Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:12]([NH2:18])[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].[CH:19]1[CH:24]=[C:23]([CH:25]=[O:26])[C:22]([CH:27]=O)=[CH:21][CH:20]=1.CCOCC>C(O)(=O)C>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:12]([N:18]2[CH2:27][C:22]3[C:23](=[CH:24][CH:19]=[CH:20][CH:21]=3)[C:25]2=[O:26])[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2]
Reactant: CCOc1cc(C(N)CS(C)(=O)=O)ccc1OC
Reactant: O=Cc1ccccc1C=O
Solvent: CCOCC
Solvent: CC(=O)O
Product: CCOc1cc(C(CS(C)(=O)=O)N2Cc3ccccc3C2=O)ccc1OC
Yield: 69.4 %

Procedure:
A stirred mixture 1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethylamine (100 mg, 0.37 mmol) and 1,2-phthalic dicarboxaldehyde (49 mg, 0.37 mmol) in acetic acid (2 mL) was heated to reflux for 15 min. Removal of solvent in vacuo and chromatography gave an oil which was stirred with ether (2 mL). The resulting suspension was filtered to yield 2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]isoindolin-1-one as a light yellow solid (100 mg, 70% yield): mp, 130.0-134.0° C.; 1H NMR (CDCl3) δ 1.45 (t, J s=7 Hz, 3H, CH3), 2.96 (s, 3H, CH3), 3.70 (dd, J=4.5, 14.7, Hz, 1H, CHH), 3.86 (s, 3H, CH3), 4.07 (q, J=6.9 Hz, 2H, CH2), 4.25 (d, J=16.5 Hz, 1H, CHH), 4.31 (dd, J=10.3, 14.5 Hz, 1H, CHH), 4.46 (d, J=16 HZ, 1H, CHH), 5.71 (dd, J=4.5, 10.3 Hz, 1H, NCH), 6.84-7.01 (m, 3H, Ar), 7.38-7.56 (m, 3H, Ar), 7.85 (d, J=6.9 Hz, 1H, Ar); 13C NMR (CDCl3) δ 14.65, 41.33, 46.27, 52.33, 55.95, 56.00, 65.56, 111.45, 112.28, 119.30, 122.85, 123.85, 128.13, 129.89, 131.80, 132.27, 141.26, 148.88, 149.62, 169.09; Anal Calcd for C20H23NO5S: C, 61.68; H, 5.95; N, 3.60. Found: C, 61.68, H, 6.06; N, 3.62.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][C:3]=1[OH:13].[Cl:14][C:15]1[CH:23]=[N:22][CH:21]=[CH:20][C:16]=1[C:17](O)=[O:18].CCN=C=NCCCN(C)C.N1C=CC=CC=1>O>[Cl:14][C:15]1[CH:23]=[N:22][CH:21]=[CH:20][C:16]=1[C:17]([NH:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([C:9]([F:12])([F:10])[F:11])=[CH:4][C:3]=1[OH:13])=[O:18]
Reactant: Nc1cc(Cl)c(C(F)(F)F)cc1O
Reactant: O=C(O)c1ccncc1Cl
Agent: CCN=C=NCCCN(C)C
Solvent: c1ccncc1
Solvent: O
Product: O=C(Nc1cc(Cl)c(C(F)(F)F)cc1O)c1ccncc1Cl
Temperature: 80 °C
Yield: 69.9 %

Procedure:
A mixture of 0.60 g of 2-amino-4-chloro-5-trifluoromethylphenol, 0.43 g of 3-chloroisonicotinic acid, 0.67 g of WSC and 5 ml of pyridine was stirred while heating at 80° C. for three hours. The reaction mixture was cooled to room temperature, and then water was added, followed by extraction with ethyl acetate three times. The combined organic layers were washed with water and a saturated sodium chloride solution, dried anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 0.67 g of 3-chloro-N-[5-chloro-2-hydroxy-4-trifluoromethylphenyl]isonicotinamide.
Reaction SMILES: [NH2:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][NH:7][S:8]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])(=[O:10])=[O:9])=[CH:4][CH:3]=1.N1C=CC=CC=1.[C:27]1([O:33][C:34](Cl)=[O:35])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>O1CCCC1.C(#N)C>[C:27]1([O:33][C:34](=[O:35])[NH:1][C:2]2[CH:20]=[CH:19][C:5]([CH2:6][NH:7][S:8](=[O:10])(=[O:9])[NH:11][C:12]([O:13][C:14]([CH3:16])([CH3:17])[CH3:15])=[O:18])=[CH:4][CH:3]=2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: O=C(Cl)Oc1ccccc1
Reactant: CC(C)(C)OC(=O)NS(=O)(=O)NCc1ccc(N)cc1
Solvent: C1CCOC1
Solvent: c1ccncc1
Solvent: CC#N
Product: CC(C)(C)OC(=O)NS(=O)(=O)NCc1ccc(NC(=O)Oc2ccccc2)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 49.1 %

Procedure:
tert-Butyl N-(4-aminobenzyl)sulfamoylcarbamate (86 mg, 0.285 mmol) was dissolved in a tetrahydrofuran/acetonitrile (1:1 mixture). Pyridine (0.03 mL, 0.342 mmol) was added, followed by addition of phenylchloroformate (0.04 mL, 0.3 mmol) at 0° C. The mixture was stirred at 0° C. for 30 min and further 30 min at room temperature. The reaction mixture was extracted with ethyl acetate and washed with brine. Drying over magnesium sulfate, evaporation of the ethyl acetate and purification by column chromatography gave the N-[4-[[(tert-butoxycarbonyl-sulfamoyl)amino]methyl]-phenyl]-carbamic acid phenyl ester (59 mg, 49%).
Reaction SMILES: [C-:1]#[N:2].[K+].[NH:4]1[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1.[O:10]1[C:14]2([CH2:19][CH2:18][CH:17]([CH:20]=O)[CH2:16][CH2:15]2)[O:13][CH2:12][CH2:11]1.C(OCC)(=O)C>C(O)C.O>[O:7]1[CH2:8][CH2:9][N:4]([CH:20]([CH:17]2[CH2:16][CH2:15][C:14]3([O:10][CH2:11][CH2:12][O:13]3)[CH2:19][CH2:18]2)[C:1]#[N:2])[CH2:5][CH2:6]1
Reactant: C1COCCN1
Reactant: [C-]#N
Reactant: O=CC1CCC2(CC1)OCCO2
Agent: [K+]
Solvent: CCO
Solvent: CCOC(C)=O
Solvent: O
Product: N#CC(C1CCC2(CC1)OCCO2)N1CCOCC1
Reaction time: 72 h

Procedure:
KCN (0.17 mol) and morpholine (14.7 g, 0.17 mol) were added to a solution of 1,4-dioxa-spiro[4.5]decane-8-carboxaldehyde (0.141 mol) in a mixture of ethanol (141 ml) and water (70 ml), and stirring was carried out for 72 h at 25° C. After addition of ethyl acetate (700 ml), the organic phase was separated off and washed in succession with water (4×150 ml) and aqueous FeSO4 solution (4×150 ml). The organic phase was separated off and dried over Na2SO4 and then filtered off. The solvent was removed in vacuo, and the product was used in the next stage without being purified further.
Reaction SMILES: [CH:1](=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].[CH2:10]([O:12]C(O)O)[CH3:11].Cl.[CH2:17](O)[CH3:18]>>[CH2:17]([O:9][CH:1]([O:12][CH2:10][CH3:11])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4])[CH3:18]
Reactant: CCOC(O)O
Reactant: CCO
Reactant: O=Cc1ccccc1O
Agent: Cl
Product: CCOC(OCC)c1ccccc1O

Procedure:
A mixture of 122 parts of salicylaldehyde, 180 parts of orthoformic acid ethyl ester and 120 parts of anhydrous ethanol was mixed with 1 ml of concentrated hydrochloric acid, whereupon the whole heated up spontaneously. After a short time, the solution was heated to the boil and then evaporated under vacuum, and the residue distilled under a high vacuum. The product passed over at 80°C under 0.15mm Hg pressure.
Reaction SMILES: F[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[O:10]1[C:14]2([CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[O:13][CH2:12][CH2:11]1.C([O-])([O-])=O.[K+].[K+].C(#N)C>O.C(OCC)C>[O:10]1[C:14]2([CH2:19][CH2:18][N:17]([C:8]3[CH:9]=[CH:2][CH:3]=[CH:4][C:5]=3[C:6]#[N:7])[CH2:16][CH2:15]2)[O:13][CH2:12][CH2:11]1
Reactant: N#Cc1ccc(F)cc1
Reactant: C1CC2(CCN1)OCCO2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Solvent: CCOCC
Product: N#Cc1ccccc1N1CCC2(CC1)OCCO2
Temperature: 25 °C
Reaction time: 72 h
Yield: 66.5 %

Procedure:
A mixture of 10 g (0.0825 mol) p-fluorobenzonitrile, 47 g (0.382 mol) of 1,4-dioxa-8-azaspiro[4.5]decane, 17 g (0.123 mol) of K2CO3, and 100 ml of acetonitrile is stirred at 90°-100° C. for three days. The reaction mixture is allowed to cool to ambient temperature, diluted with water and extracted with methylene chloride. The combined extracts are washed with brine, dried over Na2SO4, and concentrated in vacuo to give a pasty solid. Trituration with ethyl ether furnishes 13.4 g (67%) of title compound: m.p. 134°-135° C.; IR (KBr) 2210 and 1600 cm-1 ; NMR (CDCl3) δ 7.48 (d, 2H), 6.88 (d, 2H), 4.0 (s, 4H), 3.58-3.40 (m, 4H), and 1.90-1.70 (m, 4H).
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:14]=[CH:13][C:9]([C:10]([OH:12])=O)=[CH:8][C:7]=1[CH2:15][C:16]([O:18][CH3:19])=[O:17])[CH:2]([CH3:4])[CH3:3].C(Cl)(=O)C(Cl)=O.[Cl-].[Al+3].[Cl-].[Cl-].[CH2:30]([O:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([O:41][CH2:42][CH:43]([CH3:45])[CH3:44])[CH:36]=1)[CH:31]([CH3:33])[CH3:32]>C(Cl)Cl.O.C(Cl)(Cl)Cl>[CH2:42]([O:41][C:37]1[CH:36]=[C:35]([O:34][CH2:30][CH:31]([CH3:33])[CH3:32])[CH:40]=[CH:39][C:38]=1[C:10]([C:9]1[CH:13]=[CH:14][C:6]([O:5][CH2:1][CH:2]([CH3:3])[CH3:4])=[C:7]([CH2:15][C:16]([O:18][CH3:19])=[O:17])[CH:8]=1)=[O:12])[CH:43]([CH3:45])[CH3:44]
Reactant: CC(C)COc1cccc(OCC(C)C)c1
Reactant: COC(=O)Cc1cc(C(=O)O)ccc1OCC(C)C
Agent: O=C(Cl)C(=O)Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Product: COC(=O)Cc1cc(C(=O)c2ccc(OCC(C)C)cc2OCC(C)C)ccc1OCC(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 57.5 %

Procedure:
In 6 ml of methylene chloride is dissolved 0.62 g of 4-isobutoxy-3-(2-methoxy-2-oxoethyl)benzoic acid. After adding 0.25 ml of oxalyl chloride at ambient temperature, the mixture thus obtained is stirred at ambient temperature for one hour. Then, 0.62 g of aluminum chloride and 0.77 g of 1,3-diisobutoxybenzene are successively added at 5-10° C., and the mixture is stirred at ambient temperature for one hour. The reaction mixture is added to a mixture of chloroform and water, and the organic layer is separated. The organic layer is successively washed with water and saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure. The residue thus obtained is purified by silica gel column chromatography [eluent; n-hexane:ethyl acetate=95:5] to obtain 0.63 g of methyl 2-[5-(2,4-diisobutoxybenzoyl)-2-isobutoxyphenyl]acetate as a colorless oily product.
Reaction SMILES: [CH:1]1[N:2]=[CH:3][N:4]2[C:9]=1[CH2:8][CH2:7][NH:6][C:5]2=[O:10].[Br:11][CH2:12][CH3:13].C(#N)C>CN(C=O)C>[Br-:11].[CH2:12]([N+:2]1[CH:1]=[C:9]2[N:4]([C:5](=[O:10])[NH:6][CH2:7][CH2:8]2)[CH:3]=1)[CH3:13]
Reactant: O=C1NCCc2cncn21
Reactant: CCBr
Solvent: CN(C)C=O
Solvent: CC#N
Product: CC[n+]1cc2n(c1)C(=O)NCC2
Product: [Br-]
Temperature: 180 °C

Procedure:
A suspension of 7,8-dihydroimidazo[1,5-c]pyrimidin-5(6H)-one, obtained in step I as describe above (500 mg; 3.65 mmol; 1 eq), and bromoethane (816 μl; 10.94 mmol; 3 eq) in DMF (7 ml) is divided in two equals fractions and heated under microwave irradiation at 180° C. for 20 min. The reaction mixtures are combined and acetonitrile (15 ml) is added. The resulting precipitate is filtered, washed with acetonitrile and dried under vacuum, affording the title compound that is used in the next step without further purification (118.3 mg; 13%).
Reaction SMILES: [CH:1]([N:14]1[CH2:19][CH2:18][NH:17][C@@H:16]([CH3:20])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24].[CH2:30](N(CC)CC)C>CC#N>[CH:1]([N:14]1[CH2:15][CH2:16][N:17]([CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18][C@@H:19]1[CH3:30])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:1]([N:14]1[CH2:19][CH2:18][N:17]([CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C@@H:16]([CH3:20])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C[C@H]1CN(C(c2ccccc2)c2ccccc2)CCN1
Reactant: CC(C)(C)OC(=O)CBr
Reactant: CCN(CC)CC
Solvent: CC#N
Product: C[C@H]1CN(C(c2ccccc2)c2ccccc2)CCN1CC(=O)OC(C)(C)C
Product: C[C@H]1CN(CC(=O)OC(C)(C)C)CCN1C(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of a mixture of(s)-1-benzhydryl-2-methylpiperazine and (S)-1-benzhydryl-3-methylpiperazine (490 mg, 1.839 mmol) in 25 mL of MeCN was added tert-butyl bromoacetate (356 μL, 2.207 mmol), followed by slow addition of triethylamine (384 μl, 2759 μmol). The reaction mixture was stirred at rt overnight. The solution was evaporated to dryness and the residual was submitted to flash chromatography (SiO2, DCM to DCM/EtOAc=100:3 to 100:5 to 100:10) to give (S)-tert-butyl 2-(4-benzhydryl-3-methylpiperazin-1-yl)acetate as a colorless oil and (S)-tert-butyl 2-(4-benzhydryl-2-methylpiperazin-1-yl)acetate as a colorless oil.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH3:23])[CH:13]([OH:22])[C:14]([CH3:21])([CH3:20])[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)S(O[Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])(=O)=O.CC1C=CC=C(C)N=1.O>C1COCC1>[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH3:23])[CH:13]([O:22][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[C:14]([CH3:21])([CH3:20])[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Reactant: CCOC(=O)C(C)(C)C(O)[C@H](C)NC(=O)OCc1ccccc1
Solvent: Cc1cccc(C)n1
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)C(C)(C)C(O[Si](C)(C)C(C)(C)C)[C@H](C)NC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 94 %

Procedure:
A solution of ethyl(4S)-4-{[(benzyloxy)carbonyl]amino}-2,2-dimethyl-3-hydroxypentanoate (720 mg) in THF (20 mL) was cooled to 0° C., tert-butyl(dimethyl)silyl trifluoromethanesulfonate (0.589 mL) and 2,6-dimethylpyridine (0.390 mL) were added, and the mixture was stirred at room temperature for 3 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=1/0→1/1) to give ethyl(4S)-4-{[(benzyloxy)carbonyl]amino}-3-(tert-butyldimethylsilyloxy)-2,2-dimethylpentanoate as a colorless oil (yield: 0.916 g, 94%).
Reaction SMILES: [NH2:1][C:2]12[CH2:9][C:6]([C:10]([O:12][CH3:13])=[O:11])([CH2:7][CH2:8]1)[CH2:5][CH2:4][CH2:3]2.[CH3:14][C:15]1[N:20]=[C:19]([C:21](O)=[O:22])[CH:18]=[N:17][CH:16]=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.O>C(Cl)Cl>[CH3:14][C:15]1[N:20]=[C:19]([C:21]([NH:1][C:2]23[CH2:9][C:6]([C:10]([O:12][CH3:13])=[O:11])([CH2:7][CH2:8]2)[CH2:5][CH2:4][CH2:3]3)=[O:22])[CH:18]=[N:17][CH:16]=1
Reactant: Cc1cncc(C(=O)O)n1
Reactant: COC(=O)C12CCCC(N)(CC1)C2
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: ClCCl
Solvent: O
Product: COC(=O)C12CCCC(NC(=O)c3cncc(C)n3)(CC1)C2
Temperature: 25 °C
Reaction time: 8 h
Yield: 78.7 %

Procedure:
To a solution of methyl 5-aminobicyclo[3.2.1]octane-1-carboxylate (0.98 g, 5.36 mmol) and 6-methylpyrazine-2-carboxylic acid (0.89 g, 6.45 mmol) in DCM (30 mL) and TEA (2 mL) was added PyBOP (3.35 g, 6.44 mmol). After stirring at room temperature overnight, water (30 mL) was added and the mixture was extracted with DCM (3×50 mL). The combined organic layer was washed with Sat. NaHCO3 (50 mL) and brine (50 mL), dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate: 1/1) to afford 1.28 g (79%) of methyl 5-(6-methylpyrazine-2-carboxamido)bicyclo[3.2.1]octane-1-carboxylate as an off-white solid. ESI-MS m/z: 304 (M+H)+.
Reaction SMILES: [C:1]([CH2:4][CH2:5][CH:6]1[CH2:11][CH2:10][N:9]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:8][CH2:7]1)(O)=[O:2].[ClH:18].S(Cl)([Cl:21])=O>C(Cl)Cl>[ClH:21].[Cl:18][C:1]([CH2:4][CH2:5][CH:6]1[CH2:11][CH2:10][N:9]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:8][CH2:7]1)=[O:2]
Reactant: O=S(Cl)Cl
Reactant: CCOC(=O)CN1CCC(CCC(=O)O)CC1
Agent: Cl
Solvent: ClCCl
Product: CCOC(=O)CN1CCC(CCC(=O)Cl)CC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To 1.46 g of 4-(2-carboxyethyl)-1-[(ethoxycarbonyl)methyl]-piperidine in 10 ml of methylene chloride is added 1 ml of saturated ethereal hydrochloric acid. 1.2 g of thionyl chloride are added and the mixture is stirred for 3 hours at ambient temperature. The reaction mixture is concentrated by evaporation and the residue is mixed twice with toluene and again concentrated by evaporation. The crude product is reacted further in Example 1 without purification.
Reaction SMILES: [CH2:1]([C:6]1[CH:11]=[CH:10][C:9]([CH:12]=[CH:13][CH2:14][CH2:15][CH2:16][C:17]([OH:19])=[O:18])=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH2:4][CH3:5]>[Pd]>[CH2:1]([C:6]1[CH:7]=[CH:8][C:9]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([OH:19])=[O:18])=[CH:10][CH:11]=1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: CCCCCc1ccc(C=CCCCC(=O)O)cc1
Agent: [Pd]
Product: CCCCCc1ccc(CCCCCC(=O)O)cc1
Yield: 86.1 %

Procedure:
This compound was synthesized from 6-(p-pentylphenyl)-5-hexenoic acid (1.30 g, 5 mmol) by a hydrogenation reaction using Pd/C (130 mg). Crystallization (petroleum ether) afforded the product (1.13 g, 87%) as white crystals (mp 29-30° C.), IR: 3400-2500, 1730 cm-1 ; 1H-NMR: 0.89 (t, 3H), 1.32 (m, 6H), 1.60 (m, 6H), 2.35 (t, 2H), 2.58 (m, 4H), 7.07 (s, 1H), 10.30 (bs, 1H). Anal. Calcd. for C17H26O2 : C, 77.82, H, 9.99%; Found: C, 77.56, H, 9.90%.
Reaction SMILES: [C:1]1([N:7]2[C:11]3[NH:12][C:13](=[O:20])[C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=4[C:10]=3[CH:9]=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.Cl[CH2:23][C:24]1[N:25]([CH3:29])[N:26]=[CH:27][N:28]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[CH3:29][N:25]1[C:24]([CH2:23][O:20][C:13]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=3[C:10]3[CH:9]=[N:8][N:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[C:11]=3[N:12]=2)=[N:28][CH:27]=[N:26]1
Reactant: Cn1ncnc1CCl
Reactant: O=c1[nH]c2c(cnn2-c2ccccc2)c2ccccc12
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: Cn1ncnc1COc1nc2c(cnn2-c2ccccc2)c2ccccc12
Temperature: 60 °C
Reaction time: 3 h
Yield: 73.8 %

Procedure:
A mixture of 3,4-dihydro-3-phenyl-5H-pyrazolo[3,4-c]isoquinolin-5-one (0.10 g, 0.38 mmol), 3-chloromethyl-2-methyl-2H-[1,2,4]triazole hydrochloride (0.10 g, 0.57 mmol) and cesium carbonate (0.37 g, 1.14 mmol) in dry DMF (2 ml) was stirred at 60° C. under nitrogen for 3 h. Water (30 ml) was added and the mixture was filtered. The solids were washed with diethyl ether (5 ml) and dried in vacuo to give the title compound (0.10 g, 74%) as an off-white powder, m.p. 149-151° C. Found: C, 66.19; H, 4.46; N, 23.71. C20H16N6O.0.25(H2O) requires C, 66.56; H, 4.61; N, 23.29%. δH (400 MHz; CDCl3) 3.98 (3H, s), 5.82 (2H, s), 7.36 (1H, dd, J=7 and 7), 7.52-7.57 (3H, m), 7.83 (1H, dd, J=7 and 7), 7.94 (1H, s), 8.15-8.20 (3H, m), 8.33 (1H, d, J=8), 8.42 (1H, s); m/z (ES+) 356 (M+H+).
Reaction SMILES: [CH3:1][N:2]1[C:6]([NH:7][C:8]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[C:5]([NH:27][C:28](=O)[O:29]C2C=CC=CC=2)[CH:4]=[N:3]1.[NH2:37][CH:38]([C:52](=[O:64])[NH:53][CH2:54][CH2:55][NH:56][C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[C:39](=[O:51])[NH:40][CH2:41][CH2:42][NH:43][C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45].C(N(C(C)C)C(C)C)C.C(OCC)C>C(Cl)(Cl)Cl>[CH3:1][N:2]1[C:6]([NH:7][C:8]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[C:5]([NH:27][C:28]([NH:37][CH:38]([C:52](=[O:64])[NH:53][CH2:54][CH2:55][NH:56][C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[C:39](=[O:51])[NH:40][CH2:41][CH2:42][NH:43][C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])=[O:29])[CH:4]=[N:3]1
Reactant: Cn1ncc(NC(=O)Oc2ccccc2)c1NC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CC(C)(C)OC(=O)NCCNC(=O)C(N)C(=O)NCCNC(=O)OC(C)(C)C
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOCC
Solvent: ClC(Cl)Cl
Product: Cn1ncc(NC(=O)NC(C(=O)NCCNC(=O)OC(C)(C)C)C(=O)NCCNC(=O)OC(C)(C)C)c1NC(c1ccccc1)(c1ccccc1)c1ccccc1
Yield: 88 %

Procedure:
To a suspension of phenyl N-[1-methyl-5-(tritylamino)-1H-pyrazol-4-yl]carbamate (949 mg) and di-tert-butyl 7-amino-6,8-dioxo-2,5,9,12-tetraazatridecanedioate (968 mg) in dehydrated chloroform (4 ml) was added N-ethyldiisopropylamine (0.342 ml), and the mixture was stirred under reflux for 5 hours. To the reaction mixture was added diethyl ether. The resulting precipitate was collected by filtration and dried in vacuo to give di-tert-butyl 7-[({[1-methyl-5-(tritylamino)-1H-pyrazol-4-yl]amino}carbonyl)amino]-6,8-dioxo-2,5,9,12-tetraazatridecanedioate (1.38 g) as a solid.
Reaction SMILES: [CH:1]([N:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:20](=[S:22])=[S:21].I[CH3:24]>CO>[C:2]1([CH:1]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:14]2[CH2:19][CH2:18][N:17]([C:20]([S:22][CH3:24])=[S:21])[CH2:16][CH2:15]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CI
Reactant: c1ccc(C(c2ccccc2)N2CCNCC2)cc1
Reactant: S=C=S
Solvent: CO
Product: CSC(=S)N1CCN(C(c2ccccc2)c2ccccc2)CC1
Reaction time: 0.5 h

Procedure:
In 25 ml of methanol was dissolved 5.00 g (19.8 mmol.) of 1-benzhydrylpiperazine. To the solution was dropwise added under chilling with ice a solution of 1.51 g (19.8 mmol.) of carbon disulfide in 5 ml of methanol. The mixture was then stirred for 30 min. Under chilling with ice, to the stirred mixture was added a solution of 3.80 g (19.8 mmol.) of 28%-sodium methylate-in-methanol solution. The mixture was then stirred until the mixture gave a clear solution. To this was added a solution of 2.90 g (19.8 mmol.) of 97%-iodomethane in 5 ml of methanol. The mixture was then stirred at room temperature for 1.5 hours. Precipitated crystals were collected by filtration and washed with methanol, to give 5.78 g of methyl 4-diphenylmethyl-1-piperazinecarbodithioate.
Reaction SMILES: [I-].[CH3:2][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[CH2:22]1[CH2:32][C:30](=O)[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23]1.O>C1COCC1>[CH2:2]=[C:30]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23][CH2:22][CH2:32]1
Reactant: O=C1CCCc2ccccc21
Reactant: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [I-]
Solvent: O
Solvent: C1CCOC1
Product: C=C1CCCc2ccccc21
Temperature: 25 °C
Reaction time: 17 h

Procedure:
N-Butyl lithium (Aldrich) (47 cm3, 74.8 mmol, 1.6 M solution in hexane) was added dropwise to a solution of methyl triphenylphosphonium iodide (Aldrich) (27.65 g, 68 mmol) in dry THF (150 cm3), under nitrogen at 0° C. α-Tetralone (Aldrich) (10 g, 68 mmol) in dry THF (100 cm3 was then added dropwise and the mixture stirred for 17 hours at room temperature. The reaction mixture was then added to water and extracted with ethyl acetate. The combined extracts were then dried (Na2SO4), filtered and concentrated in vacuo. Purification was by column chromatography on a neutralised silica column (Et3N) (Eluant: Pet. Ether 40-60° C.) produced a colourless mobile oil.
Reaction SMILES: C(O)[C:2]([NH2:7])([CH2:5]O)CO.Cl.[N+](C1C=CC(SSC2C=CC([N+]([O-])=O)=C(C=2)C(O)=O)=CC=1C(O)=O)([O-])=O.C(SCCN[C:43](=O)[CH2:44][CH2:45][NH:46][C:47](=[O:85])[C@H:48](O)C(C)(C)COP(O)(=O)OP(O)(=O)OC[C@H]1O[C@@H](N2C3N=CN=C(N)C=3N=C2)[C@H](O)[C@@H]1OP(O)(O)=O)(=O)C.NCCCCCN>>[C:47]([NH:46][CH2:45][CH2:44][CH2:43][CH2:5][CH2:2][NH2:7])(=[O:85])[CH3:48]
Reactant: NC(CO)(CO)CO
Reactant: CC(=O)SCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)COP(=O)(O)OP(=O)(O)OC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1OP(=O)(O)O
Agent: Cl
Agent: NCCCCCN
Agent: O=C(O)c1cc(SSc2ccc([N+](=O)[O-])c(C(=O)O)c2)ccc1[N+](=O)[O-]
Product: CC(=O)NCCCCCN

Procedure:
10 mM Tris-HCl (pH 7.8), 0.1 mM DTNB (5,5′-dithiobis-(2-nitrobenzoic acid)), 0.25 mM acetyl CoA, 5 mM cadaverine, enzyme solution
Reaction SMILES: C(C1N=C(N2CCC(F)(F)C2)C2N=NN(CC)C=2N=1)(C)(C)C.[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:40][CH2:39][C:38]([F:42])([F:41])[CH2:37]2)[C:30]2[N:35]=[N:34][NH:33][C:31]=2[N:32]=1)([CH3:26])([CH3:25])[CH3:24].FC(F)(F)S(O[CH2:49][C:50]([F:53])([F:52])[F:51])(=O)=O>>[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:40][CH2:39][C:38]([F:41])([F:42])[CH2:37]2)[C:30]2[N:35]=[N:34][N:33]([CH2:49][C:50]([F:53])([F:52])[F:51])[C:31]=2[N:32]=1)([CH3:26])([CH3:24])[CH3:25]
Reactant: O=S(=O)(OCC(F)(F)F)C(F)(F)F
Reactant: CC(C)(C)c1nc(N2CCC(F)(F)C2)c2nn[nH]c2n1
Agent: CCn1nnc2c(N3CCC(F)(F)C3)nc(C(C)(C)C)nc21
Product: CC(C)(C)c1nc(N2CCC(F)(F)C2)c2nnn(CC(F)(F)F)c2n1

Procedure:
In analogy to the procedure described for the synthesis of 5-tert-butyl-7-(3,3-difluoro-pyrrolidin-1-yl)-3-ethyl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 61), the title compound was prepared from 5-tert-butyl-7-(3,3-difluoropyrrolidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 2,2,2-trifluoroethyl trifluoromethanesulfonate and isolated as light-yellow gum (0.9 mg, 6%). MS(m/e): 365.3 (MH+).