Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[NH:3][CH:4]=[CH:5][C:6]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8].[Br:12]N1C(=O)CCC1=O.O.C(OCC)C>O1CCCC1>[Br:12][C:4]1[NH:3][C:2]([CH3:1])=[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH:5]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOC(=O)c1cc[nH]c1C
Solvent: CCOCC
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)c1cc(Br)[nH]c1C
Reaction time: 0.5 h
Yield: 97.5 %

Procedure:
To a solution of ethyl 2-methyl-1H-pyrrole-3-carboxylate (1.53 g) in tetrahydrofuran (20 mL) was added N-bromosuccinimide (1.78 g) at −78° C., and the mixture was stirred at the same temperature for 30 min. Water and diethyl ether were added to extract the reaction mixture. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure at 5° C. or below. The residue was washed with hexane to give the title compound as a colorless solid (yield 2.26 g, 97%).
Reaction SMILES: [CH:1]1([CH2:9][C:10]2[N:11]=[CH:12][NH:13][CH:14]=2)[C:8]2[CH2:7][CH2:6][CH2:5][C:4]=2[CH2:3][CH2:2]1.C([O-])(O)=[O:16].[Na+].ClC(OC1C=CC=CC=1)=O>C1COCC1.O>[CH:1]1([CH2:9][C:10]2[NH:11][C:12](=[O:16])[NH:13][CH:14]=2)[C:8]2[CH2:7][CH2:6][CH2:5][C:4]=2[CH2:3][CH2:2]1
Reactant: O=C([O-])O
Reactant: c1nc(CC2CCC3=C2CCC3)c[nH]1
Agent: O=C(Cl)Oc1ccccc1
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: O=c1[nH]cc(CC2CCC3=C2CCC3)[nH]1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 4-(1,2,3,4,5,6-hexahydro-pentalen-1-ylmethyl)-1H-imidazole; fumarate salt (Intermediate A5 as described in Example A, 340 mg, 1.81 mmol) in THF (15 mL) and water (15 mL) was treated with NaHCO3 (1.52 g, 18 mmol) at rt for 30 m. Phenyl chloroformate (600 mL, 4.7 mmol) was added and stirring was continued for 1 h at 65 EC. The mixture was diluted with water (30 mL) and extracted with EtOAc (3×30 mL). The organic portions were combined and freed of solvent. The residue was dissolved in EtOH (15 mL): water (15 mL) and treated with Na2CO3 (500 mg) for 1.5 h at 95 EC. The mixture was cooled to rt and the product was collected on a glass frit to give a white solid (˜50%) 4-(1,2,3,4,5,6-Hexahydro-pentalen-1-ylmethyl)-1,3-dihydro-imidazol-2-one (Compound 41).
Reaction SMILES: Cl[S:2]([OH:5])(=[O:4])=[O:3].[Cl:6][C:7]1[C:8]([CH3:14])=[C:9]([CH:11]=[CH:12][CH:13]=1)[NH2:10].[OH-].[Na+:16]>C(Cl)(Cl)Cl.O.CCO>[CH3:14][C:8]1[C:7]([Cl:6])=[CH:13][CH:12]=[CH:11][C:9]=1[NH:10][S:2](=[O:4])(=[O:3])[O-:5].[Na+:16]
Reactant: Cc1c(N)cccc1Cl
Reactant: O=S(=O)(O)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClC(Cl)Cl
Solvent: CCO
Solvent: O
Product: Cc1c(Cl)cccc1NS(=O)(=O)[O-]
Reaction time: 1.5 h
Yield: 84.7 %

Procedure:
Chlorosulfonic acid (516 μl, 7.77 mmol) in chloroform (5 ml) was added dropwise to a solution of 3-chloro-2-methylaniline (844 μl, 6.98 mmol) and TEA (7.8 ml, 56.54 mmol) in chloroform (20 ml) at 0° C. The mixture was stirred for 90 min, concentrated in vacuo and a solution of NaOH (848 mg, 21.2 mmol) in water (10 ml) was added and the mixture stirred for 30 min at room temperature. The reaction was concentrated in vacuo and azeotroped with toluene. The solid obtained was heated in EtOH (50 ml) at 60° C. for 15 min, concentrated in vacuo and EtOAc (50 ml) added. The resulting solid was collected by filtration and the filtrate allowed to stand at room temperature for 4 h. The crystals formed were filtered, washed with EtOAc, and the solids combined to give the title compound (1.44 g, 84%).
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[CH:8](=[O:15])[C:9]1C=CC=C[CH:10]=1.C(N(CC)CC)C.C(Cl)(=O)CC>C1(C)C=CC=CC=1.O>[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8](=[O:15])[CH2:9][CH3:10])[CH2:4][CH2:3]1
Reactant: NC1CCNCC1
Reactant: O=Cc1ccccc1
Agent: CCC(=O)Cl
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Solvent: O
Product: CCC(=O)N1CCC(N)CC1
Reaction time: 1.5 h
Yield: 75.9 %

Procedure:
4-Aminopiperidine (4.01 g, 40 mmol) and benzaldehyde (4.251 g, 40 mmol) were dissolved in toluene (70 mL) and refluxed on a Dean-Stark trap until water ceased to evolve. The solvent was evaporated and the residue was reconstituted in dry THF (75 mL). Triethylamine (4.04 g, 40 mmol) was added and the reaction was cooled in an ice bath. With vigorous stirring, propionyl chloride (3.70 g, 40 mmol) was added and the reaction continued for 1.5 hours at rt. The reaction was filtered, and the filtrate was evaporated and treated with 1N HCl (50 mL) for 1 hour. The aqueous phase was washed with Et2O (3×50 mL), basified to pH>10 with NaOH, saturated with sodium chloride and extracted with DCM (5×75 mL). The combined DCM extract was evaporated and azeotropically dried with toluene to give intermediate 1 (4.74 g, 64%) as a light brown oil: 1H NMR (500 MHz, DMSO-d6) δ 4.18 (d, J=11.8 Hz, 1H), 3.74 (d, J=11.8 Hz, 1H), 3.00 (dd, J=11.8, 11.8 Hz, 1H), 2.89 (brs, 2H), 2.82-2.15 (m, 1H), 2.67 (dd, J=11.8 Hz, 11.8 Hz, 1H), 2.28 (q, J=7.1 Hz, 2H), 1.72 (d, J=11.8 Hz, 1H), 1.67 (d, J=11.8 Hz, 1H), 1.14 (q, J=10.2 Hz, 1H), 1.04 (q, J=10.2 Hz, 1H), 0.98 (t, J=7.1 Hz, 3H).
Reaction SMILES: [N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[S:19][C:18]4[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=4[C:16]=3[C:24]([C:26]3[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][NH:35][CH2:36][CH3:37])=[CH:28][CH:27]=3)=O)=[CH:11][CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.CC(C[AlH]CC(C)C)C.[SiH](CC)(CC)CC.[C:54]([OH:60])(C(F)(F)F)=[O:55].[C:61]([O-:64])([OH:63])=O.[Na+]>C1COCC1>[C:54]([OH:60])(=[O:55])[C:61]([OH:64])=[O:63].[C:54]([OH:60])(=[O:55])[C:61]([OH:64])=[O:63].[CH2:36]([NH:35][CH2:34][CH2:33][O:32][C:29]1[CH:30]=[CH:31][C:26]([CH2:24][C:16]2[C:17]3[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=3[S:19][C:15]=2[C:12]2[CH:13]=[CH:14][C:9]([O:8][CH2:7][CH2:6][N:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)=[CH:10][CH:11]=2)=[CH:27][CH:28]=1)[CH3:37]
Reactant: CCNCCOc1ccc(C(=O)c2c(-c3ccc(OCCN4CCCC4)cc3)sc3ccccc23)cc1
Reactant: O=C(O)C(F)(F)F
Reactant: O=C([O-])O
Agent: CC(C)C[AlH]CC(C)C
Agent: CC[SiH](CC)CC
Agent: [Na+]
Solvent: C1CCOC1
Product: CCNCCOc1ccc(Cc2c(-c3ccc(OCCN4CCCC4)cc3)sc3ccccc23)cc1
Product: O=C(O)C(=O)O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A 0° C. solution of 4-[2-(ethylamino)ethoxy]phenyl 2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl ketone (390 mg, 0.758 mmol; Part B) in 5 mL of anhydrous THF was treated with DIBAL-H (1.5 mL, 1.52 mmol, 1M solution in toluene) dropwise via a syringe. After 1 h at 0° C., the excess DIBAL-H was quenched with excess MeOH (approximately 1 mL), 5 mL of saturated Na+K+ tartrate and 5 mL of EtOAc were added, and the biphasic mixture was vigorously stirred for 1.5 h at ambient temperature. The layers were separated, and the aqueous layer was extracted with EtOAc (2×10 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was dissolved in 5 mL of 1,2-dichloroethane and Et3SiH (848 μL, 5.31 mmol). Upon cooling to 0° C., TFA (584 μL, 7.58 mmol) was added in a dropwise fashion. After 1.5 h, the reaction mixture was poured into 50 mL of saturated aqueous NaHCO3 solution. The aqueous phase was extracted with EtOAc (2×50 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. Purification by radial chromatography (SiO2; gradient of 90:8:2 to 85:10:5 hexanes-THF-TEA) afforded 175 mg (0.35 mmol; 42%) of a yellow oil. The free base was converted to the title dioxalate salt according to the conditions described in Example 1, Part C.
Reaction SMILES: C(OC([N:8]1[CH2:12][CH2:11][S:10][CH:9]1[C:13]([OH:15])=O)=O)(C)(C)C.C1C=CC(/C(/C2C=CC([N+]([O-])=O)=CC=2)=N/O)=CC=1.[C:34]1([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH:39]=[CH:38][C:37]([S:40](Cl)(=[O:42])=[O:41])=[CH:36][CH:35]=1.[Cl:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=1[CH2:57][NH2:58]>>[C:34]1([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH:39]=[CH:38][C:37]([S:40]([N:8]2[CH2:12][CH2:11][S:10][CH:9]2[C:13]([NH:58][CH2:57][C:52]2[CH:53]=[CH:54][CH:55]=[CH:56][C:51]=2[Cl:50])=[O:15])(=[O:42])=[O:41])=[CH:36][CH:35]=1
Reactant: CC(C)(C)OC(=O)N1CCSC1C(=O)O
Reactant: NCc1ccccc1Cl
Reactant: O=S(=O)(Cl)c1ccc(-c2ccccc2)cc1
Agent: O=[N+]([O-])c1ccc(/C(=N\O)c2ccccc2)cc1
Product: O=C(NCc1ccccc1Cl)C1SCCN1S(=O)(=O)c1ccc(-c2ccccc2)cc1

Procedure:
Following the general solid phase method as outlined Example 33, starting from 3-(tert-butoxycarbonyl)-1,3-thiazolidine-2-carboxylic acid, Kaiser oxime resin, 1,1′-biphenyl-4-sulfonyl chloride and (2-chlorophenyl)methanamine, the title compound was obtained in 85% purity by HPLC.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:15])[CH2:5][CH:6]([C:11](=O)[CH2:12][CH3:13])[C:7](=O)[CH2:8][CH3:9])[CH3:2].O.[NH2:17][NH2:18]>C(O)C>[CH2:1]([O:3][C:4](=[O:15])[CH2:5][C:6]1[C:11]([CH2:12][CH3:13])=[N:17][NH:18][C:7]=1[CH2:8][CH3:9])[CH3:2]
Reactant: CCOC(=O)CC(C(=O)CC)C(=O)CC
Reactant: NN
Solvent: CCO
Solvent: O
Product: CCOC(=O)Cc1c(CC)n[nH]c1CC
Yield: 72.9 %

Procedure:
A mixture of 4-oxo-3-propionyl-hexanoic acid ethyl ester (15 g, 70 mmol) and hydrazine hydrate (3.5 mL, 71 mmol) in absolute ethanol (150 mL) was refluxed for 16 h. Solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (methanol in methylene chloride) to provide (3,5-diethyl-1H-pyrazol-4-yl)-acetic acid ethyl ester as yellow oil (11 g, 51 mmol).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].[O:11]([C:18]1[CH:24]=[CH:23][C:21]([NH2:22])=[CH:20][CH:19]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C([O-])(C)(C)C.[K+]>CS(C)=O>[N+:8]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[NH:22][C:21]1[CH:20]=[CH:19][C:18]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:24][CH:23]=1)([O-:10])=[O:9]
Reactant: Nc1ccc(Oc2ccccc2)cc1
Reactant: O=[N+]([O-])c1ccccc1F
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: O=[N+]([O-])c1ccccc1Nc1ccc(Oc2ccccc2)cc1

Procedure:
The product (2.03 g) is obtained according to the method of stage 1 of Example 4, by using 3.7 mL of 2-fluoro-nitrobenzene and 7.88 g of 4-phenoxyaniline in the presence of 6.36 g of potassium tert-butanolate in 34 mL of DMSO.
Reaction SMILES: [S:1](=[O:31])(=[O:30])([O:3][CH2:4][C@@H:5]1[C@@H:9]([OH:10])[CH2:8][C@H:7]([N:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([CH2:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:14]=3[C:13]([C:28]#[CH:29])=[CH:12]2)[O:6]1)[NH2:2].O>CCO.[Pd]>[S:1](=[O:30])(=[O:31])([O:3][CH2:4][C@@H:5]1[C@@H:9]([OH:10])[CH2:8][C@H:7]([N:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([CH2:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:14]=3[C:13]([CH2:28][CH3:29])=[CH:12]2)[O:6]1)[NH2:2]
Reactant: C#Cc1cn([C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)O2)c2ncnc(CCc3ccccc3)c12
Agent: [Pd]
Solvent: CCO
Solvent: O
Product: CCc1cn([C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)O2)c2ncnc(CCc3ccccc3)c12
Yield: 11.8 %

Procedure:
A suspension of {(2R,3S,5R)-5-[5-ethynyl-4-(2-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]-3-hydroxytetrahydrofuran-2-yl}methyl sulfamate (0.0824 g, 0.190 mmol) and Pd/C (10% wt, ˜50% H2O, 0.01 g) in EtOH (10 mL) was stirred under an atmosphere of H2 (1 atm) for 5 h at r.t. The reaction mixture was filtered through celite and the filtrate was concentrated. The residue was purified by flash chromatography (0 to 10% MeOH/DCM) to give the title compound (0.010 g, 11%).
Reaction SMILES: C1[CH:5]2[C@@H:6]3[CH:10]=[CH:9][C@H:8]([CH:4]2C=C1)[CH2:7]3.[CH2:11]([CH2:14][C:15]([O-:17])=[O:16])[CH:12]=[CH2:13].C1(C=CC(O)=CC=1)O>>[CH:6]12[CH2:7][CH:8]([CH2:9][CH2:10]1)[CH:4]=[CH:5]2.[CH2:11]([CH2:14][C:15]([OH:17])=[O:16])[CH:12]=[CH2:13]
Reactant: C1=CC2C(C1)[C@@H]1C=C[C@H]2C1
Reactant: C=CCCC(=O)[O-]
Agent: Oc1ccc(O)cc1
Product: C1=CC2CCC1C2
Product: C=CCCC(=O)O
Temperature: 180 °C
Reaction time: 5 h
Yield: 30 %

Procedure:
DCPD (dicyclopentadiene, Aldrich, 248 ml, 1.852 mol), allylacetate (Aldrich, 500 ml, 4.63 mol), and hydroquinone (0.7 g, 0.006 mol) were put in a 2 L autoclave. After heating to 180° C., reaction was carried out for 5 hours while stirring at 300 rpm. After the reaction was completed, the reaction mixture was cooled down and transferred to a distillation unit. The reaction mixture was distilled twice at 1 torr using a vacuum pump at 56° C. to obtain the product (yield: 30%). The mole ratio of exo-isomers to endo-isomers of the product was 17:83.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][C:5](Cl)=[C:6]([CH:18]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17])=[O:8].Cl.N1[C:25]2=[N:26][CH:27]=[CH:28][C:29]([O:30][C:31]3[CH:36]=[CH:35][C:34]([NH:37]C4C(C(NC5C=CC(F)=CC=5F)=O)=CN=CC=4)=[CH:33][C:32]=3[F:55])=[C:24]2C=C1.O.C1(C)C(S(O)(=O)=O)=CC=CC=1.C[N:69]1[C:73](=[O:74])CCC1>>[Br:1][C:2]1[CH:18]=[C:6]([C:7](=[O:8])[NH:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[F:17])[C:5]([NH:37][C:34]2[CH:35]=[CH:36][C:31]([O:30][C:29]3[CH:28]=[CH:27][N:26]=[C:25]([C:73]([NH2:69])=[O:74])[CH:24]=3)=[C:32]([F:55])[CH:33]=2)=[N:4][CH:3]=1
Reactant: O=C(Nc1ccc(F)cc1F)c1cc(Br)cnc1Cl
Reactant: O=C(Nc1ccc(F)cc1F)c1cnccc1Nc1ccc(Oc2ccnc3[nH]ccc23)c(F)c1
Reactant: CN1CCCC1=O
Agent: Cc1ccccc1S(=O)(=O)O
Agent: Cl
Solvent: O
Product: NC(=O)c1cc(Oc2ccc(Nc3ncc(Br)cc3C(=O)Nc3ccc(F)cc3F)cc2F)ccn1
Temperature: 160 °C
Reaction time: 15 h
Yield: 11 %

Procedure:
To a solution of 5-bromo-2-chloro-N-(2,4-difluorophenyl)nicotinamide (126 mg, 0.51 mmol) and 4-(4-amino-2-fluorophenoxy)picolinamide (172 mg, 0.49 mmol, Compound C of Example 3) in 3 mL of NMP was added toluenesulfonic acid monohydrate (71 mg, 0.37 mmol). The mixture was stirred at 120° C. for 2 h and at 160° C. for 15 h. The solution was cooled to rt and purified on preparative (RP) HPLC. The fractions containing the desired product pooled and concentrated in vacuo. The residue was then partitioned between 1N NaOH and EtOAc and the two layers were separated. The organic layer washed with brine and dried over MgSO4. After filtration and concentration, the desired product was obtained (30 mg, 11% yield). MS (ESI+) m/z 558.22, 560.22 (M+H)+.
Reaction SMILES: [CH3:1][C:2]([O:5][C:6]([NH:8][C@@H:9]([C:20]([OH:22])=O)[CH2:10][CH2:11][CH2:12][N:13]=[C:14]([NH:16][N+:17]([O-:19])=[O:18])[NH2:15])=[O:7])([CH3:4])[CH3:3].[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][NH2:31])=[CH:26][CH:25]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>>[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30][NH:31][C:20](=[O:22])[C@@H:9]([CH2:10][CH2:11][CH2:12][NH:13][C:14]([NH2:15])=[N:16][N+:17]([O-:19])=[O:18])[NH:8][C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])=[CH:26][CH:25]=1
Reactant: NCc1ccc(Cl)cc1
Reactant: CC(C)(C)OC(=O)N[C@H](CCCN=C(N)N[N+](=O)[O-])C(=O)O
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Product: CC(C)(C)OC(=O)N[C@H](CCCNC(N)=N[N+](=O)[O-])C(=O)NCc1ccc(Cl)cc1
Yield: 87 %

Procedure:
Prepared analogously to Example 5d) from Boc-D-Arg (NO2)-OH, (4-chlorophenyl) methylamine and TBTU in a yield of 87% of theory.
Reaction SMILES: [CH2:1]([O:4][CH:5](C)[CH2:6][CH2:7][CH2:8]O)[CH:2]=[CH2:3].[Cl:11][C:12]1[CH:17]=[C:16]([O:18][CH2:19][CH:20]=[C:21]([Cl:23])[Cl:22])[CH:15]=[C:14]([Cl:24])[C:13]=1[OH:25].[C:26]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[Cl:11][C:12]1[CH:17]=[C:16]([O:18][CH2:19][CH:20]=[C:21]([Cl:23])[Cl:22])[CH:15]=[C:14]([Cl:24])[C:13]=1[O:25][CH2:26][CH2:8][CH2:7][CH2:6][CH2:5][O:4][CH2:1][CH:2]=[CH2:3]
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: C=CCOC(C)CCCO
Reactant: Oc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Solvent: C1CCOC1
Product: C=CCOCCCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Yield: 87.7 %

Procedure:
To a mixture of 0.22 g of 4-(2-propenyloxy)pentanol, 0.43 g of 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenol, 0.39 g of triphenylphosphine and 15 ml of tetrahydrofuran was slowly added dropwise 0.30 g of diisopropyl azodicarboxylate with stirring under ice cooling. After stirring at room temperature for 24 hours, the reaction mixture was concentrated. The residue was subjected to silica gel chromatography, which afforded 0.54 g of 3,5-dichloro-1-(3,3-dichloro-2-propenyloxy)-4-(5-(2-propenyloxy)pentyloxy)benzene (yield, 87%), nD23.5 1.5378.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]2[C:11](=[O:16])[NH:12][NH:13][C:14]=2[CH3:15])=[CH:5][CH:4]=1)[CH3:2].[CH2:17]([C:19]1[CH:24]=[CH:23][C:22]([CH2:25][C:26]2[C:27]([O:32][C@@H:33]3[O:50][C@H:49]([CH2:51][O:52][C:53](=[O:55])[CH3:54])[C@@H:44]([O:45][C:46](=[O:48])[CH3:47])[C@H:39]([O:40][C:41](=[O:43])[CH3:42])[C@H:34]3[O:35][C:36](=[O:38])[CH3:37])=[N:28][NH:29][C:30]=2[CH3:31])=[CH:21][CH:20]=1)[CH3:18]>>[CH2:17]([C:19]1[CH:24]=[CH:23][C:22]([CH2:25][C:26]2[C:27]([O:32][C@@H:33]3[O:50][C@H:49]([CH2:51][O:52][C:53](=[O:55])[CH3:54])[C@@H:44]([O:45][C:46](=[O:48])[CH3:47])[C@H:39]([O:40][C:41](=[O:43])[CH3:42])[C@H:34]3[O:35][C:36](=[O:38])[CH3:37])=[N:28][NH:29][C:30]=2[CH3:31])=[CH:21][CH:20]=1)[CH3:18].[CH2:1]([C:3]1[CH:4]=[CH:5][C:6]([CH2:9][C:10]2[C:11]([O:16][C@@H:33]3[O:50][C@H:49]([CH2:51][OH:52])[C@@H:44]([OH:45])[C@H:39]([OH:40])[C@H:34]3[OH:35])=[N:12][NH:13][C:14]=2[CH3:15])=[CH:7][CH:8]=1)[CH3:2]
Reactant: CCc1ccc(Cc2c(C)[nH][nH]c2=O)cc1
Agent: CCc1ccc(Cc2c(O[C@@H]3O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]3OC(C)=O)n[nH]c2C)cc1
Product: CCc1ccc(Cc2c(O[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)n[nH]c2C)cc1

Procedure:
4-[(4-Ethylphenyl)methyl]-5-methyl-3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-1H-pyrazole was prepared in a similar manner to that described in Example 15 using 4-[(4-ethylphenyl)methyl]-1,2-dihydro-5-methyl-3H-pyrazol-3-one instead of 1,2-dihydro-4-[(4-isopropoxyphenyl)methyl]-5-methyl-3H-pyrazol-3-one. Then, the title compound was prepared in a similar manner to that described in Example 35 using 4-[(4-ethylphenyl)methyl]-5-methyl-3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-1H-pyrazole instead of 4-[(4-isopropoxyphenyl)methyl]-5-methyl-3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-1H-pyrazole.
Reaction SMILES: [C:1]([O:4][CH2:5][CH:6]=[C:7]([CH3:10])[CH2:8]Br)(=[O:3])[CH3:2].[Na].[C:12]([O:20]CC)(=[O:19])[CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15].[CH:23]1C=CC=CC=1>O>[C:1]([O:4][CH2:5][CH2:6][CH:7]=[CH:10][C:13]([CH3:23])([C:12]([O-:20])=[O:19])[C:14]([O:16][CH2:17][CH3:18])=[O:15])(=[O:3])[CH3:2].[OH:4][CH2:5][CH2:6][CH:7]=[CH:8][C:13]([CH3:23])([C:12]([O-:20])=[O:19])[C:14]([O:16][CH2:17][CH3:18])=[O:15]
Reactant: c1ccccc1
Reactant: CC(=O)OCC=C(C)CBr
Reactant: CCOC(=O)CC(=O)OCC
Agent: [Na]
Solvent: O
Product: CCOC(=O)C(C)(C=CCCO)C(=O)[O-]
Product: CCOC(=O)C(C)(C=CCCOC(C)=O)C(=O)[O-]
Temperature: 10 °C
Reaction time: 1 h

Procedure:
10.5 Parts of 4-acetoxy-1-bromo-2-methyl-2-butene is added dropwise to a mixture of 1.0 part of sodium metal, 10.2 parts of diethyl malonate and 5.3 volume parts of benzene. After the dropwise addition has been completed, the mixture is stirred at 10°C for 1 hour and, following the addition of water, extracted with diethyl ether. The extract is washed with water, dried and evaporated to dryness under reduced pressure. The resultant residue is purified by column chromatography to obtain 6.17 parts of ethyl 4-acetoxy-2-methyl-2-butenylmalonate and 2.55 parts of ethyl 4-hydroxy-2-methyl-2-butenylmalonate. 1.74 part of ethyl 4-acetoxy-2-methyl-2-butenylmalonate and 1.09 part of 2,3,5-trimethylhydroquinone are dissolved in 30 volume parts of dioxane and warmed to 50°C-60°C. Then, under stirring in a current of nitrogen gas, a mixture of 5 volume parts of 47 % boron trifluoride-ethyl ether and 15 volume parts of dioxane is added dropwise. The reaction mixture is stirred for 4 hours and, following the addition of water, extracted with ether. The extract is washed with water, dried and evaporated to dryness under reduced pressure. The residue is dissolved in 30 volume parts of methanol and mixed under vigorous stirring with a 100 volume parts of 30 % solution of ferric chloride. The mixture is extracted with 500 volume parts of diethyl ether and the extract is washed with water, dried and distilled free of the solvent under reduced pressure. The residue is purified by chromatography on silicic acid and the fractions eluted with ether-hexane (1:19) are pooled and evaporated to dryness under reduced pressure. The described procedure gives 1.31 part of 2,3,5-trimethyl-6-(5',5'-diethoxycarbonyl-3'-methyl-2'-pentenyl)-1,4-benzoquinone (the quinone corresponding to Formula (V) wherein R=H3C; OY, OY'=OH, Z=C2H5), as a yellowish oil.
Reaction SMILES: [C:1]1([CH3:9])[C:2]([NH2:8])=[CH:3][CH:4]=[CH:5][C:6]=1[NH2:7].[CH2:10]=[CH:11][C:12](=[CH2:14])[CH3:13].CCCCC>>[CH3:13][C:12]([CH3:14])=[CH:11][CH2:10][C:3]1[CH:4]=[CH:5][C:6]([NH2:7])=[C:1]([CH3:9])[C:2]=1[NH2:8]
Reactant: C=CC(=C)C
Reactant: Cc1c(N)cccc1N
Solvent: CCCCC
Product: CC(C)=CCc1ccc(N)c(C)c1N

Procedure:
A 200 g (1.64 mol) portion of 2,6-toluenediamine, 167 g (2.45 mol) of isoprene, 200 g (2.78 mol) of pentane, and 20 g of powdered H-Y zeolite were reacted at 150° C. in a similar fashion as indicated in Example 1. Isolation of a catalyst free sample was obtained by hot filtration. Selective removal of all residual hydrocarbon by vacuum distillation afforded the following product mixture:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][C:12]=1[C:13]#N)[C:5](OCC)=[O:6].[H-].C([Al+]CC(C)C)C(C)C.CC(C)=[O:27].Cl>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([CH2:5][OH:6])[CH:10]=[CH:11][C:12]=1[CH:13]=[O:27]
Reactant: CC(C)=O
Reactant: CCOC(=O)c1ccc(C#N)c(Br)c1
Agent: CC(C)C[Al+]CC(C)C
Agent: Cl
Agent: [H-]
Solvent: C1CCOC1
Product: O=Cc1ccc(CO)cc1Br
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 83 %

Procedure:
To a stirring cold (−78° C.) solution of ethyl 3-bromo-4-cyanobenzoate (0.41 mol, 104 g) in THF (2.3 L was added dropwise a solution of diisobutylaluminum hydride (2.0 mol, 1.36 L; 1.5 M in toluene) over a period of 1.5 h. After addition was completed, the mixture was warmed to rt over a period of 3 h. The mixture was then cooled to 0–5° C. and 40 ml of acetone was added slowly. The mixture was then transferred via a cannula to a cold (0° C.) stirring aqueous solution of HCl (2.2 L 3 N) over a period of 1.5 h, maintaining the temperature of the aqueous solution below 30° C. After the transfer was completed, the mixture was stirred for another 0.25 h. The organic solution was separated and the aqueous was extracted twice with EtOAc (3 L). The combined organic extracts were washed with brine, dried with MgSO4 (anhyd.) and concentrated to give 74 g (83%) of the title compound as a light yellow solid.
Reaction SMILES: [C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([SH:17])=[C:10]([C:13]([F:16])([F:15])[F:14])[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[C:18]([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([S:17][CH3:18])=[C:10]([C:13]([F:14])([F:16])[F:15])[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]
Reactant: CC(=O)N1CCc2cc(S)c(C(F)(F)F)cc21
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CSc1cc2c(cc1C(F)(F)F)N(C(C)=O)CC2
Temperature: 80 °C
Yield: 96.5 %

Procedure:
A mixture of the thiol (D5) (26 g, 99 mmol), anhydrous K2CO3 (15.12 g, 109 mmol) and indomethane (18.6 ml, 300 mmol) in dry DMF (100 ml) was heated at 80° C. for 1 h. The reaction mixture was cooled, evaporated in vacuo and partitioned between water (200 ml) and dichloromethane (3×200 ml). The combined organics were washed with water (400 ml), dried (Na2S04) and evaporated to yield the title compound (26.3 g, 97%) as a yellow oil.