Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[C:3]([CH3:13])=[C:4]([N+:10]([O-:12])=[O:11])[C:5](N)=[N:6][C:7]=1[CH3:8].N([O-])=[O:15].[Na+]>FC(F)(F)C(O)=O.O>[Br:1][C:2]1[C:3]([CH3:13])=[C:4]([N+:10]([O-:12])=[O:11])[C:5]([OH:15])=[N:6][C:7]=1[CH3:8]
Reactant: O=N[O-]
Reactant: Cc1nc(N)c([N+](=O)[O-])c(C)c1Br
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: O
Product: Cc1nc(O)c([N+](=O)[O-])c(C)c1Br
Reaction time: 8 h

Procedure:
To a solution of 5-bromo-4,6-dimethyl-3-nitro-2-pyridinylamine (Heitsch, H.; et al. Bioorg. Med. Chem. 1997, 5, 673, 2.0 g, 8.1 mmol) in trifluoroacetic acid/water (v/v, 2:1, 30 mL) was added sodium nitrite (1.1 g, 16 mmol) in small portions at room temperature, and then the reaction mixture was stirred overnight. The resulting precipitates were collected by filtration, washed with water, and dried under reduced pressure to give 2.2 g (quant.) of the title compound: 1H-NMR (CDCl3) δ 2.53 (3H, s), 2.38 (3H, s).
Reaction SMILES: C(O[C:6]([N:8](C)[CH:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[C:23]([Cl:25])[CH:22]=[C:21]([Cl:26])[CH:20]=2)=[O:16])[CH2:11][CH2:10]1)=O)(C)(C)C.Cl.O1CCOCC1>C(Cl)Cl>[CH3:6][NH:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][CH2:18][C:19]2[CH:20]=[C:21]([Cl:26])[CH:22]=[C:23]([Cl:25])[CH:24]=2)=[O:16])[CH2:11][CH2:10]1
Reactant: CN(C(=O)OC(C)(C)C)C1CCN(C(=O)OCc2cc(Cl)cc(Cl)c2)CC1
Agent: Cl
Solvent: ClCCl
Solvent: C1COCCO1
Product: CNC1CCN(C(=O)OCc2cc(Cl)cc(Cl)c2)CC1
Temperature: 25 °C
Reaction time: 3.5 h

Procedure:
3,5-Dichlorobenzyl 4-((tert-butoxycarbonyl)(methyl)amino)piperidine-1-carboxylate (2.4 g, 5.75 mmol) in DCM (13 ml) was treated with and 4M HCl in dioxane (14.38 ml, 57.5 mmol) to give a colourless solution. The mixture was stirred for 3.5 hours at room temperature and then concentrated under reduced pressure to afford the title compound which was used without further purification;
Reaction SMILES: [OH:1][C:2]1[C:7]([CH2:8][CH:9]=[C:10]([CH3:12])[CH3:11])=[C:6]([OH:13])[CH:5]=[CH:4][C:3]=1[C:14](=[O:16])[CH3:15].[C:17](=O)([O-])[O-].[K+].[K+].CI>CC(C)=O>[OH:1][C:2]1[C:7]([CH2:8][CH:9]=[C:10]([CH3:11])[CH3:12])=[C:6]([O:13][CH3:17])[CH:5]=[CH:4][C:3]=1[C:14](=[O:16])[CH3:15]
Reactant: CC(=O)c1ccc(O)c(CC=C(C)C)c1O
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CC(C)=O
Product: COc1ccc(C(C)=O)c(O)c1CC=C(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 99.1 %

Procedure:
Then, 19.00 g of 2',4'-dihydroxy-3'-(3-methyl-2-butenyl)acetophenone was dissolved in 160 ml of acetone, and 14.29 g of anhydrous potassium carbonate and 6.2 ml of methyl iodide were added to the solution and the mixture was stirred at room temperature in a nitrogen current overnight. After the reaction, the solvent was removed by distillation and the obtained residue was extracted with ether, the extract was washed with water, dried with anhydrous sodium sulfate, and filtered. The solvent was removed from the filtrate by distillation to obtain 20.02 g (yield=99.1%) of 2'-hydroxy-4'-methoxy-3'-(3-methyl-2-butenyl)acetophenone in the form of a colorless oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH:18]([CH3:23])[C:19]([O:21]C)=[O:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.Cl>[OH-].[Na+].CO.CS(C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH:18]([CH3:23])[C:19]([OH:21])=[O:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1
Reactant: COC(=O)C(C)C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: CO
Product: CC(C(=O)O)C(c1ccccc1)c1ccc2c(cnn2-c2ccc(F)cc2)c1
Yield: 82 %

Procedure:
(a)(b) To a solution of (1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methanol (800 mg, 2.5 mmol) and (1-methoxyprop-1-enyloxy)trimethylsilane (1 mL, 6.25 mmol) in 30 mL of dry DCM was added TiCl4 (2.5 mL of 1.0 M DCM solution, 2.5 mmol) and then stirred 1 h. The reaction was quenched with MeOH, poured into aqueous sodium bicarbonate and extracted 2×EtOAc. The organic layers were dried over MgSO4, filtered, concentrated to give methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-methyl-3-phenylpropanoat. Crude methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-methyl-3-phenylpropanoate was heated to 100 C overnight in a mixture of 2 M NaOH/MeOH/DMSO (1:1:1). The next day, the reaction was cooled, acidified to pH 5 with HCl and extracted 2×EtOAc. The organic layers were washed with water×2, dried over MgSO4, filtered, concentrated in vacuo, and purified by HPLC to give 770 mg (82% yield, 2 steps) of acid 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-methyl-3-phenylpropanoic acid. MS found: (M+H)+=375.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](O)=[O:15])[CH:10]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN([C:27]([O:31][N:32]1N=NC2C=CC=N[C:33]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CNOC.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:27][O:31][N:32]([CH3:33])[C:14]([CH:11]1[CH2:12][CH2:13][N:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:9][CH:10]1[C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1)=[O:15]
Reactant: O=C(O)C1CCN(Cc2ccccc2)CC1c1ccc(Cl)cc1
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: CNOC
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CON(C)C(=O)C1CCN(Cc2ccccc2)CC1c1ccc(Cl)cc1
Reaction time: 0.25 h

Procedure:
In a 100 mL round bottom flask with a magnetic stirrer 900 mg (2.72 mmol) (3RS,4SR)-1-benzyl-3-(4-chloro-phenyl)-piperidine-4-carboxylic acid and 1.14 g (3 mmol) HATU was dissolved in 20 mL dry DMF. The greenish solution was stirred for 15 min, 320 mg (3.28 mmol) N,O-dimethylhydroxylamine hydrochlorideowed and 2.32 mL DIPEA was added. The mixture was stirred for 3 h at room temperature and concentrated under high vacuum. The green viscous oil was taken up in 60 mL ethyl acetate and 75 mL 5% aqueous NaHCO3-solution. The aqueous layer was separated and extracted once with 60 mL ethyl acetate. The combined organic layers were washed with 75 mL 1% AcOH/water-solution and once with 100 ml brine, dried over Na2SO4, filtered off and concentrated under vacuum. The residue was purified over silica eluting with a gradient formed from ethyl acetate/heptane to yield after evaporation of the product containing fractions 990 mg (97%) of the title compound as colorless viscous oil. MS (m/e): 373.3 [(M+H)+].
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16]O)=[C:11]([N+:18]([O-:20])=[O:19])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)(Cl)[Cl:41]>C(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][Cl:41])=[C:11]([N+:18]([O-:20])=[O:19])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: ClC(Cl)(Cl)Cl
Reactant: O=[N+]([O-])c1cc(OCc2ccccc2)ccc1CCO
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: O=[N+]([O-])c1cc(OCc2ccccc2)ccc1CCCl
Yield: 97 %

Procedure:
The synthetic approach for the proposed achiral seco-CI compounds starts from the reaction of the readily available diethyl 2-(4-benzyloxy-2-nitrophenyl)malonate (4c). Treatment of diethyl 2-(4-benzyloxy-2-nitrophenyl)malonate with NaOH in ethanol (25-80° C.), preferably refluxing, followed by acidification and mild heating (25-100° C.), preferably refluxing, the solution gave the desired 4-benzyloxy-2-nitrophenylacetic acid in 95% yield. Selective reduction of the carboxylic acid with borane at 0-50° C., preferably at room temperature, in THF produced 2-(4-benzyloxy-2-nitrophenyl)ethanol in 95% yield. The alcohol was then chlorinated at 0-50° C., preferably at room temperature, with triphenylphosphine and carbon tetrachloride in CH2Cl2 to give 2-(4-benzyloxy-2-nitrophenyl)ethyl chloride in 97% yield. The 2-(4-benzyloxy-2-nitrophenyl)ethyl bromide was obtained in 92% yield after reacting 2-(4-benzyloxy-2-nitrophenyl)ethanol with triphenylphosphine and carbon tetrabromide in acetonitrile. Catalytic reduction of 2-(4-benzyloxy-2-nitrophenyl)ethyl chloride and 2-(4-benzyloxy-2-nitrophenyl)ethyl bromide at atmospheric pressure, and at 0-50° C., preferably at room temperature, using 10% Pd/C in THF afforded 2-(2-amino-4-hydroxyphenyl)ethyl chloride and 2-(2-amino-4-hydroxyphenyl)ethyl bromide, respectively. 2-(2-Amino-4-hydroxyphenyl)ethyl bromide was directly coupled at 0-50° C., preferably at room temperature, with 5-(benzofuran-2-carboxamido)indole-2-carboxylic acid in the presence of EDCI [1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride] and DMF to give compound 4-(2-bromoethyl)-3-[5-(5-benzofuran-2-carboxamido)indole-2-carboxamido]phenol in a low 2% yield for the two steps after purification by silica gel column chromatography. Similarly, coupling of 2-(2-amino-4-hydroxyphenyl)ethyl chloride with 5-(benzofuran-2-carboxamido)indole-2-carboxylic acid in the presence of EDCI gave 4-(2-chloroethyl)-3-[5-(5-benzofuran-2-carboxamido)indole-2-carboxamido]phenol in 28% yield for the two steps following column chromatography.
Reaction SMILES: [SH:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[CH2:9](O)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C1(C)C(S(O)(=O)=O)=CC=CC=1.C1C=CC=CC=1>[CH2:9]([S:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: OCc1ccccc1
Reactant: Oc1ccc(S)cc1
Agent: Cc1ccccc1S(=O)(=O)O
Solvent: c1ccccc1
Product: Oc1ccc(SCc2ccccc2)cc1

Procedure:
4-(Benzylthio)phenol was prepared as follows. Seventy grams of 4-mercaptophenol, 30 drops of toluene sulfonic acid and 100 milliliters of benzene were placed in a flask. Eighty-three grams of benzyl alcohol were added and the flask contents stirred at reflux for five hours to collect the water formed. A white substance precipitated from solution and was filtered. It was washed with hexane. The substance had a melting point of 96° C. to 98° C., a percent sulfur of 14.4 and a hydroxyl number of 259.
Reaction SMILES: [C:1]1([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[OH:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[Na+].[Na+].Br[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][OH:27]>C(C(C)=O)C>[C:1]1([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[O:13][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][OH:27])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Oc1ccccc1-c1ccccc1
Reactant: OCCCCCCBr
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCC(C)=O
Product: OCCCCCCOc1ccccc1-c1ccccc1
Yield: 84.5 %

Procedure:
Seventy-eight point five (78.5) g (461 mmol) of 2-phenylphenol from Tokyo Chemical Industry Co., Ltd. were dissolved in 600 mL of methyl ethyl ketone from Kanto Chemical Co., Inc. to prepare a solution. One hundred ninety one (191) g (1.38 mol) of sodium carbonate from Kanto Chemical Co., Inc. and 100 g (553 mmol) of 6-bromo-1-hexanol from Tokyo Chemical Industry Co., Ltd. were added to the solution, and refluxed for 8 hrs. After the solution was cooled to have room temperature, it was filtered and a solvent was removed therefrom. The residue was dissolved in methylene chloride from Junsei Chemical Co., Ltd. and washed with water. The isolated organic layer was dried with magnesium sulfide from Kanto Chemical Co., Inc., and a solvent was removed therefrom. The residue was refined by silica gel column chromatography using a mixed solvent in which a volume ratio of methylene chloride from Junsei Chemical Co., Ltd. to methanol from Kanto Chemical Co., Inc. is 99/1 as an eluent to obtain 105.3 g of 6-(2-phenyl-phenoxy)hexane-1-ol.
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:20][CH2:21][CH3:22])[CH2:5][CH2:6][CH:7]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=1)[C:8]#[N:9])[CH3:2].Cl[CH:24]([CH3:26])[CH3:25].IC(C)C.[H-].[Na+]>CN(C=O)C>[CH2:1]([O:3][CH:4]([O:20][CH2:21][CH3:22])[CH2:5][CH2:6][C:7]([CH:24]([CH3:26])[CH3:25])([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=1)[C:8]#[N:9])[CH3:2]
Reactant: CC(C)Cl
Reactant: CCOC(CCC(C#N)c1ccc(OC)c(OC)c1)OCC
Agent: [H-]
Agent: [Na+]
Solvent: CC(C)I
Solvent: CN(C)C=O
Product: CCOC(CCC(C#N)(c1ccc(OC)c(OC)c1)C(C)C)OCC
Temperature: 40 °C
Reaction time: 0.17 h

Procedure:
The resulting acetal derivative of formula 5 is then alkylated with about 1 eq of an alkylhalide using a strong metallic base and a catalytic amount of an iodide source, e.g., 2-iodopropane or NaI, in a polar aprotic solvent at about 10°-40° C. for 2-18 hours, followed by treatment with sufficient ice water to decompose excess base, to yield a dialkylated derivative of formula 6. For example, 2-(3,3-diethoxypropyl)-2-(3,4-dimethoxyphenyl)acetonitrile (5) in DMF is treated with a slight molar excess of 2-chloropropane (and 0.1-5 mol% 2-iodopropane) at 20° C., stirred for 10 minutes, then treated with 1 eq NaH in mineral oil and slowly heated to 40° C. After adding 200 ml ice water and purifying the product, 2-(3,3-diethoxypropyl)-2-(prop-2-yl)-2-(3,4-dimethoxyphenyl)acetonitrile (6) is obtained.
Reaction SMILES: CO[CH2:3][N:4]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:5][Si](C)(C)C.C(O)(C(F)(F)F)=O.[CH3:24][O:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[C:31](=[O:35])[CH:30]=[CH:29]2>C(Cl)Cl>[CH2:10]([N:4]1[CH2:3][CH:29]2[C:28]3[CH:27]=[C:26]([O:25][CH3:24])[CH:34]=[CH:33][C:32]=3[C:31](=[O:35])[CH:30]2[CH2:5]1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: COc1ccc2c(c1)C=CC2=O
Reactant: COCN(Cc1ccccc1)C[Si](C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COc1ccc2c(c1)C1CN(Cc3ccccc3)CC1C2=O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
N-(Methoxymethyl)-N-(trimethylsilylmethyl) benzylamine (17.3 mL, 67.6 mmol) and TFA (3.4 mL) were added to a solution of 5-methoxy-inden-1-one (5.4 g, 33.8 mmol) in CH2Cl2 (165 mL) at 0° C. The reaction was stirred for 3 hours at room temperature and quenched with saturated aqueous NaHCO3 (165 mL). The organic layer was separated, washed with brine (100 mL), dried over MgSO4, and concentrated to afford the subtitle compound, which was used without further purification. MS calculated for C19H19NO2+H: 294, observed: 294.
Reaction SMILES: [BH4-].[Na+].[Si:3]([O:10][C:11]1[CH:12]=[C:13]([O:42][Si:43]([C:46]([CH3:49])([CH3:48])[CH3:47])([CH3:45])[CH3:44])[C:14]2[CH2:25][S:24][CH2:23][C@@H:22]([C:26](OC)=[O:27])[NH:21][C:20](=[O:30])[C@@H:19]([NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:18][O:17][C:16](=[O:39])[C:15]=2[C:40]=1[CH3:41])([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4]>CO.CO.O1CCCC1>[Si:3]([O:10][C:11]1[CH:12]=[C:13]([O:42][Si:43]([C:46]([CH3:49])([CH3:48])[CH3:47])([CH3:44])[CH3:45])[C:14]2[CH2:25][S:24][CH2:23][C@@H:22]([CH2:26][OH:27])[NH:21][C:20](=[O:30])[C@@H:19]([NH:31][C:32]([O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[O:33])[CH2:18][O:17][C:16](=[O:39])[C:15]=2[C:40]=1[CH3:41])([C:6]([CH3:9])([CH3:7])[CH3:8])([CH3:4])[CH3:5]
Reactant: COC(=O)[C@@H]1CSCc2c(O[Si](C)(C)C(C)(C)C)cc(O[Si](C)(C)C(C)(C)C)c(C)c2C(=O)OC[C@H](NC(=O)OC(C)(C)C)C(=O)N1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: Cc1c(O[Si](C)(C)C(C)(C)C)cc(O[Si](C)(C)C(C)(C)C)c2c1C(=O)OC[C@H](NC(=O)OC(C)(C)C)C(=O)N[C@H](CO)CSC2
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 88 %

Procedure:
To a solution of 114 mg of sodium borohydride in 1.5 ml of 80% aqueous methanol, cooled to 0° C., was added within 5 minutes a solution of 214 mg of tert-butyl (4R, 7S)-12,14-bis(tert-butyldimethylsilyloxy)-1,3,4,5,6,7,8,10-octahydro-4-(methoxycarbonyl)-11-methyl-6,10-dioxo-9,2,5-benzoxathiaazacyclododecine-7-carbamate in 1.5 ml of methanol/tetrahydro-furan (1:1, v/v). The solution was stirred at 0° C. for 30 minutes, and then poured into ice-cold 0.5N hydrochloric acid. The mixture was extracted with ethyl acetate, and the organic layer was washed with brine, and dried over sodium sulfate. The solvent was evaporated in vacuo to yield 181 mg of tert-butyl (4R, 7S)-12, 14-bis (tert-butyldimethylsilyloxy)-1,3,4,5,6,7,8, 10-octahydro-4-hydroxymethyl-11-methyl-6,10-dioxo-9,2,5-benzoxathiaazacyclododecine-7-carbamate as an amorphous solid. This material was treated with ammonium fluoride in methanol in an analogous manner to the procedure described in Example 13 to yield, after crystallization from ethyl acetate/methanol/hexane, tert-butyl (4R, 7S)-1,3,4,5,6,7,8,10 -octahydro-12,14-dihydroxy-4-hydroxymethyl-11-methyl-6,10-dioxo-9,2,5-benzoxathiaazacyclododecine-7-carbamate as a white solid.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=1.[OH-].[NH4+:13]>CO>[N:8]1[CH:9]=[CH:10][CH:11]=[C:6]([O:5][CH2:4][CH2:3][CH2:2][NH2:13])[CH:7]=1
Reactant: [NH4+]
Reactant: ClCCCOc1cccnc1
Agent: [OH-]
Solvent: CO
Product: NCCCOc1cccnc1
Temperature: 100 °C
Yield: 20.1 %

Procedure:
The 3-chloro-1-(3-pyridyloxy)propane (1.98 g, 11.6 mmol) was dissolved in methanol (25 mL) and added to concentrated ammonium hydroxide solution (29.7%, 14.8 M, 55 mL) in a heavy-walled glass pressure-tube apparatus. The tube was sealed and the mixture was stirred and heated at 100° C. (oil bath temperature) for 6 h. After cooling, the mixture was concentrated by rotary evaporation. Saturated NaCl solution (10 mL) was added to the residue, and the solution (pH 6) was extracted with ether (3×25 mL) to remove impurities. The aqueous layer was basified to pH 10 with 10% NaOH solution, and the mixture was extracted with chloroform (4×25 mL). The combined chloroform extracts were dried (Na2SO4), filtered, and concentrated by rotary evaporation to a residue that was dried briefly under high vacuum to give 0.354 g (20.1%) of an oil.
Reaction SMILES: [Mg].II.C(Br)C.[C:7]1([C:13]#[CH:14])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[O:15]([C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[CH:25]=[O:26])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>O1CCCC1.Cl>[O:15]([C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[CH:25]([OH:26])[C:14]#[C:13][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: O=Cc1cccc(Oc2ccccc2)c1
Reactant: C#Cc1ccccc1
Agent: Cl
Agent: II
Agent: [Mg]
Solvent: C1CCOC1
Solvent: CCBr
Product: OC(C#Cc1ccccc1)c1cccc(Oc2ccccc2)c1
Temperature: 0 °C
Yield: 98.7 %

Procedure:
The alcohol required for the preparation of the pyrethroid is prepared as follows: ##STR12## A reaction vessel is charged with 14.6 g of magnesium filings together with a trace of iodine crystals. 73.6 g of ethyl bromide in 25 ml of tetrahydrofuran are then added dropwise such that the tetrahydrofuran boils gently under reflux. The Grignard solution formed is added dropwise at 0°-5° C. to a solution of 62.1 g of phenylacetylene in 250 ml of tetrahydrofuran and the mixture is stirred until the evolution of gas ceases. The resultant solution is cooled to 0° C. and 99 g of 3-phenoxybenzaldehyde are added dropwise such that the temperature does no exceed +5° C. The reaction mixture is stirred overnight at room temperature and then cooled to a temperature in the range from 0° to +5° C. About 100 g of ice are added, whereupon a precipitate forms which is dissolved in 100 ml of concentrated HCl. The aqueous solution is extracted with three 150 ml portions of ether and the extracts are washed with NaHCO3 solution and then dried over Na2SO4. The ether is distilled off by rotary evaporation, affording as residue 148 g of 3-phenoxy-α-phenylethynylbenzyl alcohol with a refractive index of nD23 =1.6238 and with an NMR spectrum as shown in FIG. 2. The yield is 98.8 % of theory.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][C:5]([CH:6]=[CH:7][C:8]#[N:9])=[CH:4][CH:3]=1.[Br:12]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[Br:12][CH2:1][C:2]1[CH:11]=[CH:10][C:5]([CH:6]=[CH:7][C:8]#[N:9])=[CH:4][CH:3]=1
Reactant: Cc1ccc(C=CC#N)cc1
Reactant: O=C1CCC(=O)N1Br
Solvent: ClC(Cl)(Cl)Cl
Product: N#CC=Cc1ccc(CBr)cc1

Procedure:
88 g of 4-bromomethylcinnamonitrile (obtained by bromination of 4-methylcinnamonitrile with N-bromosuccinimide in carbon tetrachloride, and having a melting point of 105°-107° C.) are mixed with 256 g of triethylphosphite. The mixture is then slowly heated to 150° C. with stirring, and then stirred for 3 hours at this temperature. Excess phosphite is then removed in vacuo, affording the crude phosphonate of the formula ##STR68## in the form of a light brown oil.
Reaction SMILES: O[CH:2]=[C:3]1[C:15]2[N:14]3[CH:16]=[CH:17][N:18]=[C:13]3[C:12](=[O:19])[NH:11][C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]1=2.CN(C)C=O>[Pd].CO>[CH3:2][CH:3]1[C:15]2[N:14]3[CH:16]=[CH:17][N:18]=[C:13]3[C:12](=[O:19])[NH:11][C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]1=2
Reactant: O=c1[nH]c2c3ccccc3c(=CO)c2n2ccnc12
Agent: [Pd]
Solvent: CN(C)C=O
Solvent: CO
Product: CC1c2ccccc2-c2[nH]c(=O)c3nccn3c21
Yield: 37.1 %

Procedure:
10-Methyl-5H,10H-imidazo[1,2-a]indeno-[1,2-e]pyrazin-4-one may be obtained in the following way: a mixture of 1 g of 10-hydroxymethylene-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one, 80 ml of dimethylformamide and 20 ml of methanol is hydrogenated at a temperature in the region of 20° C. and at normal pressure for 4 hours in the presence of 10% palladium-on-charcoal. After filtration of the catalyst under an inert atmosphere, the solvents are evaporated off and the beige-coloured solid obtained (1.25 g) is purified by chromatography on a column of silica (100 g) with a mixture of dichloromethane and methanol (95/5 by volume). After drying at 90° C., 0.35 g of 10-methyl-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one is obtained in the form of a cream-coloured solid melting above 260° C. (Analysis, % calculated C: 70.87, H: 4.67, N: 17.71, O: 6.74, % found C: 70.5, H: 4.4, N: 17.4).
Reaction SMILES: [CH2:1]([S:3][C:4]1[O:5][C:6]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:8]=1)[CH3:2].ClC1C=C(C=CC=1)C(OO)=[O:26]>C(Cl)Cl>[CH2:1]([S:3]([C:4]1[O:5][C:6]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:8]=1)=[O:26])[CH3:2]
Reactant: CCSc1nc(-c2ccccc2)c(-c2ccccc2)o1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CCS(=O)c1nc(-c2ccccc2)c(-c2ccccc2)o1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a cooled (ice/water) solution of 4.2 g. of 2-ethylthio-4,5-diphenyl-oxazole pre-dissolved in 30 ml. of methylene chloride is added in portions over 5 minutes, 30 g. of m-chloro-peroxybenzoic acid. Examination by TLC after 2 hours indicates the presence of essentially all of the sulfinyl compound (reaction complete). The precipitated m-chloro-benzoic acid is filtered off and the methylene chloride solution is washed successively with a 10 % solution of sodium sulfite and with saturated sodium bicarbonate solution, dried, evaporated in vacuo to dryness, and the residue further dried overnight in vacuo to yield 2-ethylsulfinyl-4,5-diphenyl-oxazole, m.p. 133°-134° C.
Reaction SMILES: [C:1]([CH:9]1[C:14](=[O:15])[NH:13][CH2:12][CH2:11][N:10]1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:23](O)[CH2:24][OH:25].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(OC(OC(OC(C)(C)C)=O)=O)(C)(C)C>C1C=CC=CC=1.O>[O:15]=[C:14]1[NH:13][CH2:12][CH2:11][N:10]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH:9]1[CH:1]1[O:8][CH2:23][CH2:24][O:25][C:7]2[CH:6]=[CH:5][CH:4]=[CH:3][C:2]1=2
Reactant: OCCO
Reactant: CC(C)(C)OC(=O)N1CCNC(=O)C1C(=O)c1ccccc1
Agent: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: c1ccccc1
Product: CC(C)(C)OC(=O)N1CCNC(=O)C1C1OCCOc2ccccc21

Procedure:
A mixture of 2.0 g (6.5 mmole) of 27d, 1.25 g (20.0 mmole) of ethyleneglycol, and 1.0 g of p-toluenesulfonic acid monohydrate is refluxed in 50 ml of benzene in a Dean-Stark apparatus until the collection of water ceases. The reaction mixture is cooled, washed with saturated NaHCO3 solution and brine, dried over MgSO4, and filtered. The filtrate is stirred with 2.2 g (10 mmole) of di-t-butyldicarbonate at reflux temperature and then concentrated to a solid residue and recrystallized from benzene/hexane to yield the title compound.