Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1(C)C=CC(S(O)(=O)=O)=CC=1.CO[CH:14](OC)[C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1.[OH:25][CH2:26][CH2:27][C@H:28]([OH:40])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39].C(OCC)(=O)C>CN(C)C=O>[CH3:22][O:21][C:18]1[CH:19]=[CH:20][C:15]([CH:14]2[O:40][C@H:28]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])[CH2:27][CH2:26][O:25]2)=[CH:16][CH:17]=1
Reactant: COc1ccc(C(OC)OC)cc1
Reactant: CCCCCCCCCCC[C@@H](O)CCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCCCCCCCCCC[C@@H]1CCOC(c2ccc(OC)cc2)O1
Temperature: 25 °C
Reaction time: 2 h
Yield: 99.3 %

Procedure:
p-Toluenesulfonic acid (152 mg, 0.80 mmol) and 4-methoxybenzaldehyde dimethylacetal (2.9 g, 16.0 mmol) was added to a solution of (R)-1,3-dihydroxytetradecane (1.85 g, 8.0 mnuol) in dimethylformamide (20 ml) and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure. The residue was diluted with ethyl acetate. The ethyl acetate layer was successively washed with saturated aqueous sodium hydrogencarbonate solution and saturated aqueous sodium chloride solution, dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by chromatography on a silica gel column using cyclohexane:ethyl acetate=9:1 as the eluant to give the desired product (2.78 g, yield 99%).
Reaction SMILES: [ClH:1].[CH:2]1([C:8]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)([OH:21])[C:9]([O:11][CH2:12][CH2:13][NH:14][C:15]2[N:20]=[CH:19][CH:18]=[CH:17][N:16]=2)=[O:10])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1>[Pd].O>[ClH:1].[CH:22]1([C:8]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)([OH:21])[C:9]([O:11][CH2:12][CH2:13][NH:14][C:15]2[NH:20][CH2:19][CH2:18][CH2:17][N:16]=2)=[O:10])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]1
Reactant: O=C(OCCNc1ncccn1)C(O)(c1ccccc1)C1CCCCC1
Agent: [Pd]
Agent: Cl
Solvent: O
Product: O=C(OCCNC1=NCCCN1)C(O)(c1ccccc1)C1CCCCC1

Procedure:
A mixture of 2-(2-pyrimidyl)aminoethyl α-cyclohexylphenylglycolate hydrochloride (1.4 g) and 10% palladium on carbon (0.15 g) in H2O (150 ml), was hydrogenated at room pressure. After the absorption had ceased, the catalyst was filtered off, and the solution was evaporated in vacuo. The residue was triturated with ethylacetate, affording 0.85 of 2-(1,4,5,6-tetrahydropyrimidin-2-yl)aminoethyl α-cyclohexylphenylglycolate hydrochloride. M.p. 95° C.
Reaction SMILES: [NH2:1][C:2]1[C:3]([Br:17])=[C:4]2[N:11]([OH:12])[C:10]([C:13]([F:16])([F:15])[F:14])=[N:9][C:5]2=[N:6][C:7]=1[Br:8].CI.[C:20](=O)([O-])[O-].[K+].[K+].CC(C)=O>CCOCC>[CH3:20][O:12][N:11]1[C:4]2[C:5](=[N:6][C:7]([Br:8])=[C:2]([NH2:1])[C:3]=2[Br:17])[N:9]=[C:10]1[C:13]([F:14])([F:16])[F:15]
Reactant: O=C([O-])[O-]
Reactant: Nc1c(Br)nc2nc(C(F)(F)F)n(O)c2c1Br
Agent: [K+]
Solvent: CC(C)=O
Solvent: CI
Solvent: CCOCC
Product: COn1c(C(F)(F)F)nc2nc(Br)c(N)c(Br)c21

Procedure:
6-Amino-5,7-dibromo-2-trifluoromethyl-1-hydroxy-1H-imidazo(4,5-b)pyridine (1 gram) was mixed and stirred for 2 hours with 2 milliliters of methyl iodide, 2 grams of potassium carbonate, and 10 milliliters of acetone. The reaction mixture was then diluted with about 80 milliliters of ether and washed with five 15-milliliter portions of water. The ether layer was dried over magnesium sulfate and filtered with carbon, and the ether removed on a rotary evaporator. The resulting 1-methoxy-6-amino-5,7-dibromo-2-(trifluoromethyl)-1H-imidazo(4,5-b)pyridine product melted at 169°-72°C. A portion was recrystallized from methanol, m.p., 177°-8°C.
Reaction SMILES: [Cl:1][C:2]1[CH:20]=[CH:19][C:5]([C:6]([C:8]2[N:12]([CH3:13])[C:11]([C:14]([O:16][CH3:17])=[O:15])=[CH:10][C:9]=2[CH3:18])=[O:7])=[C:4]([O:21][CH3:22])[CH:3]=1.[Br:23]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[Br:23][CH2:18][C:9]1[CH:10]=[C:11]([C:14]([O:16][CH3:17])=[O:15])[N:12]([CH3:13])[C:8]=1[C:6](=[O:7])[C:5]1[CH:19]=[CH:20][C:2]([Cl:1])=[CH:3][C:4]=1[O:21][CH3:22]
Reactant: COC(=O)c1cc(C)c(C(=O)c2ccc(Cl)cc2OC)n1C
Reactant: O=C1CCC(=O)N1Br
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1cc(CBr)c(C(=O)c2ccc(Cl)cc2OC)n1C

Procedure:
Methyl 5-(4-chloro-2-methoxybenzoyl)-1,4-dimethylpyrrole-2-carboxylate (0.5 g, 0.0015 m) was brominated with N-bromosuccinimide (0.32 g, 0.0018 m) in carbon tetrachloride according to the procedure of Example 4, Step A, to afford methyl 4-(bromomethyl)-5-(4-chloro-2-methoxybenzoyl)-1-methyl-pyrrole-2-carboxylate.
Reaction SMILES: [H-].[Na+].[NH2:3][CH:4]1[CH2:7][CH:6]([OH:8])[CH2:5]1.[CH2:9]([O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23](F)=[C:24]([Cl:27])[CH:25]=2)[CH:20]=[CH:19][N:18]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>CC(N(C)C)=O>[CH2:9]([O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:8][CH:6]3[CH2:7][CH:4]([NH2:3])[CH2:5]3)=[C:24]([Cl:27])[CH:25]=2)[CH:20]=[CH:19][N:18]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: NC1CC(O)C1
Reactant: Fc1cc2ccnc(OCc3ccccc3)c2cc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: NC1CC(Oc2cc3ccnc(OCc4ccccc4)c3cc2Cl)C1
Reaction time: 2 h
Yield: 30.5 %

Procedure:
To a suspension of 459 mg (11.5 mmol) of sodium hydride (60%) in 16 mL of dimethyl acetamide was added a solution of 333 mg (3.82 mmol) of 3-amino-cyclobutanol (50) in 8 ml of dimethyl acetamide. After stirring for 60 min at room temperature a solution of 1.00 g (3.48 mmol) of 1-benzyloxy-7-chloro-6-fluoro-isoquinoline (11) in 16 ml of dimethyl acetamide was added and stirring was continued first at room temperature, then for 2 h at 50° C. until the reaction went to completion. The reaction was quenched by addition of water and the reaction mixture was extracted three times with a mixture of dichloromethane and 2-propanol (3:1). The combined organic layers were evaporated, water was added and the crude product was subjected to lyophilization to remove remainders of dimethyl acetamide. The obtained crude product was purified by silica gel chromatography to yield 377 mg of the title compound (51) as a mixture of diastereoisomers. Rt=0.85 min (Method H). Detected mass: 355.1 (M+H+).
Reaction SMILES: [Al].[F:2][C:3]1[CH:4]=[C:5]([C@@H:11]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH3:12])[CH:6]=[CH:7][C:8]=1[CH:9]=O.Cl.[F:22][C:23]1([F:29])[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1>>[F:22][C:23]1([F:29])[CH2:28][CH2:27][N:26]([CH2:9][C:8]2[CH:7]=[CH:6][C:5]([C@@H:11]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH3:12])=[CH:4][C:3]=2[F:2])[CH2:25][CH2:24]1
Reactant: C[C@H](NC(=O)OC(C)(C)C)c1ccc(C=O)c(F)c1
Reactant: FC1(F)CCNCC1
Agent: Cl
Agent: [Al]
Product: C[C@H](NC(=O)OC(C)(C)C)c1ccc(CN2CCC(F)(F)CC2)c(F)c1

Procedure:
Following the procedure for intermediate 111: Title compound was prepared from (S)-tert-butyl 1-(3-fluoro-4-formylphenyl)ethylcarbamate and 4,4-difluoropiperidine hydrochloride as a white solid. LCMS tR=1.63 min; MS m/z 371.5 (M−H).
Reaction SMILES: [C:1]1(=[O:11])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH2:2]1.[H][H]>[Pd].C(OCC)(=O)C>[CH2:6]([CH:2]1[CH2:3][CH2:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:1]1=[O:11])[C:5]1[CH:10]=[CH:1][CH:2]=[CH:3][CH:4]=1
Reactant: O=C1CC=Cc2ccccc21
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Product: O=C1c2ccccc2CCC1Cc1ccccc1
Yield: 114.7 %

Procedure:
A Parr® hydrogenation bottle was charged with naphthalen-1-one (15 gm), ethyl acetate (150 mL) and 1 g of 10% palladium on charcoal. The mixture was hydrogenated on a Parr® shaker for about 15 hrs under 20 psi of hydrogen. The resulting mixture was filtered through a pad of Celite® and concentrated in vacuo to afford a red oil which was purified by flash chromatography (3:1 hexane/diethyl ether) to afford 14.1 gm of benzyltetralone, mp 50-51° C. Analysis calculated for C18H18O2 : 266.1302. Found: 266.1308.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([N:7]=[CH:8][C:9](=[O:29])[N:10]2[CH2:13][CH2:14][N:15]2[CH2:20][CH2:19][CH:18]([NH:21]C(=O)OC(C)(C)C)[CH2:17][CH2:16]2)=[CH:5][CH:4]=1.FC(F)(F)C(O)=O.NC1CCN(CCN2C3C(=CC=C(F)C=3)N=CC2=O)CC1>ClCCl>[NH2:21][CH:18]1[CH2:17][CH2:16][N:15]([CH2:14][CH2:13][N:10]2[C:11]3[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:12]=3)[N:7]=[CH:8][C:9]2=[O:29])[CH2:20][CH2:19]1
Reactant: COc1ccc2ncc(=O)n(CCN3CCC(NC(=O)OC(C)(C)C)CC3)c2c1
Agent: NC1CCN(CCn2c(=O)cnc3ccc(F)cc32)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc2ncc(=O)n(CCN3CCC(N)CC3)c2c1
Yield: 77.4 %

Procedure:
tert-Butyl {1-[2-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate (Intermediate 147, 190 mg, 0.47 mmol) was reacted with trifluoroacetic acid in dichloromethane as described for Intermediate 140 to give 110 mg of the crude product as an oil.
Reaction SMILES: N1C=CC=CC=1.Cl.[NH2:8][OH:9].[CH3:10][S:11]([NH:14][C:15]1[CH:16]=[C:17]2[C:40](=[CH:41][CH:42]=1)[O:39][C:20]1([CH2:25][CH2:24][N:23]([CH2:26][CH2:27][O:28][CH2:29][CH2:30][NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:22][CH2:21]1)[CH2:19][C:18]2=O)(=[O:13])=[O:12]>CO.ClCCl>[OH:9][N:8]=[C:18]1[C:17]2[C:40](=[CH:41][CH:42]=[C:15]([NH:14][S:11]([CH3:10])(=[O:13])=[O:12])[CH:16]=2)[O:39][C:20]2([CH2:25][CH2:24][N:23]([CH2:26][CH2:27][O:28][CH2:29][CH2:30][NH:31][C:32](=[O:38])[O:33][C:34]([CH3:35])([CH3:36])[CH3:37])[CH2:22][CH2:21]2)[CH2:19]1
Reactant: CC(C)(C)OC(=O)NCCOCCN1CCC2(CC1)CC(=O)c1cc(NS(C)(=O)=O)ccc1O2
Reactant: NO
Agent: Cl
Solvent: c1ccncc1
Solvent: ClCCl
Solvent: CO
Product: CC(C)(C)OC(=O)NCCOCCN1CCC2(CC1)CC(=NO)c1cc(NS(C)(=O)=O)ccc1O2
Temperature: 25 °C
Reaction time: 1 h
Yield: 98.1 %

Procedure:
Anhydrous pyridine (40 μL, 0.5 mmol) and hydroxylamine hydrochloride (8 mg, 0.11 mmol) were added to a solution of tert-butyl 2-(2-(6-(methylsulfonamido)-4-oxospiro[chroman-2,4′-piperidine]-1′-yl)ethoxy)ethylcarbamate (12, 50 mg, 0.10 mmol) in 5 mL of anhydrous methanol. This solution was stirred at room temperature for ˜1 hour and then at ˜60° C. for ˜1 hour. Additional hydroxylamine hydrochloride (6.2 mg, 0.09 mmol) and anhydrous pyridine (40 μL, 0.5 mmol) were added and stirring was continued at 60-65° C. for ˜1 hour. More hydroxylamine hydrochloride (13.9 mg, 0.20 mmol) was added and stirring was continued at 60-65° C. for ˜80 minutes. Hydroxylamine hydrochloride (7 mg, 0.10 mmol) was added and stirring was continued at 60-65° C. for ˜2 hours. TLC (silica gel, 10% methanol in dichloromethane, UV visualization) showed complete disappearance of starting ketone 12 (Rf=0.35-0.4) and a single new spot (18, Rf=0.18-0.27). The reaction mixture was concentrated to dryness under reduced pressure on a rotary evaporator. The residue was dissolved in 5 mL of ethyl acetate and extracted successively with 10 mL of 0.5 M aqueous hydrochloric acid, mL of water, and 5 mL of saturated aqueous sodium chloride. TLC (as above) showed the product (18) in the combined aqueous extracts, which were adjusted to pH ˜13 by addition of sodium hydroxide pellets and then to pH ˜4 by addition of 3 M aqueous hydrochloric acid. The aqueous solution was extracted with three 20 mL portions of ethyl acetate. The combined ethyl acetate extract was dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure on a rotary evaporator followed by high vacuum overnight to afford 50.3 mg (98% yield) tert-butyl 2-(2-(4-(hydroxyimino)-6-(methylsulfonamido)-spiro[chroman-2,4′-piperidine]-1′-yl)ethoxy)ethylcarbamate (18).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2(O)[CH2:20][CH2:19][CH:18]([CH2:21][OH:22])[CH:17]([CH3:23])[CH:16]2[CH2:24][CH3:25])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1C=CC(S(O)(=O)=O)=CC=1>C(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]([CH2:24][CH3:25])[CH:17]([CH3:23])[CH:18]([CH2:21][OH:22])[CH2:19][CH:20]=2)=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCC1C(C)C(CO)CCC1(O)c1ccc(OCc2ccccc2)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Product: CCC1C(c2ccc(OCc3ccccc3)cc2)=CCC(CO)C1C

Procedure:
To 1-(4-benzyloxy-phenyl )-2-ethyl-4-hydroxymethyl-3-methyl-cyclohexanol (7.8 g, 0.0166 mol) was added pTSA (1.8 g, 1 eq.) in DCM (100 mL). The reaction mixture was refluxed for 8 h. DCM (200 mL) was added and the mixture was washed with aqueous saturated NaHCO3 (3×300 mL). The organic layer was separated, dried over MgSO4 and purified on SiO2 (50% ethyl acetate/hexane) twice to yield [4-(4-benzyloxy-phenyl)-5-ethyl-6-methyl-cyclohex-3-enyl]-methanol.
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([O:14][CH2:15][CH:16](O)COC(CCCCCCCCCCC)=O)=[O:13]>OCC(CO)O>[CH:15]([O:14][C:12](=[O:13])[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH3:1])=[CH2:16]
Reactant: CCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCC
Solvent: OCC(O)CO
Product: C=COC(=O)CCCCCCCCCCC

Procedure:
1,3DLa was easily purified and recovered by crystallization in dry methanol at room temperature (RT) or in hexane at −20° C. (purity >98%). When lauric acid (La) was used as an acyl-donor, solvent was added to dissolve the FFA. Though the method as described in J. Am. Oil Chem. Soc., 1992, 69:955-960, allowed faster reaction rate with high yield of 1,3-DLa (65%), the highest yield (78%) of 1,3-DLa obtained from esterification between glycerol and lauric acid vinyl ester (LaVE) at 0° C. in a solvent-free condition catalyzed by CAL-B after 24 h, as illustrated in FIG. 14. FIG. 14 summarizes data of various synthesis of 1,3-dilaurin. Method1=esterification of glycerol and lauric acid in n-hexane at 0° C. catalyzed by CAL-B; Method2=esterification of glycerol and lauric acid vinyl ester in a solvent-free condition at 0° C. catalyzed by CAL-B; Method3 (Schneider's method)=esterification of glycerol (immobilized on silica gel) and lauric acid vinyl ester in MTBE at room temperature catalyzed by Lipozyme RM IM™ (Eurzyme, Dublin, Ireland). (DG=1,3-dilaurin, MG=1-monolaurin). LaVE, as acyl donor, allowed higher yield and faster reaction with less amount of MG than La.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:4]=1[CH:5]=O.[C:13]([CH2:15]C(O)=O)#[N:14].N1CCCCC1>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:4]=1[CH:5]=[CH:15][C:13]#[N:14]
Reactant: N#CCC(=O)O
Reactant: COc1ccc(OC)c(C=O)c1
Solvent: c1ccncc1
Solvent: C1CCNCC1
Product: COc1ccc(OC)c(C=CC#N)c1
Temperature: 80 °C
Reaction time: 2 h
Yield: 69.2 %

Procedure:
A mixture of 166 g of 2,5-dimethoxybenzaldehyde, 76 g of cyanoacetic acid, 5 ml of piperidine and 400 ml of pyridine was heated at 80° C understirring for 2 hours and then refluxed with heating at 140° C for 5 hours. After the reaction, the mixture was cooled to room temperature and poured into 2 liters of ice water. The precipitated crystals were filteredout and recrystallized from ethanol to give 117 g of the end product havinga melting point of 70 ~ 71° C (yield 62%).
Reaction SMILES: Cl.[NH2:2][OH:3].[OH-].[Na+].C[O:7][C:8](=O)[CH:9]=[CH:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([NH:17][C:18](=[O:27])[CH:19]=[CH:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:12]=1>CO.O>[OH:3][NH:2][C:8](=[O:7])[CH:9]=[CH:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([NH:17][C:18](=[O:27])[CH:19]=[CH:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:12]=1
Reactant: COC(=O)C=Cc1cccc(NC(=O)C=Cc2ccccc2)c1
Reactant: NO
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C(C=Cc1cccc(NC(=O)C=Cc2ccccc2)c1)NO
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
To a suspension of hydroxylamine hydrochloride (0.14 g, 2.01 mmol) (Acros) in methanol (2.0 ml) a solution of NaOH (0.16 g, 4.00 mmol) in H2O (0.2 ml) was added and the resultant mixture was stirred at ambient temperature for 5 min. To the reaction mixture a 3-[3-(3-phenylacryloylamino)-phenyl)-acrylic acid methyl ester (8) (0.15 g, 0.49 mmol) solution in methanol (2.0 ml) was added and stirred at ambient temperature for 1.5 hour. The reaction mixture was partitioned between ethyl acetate and 2N HCl. The organic layer was washed successively with water and saturated NaCl, and the solvent was removed. The residue was crystallized from ethyl acetate-methanol giving pure title compound (0.040 g, 26%), m.p. 178° C. 1H NMR (DMSO-d6, HMDSO), δ: 6.45 (d, 1H, J=16.0 Hz); 6.85 (d, 1H, J=16.0 Hz); 7.14-7.76 (m, 10 H); 8.00 (br s, 1H); 9.03 (br s, 1H); 10.32 (br s, 1H); 10.83 (br s, 1H). HPLC analysis on Zorbax SB-C18 column: impurities 4.5% (column size 4.6×150 mm; mobile phase acetonitrile−0.1% H3PO4, gradient from 30 to 100%; sample concentration 0.25 mg/ml; flow rate 1.5 ml/min; detector: UV 270 nm). Anal. Calcd for C18H16N2O3×0.25 H2O, %: C, 69.11; H, 5.32; N, 8.95. Found, %: C, 69.09; H, 5.06; N, 8.81.
Reaction SMILES: [I-].[CH2:2]([N:9]=[C:10]([C:12]1[C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=[CH:14][N+:13]=1[CH3:21])[OH:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[H][H]>COCCO.[Pt]=O>[CH2:2]([N:9]1[C:18](=[O:19])[CH:17]2[CH:12]([N:13]([CH3:21])[CH2:14][CH2:15][CH2:16]2)[C:10]1=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: [H][H]
Reactant: C[n+]1cccc(C(=O)O)c1C(O)=NCc1ccccc1
Agent: O=[Pt]
Agent: [I-]
Solvent: COCCO
Product: CN1CCCC2C(=O)N(Cc3ccccc3)C(=O)C21

Procedure:
38 g (0.1 mol) of 1-methyl-pyridinium-2,3-dicarboxylic acid N-benzylimide iodide are hydrogenated over 1 g of platinum oxide in 450 ml of glycol monomethyl ether at 30° C. under 70 bar until the uptake of hydrogen has ended (51 hours). The catalyst is then filtered off, the filtrate is concentrated, the residue is taken up in 300 ml of chloroform and the solution is washed 2× with 300 ml of 10% strength sodium carbonate solution each time and with 300 ml of water. After drying over sodium sulphate, it is concentrated. 27 g of an oily residue remain.
Reaction SMILES: [CH3:1][C:2]1[C:11]2[C:10](=[O:12])[CH2:9][C:8]([CH3:14])([CH3:13])[CH2:7][C:6]=2[O:5][C:4](=O)[CH:3]=1.[NH3:16]>>[CH3:1][C:2]1[C:11]2[C:10](=[O:12])[CH2:9][C:8]([CH3:14])([CH3:13])[CH2:7][C:6]=2[NH:16][C:4](=[O:5])[CH:3]=1
Reactant: N
Reactant: Cc1cc(=O)oc2c1C(=O)CC(C)(C)C2
Product: Cc1cc(=O)[nH]c2c1C(=O)CC(C)(C)C2

Procedure:
Prepared from 4,7,7-trimethyl-5,6,7,8-tetrahydro- cumarin-5-one and methanolic ammonia analogously to Example C(b).
Reaction SMILES: [CH2:1]([CH:3]1[NH:8][CH2:7][CH2:6][CH2:5][S:4]1)[CH3:2].[Cl:9][C:10]1[CH:11]=[C:12]([N:16]=[C:17]=[S:18])[CH:13]=[CH:14][CH:15]=1.C1C=CC=CC=1>CCCCCC>[Cl:9][C:10]1[CH:11]=[C:12]([NH:16][C:17]([N:8]2[CH2:7][CH2:6][CH2:5][S:4][CH:3]2[CH2:1][CH3:2])=[S:18])[CH:13]=[CH:14][CH:15]=1
Reactant: S=C=Nc1cccc(Cl)c1
Reactant: CCC1NCCCS1
Solvent: CCCCCC
Solvent: c1ccccc1
Product: CCC1SCCCN1C(=S)Nc1cccc(Cl)c1
Reaction time: 64 h

Procedure:
A mixture of 2.6 g. of 2-ethyltetrahydro-2H-1,3-thiazine, 3.4 g. of 3-chlorophenyl isothiocyanate, and 30 ml. of benzene was stirred, after an initial exotherm, at ambient temperature for about 64 hours. To the reaction mixture was added about 10 ml. of hexane, which caused white crystals to form. The mixture was cooled and filtered, and the solid was washed with hexane. The solid was recrystallized from about 500 ml. of 10:1 hexane:carbon tetrachloride to give N-(3-chlorophenyl)-2-ethyltetrahydro2H-1,3-thiazine-3-carbothioamide, m.p. 69°-73°. The following elemental microanalysis was obtained:
Reaction SMILES: [O:1]=[C:2]1[CH2:6][S:5][CH2:4][CH:3]1[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]([CH3:18])[C:15](O)=[O:16])=[CH:10][CH:9]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:28])=CC=1>C1(C)C=CC=CC=1>[O:1]=[C:2]1[CH2:6][S:5][CH2:4][CH:3]1[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]([CH3:18])[C:15]([OH:16])=[S:28])=[CH:10][CH:9]=1
Reactant: CC(C(=O)O)c1ccc(CC2CSCC2=O)cc1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: Cc1ccccc1
Product: CC(C(O)=S)c1ccc(CC2CSCC2=O)cc1
Yield: 52.2 %

Procedure:
2-[4-(4-Oxothiolan-3-ylmethyl)phenyl]propionic acid (300 mg) obtained in Example 8 was dissolved in toluene (3.0 ml), and to the solution was added the Lawesson's reagent (729 mg), and then the reaction mixture was refluxed by heating for 4 hours. After completion of the reaction, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/1) to give the title compound (166 mg, 52.4%).
Reaction SMILES: [OH:1][C:2]1[C:3](=[O:9])[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1.[N+:10]([C:13]1[CH:18]=[CH:17][C:16]([S:19](Cl)(=[O:21])=[O:20])=[CH:15][CH:14]=1)([O-:12])=[O:11].O>N1C=CC=CC=1>[N+:10]([C:13]1[CH:14]=[CH:15][C:16]([S:19]([O:9][C:3]2[C:2](=[O:1])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)(=[O:21])=[O:20])=[CH:17][CH:18]=1)([O-:12])=[O:11]
Reactant: O=c1cccccc1O
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Solvent: O
Product: O=c1cccccc1OS(=O)(=O)c1ccc([N+](=O)[O-])cc1
Yield: 71 %

Procedure:
2-Hydroxycyclohepta-2,4,6-trienone (0.2 g, 1.7 mmol) was reacted with 4-nitrobenzenesulfonyl chloride (1.1 g, 4.9 mmol) in 5 mL of pyridine. Addition of 10 mL of water allowed for precipitation of PZBG-4c in 71% yield (0.38 g, 1.2 mmol) without the need for further purification. 1H NMR (400 MHz, DMSO) δ=8.45 (d, J=8.8 Hz, 2H), 8.22 (d, J=8.8 Hz, 2H), 7.52 (d, J=9.2 Hz, 1H), 7.46 (dd, J1=10.2 Hz, J2=3.6 Hz, 1H), 7.31 (dd, J1=9.8 Hz, J2=2 Hz, 1H), 7.15 (dd, J1=10.6 Hz, J2=3.6 Hz, 1H). 13C (100 MHz, CDCl3) δ=179.09, 154.86, 151.50, 141.95, 141.27, 138.59, 136.87, 132.06, 131.48, 130.42, 125.42. ESI-MS(+): m/z 308.01 [M+H]+, 324.73 [M+NH4]+
Reaction SMILES: C[O:2][C:3]1[C:10]([O:11]C)=[CH:9][C:8]([N+:13]([O-:15])=[O:14])=[CH:7][C:4]=1[CH:5]=[O:6].Br>C(O)(=O)C>[OH:2][C:3]1[C:10]([OH:11])=[CH:9][C:8]([N+:13]([O-:15])=[O:14])=[CH:7][C:4]=1[CH:5]=[O:6]
Reactant: COc1cc([N+](=O)[O-])cc(C=O)c1OC
Agent: Br
Solvent: CC(=O)O
Product: O=Cc1cc([N+](=O)[O-])cc(O)c1O
Reaction time: 7 h

Procedure:
10.0 g of 2,3-dimethoxy-5-nitrobenzaldehyde are treated with 50 ml of glacial acetic acid and 50 ml of constant-boiling hydrobromic acid and held at the reflux temperature for 7 hours. After treatment with ice the separated precipitate is filtered under suction, washed with water and taken up in ethyl acetate. The organic phase is dried over sodium sulfate and evaporated. The crude product obtained is filtered over silica gel with ethyl acetate. After crystallization from ethyl acetate/hexane there is obtained 2,3-dihydroxy-5-nitrobenzaldehyde in the form of brownish crystals of m.p. 226°-228°.
Reaction SMILES: [CH2:1]([OH:6])[CH2:2][C:3]#[C:4][CH3:5].C(N(CC)CC)C.Cl[SiH:15]([CH:19]([CH3:21])[CH3:20])[CH:16]([CH3:18])[CH3:17]>CN(C)C1C=CN=CC=1.CCCCCC>[CH:16]([SiH:15]([CH:19]([CH3:21])[CH3:20])[O:6][CH2:1][CH2:2][C:3]#[C:4][CH3:5])([CH3:18])[CH3:17]
Reactant: CC#CCCO
Reactant: CC(C)[SiH](Cl)C(C)C
Agent: CN(C)c1ccncc1
Solvent: CCCCCC
Solvent: CCN(CC)CC
Product: CC#CCCO[SiH](C(C)C)C(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a cold (0° C.) solution of 3-pentynol (5.880g, 70.0 mmol, 1.0 equiv), 4-dimethylaminopyridine (DMAP) (840 mg, 7.00 mmol, 0.10 equiv), and triethylamine (TEA) (9.80 ml, 71.0 mmol, 1.01 equiv) in 100 mL of dry hexane was added dropwise chlorodiisopropylsilane (11.0 g, 71.0 mmol, 1.01 equiv) over 20 minutes. The resulting white suspension was allowed to warm to room temperature and was stirred overnight. The reaction mixture was filtered through a short silica pad (10 g) and the solvent was then evaporated in vacuo to give a colorless liquid. Fractional distillation of this liquid afforded 11.2 g (81%) of A-7 as a colorless liquid. An analytical sample (0.48 g) was obtained by redistillation of a 0.50 g sample by Kugelrohr distillation.
Reaction SMILES: [C:1]([P:5]([C:7]([CH3:10])([CH3:9])[CH3:8])Cl)([CH3:4])([CH3:3])[CH3:2].ClCCl.[OH2:14]>>[C:1]([PH:5](=[O:14])[C:7]([CH3:10])([CH3:9])[CH3:8])([CH3:4])([CH3:3])[CH3:2]
Reactant: O
Reactant: CC(C)(C)P(Cl)C(C)(C)C
Solvent: ClCCl
Product: CC(C)(C)[PH](=O)C(C)(C)C
Reaction time: 0.5 h
Yield: 100.2 %

Procedure:
To a flask were added 1.0 g of di(tert-butyl)chlorophosphine and 5 ml of dichloromethane under nitrogen. After slow addition of 0.25 g of water, the mixture was stirred at 22 C for 30 minutes and the solvent was removed leaving a solid. After purification by sublimation, 0.9 g of a white solid was obtained.