Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:10][O:11][C:12](=[O:17])[CH2:13][CH:14]1[CH2:16][CH2:15]1>>[CH3:10][O:11][C:12](=[O:17])[CH:13]([C:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH:14]1[CH2:16][CH2:15]1
Reactant: O=C(Cl)c1ccccc1
Reactant: COC(=O)CC1CC1
Product: COC(=O)C(C(=O)c1ccccc1)C1CC1
Yield: 28 %

Procedure:
Benzoyl chloride (1.0 ml) and 2-cyclopropylacetic acid methyl ester were subjected to reaction and post-treatment in a similar manner to that described in Reference example 8(a) to obtain the title compound (1.05 g, 28%) as a colorless liquid.
Reaction SMILES: [F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[C:7]2[CH2:12][C:13]([O:15]CC)=[O:14].[OH-].[Na+]>C(O)C>[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[C:7]2[CH2:12][C:13]([OH:15])=[O:14]
Reactant: CCOC(=O)Cc1cccc2c(F)cccc12
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)Cc1cccc2c(F)cccc12
Temperature: 25 °C
Reaction time: 2 h
Yield: 82.8 %

Procedure:
To a solution of ethyl (5-fluoronaphthalen-1-yl)acetate (5.96 g) in ethanol (50 mL) was added 1N sodium hydroxide (50 mL), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, the obtained residue was poured into water, and the mixture was washed with ethyl acetate. The aqueous layer was acidified with 1N hydrochloric acid, and extracted with chloroform, and the extract was washed with water and saturated brine, dried is over magnesium sulfate, and concentrated under reduced pressure to give (5-fluoronaphthalen-1-yl)acetic acid (4.34 g). The title compound was obtained according to the method of Example 103 and using (5-fluoronaphthalen-1-yl)acetic acid.
Reaction SMILES: Cl.O1CCOCC1.[CH:8]1([C:14]([CH2:16][N:17]2[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[N:21]([CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)[CH2:20][CH:19]([NH:34]C(OC(C)(C)C)=O)[C:18]2=[O:42])=[O:15])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1>C(O)C>[CH:8]1([C:14]([CH2:16][N:17]2[C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[N:21]([CH:28]3[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]3)[CH2:20][CH:19]([NH2:34])[C:18]2=[O:42])=[O:15])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1
Reactant: CC(C)(C)OC(=O)NC1CN(C2CCCCC2)c2ccccc2N(CC(=O)C2CCCCC2)C1=O
Agent: Cl
Solvent: CCO
Solvent: C1COCCO1
Product: NC1CN(C2CCCCC2)c2ccccc2N(CC(=O)C2CCCCC2)C1=O
Temperature: 50 °C
Reaction time: 1 h
Yield: 100.9 %

Procedure:
4N HCl-dioxane (10 ml) was added to a solution of 1-cyclohexylcarbonylmethyl-2-oxo-3-tert-butoxycarbonylamino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (500 mg) in ethanol (10 ml), and the mixture was stirred at 50° C. for one hour. The reaction mixture was concentrated under reduced pressure, the residue was neutralized with saturated aqueous sodium bicarbonate, extracted with methylene chloride. The organic layer was dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, to thereby obtain 400 mg of the title compound.
Reaction SMILES: O=[C:2]1[NH:8][C:7]2=[CH:9][CH2:10][S:11][C:6]2=[CH:5][N:4]2[CH:12]=[CH:13][CH:14]=[C:3]12.B.CSC.CO>O1CCCC1>[S:11]1[C:6]2[CH2:5][N:4]3[CH:12]=[CH:13][CH:14]=[C:3]3[CH2:2][NH:8][C:7]=2[CH:9]=[CH:10]1
Reactant: O=C1NC2=CCSC2=Cn2cccc21
Agent: B
Solvent: C1CCOC1
Solvent: CSC
Solvent: CO
Product: c1cc2n(c1)Cc1sccc1NC2
Temperature: 25 °C

Procedure:
To a suspension of 7.0 g of 5-oxo-4,5-di-hydropyrrolo[1,2-a]thieno[3,2-e][1,4]diazepine in 25 ml of anhydrous tetrahydrofuran is added 9 ml of 10M borane-dimethylsulfide in tetrahydrofuran. The mixture is refluxed for 6 hours. The solution is cooled to room temperature and 25 ml of methanol added dropwise. The volatiles are removed under vacuum. To the residue is added 100 ml of 2N NaOH. The mixture is refluxed 5 hours and filtered. The solid is extracted with dichloromethane and the extract is washed with 2N citric acid, water and dried (Na2SO4). The solvent is removed to give a solid.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[N:12]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:11]([C:21]3[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=3[CH3:28])=[C:10]([C:29]([NH2:31])=[O:30])[CH:9]=2)[C:5]([C:32]#[CH:33])=[CH:4][N:3]=1.I[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.CN(C)CCN(C)C>C(#N)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[N:12]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:18])([CH3:19])[CH3:20])[C:11]([C:21]3[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=3[CH3:28])=[C:10]([C:29]([NH2:31])=[O:30])[CH:9]=2)[C:5]([C:32]#[C:33][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[CH:4][N:3]=1
Reactant: Ic1ccccc1
Reactant: C#Cc1cnc(N)nc1-c1cc(C(N)=O)c(-c2cc(Cl)ccc2C)n1COCC[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: CN(C)CCN(C)C
Solvent: CC#N
Product: Cc1ccc(Cl)cc1-c1c(C(N)=O)cc(-c2nc(N)ncc2C#Cc2ccccc2)n1COCC[Si](C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 65.2 %

Procedure:
In a sealed tube filled with argon, a mixture of 5-(2-amino-5-ethynylpyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrole-3-carboxamide (120 mg, 0.25 mmol), Pd(PPh3)2Cl2 (21 mg, 0.03 mmol), CuI (6 mg, 0.03 mmol), iodobenzene (153 mg, 0.75 mmol) and TEA (0.348 mL, 2.5 mmol) in degassed ACN (2.5 mL) was stirred at room temperature overnight. To the reaction mixture was added N,N,N′,N′-tetramethylethylenediamine (0.075 mL, 0.5 mmol) and the reaction mixture stirred at the same temperature for 15 min. The solvent was evaporated under vacuum and the residue purified by flash chromatography (hexane/EtOAc 1/1+1% TEA), to obtain the title compounds (91 mg, 65%).
Reaction SMILES: [C:1]1([CH2:9][OH:10])[C:2]([CH2:7][OH:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.[N+]([O-])(O)=O.O>C(O)(=O)C>[CH:9](=[O:10])[C:1]1[C:2](=[CH:3][CH:4]=[CH:5][CH:6]=1)[CH:7]=[O:8]
Reactant: OCc1ccccc1CO
Solvent: O=[N+]([O-])O
Solvent: O
Solvent: CC(=O)O
Product: O=Cc1ccccc1C=O
Temperature: 70 °C
Reaction time: 1 h
Yield: 84 %

Procedure:
In a 1000-ml three-neck flask equipped with a thermometer, a reflux condenser and a stirrer were placed 50 g of o-xylylene glycol, 78.4 g of 60% by weight nitric acid, 170.1 g of water, and 201.5 g of acetic acid. The mixture was raised in temperature to 70° C. on an oil bath and was stirred under these conditions for 1 hour. After cooling, the reaction mixture was analyzed by gas chromatography to find that the raw material o-xylylene glycol was completely absent and that phthalaldehyde was formed in a yield of 84%. The obtained reaction mixture was extracted with two portions of toluene, the organic layer was distilled and thereby yielded phthalaldehyde in a yield of 67% on the basis of o-xylylene glycol. Gas chromatographic analysis revealed that phthalaldehyde had a purity of 98.8%. In addition, phthalide was formed in a yield of 12%.
Reaction SMILES: [C:1]1(=[O:11])[O:6][C:4](=[O:5])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[C:12]1([C:18]2[NH:19][C:20]3[C:25]([CH:26]=2)=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C1(C)C(C)=CC=CC=1>[C:12]1([C:18]2[NH:19][C:20]3[C:25]([C:26]=2[C:4]([C:3]2[CH:7]=[CH:8][CH:9]=[CH:10][C:2]=2[C:1]([OH:6])=[O:11])=[O:5])=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=C1OC(=O)c2ccccc21
Reactant: c1ccc(-c2cc3ccccc3[nH]2)cc1
Solvent: Cc1ccccc1C
Product: O=C(O)c1ccccc1C(=O)c1c(-c2ccccc2)[nH]c2ccccc12
Temperature: 110 °C
Yield: 62.1 %

Procedure:
A suspension of 14.8 g (0.10 mole) of phthalic anhydride, 10.5 g (0.05 mole) of 2-phenylindole and 82 ml of xylene was heated to 110° C. briefly, cooled to and maintained at 95° C. for approximately two hours. The solution was cooled to ambient temperature and the solid which separated was collected by filtration and dried to obtain 10.6 g of 2-[(2-phenyl-3-indolyl)-carbonyl]benzoic acid (Formula VIII: R°=R1 =R2 =R3 =R6 =Y1 =H; R5 =C6H5) which melted at 106°-107° C. and had a nuclear magnetic resonance spectrum consistent with the assigned structure.
Reaction SMILES: [C:1]([CH2:3][C:4]([O:6][CH2:7][CH:8]([CH2:13][CH3:14])[CH2:9][CH2:10][CH2:11][CH3:12])=[O:5])#[N:2].[C:15]([NH:18][C:19]1[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][CH:20]=1)(=[O:17])[CH3:16]>C(O)(C)C>[C:15]([NH:18][C:19]1[CH:26]=[CH:25][C:22]([CH:23]=[C:3]([C:1]#[N:2])[C:4]([O:6][CH2:7][CH:8]([CH2:13][CH3:14])[CH2:9][CH2:10][CH2:11][CH3:12])=[O:5])=[CH:21][CH:20]=1)(=[O:17])[CH3:16]
Reactant: CCCCC(CC)COC(=O)CC#N
Reactant: CC(=O)Nc1ccc(C=O)cc1
Solvent: CC(C)O
Product: CCCCC(CC)COC(=O)C(C#N)=Cc1ccc(NC(C)=O)cc1
Yield: 54 %

Procedure:
A mixture of 35 g (0.18 mol) of 2-ethylhexyl cyanoacetate and 30 g (0.18 mol) of 4-acetamidobenzaldehyde in 300 ml of isopropanol is refluxed for 3 hours. The reaction mixture is then allowed to cool and is crystallized. The crystals formed are separated out by filtration and are recrystallized from a minimum amount of isopropanol. After filtration and drying, 33.3 g (54% yield) of 2-ethylhexyl 3-(4-acetylaminophenyl)-2-cyanoacrylate are obtained in the form of a pale yellow powder.
Reaction SMILES: [CH2:1]([O:8][C@H:9]([C@@H:11]([OH:22])[CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[S:20][CH3:21])[CH3:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:23][S:24](Cl)(=[O:26])=[O:25].C(N(CC)CC)C>ClCCl>[CH2:1]([O:8][C@@H:9]([CH3:10])[C@@H:11]([O:22][S:24]([CH3:23])(=[O:26])=[O:25])[CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[S:20][CH3:21])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CSc1ccccc1CC[C@H](O)[C@H](C)OCc1ccccc1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CSc1ccccc1CC[C@H](OS(C)(=O)=O)[C@H](C)OCc1ccccc1
Temperature: 4 °C
Reaction time: 0.67 h

Procedure:
To an ice-cooled solution of (2S,3S)-2-benzyloxy-5-(2-(methylthio)phenyl)pentan-3-ol (0.64 g) in dichloromethane (12 ml) was added methanesulfonyl chloride (0.234 ml) followed by triethylamine (0.421 ml). The mixture was stirred at 4° C. for 40 min. The mixture was washed with water and brine, dried and concentrated in vacuo to give 2-[(3S,4S)-4-benzyloxy-3-(methanesulfonyloxy)pentyl]-thioanisole (0.92 g) as an oil.
Reaction SMILES: [CH2:1]1[CH2:5]OC[CH2:2]1.CN1C(=O)CCC1.Cl[C:14]1[CH:21]=[C:20]([CH3:22])[C:17]([C:18]#[N:19])=[C:16]([O:23][CH3:24])[N:15]=1.C([Mg]Br)CC.Cl>C(OC(=O)C)C>[CH3:24][O:23][C:16]1[N:15]=[C:14]([CH2:2][CH2:1][CH3:5])[CH:21]=[C:20]([CH3:22])[C:17]=1[C:18]#[N:19]
Reactant: COc1nc(Cl)cc(C)c1C#N
Reactant: C1CCOC1
Agent: CCC[Mg]Br
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CN1CCCC1=O
Product: CCCc1cc(C)c(C#N)c(OC)n1
Reaction time: 0.33 h
Yield: 88 %

Procedure:
A transparent red-colored THF/NMP(50 mL/5 mL) solution of 6-chloro-2-methoxy-4-methyl-nicotinonitrile (2.00 g, 11.0 mmol) and Fe (acac)3 (387 mg, 1.1 mmol) was slowly added with 11 mL of n-propylmagnesium bromide (2M solution in diethyl ether) and then stirred for about 20 minutes. The mixture was then added with 10 mL of 1M HCl solution 10 mL and diluted with 300 mL of ethylacetate. The resulting organic layer was washed with water and a saturated solution of sodium chloride, dried with anhydrous sodium sulfate and then filtered. A silica gel column chromatography (10% EtOAc/Hexane) was performed on the residue obtained by concentrating the above filtrate under reduced pressure and obtained 2.23 g (88%) of 2-methoxy4-methyl-6-propyl-nicotinonitrile in colorless oil.
Reaction SMILES: [CH:1]1([CH2:7][NH:8][C:9]2[CH:27]=[CH:26][C:12]([C:13]([N:15]([CH2:21][C:22]([F:25])([F:24])[F:23])[CH2:16][C:17]([F:20])([F:19])[F:18])=[O:14])=[CH:11][C:10]=2[N+:28]([O-])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1>CCOC(C)=O.[Pd]>[NH2:28][C:10]1[CH:11]=[C:12]([CH:26]=[CH:27][C:9]=1[NH:8][CH2:7][CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)[C:13]([N:15]([CH2:21][C:22]([F:23])([F:24])[F:25])[CH2:16][C:17]([F:19])([F:20])[F:18])=[O:14]
Reactant: O=C(c1ccc(NCC2CCCCC2)c([N+](=O)[O-])c1)N(CC(F)(F)F)CC(F)(F)F
Agent: [Pd]
Solvent: CCOC(C)=O
Product: Nc1cc(C(=O)N(CC(F)(F)F)CC(F)(F)F)ccc1NCC1CCCCC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
4-[(Cyclohexylmethyl)amino]-3-nitro-N,N-bis(2,2,2-trifluoroethyl)benzamide (110 mg, 0.249 mmol) was dissolved in 15 mL of EtOAc containing a catalytic amount of 10% Pd/C. The solution was shaken in a Parr hydrogenation apparatus under H2 atmosphere (40 psi) overnight at rt. The solution was filtered through Celite and the solvent concentrated. The title product was used directly for the next step without further purification. Yield: 102 mg (99%). MS (ESI) (M+H)+ 411.9.
Reaction SMILES: [C:1]([CH:4]1[CH2:9][NH:8][CH2:7][CH2:6][NH:5]1)([OH:3])=[O:2].[OH-].C([N+](CCCC)(CCCC)CCCC)CCC.Br[CH2:29][CH:30]([C:32]1[CH:37]=[CH:36][C:35]([C:38]2[N:42]=[C:41]([C:43]3[C:47]([CH2:48][CH2:49][CH3:50])=[C:46]([C:51]4[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=4)[O:45][N:44]=3)[O:40][N:39]=2)=[CH:34][CH:33]=1)[OH:31].CCN(C(N1N=NN(C2C(Cl)=CC=CC=2)C1=O)=O)C1CCCCC1>CS(C)=O.CO>[OH:31][CH:30]([C:32]1[CH:37]=[CH:36][C:35]([C:38]2[N:42]=[C:41]([C:43]3[C:47]([CH2:48][CH2:49][CH3:50])=[C:46]([C:51]4[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=4)[O:45][N:44]=3)[O:40][N:39]=2)=[CH:34][CH:33]=1)[CH2:29][N:8]1[CH2:7][CH2:6][NH:5][CH:4]([C:1]([OH:3])=[O:2])[CH2:9]1
Reactant: O=C(O)C1CNCCN1
Reactant: CCCc1c(-c2nc(-c3ccc(C(O)CBr)cc3)no2)noc1-c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: CCN(C(=O)n1nnn(-c2ccccc2Cl)c1=O)C1CCCCC1
Agent: [OH-]
Solvent: CS(C)=O
Solvent: CO
Product: CCCc1c(-c2nc(-c3ccc(C(O)CN4CCNC(C(=O)O)C4)cc3)no2)noc1-c1ccccc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of 2-carboxypiperazine (47 mg, 0.36 mmol) in 0.5 mL dry DMSO was added tetrabutylammonium hydroxide (0.360 mL, 360 μmol, 1M in THF) and the reaction mixture was stirred at rt for 15 min. 2-bromo-1-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethanol, Preparation 1C (30 mg, 0.066 mmol) was dissolved in 0.5 mL DMSO and added and the reaction was agitated at 400 rpm on an INNOVA® platform shaker at 80° C. for 1.5 hours. The reaction was diluted with 250 μL of MeOH and purified by HPLC (MeOH—H2O-TFA) to give 4-(2-hydroxy-2-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperazine-2-carboxylic acid. MS (m+1)=504. HPLC RT=2.06 min Waters Masslynx instrument equipped with a 19×100 mm 5 uM C18 column and a method of 0-100% B solvent over 15 min at a flow rate of 20 mL/min. Solvent A is 5:95 acetonitrile/water; solvent B is 95:5 acetonitrile/water and both contain 0.5% TFA.
Reaction SMILES: Br.[OH:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][NH:8][CH2:7][CH2:6]2.[C:13]([O-])(=[O:15])[CH3:14].[Na+].C(OC(=O)C)(=O)C.O>C(Cl)Cl>[C:13]([N:8]1[CH2:7][CH2:6][C:5]2[C:10](=[CH:11][CH:12]=[C:3]([OH:2])[CH:4]=2)[CH2:9]1)(=[O:15])[CH3:14]
Reactant: Oc1ccc2c(c1)CCNC2
Reactant: CC(=O)[O-]
Agent: Br
Agent: [Na+]
Solvent: CC(=O)OC(C)=O
Solvent: ClCCl
Solvent: O
Product: CC(=O)N1CCc2cc(O)ccc2C1
Reaction time: 1 h
Yield: 90.9 %

Procedure:
A mixture of 57.6 g of 1,2,3,4-tetrahydro-6-hydroxy-isoquinoline-hydrobromide, 22.6 g of anhydrous sodium acetate, and 76.6 g of acetic acid anhydride in 300 ml of methylene chloride is held at the boiling point for one hour under reflux. 300 ml of water are added thereto, the organic phase is separated, and the aqueous phase is extracted several times with methylene chloride. After evaporation of the methylene chloride extract, the residue is dissolved in dilute sodium hydroxide, stirred for 30 minutes on a boiling water bath, and the reaction product is precipitated by the introduction of carbon dioxide. The filtered substance is recrystallized from ethanol. 43.5 g of 2-acetyl-1,2,3,4-tetrahydro-6-hydroxy-isoquinoline are obtained. m.p. = 135° - 136° C. (ethanol - diisopropyl ether).
Reaction SMILES: [O:1]1[CH:3]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[CH2:2]1.[Na].C1OC1.[CH2:16]([OH:20])[CH2:17][CH2:18][CH3:19]>C[O-].[Na+]>[OH:1][CH:3]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[CH2:2][O:20][CH2:16][CH2:17][CH2:18][CH3:19]
Reactant: CCCCO
Reactant: CCCCCCCCC1CO1
Agent: C[O-]
Agent: [Na+]
Agent: [Na]
Solvent: C1CO1
Product: CCCCCCCCC(O)COCCCC

Procedure:
As described in Example 1, 1 mol of 1,2-epoxydecane was caused to react with 5 times the molar quantity of n-butanol and 0.04 gm-atom of sodium. After distillation of the excess alcohol, the reaction with 10 mols of ethylene oxide was conducted in an autoclave under the conditions described in Example 1, except for the addition of the sodium methylate catalyst. The product thus obtained had a cloud point of 64°C.
Reaction SMILES: [CH2:1]1[O:9][C:8]2[C:3](=[CH:4][CH:5]=[C:6]([C:30]([O:32][CH3:33])=[O:31])[C:7]=2[C:10]2[C:11]([C:26]([O:28][CH3:29])=[O:27])=[CH:12][C:13]([O:24][CH3:25])=[C:14]([O:16]CC3C=CC=CC=3)[CH:15]=2)[O:2]1.[H][H]>O1CCCC1.CO.[C].[Pd]>[CH2:1]1[O:9][C:8]2[C:3](=[CH:4][CH:5]=[C:6]([C:30]([O:32][CH3:33])=[O:31])[C:7]=2[C:10]2[C:11]([C:26]([O:28][CH3:29])=[O:27])=[CH:12][C:13]([O:24][CH3:25])=[C:14]([OH:16])[CH:15]=2)[O:2]1
Reactant: [H][H]
Reactant: COC(=O)c1cc(OC)c(OCc2ccccc2)cc1-c1c(C(=O)OC)ccc2c1OCO2
Agent: [Pd]
Solvent: CO
Solvent: C1CCOC1
Product: COC(=O)c1cc(OC)c(O)cc1-c1c(C(=O)OC)ccc2c1OCO2
Yield: 93.5 %

Procedure:
Dimethyl 5,6-methylenedioxy-4'-methoxy-5'-benzyloxy-2,2'-biphenyldicarboxylate (1.15 g) is dissolved in tetrahydrofuran (50 ml) and methanol (50 ml), and the solution is sitrred under 40 psi hydrogen gas atmosphere in the presence of palladium-carbon (0.2 g) for 16 hours. After the reaction, the catalyst is filtered off, and the filtrate is evaporated into dryness under reduced pressure. The residue is treated with methanol to give dimethyl 5,6-methylenedioxy-4'-methoxy-5'-hydroxy-2,2'-biphenyldicarboxylate (0.86 g) as colorless crystal. M.p. 172°-173° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH2:6][C:7](=[O:13])[NH:8]2.[H-].[Na+].[Na].Br[CH2:18][CH2:19][CH2:20][Cl:21]>CN(C)C=O>[Cl:21][CH2:20][CH2:19][CH2:18][N:8]1[C:9]2[C:4](=[C:3]([O:2][CH3:1])[CH:12]=[CH:11][CH:10]=2)[CH2:5][CH2:6][C:7]1=[O:13]
Reactant: ClCCCBr
Reactant: COc1cccc2c1CCC(=O)N2
Agent: [H-]
Agent: [Na+]
Agent: [Na]
Solvent: CN(C)C=O
Product: COc1cccc2c1CCC(=O)N2CCCCl
Reaction time: 0.5 h
Yield: 77.5 %

Procedure:
To a solution of 5-methoxy-3,4-dihydrocarbostyril (53.1 g, 0.3 mole) in 200 ml of dimethylformamide (DMF) was added portionwise 60% sodium hydride in oil (19.2.g, 0.4 mole) at room temperature, and the mixture was stirred for 30 minutes. To the thus-obtained solution of the sodium salt of 5-methoxy-3,4-dihydrocarbostyril in DMF was added 1-bromo-3-chloropropane (94 ml, 0.6 mole). The mixture was stirred at 80°-90° C. for 8 hours. The DMF was distilled off under reduced pressure, and the residue was extracted with chloroform. The extract was washed with water and dried (anhydrous magnesium sulfate), the chloroform was distilled off under reduced pressure, and the residue was recrystallized from ethanol to give 59 g of 1-(3-chloropropyl)-5-methoxy-3,4-dihydrocarbostyril as colorless needles.
Reaction SMILES: [OH-].[Na+].C[O:4][C:5](=[O:26])[C:6]1[CH:11]=[C:10]([Cl:12])[C:9]([NH:13][C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])=[CH:8][C:7]=1[O:24][CH3:25]>O1CCOCC1>[CH2:17]([O:16][C:14]([NH:13][C:9]1[C:10]([Cl:12])=[CH:11][C:6]([C:5]([OH:26])=[O:4])=[C:7]([O:24][CH3:25])[CH:8]=1)=[O:15])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: COC(=O)c1cc(Cl)c(NC(=O)OCc2ccccc2)cc1OC
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: COc1cc(NC(=O)OCc2ccccc2)c(Cl)cc1C(=O)O
Reaction time: 20 h

Procedure:
200 ml 2N aqueous sodium hydroxide solution is added dropwise to a stirred solution of 72.1 g of the benzoic acid methyl ester produced in step b) in 800 ml dioxane. The mixture is stirred for 20 hours and the organic solvent removed under a vacuum. The residue is dissolved in water and adjusted to pH 5-6 with 3N hydrochloric acid. The heading compound is filtered off and washed with water. M.pt. 182°-183° (from methanol).
Reaction SMILES: Cl[C:2]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=2[Cl:17])[C:7]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[CH:6][C:3]=1[C:4]#[N:5].[Br-].[F:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][C:34]=1[F:35])[CH2:30][Zn+]>C1COCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:24][C:21]1[CH:20]=[CH:19][C:18]([C:7]2[C:8]([C:10]3[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=3[Cl:17])=[N:9][C:2]([CH2:30][C:29]3[CH:32]=[CH:33][C:34]([F:35])=[C:27]([F:26])[CH:28]=3)=[C:3]([CH:6]=2)[C:4]#[N:5])=[CH:23][CH:22]=1
Reactant: Fc1ccc(C[Zn+])cc1F
Reactant: N#Cc1cc(-c2ccc(Cl)cc2)c(-c2ccc(Cl)cc2Cl)nc1Cl
Agent: [Pd]
Agent: [Br-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: N#Cc1cc(-c2ccc(Cl)cc2)c(-c2ccc(Cl)cc2Cl)nc1Cc1ccc(F)c(F)c1
Temperature: 50 °C
Reaction time: 16 h

Procedure:
To a dried round bottom flask was added THF (1 mL), the product of Example 36 (0.050 g; 0.127 mmol), 3,4-diflourobenzylzinc bromide (0.27 mL of a 0.5 M solution in THF; 0.134 mmol), and tetrakis(triphenylphosphine) palladium (0) (0.008 g; 5 mol %). The reaction was evacuated and purged with nitrogen several times and stirred at 50° C. for 16 hours. The reaction mixture was cooled to room temperature and diluted with ethyl acetate and washed with saturated aq. NaHCO3 solution (3×), and brine. The organic portion was dried (Na2SO4), filtered, and concentrated in vacuo. Purification done by MPLC (silica gel; 0-10% ethyl acetate/hexane gradient) afforded the desired product: m/e=487 (M+3); Rt=4.8 min.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([NH:16][C:17](=[O:22])[C:18]([F:21])([F:20])[F:19])[CH:7]=[C:8]([S:10]([F:15])([F:14])([F:13])([F:12])[F:11])[CH:9]=1)(=[O:3])[CH3:2].[Br:23]Br>C(O)(=O)C.O>[Br:23][CH2:2][C:1]([C:4]1[CH:5]=[C:6]([NH:16][C:17](=[O:22])[C:18]([F:21])([F:19])[F:20])[CH:7]=[C:8]([S:10]([F:14])([F:15])([F:13])([F:12])[F:11])[CH:9]=1)=[O:3]
Reactant: CC(=O)c1cc(NC(=O)C(F)(F)F)cc(S(F)(F)(F)(F)F)c1
Reactant: BrBr
Solvent: O
Solvent: CC(=O)O
Product: O=C(CBr)c1cc(NC(=O)C(F)(F)F)cc(S(F)(F)(F)(F)F)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
N-(3-Acetyl-5-pentafluorosulfanylphenyl)-2,2,2-trifluoroacetamide (20 mg) was initially introduced dissolved in glacial acetic acid (1 ml), and bromine (9 mg) dissolved in glacial acetic acid (90 μl) was slowly added dropwise. After stirring at RT for 30 min, the mixture was warmed at 60° C. for 1 h. After cooling to RT, the glacial acetic acid was diluted with a large quantity of water and extracted three times with ethyl acetate. The combined extracts were washed with sodium hydrogencarbonate solution until acid-free, dried over magnesium sulfate, filtered and concentrated. The crude product obtained (24 mg) was employed in the next stage without further purification.