Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]2[C:4]=1[C:5](=[O:27])[NH:6][C:7]([C:15]1[CH:20]=[CH:19][C:18]([N:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)=[CH:17][CH:16]=1)=[N:8]2.[F:28][C:29]1[CH:36]=[CH:35][C:32]([CH2:33]Br)=[CH:31][CH:30]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[F:28][C:29]1[CH:36]=[CH:35][C:32]([CH2:33][N:24]2[CH2:23][CH2:22][N:21]([C:18]3[CH:19]=[CH:20][C:15]([C:7]4[NH:6][C:5](=[O:27])[C:4]5[C:9](=[CH:10][C:11]([O:13][CH3:14])=[CH:12][C:3]=5[O:2][CH3:1])[N:8]=4)=[CH:16][CH:17]=3)[CH2:26][CH2:25]2)=[CH:31][CH:30]=1
Reactant: COc1cc(OC)c2c(=O)[nH]c(-c3ccc(N4CCNCC4)cc3)nc2c1
Reactant: Fc1ccc(CBr)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1cc(OC)c2c(=O)[nH]c(-c3ccc(N4CCN(Cc5ccc(F)cc5)CC4)cc3)nc2c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 65.1 %

Procedure:
To a solution of 5,7-dimethoxy-2-(4-(piperazin-1-yl)phenyl)quinazolin-4(3H)-one (0.200 g, 0.55 mmol) in DMF (5 mL) was added 4-fluorobenzyl bromide (0.07 mL, 0.55 mmol) and K2CO3 (0.15 g, 1.10 mmol). The reaction was stirred at room temperature for 2 hours then diluted with H2O and the solids filtered off to afford the title compound (0.17 g, 65%) as a light brown solid. 1H NMR (300 MHz, DMSO-d6): δ 11.76 (br s, 1H), 8.09 (d, J=8.1 Hz, 2H), 7.26-7.52 (m, 2H), 7.08-7.25 (m, 2H), 7.00 (d, J=8.0 Hz, 2H), 6.68 (s, 1H), 6.46 (s, 1H), 3.87 (s, 3H), 3.83 (s, 3H), 3.51 (s, 2H), 3.08-3.41 (m, 4H), 2.23-2.68 (m, 4H). APCI MS m/z 475 [M+H]+.
Reaction SMILES: Cl.C[O:3][C:4](=O)[C@H:5]([CH3:7])[NH2:6].[C:9]1([Mg]Br)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C1COCC1>[NH2:6][C@@H:5]([CH3:7])[C:4]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[OH:3]
Reactant: Br[Mg]c1ccccc1
Reactant: COC(=O)[C@H](C)N
Agent: Cl
Solvent: C1CCOC1
Product: C[C@H](N)C(O)(c1ccccc1)c1ccccc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 7.2 %

Procedure:
L-Alanine methyl ester hydrochloride (9.9 g, 70.9 mmol) was added portionwise to a 1.0 M solution of phenylmagnesium bromide (78.0 g, 0.43 mol) in THF at 0° C. and then heated under reflux for 21 h. The reaction mixture was cooled to 0° C., quenched with dropwise addition of saturated NH4Cl, and stirred for 1 h. After collecting insoluble products through the Buchner funnel, organic products were extracted into AcOEt (3×100 ml). The combined organic extracts were dried over K2CO3/MgSO4, and concentrated under reduced pressure to obtain a crude product. Impurities were washed with dichloromethane over silica gel by means of dry-flash column chromatography, further elution with a mixture of AcOEt and petrol, ranging from 20% up to 100%, gave the title compound (10) (1.16 g, 9%) as a white solid. m.p. 100–101° C. (litii,v 100–102° C.). [α]D25=−85.59° (c, 0.0362 in CHCl3) (litii: −82.38° (c, 0.814 in CHCl3; litv: −85.9° (c, 2.77 in CHCl3). δH 0.94 (3H, d, 3J=6.30 Hz, CH3), 1.23 (2H, broad s, NH2), 4.15 (1H, q, 3J=6.30 Hz, CH—NH2), 4.25 (1H, broad s, OH), 7.10–7.66 (10H, m, Ar—H). δC 17.4 (CH3), 52.1 (CH—NH2), 78.7 (C—OH), 125.7, 126.1, 126.6, 126.9, 128.2 and 128.7 (o-, m- and p-Ar), 145.0 and 147.2 (α-Ar). Anal. Calcld. for C15H17NO: C 79.26; H 7.54; N 6.16. Found: C 79.30; H 7.66; N 6.27. ir 3432 (OH), 3389 (NH2). m/e (CI—NH3) 228 (MH+, 100%).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[Br:21])[CH2:10][CH2:9]1)=O)(C)(C)C.[C:22]([OH:28])([C:24]([F:27])([F:26])[F:25])=[O:23]>ClCCl>[F:25][C:24]([F:27])([F:26])[C:22]([OH:28])=[O:23].[Br:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[O:14][CH:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1
Reactant: CC(C)(C)OC(=O)N1CCC(Oc2ccccc2Br)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Brc1ccccc1OC1CCNCC1
Reaction time: 3 h
Yield: 96 %

Procedure:
To a stirred solution of 2-bromophenol (0.5 g, 0.00289 mole) in DMF (4 mL) was added potassium carbonate (0.478 g, 0.003468 mole), followed by 4-methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (0.888 g, 0.00318 mole). The reaction mixture was heated at 80° C. for 6 hours. The mixture was then diluted with water and the product was extracted with ethyl acetate. The ethyl acetate layer was washed with brine solution, dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by column chromatography using silica gel 60-120 mesh (2% ethyl acetate in hexane) to afford 0.64 g (68%) of 4-(2-bromo-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester. LCMS: 356.08 (M+1)+, 99.56%. A solution of 4-(2-bromo-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester (0.64 g, 0.0018 mole) in dichloromethane (6.4 mL) was stirred at 0-5° C. To the cold solution was added TFA (3.2 mL) dropwise and stirring was continued at ambient temperature for 3 hours. The reaction mixture was concentrated under reduced pressure and the resulting residue was washed with hexane to afford 0.64 g (96%) of 4-(2-bromo-phenoxy)-piperidine trifluoroacetate. LCMS: 370.02 (M+1)+, 91.37%. 1H NMR (CDCl3-D2O): δ 7.6-7.54 (d, 1H), 7.32-7.26 (d, 1H), 6.94-6.86 (d, 2H), 4.8-4.7 (bs, 1H), 3.5-3.4 (m, 2H), 3.3-3.2 (m, 2H), 2.2-2.1 (s, 4H).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][O:3][CH:2]1[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[S:14][C:15]3[C:20]([N:21]=2)=[CH:19][CH:18]=[C:17]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:16]=3)=[C:9]([F:29])[CH:8]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:40]1[CH2:44]O[CH2:42][CH2:41]1.BrCCC=C>CN(C=O)C>[O:3]1[CH2:4][CH2:5][CH2:6][O:1][CH:2]1[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[S:14][C:15]3[C:20]([N:21]=2)=[CH:19][CH:18]=[C:17]([CH:22]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:42][CH2:41][CH:40]=[CH2:44])[N:16]=3)=[C:9]([F:29])[CH:8]=1
Reactant: C1CCOC1
Reactant: Fc1cc(C2OCCCO2)ccc1-c1nc2ccc(Cc3ccccc3)nc2s1
Agent: C=CCCBr
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CN(C)C=O
Product: C=CCCC(c1ccccc1)c1ccc2nc(-c3ccc(C4OCCCO4)cc3F)sc2n1
Reaction time: 0.21 h

Procedure:
Argon was bubbled through a slurry of 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-benzylthiazolo[5,4-b]pyridine (1.00 g, 2.46 mmol) in 20 mL DMF for 5 min. To the rapidly stirring reaction mixture was added LiHMDS 1.0M in THF (2.71 mL, 2.71 mmol) rapidly dropwise. The resulting deep blue reaction mixture was stirred for 2 min, at which point 4-bromo-1-butene (0.499 mL, 4.92 mmol) was added rapidly via syringe. The color of the reaction slowly became purple over 5 min, then brown over about 10-15 min additional. After 1.5 h, the reaction mixture was quenched with sat'd aq. NH4Cl and MTBE. The organic layer was washed with water, brine, dried over sodium sulfate, filtered, and concentrated in vacuo to give 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-(1-phenylpent-4-enyl)thiazolo[5,4-b]pyridine as an orange solid MS (ESI) m/z: Calculated: 460.2; Observed: 461.1 (M++1).
Reaction SMILES: Br[C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[CH3:9][C:10]1([CH3:19])[CH2:15][CH2:14][C:13](B(O)O)=[CH:12][CH2:11]1>>[CH3:9][C:10]1([CH3:19])[CH2:15][CH2:14][C:13]([C:2]2[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=2[NH2:4])=[CH:12][CH2:11]1
Reactant: CC1(C)CC=C(B(O)O)CC1
Reactant: Nc1ccccc1Br
Product: CC1(C)CC=C(c2ccccc2N)CC1

Procedure:
The title compound was prepared by Suzuki coupling of 2-bromoaniline and 4,4-dimethyl-1-cyclohexen-1-yl boronic acid according to the procedure in Example 44, step (b). Mass spectrum (ESI, m/z): Calcd. for C14H19N, 202.1 (M+H), found 202.1.
Reaction SMILES: C(Cl)(Cl)Cl.CCCCCC.C1CO[C:13]2([C:19]3[CH:20]=[CH:21][C:22]([CH2:24][C:25](N)=[O:26])=[CH:23][C:18]=3[CH:17]=[CH:16][C:15]3[CH:28]=[CH:29][CH:30]=[CH:31][C:14]2=3)[O:12]1.CC(C)=[O:36].CCCCCC>>[CH:21]1[C:20]2[CH:17]=[CH:16][C:15]3[CH:28]=[CH:29][CH:30]=[CH:31][C:14]=3[C:13](=[O:12])[C:19]=2[CH:18]=[CH:23][C:22]=1[CH2:24][C:25]([OH:36])=[O:26]
Reactant: NC(=O)Cc1ccc2c(c1)C=Cc1ccccc1C21OCCO1
Reactant: CC(C)=O
Solvent: ClC(Cl)Cl
Solvent: CCCCCC
Product: O=C(O)Cc1ccc2c(=O)c3ccccc3ccc2c1

Procedure:
11.0 Gm. of 2-(5,5-ethylenedioxy-5H-dibenzo[a,d]cyclohepten-2-yl)propionamide is refluxed for 2 hours in 70 ml. of acetic acid and 105 ml. of concentrated hydrochloric acid. The mixture is cooled and diluted, then extracted with ether. The ethereal solution is extracted with aqueous sodium carbonate and the extract acidified and extracted with ethyl acetate to afford a 70% yield of 2-(5H-dibenzo[a,d]cyclohepten-5-on-2-yl)propionic acid., m.p. (chloroform-hexane) 138°-139° C.; m.p. (acetone-hexane) 113°-115° C. Use of 2-(5,5-ethylenedioxy-5H-dibenzo[a,d]cyclohepten-2-yl)acetamide gives a similar yield of 2-(5H-dibenzo[a,d]cyclohepten-5-on-2-yl)acetic acid, m.p. (acetone-hexane) 148°-149.5° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([OH:16])[CH:5]=[C:6]([C:8]2([O:14][CH3:15])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:7]=1.Br[CH2:18][C:19]1[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][CH:20]=1.C([O-])([O-])=O.[K+].[K+].O>CC(N(C)C)=O.C1OCCOCCOCCOCCOCCOC1>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[C:6]([C:8]2([O:14][CH3:15])[CH2:9][CH2:10][O:11][CH2:12][CH2:13]2)[CH:7]=1)[O:16][CH2:18][C:19]1[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][CH:20]=1
Reactant: COC(=O)c1ccc(CBr)cc1
Reactant: COC1(c2cc(O)cc(F)c2)CCOCC1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC(=O)N(C)C
Product: COC(=O)c1ccc(COc2cc(F)cc(C3(OC)CCOCC3)c2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 89 %

Procedure:
A mixture of 3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenol (Example 8, Step 4) (1.5 g, 6.6 mmol), methyl 4-(bromomethyl)benzoate (1.7 g, 7.4 mmol), K2CO3 (0.6 g, 4.3 mmol), 18-crown-6 (0.05 g) and KI (0.05 g) in dimethylacetamide (5.00 mL) was stirred at room temperature for 16 h, and at 80° C. for 2 h. The reaction mixture was poured into cold water (100 mL) and extracted with EtOAc (2×25 mL). The combined organic extracts were washed with water (2×25 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel, eluting with 20% EtOAc in hexane, to furnish 2.2 g (88%) of methyl 4-[3-fluoro-5-(4-methoxy-3,4,5,6-tetrahydro-2H-pyran-4-yl)phenoxymethyl]benzoate as a white solid: m.p. 88-89° C. 1H NMR (CDCl3/300 MHz) δ 8.07 (d, 2H, J=7.8 Hz), 7.5 (d, 2H, J=7.8 Hz), 6.81 (s, 1H), 6.72 (d, 1H, J=9.9 Hz), 6.6 (d, 1H, J=9.9 Hz), 5.12 (s, 2H), 3.93 (s, 3H), 3.82 (m, 4H), 2.97 (s, 3H), 1.92 (m, 4H). FABMS m/z 375 (M+H).
Reaction SMILES: [CH3:1][O:2][CH:3]=[CH:4][C:5]1[C:6]([NH2:11])=[N:7][N:8]([CH3:10])[CH:9]=1.Br[CH2:13][CH2:14][CH2:15][CH2:16][C:17](Cl)=[O:18].[OH-].[K+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[CH3:1][O:2][CH:3]=[CH:4][C:5]1[C:6]([N:11]2[CH2:13][CH2:14][CH2:15][CH2:16][C:17]2=[O:18])=[N:7][N:8]([CH3:10])[CH:9]=1
Reactant: COC=Cc1cn(C)nc1N
Reactant: O=C(Cl)CCCCBr
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: COC=Cc1cn(C)nc1N1CCCCC1=O

Procedure:
A mixture of 4-(2-methoxyvinyl)-1-methyl-1H-pyrazol-3-amine a17-1 (500 mg, 3.27 mmol, 1 eq), 5-bromovaleryl chloride (651.9 mg, 3.27 mmol, 1 eq), potassium hydroxide (550.1 mg, 9.80 mmol, 3 eq), 4-dimethymaminopyridine (39.9 mg, 0.33 mmole, 0.1 eq) and N,N,N-tributylbutan-1-aminium bromide (105.3 mg, 0.33 mmole, 0.1 eq) in toluene (15 ml) is heated to reflux overnight. After filtration and evaporation the residue is purified by reverse phase chromatography (basic mode, gradient: H2O/acetonitrile/NH4OH from 80/20/0.1 to 50/50/0.1 in 10 minutes) to afford 1-[4-(2-methoxyvinyl)-1-methyl-1H-pyrazol-3-yl]piperidin-2-one a17-2.
Reaction SMILES: [NH:1]([C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18])[C@H:2]([C:7]([O:9]N1C(=O)CCC1=O)=O)[C@H:3]([CH2:5][CH3:6])[CH3:4].CCN(CC)CC.C(OC(C)C)(C)C.[NH2:41][C@H:42]([C:49]([NH:51][C@H:52]([C:65]([O:67][CH3:68])=[O:66])[CH2:53][CH2:54][CH2:55][CH2:56][NH:57][C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])=[O:50])[CH2:43][C:44]1[N:48]=[CH:47][NH:46][CH:45]=1>CN(C=O)C>[NH:1]([C:17]([O:19][CH2:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)=[O:18])[C@H:2]([C:7]([NH:41][C@H:42]([C:49]([NH:51][C@H:52]([C:65]([O:67][CH3:68])=[O:66])[CH2:53][CH2:54][CH2:55][CH2:56][NH:57][C:58]([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])=[O:59])=[O:50])[CH2:43][C:44]1[N:48]=[CH:47][NH:46][CH:45]=1)=[O:9])[C@H:3]([CH2:5][CH3:6])[CH3:4]
Reactant: COC(=O)[C@H](CCCCNC(=O)OC(C)(C)C)NC(=O)[C@@H](N)Cc1c[nH]cn1
Reactant: CC[C@H](C)[C@H](NC(=O)OCc1ccccc1)C(=O)ON1C(=O)CCC1=O
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: CC(C)OC(C)C
Product: CC[C@H](C)[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CCCCNC(=O)OC(C)(C)C)C(=O)OC
Reaction time: 8 h

Procedure:
1.32 g of Z-Ile-OSu [G. W. Anderson et. al., J. Amer. Chem. Soc. 86, 1839 (1964)] are dissolved in the above solution of H-His-Lys(Boc)-OMe in approximately 10 ml of DMF and mixed with 0.41 ml of NEt3. The whole is left to stand for 8 hours at room temperature, 15 ml of diisopropyl ether are added, and the whole is homogenised and filtered. The residue obtained by filtering with suction is dissolved in 15 ml of methanol and added at 0° to 23 ml of aqueous NaHCO3 solution. The resulting precipitate is filtered off, washed with H2O, dried and dissolved and reprecipitated from MeOH/ethyl acetate/petroleum ether, yielding Z-Ile-His-Lys(Boc)-OMe in the form of amorphous powder; Rf (B)=0.65; Rf (I)=0.48.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[CH:6]=[CH:5][N:4]=1.[Li]CCCC.[CH2:15]=[O:16]>C1COCC1>[OH:16][CH2:15][CH2:9][C:7]1[CH:6]=[CH:5][N:4]=[C:3]([O:2][CH3:1])[CH:8]=1
Reactant: C=O
Reactant: COc1cc(C)ccn1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: COc1cc(CCO)ccn1
Temperature: -78 °C
Reaction time: 1 h
Yield: 50.6 %

Procedure:
To a stirred solution of 2-methoxy-4-methylpyridine (6 g, 49 mmol) in anhydrous THF (200 mL) at −78° C. under nitrogen was added dropwise 29.4 mL (73.5 mmol) of n-BuLi (2.5 M solution in hexanes). The mixture was stirred at −78° C. for 1 h, and then warmed slowly to 0° C. and stirred at 0° C. for 30 min. The mixture was recooled to −78° C. and paraformaldehyde (10 g) was added in one portion. The mixture was warmed slowly to room temperature and stirred at room temperature for 8 h. The reaction was quenched by addition of saturated aq. NH4Cl and extracted with EtOAc (150 mL×3). The combined organic layers were washed with brine, dried (MgSO4), and concentrated. The residue was purified by chromatography with hexane/EtOAc (2:1) to afford 4-(2-hydroxyethyl)-2-methoxypyridine as a colorless oil (3.8 g, 51%). 1H NMR (CDCl3) δ 8.06 (d, 1H, J=5.1 Hz), 6.77 (d, 1H, J=5.1 Hz), 6.62 (s, 1H), 3.92 (s, 3H), 3.87 (t, 2H, J=6.6 Hz), 2.81 (t, 2H, J=6.6 Hz), 1.98 (br s, 1H); 13C NMR (CDCl3) δ 164.48, 150.63, 146.71, 117.76, 110.91, 62.43, 53.34, 38.30. MS m/z (%): 153 (M, 73), 152 (100), 123 (48).
Reaction SMILES: B(F)(F)F.C[CH2:6][O:7]CC.[Cl:10][C:11]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=1[C:18]1([CH2:21][CH2:22][CH3:23])[O:20][CH2:19]1.C(=O)(O)[O-].[Na+]>CO>[Cl:10][C:11]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=1[C:18]([O:20][CH3:19])([CH2:21][CH2:22][CH3:23])[CH2:6][OH:7]
Reactant: CCOCC
Reactant: CCCC1(c2ccc(Cl)cc2Cl)CO1
Agent: FB(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Product: CCCC(CO)(OC)c1ccc(Cl)cc1Cl
Temperature: 30 °C
Reaction time: 6 h

Procedure:
12.5 ml of boron trifluoride ethyl etherate are added dropwise slowly to a solution of 20.7 g (90 mmoles) of 2-(2,4-dichlorophenyl)-1,2-epoxypentane in 100 ml of absolute methanol. The temperature is kept at 18°-20° C. by occasional cooling. The temperature is then kept at 18°-20° C. for a further 6 hours, and the mixture is then stirred for a further hour at 30° C. The solution is poured into ice-cold, dilute sodium bicarbonate solution, and the resulting mixture is extracted twice with diethyl ether. The combined ether extracts are washed twice with half-saturated sodium bicarbonate solution and then twice with sodium chloride solution and are dried over sodium sulfate, filtered and concentrated. This gives 26.2 g of a yellowish, slightly viscous liquid, which is distilled in a high vacuum using a Vigreux column. The 2-(2,4-dichlorophenyl)-2-methoxypentan-1-ol thus obtained is a colourless, viscous oil of boiling point 88°-90° C./10.7×10-3 mbar and n50D 1.5322. Yield 12.1 g (=51% of theory), 100 mHz-1H-NMR(CDCl3): δ=7.15-7.6 ppm (m, 3H, aromatic); 4.1 ppm (dd, 2H, --CH2OH); 3.25 ppm (s, 3H, --OCH3); 1.7-2.3 ppm (m, 3H, ##STR19## 1H disappears on adding D2O); 0.7-1.25 ppm (m, 5H, --CH2CH2CH3).
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:31])=[C:4]([CH:8]2[C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[CH:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][CH:9]2[C:28](O)=[O:29])[CH:5]=[CH:6][CH:7]=1.[NH2:32][C:33]1[CH:38]=[CH:37][C:36]([C:39](=[O:42])[CH2:40][Br:41])=[CH:35][CH:34]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[Br:41][CH2:40][C:39]([C:36]1[CH:37]=[CH:38][C:33]([NH:32][C:28]([CH:9]2[CH:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=3[F:31])[C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[CH:11]([CH2:23][C:24]([CH3:27])([CH3:25])[CH3:26])[NH:10]2)=[O:29])=[CH:34][CH:35]=1)=[O:42]
Reactant: CC(C)(C)CC1NC(C(=O)O)C(c2cccc(Cl)c2F)C1(C#N)c1ccc(Cl)cc1F
Reactant: Nc1ccc(C(=O)CBr)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)CC1NC(C(=O)Nc2ccc(C(=O)CBr)cc2)C(c2cccc(Cl)c2F)C1(C#N)c1ccc(Cl)cc1F
Yield: 7.2 %

Procedure:
In a manner similar to the method described in Examples 1e, rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (0.35 g, 0.75 mmol) was reacted with 1-(4-amino-phenyl)-2-bromo-ethanone (Astatech) (0.17 g, 0.9 mmol), HATU (0.5 g, 1.3 mmol) and iPr2NEt (0.33 mL, 2.6 mmol) in CH2Cl2 at room temperature to give rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid [4-(2-bromo-acetyl)-phenyl]-amide as a white solid (36 mg, 7%).
Reaction SMILES: Cl.[C:2]([C:4]1[CH:5]=[C:6]([NH:11][NH2:12])[CH:7]=[CH:8][C:9]=1[F:10])#[N:3].ClC1C=C(N2[C:25]([C:26]3[CH:31]=[C:30](F)[CH:29]=[C:28]([Cl:33])[CH:27]=3)=[CH:24][C:23]([C:34]([O:36][CH2:37][CH3:38])=[O:35])=N2)C=CC=1F>>[Cl:33][C:28]1[CH:27]=[C:26]([C:25]2[N:11]([C:6]3[CH:7]=[CH:8][C:9]([F:10])=[C:4]([C:2]#[N:3])[CH:5]=3)[N:12]=[C:23]([C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH:24]=2)[CH:31]=[CH:30][CH:29]=1
Reactant: N#Cc1cc(NN)ccc1F
Reactant: CCOC(=O)c1cc(-c2cc(F)cc(Cl)c2)n(-c2ccc(F)c(Cl)c2)n1
Agent: Cl
Product: CCOC(=O)c1cc(-c2cccc(Cl)c2)n(-c2ccc(F)c(C#N)c2)n1

Procedure:
The preparation of the title compound takes place starting from the compound of Example 3A and 3-cyano-4-fluorophenylhydrazine hydrochloride in analogy to the synthesis of the compound of Example 21A. 0.76 g of the title compound with 46% purity (23% of theory) are obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:3]=1[CH:4]=O.[CH3:11][C:12]([CH3:14])=[O:13].[OH-].[K+]>>[Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:3]=1/[CH:4]=[CH:11]/[C:12](=[O:13])/[CH:14]=[CH:4]/[C:3]1[C:2]([Cl:1])=[CH:9][CH:8]=[CH:7][C:6]=1[Cl:10]
Reactant: O=Cc1c(Cl)cccc1Cl
Reactant: CC(C)=O
Agent: [K+]
Agent: [OH-]
Product: O=C(/C=C/c1c(Cl)cccc1Cl)/C=C/c1c(Cl)cccc1Cl
Temperature: 25 °C
Reaction time: 18 h

Procedure:
(73) To a 0.33 M solution of 2,6-dichlorobenzaldehyde (1.75 g, 10 mmol) and acetone (290 mg, 5 mmol) in 30 was added 5 ml of 40% potassium hydroxide at 10° C. After stirring for 18 hr at room temperature, a solid precipitated and was filtered. The precipitate was recrystallized from ethanol to afford 1.46 g (78.5%) of pale yellow, cotton-like flakes: mp 154.0-154.4° C. (lit. mp 145-146° C., Unterhalt, Arch. Pharm., 1978, 311, 262-267). 1H NMR (250 MHz) δ 7.85-7.79 (d, 2H), 7.40-7.36 (d, 4H), 7.26-7.19 (d, 2H), 7.24-7.18 (m, 2H); 13C NMR (62.7 MHz) 189.1, 137.6, 135.4, 133.3, 132.5, 130.2, 129.1 ppm.
Reaction SMILES: C1O[C@H]2[C@@H](O)[C@H]([O:9][C@@H:10]3[C@@H:15]([OH:16])[C@H:14]([O:17][C@H:18]4[C@@H:22]5[C@@H:23]([OH:59])[C@H:24]([O:26][C@@H:27]6[C@@H:32]([OH:33])[C@H:31]([O:34][C@H:35]7[C@@H:39]8[C@@H:40]([OH:55])[C@H:41]([O:43][C@@H:44]9[C@@H:49]([OH:50])[CH:48]([OH:51])[O:47][C@H:46]([CH2:52][OH:53])[C@@H:45]9[OH:54])[O:42][C@H:36]7[CH2:37][O:38]8)[O:30][C@H:29]([CH2:56][OH:57])[C@@H:28]6[OH:58])[O:25][C@H:19]4[CH2:20][O:21]5)[O:13][C@H:12]([CH2:60][OH:61])[C@@H:11]3[OH:62])O[C@@H]1[C@H]2O>P([O-])([O-])([O-])=O>[CH2:20]1[O:21][C@H:22]2[C@H:23]([OH:59])[C@H:24]([O:26][C@@H:27]3[C@@H:32]([OH:33])[C@H:31]([O:34][C@H:35]4[C@@H:39]5[C@H:40]([OH:55])[C@H:41]([O:43][C@@H:44]6[C@@H:49]([OH:50])[C@H:48]([OH:51])[O:47][C@H:46]([CH2:52][OH:53])[C@@H:45]6[OH:54])[O:42][C@H:36]4[CH2:37][O:38]5)[O:30][C@H:29]([CH2:56][OH:57])[C@@H:28]3[OH:58])[O:25][C@@H:19]1[C@H:18]2[O:17][C@@H:14]1[O:13][C@H:12]([CH2:60][OH:61])[C@H:11]([OH:62])[C@H:10]([OH:9])[C@H:15]1[OH:16]
Reactant: OC[C@H]1O[C@@H](O[C@H]2[C@H]3OC[C@@H]2O[C@@H](O[C@H]2[C@@H](O)[C@@H](CO)O[C@@H](O[C@H]4[C@H]5OC[C@@H]4O[C@@H](O[C@H]4[C@@H](O)[C@@H](CO)OC(O)[C@@H]4O)[C@@H]5O)[C@@H]2O)[C@@H]3O)[C@H](O)[C@@H](O[C@@H]2O[C@H]3CO[C@@H]([C@H]2O)[C@@H]3O)[C@H]1O
Agent: O=P([O-])([O-])[O-]
Product: OC[C@H]1O[C@@H](O[C@H]2[C@H]3OC[C@@H]2O[C@@H](O[C@H]2[C@@H](O)[C@@H](CO)O[C@@H](O[C@H]4[C@H]5OC[C@@H]4O[C@@H](O[C@@H]4[C@@H](O)[C@H](O)O[C@H](CO)[C@@H]4O)[C@H]5O)[C@@H]2O)[C@H]3O)[C@H](O)[C@@H](O)[C@H]1O
Reaction time: 5 h

Procedure:
An amount of 30 mg of neoagarohexaose was dissolved in 10 ml of phosphate buffer of pH 7.8. Into this solution, a solution of 0.1 ml of phosphate buffer (pH 7.8) which dissolved 1.5 U of α-NAOS hydrolase isolated and purified from Vibrio sp. JT0107-L4 was added. The resultant solution was incubated at 30° C. for 5 hours; thereby, neoagarohexaose was decomposed. The reaction solution was applied to an activated carbon column (5 mmφ×50 mm), which was then washed with 1 ml of water and 1 ml of 10% ethanol followed by elution with 3 ml of 30% ethanol. The solvents of the 30% ethanol fraction were removed by distillation using a rotary evaporator. Thereafter, freeze-drying was applied and the weight was determined; the weight was 13.5 mg. This reaction product was analyzed by thin layer chromatography; thereby, a substance of Rf=0.21 (developing solvent; butanol:ethanol:water=3:1:1) was confirmed. In addition, the mass number of the reaction product was determined using a fast atom bombardment mass spectrometer and found to be 792. From these facts, the substance was identified as agaropentaose. The yield of the resulting agaropentaose was calculated as 80%. The structure of agaropentaose is shown below. ##STR3##