Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Al+3].[Cl-].[Cl-].[Cl-].[CH2:5]([O:7][C:8](=[O:11])[CH:9]=[CH2:10])C.[O:12]1[CH:16]=[CH:15][CH:14]=[CH:13]1>>[C:8]([CH:9]1[CH2:10][CH:13]2[O:12][CH:16]1[CH:15]=[CH:14]2)([O:7][CH3:5])=[O:11]
Reactant: C=CC(=O)OCC
Reactant: c1ccoc1
Agent: [Al+3]
Agent: [Cl-]
Product: COC(=O)C1CC2C=CC1O2
Reaction time: 1 h

Procedure:
4.5 g (0,033 Mol) AlCl3 are added to 100 g (1 Mol) ethylacrylate and dissolved with stirring. 68 g (1 Mol) furane is then added drop-wise, during cooling to 20° to 25° C. After one hour, the exothermic reaction is terminated, followed by stirring for one hour at 25° C. and 30 g water is added. The organic phase is separated. First, the non-converted furane and ethylacrylate is distilled off under a pressure of 10 Torr. The 2-carbomethoxy-7-oxabicyclo(2.2.1)hept-5-ene boils at 60° C. and is obtained in a yield of 67.2 g (40% theoretical).
Reaction SMILES: [OH-].[Na+].[CH3:3][C:4]([C:7]1[CH:8]=[C:9]([C:18]2[S:22][C:21](=[S:23])[NH:20][N:19]=2)[CH:10]=[C:11]([C:14]([CH3:17])([CH3:16])[CH3:15])[C:12]=1[OH:13])([CH3:6])[CH3:5].Br[CH2:25][C:26]([OH:28])=[O:27]>CO>[CH3:6][C:4]([C:7]1[CH:8]=[C:9]([C:18]2[S:22][C:21]([S:23][CH2:25][C:26]([OH:28])=[O:27])=[N:20][N:19]=2)[CH:10]=[C:11]([C:14]([CH3:15])([CH3:16])[CH3:17])[C:12]=1[OH:13])([CH3:3])[CH3:5]
Reactant: O=C(O)CBr
Reactant: CC(C)(C)c1cc(-c2n[nH]c(=S)s2)cc(C(C)(C)C)c1O
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CC(C)(C)c1cc(-c2nnc(SCC(=O)O)s2)cc(C(C)(C)C)c1O
Reaction time: 4 h

Procedure:
Aqueous 1M NaOH (12.4 ml, 0.0124 mole) is added to 0° C. solution of 5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-1,3,4-thiadiazole-2(3H)-thione (2.0 g, 0.0062 mole) in methanol (20 ml). This is followed by addition of 2-bromoacetic acid (0.95 g, 0.0068 mole) in one portion. The resulting mixture is allowed to stir four hours with periodic warming. The solution is concentrated in vacuo and the residue is partitioned between ether and water. The layers are separated and the aqueous phase is made acidic with aqueous 6M HCl. The aqueous layer is extracted with 1:1 ethyl acetate/ether (2×). The combined organic layers are washed with saturated aqueous NaCl, and dried over MgSO4. Filtration and concentration in vacuo provides a solid which is recrystallized from ethyl acetate/hexane to give 1.6 g (2.4 g theor., 68%) of [[5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-1,3,4-thiadiazole-2-yl[thio]acetic acid, mp 187.5° C.
Reaction SMILES: C([O:3][C:4]([C:6]1[C:7]([CH3:12])=[N:8][N:9]([CH3:11])[CH:10]=1)=O)C.CC(C[AlH]CC(C)C)C>O1CCCC1>[CH3:11][N:9]1[CH:10]=[C:6]([CH2:4][OH:3])[C:7]([CH3:12])=[N:8]1
Reactant: CCOC(=O)c1cn(C)nc1C
Agent: CC(C)C[AlH]CC(C)C
Solvent: C1CCOC1
Product: Cc1nn(C)cc1CO
Temperature: 0 °C
Reaction time: 2 h
Yield: 98.7 %

Procedure:
To a cooled solution (0° C.) of 1,3-dimethyl-1H-pyrazole-4-carboxylic acid ethyl ester (5.0 g, 29.7 mmol) in anhydrous tetrahydrofuran (1000 ml), is added a solution of DIBAL-H (95.1 ml, 95.1 mmol). The reaction mixture is stirred at 0° C. for 2 hours and then quenched with saturated aqueous sodium potassium tartrate and stirred for 2 hours. The layers are separated and the aqueous layer is extracted with ethyl acetate. The combined organic extracts are dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 1,3-dimethyl-1H-pyrazol-4-methanol (3.7 g, 100%) which is used without purification. 1H NMR (CDCl3): δ=7.22 (1H, s), 4.46 (2H, s), 3.74 (3H, s), 2.20 (3H, s).
Reaction SMILES: [CH2:1]([NH:11][C:12](=[O:29])[CH:13]=[CH:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][C:22](=[O:28])/[CH:23]=[CH:24]\[C:25]([OH:27])=[O:26])[CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH2:42]([N:44]([CH2:47][CH2:48]O)[CH2:45][CH3:46])[CH3:43]>O1CCCC1>[CH2:1]([NH:11][C:12](=[O:29])[CH:13]=[CH:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][C:22](=[O:28])/[CH:23]=[CH:24]\[C:25]([O:27][CH2:43][CH2:42][N:44]([CH2:47][CH3:48])[CH2:45][CH3:46])=[O:26])[CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCCCCCCCCCNC(=O)C=Cc1cccc(NC(=O)/C=C\C(=O)O)c1
Reactant: CCN(CC)CCO
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: CCCCCCCCCCNC(=O)C=Cc1cccc(NC(=O)/C=C\C(=O)OCCN(CC)CC)c1
Temperature: 25 °C

Procedure:
To a stirred solution of 800 mg. of N-decyl-3-(3-[cis-3-carboxypropenamido]phenyl)propenamide in 25 ml. of tetrahydrofuran is added 357 mg. of carbonyldiimidazole. The mixture is heated under reflux for 10 minutes, and then 258 mg. of 2-(N,N-diethylamino)ethanol is added. The mixture is again heated under reflux for 10 minutes, and then an additional 258 mg. of 2-(N,N-diethylamino)ethanol is added. The mixture is heated under reflux for 15 minutes and then it is cooled to room temperature. The solvent is removed by evaporation in vacuo, and the residue is dissolved in 75 ml. of ethyl acetate. The ethyl acetate solution is washed successively with water, 1 N sodium hydroxide, water and saturated sodium chloride solution. The ethyl acetate solution is then dried and evaporated in vacuo to give the title compound.
Reaction SMILES: [NH2:1][C:2]1[C:11]([F:12])=[CH:10][C:5]2[NH:6][C:7](=[O:9])[O:8][C:4]=2[CH:3]=1.[O:13]1[CH2:18][CH2:17][CH2:16][CH:15]([CH2:19][CH2:20][CH:21]=O)[CH2:14]1.C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[F:12][C:11]1[C:2]([NH:1][CH2:21][CH2:20][CH2:19][CH:15]2[CH2:16][CH2:17][CH2:18][O:13][CH2:14]2)=[CH:3][C:4]2[O:8][C:7](=[O:9])[NH:6][C:5]=2[CH:10]=1
Reactant: O=CCCC1CCCOC1
Reactant: Nc1cc2oc(=O)[nH]c2cc1F
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: O=c1[nH]c2cc(F)c(NCCCC3CCCOC3)cc2o1
Reaction time: 1 h
Yield: 38.1 %

Procedure:
To a solution of 6-amino-5-fluoro-benzoxazolin-2-one (2.1 g, 12.5 mmole) in methanol (80 ml) were added 3-(tetrahydro-2H-pyran-3-yl) propanal (1.95 g, 13.7 mmole) and acetic acid (1 ml) at room temperature, and then the mixture was stirred for 1 hour. Sodium cyanoborohydride (0.867 g, 13.7 mmole) was combined and stirring continued for 17 hours at room temperature. The reaction mixture was concentrated in vacuo, and the residue was treated with aqueous ammonium chloride solution. The organic substance was extracted with ethyl acetate/tetrahydrofuran. The extracts were washed with brine, dried over magnesium sulfate, and concentrated to afford crude product. This crude product was recrystallized from methanol to give 1.40 g of the title compound: m.p. 144°-145° C.
Reaction SMILES: [CH3:1][CH:2]([N:4]([CH:17]1[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:19][CH2:18]1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[N+:14]([O-])=O)=[S:6])[CH3:3].N.[H][H]>[Pd].[Pt].CO>[NH2:14][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=1[NH:7][C:5]([N:4]([CH:2]([CH3:3])[CH3:1])[CH:17]1[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:19][CH2:18]1)=[S:6]
Reactant: CC(C)N(C(=S)Nc1ccccc1[N+](=O)[O-])C1CCN(CCc2ccccc2)CC1
Reactant: [H][H]
Agent: [Pd]
Agent: [Pt]
Agent: N
Solvent: CO
Product: CC(C)N(C(=S)Nc1ccccc1N)C1CCN(CCc2ccccc2)CC1
Yield: 100 %

Procedure:
A mixture of 43 parts of N-(1-methylethyl)-N'-(2-nitrophenyl)-N-[1-(2-phenylethyl)-4-piperidinyl]thiourea and 800 parts of methanol, saturated with ammonia is hydrogenated at normal pressure and at room temperature with 6 parts of palladium-on-charcoal catalyst 10% and 6 parts of platinum-on-charcoal catalyst 5%. After the calculated amount of hydrogen is taken up, the catalysts are filtered off over Hyflo and the filtrate is evaporated, yielding 39 parts (100%) of N-(2-aminophenyl)-N'-(1-methylethyl)-N'-[1-(2-phenylethyl)-4-piperidinyl]thiourea as a residue.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:22]([CH3:30])[CH2:23][CH:24]([CH3:29])[CH2:25][CH2:26][CH:27]=[CH2:28])[C:10]([N:12]1[CH2:16][C@H:15]([OH:17])[CH2:14][C@H:13]1[C:18]([O:20]C)=[O:19])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1COCC1.[OH-].[Li+]>CO>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:22]([CH3:30])[CH2:23][CH:24]([CH3:29])[CH2:25][CH2:26][CH:27]=[CH2:28])[C:10]([N:12]1[CH2:16][C@H:15]([OH:17])[CH2:14][C@H:13]1[C:18]([OH:20])=[O:19])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: C=CCCC(C)C[C@@H](C)[C@H](NC(=O)OC(C)(C)C)C(=O)N1C[C@H](O)C[C@H]1C(=O)OC
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: C=CCCC(C)C[C@@H](C)[C@H](NC(=O)OC(C)(C)C)C(=O)N1C[C@H](O)C[C@H]1C(=O)O
Reaction time: 1.5 h
Yield: 83.8 %

Procedure:
To a 250 mL round-bottom flask equipped with a large stir bar was added (2S,4R)-methyl 1-((2S,3R)-2-((tert-butoxycarbonyl)amino)-3,5-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylate (10.9 g, 25.5 mmol), then THF (75 mL) and methanol (75 mL). To the stirred solution was added aq. lithium hydroxide (2.0 M, 38 mL, 77 mmol). The mixture was vigorously stirred for 1.5 h. The volatiles were removed organics were removed in vacuo and the resulting aqueous solution and solid residue was transfered to a 500 mL separatory funnel. The aqueous phase was adjusted to pH 2.5 using aqueous 2N HCl and was then extracted with EtOAc (3×100 mL). The combined organics were washed with aqueous sat. NaCl adjusted to pH 2.5 with aqueous HCl, dried over MgSO4; filtered; then concentrated in vacuo to afford (2S,4R)-1-((2S,3R)-2-((tert-butoxycarbonyl)amino)-3,5-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylic acid as a colorless foam (8.82 g, 84%). MS: MS m/z 413.2 (M++1).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:7])[CH2:5]Br)[CH3:2].[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2([C:19]#[N:20])[CH2:18][CH2:17][CH2:16]2)=[CH:11][CH:10]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.[Zn]>[NH2:20][C:19]([C:15]1([C:12]2[CH:11]=[CH:10][C:9]([Cl:8])=[CH:14][CH:13]=2)[CH2:16][CH2:17][CH2:18]1)=[CH:5][C:4]([O:3][CH2:1][CH3:2])=[O:7]
Reactant: N#CC1(c2ccc(Cl)cc2)CCC1
Reactant: CCOC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Zn]
Solvent: C1CCOC1
Product: CCOC(=O)C=C(N)C1(c2ccc(Cl)cc2)CCC1
Reaction time: 0.25 h

Procedure:
A suspension of zinc dust (25.5 g) (which had been activated by treatment with excess 3N hydrochloric acid followed by washing with water, ethanol and ether and drying) in dry tetrahydrofuran (250 ml) was stirred and heated under reflux while ethylbromoacetate (5 ml) was added dropwise. Stirring was continued for 15 minutes and 1-(4-chlorophenyl)cyclobutanecarbonitrile (15 g) was added. The mixture was heated under reflux and ethyl bromoacetate (60 g) was added over a period of 1 hour and the heating continued for a further 15 minutes. The mixture was then cooled and tetrahydrofuran (700 ml) and 25% aqueous potassium carbonate solution (300 ml) were added and the mixture was stirred for 15 minutes. The aqueous phase of the reaction mixture was separated, extracted with ether and the extracts combined with the organic phase of the reaction mixture, washed with brine and dried. Removal of the solvents gave an oil which was extracted with petroleum ether (b.p. 40°-60° C.). Removal of the solvent by evaporation gave ethyl 3-amino-3-[1-(4-chlorophenyl)cyclobutyl]acrylate.
Reaction SMILES: [N:1]([CH2:4][CH:5]1[CH2:14][CH2:13][C:12]2[C:7](=[C:8]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[Cl:22])[CH:9]=[C:10]([F:15])[CH:11]=2)[O:6]1)=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OCC)C.Cl>O1CCCC1.O.CC(O)C.CCCCCC>[ClH:22].[Cl:22][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[C:8]1[CH:9]=[C:10]([F:15])[CH:11]=[C:12]2[C:7]=1[O:6][CH:5]([CH2:4][NH2:1])[CH2:14][CH2:13]2
Reactant: [N-]=[N+]=NCC1CCc2cc(F)cc(-c3ccccc3Cl)c2O1
Agent: Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC(C)O
Solvent: C1CCOC1
Solvent: CCOCC
Product: NCC1CCc2cc(F)cc(-c3ccccc3Cl)c2O1
Temperature: 25 °C
Reaction time: 24 h
Yield: 134.4 %

Procedure:
To a solution of 2-azidomethyl-8-(2-chloro-phenyl)-6-fluoro-chroman (170 mg, 0.535 mmol) in tetrahydrofuran (5 mL) and water (0.5 mL) was added polymer-bound triphenylphosphine (˜3 mmol/g, 0.535 g, 1.605 mmol) and the reaction mixture stirred at room temperature for 24 hours. The brown suspension was then filtered through celite, the filter cake washed with ethyl acetate (50 mL) and the combined filtrates concentrated under reduced pressure to afford a yellow syrup. The product was dissolved in 2-propanol (1 mL) and diethyl ether (2 mL) and a solution of hydrogen chloride (1.0 M in diethyl ether, 0.51 mL, 0.51 mmol) added followed hexane (4 mL). The resulting white precipitate was filtered to afford 118 mg (67%) of {[8-(2-chlorophenyl)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]methyl}amine hydrochloride as a white solid. HRMS: calcd for C16H15ClFNO+H+, 292.08990. found (ESI, [M+H]+), 292.0903.
Reaction SMILES: [C:1]1(=O)CCCCC1.[OH:8][C:9]1[C:14]([CH3:15])=[C:13]([OH:16])[C:12]([OH:17])=[C:11](C)[C:10]=1[OH:19]>>[OH:19][C:10]1[C:9]([OH:8])=[C:14]([CH3:15])[CH:13]([OH:16])[C:12]([OH:17])([CH3:1])[CH:11]=1
Reactant: O=C1CCCCC1
Reactant: Cc1c(O)c(O)c(C)c(O)c1O
Product: CC1=C(O)C(O)=CC(C)(O)C1O

Procedure:
Attempts to form acetals from polyhydric phenols with two or more pairs of ortho-positioned hydroxy groups have been less successful. Soloway in U.S. Pat. No. 2,927,096 describes the preparation of resins from aldehydes and polyhydric phenols, such as 1,2,4,5-tetrahydroxybenzene and pentahydroxy benzene. Dallacker et al in Annalen, Band 719 (1968), pp. 112-118 describe the preparation benzo [1.2-d:4.5-d']bis[1.3] dioxoles of the formula (III) wherein R is hydrogen, methoxy or allyl, by heating the corresponding mono-dioxole (IV) with chlorobromomethane in dimethyl formamide in the presence of potassium carbonate ##STR1## Kaye describes in the 13th Annual Report on Research, Petroleum Research Fund (1968) how reaction of catechol with cyclohexanone in the presence of toluene sulphonic acid in benzene gives only a 49% yield of the acetal, with some alkylation of the aromatic ring. Under the same conditions, no reaction took place between cyclohexanone and 1,2,4,5-tetrahydroxy-3,6-dimethylbenzene. He showed, however, in Abstracts of Research Supported by the Petroleum Research Fund (1968) p. 21 that 1,2,4,5-tetrahydroxy-3,5-dimethylbenzene formed an acetal (V) when heated with dichlorodiphenyl methane. ##STR2##
Reaction SMILES: [CH3:1][O:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH:11]=[CH2:12].[OH-].[Na+].O.[CH:16]([Cl:19])(Cl)[Cl:17]>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1>[Cl:17][C:16]1([Cl:19])[CH2:12][CH:11]1[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=1[O:4][CH2:3][O:2][CH3:1]
Reactant: C=Cc1ccccc1OCOC
Reactant: ClC(Cl)Cl
Agent: CC[N+](CC)(CC)Cc1ccccc1
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Product: COCOc1ccccc1C1CC1(Cl)Cl
Temperature: 25 °C
Reaction time: 8 h
Yield: 84.4 %

Procedure:
In chloroform (12 mL) was dissolved 305 mg (1.86 mmol) of 1-(methoxymethoxy)-2-vinylbenzene obtained in Example 7(2), 5 mL (63 mmol) of 50% aqueous sodium hydroxide solution was added dropwise to the solution, and then, 54.1 mg (0.237 mmol) of benzyl(triethyl)ammonium chloride was added to the same and the resulting mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and extracted with chloroform. The organic layer was successively washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off and the obtained residue was purified by preparative thin-layer chromatography (available from MERCK CO., 1.05744, 3 plates were used, developed by ethyl acetate:hexane=1:2) to obtain 387 mg (1.57 mmol, Yield: 84.4%) of 1-(2,2-dichlorocyclopropyl)-2-(methoxymethoxy)benzene.
Reaction SMILES: [C:1]([OH:13])(=O)[CH2:2][NH:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5].P(Cl)(Cl)(Cl)(Cl)[Cl:15]>C(Cl)(=O)C>[C:1]([Cl:15])(=[O:13])[CH2:2][NH:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5]
Reactant: O=C(O)CNC(=O)c1ccccc1
Reactant: ClP(Cl)(Cl)(Cl)Cl
Solvent: CC(=O)Cl
Product: O=C(Cl)CNC(=O)c1ccccc1

Procedure:
The title compound was prepared by the chlorination of hippuric acid using phosphorus pentachloride in acetyl chloride according to a literature procedure, mp 124°-126° C. dec (McInally, I. et al J. Polymer Sci. Polymer Chem. Ed. (1977), 15, 2511, mp 125° C. dec.).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[CH3:12][C:13]([CH3:17])([CH3:16])[CH:14]=O.N1CCCC1>CO>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5](/[C:6](=[CH:12]\[C:13]([CH3:17])([CH3:16])[CH3:14])/[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1
Reactant: CC(C)(C)C=O
Reactant: O=C1Cc2ccc(Cl)cc2N1
Solvent: CO
Solvent: C1CCNC1
Product: CC(C)(C)/C=C1/C(=O)Nc2cc(Cl)ccc21

Procedure:
In a manner similar to the method described in example 1a, 6-chlorooxindole (0.88 g, 5 mmol) was reacted with 2,2-dimethyl-propionaldehyde (0.43 g, 5 mmol) (Aldrich), pyrrolidine (0.36 g, 5 mmol) in methanol to give a mixture of E- and Z-6-Chloro-3-(2,2-dimethyl-propylidene)-1,3-dihydro-indol-2-one. Purification by chromatography (EtOAc:hexanes=1:2) led to E-6-chloro-3-(2,2-dimethyl-propylidene)-1,3-dihydro-indol-2-one as an off-white foam (Yield 0.82 g, 70%).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:33]=[CH:32][CH:31]=[CH:30][C:8]=1[C:9]([NH:11][CH2:12][C@H:13]([CH:27]([CH3:29])[CH3:28])[CH2:14][C@H:15]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[C@@H:16]1[CH2:18][O:17]1)=[O:10].[NH:34]1[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1>C(O)(C)C>[OH:17][C@H:16]([C@@H:15]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:14][C@H:13]([CH2:12][NH:11][C:9](=[O:10])[C:8]1[CH:30]=[CH:31][CH:32]=[CH:33][C:7]=1[O:6][CH2:5][CH2:4][CH2:3][O:2][CH3:1])[CH:27]([CH3:29])[CH3:28])[CH2:18][N:34]1[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1
Reactant: C1CCNCC1
Reactant: COCCCOc1ccccc1C(=O)NC[C@@H](C[C@H](NC(=O)OC(C)(C)C)[C@@H]1CO1)C(C)C
Solvent: CC(C)O
Product: COCCCOc1ccccc1C(=O)NC[C@@H](C[C@H](NC(=O)OC(C)(C)C)[C@@H](O)CN1CCCCC1)C(C)C

Procedure:
A solution of 0.030 g of tert-butyl (3(S)-{[2-(3-methoxypropoxy)benzoylamino]methyl}-4-methyl-1(S)—(R)-oxiranylpentyl)carbamate in 0.60 ml of isopropanol and 0.050 ml of piperidine is stirred at 70° C. over 1 hour. The reaction mixture is concentrated by evaporation, and the residue is admixed with water and extracted with tert-butyl methyl ether (2×). The combined organic phases are washed with water and brine, dried over sodium sulphate and concentrated by evaporation. The title compound is obtained from the residue by means of flash chromatography (SiO2 60F) as a slightly yellowish oil. Rf=0.34 (200:20:1 dichloromethane-methanol-25% conc. ammonia); Rt=4.08 (gradient I).
Reaction SMILES: [CH3:1][CH:2]([CH:27]([CH3:30])[CH2:28][CH3:29])[C:3]([NH:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[CH:11][N:10]=[C:9]2[NH:16][CH:17]=[C:18]([C:23]([O:25][CH3:26])=[O:24])[C:19](OC)=[O:20])=[O:4]>C1(OC2C=CC=CC=2)C=CC=CC=1>[O:20]=[C:19]1[N:10]2[CH:11]=[N:12][C:13]3[CH:14]=[CH:15][C:6]([NH:5][C:3](=[O:4])[CH:2]([CH3:1])[CH:27]([CH3:30])[CH2:28][CH3:29])=[CH:7][C:8]=3[C:9]2=[N:16][CH:17]=[C:18]1[C:23]([O:25][CH3:26])=[O:24]
Reactant: CCC(C)C(C)C(=O)Nc1ccc2ncnc(NC=C(C(=O)OC)C(=O)OC)c2c1
Solvent: c1ccc(Oc2ccccc2)cc1
Product: CCC(C)C(C)C(=O)Nc1ccc2ncn3c(=O)c(C(=O)OC)cnc3c2c1
Temperature: 255 °C
Reaction time: 0.25 h
Yield: 7.5 %

Procedure:
A mixture of dimethyl [[6-(2,3-dimethylpentanamido)-4-quinazolinylamino]methylene]propanedioate (5.75 g) in diphenyl ether (28 ml) was stirred at 255° C. for 15 minutes and cooled to ambient temperature. The resulting solid was collected by filtration, washed with hexane, and dried. The crude crystals were chromatographed on silica gel with 4% methanol-chloroform. The product was recrystallized from a mixture of methanol and chloroform. There was obtained methyl 4-oxo-10-(2,3-dimethylpentanamido)-4H-pyrimido[1,2-C]quinazoline-3-carboxylate (0.4 g). Concentration of the mother liquor gave a crystalline residue, which was recrystallized from a mixture of chloroform and hexane to give additional 4.25 g of the same product.
Reaction SMILES: [CH:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C)C=O.[C-]#N.[Na+].CN(C)[CH2:19][CH2:20][C:21](=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C(O)C.O>[C:1]([CH:20]([C:21](=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH3:19])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=Cc1ccccc1
Reactant: CN(C)CCC(=O)c1ccccc1
Agent: [C-]#N
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCO
Product: CC(C(=O)c1ccccc1)C(=O)c1ccccc1

Procedure:
A solution of 21.2 g (0.2 mol) of benzaldehyde and 100 ml of absolute dimethylformamide is added dropwise in the course of 1/2 hour to a mixture of 9.8 g (0.2 mol) of NaCN and 100 ml of absolute dimethylformamide in a manner analogous to Example 3. Stirring is continued for 21/2 hours at 35° C. A solution of 26.6 g (0.15 mol) of dimethyl-β-benzoyl-ethylamine and 100 ml of absolute dimethylformamide is then slowly added dropwise in the course of 2 hours. Stirring is continued for 2 hours at the same temperature and water is then added to the reaction mixture in three times its quantity. The reaction product precipitates immediately. After cooling in an ice bath, the precipitated product is suction filtered and thoroughly washed with water. 34.3 g of crude product are isolated. 21.6 g (60.5% of the theory) of dibenzoyl ethane are isolated by recrystallisation from ethanol; m.p. 143° C.
Reaction SMILES: [CH3:1][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=O.Cl.[NH2:13][OH:14].C([O-])(=O)C.[Na+]>C(O)C.O>[CH3:1][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[N:13][OH:14]
Reactant: CC1Cc2ccccc2C1=O
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CC1Cc2ccccc2C1=NO
Temperature: 60 °C
Yield: 89.8 %

Procedure:
A mixture of 2-methyl-1-indanone (10 g, 0.0684 mol) and hydroxylamine hydrochloride (9.5 g, 0.1368 mol) in ethanol was stirred at 60° C., and a solution of sodium acetate (16.8 g, 0.2052 mol) in water added. The resulting mixture was then heated at reflux for 90 minutes, then cooled and the solid filtered. The crude product was washed with water and filtered to give 2-methyl-indan-1-one oxime (9.9 g, yield 81%), mp. 82-91° C., in 90% purity.
Reaction SMILES: [F:1][C:2]1[CH:23]=[CH:22][C:5]([NH:6][C:7]2[CH:19]=[C:18]([CH:20]=[CH2:21])[CH:17]=[CH:16][C:8]=2[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[CH:4][CH:3]=1.Br[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH3:31])[C:26]=1[CH3:32].C(N(CCCC)CCCC)CCC.F[B-](F)(F)F.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.CN(C)C(=O)C>[CH3:32][C:26]1[C:27]([CH3:31])=[CH:28][CH:29]=[CH:30][C:25]=1/[CH:21]=[CH:20]/[C:18]1[CH:17]=[CH:16][C:8]([C:9]([O:11][C:12]([CH3:15])([CH3:13])[CH3:14])=[O:10])=[C:7]([NH:6][C:5]2[CH:22]=[CH:23][C:2]([F:1])=[CH:3][CH:4]=2)[CH:19]=1
Reactant: Cc1cccc(Br)c1C
Reactant: C=Cc1ccc(C(=O)OC(C)(C)C)c(Nc2ccc(F)cc2)c1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Solvent: CCOC(C)=O
Solvent: CCCCN(CCCC)CCCC
Solvent: CC(=O)N(C)C
Product: Cc1cccc(/C=C/c2ccc(C(=O)OC(C)(C)C)c(Nc3ccc(F)cc3)c2)c1C
Temperature: 120 °C
Reaction time: 2 h

Procedure:
To N,N-dimethylacetamide 2.0 mL solution of tert-butyl 2-(4-fluoroanilino)-4-vinylbenzoate 0.10 g were added 3-bromo-o-xylene 0.064 mL, tributylamine 0.15 mL, palladium acetate 4.0 mg and tri-tert-butylphosphine tetrafluoroborate 3.0 mg at room temperature, and it was stirred under nitrogen atmosphere at 120° C. for 2 hours. Palladium acetate 4.0 mg and tri-tert-butylphosphine tetrafluoroborate 3.0 mg were added to it, and it was stirred under nitrogen atmosphere at 120° C. for 2 hours. 3-Bromo-o-xylene 0.064 mL, tributylamine 0.11 mL, palladium acetate 4.0 mg and tri-tert-butylphosphine tetrafluoroborate 3.0 mg were added to it, and it was stirred under nitrogen atmosphere at 120° C. for 5 hours. After the reaction mixture was cooled to room temperature, ethyl acetate and 10% citric acid aqueous solution were added to it. The organic layer was separated and collected, dried over anhydrous magnesium sulfate after sequential washing with 10% citric acid aqueous solution and saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [Fuji SILYSIA Chemical Ltd., PSQ100B(spherical type), eluent; hexane:ethyl acetate=10:1] to give tert-butyl 4-((E)-2-(2,3-dimethylphenyl)vinyl)-2-(4-fluoroanilino)benzoate.