Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][C:9]2=[O:12])=[CH:4][CH:3]=1.[C:13](OC(=O)C)(=[O:15])C>C(O)=O>[CH:13]([NH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][C:9]2=[O:12])=[CH:4][CH:3]=1)=[O:15]
Reactant: Nc1ccc2c(c1)C(=O)CCC2
Reactant: CC(=O)OC(C)=O
Solvent: O=CO
Product: O=CNc1ccc2c(c1)C(=O)CCC2
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 91 %

Procedure:
To a solution of 7-amino-1-tetralone (1.70 g, 10.5 mmol) in formic acid (3 ml) was added a mixture of formic acid (8 ml) and acetic anhydride (3 ml), followed by stirring for 10 minutes at room temperature. The reaction mixture was concentrated under reduced pressure. The concentrate was neutralized with a saturated aqueous solution of sodium hydrogencarbonate, which was subjected to extraction with ethyl acetate. The extract solution was washed with brine and dried over anhydrous magnesium sulfate, followed by distilling off the solvent under reduced pressure. The residue was recrystallized from ethyl acetate/isopropyl ether to give 1.80 g (yield 91%) of the above-titled compound, m.p.137-138° C.
Reaction SMILES: [CH3:1][CH:2]([NH2:9])[CH2:3][C:4]1[S:5][CH:6]=[CH:7][CH:8]=1.[CH:10](OCC)=[O:11]>>[CH3:1][CH:2]([NH:9][CH:10]=[O:11])[CH2:3][C:4]1[S:5][CH:6]=[CH:7][CH:8]=1
Reactant: CCOC=O
Reactant: CC(N)Cc1cccs1
Product: CC(Cc1cccs1)NC=O

Procedure:
A solution of 5.9 g (33.4 mmol) 1-methyl-2-thiophen-2-yl-ethylamine in 34.8 ml (417.7 mmol) ethyl formate is refluxed for 16 hours. Then the mixture is cooled and evaporated to dryness i. vac.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([Cl:20])[C:5]2[O:9][CH:8]([CH2:10][N:11]([CH2:15][CH2:16][CH2:17][CH3:18])[C:12](Cl)=[O:13])[CH2:7][C:6]=2[CH:19]=1.[NH:21]1[CH:25]=[N:24][C-:23]=[N:22]1.[Na+]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([Cl:20])[C:5]2[O:9][CH:8]([CH2:10][N:11]([CH2:15][CH2:16][CH2:17][CH3:18])[C:12]([N:21]3[CH:25]=[N:24][CH:23]=[N:22]3)=[O:13])[CH2:7][C:6]=2[CH:19]=1
Reactant: [c-]1nc[nH]n1
Reactant: CCCCN(CC1Cc2cc(Cl)cc(Cl)c2O1)C(=O)Cl
Agent: [Na+]
Solvent: C1CCOC1
Product: CCCCN(CC1Cc2cc(Cl)cc(Cl)c2O1)C(=O)n1cncn1
Temperature: 65 °C
Reaction time: 6 h
Yield: 88.7 %

Procedure:
13.5 g (0.04 mole) of N-(5,7-dichloro-2,3-dihydrobenzofuran-2-ylmethyl)-N-butylcarbamyl chloride were added dropwise to a suspension of 5.5 g (0.06 mole) of sodium 1,2,4-triazolide in 120 ml of dry tetrahydrofuran at 20° C. The mixture was stirred for 6 hours at 65° C., after which it was cooled to 20° C., and the precipitate was filtered off under suction. The filtrate was evaporated down, the residue was suspended in 30 ml of diethyl ether, and the product was filtered off under suction. 13.1 g of 1-(N-(5,7-dichloro-2,3-dihydrobenzofuran-2-ylmethyl)-N-butylcarbamyl)-1,2,4-triazole were obtained as colorless crystals of melting point 122°-124° C. (compound NO. 2).
Reaction SMILES: [H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([OH:16])[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Cl[C:18]1[C:23]([CH3:24])=[CH:22][C:21]([N+:25]([O-:27])=[O:26])=[CH:20][N:19]=1>C1COCC1>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([O:16][C:18]2[C:23]([CH3:24])=[CH:22][C:21]([N+:25]([O-:27])=[O:26])=[CH:20][N:19]=2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]
Reactant: CC(C)(C)OC(=O)N1CCC(O)CC1
Reactant: Cc1cc([N+](=O)[O-])cnc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1cc([N+](=O)[O-])cnc1OC1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 66.5 %

Procedure:
Add a suspension of pre-washed NaH (1.27 g, 31.87 mmol, 60% dispersion in mineral oil) in THF (20 mL) to an ice cold solution of 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (6.41 g, 31.87 mmol) in dry THF (80 mL). Allow the mixture to stir for 20 minutes, then add 2-chloro-3-methyl-5-nitro pyridine (5 g, 28.97 mmol) in portions. After addition is completed, remove cooling bath and stir the reaction mixture at 22° C. overnight. Cool the reaction mixture with an ice bath and add a saturated aq. sodium bicarbonate solution (50 mL). Distribute the reaction mixture between ethyl acetate (350 mL) and distilled water (150 mL). Isolate the aqueous phase and extract with ethyl acetate (1×100 mL). Combine organic layers and wash with saturated aq. sodium chloride solution (2×150 mL). Dry the combined organic phases over sodium sulfate and concentrate. Subject residue to silica gel chromatography eluting with hexanes and ethyl acetate to give 4-(3-methyl-5-nitro-pyridin-2-yloxy)-piperidine-1-carboxylic acid tert-butyl ester as a white solid (6.5 g, 67% yield). MS(ES): m/z=360.3 [M+Na].
Reaction SMILES: C([O:3][C:4](=O)[C:5]([NH:7][CH:8]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:9]([O:11][CH:12]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])=[O:6])C.[NH3:32]>C(O)C>[NH2:32][C:4](=[O:3])[C:5]([NH:7][CH:8]([C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)[C:9]([O:11][CH:12]([C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:10])=[O:6]
Reactant: CCOC(=O)C(=O)NC(C(=O)OC(c1ccccc1)c1ccccc1)c1ccccc1
Reactant: N
Solvent: CCO
Product: NC(=O)C(=O)NC(C(=O)OC(c1ccccc1)c1ccccc1)c1ccccc1

Procedure:
A mixture of 10mM of DL-α-[(2-ethoxy-1,2-dioxoethyl)-amino]phenylacetic acid, diphenylmethyl ester in 50 ml. of ethanol containing 13mM of ammonia is stirred for 15 minutes. After a short time, a thick slurry forms. The product, DL-α-[(2-amino-1,2-dioxoethyl)amino]phenylacetic acid, diphenylmethyl ester, is filtered off and recrystallized from toluene in the form of white filaments, m.p. 168°.
Reaction SMILES: [CH:1]([Mg]Br)=[CH2:2].[Br:5][C:6]1[C:11]([O:12][CH3:13])=[CH:10][C:9]([N+:14]([O-])=O)=[C:8]([Br:17])[N:7]=1>C1COCC1>[Br:5][C:6]1[C:11]([O:12][CH3:13])=[C:10]2[C:9](=[C:8]([Br:17])[N:7]=1)[NH:14][CH:2]=[CH:1]2
Reactant: C=C[Mg]Br
Reactant: COc1cc([N+](=O)[O-])c(Br)nc1Br
Solvent: C1CCOC1
Product: COc1c(Br)nc(Br)c2[nH]ccc12
Temperature: -20 °C
Reaction time: 8 h
Yield: 15.2 %

Procedure:
Vinylmagnesium bromide (0.85 M in THF, 97.7 mL, 83.0 mmol) was added over 30 min. to a stirring solution of 2,6-dibromo-3-methoxy-5-nitropyridine (7.4 g, 23.7 mmol) in THF (160 mL) at −75° C. The solution was stirred 1 h at −75° C., overnight at −20° C., recooled to −75° C. and quenched with saturated aqueous NH4Cl (˜100 mL). The reaction mixture was allowed to warm to rt, washed with brine (˜100 mL) and extracted with Et2O (150 mL) and CH2Cl2 (2×100 mL). The combined organics were dried (MgSO4), filtered and concentrated. The residue was purified by flash column chromatography (SiO2, 3:1 hexanes/EtOAc) to yield 5,7-dibromo-4-methoxy-6-azaindole 36 (1.10 g, 3.60 mmol, 15%) as a pale yellow solid.
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]([S:10][CH2:11][CH3:12])[N:3]=1.CO[CH:15](OC)[N:16]([CH3:18])[CH3:17]>C1(C)C=CC=CC=1>[C:8]([C:7]1[C:2]([N:1]=[CH:15][N:16]([CH3:18])[CH3:17])=[N:3][C:4]([S:10][CH2:11][CH3:12])=[N:5][CH:6]=1)#[N:9]
Reactant: CCSc1ncc(C#N)c(N)n1
Reactant: COC(OC)N(C)C
Solvent: Cc1ccccc1
Product: CCSc1ncc(C#N)c(N=CN(C)C)n1
Temperature: 25 °C
Yield: 99.5 %

Procedure:
A solution of the product from Example 156A (200 mg, 1.11 mmol) and N,N-dimethylformamide dimethyl acetal (0.15 mL, 1.11 mmol) in toluene (10 mL) was refluxed for 2.5 hours. After cooling to room temperature the solution was concentrated under vacuum to provide the title compound as a colorless solid (260 mg, 100%).
Reaction SMILES: C([O:3][C:4]([CH:6]1[CH2:11][CH2:10][N:9]([CH2:12][CH2:13][CH:14]=[C:15]2[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[O:20][CH2:19][O:18][C:17]3[CH:27]=[CH:28][CH:29]=[CH:30][C:16]2=3)[CH2:8][CH2:7]1)=[O:5])C.[OH-].[Na+].[ClH:33]>C(O)C.ClCCl>[ClH:33].[CH:30]1[C:16]2[C:15](=[CH:14][CH2:13][CH2:12][N:9]3[CH2:10][CH2:11][CH:6]([C:4]([OH:5])=[O:3])[CH2:7][CH2:8]3)[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[O:20][CH2:19][O:18][C:17]=2[CH:27]=[CH:28][CH:29]=1
Reactant: CCOC(=O)C1CCN(CCC=C2c3ccccc3OCOc3ccccc32)CC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CCO
Product: O=C(O)C1CCN(CCC=C2c3ccccc3OCOc3ccccc32)CC1
Temperature: 25 °C
Reaction time: 7 h
Yield: 73 %

Procedure:
The above ester (2.30 g, 5.6 mmol) was dissolved in ethanol (30 ml), a 20% solution of sodium hydroxide (3.5 ml) was added and the mixture was stirred at room temperature for 7 h. The solution was diluted with dichloromethane (240 ml) and acidified with concentrated hydrochloric acid (3 ml). The mixture was washed with water (10 ml), the organic phase was dried over MgSO4 and evaporated in vacuo. The solid residue was washed with acetone, filtered off and dried in vacuo, affording the title compound (1.8 g, 73%).
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]2[C:7]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[N:8][O:9][C:10]=2[C:11]([F:14])([F:13])[F:12])[N:3]=[CH:2]1.[CH3:21][O:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1>>[CH3:21][O:22][C:23]1[CH:28]=[CH:27][C:26]([N:1]2[CH:5]=[C:4]([C:6]3[C:7]([C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=4)=[N:8][O:9][C:10]=3[C:11]([F:14])([F:12])[F:13])[N:3]=[CH:2]2)=[CH:25][CH:24]=1
Reactant: COc1ccc(B(O)O)cc1
Reactant: FC(F)(F)c1onc(-c2ccccc2)c1-c1c[nH]cn1
Product: COc1ccc(-n2cnc(-c3c(-c4ccccc4)noc3C(F)(F)F)c2)cc1
Yield: 65 %

Procedure:
As described for Example 1j, 4-(1H-imidazol-4-yl)-3-phenyl-5-trifluoromethyl-isoxazole (100 mg, 0.36 mmol) was converted, using 4-methoxyphenylboronic acid instead of phenylboronic acid, to the title compound (90 mg, 65%) which was obtained as a white solid. MS (ESI): m/e=386.1 [M+H]+.
Reaction SMILES: I[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.C([Mg]Cl)(C)C.[CH:15]1[N:19]=[CH:18][N:17]2[CH2:20][CH2:21][C:22](=[O:23])[C:16]=12.Cl.ClCCl>O1CCCC1>[OH:23][C:22]1([C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=2)[C:16]2[N:17]([CH:18]=[N:19][CH:15]=2)[CH2:20][CH2:21]1
Reactant: N#Cc1ccc(I)cc1
Reactant: O=C1CCn2cncc21
Agent: CC(C)[Mg]Cl
Agent: Cl
Solvent: ClCCl
Solvent: C1CCOC1
Product: N#Cc1ccc(C2(O)CCn3cncc32)cc1
Reaction time: 0.25 h

Procedure:
A solution of 8.18 mmol of 4-iodobenzonitrile [3058-39-7] in 20 ml of tetrahydrofuran at −20° C. is admixed dropwise with 8.18 mmol of isopropylmagnesium chloride (2M in tetrahydrofuran) and the reaction mixture is subsequently stirred for 15 minutes. A mixture of 4.09 mmol of 5,6-dihydropyrrolo[1,2-c]imidazol-7-one [426219-43-4] in 5 ml of tetrahydrofuran is added. After 1 hour the reaction mixture is poured into 1:1 1N HCl/dichloromethane and the phases are separated. The aqueous phase is rendered basic with saturated sodium hydrogen carbonate solution, stirred thoroughly, extracted with tert-butyl methyl ether (in order to separate unreacted ketone) and then extracted with dichloromethane (3×). The combined dichloromethane phases are dried with sodium sulphate and evaporated. From the residue the title compound is obtained by means of flash chromatography (SiO2 60F) as a white foam. Rf=0.20 (dichloromethane/ammonia (2M in EtOH) 95:5), Rt=3.81 (Gradient I).
Reaction SMILES: [BH4-].[Na+].[F:3][C:4]1[CH:37]=[CH:36][C:7]([CH2:8][NH:9][C:10](=[O:35])[C:11]2[CH:16]=[CH:15][C:14]([S:17]([N:20]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[C:22]([CH:29]4[CH2:33][CH2:32][C:31](=[O:34])[CH2:30]4)=[CH:21]3)(=[O:19])=[O:18])=[CH:13][CH:12]=2)=[CH:6][CH:5]=1.O>CO>[F:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:8][NH:9][C:10](=[O:35])[C:11]2[CH:12]=[CH:13][C:14]([S:17]([N:20]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[C:22]([CH:29]4[CH2:33][CH2:32][CH:31]([OH:34])[CH2:30]4)=[CH:21]3)(=[O:18])=[O:19])=[CH:15][CH:16]=2)=[CH:36][CH:37]=1
Reactant: O=C1CCC(c2cn(S(=O)(=O)c3ccc(C(=O)NCc4ccc(F)cc4)cc3)c3ccccc23)C1
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: O=C(NCc1ccc(F)cc1)c1ccc(S(=O)(=O)n2cc(C3CCC(O)C3)c3ccccc32)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 69.2 %

Procedure:
Add sodium borohydride (23 mg, 0.601 mmol) to a 0° C. solution of N-(4-fluoro-benzyl)-4-[3-(3-oxo-cyclopentyl)-indole-1-sulfonyl]-benzamide (295 mg, 0.601 mmol) in MeOH (7 ml) under N2. Stir for 30 min and them warm to room temperature. Stir for 18 hours. Add a small amount of water to quench reaction and then remove MeOH on rotovap. Add EtOAc and water and extract the product into organics. Separate, and dry organics over MgSO4. Condense organics on rotovap and then purify by silica gel chromatography to give N-(4-fluoro-benzyl)-4-[3-(3-hydroxy-cyclopentyl)-indole-1-sulfonyl]-benzamide (205 mg, 69% yield) as a light orange solid. Mass Spectrum (m/e): 493.01 (MH+).
Reaction SMILES: [C:1]([NH:8][C@H:9]([C@H:17]1[O:21][C:20](=[O:22])[C@H:19]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=2[F:31])[CH2:18]1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[OH-:32].[Li+]>C(COC)OC.O>[C:1]([NH:8][C@@H:9]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C@@H:17]([OH:32])[CH2:18][C@@H:19]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=1[F:31])[C:20]([OH:21])=[O:22])([O:3][C:4]([CH3:6])([CH3:5])[CH3:7])=[O:2]
Reactant: [OH-]
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)[C@@H]1C[C@@H](Cc2ccc(F)cc2F)C(=O)O1
Agent: [Li+]
Solvent: O
Solvent: COCCOC
Product: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)[C@@H](O)C[C@@H](Cc1ccc(F)cc1F)C(=O)O

Procedure:
Analogously to Example 1i), 3.1 g (7.18 mmol) of 5(S)-[1(S)-(Boc-amino)-2-phenylethyl]-3(R)-[(2,4-difluorophenyl)methyl]-dihydrofuran-2-(3H)-one in 77 ml of dimethoxyethane and 19 ml of water are hydrolysed with 28.7 ml of 1M lithium hydroxide solution (19 h RT): tRet (I)=14.7 min.
Reaction SMILES: N[CH:2]1[C:14](=[O:15])[N:4]2[C:5]([C:11]([OH:13])=[O:12])=[C:6](C=O)[CH2:7][S:8][C@H:3]12.[CH2:16](OP(CC(OCC)=O)(=O)OCC)[CH3:17]>C1COCC1>[CH:16]([CH:7]1[CH:6]=[C:5]([C:11]([OH:13])=[O:12])[N:4]2[C:14](=[O:15])[CH2:2][C@H:3]2[S:8]1)=[CH2:17]
Reactant: NC1C(=O)N2C(C(=O)O)=C(C=O)CS[C@H]12
Reactant: CCOC(=O)CP(=O)(OCC)OCC
Solvent: C1CCOC1
Product: C=CC1C=C(C(=O)O)N2C(=O)C[C@H]2S1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A suspension of 200 mg of 7-amino-3-formyl-3-cephem-4-carboxylic acid in 2 ml of THF is treated at room temperature with 1.08 ml of BSA. The reaction mixture is stirred at room temperature for 10 minutes. A clear solution is obtained containing N,O-bistrimethylsilyl-7-amino-3-formyl-3-cephem-4-carboxylic acid. The solution is cooled to 0° and treated dropwise with a mixture of 197 mg of diethylethoxycarbonylmethyl-phosphonate and 98 mg of potassium tert.butylate in 2 ml of THF. After 18 hours stirring at 0° the reaction mixture is worked up as described in example 23). 39 mg (15.5%) of 7-amino-3[E)-2-ethoxycarbonyl]ethenyl-3-cephem-4-carboxylic acid as a brown coloured powder are thus obtained.
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]([C:12]([O:14][CH3:15])=[O:13])[C:9](Br)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[Br-].[S:18]1[CH:22]=[CH:21][CH:20]=[C:19]1[Zn+].O>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:7][O:6][C:4](=[O:5])[C:3]1[CH:8]=[C:9]([C:19]2[S:18][CH:22]=[CH:21][CH:20]=2)[C:10]([C:12]([O:14][CH3:15])=[O:13])=[CH:11][C:2]=1[C:19]1[S:18][CH:22]=[CH:21][CH:20]=1
Reactant: COC(=O)c1cc(Br)c(C(=O)OC)cc1Br
Reactant: [Zn+]c1cccs1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Br-]
Solvent: O
Solvent: C1CCOC1
Product: COC(=O)c1cc(-c2cccs2)c(C(=O)OC)cc1-c1cccs1
Temperature: 67 °C
Yield: 87.2 %

Procedure:
Dimethyl 2,5-dibromoterephthalate (6.09 g, 17.30 mmol) is dissolved in anhydrous THF (100 cm3), followed by the addition of 2-thienylzinc bromide (0.50 M in THF, 90 cm3, 45.0 mmol) and Pd(PPh3)4 (0.50 g, 0.43 mmol). The mixture is heated at 67° C. for 2 hours. After cooling, the reaction mixture is poured into water. The precipitate is collected by filtration and washed with water, methanol and diethyl ether then dried in vacuo, to yield the product as a pale yellow solid (5.41 g, 87%). 1H NMR (300 MHz, CDCl3): δ(ppm) 7.82 (s, 2H, Ar—H), 7.40 (dd, J=4.8 and 1.4 Hz, 2H, Ar—H), 7.07-7.12 (m, 4H, Ar—H), 3.78 (s, 6H, CH3); 13C NMR (75 MHz, CDCl3): δ(ppm) 168.1 (C═O), 140.3 (q), 133.6 (q), 133.4 (q), 131.9 (CH), 127.5 (CH), 127.0 (CH), 126.7 (CH), 52.6 (CH3); MS (m/e): 358 (M+, 100%), 327, 299, 240, 195.
Reaction SMILES: Cl.[NH2:2][C:3]([NH2:5])=[NH:4].CN(C)[CH:8]=[CH:9][C:10]([C:12]1[C:21]([F:22])=[C:20]2[C:15]([C:16](=[O:30])[C:17]([C:25]([O:27]CC)=[O:26])=[CH:18][N:19]2[CH2:23][CH3:24])=[CH:14][C:13]=1[F:31])=O>>[NH2:4][C:3]1[N:5]=[C:10]([C:12]2[C:21]([F:22])=[C:20]3[C:15]([C:16](=[O:30])[C:17]([C:25]([OH:27])=[O:26])=[CH:18][N:19]3[CH2:23][CH3:24])=[CH:14][C:13]=2[F:31])[CH:9]=[CH:8][N:2]=1
Reactant: N=C(N)N
Reactant: CCOC(=O)c1cn(CC)c2c(F)c(C(=O)C=CN(C)C)c(F)cc2c1=O
Agent: Cl
Product: CCn1cc(C(=O)O)c(=O)c2cc(F)c(-c3ccnc(N)n3)c(F)c21

Procedure:
In a similar fashion the 7-(2-amino-4-pyrimidinyl)-1-ethyl-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, mp 285°-286° C. (42a) was prepared using guanidine hydrochloride and ethyl 7-(2'-dimethylaminoethenyl)carbonyl-1-ethyl-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate.
Reaction SMILES: [CH2:1]1[CH:8]2[N:4]([C:5](=[O:9])[CH2:6][CH2:7]2)[C:3](=[O:10])[CH2:2]1.Cl.[Cl:12][C:13]1[CH:20]=[CH:19][CH:18]=[CH:17][C:14]=1[CH2:15][OH:16]>C(OCC)C>[Cl:12][C:13]1[CH:20]=[CH:19][CH:18]=[CH:17][C:14]=1[CH2:15][O:16][C:5](=[O:9])[CH2:6][CH2:7][CH:8]1[CH2:1][CH2:2][C:3](=[O:10])[NH:4]1
Reactant: OCc1ccccc1Cl
Reactant: O=C1CCC2CCC(=O)N12
Agent: Cl
Solvent: CCOCC
Product: O=C1CCC(CCC(=O)OCc2ccccc2Cl)N1
Temperature: 100 °C

Procedure:
Five grams of dihydro 1H-pyrrolizine-3,5(2H, 6H) dione is dissolved in 31 g of o-chlorobenzyl alcohol and 0.2 ml of concentrated hydrochloric acid is added. The solution is heated at 100° C. for 71 hours. The mixture is cooled and dissolved in 150 ml of anhydrous diethylether. The solution is cooled to induce crystallization and the resulting crystals are isolated by filtration. Recrystallization from toluene-diethyl ether yields 5-oxo-2-pyrrolidinepropanoic acid o-chlorobenzyl ester with a melting point of 99°-100° C.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][N:7]([S:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)(=[O:11])=[O:10])[CH:8]=1)([O-])=O>CO.[Pd]>[C:12]1([S:9]([N:7]2[CH:8]=[C:4]([NH2:1])[CH:5]=[N:6]2)(=[O:10])=[O:11])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=[N+]([O-])c1cnn(S(=O)(=O)c2ccccc2)c1
Agent: [Pd]
Solvent: CO
Product: Nc1cnn(S(=O)(=O)c2ccccc2)c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 81 %

Procedure:
To a solution of 4-nitro-1-(phenylsulfonyl)-1H-pyrazole (21.0 g, 82.9 mmol) in methanol (300 mL) was added Pd/C (10% wt, 4.0 g), and the mixture was stirred for 12 h at room temperature under a H2 atmosphere. After filtration, the filtrate was concentrated under reduced pressure. The resulting residue was washed with petroleum ether and dried to afford the product as a white solid (15.0 g, 81.1% yield).
Reaction SMILES: [C:1]([O:5][C:6](=[O:26])[NH:7][C:8]([CH2:24][OH:25])([CH2:22][OH:23])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([C:18]([F:21])([F:20])[F:19])[CH:12]=1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[C:33]1([CH2:39][CH2:40][CH2:41][CH2:42]Br)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.O>CN(C)C=O>[C:1]([O:5][C:6](=[O:26])[NH:7][C:8]([CH2:22][OH:23])([CH2:24][OH:25])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:42][CH2:41][CH2:40][CH2:39][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[C:13]([C:18]([F:20])([F:19])[F:21])[CH:12]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: BrCCCCc1ccccc1
Reactant: CC(C)(C)OC(=O)NC(CO)(CO)CCc1ccc(O)c(C(F)(F)F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)OC(=O)NC(CO)(CO)CCc1ccc(OCCCCc2ccccc2)c(C(F)(F)F)c1
Temperature: 80 °C
Reaction time: 6 h
Yield: 103.8 %

Procedure:
Compound 3-6 (350 mg) was dissolved in N,N-dimethylformamide (10 ml), potassium carbonate (255 mg) and 4-phenylbutylbromide (235 mg) were added, and the mixture was stirred at 80° C. for 6 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate, washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the object product (490 mg) as a colorless oil.
Reaction SMILES: [NH:1]([C:20]([O:22]C(C)(C)C)=O)[C@H:2]([C:13]([NH:15][CH2:16][C:17]([NH2:19])=[O:18])=[O:14])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:12])[NH:8][N+:9]([O-:11])=[O:10].Cl.CCOC(C)=O.[N:34]1([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:48][CH2:47][CH2:46][C@H:35]1C(ON1C(=O)CCC1=O)=O>CCN(CC)CC>[N:34]1([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:48][CH2:47][CH2:46][C@H:35]1[C:20]([NH:1][C@H:2]([C:13]([NH:15][CH2:16][C:17]([NH2:19])=[O:18])=[O:14])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:12])[NH:8][N+:9]([O-:11])=[O:10])=[O:22]
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)ON1C(=O)CCC1=O
Reactant: CC(C)(C)OC(=O)N[C@@H](CCCNC(=N)N[N+](=O)[O-])C(=O)NCC(N)=O
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N[N+](=O)[O-])C(=O)NCC(N)=O

Procedure:
The desired compound was prepared from 6.0 g of Boc-Arg(NO2)-Gly-NH2, 40 ml of 4 N HCl-AcOEt, 3.4 ml of Et3N and 5.1 g of Boc-Pro-OSu in the same manner as in Example 26-(4).
Reaction SMILES: [OH:1][CH2:2][CH:3]([CH2:5][OH:6])[OH:4].[CH2:7]([OH:14])[C@@H:8]([C@@H:10]([CH2:12][OH:13])[OH:11])[OH:9]>>[C@@H:2]1([O:9][C@H:8]([C@@H:10]([CH2:12][OH:13])[OH:11])[CH2:7][OH:14])[O:1][C@H:3]([CH2:5][OH:6])[C@@H:2]([OH:1])[C@H:5]([OH:6])[C@H:3]1[OH:4]
Reactant: OC[C@@H](O)[C@@H](O)CO
Reactant: OCC(O)CO
Product: OC[C@@H](O)[C@H](CO)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O

Procedure:
In addition to glycerol (2.0 mol) and erythritol (0.14 mol) given in Table 3 above, 2-O-β-D-glucosyl-D-erythritol (0.74 mol) and 2,4-bis-hydroxymethyl-5-O-β-D-glucosyl-1,3-dioxane (0.35 mol) were obtained as the controlled Smith-degradation products of mannoglucan. Furthermore, acetolysis of mannoglucan gave 3-O-α-D-mannosyl-D-glucose and cellobiose, and partial acid hydrolysis of mannoglucan (0.33N sulfuric acid, 100° C., 7 hrs.) yielded 6-O-α-D-mannosyl-D-glucose and cellobiose.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][CH3:9])[CH:3]=1.[Cl:10][C:11]1[CH:12]=[C:13]([CH:15]=[CH:16][CH:17]=1)[NH2:14]>>[Cl:10][C:11]1[CH:12]=[C:13]([NH:14][C:2]2[CH:3]=[C:4]([NH:8][CH3:9])[N:5]=[CH:6][N:7]=2)[CH:15]=[CH:16][CH:17]=1
Reactant: Nc1cccc(Cl)c1
Reactant: CNc1cc(Cl)ncn1
Product: CNc1cc(Nc2cccc(Cl)c2)ncn1

Procedure:
The title compound is prepared analogously as described in Example 105A from (6-chloro-pyrimidin-4-yl)-methyl-amine and 3-chloroaniline. The ethyl acetate layer is dried over Na2SO4 and evaporated. The solid residue is suspended in CH2Cl2, filtered off and dried in vacuo to afford the title compound.