Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[CH:9]([NH2:15])[CH2:8][CH2:7][CH2:6][C:5]2=1.Cl[C:17]([O:19][CH3:20])=[O:18]>>[Br:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[CH:9]([NH:15][C:17](=[O:18])[O:19][CH3:20])[CH2:8][CH2:7][CH2:6][C:5]2=1
Reactant: COC(=O)Cl
Reactant: NC1CCCc2c1[nH]c1ccc(Br)cc21
Product: COC(=O)NC1CCCc2c1[nH]c1ccc(Br)cc21

Procedure:
Methyl 6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-ylcarbamate was prepared from 6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-amine and methyl chloroformate to give a yellow oil (8% yield). 1H-NMR (CDCl3): δ 8.70 (s, 1H), 7.60 (m, 1H), 7.28-7.16 (m, 2H), 4.98 (m, 1H), 4.90 (m, 1H), 3.74 (s, 3H), 2.66 (m, 2H), 2.21 (m, 1H), 1.90 (m, 2H), 1.81 (m, 1H); MS m/z 324 (M+1).
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH3:14])([CH3:13])[C:11]#[N:12])=[C:6]([Cl:15])[CH:5]=1)(=O)[CH3:2].[BH4-].[Na+].Cl.CC(O)C.[NH3:23]>CO.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].O>[ClH:15].[NH2:23][CH:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH3:14])([CH3:13])[C:11]#[N:12])=[C:6]([Cl:15])[CH:5]=1)[CH3:2]
Reactant: CC(=O)c1ccc(C(C)(C)C#N)c(Cl)c1
Reactant: N
Agent: [Ti+4]
Agent: CC(C)[O-]
Agent: Cl
Solvent: CO
Solvent: CC(C)O
Solvent: O
Product: CC(N)c1ccc(C(C)(C)C#N)c(Cl)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 64 %

Procedure:
To a stirred solution of 2-(4-acetyl-2-chlorophenyl)-2-methylpropanenitrile (1.57 g, 7.08 mmol) in 7 M ammonia in methanol solution (35 mL) is added freshly distilled titanium (IV) isopropoxide (4.2 mL, 14.2 mmol). The reaction mixture is left stirring 18 h at room temperature. After cooling to 0° C., sodium borohydride (0.40 g, 10.6 mmol) is added and the reaction mixture is stirred at 0° C. until no more gas evolved and then at room temperature for 4 h. Water (40 mL) is then added and the titanium oxide is removed by filtration on a Buchner funnel. The filtrate is extracted with EtOAc (3×50 mL) and the combined organic layers are concentrated under reduced pressure. The resulting residue is dissolved in Et2O (200 mL), washed with brine, dried over anhydrous MgSO4 and filtered. To this solution is then added 5 N HCl in 2-propanol (1.8 mL, 8.85 mmol). The resulting precipitate is filtered on a Buchner funnel and dried to provide the desired 2-(4-(1-aminoethyl)-2-chlorophenyl)-2-methylpropanenitrile hydrochloride (1.17 g, 64%) as a white solid. 1H NMR (300 MHz, CD3OD): δ 7.69 (1H, d, J=10.7 Hz), 7.68 (1H, s), 7.52 (1H, dd, J=8.3, 2.0 Hz), 4.53 (1H, q, J=6.8 Hz), 1.90 (6H, s), 1.66 (3H, d, J=6.9 Hz). 13C NMR (75 MHz, CD3OD): δ 142.5, 140.2, 136.0, 132.0, 130.1, 127.9, 52.0, 37.8, 28.4, 21.3.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:25]([F:28])([F:27])[F:26])[O:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][C:17]([C:20]4([F:24])[CH2:23][NH:22][CH2:21]4)=[CH:16][CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.C(N(CC)CC)C.[CH:36]1([C:39](Cl)=[O:40])[CH2:38][CH2:37]1.O>C(Cl)Cl>[CH:36]1([C:39]([N:22]2[CH2:23][C:20]([C:17]3[CH:18]=[CH:19][C:14]([C:11]4[CH2:10][C:9]([C:4]5[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=5)([C:25]([F:27])([F:26])[F:28])[O:13][N:12]=4)=[CH:15][CH:16]=3)([F:24])[CH2:21]2)=[O:40])[CH2:38][CH2:37]1
Reactant: FC1(c2ccc(C3=NOC(c4cc(Cl)cc(Cl)c4)(C(F)(F)F)C3)cc2)CNC1
Reactant: O=C(Cl)C1CC1
Solvent: O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(C1CC1)N1CC(F)(c2ccc(C3=NOC(c4cc(Cl)cc(Cl)c4)(C(F)(F)F)C3)cc2)C1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 89.1 %

Procedure:
To a solution of the 5-(3,5-dichlorophenyl)-3-(4-(3-fluoroazetidin-3-yl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole (Preparation 15, 65 mg) in 2 mL CH2Cl2 was added triethyl amine (50 μL) followed by cyclopropane carbonyl chloride (19 mg). The reaction was allowed to stir at room temperature for 30 minutes. Water (5 mL) was added. The reaction was diluted with an additional 5 mL of CH2Cl2, stirred for 5 minutes at room temp then passed through a phase separation tube. The CH2Cl2 layer was collected and condensed. The crude material was adsorbed on silica and chromatographed on a 12 g silica column, eluting with a gradient of 0% to 100% ethyl acetate in heptane. Fractions containing the desired material were combined and concentrated. Et2O (˜½ mL) was added to the resulting film. Placing the flask on high vacuum overnight resulted in formation of a white foam. Yield 67 mg (98%) of the desired product. 1H NMR (CDCl3) δ ppm 7.76 (d, 2H), 7.63-7.51 (s, 4H), 7.45 (s, 1H), 4.8-4.7 (m, 1H), 4.6-4.3 (m, 3H), 4.12 (d, 1H), 3.74 (d, 1H), 1.6-1.4 (m, 1H), 1.07 (m, 2H), 0.86 (m, 2H). LC/MS retention time=3.654 minutes, MS calculated for (C23H18Cl2F4N2O2), 500.07; found 501.0 M+H.
Reaction SMILES: [Br:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([CH2:8][C:9]#[N:10])=[O:7])=[CH:4][CH:3]=1.C([BH3-])#N.[Na+]>C(O)C.C(O)(=O)C.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:6]([OH:7])[CH2:8][C:9]#[N:10])=[CH:11][CH:12]=1
Reactant: N#CCC(=O)c1ccc(Br)cc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Solvent: CCO
Product: N#CCC(O)c1ccc(Br)cc1
Temperature: 25 °C
Yield: 98.3 %

Procedure:
A suspension of 4-bromobenzoylacetonitrile (500 mg) in ethanol (5 mL) and acetic acid (300 μL) was heated with sodium cyanoborohydride (280 mg) using an 80° C. hot plate for 2 hours. After cooling to ambient temperature, the mixture was diluted with water and concentrated to a syrup, which was diluted with ethyl acetate and washed with water, sat. NaHCO3, and brine. The extract was dried with MgSO4, filtered, and evaporated to provide 510 mg of a cloudy oil, which was filtered through silica gel using 1:1 ethyl acetate/hexane to provide the product (496 mg) as a thick oil.
Reaction SMILES: [Cl:1][S:2]([OH:5])(=O)=[O:3].[Cl:6][C:7]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:8]=1[C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:10]>>[Cl:6][C:7]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:8]=1[C:9]([C:11]1[CH:16]=[C:15]([S:2]([Cl:1])(=[O:5])=[O:3])[CH:14]=[CH:13][CH:12]=1)=[O:10]
Reactant: O=C(c1ccccc1)c1cc(Cl)ccc1Cl
Reactant: O=S(=O)(O)Cl
Product: O=C(c1cccc(S(=O)(=O)Cl)c1)c1cc(Cl)ccc1Cl
Temperature: 0 °C

Procedure:
Chlorosulfonic acid (233.0 g, 2 mol) was added into a 3 L three-necked flask equipped with a stirrer and cooling pipe, followed by adding 2,5-dichlorobenzophenone (100.4 g, 400 mmol), and the reactant was allowed to react for 8 hours using an oil bath at 100° C. After a predetermined time, the reaction liquid was slowly poured into crushed ice (1000 g) and extracted with ethyl acetate. The organic layer was washed with sodium chloride solution and dried with magnesium sulfate, and then ethyl acetate was removed to obtain a light yellow crude crystal (3-(2,5-dichlorobenzoyl)benzenesulfonic acid chloride. The crude crystal was not purified and directly used in the following step.
Reaction SMILES: [CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(=O)C.C[O:14][CH:15]1[CH:19]([CH:20]=O)[CH2:18][CH:17](OC)O1.O>C(OCC)(=O)C>[CH2:1]([N:8]1[CH:17]=[CH:18][C:19]([CH:15]=[O:14])=[CH:20]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC1CC(C=O)C(OC)O1
Reactant: NCc1ccccc1
Solvent: CCOC(C)=O
Solvent: O
Solvent: CC(=O)O
Product: O=Cc1ccn(Cc2ccccc2)c1
Temperature: 90 °C
Reaction time: 0.33 h
Yield: 86 %

Procedure:
Benzylamine (540 mg, 5.00 mmol) and acetic acid (10 mL) were added to 2,5-dimethoxy-tetrahydrofuran-3-carbaldehyde (1 g, 6.25 mmol), and the solution was stirred for 20 minutes at 90° C. Water and ethyl acetate were added to the reaction solution, which was then partitioned, the organic layer was washed with an aqueous solution 2N sodium hydroxide once and with water twice, filtered with a glass filter lined with silica gel, the filtrate was evaporated in vacuo, and title compound (800 mg, 4.3 mmol, 68.8%) was obtained as a brown oil.
Reaction SMILES: C([Li])CCC.[Br-].[CH2:7]([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].C[O:39][C:40](=[O:51])[CH2:41][CH2:42][CH2:43]/[CH:44]=[CH:45]\[C:46]([CH3:50])([CH3:49])[CH:47]=O.CCOCC>O1CCCC1.CN(C)P(=O)(N(C)C)N(C)C.O1CCCC1>[CH3:49][C:46]([CH3:50])(/[CH:47]=[CH:18]\[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH3:7])/[CH:45]=[CH:44]\[CH2:43][CH2:42][CH2:41][C:40]([OH:39])=[O:51]
Reactant: COC(=O)CCC/C=C\C(C)(C)C=O
Reactant: CCCCCCCCCCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: CCOCC
Product: CCCCCCCCCCC/C=C\C(C)(C)/C=C\CCCC(=O)O
Temperature: 0 °C
Reaction time: 0.75 h
Yield: 49 %

Procedure:
A 1.4 ml. portion of n-butyllithium (1.6 M solution in hexane) was added to a solution of 1.4 g (2.74 mmol) of n-dodecyltriphenylphosphonium bromide in 5.5 ml of 2:1 tetrahydrofuran-hexamethylphosphorictriamide, at -78° C., under argon. The solution turned orange-red in color. To this solution was then added 0.350 g (1.77 mmoles) of (Z)-8-oxo-7,7-dimethyl-5-octenoic acid methyl ester dissolved in 1 ml of tetrahydrofuran, using a syringe. The reaction mixture was stirred for 30 minutes at -78° C. and an additional 45 minutes at 0° C. The product was isolated by ether extraction using the conventional workup procedure and then chromatographed on silica gel. Hexane-ether (19:1) eluted 0.600 g (97%) of (Z,Z)-7,7-dimethyl-5,8-eicosadienoic acid methyl ester. This material was dissolved in 6 ml of methanol and treated with 0.6 ml of 5% aqueous potassium hydroxide. After stirring at room temperature for 17 hours, 3 ml of the methanol was evaporated in vacuo. The remaining solution was acidified with oxalic acid and the product was extracted with ether. The ether extracts were washed with brine, dried over MgSO4 and the solvent evaporated at reduced pressure. Purification of the crude acid on a silica gel column provided 0.292 g (50.7%) of (Z,Z)-7,7-dimethyl-5,8-eicosadienoic acid (ca. 100% pure by GC analysis).
Reaction SMILES: [CH:1]1([C:4]([N:6]([CH2:9][C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=2[C:20]2[C:25]([O:26][CH3:27])=[CH:24][CH:23]=[C:22]([CH:28]([CH3:32])[C:29](O)=[O:30])[CH:21]=2)[CH2:7][CH3:8])=[O:5])[CH2:3][CH2:2]1.C(N(CC)CC)C.C(Cl)(=O)C([Cl:43])=O.CN(C=O)C>C(Cl)Cl>[CH:1]1([C:4]([N:6]([CH2:9][C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=2[C:20]2[C:25]([O:26][CH3:27])=[CH:24][CH:23]=[C:22]([CH:28]([CH3:32])[C:29]([Cl:43])=[O:30])[CH:21]=2)[CH2:7][CH3:8])=[O:5])[CH2:3][CH2:2]1
Reactant: O=C(Cl)C(=O)Cl
Reactant: CCN(Cc1cc(C(F)(F)F)ccc1-c1cc(C(C)C(=O)O)ccc1OC)C(=O)C1CC1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCN(Cc1cc(C(F)(F)F)ccc1-c1cc(C(C)C(=O)Cl)ccc1OC)C(=O)C1CC1
Temperature: 0 °C
Reaction time: 1.5 h

Procedure:
To 2-{2′-[(cyclopropanecarbonyl-ethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-propionic acid (0.096 g, 0.21 mmol) and triethylamine (0.04 mL, 0.26 mmol) in CH2Cl2 (2 mL) at 0° C. was added oxalyl chloride (0.02 mL, 0.26 mmol), followed by DMF (2 drop and the reaction was stirred at 0° C. for 1.5 hours. The mixture was concentrated to give the title compound.
Reaction SMILES: C(=O)([O-])[O-].[Na+].[Na+].[Cl:7][CH2:8][C:9](=[O:15])[CH2:10][C:11]([O:13][CH3:14])=[O:12].Cl[CH2:17][C:18](=[O:20])[CH3:19].Cl>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.C(#N)C>[Cl:7][CH2:8][C:9](=[O:15])[CH:10]([CH2:17][C:18]([CH3:19])=[O:20])[C:11]([O:13][CH3:14])=[O:12]
Reactant: CC(=O)CCl
Reactant: COC(=O)CC(=O)CCl
Agent: CC[N+](CC)(CC)Cc1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CC#N
Product: COC(=O)C(CC(C)=O)C(=O)CCl
Yield: 15.6 %

Procedure:
127.2 g (1.2 mol) of sodium carbonate and 4.6 g (0.02 mol) of benzyltriethylammonium chloride are suspended in 800 ml of acetonitrile. While stirring there is added dropwise thereto within 8 hours a solution of 150.5 g (1 mol) of methyl 4-chloroacetoacetate and 138.8 g (1.5 mol) of chloroacetone in 200 ml of acetonitrile. The mixture is stirred at 20°-25° C. for a further 15 hours. The reaction mixture is poured into 750 ml of 2N HCl (pH value=1) and extracted three times with 300 ml of ether. The combined organic phases are dried over magnesium sulphate and concentrated on a rotary evaporator. The residue is treated with 200 ml of ether, the precipitated 2,5-bimethoxycarbonyl-1,4-cyclohexanedione is filtered off under suction and the filtrate is again concentrated. The crude product is column chromatographed on silica gel with ether/hexane 1:1 and gives 32.28 g (15.6%) of methyl 4-chloro-2-acetonylacetoacetate.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]2[CH2:12][NH:11][CH2:10][CH2:9][C:5]=2[N:6]=[CH:7][N:8]=1.Br[C:14]1[CH:15]=[N:16][CH:17]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH3:1][O:2][C:3]1[C:4]2[CH2:12][N:11]([C:14]3[CH:15]=[N:16][CH:17]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:19]=3)[CH2:10][CH2:9][C:5]=2[N:6]=[CH:7][N:8]=1
Reactant: COc1ncnc2c1CNCC2
Reactant: FC(F)(F)c1cncc(Br)c1
Agent: [Pd]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: COc1ncnc2c1CN(c1cncc(C(F)(F)F)c1)CC2
Temperature: 110 °C
Reaction time: 1.5 h
Yield: 38.1 %

Procedure:
To a glass vial was added 4-methoxy-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine (0.273 g, 1.65 mmol), 3-bromo-5-(trifluoromethyl)pyridine (0.373 g, 1.65 mmol), cesium carbonate (1.08 g, 3.31 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.076 g, 0.083 mmol), X-Phos (0.079 g, 0.165 mmol) and anhydrous dioxane (5 mL). The vial was flushed with a stream of argon for 15 sec and capped. The mixture was heated with stirring for 1.5 h at 110° C. Filtered through a celite pad, concentrated in vacuo and purified by flash chromatography on silica gel with heptanes/EtOAc, 100/0 to 0/100 to give 4-methoxy-6-(5-trifluoromethyl-pyridin-3-yl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine as an orange gum (195 mg, 34% yield) 1H NMR (DMSO-d6, 298K) 2.95 (t, 2H) 3.77 (t, 2H) 4.02 (s, 3H) 4.37 (s, 2H) 7.67-7.71 (m, 1H) 8.30-8.34 (m, 1H) 8.63 (s, 1H) 8.67-8.71 (1H, m) LCMS: [M+H]+=311.2, Rt(4)=0.94 min.
Reaction SMILES: [Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[F:9].P(Cl)(Cl)Cl.[Cl:14][C:15]1[CH:23]=[C:19]([C:20](O)=[O:21])[C:18]([OH:24])=[CH:17][CH:16]=1.C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:20](=[O:21])[C:19]2[CH:23]=[C:15]([Cl:14])[CH:16]=[CH:17][C:18]=2[OH:24])=[CH:4][C:3]=1[F:9]
Reactant: O=C(O)c1cc(Cl)ccc1O
Reactant: Nc1ccc(Br)c(F)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClP(Cl)Cl
Solvent: Cc1ccccc1
Product: O=C(Nc1ccc(Br)c(F)c1)c1cc(Cl)ccc1O
Yield: 90 %

Procedure:
4-Bromo-3-fluoroaniline (0.570 g, 3.00 mmol) and phosphorus trichloride (0.176 ml, 2.0 mmol) were added to a solution of 5-chlorosalicylic acid (0.690 g, 4.00 mmol) in toluene (30 ml), and the mixture was refluxed for 2 hours. Saturated aqueous sodium hydrogencarbonate was added to the reaction mixture, and the mixture was concentrated under reduced pressure and extracted with tetrahydrofuran. The organic layer was washed with saturated aqueous sodium hydrogencarbonate and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give the title compound (0.930 g, 90%) as a white solid.
Reaction SMILES: CS([Cl:5])(=O)=O.CCN(CC)CC.[CH3:13][O:14][C:15]1[CH:16]=[CH:17][C:18]([N+:23]([O-:25])=[O:24])=[C:19]([CH:22]=1)[CH2:20]O>C(Cl)Cl>[CH3:13][O:14][C:15]1[CH:16]=[CH:17][C:18]([N+:23]([O-:25])=[O:24])=[C:19]([CH:22]=1)[CH2:20][Cl:5]
Reactant: CS(=O)(=O)Cl
Reactant: COc1ccc([N+](=O)[O-])c(CO)c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccc([N+](=O)[O-])c(CCl)c1
Yield: 94.9 %

Procedure:
MsCl (1.9 mL, 24 mmol) was added to Et3N (4.5 mL, 32 mmol) and 5-methoxy-2-nitrobenzyl alcohol (1.48 g, 8.1 mmol) in CH2Cl2 (80 mL) and the ni-xture kept at reflux for 12 h. The solution was cooled, washed with dilute HCl (2N, 2×50 mL), dried (Na2SO4), concentrated, and filtered through a short column of silica (eluting with 9:1 petroleum ether:EtOAc) to give 5-methoxy-2-nitrobenzyl chloride as a yellow liquid (1.55 g, 95%). 1H N (CDCl3) δ 8.17 (d, J=9.1 Hz, 1 H, H-3), 7.20 (d, J=2.8Hz, 1 H, H-6), 6.93 (dd, J=9.1, 2.8 Hz, 1 H, H-4), 5.03 (s, 2 H, ArCH2Cl), 3.93 (s, 3 H, ArOCH3); 13C NMR (CDCl3) δ 163.7 (C-2), 140.7, 135.5, 128.2, 116.5, 113.7 (C-1,3,4,5,6), 56.1 (OCH3), 43.7 (CH2Cl); MS (EI) m/z 201 [70%, M+ (35Cl)], 184 (100%), 166 (60%, M - Cl), 156 (50%), 106 (70%); HRMS (EI) Calcd. for C8H8ClNO3 203.0163 (35Cl). Found 203.0165.
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=1.N1C=CC=CC=1.[CH2:19]([S:22](Cl)(=[O:24])=[O:23])[CH2:20][CH3:21]>C(Cl)Cl>[CH2:19]([S:22]([NH:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])[N:6]=1)(=[O:24])=[O:23])[CH2:20][CH3:21]
Reactant: CCCS(=O)(=O)Cl
Reactant: CCOC(=O)Cc1csc(N)n1
Agent: CCOC(=O)Cc1csc(=N)[nH]1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCCS(=O)(=O)Nc1nc(CC(=O)OCC)cs1
Temperature: 40 °C

Procedure:
A mixture of ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate, which can be represented as ethyl 2-(2-imino-2,3-dihydro-1,3-thiazol-4-yl)acetate, (40 g.) and pyridine (200 ml.) was stirred in a stream of nitrogen gas at 40° C., and to the mixture was dropwise added a mixture of propanesulfonyl chloride (61.3 g.) and methylene chloride (100 ml.) over 2 hours, and then the mixture was stirred for 2 hours at the same temperature. After the reaction, pyridine and methylene chloride were distilled off from the reaction mixture. The residue was dissolved in ethyl acetate, and the solution was washed with water, 1/2N hydrochloric acid and water in turn and then dried. The ethyl acetate was distilled off from the solution, and the residue was washed with a mixture of ethyl acetate and diethyl ether and then dried to give ethyl 2-(2-propanesulfonylamino-1,3-thiazol-4-yl)acetate, which can be represented as ethyl 2-(2-propanesulfonylimino-2,3-dihydro-1,3-thiazol-4-yl)acetate, (16.4 g.), mp 140° to 142° C.
Reaction SMILES: [CH2:1]1[O:9][C:8]2[CH:7]=[CH:6][C:5]([CH3:10])=[CH:4][C:3]=2[O:2]1.[N+:11]([O-])(O)=O.O>C(O)(=O)C>[CH2:1]1[O:2][C:3]2[CH:4]=[C:5]([CH3:10])[C:6]([NH2:11])=[CH:7][C:8]=2[O:9]1
Reactant: O=[N+]([O-])O
Reactant: Cc1ccc2c(c1)OCO2
Solvent: O
Solvent: CC(=O)O
Product: Cc1cc2c(cc1N)OCO2
Reaction time: 0.75 h
Yield: 87 %

Procedure:
To a solution of (3,4-methylenedioxy)toluene (5 ml) in acetic acid (20 ml) cooled with a cold water bath was added, dropwise, nitric acid (70%, 5 ml). The mixture was stirred for 45 min. To work up, water (100 ml) was added and the resulting yellow precipitate was filtered and washed with water until the aqueous filtrate was colorless. The yellow solid was dissolved in EtOAc (250 ml) and dried (MgSO4), and the solid was filtered off. The filtrate was subjected to catalytic hydrogenation (10% Pd/C, 1 atm) for 12 hours. The reaction mixture was then filtered off the catalyst and the filtrate was concentrated on a rotavap to give (3,4-methylenedioxy)-6-methylaniline as a brownish grey solid (5.49 g, 87% yield).
Reaction SMILES: [N+:1]([C:4]1[S:5][CH:6]=[C:7]2[C:11](=[O:12])[N:10]([CH:13]3[CH2:18][CH2:17][C:16](=[O:19])[NH:15][C:14]3=[O:20])[C:9](=[O:21])[C:8]=12)([O-])=O.C(O)(=O)C>C(O)C.O.[Fe]>[NH2:1][C:4]1[S:5][CH:6]=[C:7]2[C:11](=[O:12])[N:10]([CH:13]3[CH2:18][CH2:17][C:16](=[O:19])[NH:15][C:14]3=[O:20])[C:9](=[O:21])[C:8]=12
Reactant: O=C1CCC(N2C(=O)c3csc([N+](=O)[O-])c3C2=O)C(=O)N1
Agent: [Fe]
Solvent: O
Solvent: CCO
Solvent: CC(=O)O
Product: Nc1scc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O
Yield: 34 %

Procedure:
0.309 g of 1-nitryl-5-(2,6-dioxopiperidin-3-yl)-5H-thieno(3,4-c)pyrrole-4,6-dione was suspended in 20 mL of ethanol and 20 mL of water, and 0.7 g freshly-activated iron powder (washed with water after hydrochloric acid treatment) and 5 mL acetic acid were added and refluxed for 2 h. The reaction mixture was cooled and filtered. The filtered solution was evaporated to dryness; and the remaining residue was dissolved in 150 mL of ethyl acetate, washed with 40 mL of water and 40 mL of brine, dried over anhydrous MgSO4, filtered, and evaporated to dryness. The remaining residue was purified on silica gel column chromatography to obtain a solid (0.095 g).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]3[CH:10]=[CH:11][C:12]([CH2:14][OH:15])=[CH:13][C:8]=3[O:7][C:6]=2[CH:16]=1.[Si:17](Cl)([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18].C(N(CC)CC)C.C(OCC)C>C1COCC1.CN(C)C1C=CN=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]3[CH:10]=[CH:11][C:12]([CH2:14][O:15][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])=[CH:13][C:8]=3[O:7][C:6]=2[CH:16]=1
Reactant: OCc1ccc2c(c1)oc1cc(Br)ccc12
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: CN(C)c1ccncc1
Solvent: CCOCC
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)(C)[Si](C)(C)OCc1ccc2c(c1)oc1cc(Br)ccc12
Temperature: 25 °C
Reaction time: 20 h
Yield: 82.6 %

Procedure:
To a solution of 3-bromo-7-hydroxymethyl-dibenzofuran 3 (2.74 g, 9.9 mmol) and t-butyldimethylsilyl chloride (1.93 g, 12.8 mmol) in THF (60 ml) was added triethylamine (1.95 ml, 13.8 mmol) followed by 4-dimethylaminopyridine (120.7 mg, 0.99 mmol). After stirring at room temperature for 20 hours, the solution was poured into ethyl ether (180 ml) and washed successively with saturated NH4Cl, saturated NaHCO3, H2O, and brine. Drying (MgSO4) and evaporation gave a brown solid which was purified by flash chromatography through 100 g silica gel (10% CH2Cl2 hexane) to yield 3.2 g (82%) of the title compound as a pale yellow solid.
Reaction SMILES: C(O)[C@H]1O[C@H](O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@@H](O)[C@@H]1O.N[C@@H](CCC(N[C@H](C(NCC(O)=O)=O)CS)=O)C(O)=O.C(N(CC([O-])=O)CC(O)=O)CN(CC([O-])=O)CC(O)=O.[Na+].[Na+].[CH:66]1[CH:71]=[N+:70]([C@@H:72]2[O:76][C@H:75]([CH2:77][O:78][P:79]([O:82][P:83]([O:86][CH2:87][C@H:88]3[O:92][C@@H:91]([N:93]4[C:97]5[N:98]=[CH:99][N:100]=[C:101]([NH2:102])[C:96]=5[N:95]=[CH:94]4)[C@H:90]([O:103][P:104]([OH:107])([OH:106])=[O:105])[C@@H:89]3[OH:108])([OH:85])=[O:84])([OH:81])=[O:80])[C@@H:74]([OH:109])[C@H:73]2[OH:110])[CH:69]=[C:68]([C:111]([NH2:113])=[O:112])[CH:67]=1.[Cl-].[Mg+2].[Cl-].C(OP(O)(O)=O)[C@H]1O[C@H](OP(O)(O)=O)[C@H](O)[C@@H](O)[C@@H]1O.P(OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)(O)(O)=O>P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[CH:99]1[N:100]=[C:101]([NH2:102])[C:96]2[N:95]=[CH:94][N:93]([C@@H:91]3[O:92][C@H:88]([CH2:87][O:86][P:83]([O:82][P:79]([O:78][CH2:77][C@H:75]4[O:76][C@@H:72]([N:70]5[CH:69]=[C:68]([C:111]([NH2:113])=[O:112])[CH2:67][CH:66]=[CH:71]5)[C@H:73]([OH:110])[C@@H:74]4[OH:109])([OH:81])=[O:80])([OH:85])=[O:84])[C@@H:89]([OH:108])[C@H:90]3[O:103][P:104]([OH:107])([OH:106])=[O:105])[C:97]=2[N:98]=1
Reactant: NC(=O)c1ccc[n+]([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@H](n4cnc5c(N)ncnc54)[C@H](OP(=O)(O)O)[C@@H]3O)[C@@H](O)[C@H]2O)c1
Agent: N[C@@H](CCC(=O)N[C@@H](CS)C(=O)NCC(=O)O)C(=O)O
Agent: O=C([O-])CN(CCN(CC(=O)[O-])CC(=O)O)CC(=O)O
Agent: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)COP(=O)(O)O
Product: NC(=O)C1=CN([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@H](n4cnc5c(N)ncnc54)[C@H](OP(=O)(O)O)[C@@H]3O)[C@@H](O)[C@H]2O)C=CC1

Procedure:
The enzymic activity is determined according to the following procedure: 10.8 g of trehalose, 860 mg of glutathione, and 17.2 mg of Na2EDTA are dissolved in a 57 mM potassium phosphate buffer solution (pH 7.0) to prepare 100 ml of a solution. A mixture of 1.40 ml of the thus prepared solution, 100 μl of a 20 mM NADP+ solution, 100 μl of a 26 mM magnesium chloride solution, 100 μl of a 1.34 mM glucose 1,6-diphosphate solution, 100 μl of a 31 unit/ml phosphoglucomutase solution, 100 μl of a 35 unit/ml glucose 6-phosphate dehydrogenase solution, and 100 μl of a sample solution is incubated at 30° C. and the quantity of produced NADPH is monitored consecutively by means of absorption spectrophotometry at 340 nm. One unit refers to the amount of enzyme which is capable of producing 1 μmol of NADPH for 1 min. under the conditions.