Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([NH:4][C:5]2[CH:10]=[CH:9][N:8]=[CH:7][C:6]=2[N+:11]([O-])=O)[CH2:3][CH2:2]1.OCC1(OC[C@@H](O)[C@@H](O)[C@H]1O)O>C(O)C.[Pd]>[CH:1]1([NH:4][C:5]2[CH:10]=[CH:9][N:8]=[CH:7][C:6]=2[NH2:11])[CH2:3][CH2:2]1
Reactant: O=[N+]([O-])c1cnccc1NC1CC1
Agent: [Pd]
Agent: OCC1(O)OC[C@@H](O)[C@@H](O)[C@H]1O
Solvent: CCO
Product: Nc1cnccc1NC1CC1
Yield: 95.7 %

Procedure:
A mixture of the intermediate 5-b (167 g, 932 mmol) in ethanol (1400 mL) was hydrogenated (50 Psi) at 20° C. with wet 10% Pd/C (34 g) as a catalyst overnight. After uptake of H2 (3 eq.), the catalyst was filtered off and the filtrate was evaporated. The residue was washed with MTBE to afford compound 5-c as a yellow powder (133 g, 95%).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][NH:4][C:5]([N:7]([CH2:19][CH3:20])[CH:8]1[O:16][C@H:15]([CH2:17][OH:18])[C@@H:13]([OH:14])[C@H:11]([OH:12])[C@H:9]1[OH:10])=[O:6].C(=O)([O-])[O-].[Na+].[Na+].[N+:27]([O-])([N+]([O-])=O)=[O:28]>O1CCCC1.C(Cl)Cl>[Cl:1][CH2:2][CH2:3][N:4]([N:27]=[O:28])[C:5]([N:7]([CH2:19][CH3:20])[CH:8]1[O:16][C@H:15]([CH2:17][OH:18])[C@@H:13]([OH:14])[C@H:11]([OH:12])[C@H:9]1[OH:10])=[O:6]
Reactant: O=[N+]([O-])[N+](=O)[O-]
Reactant: CCN(C(=O)NCCCl)C1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: ClCCl
Product: CCN(C(=O)N(CCCl)N=O)C1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Yield: 76.8 %

Procedure:
3.1 g of 1-(2-chloroethyl)-3-ethyl-3-D-glucopyranosylurea are dissolved in a mixture of 80 ml of tetrahydrofuran and 80 ml of methylene chloride, and 15 g of sodium carbonate anhydrate are added thereto. 5 g of nitrogen tetroxide gas are introduced into the mixture for 10 minutes under ice-cooling. The mixture is treated in the same manner as described in Example 2. 2.6 g of 1-(2-chloroethyl)-1-nitroso-3-ethyl-3-D-glucopyranosylurea are thereby obtained as pale yellow caramel.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]([N:12]1[CH2:16][C@@H:15]([OH:17])[CH2:14][O:13]1)=[O:11].C(N(CC)C(C)C)(C)C.[CH3:28][S:29](Cl)(=[O:31])=[O:30]>ClCCl>[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]([N:12]1[CH2:16][C@@H:15]([O:17][S:29]([CH3:28])(=[O:31])=[O:30])[CH2:14][O:13]1)=[O:11]
Reactant: CS(=O)(=O)Cl
Reactant: COC(=O)c1ccccc1C(=O)N1C[C@@H](O)CO1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1ccccc1C(=O)N1C[C@@H](OS(C)(=O)=O)CO1
Temperature: 25 °C
Reaction time: 18 h
Yield: 100 %

Procedure:
2-[(R)-4-Hydroxyisoxazolidine-2-carbonyl]benzoic acid methyl ester (prepared by the method of Martin et al., Tetrahedron Lett., 2007, 47, 7635) (3.50 g, 14.0 mmol) was dissolved in dichloromethane (100 mL) and N,N-diisopropylethylamine (3.55 mL, 20.3 mmol), then methanesulfonyl chloride (1.40 mL, 18.5 mmol) was added and the mixture was stirred at room temperature for 18 hours. The mixture was washed with 0.1M HCl solution (100 mL), dried (Na2SO4) and concentrated in vacuo to give the title compound as a yellow oil (5.00 g, 100%). δH (DMSO-d6) 7.92-7.46 (4H, m), 4.28 (1H, m) 4.17-4.14 (2H, m), 4.06-3.92 (2H, m), 3.82 (3H, s), 3.31 (3H, s). LCMS (ES+) RT 1.45 minutes, 330 (M+H)+ (pH 3).
Reaction SMILES: [F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:16]=[N:17][N:18]([CH2:20][C:21]([OH:23])=[O:22])[CH:19]=2)[CH2:10][C@H:9]1[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[C:27]([CH3:32])[CH:26]=1)=[O:7].O.ON1C2C=CC=CC=2N=N1.[ClH:53].C(N=C=NCCCN(C)C)C.[NH:65]1[CH2:70][CH2:69][O:68][CH2:67][CH2:66]1.Cl.C(OC(C)C)(C)C>O1CCCC1.C(OCC)(=O)C>[ClH:53].[F:39][C:36]([F:38])([F:37])[C:34]1[CH:33]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:40])[F:41])[CH:35]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:16]=[N:17][N:18]([CH:20]([N:65]3[CH2:70][CH2:69][O:68][CH2:67][CH2:66]3)[C:21]([OH:23])=[O:22])[CH:19]=2)[CH2:10][C@H:9]1[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[C:27]([CH3:32])[CH:26]=1)=[O:7]
Reactant: Cc1ccc(C[C@@H]2CN(Cc3cnn(CC(=O)O)c3)CCN2C(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)cc1C
Reactant: C1COCCN1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: C1CCOC1
Solvent: O
Solvent: CC(C)OC(C)C
Product: Cc1ccc(C[C@@H]2CN(Cc3cnn(C(C(=O)O)N4CCOCC4)c3)CCN2C(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)cc1C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[[1-(carboxymethyl)-1H-pyrazol-4-yl]methyl]-2-(3,4-dimethylbenzyl)piperazine (120 mg) in tetrahydrofuran (1 ml) were added 1-hydroxybenzotriazole hydrate (176 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (240 mg) and morpholine (0.11 ml) at room temperature, and the mixture was stirred at room temperature overnight. The mixture was quenched with water, and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and evaporated under reduced pressure. The residue was purified by column chromatography on a silica gel using a mixture of methanol and ethyl acetate (1:9) as eluent to give a crude oil (76.7 mg). The oil was dissolved in ethyl acetate (0.7 ml) and added 4N hydrogen chloride in ethyl acetate (0.15 ml) at room temperature. After the addition of isopropyl ether, the resulting precipitate was filtered off and dried under reduced pressure to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[[1-(morpholinocarboxymethyl)-1H-pyrazol-4-yl]methyl]piperazine hydrochloride (40 mg) as a powder.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.Br[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9]>CN(C)C=O>[CH2:11]([O:10][C:8](=[O:9])[CH2:7][N:1]1[CH:5]=[CH:4][N:3]=[CH:2]1)[CH3:12]
Reactant: c1c[nH]cn1
Reactant: CCOC(=O)CBr
Solvent: CN(C)C=O
Product: CCOC(=O)Cn1ccnc1
Reaction time: 4 h
Yield: 17 %

Procedure:
5.0 g (73.4 mmol) of imidazole and 3.36 ml(29.4 mmol) of ethyl bromoacetate were dissolved in 50 ml of dimethylformamide and stirred for 4 hours. Dimethylformamide was removed in vacuo. Then, 100 ml of ethyl acetate was added to the residue and it was washed with saturated sodium chloride solution. Removal of the organic solvent under reduced pressure provided 0.77 g(Yield: 17%) of the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:5]=3[C:4]=2[CH:3]=1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:39]#[C:40][C:41]1[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][CH:42]=1>C1(C)C=CC=CC=1.S([O-])([O-])(=O)=O.[Cu+2]>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([C:39]#[C:40][C:41]3[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][CH:42]=3)[C:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:5]=3[C:4]=2[CH:3]=1
Reactant: CN1CCc2[nH]c3ccc(Cl)cc3c2C1
Reactant: Clc1ccc(C#CBr)cc1
Agent: [Cu+2]
Agent: O=P([O-])([O-])[O-]
Agent: O=S(=O)([O-])[O-]
Solvent: Cc1ccccc1
Product: CN1CCc2c(c3cc(Cl)ccc3n2C#Cc2ccc(Cl)cc2)C1
Temperature: 80 °C
Yield: 33.8 %

Procedure:
8-Chloro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (220 mg, 1 mmol) was dissolved in toluene (8-10 mL). Copper sulfate (50 mg, 0.2 mmol), 1,10-phenanthroline (72 mg, 0.4 mmol), potassium phosphate (425 mg, 2 mmol) and 1-(bromoethynyl)-4-chlorobenzene (237 mg, 1.1 mmol) was added and the mixture flushed with nitrogen. The reaction mixture was heated at 80° C. overnight (16 h). Product was detected by LCMS. The reaction mixture was filtered through Celite, washed with DCM. The combined organic layer was concentrated under vacuum to obtain product, which was purified by column chromatography using silica and 60-80% EtOAc in hexane as eluent to obtain product (120 mg) as a brown semi solid. 1H NMR (CDCl3, HCl salt) δ (ppm): 7.52-7.42 (m, 3H), 7.38-7.32 (m, 2H), 7.30 (s, 1H), 7.23-7.20 (d, 1H), 3.62 (s, 2H), 3.02-2.97 (m, 2H), 2.96-2.86 (m, 2H), 2.60 (s, 3H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[CH2:4][CH2:5][S:6][CH2:7][C:8](OC)=[O:9].CCCCCC.[H-].[Na+]>C1COCC1>[CH3:1][O:2][C:3]([CH:4]1[C:8](=[O:9])[CH2:7][S:6][CH2:5]1)=[O:12]
Reactant: COC(=O)CCSCC(=O)OC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCCCCC
Product: COC(=O)C1CSCC1=O
Yield: 35.4 %

Procedure:
A solution of 3-methoxycarbonylmethylsulfanyl-propionic acid methyl ester (32) (58 g, 300 mmol) in dry T HF (800 mL) was added slowly within 4 h to a refluxing solution of hexane washed NaH (60% in mineral oil, 13.24 g, 331 mmol) in THF. The solution was further refluxed for 5 h. The solution was cooled and the solvent was evaporated. The residue was taken in water, acidified to pH˜1 by cold HCl solution, and extracted by CH2Cl2. The combined organic phase was dried over MgSO4 and concentrated under vacuum to get a viscous residue. The residue was purified by flash chromatography eluting with hexane to yield 17 g (35%) of 4-oxo-tetrahydro-thiophene-3-carboxylic acid methyl ester as colorless viscous oil which solidified on keeping overnight under vacuum. MP 51° C.; 1H NMR (400 MHz, CDCl3) δ 3.17-3.82 (m, 6.5 H), 10.94 (s, 0.5H) ppm. The isomeric mixture was used to next step without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:16]2[C:11](=[N:12][C:13]([O:22][C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[F:30])=[N:14][C:15]=2[NH:17][CH2:18][C@@H:19]([OH:21])[CH3:20])[NH:10][N:9]=1.[P:31]([O:36]C)([O:34][CH3:35])[O:32][CH3:33].C(Br)(Br)(Br)Br.Cl>N1C=CC=CC=1>[CH3:33][O:32][P:31](=[O:36])([O:34][CH3:35])[O:21][CH:19]([CH3:20])[CH2:18][NH:17][C:15]1[N:14]=[C:13]([O:22][C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=2[F:30])[N:12]=[C:11]2[NH:10][N:9]=[C:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])[C:16]=12
Reactant: COP(OC)OC
Reactant: C[C@H](O)CNc1nc(Oc2ccc(F)cc2F)nc2[nH]nc(-c3ccccc3Cl)c12
Agent: BrC(Br)(Br)Br
Agent: Cl
Solvent: c1ccncc1
Product: COP(=O)(OC)OC(C)CNc1nc(Oc2ccc(F)cc2F)nc2[nH]nc(-c3ccccc3Cl)c12
Temperature: 0 °C

Procedure:
(S)-1-[3-(2-chlorophenyl)-6-(2,4-difluorophenoxy)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]propan-2-ol (2.5 g, 5.79 mmol) was dissolved in 20 mL pyridine at room temperature, and the mixture was cooled to 0° C. with stirring. P(OCH3)3 (1.93 mL, excess) and CBr4 (0.96 g) were added slowly, and the reaction mixture was allowed to warm up to room temperature over 20 minutes with stirring. The reaction mixture was poured into cold 1N HCl, and the resulting solution was extracted with EtOAc. The combined organic layers were washed with 1N HCl, followed by saturated aqueous NaHCO3, then with saturated brine. The organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, 30%-60% EtOAc in methylene chloride) to give 3.132 g of phosphoric acid 2-[3-(2-chloro-phenyl)-6-(2,4-difluoro-phenoxy)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-1-methyl-ethyl ester dimethyl ester, MS (M+H)=540.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14](=[O:20])[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:10][CH:9]=1.[H][H]>[Pt]=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([CH:14]([OH:20])[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:10][CH:9]=1
Reactant: CCOC(=O)C(=O)c1ccc(-c2ccccc2Cl)cc1
Reactant: [H][H]
Agent: O=[Pt]
Product: CCOC(=O)C(O)c1ccc(-c2ccccc2Cl)cc1

Procedure:
Into a Paar hydrogenation bottle is added 41.5 g. (0.144 mole) of ethyl 2'-chloro-4-biphenylylglyoxylate, 2 ml. of 0.1 M-ferrous sulfate solution, 220 ml. of isopropionyl and 1.0 g. of 85.1% platinum oxide. The mixture is shaken for 2 hours at room temperature with hydrogen gas until 0.144 mole of hydrogen is absorbed. The catalyst is then filtered off and the solution is evaporated in vacuo and the residue fractionally distilled to obtain ethyl 2'-chloro-4-biphenylylglycolate.
Reaction SMILES: [CH2:1]([O:3][P:4]([C:9]1[CH:10]=[C:11]([CH2:15][C:16]([O:18]CC)=[O:17])[CH:12]=[CH:13][CH:14]=1)([O:6][CH2:7][CH3:8])=[O:5])[CH3:2].O[Li].O>C(O)C.O>[CH2:7]([O:6][P:4]([C:9]1[CH:10]=[C:11]([CH2:15][C:16]([OH:18])=[O:17])[CH:12]=[CH:13][CH:14]=1)([O:3][CH2:1][CH3:2])=[O:5])[CH3:8]
Reactant: CCOC(=O)Cc1cccc(P(=O)(OCC)OCC)c1
Agent: [Li]O
Solvent: O
Solvent: CCO
Product: CCOP(=O)(OCC)c1cccc(CC(=O)O)c1
Reaction time: 8 h

Procedure:
A mixture of ethyl 2-(3-(diethoxyphosphoryl)phenyl)acetate, 35i-c, (26 g, 86.7 mmol) and LiOH.H2O (5.5 g, 130 mmol) in ethanol (40 mL) and H2O (40 mL) was stirred overnight. The resulting mixture was concentrated and washed by ethyl acetate. The aqueous layers were adjusted to about pH 1-2 with HCl. The mixture was extracted by ethyl acetate. The combined organic layers were washed by brine, dried over Na2SO4 and concentrated to afford the title compound, 35i-d, as brown oil (19 g, 81%). 1H NMR (300 MHz, CDCl3) δ1.15-1.25 (m, 6H), 3.68 (s, 2H), 3.95-4.06 (m, 4H), 7.43-7.64 (m, 4H), 12.32 (s, 1H). LC-MS (M+H)+ 273.
Reaction SMILES: [CH:1]1([N:4]([CH:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)[C:5](=[O:17])[C:6]2[CH:11]=[CH:10][C:9]([C:12]3[O:16][CH:15]=[N:14][CH:13]=3)=[CH:8][CH:7]=2)[CH2:3][CH2:2]1.Cl[C:25]1[N:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][N:26]=1>>[CH:1]1([N:4]([CH:18]2[CH2:23][CH2:22][N:21]([C:25]3[N:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][N:26]=3)[CH2:20][CH2:19]2)[C:5](=[O:17])[C:6]2[CH:7]=[CH:8][C:9]([C:12]3[O:16][CH:15]=[N:14][CH:13]=3)=[CH:10][CH:11]=2)[CH2:3][CH2:2]1
Reactant: COc1cnc(Cl)nc1
Reactant: O=C(c1ccc(-c2cnco2)cc1)N(C1CCNCC1)C1CC1
Product: COc1cnc(N2CCC(N(C(=O)c3ccc(-c4cnco4)cc3)C3CC3)CC2)nc1

Procedure:
The title compound is prepared from N-cyclopropyl-4-oxazol-5-yl-N-piperidin-4-yl-benzamide and 2-chloro-5-methoxy-pyrimidine following a procedure analogous to that described in Example 19. LC (method 9): tR=1.88 min; Mass spectrum (ESI+): m/z=420 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][CH2:11]O)[CH:5]=[CH:6][C:7]=1[F:8].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:32]N1C(=O)CCC1=O>C(Cl)Cl>[Br:32][CH2:11][CH2:10][CH2:9][C:4]1[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=1
Reactant: OCCCc1ccc(F)c(Cl)c1
Reactant: O=C1CCC(=O)N1Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: Fc1ccc(CCCBr)cc1Cl
Yield: 92.9 %

Procedure:
Compound 61-2 (2.47 g) was dissolved in methylene chloride (20 ml), triphenylphosphine (3.78 g) and N-bromosuccinimide (2.56 g) were added under ice-cooling, and the mixture was stirred under ice-cooling for 1 hr. The reaction mixture was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. Diethyl ether (100 ml) was added, and the precipitated triphenylphosphine oxide was filtered off. The concentrate of the filtrate was purified by silica gel column chromatography (hexane alone) to give the object product (3.06 g) as a colorless oil.
Reaction SMILES: [C:1]([C:5]1[N:10]=[C:9]([NH:11][CH2:12][C:13]2[O:14][CH:15]=[CH:16][CH:17]=2)[C:8]([C:18]([N:20]([CH2:36][CH:37]([CH3:39])[CH3:38])[CH:21]2[CH2:26][CH:25]([CH2:27][OH:28])[CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22]2)=[O:19])=[CH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+]>FC(F)(F)C(O)=O>[C:1]([C:5]1[N:10]=[C:9]([NH:11][CH2:12][C:13]2[O:14][CH:15]=[CH:16][CH:17]=2)[C:8]([C:18]([N:20]([CH:21]2[CH2:26][CH:25]([CH2:27][OH:28])[CH2:24][NH:23][CH2:22]2)[CH2:36][CH:37]([CH3:39])[CH3:38])=[O:19])=[CH:7][N:6]=1)([CH3:3])([CH3:4])[CH3:2]
Reactant: CC(C)CN(C(=O)c1cnc(C(C)(C)C)nc1NCc1ccco1)C1CC(CO)CN(C(=O)OC(C)(C)C)C1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O=C(O)C(F)(F)F
Product: CC(C)CN(C(=O)c1cnc(C(C)(C)C)nc1NCc1ccco1)C1CNCC(CO)C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 59.8 %

Procedure:
tert-Butyl 3-[({2-tert-butyl-4-[(furan-2-ylmethyl)amino]pyrimidin-5-yl}carbonyl)(2-methylpropyl)amino]-5-(hydroxymethyl)piperidine-1-carboxylate (50.0 mg) was dissolved in trifluoroacetic acid (50% 1,2-dichloroethane solution, 4 ml), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was basified with saturated aqueous potassium carbonate solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and the fraction eluted with ethyl acetate-hexane-methanol (50:50:0-100:0:0-85:0:15) was concentrated under reduced pressure to give the object compound (24.4 mg).
Reaction SMILES: C(OC(=O)[NH:7][C@@H:8]1[CH2:13][C@@H:12]([CH3:14])[CH2:11][N:10]([C:15](=[O:17])[CH3:16])[CH2:9]1)(C)(C)C.[ClH:19].O1CCOCC1>C(Cl)Cl>[ClH:19].[NH2:7][C@@H:8]1[CH2:13][C@@H:12]([CH3:14])[CH2:11][N:10]([C:15](=[O:17])[CH3:16])[CH2:9]1
Reactant: CC(=O)N1C[C@H](C)C[C@@H](NC(=O)OC(C)(C)C)C1
Agent: Cl
Solvent: C1COCCO1
Solvent: ClCCl
Product: CC(=O)N1C[C@H](C)C[C@@H](N)C1
Temperature: 25 °C
Yield: 95 %

Procedure:
((3R,5R)-1-Acetyl-5-methyl-piperidin-3-yl)-carbamic acid tert-butyl ester (0.5 g, 1.971 mmol) was dissolved in DCM (15 ml) and HCl 4M in dioxane (2.5 ml, 10 mmol) was added. The resulting colorless solution was stirred at RT until precipitation of a solid was observed. The solvent was evaporated and the residue was dried under high vacuum. To give 0.45 g of 1-((3R,5R)-3-amino-5-methyl-piperidin-1-yl)-ethanone hydrochloride as an off-white solid (>95% yield).
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9].[CH:13](OCC)=[O:14].[H-].[Na+]>COCCOC>[CH:13]([CH:7]([CH2:6][C:2]1[O:1][CH:5]=[CH:4][CH:3]=1)[C:8]([O:10][CH2:11][CH3:12])=[O:9])=[O:14]
Reactant: CCOC(=O)CCc1ccco1
Reactant: CCOC=O
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Product: CCOC(=O)C(C=O)Cc1ccco1
Yield: 75 %

Procedure:
Ethyl 3-(2-furyl)propionate was reacted with 1.1 equivalents ethyl formate and 1.0 equivalents sodium hydride in 1,2-dimethoxyethane at room temperature to give ethyl 2-formyl-3-(2-furyl)propionate as an oil in 75% yield.
Reaction SMILES: [CH3:1][NH:2][CH3:3].Br[CH2:5][CH2:6][CH2:7][CH2:8][O:9][C:10]1[C:11]([O:30][CH3:31])=[CH:12][CH:13]=[C:14]2[C:19]=1[O:18][C:17](=[O:20])[CH:16]=[C:15]2[NH:21][C:22]1[C:27]([Cl:28])=[CH:26][N:25]=[CH:24][C:23]=1[Cl:29]>CS(C)=O>[Cl:29][C:23]1[CH:24]=[N:25][CH:26]=[C:27]([Cl:28])[C:22]=1[NH:21][C:15]1[C:14]2[C:19](=[C:10]([O:9][CH2:8][CH2:7][CH2:6][CH2:5][N:2]([CH3:3])[CH3:1])[C:11]([O:30][CH3:31])=[CH:12][CH:13]=2)[O:18][C:17](=[O:20])[CH:16]=1
Reactant: COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCBr
Reactant: CNC
Solvent: CS(C)=O
Product: COc1ccc2c(Nc3c(Cl)cncc3Cl)cc(=O)oc2c1OCCCCN(C)C
Reaction time: 1 h

Procedure:
A solution of dimethylamine (3 mL, 2M THF, 6 mmol) was added to a solution of 8-(4-bromobutoxy)-4-(3,5-dichloropyridin-4-ylamino)-7-methoxy-2H-chromen-2-one (293 mg, 0.6 mmol, Example 25) and DMSO (6 mL). After 1 h, the reaction was concentrated and purified by reverse-phase HPLC (1:4→3:2; acetonitrile:water) to give 4-(3,5-dichloropyridin-4-ylamino)-8-(4-(dimethylamino)butoxy)-7-methoxy-2H-chromen-2-one: 1H NMR (400 MHz, DMSO-d6): δ 9.53 (br s, 1H), 8.58 (s, 2H), 7.87 (d, 1H), 7.07 (d, 1H), 4.22 (br s, 1H), 3.99 (t, 2H), 3.90 (s, 3H), 2.76 (br, 2H), 2.47 (s, 6H), 1.85-1.65 (m, 4H); MS (ESI): 451.9.
Reaction SMILES: [Si:1]([O:8][C:9]([C:11]([F:35])([F:34])[C@:12](OS(C(F)(F)F)(=O)=O)([C@@H:14]([CH:16]([C:18](=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[OH:17])[OH:15])O)=[O:10])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[N-:36]=[N+:37]=[N-:38].[Li+]>CN(C)C=O>[Si:1]([O:8][C:9]([C:11]([F:35])([F:34])[C@H:12]([N:36]=[N+:37]=[N-:38])[C@@H:14]([CH:16]([C:18](=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[OH:17])[OH:15])=[O:10])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)OC(=O)C(F)(F)[C@](O)(OS(=O)(=O)C(F)(F)F)[C@H](O)C(O)C(=O)c1ccccc1
Reactant: [N-]=[N+]=[N-]
Agent: [Li+]
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OC(=O)C(F)(F)[C@H](N=[N+]=[N-])[C@H](O)C(O)C(=O)c1ccccc1
Temperature: 70 °C
Yield: 55.9 %

Procedure:
To a solution of 4.53 g (8.7 mmol) 1-t-butyldimethylsilyloxy-5-benzoyl-3-trifluoromethanesulfonyloxy-2-deoxy-2,2-difluoroxylose in dimethylformamide (50 ml) were added 1.2 g (25.2 mmol) lithium azide and the reaction mixture was heated at 70° C. for 40 minutes. The reaction mixture was then concentrated under reduced pressure and the residue dissolved in ethyl acetate. This solution was washed several times with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. The residue was redissolved in a small amount of ethyl acetate and poured over a pad of silica gel, eluting with ethyl acetate. The filtrates were concentrated under reduced pressure to give 2.09 g (58%) of the desired compound as a colorless oil. FD-MS: m/e=356, (M-57, loss of t-butyl), 357((M+1)-57, loss of t-butyl). IR(neat): 2114 cm-1, N3.
Reaction SMILES: FC(F)(F)C(O)=O.C([O:12][C:13]([CH2:15][O:16][N:17]=[C:18]([C:48]1[N:49]=[CH:50][S:51][CH:52]=1)[C:19]([NH:21][CH:22]1[C:46](=[O:47])[N:24]2[C:25]([C:30]([O:32]C(C3C=CC=CC=3)C3C=CC=CC=3)=[S:31])=[C:26]([CH3:29])[CH2:27][S:28][C@H:23]12)=[O:20])=[O:14])(C)(C)C.C(OC(C)C)(C)C.CCCCCC>ClCCl.C1(OC)C=CC=CC=1>[C:13]([CH2:15][O:16][N:17]=[C:18]([C:48]1[N:49]=[CH:50][S:51][CH:52]=1)[C:19]([NH:21][CH:22]1[C:46](=[O:47])[N:24]2[C:25]([C:30]([OH:32])=[S:31])=[C:26]([CH3:29])[CH2:27][S:28][C@H:23]12)=[O:20])([OH:14])=[O:12]
Reactant: CC1=C(C(=S)OC(c2ccccc2)c2ccccc2)N2C(=O)C(NC(=O)C(=NOCC(=O)OC(C)(C)C)c3cscn3)[C@H]2SC1
Solvent: ClCCl
Solvent: CC(C)OC(C)C
Solvent: COc1ccccc1
Product: CC1=C(C(O)=S)N2C(=O)C(NC(=O)C(=NOCC(=O)O)c3cscn3)[C@H]2SC1
Reaction time: 1.5 h
Yield: 44.2 %

Procedure:
Trifluoroacetic acid (14 ml) was added to a stirred suspension of benzhydryl 7-[2-(t-butoxycarbonylmethoxyimino)-2-(4-thiazolyl)acetamido]-3-methylthio-3-cephem-4-carboxylate (syn isomer) (3.5 g) in dichloromethane (7 ml) and anisole (3.5 ml) at ambient temperature and the mixture was stirred for 1.5 hours at the same temperature. To the resulting solution was added isopropyl ether (50 ml) and n-hexane (30 ml) and stirred. The precipitates were collected by filtration, washed with solution of isopropyl ether and n-hexane (1:1). The precipitates were added to a mixture of ethyl acetate and water and adjusted to pH 7.0 with saturated aqueous potassium carbonate. The separated aqueous layer was adjusted to pH 4.0 with 10% hydrochloric acid and the solution was washed with ethyl acetate. The aqueous layer was adjusted to pH 1.8 with 10% hydrochloric acid under ice cooling. The precipitates were filtered off, washed with cold water and dried over phosphorus pentoxide in vacuo to give 7-[2-(carboxymethoxyimino)-2-(4-thiazolyl)acetamido] -3-methylthio-3-cephem-4-carboxylic acid (syn isomer) (1.03 g).
Reaction SMILES: N[C:2]1[C:15]2C(=S)[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]([C:18]2C=CC=CC=2)=[CH:4][C:3]=1Br.[OH:25]CCS(C1C=C(O)C=CC=1)(=O)=O>>[CH:12]1[C:13]2[C:18](=[O:25])[C:5]3[C:6](=[CH:15][CH:2]=[CH:3][CH:4]=3)[C:7](=[O:17])[C:8]=2[CH:9]=[CH:10][CH:11]=1
Reactant: Nc1c(Br)cc(-c2ccccc2)c2c1C(=S)c1ccccc1C2=O
Reactant: O=S(=O)(CCO)c1cccc(O)c1
Product: O=C1c2ccccc2C(=O)c2ccccc21

Procedure:
Example 7 was repeated, except that the compounds shown in 1st and 2nd columns of the following table were used in place of the 1-amino-2-bromo-4-phenylthioanthraquinone and 3-β-hydroxyethylsulfonylphenol, respectively, thereby obtaining a corresponding anthraquinone compound. The color shade obtained by dyeing cotton with the compound is as shown in a 3rd column of the above. Each compound can exhibit superior dye performances as described hereinabove.