Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=1.C([Li])CCC.[CH:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[CH:19][C:18]=1[C:27]1[CH:40]=[CH:39][C:38]2[C:37](=O)[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH2:30][C:29]=2[CH:28]=1.Cl>C1COCC1.CCCCCC>[CH:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[CH:19][C:18]=1[C:27]1[CH:40]=[CH:39][C:38]2[C:29](=[CH:30][C:31]3[C:36]([C:37]=2[C:2]2[CH:11]=[CH:10][C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[CH:3]=2)=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH:28]=1
Reactant: Brc1ccc2ccccc2c1
Reactant: O=C1c2ccccc2Cc2cc(-c3ccc4ccccc4c3)ccc21
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: c1ccc2cc(-c3ccc4c(-c5ccc6ccccc6c5)c5ccccc5cc4c3)ccc2c1
Temperature: -78 °C
Reaction time: 1 h
Yield: 31.9 %

Procedure:
Under an argon atmosphere, a solution of 4.81 g of 2-bromonaphthalene in 30 mL of THF was cooled to −78° C. Subsequently, 25 mL of a 1.6-M solution of n-butyllithium in hexane were dropped to the solution, and then the mixture was stirred at −78° C. for 1 hour. A solution of 6.76 g of 2-(2-naphthyl)-10-anthrone in 20 mL of THF was added to the mixture, and then the resultant reaction solution was stirred for 5 hours at 50° C. under heat. After the reaction solution had been cooled to room temperature, 100 mL of 10% hydrochloric acid were added to the solution. After the water layer had been removed, the organic layer was washed with water and a saturated salt solution. Then, the organic layer was dried with magnesium sulfate. The solvent was removed by distillation under reduced pressure, and then the residue was purified by silica gel column chromatography. Thus, 2.90 g of 2,10-di(2-naphthyl)anthracene were obtained (in 32% yield).
Reaction SMILES: [C:1]([CH2:4][NH:5][CH:6]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:28])[CH:19]([C:21]3[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=3)[CH3:20])=[CH:13][CH:12]=2)[CH2:7]1)(=[O:3])[CH3:2].Br[CH2:30][CH:31]1[CH2:33][CH2:32]1>>[C:1]([CH2:4][NH:5][CH:6]1[CH2:10][CH2:9][N:8]([C:11]2[CH:12]=[CH:13][C:14]([NH:17][C:18](=[O:28])[CH:19]([C:21]3[CH:26]=[CH:25][C:24]([O:27][CH2:30][CH:31]4[CH2:33][CH2:32]4)=[CH:23][CH:22]=3)[CH3:20])=[CH:15][CH:16]=2)[CH2:7]1)(=[O:3])[CH3:2]
Reactant: BrCC1CC1
Reactant: CC(=O)CNC1CCN(c2ccc(NC(=O)C(C)c3ccc(O)cc3)cc2)C1
Product: CC(=O)CNC1CCN(c2ccc(NC(=O)C(C)c3ccc(OCC4CC4)cc3)cc2)C1

Procedure:
N-{4-[3-(Acetylmethylamino)pyrrolidin-1-yl]phenyl}-2-(4-hydroxyphenyl)propionamide was reacted with bromomethylcyclopropane by method H. This resulted in the product with the molecular weight of 435.57 (C26H33N3O3); MS(ESI): 436 (M+H+).
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:15]=[CH:16][C:17]3[C:23](=[O:24])[N:22]([CH2:25][CH3:26])[CH:21]=[C:20]([CH3:27])[C:18]=3[N:19]=2)[CH2:10][CH2:9]1)C1C=CC=CC=1.C(O)C.[H][H]>[Pd].C(O)(=O)C>[CH2:25]([N:22]1[CH:21]=[C:20]([CH3:27])[C:18]2[N:19]=[C:14]([N:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)[N:15]=[CH:16][C:17]=2[C:23]1=[O:24])[CH3:26]
Reactant: CCn1cc(C)c2nc(N3CCN(Cc4ccccc4)CC3)ncc2c1=O
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Solvent: CC(=O)O
Product: CCn1cc(C)c2nc(N3CCNCC3)ncc2c1=O
Yield: 88.2 %

Procedure:
Added to 300 mg (0.83 mmol) of the 2-(4-benzylpiperazino)-6-ethyl-8-methylpyrido[4,3-d]pyrimidine-5(6H)-one obtained in Referential Example 11 were 6 ml of ethanol, 2 ml of acetic acid and 30 mg of 10% Pd-C. The resultant mixture was stirred at 45° C. for 3.5 hours in a hydrogen atmosphere. The Pd-C was removed from the reaction mixture, followed by concentration under reduced pressure. The concentrate was added with 20 ml of water, to which potassium carbonate was added until no foams were developed. The resultant mixture was extracted three times with 50 ml of chloroform. The chloroform layer was dried with sodium sulfate and then concentrated under reduced pressure, thereby obtaining 200 mg of 6-ethyl-8-methyl-2-piperazinopyrido[4,3-d]pyrimidine-5(6H)-one as colorless crystals (yield: 88%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:18]([CH:19]=[O:20])=[CH:17][C:16]2[C:11](=[C:12]([CH3:21])[CH:13]=[CH:14][CH:15]=2)[N:10]=1.[BH4-].[Na+]>C1COCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:18]([CH2:19][OH:20])=[CH:17][C:16]2[C:11](=[C:12]([CH3:21])[CH:13]=[CH:14][CH:15]=2)[N:10]=1
Reactant: COc1ccccc1-c1nc2c(C)cccc2cc1C=O
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1ccccc1-c1nc2c(C)cccc2cc1CO

Procedure:
Prepared according to Procedure B using 2-(2-methoxyphenyl)-8-methylquino-line-3-carbaldehyde (0.250 g, 0.9 mmol), and sodium borohydride (0.0378 g, 1.35 mmol, 1.5 eq), in THF (5 mL). (2-(2-Methoxyphenyl)-8-methylquinolin-3-yl)-methanol was obtained as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.41 (1 H, s), 7.92 (1 H, d, J=7.8 Hz), 7.64 (1 H, d, J=7.0 Hz), 7.50-7.59 (2 H, m), 7.33 (1 H, dd, J=7.4, 1.6 Hz), 7.22 (1 H, d, J=7.8 Hz), 7.16 (1 H, t, J=7.2 Hz), 5.37 (1 H, t, J=5.5 Hz), 3.79 (3 H, s), 2.72 (3 H, s) Mass Spectrum (ESI) m/e=280.1 (M+1)
Reaction SMILES: COC1C=CC(C[N:8]2[C:12]3[N:13]=[CH:14][C:15]4[CH2:16][NH:17][CH2:18][CH2:19][C:20]=4[C:11]=3[CH:10]=[N:9]2)=CC=1.C1(C)C=CC=CC=1.[F:30][C:31]([F:36])([F:35])[C:32]([OH:34])=[O:33]>>[CH:10]1[C:11]2[C:20]3[CH2:19][CH2:18][NH:17][CH2:16][C:15]=3[CH:14]=[N:13][C:12]=2[NH:8][N:9]=1.[C:32]([OH:34])([C:31]([F:36])([F:35])[F:30])=[O:33]
Reactant: COc1ccc(Cn2ncc3c4c(cnc32)CNCC4)cc1
Solvent: Cc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: c1nc2[nH]ncc2c2c1CNCC2

Procedure:
A solution of 3-(4-methoxy-benzyl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridine (0.14 g, 0.47 mmol) in trifluoroacetic acid (2 mL) was heated at 65° C. for 16 hours. On completion of the reaction, toluene (5 mL) was added. The solvent was then removed under reduced pressure to give a dark brown solid. The solvent was removed under reduced pressure to give 6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridine as a TFA salt. LCMS [M+H]: 175.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]([C:12]2[C:13]([CH3:25])([CH3:24])[C:14](=[O:23])[N:15]([CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)[N:16]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH3:11].[N:26]1[C:35]2[CH:34]=[CH:33][N:32]=[C:31]([C:36](O)=[O:37])[C:30]=2[CH:29]=[CH:28][CH:27]=1>>[CH3:2][O:3][C:4]1[CH:5]=[C:6]([C:12]2[C:13]([CH3:25])([CH3:24])[C:14](=[O:23])[N:15]([CH:17]3[CH2:22][CH2:21][N:20]([C:36]([C:31]4[N:32]=[CH:33][CH:34]=[C:35]5[C:30]=4[CH:29]=[CH:28][CH:27]=[N:26]5)=[O:37])[CH2:19][CH2:18]3)[N:16]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH3:11]
Reactant: COc1ccc(C2=NN(C3CCNCC3)C(=O)C2(C)C)cc1OC
Reactant: O=C(O)c1nccc2ncccc12
Agent: Cl
Product: COc1ccc(C2=NN(C3CCN(C(=O)c4nccc5ncccc45)CC3)C(=O)C2(C)C)cc1OC

Procedure:
The title compound is prepared analogously as described for GP2-WU2 using 5-(3,4-dimethoxyphenyl)-4,4-dimethyl-2-(piperidin-4-yl)-2,4-dihydro-3H-pyrazol-3-one (compound B1) and 1,6-naphthyridine-5-carboxylic acid as starting compounds. The crude product is purified by chromatography (silica gel and DCM/methanol=95:5) to yield the title compound.
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[O:11][C:10]2[C:5](=[CH:6][C:7]([C:12]#[N:13])=[CH:8][CH:9]=2)[CH:4]2[O:14][CH:3]12.[N+:16]([C:19]1[CH:24]=[CH:23][C:22]([N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)=[CH:21][CH:20]=1)([O-:18])=[O:17]>>[OH:14][CH:3]1[CH:4]([N:28]2[CH2:29][CH2:30][N:25]([C:22]3[CH:21]=[CH:20][C:19]([N+:16]([O-:18])=[O:17])=[CH:24][CH:23]=3)[CH2:26][CH2:27]2)[C:5]2[C:10](=[CH:9][CH:8]=[C:7]([C:12]#[N:13])[CH:6]=2)[O:11][C:2]1([CH3:15])[CH3:1]
Reactant: CC1(C)Oc2ccc(C#N)cc2C2OC21
Reactant: O=[N+]([O-])c1ccc(N2CCNCC2)cc1
Product: CC1(C)Oc2ccc(C#N)cc2C(N2CCN(c3ccc([N+](=O)[O-])cc3)CC2)C1O

Procedure:
Following the procedure in Example 1, using (±)-2,2-dimethyl-1a,7b-dihydro-2H-1,3-dioxa-cyclopropa[a]naphthalene-6-carbonitrile and 1-(4-nitro-phenyl)-piperazine as starting material, the title compound was prepared as a white solid.
Reaction SMILES: [C:1]([C:7]1[C:8]([CH3:20])=[C:9]([CH3:19])[C:10]2[O:14][CH:13]([C:15]([OH:17])=[O:16])[CH2:12][C:11]=2[CH:18]=1)(=[O:6])[CH2:2][CH:3]([CH3:5])[CH3:4].C=O.Cl.[CH3:24]NC.Cl>CN(C)C=O.C(O)(=O)C>[CH2:24]=[C:2]([CH:3]([CH3:5])[CH3:4])[C:1]([C:7]1[C:8]([CH3:20])=[C:9]([CH3:19])[C:10]2[O:14][CH:13]([C:15]([OH:17])=[O:16])[CH2:12][C:11]=2[CH:18]=1)=[O:6]
Reactant: Cc1c(C(=O)CC(C)C)cc2c(c1C)OC(C(=O)O)C2
Reactant: CNC
Agent: C=O
Agent: Cl
Solvent: CN(C)C=O
Solvent: CC(=O)O
Product: C=C(C(=O)c1cc2c(c(C)c1C)OC(C(=O)O)C2)C(C)C
Temperature: 0 °C

Procedure:
A mixture 2,3-dihydro-5-isovaleryl-6,7-dimethylbenzofuran-2-carboxylic acid (8.5 g.), paraformaldehyde (2.0 g.), dimethylamine hydrochloride (3.3 g.) and acetic acid (1 ml.) is heated at 95° for 2.5 hours, treated with dimethylformamide (75 ml.), heated an additional 3.5 hours then poured into ice water (300 ml.) containing hydrochloric acid (5 ml.). The product is extracted into ether, washed with water, dried over magnesium sulfate and the solvent evaporated at reduced pressure to afford 2,3-dihydro-5-(2-methyleneisovaleryl)-6,7-dimethylbenzofuran-2-carboxylic acid which melts at 97°C. after recrystallization from cyclohexane.
Reaction SMILES: [C:1]([O:5][C:6](=[O:29])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:14]=[C:15]([C:19]2[N:24]=[C:23]([C:25]([O:27]C)=[O:26])[CH:22]=[CH:21][CH:20]=2)[CH:16]=[CH:17][CH:18]=1)([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>CO.O>[C:1]([O:5][C:6](=[O:29])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:14]=[C:15]([C:19]2[N:24]=[C:23]([C:25]([OH:27])=[O:26])[CH:22]=[CH:21][CH:20]=2)[CH:16]=[CH:17][CH:18]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)c1cccc(-c2cccc(OCCCCCC(=O)OC(C)(C)C)c2)n1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CC(C)(C)OC(=O)CCCCCOc1cccc(-c2cccc(C(=O)O)n2)c1
Temperature: 25 °C
Yield: 100.1 %

Procedure:
To a solution of compound 8 (840 mg, 2.1 mmol, 1 eq.) in methanol (5 mL) was added NaOH (168 mg, 4.2 mmol, 2 eq.) dissolved in a minimum amount of water. The mixture was stirred at room temperature and monitored by TLC. After completion of the reaction volatiles were removed in vacuo and ethyl acetate added. The solution was washed with NaH2PO4 buffer (pH 5, 1M) and brine, dried over Na2SO4 and concentrated in vacuo to give 810 mg of crude compound 9, which was used directly in the next step. MS m/z 386 [M+H]+
Reaction SMILES: [CH3:1][O:2]/[C:3](/[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH3:15])=[CH:4]/[C:5]([O:7][CH3:8])=[O:6].[Br:16]N1C(=O)CCC1=O>CO>[CH3:1][O:2]/[C:3](/[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH2:15][Br:16])=[CH:4]/[C:5]([O:7][CH3:8])=[O:6]
Reactant: COC(=O)/C=C(/OC)c1ccccc1C
Reactant: O=C1CCC(=O)N1Br
Solvent: CO
Product: COC(=O)/C=C(/OC)c1ccccc1CBr

Procedure:
200 g (0.97 mol) of methyl (E)-β-methoxy-2-methylcinnamate and 190 g (1.07 mol) of N-bromosuccinimide which has been washed with methanol and dried, in 2 1 of dry tetrachloromethane, are irradiated with a 300 watt UV lamp for 75 min, during which the solution begins to reflux.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.CC(C)([O-])C.[K+].[CH2:12]([O:15][C:16]([N:18]1[CH2:22][C@H:21]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH2:20][C@H:19]1[CH2:31][CH2:32][CH2:33]OS(C)(=O)=O)=[O:17])[CH:13]=[CH2:14].O>CN(C)C=O>[CH2:12]([O:15][C:16]([N:18]1[CH2:22][C@H:21]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:25])[CH3:26])[CH2:20][C@H:19]1[CH2:31][CH2:32][CH2:33][N:1]1[CH:5]=[CH:4][N:3]=[CH:2]1)=[O:17])[CH:13]=[CH2:14]
Reactant: c1c[nH]cn1
Reactant: C=CCOC(=O)N1C[C@H](O[Si](C)(C)C(C)(C)C)C[C@H]1CCCOS(C)(=O)=O
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: C=CCOC(=O)N1C[C@H](O[Si](C)(C)C(C)(C)C)C[C@H]1CCCn1ccnc1
Temperature: 60 °C
Reaction time: 0.17 h
Yield: 96.5 %

Procedure:
To a solution of imidazole (3.57 g) in dimethylformamide (100 ml) was added potassium t-butoxide (5.89 g) portionwise at room temperature and the mixture was stirred at the same temperature for 10 minutes. Then a solution of (2R,4R)-1-allyloxycarbonyl-4-t-butyldimethylsilyloxy-2-(3-methanesulfonyloxypropyl)pyrrolidine (20.1 g), in dimethylformamide (20 ml) was added and the mixture was heated at 60° C. After stirring for 1 hour, water (200 ml) was added and the mixture was extracted with hexane-ethyl acetate (2:1) (200 ml×5). The combined extract was washed with water (1 l), brine (1 l), and dried over magnesium sulfate. Evaporation of the solvent gave (2R,4R)-1-allyloxycarbonyl-4-t-butyldimethylsilyloxy-2-[3-(imidazol-1-yl)propyl]pyrrolidine (18.1 g) as a yellow paste.
Reaction SMILES: Cl[C:2]1[C:11]2[N:12]=[CH:13][N:14]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.[NH3:19]>CO>[CH3:17][CH:16]([CH3:18])[CH2:15][N:14]1[C:10]2[C:9]3[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=3[N:3]=[C:2]([NH2:19])[C:11]=2[N:12]=[CH:13]1
Reactant: N
Reactant: CC(C)Cn1cnc2c(Cl)nc3ccccc3c21
Solvent: CO
Product: CC(C)Cn1cnc2c(N)nc3ccccc3c21
Temperature: 20 °C

Procedure:
A solution of 4-chloro-l-(2-methylpropyl)-1H-imidazo[4,5-c]quinoline (0.86 g) in 7 g of a methanol solution containing 20% by weight of ammonia was placed in a steel bomb for 20 h at 150° C. After cooling to 20° C., the solid formed was collected by filtration and washed with methanol. The crude product 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine was recystallized from N,N-dimethylformamide.
Reaction SMILES: [C:1]1([S:7][CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N12CCN(CC1)CC2.C([Li:21])CCC.CCCCCC>O1CCCC1>[C:1]1([S:7][CH2:8][Li:21])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: [Li]CCCC
Reactant: CSc1ccccc1
Agent: C1CN2CCN1CC2
Solvent: C1CCOC1
Solvent: CCCCCC
Product: [Li]CSc1ccccc1
Temperature: 0 °C

Procedure:
A solution of 5.4 g (44 mmol) of thioanisole and 4.89 g (43.6 mmol) of 1,4-diazabicyclo[2,2,2]octane in 44 ml of tetrahydrofuran was placed in an oven-dried flask and cooled to 0° C. A 2.5 M solution of butyl lithium in hexane (17.4 ml, 43.6 mmol) was added with stirring and the mixture allowed to warm to room temperature and react for about 1 hour to form phenylthiomethyl lithium. A solution of 3.14 g (8.71 mmol) of 1-(2-methoxymethoxyphenyl)-1-(3,4-dimethoxy-2-methoxymethoxyphenyl)ethene in tetrahydrofuran was added and the mixture heated to reflux with stirring under an argon atmosphere After 10 hours another 21 8 mmol of phenylthiomethyl lithium was prepared and added to the mixture and refluxing was continued overnight. The mixture was then cooled and poured into 200 ml of 5 percent aqueous sodium hypochlorite solution and 200 g of ice and 150 ml of ether added. The organic phase was separated, dried over magnesium sulfate and concentrated by evaporation under reduced pressure to obtain 6.61 g of an oil. This was purified by silica gel chromatography (80 mm×3" filter funnel), eluting with hexane containing ever increasing amounts of ether to obtain 1.16 g of the title compound as an oil. The proton and carbon NMR and infrared spectra were consistent with the assigned structure.
Reaction SMILES: [CH3:1][C:2]1[C:3]([CH2:11]O)=[N:4][CH:5]=[C:6]([CH3:10])[C:7]=1[O:8][CH3:9].S(Cl)([Cl:15])=O>>[CH3:1][C:2]1[C:3]([CH2:11][Cl:15])=[N:4][CH:5]=[C:6]([CH3:10])[C:7]=1[O:8][CH3:9]
Reactant: COc1c(C)cnc(CO)c1C
Reactant: O=S(Cl)Cl
Product: COc1c(C)cnc(CCl)c1C

Procedure:
If desired, the 3,5-dimethyl-4-methoxy-2-hydroxymethylpyridine prepared in this way is then reacted with thionyl chloride to give 3,5-dimethyl-4-methoxy-2-chloromethylpyridine.
Reaction SMILES: [NH2:1][CH2:2][C:3]([C@@H:5]1[C@@H:10]([OH:11])[C@H:9]([OH:12])[C@@H:8]([CH2:13][OH:14])[O:7][C@@:6]1([NH2:43])[N:15]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[C:16](=[O:28])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])=[O:4].[C:44]([NH:54][CH2:55][C:56](O)=[O:57])([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45]>ClCCl>[C:44]([NH:54][CH2:55][C:56]([NH:1][CH2:2][C:3]([C@@H:5]1[C@@H:10]([OH:11])[C@H:9]([OH:12])[C@@H:8]([CH2:13][OH:14])[O:7][C@@:6]1([NH2:43])[N:15]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[C:16](=[O:28])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])=[O:4])=[O:57])([O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)=[O:45]
Reactant: CCCCCCCCCCCCCCN(C(=O)CCCCCCCCCCC)[C@]1(N)O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1C(=O)CN
Reactant: O=C(O)CNC(=O)OCc1ccccc1
Solvent: ClCCl
Product: CCCCCCCCCCCCCCN(C(=O)CCCCCCCCCCC)[C@]1(N)O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1C(=O)CNC(=O)CNC(=O)OCc1ccccc1
Yield: 47 %

Procedure:
from N-(2-glycyl-amino-2-deoxy-β-D-glucopyranosyl)-N-tetradecyl-dodecanamide and N-carbobenzoxy-glycine. Yield 47%. [α]D =+18.7° (c=0.95, dichloromethane). m.p. 108-109°.
Reaction SMILES: [C:1]([NH:4][CH2:5][C@@H:6]1[O:10][C:9](=[O:11])[N:8]([C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[N:18]([C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[C@H:17]([CH3:32])[CH2:16][CH2:15]3)[CH2:7]1)(=O)[CH3:2].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:42])=CC=1>C1(C)C=CC=CC=1>[C:1]([NH:4][CH2:5][C@@H:6]1[O:10][C:9](=[O:11])[N:8]([C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[N:18]([C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[C@H:17]([CH3:32])[CH2:16][CH2:15]3)[CH2:7]1)(=[S:42])[CH3:2]
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: CC(=O)NC[C@H]1CN(c2ccc3c(c2)CC[C@@H](C)N3C(=O)OCc2ccccc2)C(=O)O1
Solvent: Cc1ccccc1
Product: CC(=S)NC[C@H]1CN(c2ccc3c(c2)CC[C@@H](C)N3C(=O)OCc2ccccc2)C(=O)O1

Procedure:
The product of EXAMPLE 14, Step 2 (1.0 g, 2.3 mmol) and Lawesson's Reagent (0.50 g, 1.3 mmol) are stirred in Toluene (20 mL) at reflux for 2 hours. Solvent is removed by evaporation and the residue is chromatographed on silica gel using 0-4% MeOH/CH2Cl2 eluant. The title compound is isolated as a white solid 1.0 g (97%); HRMS (FAB) calcd for C24H27N3O4S+H1 454.1800, found 454.1813.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([S:11][CH2:12][CH2:13][CH2:14][CH2:15][O:16][C:17]2[C:18]([N+:30]([O-:32])=[O:31])=[CH:19][C:20]3[NH:25][C:24](=[O:26])[O:23][C:22]([CH3:28])([CH3:27])[C:21]=3[CH:29]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[OH:33]O>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([S:11]([CH2:12][CH2:13][CH2:14][CH2:15][O:16][C:17]2[C:18]([N+:30]([O-:32])=[O:31])=[CH:19][C:20]3[NH:25][C:24](=[O:26])[O:23][C:22]([CH3:27])([CH3:28])[C:21]=3[CH:29]=2)=[O:33])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: OO
Reactant: COc1ccc(SCCCCOc2cc3c(cc2[N+](=O)[O-])NC(=O)OC3(C)C)cc1OC
Product: COc1ccc(S(=O)CCCCOc2cc3c(cc2[N+](=O)[O-])NC(=O)OC3(C)C)cc1OC

Procedure:
Prepared analogously to Example 2 from 6-[4-(3,4-dimethoxy-phenylmercapto)-butoxy]-7-nitro-4,4-dimethyl-4H-3,1-benzoxazin-2-one and hydrogen peroxide.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6](F)[CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[C:12]([N:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)(=[O:14])[CH3:13].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]([N:18]2[CH2:19][CH2:20][N:15]([C:12](=[O:14])[CH3:13])[CH2:16][CH2:17]2)[CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10]
Reactant: O=[N+]([O-])c1ccc(F)cc1Cl
Reactant: CC(=O)N1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(=O)N1CCN(c2ccc([N+](=O)[O-])c(Cl)c2)CC1
Temperature: 50 °C
Reaction time: 8 h

Procedure:
2-chloro-4-fluoronitrobenzene (350 mg), N-acetylpiperazine (0.5 ml) and potassium carbonate (500 mg) were dissolved in dimethylformamide (3 ml) and stirred at 50° C. overnight. The reaction mixture was distilled under reduced pressure to remove dimethylformamide and added with distilled water. Then, the recrystallized yellow solid was filtered and the subsequent reaction was proceeded without further purification.
Reaction SMILES: [CH3:1][O:2][N:3]([C:32]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:4]1[NH:5][C:6](=[O:31])[C:7]2[N:8]=[CH:9][N:10]([C@@H:13]3[O:18][C@H:17]([CH2:19][O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])[C@@H:15]([OH:16])[C@@:14]3([C:29]#[CH:30])[F:28])[C:11]=2[N:12]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[O:62]1[CH:67]=[CH:66][CH2:65][CH2:64][CH2:63]1>C1COCC1.C(Cl)Cl>[CH3:1][O:2][N:3]([C:32]([C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1)([C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[C:4]1[NH:5][C:6](=[O:31])[C:7]2[N:8]=[CH:9][N:10]([C@@H:13]3[O:18][C@H:17]([CH2:19][O:20][Si:21]([C:24]([CH3:27])([CH3:25])[CH3:26])([CH3:22])[CH3:23])[C@@H:15]([O:16][CH:63]4[CH2:64][CH2:65][CH2:66][CH2:67][O:62]4)[C@@:14]3([C:29]#[CH:30])[F:28])[C:11]=2[N:12]=1
Reactant: C1=COCCC1
Reactant: C#C[C@@]1(F)[C@H](O)[C@@H](CO[Si](C)(C)C(C)(C)C)O[C@H]1n1cnc2c(=O)[nH]c(N(OC)C(c3ccccc3)(c3ccccc3)c3ccccc3)nc21
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: C1CCOC1
Solvent: ClCCl
Product: C#C[C@@]1(F)[C@H](OC2CCCCO2)[C@@H](CO[Si](C)(C)C(C)(C)C)O[C@H]1n1cnc2c(=O)[nH]c(N(OC)C(c3ccccc3)(c3ccccc3)c3ccccc3)nc21
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a stirred solution of 13 (0.8 mmol), in anh THF (20 ml/mmol), at room temperature, was added p-toluen sulfonic acid (0.12 mmol) and dihydropyran (2 ml/mmol). The reaction mixture was stirred at room temperature for 3 days and neutralized with TEA. The mixture was diluted with DCM, washed twice with H2O. The organic phase was dried over Na2SO4, filtered and evaporated. The crude material was purified by silica gel chromatography (DCM/MeOH) to yield the title compound. Molecular Formula C43H52FN5O6Si. Scan ES+ 780 (M+H)+
Reaction SMILES: C(O[C:4]([C:6]1[N:11]=[CH:10][C:9]2[N:12]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([O:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[CH:17][CH:16]=3)[S:14][C:8]=2[C:7]=1[OH:28])=[O:5])C.[NH2:29][CH2:30][C:31]([OH:33])=[O:32]>C[O-].[Na+].CO>[OH:28][C:7]1[C:8]2[S:14][C:13]([C:15]3[CH:16]=[CH:17][C:18]([O:21][C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)=[CH:19][CH:20]=3)=[N:12][C:9]=2[CH:10]=[N:11][C:6]=1[C:4]([NH:29][CH2:30][C:31]([OH:33])=[O:32])=[O:5]
Reactant: NCC(=O)O
Reactant: CCOC(=O)c1ncc2nc(-c3ccc(Oc4ccccc4)cc3)sc2c1O
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: O=C(O)CNC(=O)c1ncc2nc(-c3ccc(Oc4ccccc4)cc3)sc2c1O
Temperature: 25 °C
Yield: 68.7 %

Procedure:
A mixture of 7-hydroxy-2-(4-phenoxy-phenyl)-thiazolo[4,5-c]pyridine-6-carboxylic acid ethyl ester (75 mg, 0.19 mmole) and glycine (286 mg, 3.81 mmole) in 0.5 M sodium methoxide/methanol (7.2 ml) was refluxed for three days before it was cooled to room temperature and concentrated in vacuo. Water (75 ml) was added and pH was adjusted to 10 with 1N HCl (2 ml). The mixture was extracted with methyl tert-butyl ether (2×30 ml) and dichloromethane (30 ml). The remaining aqueous layer was acidified to pH=3 with 1N HCl (3 ml). The solid precipitate was filtered, washed with water and dried in vacuo to give the title compound as a white solid (55 mg). 1H NMR (DMSO-d6, 200 MHz): δ=9.45 (br s, 1H), 8.87 (s, 1H), 8.17 (m, 2H), 7.47 (m, 2H), 7.17 (m, 5H), 4.03 (d, J=6.3 Hz, 2H); MS: (+) m/z 421.07 (M+1). (−) m/z 419.87 (M−1).
Reaction SMILES: [C:1]([C:4]1[CH:12]=[CH:11][CH:10]=[CH:9][C:5]=1[C:6](O)=[S:7])(=[O:3])[CH3:2].[C:13]([O:17][C:18](=[O:26])[CH2:19][NH:20][CH:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1)([CH3:16])([CH3:15])[CH3:14]>C(Cl)Cl>[C:13]([O:17][C:18](=[O:26])[CH2:19][N:20]([C:6](=[S:7])[C:5]1[CH:9]=[CH:10][CH:11]=[CH:12][C:4]=1[C:1](=[O:3])[CH3:2])[CH:21]1[CH2:22][CH2:23][CH2:24][CH2:25]1)([CH3:16])([CH3:14])[CH3:15]
Reactant: CC(=O)c1ccccc1C(O)=S
Reactant: CC(C)(C)OC(=O)CNC1CCCC1
Solvent: ClCCl
Product: CC(=O)c1ccccc1C(=S)N(CC(=O)OC(C)(C)C)C1CCCC1
Reaction time: 8 h

Procedure:
N,N1 -Dicyclohexylcarbodiimide (15.9 g, 77 mmol) in methylene chloride was added slowly to a mixture of 2-acetylthiobenzoic acid (15.2 g, 77 mmol) and N-cyclopentylglycine t-butyl ester (15.4 g) in methylene chloride maintained at 0°-5°. The mixture was brought to room temperature overnight, filtered, and the filtrate washed successively with dilute hydrochloric acid, saturated sodium bicarbonate and saturated sodium chloride solutions. After drying, the organic portion was concentrated, the residue dissolved in ether and the resulting solution filtered. Concentration of the filtrate gave crude N-(2-acetylthiobenzoyl)-N-cyclopentylglycine t-butyl ester as an oil.