Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:17]=[CH:16][C:15]([CH2:18][CH2:19][O:20][CH2:21][O:22][CH3:23])=[CH:14][C:10]=1[C:11](O)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N1C=CN=C1)([N:26]1C=CN=C1)=O.[OH-].[NH4+].O>O1CCCC1>[CH2:1]([O:8][C:9]1[CH:17]=[CH:16][C:15]([CH2:18][CH2:19][O:20][CH2:21][O:22][CH3:23])=[CH:14][C:10]=1[C:11]([NH2:26])=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: COCOCCc1ccc(OCc2ccccc2)c(C(=O)O)c1
Agent: [NH4+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: COCOCCc1ccc(OCc2ccccc2)c(C(N)=O)c1
Reaction time: 1 h
Yield: 78 %

Procedure:
To a stirred solution of 2-benzyloxy-5-(2-methoxymethoxyethyl)benzoic acid (900 mg) in tetrahydrofuran (25 ml) was added 1,1′-carbonyldiimidazole (507 mg) at room temperature, and the mixture was stirred for 1 hour. To the reaction mixture was added 28% ammonium hydroxide (3 ml), and the resulting mixture was stirred for 30 minutes at room temperature. Water was added to the reaction mixture, and the resulting mixture was extracted with ethyl acetate. The extract was washed with brine and dried over anhydrous magnesium sulfate. After the solvent was removed under reduced pressure, crystallization of the residue from hexane and diethyl ether (1/1) gave 2-benzyloxy-5-(2-methoxymethoxyethyl)benzamide (700 mg).
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)=O.[Br:12][C:13]1[N:14]=[CH:15][C:16]([NH2:19])=[N:17][CH:18]=1>C(#N)C>[Br:12][C:13]1[N:14]=[CH:15][C:16]2[N:17]([CH:2]=[C:3]([C:5]3[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=3)[N:19]=2)[CH:18]=1
Reactant: Nc1cnc(Br)cn1
Reactant: O=C(CBr)c1ccc(O)cc1
Solvent: CC#N
Product: Oc1ccc(-c2cn3cc(Br)ncc3n2)cc1
Temperature: 110 °C
Yield: 31.4 %

Procedure:
4.66 g (corresponding to 21.6 mmol) of 2-bromo-4′-hydroxyacetophenone and 2.53 g (corresponding to 14.5 mmol) of 5-bromo-2-aminopyrazine were dissolved in 100 mL of acetonitrile. The resulting solution was refluxed in an oil bath at 110° C. for 3.5 hours. After the completion of the reaction, the reaction solution was cooled down to room temperature, and precipitates were filtered and recovered. The precipitates were washed with acetonitrile and dried under reduced pressure. The resulting crude crystals were suspended in a mixed solution of 10 mL of water and 10 mL of methanol. Then, about 20 mL of a saturated sodium hydrogencarbonate solution was added thereto, and the mixture was sonicated for 10 minutes using an ultrasonic washing machine. Precipitates were filtered and recovered from the resulting mixture, sufficiently washed with water, and dried under reduced pressure, to obtain 1.32 g (corresponding to 4.55 mmol) of 6-bromo-2-(4′-hydroxyphenyl)imidazo[1,2-a]pyrazine (FIG. 11, Step 2).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([CH3:23])=[CH:8][C:9](=[O:22])[N:10]2[CH2:13][CH2:14][CH:15]2[CH2:20][CH2:19][C:18](=O)[CH2:17][CH2:16]2)=[CH:5][CH:4]=1.C([O-])(=O)C.[NH4+].C([BH3-])#[N:30].[Na+]>C(O)C>[NH2:30][CH:18]1[CH2:19][CH2:20][CH:15]([CH2:14][CH2:13][N:10]2[C:11]3[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:12]=3)[C:7]([CH3:23])=[CH:8][C:9]2=[O:22])[CH2:16][CH2:17]1
Reactant: COc1ccc2c(C)cc(=O)n(CCC3CCC(=O)CC3)c2c1
Reactant: [BH3-]C#N
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CCO
Product: COc1ccc2c(C)cc(=O)n(CCC3CCC(N)CC3)c2c1
Reaction time: 1 h

Procedure:
To 1.5 mL of an ethanol solution containing 10 mg of 7-methoxy-4-methyl-1-(2-(4-oxocyclohexyl)ethyl)quinolin-2(1H)-one, 3.7 mg of ammonium acetate and 15 mg of molecular sieves 3A were added at room temperature, the mixture was stirred for 1 hour, then thereto was added 5.0 mg of sodium cyanoborohydride, and the mixture was stirred at the same temperature for 4 hours and 30 minutes. Thereto was further added 3.0 mg of sodium cyanoborohydride, and the mixture was stirred for 30 minute, and then left to stand overnight. The solvent was removed under reduced pressure, water and ethyl acetate were added thereto, the reaction mixture was adjusted to pH 3 to 4 (pH test paper) with 2.0 mol/L hydrochloric acid, and the aqueous layer was separated. The aqueous layer was added with ethyl acetate, and the resultant solution was adjusted to pH 8 to 9 (pH test paper) with a 2.0 mol/L aqueous sodium hydroxide solution. The organic layer was separated, washed with an aqueous saturated sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to obtain 6.0 mg of a colorless oily substance, 1-(2-(4-aminocyclohexyl)ethyl)-7-methoxy-4-methylquinolin-2(1H)-one.
Reaction SMILES: [H-].[Na+].C1COCC1.[C:8]([O:12][C:13](=[O:21])/[CH:14]=[CH:15]/[C:16]1[CH:20]=[CH:19][NH:18][CH:17]=1)([CH3:11])([CH3:10])[CH3:9].[Br:22][C:23]1[CH:24]=[C:25]([S:29](Cl)(=[O:31])=[O:30])[CH:26]=[CH:27][CH:28]=1>O>[C:8]([O:12][C:13](=[O:21])/[CH:14]=[CH:15]/[C:16]1[CH:20]=[CH:19][N:18]([S:29]([C:25]2[CH:26]=[CH:27][CH:28]=[C:23]([Br:22])[CH:24]=2)(=[O:31])=[O:30])[CH:17]=1)([CH3:11])([CH3:9])[CH3:10]
Reactant: CC(C)(C)OC(=O)/C=C/c1cc[nH]c1
Reactant: O=S(=O)(Cl)c1cccc(Br)c1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)/C=C/c1ccn(S(=O)(=O)c2cccc(Br)c2)c1
Temperature: -30 °C
Reaction time: 0.5 h
Yield: 83.5 %

Procedure:
A mixture of 0.77 g NaH (60%) with 65.0 ml THF is cooled to −30° C. Then 3.2 g 3.1 g (E)-3-(1H-pyrrol-3-yl)-acrylic acid tert-butyl ester are added. During the addition there is liberated a gas. The solution is stirred at ambient temperature for 0.5 h. Finally 5.0 g 3-bromobenzenesulfonylchloride are added at −30° C. The suspension is stirred at ambient temperature for 24 h. The suspension is treated with water and the solution is extracted with ethyl acetate. The organic layer is dried over sodium sulfate and evaporated. The residue (oil) is crystallized from methanol. The crystals are dried in vacuo. By this method 5.7 g of colorless crystals are obtained.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:26])[C:9]([C:15]2[CH:16]=[CH:17][C:18](=[O:25])[N:19]3[C:24]=2[CH:23]=[CH:22][CH:21]=[CH:20]3)([OH:14])[C:10]([F:13])([F:12])[F:11])=[C:4]([Cl:27])[CH:3]=1.[F:28][C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][C:34]=1[C:35]([O:37][CH3:38])=[O:36]>>[CH3:38][O:37][C:35]([C:34]1[CH:33]=[CH:32][C:31]([C:2]2[CH:7]=[CH:6][C:5]([CH:8]([CH3:26])[C:9]([OH:14])([C:15]3[CH:16]=[CH:17][C:18](=[O:25])[N:19]4[C:24]=3[CH:23]=[CH:22][CH:21]=[CH:20]4)[C:10]([F:11])([F:13])[F:12])=[C:4]([Cl:27])[CH:3]=2)=[CH:30][C:29]=1[F:28])=[O:36]
Reactant: CC(c1ccc(Br)cc1Cl)C(O)(c1ccc(=O)n2ccccc12)C(F)(F)F
Reactant: COC(=O)c1ccc(B(O)O)cc1F
Product: COC(=O)c1ccc(-c2ccc(C(C)C(O)(c3ccc(=O)n4ccccc34)C(F)(F)F)c(Cl)c2)cc1F

Procedure:
In analogy to Example 17, step 2, 1-[2-(4-bromo-2-chloro-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-quinolizin-4-one was reacted with 3-fluoro-4-methoxycarbonylphenylboronic acid to give the title compound as a light yellow solid. MS (m/e)=534.2 [M+H+].
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[C:3]1[CH:12]=[C:11](O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.P(Br)(Br)([Br:18])=O>>[F:1][C:2]([F:15])([F:14])[C:3]1[CH:12]=[C:11]([Br:18])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1
Reactant: Oc1cc(C(F)(F)F)nc2ccccc12
Reactant: O=P(Br)(Br)Br
Product: FC(F)(F)c1cc(Br)c2ccccc2n1

Procedure:
2-Trifluoromethyl cinchoninic acid, and substituted 2-trifluoromethyl cinchoninic acids, are known plant growth regulating materials. Such compounds can be prepared, as disclosed by B. M. Pinder and A. Burger (J. Med. Chem, 11, pp 267-269 (1968), by condensation of aniline, or a substituted aniline, with ethyl 4,4,4-trifluoroacetoacetate in the presence of polyphosphoric acid to produce a 2-trifluoromethyl-4-hydroxyquinoline from which the desired 2-trifluoromethyl cinchoninic acid can be obtained by two alternative procedures. In the first of such procedures, the 2-trifluoromethyl-4-hydroxyquinoline is brominated with phosphorus oxybromide to produce the corresponding 2-trifluoromethyl-4-bromoquinoline which is then reacted with n-butyllithium to produce a lithioquinoline which can in turn be treated with dry carbon dioxide to produce the desired 2-trifluoromethyl cinchoninic acid. In the second of such procedures, the 2-trifluoromethyl-4-hydroxyquinoline is chlorinated with phosphorus oxychloride and the resulting 2-trifluoromethyl-4-chloroquinoline is reacted with cuprous cyanide in N-methylpyrrolidone to convert it to the corresponding nitrile which is then hydrolyzed to the desired 2-trifluoromethyl cinchoninic acid. However, not only are both these procedures complex and involved, but they involve the use of corrosive materials such as phosphorus oxybromide and phosphorus oxychloride as well as air- and water-sensitive materials such as butyllithium and copper cyanide.
Reaction SMILES: [C:1]1([CH:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:8][OH:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[N+]([C:21]1[CH:26]=[CH:25][N+:24]([O-:27])=[CH:23][CH:22]=1)([O-])=O.C1(C)C=CC=CC=1>CN(C)C=O>[C:10]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:8][O:9][C:21]2[CH:26]=[CH:25][N+:24]([O-:27])=[CH:23][CH:22]=2)[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: O=[N+]([O-])c1cc[n+]([O-])cc1
Reactant: OCC(c1ccccc1)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Product: [O-][n+]1ccc(OCC(c2ccccc2)c2ccccc2)cc1

Procedure:
2,2-diphenylethanol (4 g, 0.02 m) was added portionwise to a suspension of sodium hydride (0.48 g, 0.02 m) in dry dimethylformamide (200 ml) under nitrogen. After the reaction had ceased, the mixture was added dropwise to a solution of 4-nitropyridine-1-oxide (2.8 g, 0.02 m) in dry dimethylformamide (100 ml) at 35°-40° C. The mixture was maintained at this temperature for 12 hours and then filtered. The solvent was removed under reduced pressure, leaving a residue that was heated with successive portions of toluene. The toluene solution was evaporated to an oil which was crystallised from a mixture of toluene and 60-80 petrol (1:1). This gave 4-(2,2-diphenylethoxy)pyridine-1-oxide (2.2 g) as orange crystals, m.pt. 134°-138° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11](/[CH:14]=[C:15]2/[C:16](=[O:31])[C:17]([C:22]3[C:27]([CH3:28])=[CH:26][C:25]([CH3:29])=[CH:24][C:23]=3[CH3:30])=[C:18]([O:20][CH3:21])[CH2:19]/2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(O)C.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([CH2:14][CH:15]2[CH2:19][C:18]([O:20][CH3:21])=[C:17]([C:22]3[C:27]([CH3:28])=[CH:26][C:25]([CH3:29])=[CH:24][C:23]=3[CH3:30])[C:16]2=[O:31])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COC1=C(c2c(C)cc(C)cc2C)C(=O)/C(=C/C2CCN(C(=O)OC(C)(C)C)CC2)C1
Agent: [Pd]
Solvent: CCO
Product: COC1=C(c2c(C)cc(C)cc2C)C(=O)C(CC2CCN(C(=O)OC(C)(C)C)CC2)C1
Yield: 100 %

Procedure:
To a solution of 4-[4-methoxy-2-oxo-3-(2,4,6-trimethyl-phenyl)-cyclopent-3-en-(E)-ylidenemethyl]-piperidine-1-carboxylic acid tert-butyl ester (15.33 g, 36.02 mmol) in ethanol (150 ml) is added 10% palladium on activated charcoal (1.53 g) and the reaction stirred under hydrogen (4 bar) for hours. The reaction is filtered through a pad of Celite and the solvent removed under reduced pressure to give 4-[4-methoxy-2-oxo-3-(2,4,6-trimethyl-phenyl)-cyclopent-3-enylmethyl]-piperidine-1-carboxylic acid tert-butyl ester (15.4 g)
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[N:5]1([CH:10]([O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:11]([OH:16])[C:12]([CH3:15])([CH3:14])[CH3:13])[CH:9]=[CH:8][N:7]=[CH:6]1>C(OCC)(=O)C>[C:1]([O:16][CH:11]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:10]([O:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[N:5]1[CH:9]=[CH:8][N:7]=[CH:6]1)(=[O:3])[CH3:2]
Reactant: CC(C)(C)C(O)C(Oc1ccccc1)n1ccnc1
Reactant: CC(=O)Cl
Solvent: CCOC(C)=O
Product: CC(=O)OC(C(Oc1ccccc1)n1ccnc1)C(C)(C)C
Yield: 68.1 %

Procedure:
8.0 g (0.1 mol) of acetyl chloride are added to 20.6 g (0.1 mol) of 1-imidazol-1-yl-1-phenoxy-3,3-dimethyl-butan-2-ol in 100 ml of ethyl acetate at room temperature. The mixture is then heated under reflux for 4 hours. It is allowed to cool and concentrated by distilling off the solvent in vacuo. The residue is taken up in benzene and the solution is washed with aqueous sodium bicarbonate solution and dried over sodium sulphate. The solvent is distilled off under a water pump vacuum and the residue is recrystallized from petroleum ether. 20.6 g (45% of theory) of 2-acetoxy-1-phenoxy-1-imidazol-1-yl-3,3-dimethyl-butane are obtained as a mixture of isomers with a melting point of 114°-121° C.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:15])[CH2:10][CH:9]2[O:24][CH2:25][C:26]2[CH:27]=[CH:28][C:29]3[O:34][CH2:33][CH2:32][N:31]([CH2:35][CH2:36][CH2:37][O:38][CH3:39])[C:30]=3[CH:40]=2)=[CH:4][CH:3]=1.C1(C)C=CC(S(O[CH:51]2[CH2:55][CH2:54][O:53][CH2:52]2)(=O)=O)=CC=1>>[CH3:39][O:38][CH2:37][CH2:36][CH2:35][N:31]1[C:30]2[CH:40]=[C:26]([CH2:25][O:24][CH:9]3[CH:8]([C:5]4[CH:6]=[CH:7][C:2]([O:1][CH:51]5[CH2:55][CH2:54][O:53][CH2:52]5)=[CH:3][CH:4]=4)[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[O:15])[CH2:10]3)[CH:27]=[CH:28][C:29]=2[O:34][CH2:33][CH2:32]1
Reactant: Cc1ccc(S(=O)(=O)OC2CCOC2)cc1
Reactant: COCCCN1CCOc2ccc(COC3CN(C(=O)OCc4ccccc4)CCC3c3ccc(O)cc3)cc21
Product: COCCCN1CCOc2ccc(COC3CN(C(=O)OCc4ccccc4)CCC3c3ccc(OC4CCOC4)cc3)cc21

Procedure:
Analogously to Method D, 0.065 g of benzyl 4-(4-hydroxyphenyl)-3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate and 0.0288 g of tetrahydrofuran-3-yl toluene-4-sulphonate are reacted. The title compound is obtained as an orange oil. Rf=0.22 (2:1 EtOAc-heptane). Rt=5.25.
Reaction SMILES: [CH2:1]([CH:3]1[C:9](=[O:10])[N:8]2[CH:4]1[CH2:5][C:6]([S:21][CH2:22][CH2:23][NH:24]C(OCC1C=CC=CC=1)=O)=[C:7]2[C:11]([O:13]CC1C=CC=CC=1)=[O:12])[CH3:2]>[Pd].O1CCOCC1.O>[CH2:1]([CH:3]1[C:9](=[O:10])[N:8]2[CH:4]1[CH2:5][C:6]([S:21][CH2:22][CH2:23][NH2:24])=[C:7]2[C:11]([OH:13])=[O:12])[CH3:2]
Reactant: CCC1C(=O)N2C(C(=O)OCc3ccccc3)=C(SCCNC(=O)OCc3ccccc3)CC12
Agent: [Pd]
Solvent: O
Solvent: C1COCCO1
Product: CCC1C(=O)N2C(C(=O)O)=C(SCCN)CC12
Reaction time: 1 h

Procedure:
A mixture of benzyl 6-ethyl-3-(2-benzyloxycarbonyl aminoethyl)thio-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (10 mg) and 10% Pd/C (20 mg) in 1:1 dioxane-H2O (4 ml) is hydrogenated at 40 psi for 1 hr. The mixture is filtered to remove the catalyst which is washed with more H2O (4 ml). The combined filtrate and washings are concentrated in vacuo to 2 ml and loaded onto a column of 200-400 mesh Dowex-50×4 (Na form) ion-exchange resin. The column is eluted with deionized H2O. The appropriate fractions are pooled and lyophilized to provide 6-ethyl-3-(2-aminoethyl)thio-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][CH:8]=[C:9]2[NH2:14])([O-])=O.[H][H]>C1(C)C=CC=CC=1.[Pd]>[C:4]1([NH2:1])[C:5]2[CH:6]=[CH:7][CH:8]=[C:9]([NH2:14])[C:10]=2[CH:11]=[CH:12][CH:13]=1
Reactant: [H][H]
Reactant: Nc1cccc2c([N+](=O)[O-])cccc12
Agent: [Pd]
Solvent: Cc1ccccc1
Product: Nc1cccc2c(N)cccc12
Yield: 97.5 %

Procedure:
8.20 g of 5-nitro-1-naphthylamine (43.6 mmol) in 35 ml of toluene are placed in a 0.1 liter autoclave with 0.5 g of palladium on carbon (5%) and hydrogenated at 50° C. and 40 bar hydrogen pressure for 5 h, stirring. On completion of the reaction, the cooled autoclave is depressurised and the catalyst is filtered off. With a quantitative conversion, 6.72 g of 1,5-naphthalenediamine (42.5 mmol, 97.5%) are formed.
Reaction SMILES: [NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]([S:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[N+](C1C=CC=CC=1)([O-])=O.Br[C:41]1[CH:46]=[CH:45][C:44]([CH3:47])=[C:43]([N+:48]([O-:50])=[O:49])[CH:42]=1>>[CH3:47][C:44]1[CH:45]=[CH:46][C:41]([NH:1][C:2]2[C:15]3[C:14](=[O:16])[C:13]4[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=4)[C:7](=[O:17])[C:6]=3[C:5]([S:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[CH:4][CH:3]=2)=[CH:42][C:43]=1[N+:48]([O-:50])=[O:49]
Reactant: Nc1ccc(Sc2ccccc2)c2c1C(=O)c1ccccc1C2=O
Reactant: Cc1ccc(Br)cc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O=[N+]([O-])c1ccccc1
Product: Cc1ccc(Nc2ccc(Sc3ccccc3)c3c2C(=O)c2ccccc2C3=O)cc1[N+](=O)[O-]
Yield: 90 %

Procedure:
A mixture of 23.2 parts of 1-amino-4-phenylmercaptoanthraquinone, 9 parts of sodium carbonate and 150 parts of nitrobenzene is heated to the boil, whilst stirring, and dehydrated in the course of one hour, whilst a stream of nitrogen is passed through. 30 parts of 4-bromo-2-nitrotoluene and 1 part of copper-I chloride are then added to the mixture, which has been cooled to 150°. After stirring for 15 hours at 150° and, at the same time, passing a moderate stream of nitrogen through the mixture, the reaction mixture is allowed to cool. The reaction product is precipitated by gradually adding 200 parts of methanol and is filtered off, washed with methanol and hot water and finally boiled thoroughly with 5% strength hydrochloric acid. This gives 29.5 parts (90% of theory) of 1-(4'-methyl-3'-nitrophenylamino)-4-phenylmercaptoanthraquinone with a melting point of 199°-201°. The colorant dyes polyester violet in bulk.
Reaction SMILES: [NH2:1][CH:2]1[C:25](=[O:26])[N:4]2[C:5]([C:22]([OH:24])=[O:23])=[C:6]([CH:9]([S:16][C:17]3[NH:21][N:20]=[N:19][N:18]=3)[CH2:10][CH2:11][S:12](=[O:15])(=[O:14])[NH2:13])[CH2:7][S:8][C@H:3]12.C(=O)(O)[O-].[Na+].[CH3:32][CH2:33][C:34](Cl)=[S:35].[OH-].[Na+]>CC(C)=O>[CH3:32][CH2:33][C:34]([NH:1][CH:2]1[C:25](=[O:26])[N:4]2[C:5]([C:22]([OH:24])=[O:23])=[C:6]([CH:9]([S:16][C:17]3[NH:18][N:19]=[N:20][N:21]=3)[CH2:10][CH2:11][S:12](=[O:14])(=[O:15])[NH2:13])[CH2:7][S:8][C@H:3]12)=[S:35]
Reactant: CCC(=S)Cl
Reactant: NC1C(=O)N2C(C(=O)O)=C(C(CCS(N)(=O)=O)Sc3nnn[nH]3)CS[C@H]12
Agent: O=C([O-])O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)=O
Product: CCC(=S)NC1C(=O)N2C(C(=O)O)=C(C(CCS(N)(=O)=O)Sc3nnn[nH]3)CS[C@H]12
Reaction time: 0.33 h

Procedure:
To a stirred, cooled (-20° ) solution of 10.8 g. (0.026 mol.) of 7-amino-3-[1-(2-sulfamoylethyl)tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acid in 220 ml. of 3% sodium bicarbonate and 220 ml. of acetone is dropwise added a solution of 3.66 g. (0.029 mol.) of methylthioacetyl chloride in 52 ml. of acetone, during which time the pH of the reaction mixture is maintained at 8.0 by addition of 10% sodium hydroxide. After addition the reaction mixture is stirred an additional 20 minutes at -15°, then is warmed to 25° and extracted with ether. The remaining aqueous phase is cooled, 250 ml. of ethyl acetate is added and the slurry is acidified with 3N hydrochloric acid. The layers are separated and the aqueous phase is extracted twice more with ethyl acetate. The combined extracts are dried (MgSO4) and evaporated to dryness to yield the title compound.
Reaction SMILES: [CH:1]1([Si:6]([O:11][CH3:12])([O:9][CH3:10])[O:7][CH3:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:13]1(O)[CH2:18][CH2:17]C[CH2:15][CH2:14]1>C[O-].[Na+]>[CH:10]1([O:9][Si:6]([CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)([O:11][CH3:12])[O:7][CH3:8])[CH2:17][CH2:18][CH2:13][CH2:14][CH2:15]1
Reactant: OC1CCCCC1
Reactant: CO[Si](OC)(OC)C1CCCC1
Agent: C[O-]
Agent: [Na+]
Product: CO[Si](OC)(OC1CCCCC1)C1CCCC1
Yield: 83.3 %

Procedure:
The procedures of Example 2 were repeated with the exception that 10.0 g (0.0526 mole) of cyclopentyl trimethoxysilane, 85.1 mg (1.58 m mole) of sodium methoxide, and 52.7 g (0.526 mole) of cyclohexanol in place of sec-butyl alcohol were used and the reaction time was one and a half hours. Then, 11.3 g (0.0438 mole) of cyclohexyloxy cyclopentyl dimethoxysilane were obtained. Its structure was confirmed as in Example 1. FIGS. 3 and 4 are the charts of 1H-NMR and IR, respectively. The yield was 83%.
Reaction SMILES: [CH2:1]([CH:4]([CH2:13][CH2:14][CH3:15])[C:5]([O:7][CH2:8][CH2:9][C:10]([OH:12])=[O:11])=[O:6])[CH2:2][CH3:3].[CH2:16]1[O:21][CH:20]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[O:19][CH2:18][CH:17]1O.C(N(CC)CC)C>C(Cl)Cl>[CH2:13]([CH:4]([CH2:1][CH2:2][CH3:3])[C:5]([O:7][CH2:8][CH2:9][C:10](=[O:12])[O:11][CH:17]1[CH2:18][O:19][CH:20]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[O:21][CH2:16]1)=[O:6])[CH2:14][CH3:15]
Reactant: OC1COC(c2ccccc2)OC1
Reactant: CCCC(CCC)C(=O)OCCC(=O)O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCC(CCC)C(=O)OCCC(=O)OC1COC(c2ccccc2)OC1
Reaction time: 72 h
Yield: 83 %

Procedure:
3-(2-propylpentanoyloxy)propanoic acid (2.05 g, 9.5 mmol) was dissolved in anhydrous CH2Cl2 (200 ml) under argon. 1,3-O-benzylideneglycerol (2.50 g, 13.67 mmol triethylamine (4.04 g, 40.0 mmol) and O-benzotriazol-1-yl-N,N, N′,N′-trimethyluronium hexafluorophosphate (4.2 g, 11.0 mmol) were added successively. The reaction mixture was stirred under argon for 72 h. The reaction mixture was washed with saturated NaHCO3 solution (1×90 ml), water (1×90 ml) and dried over Na2SO4. The organic solvent was removed under reduced pressure giving a pale, pink solid (2.99 g, 7.9 mmol, 83%).
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[F:19][C:20]1[C:21]([C:31]2[C:40]3[C:35](=[CH:36][CH:37]=[C:38]([C:41]([O:43][CH3:44])=[O:42])[CH:39]=3)[C:34]([F:45])=[CH:33][N:32]=2)=[N:22][CH:23]=[C:24]([F:30])[C:25]=1[Si](C)(C)C.C1COCC1>O>[F:19][C:20]1[C:21]([C:31]2[C:40]3[C:35](=[CH:36][CH:37]=[C:38]([C:41]([O:43][CH3:44])=[O:42])[CH:39]=3)[C:34]([F:45])=[CH:33][N:32]=2)=[N:22][CH:23]=[C:24]([F:30])[CH:25]=1
Reactant: COC(=O)c1ccc2c(F)cnc(-c3ncc(F)c([Si](C)(C)C)c3F)c2c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: COC(=O)c1ccc2c(F)cnc(-c3ncc(F)cc3F)c2c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Tetrabutylammonium fluoride (1M THF solution, 0.35 mL) was added to a mixture of methyl 1-[3,5-difluoro-4-(trimethylsilyl)pyridin-2-yl]-4-fluoroisoquinoline-7-carboxylate and THF (1.8 mL), and stirred at room temperature overnight. The reaction mixture was diluted with water, and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried, and concentrated under reduced pressure. The resulting residue was purified under silica gel column chromatography (hexane/ethyl acetate) to obtain methyl 1-(3,5-difluoropyridin-2-yl)-4-fluoroisoquinoline-7-carboxylate (55 mg).
Reaction SMILES: [Br:1][C:2]1[CH:11]=[CH:10][C:5]2[NH:6][C:7](Cl)=[N:8][C:4]=2[CH:3]=1.[F:12][C:13]([F:23])([F:22])[C:14]1[CH:21]=[CH:20][C:17]([CH2:18][NH2:19])=[CH:16][CH:15]=1>>[Br:1][C:2]1[CH:11]=[CH:10][C:5]2[NH:6][C:7]([NH:19][CH2:18][C:17]3[CH:16]=[CH:15][C:14]([C:13]([F:12])([F:22])[F:23])=[CH:21][CH:20]=3)=[N:8][C:4]=2[CH:3]=1
Reactant: NCc1ccc(C(F)(F)F)cc1
Reactant: Clc1nc2cc(Br)ccc2[nH]1
Product: FC(F)(F)c1ccc(CNc2nc3cc(Br)ccc3[nH]2)cc1
Temperature: 200 °C
Yield: 63 %

Procedure:
A mixture of 5-bromo-2-chloro-1H-benzoimidazole (0.100 g, 0.432 mmol) and 4-trifluoromethyl-benzylamine (0.8 mL) was heated in a microwave apparatus at 200° C. for 1 hour. The reaction mixture was cooled, and purified by chromatography (silica, hexanes: EtOAc, 1:1) to afford the title product as a white solid (0.101 g, 63%).
Reaction SMILES: [NH2:1][CH:2]([CH2:6][CH3:7])[C:3]([OH:5])=[O:4].[C:8](OC(=O)C)(=[O:10])[CH3:9]>C(O)(=O)C>[C:8]([NH:1][CH:2]([CH2:6][CH3:7])[C:3]([OH:5])=[O:4])(=[O:10])[CH3:9]
Reactant: CCC(N)C(=O)O
Reactant: CC(=O)OC(C)=O
Solvent: CC(=O)O
Product: CCC(NC(C)=O)C(=O)O
Temperature: 100 °C
Reaction time: 2 h

Procedure:
163 g (1.58 mol) 2-aminobutanoic acid are dissolved in acetic acid, and 242 g (2.37 mol) acetic anhydride are added dropwise. The mixture is stirred for 2 h at 100° C. until completion of reaction, then the solution evaporated to dryness in vacuo. The solid residue is suspended in ethyl acetate, filtered and washed with diethyl ether.