Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1(Br)[C:10]2[C:9]([Cl:11])=[N:8][CH:7]=[N:6][C:5]=2[NH:4][C:3]1=[O:12].[Cl-].[NH4+].CO.C(Cl)Cl>C1COCC1.[Zn]>[Cl:11][C:9]1[C:10]2[CH2:2][C:3](=[O:12])[NH:4][C:5]=2[N:6]=[CH:7][N:8]=1
Reactant: O=C1Nc2ncnc(Cl)c2C1(Br)Br
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: CO
Solvent: C1CCOC1
Solvent: ClCCl
Product: O=C1Cc2c(Cl)ncnc2N1
Reaction time: 0.33 h
Yield: 378.4 %

Procedure:
Add zinc (2 equiv; 12.12 mmol; 792 mg) to a suspension of 5,5-dibromo-4-chloro-5,7-dihydro-pyrrolo[2,3-d]pyrimidin-6-one (6.06 mmol; 1.98 g) in THF (20 mL) and add saturated ammonium chloride aqueous (3 mL) at 20° C. (exothermic). Stir 20 min then filter through Celite®, rinse with THF, wash the organic phase twice with saturated ammonium chloride. Extract combined aqueous layers four times with 100 mL 1:1 THF:EA, wash the combined organic phases with saturated ammonium chloride, dry over MgSO4, filter through silica gel plug, rinse with 1 L 5% MeOH/DCM and evaporate filtrates. Suspend crude solid in refluxing mixtures of DCM/EA and load onto 330 g of dry silica gel. Chromatograph with 0 to 2% MeOH/DCM to provide the title compound 3.89 g (22.93 mmol; 59%). MS (ES+): m/z=168 (M−H).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=[CH:2]1.[H-].[Na+].Br[CH2:13][C:14]1[CH:32]=[CH:31][C:17]([C:18]([N:20]([CH:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)[CH:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)=[O:19])=[CH:16][C:15]=1[O:33][CH3:34]>CN(C)C=O>[CH:26]1([N:20]([CH:21]2[CH2:22][CH2:23][CH2:24][CH2:25]2)[C:18](=[O:19])[C:17]2[CH:31]=[CH:32][C:14]([CH2:13][N:1]3[C:9]4[C:4](=[N:5][CH:6]=[CH:7][CH:8]=4)[NH:3][CH2:2]3)=[C:15]([O:33][CH3:34])[CH:16]=2)[CH2:27][CH2:28][CH2:29][CH2:30]1
Reactant: c1cnc2nc[nH]c2c1
Reactant: COc1cc(C(=O)N(C2CCCC2)C2CCCC2)ccc1CBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1cc(C(=O)N(C2CCCC2)C2CCCC2)ccc1CN1CNc2ncccc21
Reaction time: 2 h

Procedure:
To a stirred solution of imidazo[4,5-b]pyridine (350 mg, 2.94 mmol) in N,N-dimethylformamide (25 mL), sodium hydride (118 mg, 60% dispersion in mineral oil, 2.94 mmol) was added. After stirring for 2 hr, 4-bromomethyl-3-methoxy-N,N-dicyclopentyl benzamide (1.4 g, 3.57 mmol) was added in small installments over 10 min. The reaction mixture was stirred under argon at 25° C. After 18 h, the reaction was quenched by adding acetic acid (0.5 mL) and the solvent was removed under reduced pressure at <45° C. The crude mixture (2 g) was chromatographed (silica gel, CH2Cl2 -MeOH-NH4OH 90-10-1) to give the title compound. (320 mg, 26%) DSC 185° C.; Anal calcd. for C25H30N4O2 ·0.6H2O: C, 69.94; H, 7.32; N, 13.05. Found C, 69.96; H, 7.58; N, 12.68.
Reaction SMILES: [CH3:1][CH:2]([CH3:25])[CH:3]([NH:8][C:9]([C:11]1[S:12][C:13]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=2)=[CH:14][N:15]=1)=[O:10])[C:4]([O:6][CH3:7])=[O:5].[C:26](=O)([O-])[O-].[Cs+].[Cs+].CI>CS(C)=O>[CH3:1][CH:2]([CH3:25])[CH:3]([N:8]([CH3:26])[C:9]([C:11]1[S:12][C:13]([C:16]2[CH:17]=[CH:18][C:19]([N+:22]([O-:24])=[O:23])=[CH:20][CH:21]=2)=[CH:14][N:15]=1)=[O:10])[C:4]([O:6][CH3:7])=[O:5]
Reactant: O=C([O-])[O-]
Reactant: COC(=O)C(NC(=O)c1ncc(-c2ccc([N+](=O)[O-])cc2)s1)C(C)C
Agent: [Cs+]
Solvent: CS(C)=O
Solvent: CI
Product: COC(=O)C(C(C)C)N(C)C(=O)c1ncc(-c2ccc([N+](=O)[O-])cc2)s1
Reaction time: 0.08 h

Procedure:
To methyl 3-methyl-2-(5-(4-nitrophenyl)thiazole-2-carboxamido)butanoate (Intermediate 2, step C, 1 g) in DMSO (10 ml), to this cesium carbonate (1.346 gm) was added and the reaction mixture was stirred for 5 minutes. To this, methyliodide (0.258 ml) was added and the reaction mixture was stirred for 1 hour. Reaction mixture was quenched using water. The residue obtained was filtered and dried to obtain the title compound. Yield: 0.870 gm (83%); 1H NMR (DMSO-d6, 300 MHz): δ 8.65 (s, 1H), 8.33 (d, 2H), 8.08 (d, 2H), 6.18-4.75 (d, 1H), 3.68 (s, 3H), 3.46-2.96 (s, 3H), 2.38 (m, 1H), 1.03 (d, 3H), 0.91 (d, 3H); MS (ESI) m/z 378 [M+H]+, 400 [M+Na]+
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][NH:7][CH:8]=1)([O-:3])=[O:2].C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:16][C:17]1[C:18]([CH3:23])=[N:19][O:20][C:21]=1[CH3:22]>CN(C=O)C.O>[CH3:23][C:18]1[C:17]([CH2:16][N:6]2[CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:8]=[N:7]2)=[C:21]([CH3:22])[O:20][N:19]=1
Reactant: Cc1noc(C)c1CCl
Reactant: O=[N+]([O-])c1cn[nH]c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1noc(C)c1Cn1cc([N+](=O)[O-])cn1
Yield: 67.5 %

Procedure:
1H-pyrazole (10 g, 147 mmol) was added in small portions to concentrated H2SO4 (100 mL), cooled to 0° C. via an ice/water bath, maintaining the internal reaction temperature below 40° C. Concentrated HNO3 (10 mL) was carefully added, dropwise, to the reaction mixture maintaining the internal reaction temperature below 55° C. The reaction was then heated to 55° C. and stirred for 5 hours. The mixture was cooled to 0° C. and carefully made basic (pH˜8) with aqueous NaOH solution (110 g NaOH in 150 mL H2O) until a white precipitate formed, carefully ensuring the internal temperature of the solution remain below 40° C. The white solid was collected by filtration and washed with ethyl acetate/hexanes (1/3) then dried en vacuo to afford 4-nitro-1H-pyrazole (7 g, 42%, isolated yield). 13C NMR (DMSO-d6, 137.0, 126.4. To 4-nitro-1H-pyrazole (9 g, 80 mmol) in DMF (100 mL) 100 MHz) δ was added cesium carbonate (26 g, 80 mmol) followed by the addition of 4-(chloromethyl)-3,5-dimethylisoxazole (12.3 g, 85 mmol). The reaction mixture was stirred in DMF (100 mL) at 80° C. for 30 minutes, then cooled, diluted with H2O (150 mL) and extracted with ethyl acetate (3×, 75 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was taken up in ethyl acetate (200 mL) and washed with H2O (2×, 100 mL). The organic layer was dried over sodium sulfate, filtered and concentrated. The solid product was triturated with ethyl acetate/hexanes (1/9) and collected by filtration. The product was dried under high vacuum to afford 3,5-dimethyl-4-((4-nitro-1H-pyrazol-1-yl)methyl)isoxazole (12 g, 67%) as a light yellow solid. 1H NMR (CDCl3, 400 MHz): δ 2.23 (s, 3H), 2.46 (s, 3H), 5.08 (s, 2H), 8.02 (s, 1H), 8.08 (s, 1H).
Reaction SMILES: [NH2:1][C:2]1[N:3]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:4]=[C:5]2[C:14]3[CH:13]=[CH:12][C:11](N)=[CH:10][C:9]=3[NH:8][C:7](=[O:16])[C:6]=12.S(=O)(=O)(O)[OH:24].N([O-])=O.[Na+].C(=O)([O-])O.[Na+]>O.CO.C(OCC)(=O)C>[NH2:1][C:2]1[N:3]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:4]=[C:5]2[C:14]3[CH:13]=[CH:12][C:11]([OH:24])=[CH:10][C:9]=3[NH:8][C:7](=[O:16])[C:6]=12
Reactant: O=S(=O)(O)O
Reactant: Nc1ccc2c(c1)[nH]c(=O)c1c(N)n(-c3ccccc3)nc12
Agent: O=C([O-])O
Agent: O=N[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CO
Product: Nc1c2c(=O)[nH]c3cc(O)ccc3c2nn1-c1ccccc1
Temperature: 90 °C
Reaction time: 1 h

Procedure:
A mixture, which is cooled to 0° C., of 3,7-diamino-2-phenyl-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-one (100 mg), concentrated sulfuric acid (0.7 ml) and water (4 ml) was added dropwise a solution of sodium nitrite (46 mg) in water (1 ml), stirred at 0° C. for 30 minutes, at 90° C. for 1 hour and at room temperature for one night. The reaction mixture was neturalized by adding 5% sodium hydrogen carbonate, and ethyl acetate and methanol were added thereto. The insoluble materials were filtered off. The filtrate was extracted with ethyl acetate. The extract was washed with water and brine, dried over anhydrous magnesium sulfate and then the solvent was distilled off under reduced pressure. The residue was purified with silica gel column chromatography to obtain the target compound (18 mg).
Reaction SMILES: [Br:1]Br.[C:3]([O:6][CH2:7][C:8]1[CH:9]=[C:10]([C:18](=[O:20])[CH3:19])[CH:11]=[CH:12][C:13]=1[O:14][C:15](=[O:17])[CH3:16])(=[O:5])[CH3:4]>C(Cl)(Cl)Cl>[C:3]([O:6][CH2:7][C:8]1[CH:9]=[C:10]([C:18](=[O:20])[CH2:19][Br:1])[CH:11]=[CH:12][C:13]=1[O:14][C:15](=[O:17])[CH3:16])(=[O:5])[CH3:4]
Reactant: CC(=O)OCc1cc(C(C)=O)ccc1OC(C)=O
Reactant: BrBr
Solvent: ClC(Cl)Cl
Product: CC(=O)OCc1cc(C(=O)CBr)ccc1OC(C)=O
Yield: 69.1 %

Procedure:
A solution of bromine (7.1 g.) in chloroform (20 ml.) was added dropwise to a stirred solution of 3'-acetoxymethyl-4'-acetoxyacetophenone (11.0 g.) in chloroform (150 ml.) at room temperature. After completion of the addition, the solution was washed with water (2×150 ml.) and brine (100 ml.). The organic phase was dried (MgSO4), filtered and evaporated to give 3'-acetoxymethyl-4'-acetoxy-2-bromoacetophenone (10.0 g.) which was judged to be sufficiently pure by IR and TLC [SiO2 ; 1:1 v/v EtOAc/petrol (60°-80° C.)] for use without further purification or characterisation. A solution of 3'-acetoxymethyl-4'-acetoxy-2-bromoacetophenone (10.0 g.) in dimethylsulphoxide (150 ml.) was stirred at room temperature for 48 hours. The solution was then poured into ice-water (500 ml.) and extracted with ethyl acetate (3×200 ml.). The organic layers were combined, dried (MgSO4) filtered. The solvent was removed by evaporation to give 3'-acetoxymethyl- 4'-acetoxy-phenylglyoxal hydrate as a yellow oil (6.5 g. 81%). The glyoxal derivative had a satisfactory IR spectrum and was judged pure by TLC (SiO2 : EtOAc) and was therefore used without full characterisation or isolation.
Reaction SMILES: Cl.[NH:2]1[CH2:6][CH2:5][C@@H:4]([OH:7])[CH2:3]1.[Br:8][C:9]1[C:10]([CH3:16])=[N:11][C:12](Cl)=[N:13][CH:14]=1.CCN(C(C)C)C(C)C>CCO>[Br:8][C:9]1[C:10]([CH3:16])=[N:11][C:12]([N:2]2[CH2:6][CH2:5][C@@H:4]([OH:7])[CH2:3]2)=[N:13][CH:14]=1
Reactant: O[C@@H]1CCNC1
Reactant: Cc1nc(Cl)ncc1Br
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CCO
Product: Cc1nc(N2CC[C@@H](O)C2)ncc1Br
Temperature: 70 °C
Yield: 89.5 %

Procedure:
In a 500 mL pear flask equipped with a magnetic stir bar were mixed (R)-pyrrolidin-3-ol hydrochloride (8.94 g, 72.3 mmol), 5-bromo-2-chloro-4-methylpyrimidine (15 g, 72.3 mmol), DIPEA (31.6 mL, 181 mmol), and EtOH (150 mL). The resulting yellow suspension was heated in a sand bath to 70° C. for 18 hours. At this time about half of the solvent was evaporated. Water (250 mL) was added to the flask while rapidly stirring the solution. An off-white precipitate formed and was filtered off, washed with water (100 mL) and dried to give the title compound (16.7 g, 89.5%).
Reaction SMILES: [C:1]([CH2:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]2[C:13]([NH2:18])=[CH:14][CH:15]=[CH:16][CH:17]=2)=[CH:7][CH:6]=1)([OH:3])=[O:2].[C:19](OCC)(=[O:23])[C:20]([CH3:22])=O>>[C:1]([CH2:4][C:5]1[CH:6]=[CH:7][C:8]([N:11]2[C:12]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:18]=[C:20]([CH3:22])[C:19]2=[O:23])=[CH:9][CH:10]=1)([OH:3])=[O:2]
Reactant: Nc1ccccc1Nc1ccc(CC(=O)O)cc1
Reactant: CCOC(=O)C(C)=O
Product: Cc1nc2ccccc2n(-c2ccc(CC(=O)O)cc2)c1=O

Procedure:
Preparation as in Example 1 but using N-(4-carboxymethylphenyl)benzene-1,2-diamine and ethyl pyruvate gave the title compound mp 179°-181.5° C.
Reaction SMILES: CCN(C(C)C)C(C)C.Cl.Cl.[CH3:12][C@H:13]1[C:21]2[C:20]([N:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)=[N:19][CH:18]=[N:17][C:16]=2[C:15]([CH3:29])([OH:28])[CH2:14]1.[C:30]([O:34][C:35]([N:37]([CH:50]([CH3:52])[CH3:51])[CH2:38][CH:39]([C:43]1[CH:48]=[CH:47][C:46]([Cl:49])=[CH:45][CH:44]=1)[C:40](O)=[O:41])=[O:36])([CH3:33])([CH3:32])[CH3:31].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>C(Cl)Cl>[Cl:49][C:46]1[CH:47]=[CH:48][C:43]([CH:39]([C:40]([N:25]2[CH2:24][CH2:23][N:22]([C:20]3[C:21]4[C@H:13]([CH3:12])[CH2:14][C:15]([OH:28])([CH3:29])[C:16]=4[N:17]=[CH:18][N:19]=3)[CH2:27][CH2:26]2)=[O:41])[CH2:38][N:37]([CH:50]([CH3:51])[CH3:52])[C:35](=[O:36])[O:34][C:30]([CH3:32])([CH3:31])[CH3:33])=[CH:44][CH:45]=1
Reactant: C[C@@H]1CC(C)(O)c2ncnc(N3CCNCC3)c21
Reactant: CC(C)N(CC(C(=O)O)c1ccc(Cl)cc1)C(=O)OC(C)(C)C
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)N(CC(C(=O)N1CCN(c2ncnc3c2[C@H](C)CC3(C)O)CC1)c1ccc(Cl)cc1)C(=O)OC(C)(C)C
Reaction time: 1 h
Yield: 100.1 %

Procedure:
A solution of tert-butyl 4-((5R)-7-hydroxy-5,7-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (28 mg, 0.080 mmol) in DCM (6 mL) was added to a 4.0M HCl solution in dioxane (1.4 mL, 5.63 mmol). The mixture was stirred at room temperature for 4 hours. A 4.0M HCl solution in dioxane (1.4 mL, 5.63 mmol) from a different bottle was added. The resulting mixture was stirred for 18 hours. The solvents were removed in vacuo to give (5R)-5,7-dimethyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol dihydrochloride. DIPEA (41.5 mg, 0.321 mmol) was added to a suspension of this (5R)-5,7-dimethyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol dihydrochloride (25.8 mg, 0.0803 mmol), 3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)propanoic acid (32.9 mg, 0.0964 mmol), and O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (36.6 mg, 0.0964 mmol) in CH2Cl2 (6 mL) at room temperature. The resulting mixture was stirred for 1 hour. The solvent was removed in vacuo. The residue was purified by a silica cartridge (5.0 g) eluted by EtOAc to give tert-butyl 2-(4-chlorophenyl)-3-(4-((5R)-7-hydroxy-5,7-dimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-3-oxopropyl(isopropyl)carbamate (46 mg, 100%) as a gel. LCMS (APCI+) [M-Boc+H]+ 472.2; Rt: 3.51 min.
Reaction SMILES: Br[C:2]1[N:6]2[N:7]=[C:8]([NH:11][CH2:12][CH2:13][N:14]([CH2:17][CH3:18])[CH2:15][CH3:16])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[CH:19](/B(O)O)=[CH:20]\[CH2:21][CH2:22][CH2:23][CH3:24].[ClH:28]>CCOCC>[ClH:28].[CH2:15]([N:14]([CH2:17][CH3:18])[CH2:13][CH2:12][NH:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2](/[CH:19]=[CH:20]/[CH2:21][CH2:22][CH2:23][CH3:24])=[CH:3][N:4]=2)[N:7]=1)[CH3:16]
Reactant: CCN(CC)CCNc1ccc2ncc(Br)n2n1
Reactant: CCCC/C=C/B(O)O
Agent: Cl
Solvent: CCOCC
Product: CCCC/C=C/c1cnc2ccc(NCCN(CC)CC)nn12
Yield: 59 %

Procedure:
Prepared from the product of step A and (E)-1-hexeneboronic acid according to general procedure 2. The free-base was converted to the HCl salt with 2N HCl in Et2O to provide the title compound (74 mg, 59%) as a brown solid; 1H NMR (500 MHz, CD3OD) δ 7.74 (d, J=9.6 Hz, 1H), 7.62 (s, 1H), 6.85 (d, J=9.6 Hz, 1H), 6.71-6.62 (m, 2H), 3.83 (t, J=6.3 Hz, 2H), 3.51 (t, J=6.4 Hz, 2H), 3.34 (q, J=7.0 Hz, 4H), 2.32-2.39 (m, 2H), 1.54-1.48 (m, 2H), 1.46-1.40 (m, 2H), 1.38-1.34 (t, J=7.3 Hz, 6H), 0.96 (t , J=7.3 Hz, 3H); 13C NMR (125 MHz, CD3OD) δ 155.7, 136.6, 135.3, 129.5, 125.7, 125.1, 115.8, 115.4, 51.0, 37.6, 34.4, 32.7, 23.4, 14.3, 9.2 (one signal overlapping with solvent); HPLC tR=9.3 min (Luna), 96.7%; ES-MS: (M+H)=316 m/z.
Reaction SMILES: C([O-])(=O)C.[Ca+2].C([O-])(=O)C.[CH2:10]([OH:32])[C@H:11]1[O:16][C@H:15]([O:17][C@H:18]2[C@H:23]([OH:24])[C@@H:22]([OH:25])[C@H:21]([OH:26])[O:20][C@@H:19]2[CH2:27][OH:28])[C@H:14]([OH:29])[C@@H:13]([OH:30])[C@@H:12]1[OH:31].Cl.[O:34]=[CH:35][C@@H:36]([C@H:38]([C@@H:40]([C@@H:42]([CH2:44][OH:45])[OH:43])O)[OH:39])[OH:37]>C([O-])(=O)C.[Na+]>[CH2:10]([OH:32])[C@H:11]1[O:16][C@H:15]([O:17][C@H:18]2[C@H:23]([OH:24])[C@@H:22]([OH:25])[C@@H:21]([O:26][C@H:40]3[C@H:38]([OH:39])[C@@H:36]([OH:37])[C@@H:35]([OH:34])[O:43][C@@H:42]3[CH2:44][OH:45])[O:20][C@@H:19]2[CH2:27][OH:28])[C@H:14]([OH:29])[C@@H:13]([OH:30])[C@@H:12]1[OH:31]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Reactant: OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Ca+2]
Product: OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O[C@H]3[C@H](O)[C@@H](O)[C@@H](O)O[C@@H]3CO)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O

Procedure:
Further, each fraction of FG3 and FG5 was taken out and dissolved in a 0.1M sodium acetate buffer containing 10 mM calcium acetate buffer solution (pH 5.5), followed by addition of takaamylase A for hydrolyses at 37° C. for 3 hours. The hydrolyzed products were tested by HPLC and TLC. From FG5, there were produced FG3 and maltose, but FG3 was not hydrolyzed by takaamylase A. When FG3 was added to 0.3N HCl and hydrolyzed at 100° C. for 30 minutes, the products were maltose, glucose and 2 kinds of compounds having fluorescence but no maltotriose was produced.
Reaction SMILES: ClC1C=C(CC(O)=O)C=C(Cl)C=1OC1C=CC(NC(=O)C(C)C)=C(Br)C=1.Cl.CNCC(O)=O.C[N:35]([C:40](=[O:64])[CH2:41][C:42]1[CH:47]=[C:46]([Cl:48])[C:45]([O:49][C:50]2[CH:55]=[CH:54][C:53]([NH:56][C:57](=[O:61])[CH:58]([CH3:60])[CH3:59])=[C:52]([Br:62])[CH:51]=2)=[C:44]([Cl:63])[CH:43]=1)[CH2:36][C:37]([OH:39])=[O:38]>>[Cl:48][C:46]1[CH:47]=[C:42]([CH2:41][C:40]([NH:35][CH2:36][C:37]([OH:39])=[O:38])=[O:64])[CH:43]=[C:44]([Cl:63])[C:45]=1[O:49][C:50]1[CH:55]=[CH:54][C:53]([NH:56][C:57](=[O:61])[CH:58]([CH3:60])[CH3:59])=[C:52]([Br:62])[CH:51]=1
Reactant: CC(C)C(=O)Nc1ccc(Oc2c(Cl)cc(CC(=O)N(C)CC(=O)O)cc2Cl)cc1Br
Agent: CC(C)C(=O)Nc1ccc(Oc2c(Cl)cc(CC(=O)O)cc2Cl)cc1Br
Agent: CNCC(=O)O
Agent: Cl
Product: CC(C)C(=O)Nc1ccc(Oc2c(Cl)cc(CC(=O)NCC(=O)O)cc2Cl)cc1Br
Yield: 22 %

Procedure:
3,5-Dichloro-4-(3-bromo-4-isobutyramidophenoxy)phenylacetic acid (56 mg) was coupled with methyl glycine hydrochloride (31 mg) using the method described in Example 9. This gave methyl N-[3,5-dichloro-4-(3-bromo-4-isobutyramidophenoxy)phenylacetyl]-glycine, which was hydrolyzed using the method described in Example 1(i) and purified as in Example 9, to give 14 mg (22%) of N-[3,5-dichloro-4-(3-bromo-4-isobutyramidophenoxy)phenylacetyl]glycine, m/z 518.
Reaction SMILES: [CH:1]([NH:4][CH2:5][CH2:6][NH2:7])([CH3:3])[CH3:2].N[C:9](N)=[O:10]>>[CH:1]([N:4]1[CH2:5][CH2:6][NH:7][C:9]1=[O:10])([CH3:3])[CH3:2]
Reactant: NC(N)=O
Reactant: CC(C)NCCN
Product: CC(C)N1CCNC1=O
Temperature: 125 °C
Yield: 98.5 %

Procedure:
A five-liter three necked flask equipped with a thermometer, condenser, stirrer, and nitrogen inlet was charged with 2-isopropylaminoethylamine (2550 g, 25 moles) and urea (1500 g, 25 moles). The reaction mixture was heated to 125° C. for seven hours and then 170° C. until no more gas releasing was observed. About 3155 g of N-isopropyl-2-imidazolidone was obtained. The reaction is represented as follows: ##STR10##
Reaction SMILES: [CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[CH2:15][CH2:16][CH:17]=[CH2:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].CC([N-]C(C)C)C.Br[CH2:29][C:30]1[C:35]([Cl:36])=[CH:34][C:33]([O:37][CH3:38])=[CH:32][C:31]=1[Cl:39]>C1COCC1.O.CCOCC>[CH2:1]([CH:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:19])[C@H:15]([CH2:29][C:30]1[C:31]([Cl:39])=[CH:32][C:33]([O:37][CH3:38])=[CH:34][C:35]=1[Cl:36])[CH2:16][CH:17]=[CH2:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C=CCCC(=O)N1C(=O)OC[C@H]1Cc1ccccc1
Reactant: COc1cc(Cl)c(CBr)c(Cl)c1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: O
Solvent: CCOCC
Solvent: C1CCOC1
Product: C=CC[C@@H](Cc1c(Cl)cc(OC)cc1Cl)C(=O)N1C(=O)OCC1Cc1ccccc1
Temperature: -60 °C
Yield: 76 %

Procedure:
Stir a mixture of (R)-4-benzyl-3-pent-4-enoyl-oxazolidin-2-one (5.0 g, 19.3 mmol) and tetrahydrofuran (75 mL) in a 250 mL round bottom flask at −75° C. Transfer 2 M LDA (14.5 mL) to the flask via syringe and add at a rate such that the internal temperature does not reach above −60° C. After the addition is complete, allow the reaction to stir at −25° C. for 30 min then cool to about −60° C. At this point, add a solution of 2-bromomethyl-1,3-dichloro-5-methoxy-benzene (7.76 g, 28.96 mmol) in THF (25 mL). After the addition is complete, the reaction vessel is allowed to slowly warm up to 0° C., and maintain the internal reaction temperature at 0° C. for 4 hr. Quench the reaction with 30 mL aqueous 1N hydrochloric acid. Transfer the mixture to a 500 mL separatory funnel and dilute with 100 mL water and 100 mL ether. Separate the layers and extract the aqueous layer with ether. Dry the combined organic phase over anhydrous sodium sulfate, filter and concentrate to give a thick oil. Purify by silica gel chromatography using hexanes:ethyl acetate to obtain 6.65 g, (76%) of a pale yellow oil.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[S:11](=[O:13])(=[O:12])[CH2:10][CH2:9][C:8]([C:14]([OH:16])=O)=[CH:7][C:6]=2[CH:17]=1.S(Cl)(Cl)=O.CN(C=O)C.[CH3:27][N:28]([CH2:35][C:36]1[CH:42]=[CH:41][C:39]([NH2:40])=[CH:38][CH:37]=1)[CH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1>C1COCC1.C(N(CC)CC)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[S:11](=[O:12])(=[O:13])[CH2:10][CH2:9][C:8]([C:14]([NH:40][C:39]3[CH:41]=[CH:42][C:36]([CH2:35][N:28]([CH3:27])[CH:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[CH:37][CH:38]=3)=[O:16])=[CH:7][C:6]=2[CH:17]=1
Reactant: O=C(O)C1=Cc2cc(Br)ccc2S(=O)(=O)CC1
Reactant: CN(Cc1ccc(N)cc1)C1CCOCC1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CN(Cc1ccc(NC(=O)C2=Cc3cc(Br)ccc3S(=O)(=O)CC2)cc1)C1CCOCC1
Reaction time: 1 h
Yield: 67.5 %

Procedure:
To a suspension of 7-bromo-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylic acid (4.47 g) in THF (90 ml) were added at room temperature thionyl chloride (1.03 ml) and DMF (1 ml), and the mixture was stirred for 1 hour and added dropwise to a solution of 4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]aniline (3.41 g) and triethylamine (7.9 ml) in THF (30 ml), at 0° C. The mixture was stirred for 3 hours and concentrated under reduced pressure, to which were added water. Precipitated colorless crystals were collected by filtration, and the crystals were washed with water, ethanol, 2-propanol and diisopropylether to give colorless crystals of 7-bromo-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide (4.94 g).
Reaction SMILES: [P:1](Cl)([Cl:4])([Cl:3])=[O:2].[CH2:6]([OH:10])[CH2:7][CH2:8][CH3:9]>C(Cl)(Cl)(Cl)Cl>[P:1]([Cl:4])([Cl:3])([O:10][CH2:6][CH2:7][CH2:8][CH3:9])=[O:2]
Reactant: O=P(Cl)(Cl)Cl
Reactant: CCCCO
Solvent: ClC(Cl)(Cl)Cl
Product: CCCCOP(=O)(Cl)Cl

Procedure:
To phosphoryl chloride (50 ml) in 40 ml of carbon tetrachloride at ambient temperature was added dropwise n-butanol (29.65 g). After the initial exothermic reaction subsided, the reaction mixture was refluxed for 3 hours. Vacuum distillation at 88°-103° C. yielded 59.114 g of n-butyl dichlorophosphate.
Reaction SMILES: C([O:8][C@H:9]1[C@H:15]([O:16]CC2C=CC=CC=2)[C@@H:14]([O:24]CC2C=CC=CC=2)[C@:13]2([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]4[CH:46]=[CH:45][C:44]([O:47][C:48]([F:51])([F:50])[F:49])=[CH:43][CH:42]=4)[CH:34]=3)[O:32][C@@:10]1([CH:52]([OH:54])[CH3:53])[CH2:11][O:12]2)C1C=CC=CC=1.ClC1C=CC=CC=1Cl>[Pd].CO.O1CCCC1>[Cl:39][C:36]1[CH:37]=[CH:38][C:33]([C@@:13]23[O:32][C@@:10]([CH:52]([OH:54])[CH3:53])([CH2:11][O:12]2)[C@@H:9]([OH:8])[C@H:15]([OH:16])[C@H:14]3[OH:24])=[CH:34][C:35]=1[CH2:40][C:41]1[CH:46]=[CH:45][C:44]([O:47][C:48]([F:50])([F:49])[F:51])=[CH:43][CH:42]=1
Reactant: CC(O)[C@@]12CO[C@@](c3ccc(Cl)c(Cc4ccc(OC(F)(F)F)cc4)c3)(O1)[C@H](OCc1ccccc1)[C@@H](OCc1ccccc1)[C@@H]2OCc1ccccc1
Agent: [Pd]
Solvent: Clc1ccccc1Cl
Solvent: CO
Solvent: C1CCOC1
Product: CC(O)[C@@]12CO[C@@](c3ccc(Cl)c(Cc4ccc(OC(F)(F)F)cc4)c3)(O1)[C@H](O)[C@@H](O)[C@@H]2O
Temperature: 25 °C
Reaction time: 2 h
Yield: 28.2 %

Procedure:
To a solution of 1-[(1R,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[4-[4-(trifluoromethoxy) phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]ethanol 15q (102 mg, 0.13 mmol) in a methanol/tetrahydrofuran mixture (v/v=4/1, 10 mL) were added o-dichlorobenzene (95 mg, 0.65 mmol) and 10% Pd/C (41 mg, 0.39 mmol) at room temperature. The mixture was stirred under H2 at room temperature for 2 hours and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=1/5 to give the title compound 15 as a white solid (18 mg, 28.2%, HPLC: 96.2%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 535.2[M+HCOO]−; and 1H NMR (400 MHz, DMSO-d6) δ(ppm): 7.47 (d, 1H), 7.42 (d, 1H), 7.37-7.26 (m, 5H), 5.27 (d, 1H), 4.92 (m, 2H), 4.61 (d, 1H), 4.12 (s, 2H), 4.01 (dd, 1H), 3.81 (dd, 1H), 3.54 (d, 1H), 3.47-3.37 (m, 3H), 1.17 (d, 3H).