyl)oxy]benzaldehyde was dissolved in anhydrous tetrahydrofuran (1 ml) to prepare a solution. A 1 M tetrahydrofuran solution (0.5 ml) of ethylmagnesium bromide was added to the solution at 0° C., and the mixture was stirred at 0° C. for one hr. Water (1 ml) was added dropwise to the reaction solution to stop the reaction. The mixture was extracted with ethyl acetate, and the ethyl acetate layer was then washed with water and saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure to give 1-{5-chloro-2-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-1-propanol.
Reaction SMILES: [Si]([O:18][C:19]1[CH:62]=[CH:61][C:22]([O:23][CH2:24][C@@H:25]([OH:60])[CH2:26][NH:27][CH2:28][CH2:29][C:30]2[CH:59]=[CH:58][C:33]([NH:34][CH:35]3[CH2:40][CH2:39][N:38]([C:41]([NH:43][CH2:44][CH2:45][CH2:46][CH2:47][C:48]4[CH:53]=[CH:52][C:51]([O:54][CH3:55])=[C:50]([O:56][CH3:57])[CH:49]=4)=[O:42])[CH2:37][CH2:36]3)=[CH:32][CH:31]=2)=[CH:21][CH:20]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>C(Cl)(Cl)Cl.CO>[CH3:57][O:56][C:50]1[CH:49]=[C:48]([CH2:47][CH2:46][CH2:45][CH2:44][NH:43][C:41]([N:38]2[CH2:37][CH2:36][CH:35]([NH:34][C:33]3[CH:58]=[CH:59][C:30]([CH2:29][CH2:28][NH:27][CH2:26][CH:25]([OH:60])[CH2:24][O:23][C:22]4[CH:61]=[CH:62][C:19]([OH:18])=[CH:20][CH:21]=4)=[CH:31][CH:32]=3)[CH2:40][CH2:39]2)=[O:42])[CH:53]=[CH:52][C:51]=1[O:54][CH3:55]
Reactant: COc1ccc(CCCCNC(=O)N2CCC(Nc3ccc(CCNC[C@H](O)COc4ccc(O[Si](c5ccccc5)(c5ccccc5)C(C)(C)C)cc4)cc3)CC2)cc1OC
Solvent: CO
Solvent: ClC(Cl)Cl
Product: COc1ccc(CCCCNC(=O)N2CCC(Nc3ccc(CCNCC(O)COc4ccc(O)cc4)cc3)CC2)cc1OC
Yield: 89.4 %

Procedure:
4-[4-(2-{[(2S)-3-(4-{[tert-Butyl(diphenyl)silyl]oxy}phenoxy)-2-hydroxy-propyl]amino}ethyl)anilino]-N-[4-(3,4-dimethoxyphenyl)butyl]-1-piperidinecarboxamide (0.40 g, 0.47 mmol) was reacted according to Procedure H (eluant: 10:1 chloroform-methanol containing 2% triethylamine) to give the title compound (0.26 g, 0.42 mmol).
Reaction SMILES: [CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH:26]([CH3:28])[CH3:27])[CH2:23][CH2:22][C:21]([C:29]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([S:38][CH2:39][C:40]5[N:44]([CH2:45][CH2:46][CH3:47])[CH:43]=[N:42][N:41]=5)=[C:34]([CH3:48])[CH:33]=4)=[O:30])=[CH:20][C:19]=3[CH:49]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].ClC1C=CC=C(C(OO)=[O:58])C=1.S([O-])([O-])(=O)=S.[Na+].[Na+]>ClCCl>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH:26]([CH3:27])[CH3:28])[CH2:23][CH2:22][C:21]([C:29]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([S:38]([CH2:39][C:40]5[N:44]([CH2:45][CH2:46][CH3:47])[CH:43]=[N:42][N:41]=5)=[O:58])=[C:34]([CH3:48])[CH:33]=4)=[O:30])=[CH:20][C:19]=3[CH:49]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(SCc4nncn4CCC)c(C)c2)CCN3CC(C)C)cc1
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClCCl
Product: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(S(=O)Cc4nncn4CCC)c(C)c2)CCN3CC(C)C)cc1
Temperature: -78 °C
Reaction time: 1 h
Yield: 78.7 %

Procedure:
7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[3-methyl-4-[(4-propyl-4H-1,2,4-triazol-3-yl)methylthio]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (0.67 g) was suspended in dichloromethane (100 ml) and the suspension was cooled to −78° C. A solution of 3-chloroperbenzoic acid (0.35 g) in dichloromethane (5 ml) was added dropwise to the suspension. The mixture was stirred for 1 hour at −78° C., and then, sodium thiosulfate solution was added to the mixture, and the mixture was concentrated, and extracted with ethyl acetate. The organic layer was washed with sodium bicarbonate solution, water and saturated brine, and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off. The residue was purified by silica gel column chromatography (elution solvent: triethylamine/methanol/ethyl acetate), to give 7-[4-(2-butoxyethoxy)phenyl]-1-isobutyl-N-[3-methyl-4-[(4-propyl-4H-1,2,4-triazol-3-yl)methylsulfinyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 41) (0.54 g) as yellow amorphous.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][C:17](C)=[CH2:18])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.[C:20]1(C)C=CC=CC=1>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]3[C:11](=[CH:18][CH:17]=[C:16]([CH3:20])[CH:15]=3)[CH:10]=2)=[CH:5][CH:4]=1
Reactant: Cc1ccccc1
Reactant: C=C(C)CCc1ccc(-c2ccc(OC)cc2)cc1
Product: COc1ccc(-c2ccc3cc(C)ccc3c2)cc1

Procedure:
Into the reactor were fed a solution of 12.4 g (0.049 mol) of the four isomers of 4-methoxy-4'-isopentenyl biphenyl of Example 6 in 237.6 g of toluene at a rate of 10 g/hour. Lower boiling point compounds were removed by distillation from the reaction mixture. The reaction mixture was concentrated to 30 g. The reaction mixture was left to stand. The deposited crystal was filtered to separate it off. The product was recrystallized with toluene for purification. As a result, 2-(4'-methoxyphenyl)-6-methyl naphthalene (5.0 g) was obtained. The yield of the product was 45 mol % on the basis of the olefin compound (4-methoxy-4'-isopentenyl biphenyl).