Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:13]([OH:15])=[O:14])[CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[Br:16]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[Br:16][CH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([C:13]([OH:15])=[O:14])[CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:6][CH:7]=1
Reactant: Cc1ccc(C2(C(=O)O)CCCC2)cc1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: O=C(O)C1(c2ccc(CBr)cc2)CCCC1
Yield: 133.4 %

Procedure:
To a solution of 1-(4-methylphenyl)cyclopentane carboxylic acid tbutyl ester (2.00 g, 7.68 mmol) in CCl4 (80 mL) was added N-bromosuccinimide (1.37 g, 7.68 mmol) and benzoyl peroxide (0.050 g). This mixture was brought to reflux by heating, and maintained at reflux for 2 hours using a sun lamp (250 W). Additional N-bromosuccinimide (0.34 g, 1.9 mmol) was added, and after 20 minutes the solution was concentrated to 40 mL. The white precipitate was removed by filtration. The filtrate was concentrated to give 1-(4-bromomethylphenyl)cyclopentane carboxylic acid tbutyl ester (2.9 g, 100%) as a yellow oil which was used without additional purification.
Reaction SMILES: Br[C:2]1[CH:12]=[N:11][C:5]2[NH:6][CH2:7][CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1.[C:13]([O:17][CH2:18][CH3:19])(=[O:16])[CH:14]=[CH2:15].C(N(C(C)C)CC)(C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:18]([O:17][C:13](=[O:16])[C:14]([C:2]1[CH:12]=[N:11][C:5]2[NH:6][CH2:7][CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1)=[CH2:15])[CH3:19]
Reactant: Brc1cnc2c(c1)OCCCN2
Reactant: C=CC(=O)OCC
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CCC#N
Solvent: CCN(C(C)C)C(C)C
Product: C=C(C(=O)OCC)c1cnc2c(c1)OCCCN2
Temperature: 100 °C
Reaction time: 8 h
Yield: 63.2 %

Procedure:
A solution of 3-bromo-6,7,8,9-tetrahydro-5-oxa-1,9-diaza-benzocycloheptene (1.1 g, 4.80 mmol), ethyl acrylate (1.5 mL, 14.4 mmol) and diisopropylethylamine (2.5 mL, 14.4 mmol) in propionitrile (100 mL) was purged with an Argon stream for 10 min. Pd(OAc)2 (108 mg, 048 mmol) and P(o-tol)3 (292 g, 0.96 mmol) were added and the Argon purge was repeated. The mixture was stirred at 100° C. for 8 h under Argon. Upon cooling, the resultant mixture was filtered through celite; the filtrate was evaporated. The crude product was purified by chromatography (silica, 0-2% MeOH CH2Cl2) to afford the title compound (0.753 g, 63%). 1H NMR (300 MHz, DMSO-d6, δ): 7.98 (d, J=1.9 Hz, 1H), 7.52 (d, J=1.9 Hz, 1H), 7.51 (d, J=16 Hz, 1H), 6.83 (s, br, 1H), 6.42 (d, J=16 Hz, 1H), 4.15 (m, 4H), 3.34 (m, 2H), 1.98 (m, 2H), 1.25 (t, J=2 Hz, 3H).
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].Br[CH:6]1[CH2:10][C:9](=[O:11])[CH:8]=[CH:7]1>CN(C)C=O.C(OCC)(=O)C>[N:1]([CH:6]1[CH2:10][C:9](=[O:11])[CH:8]=[CH:7]1)=[N+:2]=[N-:3]
Reactant: O=C1C=CC(Br)C1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: [N-]=[N+]=NC1C=CC(=O)C1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 71.1 %

Procedure:
To a solution of sodium azide (2.12 g, 32.6 mmol) in dimethylformamide (15 mL) cooled to 0° C. was added dropwise with stirring 4-bromocyclopent-2-enone (DePuy, C. H.; Isaks, M.; Eilers, K. L.; Morris, G. F. J. Org. Chem. 1964. 29, 3503; 3.5 g, 21.7 mmol) in dimethyl-formamide (5 mL) over a period of 5 min. The reaction mixture was stirred at 0° C. for 30 min and diluted with ethyl acetate (20 mL). The reaction mixture was washed with water (2×20 mL) and brine (20 mL), dried (MgSO4), filtered, and concentrated in vacuo to furnish an oily residue. Purification of the crude oil by flash column chromatography (10-15% ethyl acetate in hexane) gave 1.9 g (71%) of 4-azidocyclopent-2-enone as a light-yellow oil.
Reaction SMILES: CC1(C)[O:7][C:6](=[O:8])[CH:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:4](=[O:15])O1.[CH3:17][C:18]1([CH3:30])[S:22][C@@H:21]2[C@H:23]([NH2:26])[C:24](=[O:25])[N:20]2[C@H:19]1[C:27]([OH:29])=[O:28]>>[CH3:17][C:18]1([CH3:30])[S:22][C@@H:21]2[C@H:23]([NH:26][C:4]([CH:5]([C:6]([OH:7])=[O:8])[C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=3)=[O:15])[C:24](=[O:25])[N:20]2[C@H:19]1[C:27]([OH:29])=[O:28]
Reactant: CC1(C)S[C@@H]2[C@H](N)C(=O)N2[C@H]1C(=O)O
Reactant: CC1(C)OC(=O)C(c2ccccc2)C(=O)O1
Product: CC1(C)S[C@@H]2[C@H](NC(=O)C(C(=O)O)c3ccccc3)C(=O)N2[C@H]1C(=O)O

Procedure:
When an equivalent amount of 2.2-tetramethylene-5-phenyl-1.3-dioxane-4.6-dione prepared in the example 3 is substituted for 2.2-dimethyl-5-phenyl-1.3-dioxane-4.6-dione and the reaction with 6-aminopenicillanic acid is carried out as disclosed in the example 1, 6-(α-carboxy-α-phenylacetamido)penicillanic acid (carbenicillin) is obtained.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([OH:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[C:17]1[N:22]=[CH:21][N:20]=[C:19]2[N:23]([C:26]3[CH:31]=[CH:30][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:28][C:27]=3[F:36])[N:24]=[CH:25][C:18]=12>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([O:13][C:17]2[N:22]=[CH:21][N:20]=[C:19]3[N:23]([C:26]4[CH:31]=[CH:30][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:28][C:27]=4[F:36])[N:24]=[CH:25][C:18]=23)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CS(=O)(=O)c1ccc(-n2ncc3c(Cl)ncnc32)c(F)c1
Reactant: CC(C)(C)OC(=O)N1CCC(O)C1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(Oc2ncnc3c2cnn3-c2ccc(S(C)(=O)=O)cc2F)C1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 67.8 %

Procedure:
A mixture of 3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (431 mg, 2.3 mmol) and sodium hydride (92 mg, 3.82 mmol) in THF (10 mL) was stirred for 30 minutes at room temperature. Then 4-chloro-1-(2-fluoro-4-methanesulfonyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidine (500 mg, 1.53 mmol) was added and stirred overnight at room temperature. The reaction mixture was quenched with water and the product extracted with ethyl acetate. The ethylacetate layer was dried over MgSO4, concentrated in vacuo, and purified by flash chromatography to afford compound A140 as a white solid (495 mg, 45%). Exact mass calculated for C21H24FN5O5S 477.15, found 478.2 (MH+).
Reaction SMILES: [F:1][C:2]1[C:11]2[CH:12]([CH2:14][NH:15][CH2:16][CH2:17][C@@H:18]3[O:22][C:21](=[O:23])[N:20]([C:24]4[CH:25]=[CH:26][C:27]5[S:32][CH2:31][C:30](=[O:33])[NH:29][C:28]=5[CH:34]=4)[CH2:19]3)[CH2:13][N:9]3[C:10]=2[C:5]([CH:6]=[CH:7][C:8]3=[O:35])=[CH:4][CH:3]=1.[Si:36]([O:43][CH2:44][CH:45]=O)([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37]>>[C:39]([Si:36]([CH3:38])([CH3:37])[O:43][CH2:44][CH2:45][N:15]([CH2:14][CH:12]1[C:11]2=[C:10]3[C:5](=[CH:4][CH:3]=[C:2]2[F:1])[CH:6]=[CH:7][C:8](=[O:35])[N:9]3[CH2:13]1)[CH2:16][CH2:17][C@@H:18]1[O:22][C:21](=[O:23])[N:20]([C:24]2[CH:25]=[CH:26][C:27]3[S:32][CH2:31][C:30](=[O:33])[NH:29][C:28]=3[CH:34]=2)[CH2:19]1)([CH3:42])([CH3:41])[CH3:40]
Reactant: CC(C)(C)[Si](C)(C)OCC=O
Reactant: O=C1CSc2ccc(N3C[C@H](CCNCC4Cn5c(=O)ccc6ccc(F)c4c65)OC3=O)cc2N1
Product: CC(C)(C)[Si](C)(C)OCCN(CC[C@H]1CN(c2ccc3c(c2)NC(=O)CS3)C(=O)O1)CC1Cn2c(=O)ccc3ccc(F)c1c32
Yield: 59 %

Procedure:
Starting from the compound of Example 4 and tert-butyldimethylsilyloxy-acetaldehyde and using procedure E, the title compound was obtained as a yellow foam (55 mg; 59% yield).
Reaction SMILES: Cl.[O:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7]([CH2:9][NH2:10])=[O:8].C(=O)(O)[O-].[Na+].C(OCC)(=O)C.[Cl:22][C:23]1[CH:31]=[CH:30][C:26]([C:27](Cl)=[O:28])=[CH:25][CH:24]=1>O>[Cl:22][C:23]1[CH:31]=[CH:30][C:26]([C:27]([NH:10][CH2:9][C:7]([C:3]2[O:2][CH:6]=[CH:5][CH:4]=2)=[O:8])=[O:28])=[CH:25][CH:24]=1
Reactant: NCC(=O)c1ccco1
Reactant: O=C(Cl)c1ccc(Cl)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Product: O=C(NCC(=O)c1ccco1)c1ccc(Cl)cc1
Yield: 98.1 %

Procedure:
To a mixture of 10 g of (2-furylcarbonyl)methylamine hydrochloride, 12.5 g of sodium bicarbonate, 200 ml of ethyl acetate and 100 ml of water are dropwise added 12.0 g of 4-chlorobenzoyl chloride at a temperature below 10° C. under stirring. The mixture is stirred at room temperature for 3 hours. Then, the ethyl acetate layer is collected, washed with water and dried. Said ethyl acetate layer is evaporated under reduced pressure to remove solvent. 16.0 g of N-(4-chlorobenzoyl)-(2-furylcabonyl)methylamine are thereby obtained. Yield: 98.2%
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[OH:8].C(N(C(C)C)C(C)C)C.[C:18](Cl)(=[O:20])[CH3:19]>ClCCl>[OH:8][C:7]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[NH:1][C:18](=[O:20])[CH3:19]
Reactant: Nc1cnccc1O
Reactant: CC(=O)Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)Nc1cnccc1O

Procedure:
3-Amino-pyridin-4-ol (15.0, 136 mmol) was suspended in 200 ml dichloromethane and N-ethyldiisopropylamine (82 ml, 477 mmol) was added. A solution of acetylchloride (10.6 ml, 150 mmol) in 150 ml dichloromethane was added dropwise at ambient temperature. The reaction mixture was stirred at reflux for 3 hrs and evaporated to dryness. The residue was stirred in methanol and filtered. The solvent was evaporated and the desired product was obtained as a white solid (7.2 g, 35%), MS: m/e=151.1 (M+H+).
Reaction SMILES: [CH2:1]([NH:4][C:5]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH3:16])=[CH:12][CH:13]=2)[C:8]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:7]([C:23]#[N:24])[N:6]=1)[CH:2]=[CH2:3].[N:25]1C=C[CH:28]=[CH:27][C:26]=1CN>>[CH3:16][O:15][C:11]1[CH:10]=[C:9]2[C:14](=[CH:13][CH:12]=1)[C:5]([NH:4][CH2:1][C:2]1[CH:3]=[CH:28][CH:27]=[CH:26][N:25]=1)=[N:6][C:7]([C:23]#[N:24])=[C:8]2[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: C=CCNc1nc(C#N)c(-c2ccccc2)c2cc(OC)ccc12
Reactant: NCc1ccccn1
Product: COc1ccc2c(NCc3ccccn3)nc(C#N)c(-c3ccccc3)c2c1

Procedure:
Following the procedure for 1-(allylamino)-6-methoxy-4-phenylisoquinoline-3-carbonitrile, using (pyridin-2-ylmethyl)amine in place of allylamine and heating for 35 min instead of 1 h, the title compound was synthesized.
Reaction SMILES: C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([CH3:21])=[C:18]([Pb+3])[CH:19]=1.[CH:22]12[CH2:29][CH:26]([CH2:27][CH2:28]1)[C:25](=[O:30])[CH2:24][C:23]2=[O:31].C1(C)C=CC=CC=1>C(Cl)(Cl)Cl.CN(C)C1C=CN=CC=1>[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([CH3:21])=[C:18]([CH:24]2[C:25](=[O:30])[CH:26]3[CH2:29][CH:22]([CH2:28][CH2:27]3)[C:23]2=[O:31])[CH:19]=1
Reactant: Cc1ccc(Cl)cc1[Pb+3]
Reactant: O=C1CC(=O)C2CCC1C2
Agent: CC(=O)[O-]
Agent: CN(C)c1ccncc1
Solvent: Cc1ccccc1
Solvent: ClC(Cl)Cl
Product: Cc1ccc(Cl)cc1C1C(=O)C2CCC(C2)C1=O
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 33.3 %

Procedure:
To a solution of 5-chloro-2-methylphenyllead triacetate (0.41 g, 0.80 mmol) in chloroform (4 ml) is added bicyclo[3.2.1]octane-2,4-dione (0.10 g, 0.72 mmol) and 4-dimethylaminopyridine (0.46 g, 3.62 mmol), and the reaction mixture is stirred at room temperature for 5 minutes. Next toluene (1 ml) is added, and the mixture is stirred at 80° C. for 1 hour (pre-heated oil bath). The reaction mixture is allowed to cool to room temperature, quenched with 1M hydrochloric acid, and the organic phase separated. The aqueous phase is further washed with dichloromethane (×2), and again the phases are separated. All organics are combined then evaporated under reduced pressure to give a crude oil. Purification by preparative reverse-phase HPLC furnishes 3-(5-chloro-2-methylphenyl)bicyclo[3.2.1]octane-2,4-dione (0.063 g, 33%) as a colourless gum.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]([C:12]2[CH:17]=[C:16]([O:18][CH2:19][C:20]#[CH:21])[CH:15]=[CH:14][C:13]=2[NH:22][CH2:23][C:24]2[N:25]=[N:26][N:27]([CH2:29][CH2:30][O:31][CH3:32])[N:28]=2)=O)=[CH:6][CH:5]=1)([CH3:3])[CH3:2].C([N:41]=[C:42]=[S:43])(=O)C1C=CC=CC=1>>[CH:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:12]3[C:13](=[CH:14][CH:15]=[C:16]([O:18][CH2:19][C:20]#[CH:21])[CH:17]=3)[N:22]([CH2:23][C:24]3[N:25]=[N:26][N:27]([CH2:29][CH2:30][O:31][CH3:32])[N:28]=3)[C:42](=[S:43])[N:41]=2)=[CH:6][CH:5]=1)([CH3:3])[CH3:2]
Reactant: O=C(N=C=S)c1ccccc1
Reactant: C#CCOc1ccc(NCc2nnn(CCOC)n2)c(C(=O)c2ccc(C(C)C)cc2)c1
Product: C#CCOc1ccc2c(c1)c(-c1ccc(C(C)C)cc1)nc(=S)n2Cc1nnn(CCOC)n1

Procedure:
The title compound (red foam) is prepared from (4-isopropyl-phenyl)-(2-{[2-(2-methoxy-ethyl)-2H-tetrazol-5-ylmethyl]-amino}-5-prop-2-ynyloxy-phenyl)-methanone and benzoylisothiocyanate as described for the preparation of example 111.
Reaction SMILES: [CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:11][CH:12]([OH:28])[CH2:13][NH:14][C:15](=[O:27])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH:22]2[CH2:26][CH2:25][CH2:24][NH:23]2)[CH:17]=1.C=O.[CH3:31]C(O)=O.[BH3-]C#N.[Na+]>CO>[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:11][CH:12]([OH:28])[CH2:13][NH:14][C:15](=[O:27])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH:22]2[CH2:26][CH2:25][CH2:24][N:23]2[CH3:31])[CH:17]=1
Reactant: CC(=O)O
Reactant: O=C(NCC(O)CN1CCc2ccccc2C1)c1cccc(C2CCCN2)c1
Agent: C=O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: CN1CCCC1c1cccc(C(=O)NCC(O)CN2CCc3ccccc3C2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 16.8 %

Procedure:
To a solution of N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-3-(pyrrolidin-2-yl)benzamide (20 mg, 0.13 mmol) in MeOH (20 mL) was added HCHO (1 mL) and AcOH (0.05 mL). The reaction mixture was stirred at room temperature for 30 min at which time NaBH3CN (200 mg, 3.22 mmol) was added. The reaction mixture was stirred at room temperature for 2 h. The solvent was removed and the crude product was purified by prep-HPLC to give the desired product (8.5 mg, Yield 16.8%). 1H NMR (CD3OD, 400 MHz): δ 7.80 (brs, 1H), 7.67 (d, J=7.6 Hz, 1H), 7.52 (d, J=7.6 Hz, 1H), 7.35-7.41 (m, 1H), 7.09-7.15 (m, 3H), 7.09-7.15 (m, 1H), 7.02-7.08 (m, 1H), 4.10-4.16 (m, 1H), 3.73-3.81 (m, 2H), 3.49-3.58 (m, 2H), 3.20-3.28 (m, 1H), 3.08-3.16 (m, 1H), 2.84-2.97 (m, 4H), 2.64-2.75 (m, 2H), 2.33-2.40 (m, 1H), 2.20-2.27 (m, 1H), 2.16 (s, 3H), 1.95-2.05 (m, 1H), 1.77-1.93 (m, 2H). LCMS (m/z): 394.1 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:8])[CH2:4][N+:5]([O-:7])=[O:6].[CH:9](OCC)(OCC)[O:10][CH2:11][CH3:12].C(OC(=O)C)(=O)C>>[CH3:1][O:2][C:3](=[O:8])[C:4]([N+:5]([O-:7])=[O:6])=[CH:9][O:10][CH2:11][CH3:12]
Reactant: CCOC(OCC)OCC
Reactant: COC(=O)C[N+](=O)[O-]
Solvent: CC(=O)OC(C)=O
Product: CCOC=C(C(=O)OC)[N+](=O)[O-]
Yield: 84.5 %

Procedure:
A 12-l. three-necked flask, equipped with a thermometer, mechanical stirrer and a reflux condenser was charged under an atmosphere of nitrogen with 746 g (6.26 moles) of nitroacetic acid methylester, 1392 g (9.4 moles) of triethyl orthoformate and 1.92 l of acetic anhydride. The mixture was stirred and heated at reflux for 23 hours. The volatile components were distilled off first at atmospheric pressure (pot temperature up to 100° C., then at aspirator vacuum and finally at 0.17 mmHg (pot temperature up to 70°), leaving 926 g (84%) of crude alpha-nitro-beta-ethoxyacrylic acid methylester as an orange oil.
Reaction SMILES: [CH2:1]([Mg]Cl)[CH3:2].[CH3:5][O:6][C:7]1[CH:22]=[CH:21][C:10]([C:11]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[O:12])=[CH:9][CH:8]=1.[Cl-].[NH4+]>C1COCC1>[CH3:20][O:19][C:16]1[CH:17]=[CH:18][C:13]([C:11]([C:10]2[CH:9]=[CH:8][C:7]([O:6][CH3:5])=[CH:22][CH:21]=2)([OH:12])[CH2:1][CH3:2])=[CH:14][CH:15]=1
Reactant: CC[Mg]Cl
Reactant: COc1ccc(C(=O)c2ccc(OC)cc2)cc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CCC(O)(c1ccc(OC)cc1)c1ccc(OC)cc1
Temperature: 4 °C
Reaction time: 1 h
Yield: 54.5 %

Procedure:
Into a reactor were introduced 31.9 mL (30.9 mol; 0.97 M THF solution) of ethylmagnesium chloride and 20 mL of THF under a nitrogen atmosphere. The contents were cooled to 4° C. Thereafter, a solution prepared by mixing 5.00 g (20.6 mmol) of 4,4′-dimethoxybenzophenone with 20 mL of THF was gradually added dropwise thereto, and this mixture was stirred at room temperature for 1 hour. Saturated aqueous ammonium chloride solution was added to the reaction mixture. The organic layer was extracted with ethyl acetate, and the extract was dried with anhydrous magnesium sulfate and then concentrated under reduced pressure. The concentrate was purified by column chromatography to obtain 3.06 g (55%) of the target compound as a light-yellow oily substance.
Reaction SMILES: [O-]CC.[Na+].[Cl:5][C:6]1[CH:25]=[CH:24][C:9]([C:10]([NH:12][CH:13]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[O:11])=[CH:8][CH:7]=1.Br[CH2:27][C:28]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[NH:31][C:30](=[O:38])[CH:29]=1>C(O)C>[Cl:5][C:6]1[CH:7]=[CH:8][C:9]([C:10]([NH:12][C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])([CH2:27][C:28]2[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[NH:31][C:30](=[O:38])[CH:29]=2)[C:19]([O:21][CH2:22][CH3:23])=[O:20])=[O:11])=[CH:24][CH:25]=1
Reactant: CCOC(=O)C(NC(=O)c1ccc(Cl)cc1)C(=O)OCC
Reactant: O=c1cc(CBr)c2ccccc2[nH]1
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)C(Cc1cc(=O)[nH]c2ccccc12)(NC(=O)c1ccc(Cl)cc1)C(=O)OCC
Reaction time: 1 h

Procedure:
100 ml of anhydrous ethyl alcohol and 2.23 g of sodium ethoxide (96%) were added to a 500 ml flask, and the mixture was cooled down to below 5° C. After adding 7.91 g of diethyl 4-chlorobenzamidomalonate, the resulting solution was stirred at below 5° C. for one hour. 5.00 g of 4-bromomethylquinolinon was added to the mixture and the resulting solution was stirred at the room temperature for 16 hours to produce an intermediate, ethyl 2-(4-chlorobenzoylamino)-2-ethoxycarbonyl-3-[2(1H)-quinolinon-4-yl]propionate. After the completion of the reaction, 2.71 g of sodium hydroxide (93%) was added to the above solution, which was then stirred at the room temperature for about 2 hours. Subsequently, the resulting solution was warmed to about 60° C. and stirred for 4 hours to complete the reaction. The concentrated hydrochloric acid were added to the residue for crystallization. The crystal thus obtained was filtered and then subjected to recrystallization with DMF and water to yield 7.15 g (91.78%) of 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl]propionic acid.
Reaction SMILES: [CH2:1]([S:5][C:6]1[S:7][C:8]2[CH:14]=[C:13]([S:15]([OH:18])(=O)=[O:16])[CH:12]=[CH:11][C:9]=2[N:10]=1)[CH2:2][CH2:3][CH3:4].O=S(Cl)[Cl:21]>>[CH2:1]([S:5][C:6]1[S:7][C:8]2[CH:14]=[C:13]([S:15]([Cl:21])(=[O:18])=[O:16])[CH:12]=[CH:11][C:9]=2[N:10]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCSc1nc2ccc(S(=O)(=O)O)cc2s1
Reactant: O=S(Cl)Cl
Product: CCCCSc1nc2ccc(S(=O)(=O)Cl)cc2s1
Reaction time: 1 h

Procedure:
2-mercaptobenzthiazol (83.4 g, 0.5 mol) was dispersed in 100 mL of methanol, and added a solution containing 24 g of NaOH in 50 mL of H2O. When 2-mercaptobenzthiazol was completely dissolved, n-butylbromide (54 mL, 0.5 mol) was added and the reaction solution was refluxed for 12 hours. Then, methanol was removed from the solution under reduced pressure and 300 mL of ethylacetate was added to the solution which was then washed with H2O and 1M K2CO3 in a sequential order. The separated organic solution was dried over MgSO4 and then distilled under reduced pressure to give about 100 g of pure 2-n-butylthio-6-benzthiazol (89%), which was subsequentially transferred to a flask of 500 mL without further purification and cooled down to a temperature of 0° C. Chlorosulfonic acid (130 g, 2.5 equi.) was slowly added into the flask. The reaction solution was reacted for 24 hours at about 110° C. When starting material was completely exhausted, the reaction solution was cooled down to room temperature (RT) and stirred vigorously after adding ice water. Then, the solid product was obtained by filtering. The filtered solid was treated with ethylacetate (300 mL) followed by stirring for 1 hour. The undissolved solid was filtered and washed with ethylacetate to give 2-n-butylthio-6-benzthiazolsulfonic acid (30 g). The filtrated ethylacetate solution was treated with 5 g of activated carbon and MgSO4 and stirred for 1 hour. Then, the ethylacetate solution was filtered on activated carbon and MgSO4 again and dried under reduced pressure to remove the solvent, to give the titled compound, 2-n-butylthio-6-benzthiazolsulfonyl chloride (about 60 g) in a solid form. The titled compound was treated with n-hexane (150 mL), followed by stirring for 1 hour. After filtering, pure 2-n-butylthio-6-benzthiazolsulfonyl chloride (55 g) was obtained. A 30 mL of SOCl2 as solvent and as reagent was added to 2-n-butylthio-6-benzthiazolsulfonic acid (30 g) obtained above. The reaction solution was refluxed for 5 hours, dried under reduced pressure, and then, treated with H2O. The solid product was obtained by filtering. The solid was stirred with ethylacetate (100 mL) for 1 hour. The ethylacetate solution was treated with 5 g of activated carbon and MgSO4 and stirred for 1 hour. The solution after filtering on activated carbon and MgSO4 was dried under reduced pressure to remove the solvent, to give the titled compound, 2-n-butylthio-6-benzthiazolsulfonyl chloride (about 30 g) in a solid form. The compound was purified with n-hexane as described above, to give a pure 2-n-butylthio-6-benzthiazolsulfonyl chloride (25 g). Consquently, about 80 g of titled compound (about 56%) was prepared by two processes.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][NH2:13])[CH2:9][CH:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[C:6]=2[CH:20]=1.[CH:21](OCC)(OCC)OCC>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:21]=[N:13][N:12]=[C:10]3[CH2:9][CH:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[C:6]=2[CH:20]=1
Reactant: NNC1=Nc2ccc(Br)cc2C(c2ccccn2)=CC1
Reactant: CCOC(OCC)OCC
Product: Brc1ccc2c(c1)C(c1ccccn1)=CCc1nncn1-2

Procedure:
In analogy to Example 16(b), by reacting 7-bromo-2-hydrazino-5-(2-pyridyl)-3H-1-benzazepine with triethyl orthoformate there is obtained 8-bromo-6-(2-pyridyl)-4H-s-triazolo[4,3-a][1]benzazepine of melting point 219°.
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[C:11]2[CH:10]=[C:9]([C:12](Cl)=[O:13])[CH:8]=[CH:7][C:6]=2[CH2:5][CH2:4][CH2:3]1.[OH:16][C:17]1[CH:26]=[C:25]([C:27]#[C:28][Si](C)(C)C)[CH:24]=[CH:23][C:18]=1[C:19]([O:21][CH3:22])=[O:20].[Al+3].[Cl-].[Cl-].[Cl-]>ClCCl>[OH:16][C:17]1[CH:26]=[C:25]([C:27]#[C:28][C:12](=[O:13])[C:9]2[CH:8]=[CH:7][C:6]3[CH2:5][CH2:4][CH2:3][C:2]([CH3:15])([CH3:1])[C:11]=3[CH:10]=2)[CH:24]=[CH:23][C:18]=1[C:19]([O:21][CH3:22])=[O:20]
Reactant: CC1(C)CCCc2ccc(C(=O)Cl)cc21
Reactant: COC(=O)c1ccc(C#C[Si](C)(C)C)cc1O
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: COC(=O)c1ccc(C#CC(=O)c2ccc3c(c2)C(C)(C)CCC3)cc1O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
12 g (54 mmol) of 8,8-dimethyl-5,6,7,8-tetrahydro-2-naphthoyl chloride, 14.7 g (59 mmol) of methyl 2-hydroxy-4-trimethylsilylethynylbenzoate (prepared in Example 5(a) of patent EP 0,661,258) and 200 ml of dichloromethane are introduced into a round-bottomed flask. 21.6 g (162 mmol) of AlCl3 are added portionwise at 0° C. and the mixture is stirred at room temperature for 8 hours. The reaction medium is poured into ice and extracted with dichloromethane, and the organic phase is separated out after settling has taken place, dried over magnesium sulphate and evaporated. The residue obtained is purified by chromatography on a column of silica eluted with a mixture of dichloromethane and hexane (50/50). 12.5 g (64%) of the expected product are collected, with a melting point of 114-6° C.