Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH:4]([C:8](O)=[O:9])[CH2:3]1>O1CCCC1.CCOCC>[OH:9][CH2:8][CH:4]1[CH2:5][CH2:6][CH2:7][CH:2]([CH3:1])[CH2:3]1
Reactant: CC1CCCC(C(=O)O)C1
Solvent: C1CCOC1
Solvent: CCOCC
Product: CC1CCCC(CO)C1
Reaction time: 1 h
Yield: 74.7 %

Procedure:
To a boran-methyl sulfide complex (1.7 ml, 0.028 mole) in 7 ml tetrahydrofuran, at 0° C., was added dropwise 2 g of 3-methylcyclohexanecarboxylic acid (0.014 mole) in 7 ml tetrahydrofuran. Stirring was continued for one hour. The reaction mixture was diluted with ether and washed with 1N aqueous sodium hydroxide and then with brine. Concentration and distillation gave 1.34 g of the title compound The NMR spectrum showed absorption at 0.54-0.74 (m, 1H), 0.90, 0.93 (s, 3H), 1.17-1.53 (m, 3H), 1.65-1.77 (m, 3H) and 3.39-3.52 (m, 2H).
Reaction SMILES: [O:1]1[C@H:3]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9])[CH2:2]1.[ClH:10]>C(OCC)C>[Cl:10][CH2:2][C@H:3]([OH:1])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: Cl
Reactant: CCCCCC[C@@H]1CO1
Solvent: CCOCC
Product: CCCCCC[C@@H](O)CCl
Temperature: 0 °C
Reaction time: 2.5 h

Procedure:
Under nitrogen atmosphere, 10 g (65.5 mM) of (R)-1,2-epoxyoctane and 100 ml of dry diethyl ether (Et2O) were placed in a 200 ml two-necked round-bottomed flask and cooled on an ice bath. Into the mixture, hydrogen chloride gas was blown, followed by stirring for 2.5 hours. Then, the ice bath was removed and the mixture was further stirred for 2 hours at room temperature. After the reaction, the reaction mixture was poured into 250 ml of ice water and subjected to extraction with diethyl ether. The organic layer was washed with distilled water and dried with anhydrous magnesium sulfate, followed by distilling-off of the solvent to obtain 10.4 g of (R)-1-chloro-2-octanol.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C@@H:9]2[CH2:13][CH2:12][C@H:11](/[CH:14]=[CH:15]/[C:16]([O:18][CH3:19])=[O:17])[N:10]2[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH:5]=[CH:6][C:7]=1[F:8].[H][H]>C(OCC)(=O)C.[C].[Pd]>[F:1][C:2]1[CH:3]=[C:4]([C@@H:9]2[CH2:13][CH2:12][C@H:11]([CH2:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])[N:10]2[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: COC(=O)/C=C/[C@H]1CC[C@@H](c2ccc(F)c(F)c2)N1C(=O)OC(C)(C)C
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Product: COC(=O)CC[C@H]1CC[C@@H](c2ccc(F)c(F)c2)N1C(=O)OC(C)(C)C
Yield: 90.6 %

Procedure:
Palladium-carbon (containing 50% water, 900 mg) was added to a solution of tert-butyl (E)-(2S,5R)-2-(3,4-difluorophenyl)-5-(2-methoxycarbonylvinyl)pyrrolidine-1-carboxylate (4.5 g) in ethyl acetate (100 mL), and the reaction solution was stirred in a hydrogen atmosphere at room temperature for 2.5 hours. Palladium-carbon in the reaction solution was removed by filtration through celite, and the filtrate was concentrated under reduced pressure to obtain 4.1 g of the title compound. The property values of the compound are as follows.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[N:9][N:8]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)[C:5]2=[CH:6][N:7]=1.C([Sn]([C:36]1[C:37](=[O:41])[O:38][CH2:39][CH:40]=1)(CCCC)CCCC)CCC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1(C)C=CC=CC=1>[C:11]1([C:10]2[C:4]3[C:5](=[CH:6][N:7]=[C:2]([C:40]4[CH2:39][O:38][C:37](=[O:41])[CH:36]=4)[CH:3]=3)[N:8]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)[N:9]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: Brc1cc2c(-c3ccccc3)nn(C3CCCCO3)c2cn1
Reactant: CCCC[Sn](CCCC)(CCCC)C1=CCOC1=O
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: Cc1ccccc1
Product: O=C1C=C(c2cc3c(-c4ccccc4)nn(C4CCCCO4)c3cn2)CO1
Temperature: 110 °C
Reaction time: 72 h
Yield: 32.1 %

Procedure:
A high-pressure reaction vessel was charged with 5-bromo-3-phenyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine (400.0 mg, 1.12 mmol), bis(triphenylphosphine)palladium(II) chloride (79.0 mg, 0.11 mmol), and anhydrous toluene (8.0 mL). Tributylstannanyl-5H-furan-2-one (437.5 mg, 1.17 mmol) was added, and the reaction mixture was vacuum-purged and back filled with nitrogen (3×). The vessel was sealed, and the reaction mixture was stirred at 110° C. for 3 days. The reaction was cooled to RT and slowly poured into saturated aqueous sodium bicarbonate solution (30 mL). The resultant mixture was extracted with ethyl acetate (3×75 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified using flash column chromatography (Si-PPC gradient elution, solvent: 0-100% ethyl acetate in heptanes) to give 4-(3-phenyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)furan-2(5H)-one as white solid (130.0 mg, 32.2%). LC/MS: m/z 362.3 [M+1].
Reaction SMILES: [CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:6]=[C:7]([C:11]2[C:16]([O:17][CH3:18])=[CH:15][CH:14]=[CH:13][C:12]=2[CH2:19][NH:20][CH2:21][CH2:22][CH2:23][N:24]2[CH2:28][CH2:27][CH2:26][C:25]2=[O:29])[CH:8]=[CH:9][CH:10]=1.[CH:31](=O)[CH3:32]>>[CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:6]=[C:7]([C:11]2[C:16]([O:17][CH3:18])=[CH:15][CH:14]=[CH:13][C:12]=2[CH2:19][N:20]([CH2:31][CH3:32])[CH2:21][CH2:22][CH2:23][N:24]2[CH2:28][CH2:27][CH2:26][C:25]2=[O:29])[CH:8]=[CH:9][CH:10]=1
Reactant: COC(=O)Cc1cccc(-c2c(CNCCCN3CCCC3=O)cccc2OC)c1
Reactant: CC=O
Product: CCN(CCCN1CCCC1=O)Cc1cccc(OC)c1-c1cccc(CC(=O)OC)c1

Procedure:
Prepared according to the procedure described in Example 33, Step 4, using the following starting materials: (6′-methoxy-2′-{[3-(2-oxo-pyrrolidin-1-yl)-propylamino]-methyl}-biphenyl-3-yl)-acetic acid methyl ester and acetaldehyde.
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:28][C:29]1[CH:34]=[CH:33][C:32]([CH2:35][O:36][CH2:37][CH2:38]O)=[CH:31][CH:30]=1>C(Cl)Cl.[Al]>[Br:28][C:29]1[CH:34]=[CH:33][C:32]([CH2:35][O:36][CH2:37][CH2:38][Br:1])=[CH:31][CH:30]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: OCCOCc1ccc(Br)cc1
Agent: [Al]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: BrCCOCc1ccc(Br)cc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 49.2 %

Procedure:
A solution of N-bromosuccinimide (272 mg, 1.53 mmol) in DCM (2.5 mL) was added to resin-bound triphenylphosphine (510 mg, 1.53 mEquiv, Fluka) in DCM (2.5 mL), and the reaction was stirred at rt for 10 min. A solution of 2-{[(4-bromophenyl)methyl]oxy}ethanol (139 mg, 0.601 mmol) in DCM (1.5 mL) was added to the reaction, and the residual alcohol was transferred with additional DCM (1.5 mL). The reaction vial was capped, wrapped in aluminum foil, and stirred at rt for 20 h. The reaction was filtered through a SPE cartridge (5 g silica) eluting with the following 10 mL fractions: DCM (fraction 1), 30% EtOAc/hexanes (fraction 2), and 50% EtOAc/hexanes (fraction 3) to give the title compound (87 mg, 49%). The product was characterized by 1H NMR (400 MHz) in CDCl3.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[S:13][C:14]([C:18]([OH:20])=O)=[C:15]([CH3:17])[N:16]=2)=[CH:8][CH:7]=1.C(N(CC)CC)C.ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC.[NH:49]1[CH2:54][CH2:53][O:52][CH2:51][CH2:50]1>ClCCl>[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]2[S:13][C:14]([C:18]([N:49]3[CH2:54][CH2:53][O:52][CH2:51][CH2:50]3)=[O:20])=[C:15]([CH3:17])[N:16]=2)=[CH:10][CH:11]=1
Reactant: Cc1nc(-c2ccc(OCCCCl)cc2)sc1C(=O)O
Reactant: C1COCCN1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1nc(-c2ccc(OCCCCl)cc2)sc1C(=O)N1CCOCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 63 %

Procedure:
To a solution of 2-[4-(3-chloropropoxy)phenyl]-4-methyl-1,3-thiazole-5-carboxylic acid i106 (1.6 mmol, 1 eq, 0.5 g), triethylamine (3.2 mmol, 2 eq, 0.45 ml) in dichloromethane (20 ml) is added 1-hydroxybenzotriazole (0.32 mmol, 0.2 eq, 43 mg), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (1.76 mmol, 1.1 eq, 0.33 g) and morpholine (1.92 mmol, 1.2 eq, 0.17 g). The mixture is stirred at room temperature overnight. The organic layer is washed with water and with a saturated aqueous solution of ammonium chloride, then dried over magnesium sulfate and filtered. The solvent is removed under reduced pressure. The crude product is purified by flash chromatography over silicagel (eluent: dichloromethane/ethanol 99:1 to 95:5) to afford 380 mg of 4-({2-[4-(3-chloropropoxy)phenyl]-4-methyl-1,3-thiazol-5-yl}carbonyl)morpholine i107.
Reaction SMILES: [Cl:1][CH2:2][CH:3]1[C:11]2[C:10]3[CH:12]=[C:13]([S:19]([NH2:22])(=[O:21])=[O:20])[C:14]([N+:16]([O-:18])=[O:17])=[CH:15][C:9]=3[CH:8]=[CH:7][C:6]=2[N:5]([C:23](=[O:28])[C:24]([F:27])([F:26])[F:25])[CH2:4]1.[N+:29]([O-])([O-:31])=[O:30].[K+]>OS(O)(=O)=O>[Cl:1][CH2:2][CH:3]1[C:11]2[C:10]3[CH:12]=[C:13]([S:19]([NH2:22])(=[O:21])=[O:20])[C:14]([N+:16]([O-:18])=[O:17])=[CH:15][C:9]=3[C:8]([N+:29]([O-:31])=[O:30])=[CH:7][C:6]=2[N:5]([C:23](=[O:28])[C:24]([F:27])([F:26])[F:25])[CH2:4]1
Reactant: O=[N+]([O-])[O-]
Reactant: NS(=O)(=O)c1cc2c3c(ccc2cc1[N+](=O)[O-])N(C(=O)C(F)(F)F)CC3CCl
Agent: O=S(=O)(O)O
Agent: [K+]
Product: NS(=O)(=O)c1cc2c3c(cc([N+](=O)[O-])c2cc1[N+](=O)[O-])N(C(=O)C(F)(F)F)CC3CCl
Temperature: 0 °C
Yield: 21 %

Procedure:
Ice cold H2SO4 (98%, 5 mL) was added to 218 (30 mg, 0.069 mmol) at 0° C. with stirring. An ice-cold solution of KNO3 (9 mg, 0.089 mmol) in H2SO4 (98%, 1 mL) was then added dropwise. After 1 h the mixture was poured into ice water and extracted with EtOAc (×3). The combined EtOAc extracts were washed with H2O, brine and dried. Chromatography eluting with petroleum ether/EtOAc (1:1) gave 1-(chloromethyl)-5,7-dinitro-3-(trifluoroacetyl)-1,2-dihydro-3H-benzo[e]indole-8-sulfonamide (219) (7 mg, 21%) as an orange powder: mp 201-204° C.; 1H NMR (CDCl3) δ 9.49 (s, 1H), 9.29 (s, 1H), 8.71 (s, 1H), 5.67 (s, 2H), 4.73 (d, J=10.8 Hz, 1H), 4.62 (dd, J=11.3, 8.8 Hz, 1H), 4.52-4.45 (m, 1H), 3.97 (dd, J=11.8, 3.5 Hz, 1H), 3.85 (dd, J=11.8, 6.3 Hz, 1H). HRMS (FAB) calcd. for C15H1135ClF3N4O7S (MH+) m/z 482.9989, found 482.9988.
Reaction SMILES: [CH:1]1([NH:4][CH:5]2[CH2:10][CH2:9][N:8]([C:11]3[O:15][N:14]=[C:13]([CH:16]([CH3:18])[CH3:17])[N:12]=3)[CH2:7][CH2:6]2)[CH2:3][CH2:2]1.[O:19]1[C:23]([C:24]2[N:25]=[CH:26][C:27]([C:30](O)=[O:31])=[N:28][CH:29]=2)=[CH:22][N:21]=[CH:20]1.F[P-](F)(F)(F)(F)F.ClC(N(C)C)=[N+](C)C>O1CCCC1>[CH:1]1([N:4]([CH:5]2[CH2:10][CH2:9][N:8]([C:11]3[O:15][N:14]=[C:13]([CH:16]([CH3:18])[CH3:17])[N:12]=3)[CH2:7][CH2:6]2)[C:30]([C:27]2[CH:26]=[N:25][C:24]([C:23]3[O:19][CH:20]=[N:21][CH:22]=3)=[CH:29][N:28]=2)=[O:31])[CH2:2][CH2:3]1
Reactant: CC(C)c1noc(N2CCC(NC3CC3)CC2)n1
Reactant: O=C(O)c1cnc(-c2cnco2)cn1
Agent: CN(C)C(Cl)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: C1CCOC1
Product: CC(C)c1noc(N2CCC(N(C(=O)c3cnc(-c4cnco4)cn3)C3CC3)CC2)n1

Procedure:
The title compound is prepared from cyclopropyl-[1-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-4-yl]-amine and 5-oxazol-5-yl-pyrazine-2-carboxylic acid following a procedure analogous to that described in Example 1 using chloro-N,N,N′,N′-tetramethylformamidinium hexafluorophosphate as reagent and tetrahydrofuran as solvent. LC (method 8): tR=1.47 min; Mass spectrum (ESI+): m/z=424 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][N:7]([CH3:12])[C:8]2=[O:11])=[CH:4][C:3]=1[N+:13]([O-])=O.O.O.Cl[Sn]Cl.C(Cl)Cl.[OH-].[Na+]>C(O)C.O>[NH2:13][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:2]=1[Cl:1])[C:8](=[O:11])[N:7]([CH3:12])[CH2:6]2
Reactant: CN1Cc2cc([N+](=O)[O-])c(Cl)cc2C1=O
Agent: Cl[Sn]Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Solvent: CCO
Product: CN1Cc2cc(N)c(Cl)cc2C1=O
Temperature: 65 °C
Yield: 85.1 %

Procedure:
To 6-chloro-2-methyl-5-nitroisoindolin-1-one (340 mg, 1.5 mmol) in ethanol (9 mL) and water (0.9 mL) was added SnCl2.2H2O (1.35 g, 6 mmol) and the mixture was heated to 65° C. for 5 h. DCM (20 mL) and 2M NaOH(aq) (10 mL) were added and the mixture was passed through a hydrophobic frit. The solvent was removed in vacuo to give 5-amino-6-chloro-2-methylisoindolin-1-one (251 mg, 85%) as an off-white solid. LCMS (10 cm_ESCI_Bicarb_MeCN): [M+H]+=197 at 2.31 min. 1H NMR (400 MHz, d6-DMSO): δ 7.45 (s, 1H), 6.90 (s, 1H), 5.99 (br s, 2H), 4.32 (s, 2H), 3.01 (s, 3H).
Reaction SMILES: C(=O)(O)[O-:2].[Na+].Cl.NO.[Cl:9][C:10]1[C:11]([C:24]#[N:25])=[N:12][CH:13]=[C:14]([Cl:23])[C:15]=1[O:16][CH:17]([CH3:22])[C:18]([F:21])([F:20])[F:19]>C(O)C>[Cl:9][C:10]1[C:11]([C:24]([NH2:25])=[O:2])=[N:12][CH:13]=[C:14]([Cl:23])[C:15]=1[O:16][CH:17]([CH3:22])[C:18]([F:21])([F:19])[F:20]
Reactant: CC(Oc1c(Cl)cnc(C#N)c1Cl)C(F)(F)F
Reactant: O=C([O-])O
Agent: Cl
Agent: NO
Agent: [Na+]
Solvent: CCO
Product: CC(Oc1c(Cl)cnc(C(N)=O)c1Cl)C(F)(F)F
Yield: 91.2 %

Procedure:
To 5 ml of ethanol were added 0.4 g of sodium bicarbonate and 0.33 g of hydroxylamine hydrochloride, and the mixture was heated to reflux for 1 hour. After allowing to cool, 0.67 g of 3,5-dichloro-4-(2,2,2-trifluoro-1-methylethoxy)pyridine-2-carbonitrile at room temperature, and the mixture was stirred for 4 hours, and concentrated. To the residue was added water, the resultant solution was extracted with ethyl acetate three times, and the organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried with anhydrous magnesium sulfate, and concentrated. The residue was washed with hexane three times to obtain 0.65 g of 3,5-dichloro-4-(2,2,2-trifluoro-1-methylethoxy)pyridine-2-carboxamide=oxime.
Reaction SMILES: [NH2:1][CH2:2][CH:3]([OH:23])[CH2:4][N:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]([NH:14][C:15]2[C:20]([CH3:21])=[CH:19][CH:18]=[CH:17][C:16]=2[CH3:22])=[O:13])[CH2:7][CH2:6]1.C(N(CC)CC)C.Cl[C:32]1[S:33][C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1>C(O)C>[S:33]1[C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=[C:32]1[NH:1][CH2:2][CH:3]([OH:23])[CH2:4][N:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]([NH:14][C:15]2[C:20]([CH3:21])=[CH:19][CH:18]=[CH:17][C:16]=2[CH3:22])=[O:13])[CH2:7][CH2:6]1
Reactant: Cc1cccc(C)c1NC(=O)CN1CCN(CC(O)CN)CC1
Reactant: Clc1nc2ccccc2s1
Solvent: CCO
Solvent: CCN(CC)CC
Product: Cc1cccc(C)c1NC(=O)CN1CCN(CC(O)CNc2nc3ccccc3s2)CC1

Procedure:
To a solution of compound 37 (75 mg) in ethanol (2 mL) was added triethylamine (0.13 mL) and 2-chlorobenzthiazole (87 mg) followed by warming to reflux for 16 h. The reaction mixture was concentrated and purified by preparative TLC (5%MeOH/Dichloromethane) to give Compound 39 as a white solid. Mass Spectrum (MH+)=454.4.
Reaction SMILES: [CH2:1]=[CH:2][CH2:3][CH2:4][CH:5]=[CH2:6].[CH3:7][O:8][CH:9]([SiH3:12])[O:10][CH3:11]>[H+].[H+].Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl.C(O)CCC>[CH3:7][O:8][CH:9]([SiH2:12][CH2:1][CH2:2][CH2:3][CH2:4][CH:5]([SiH2:12][CH:9]([O:10][CH3:11])[O:8][CH3:7])[CH3:6])[O:10][CH3:11]
Reactant: C=CCCC=C
Reactant: COC([SiH3])OC
Agent: Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl
Agent: [H+]
Solvent: CCCCO
Product: COC(OC)[SiH2]CCCCC(C)[SiH2]C(OC)OC

Procedure:
Butanol solution of chloroplatinic acid was added to 41.1 g of 1,5-hexadiene, and to this mixture, 106.2 g of dimethoxymethylsilane was gradually added dropwise. Due to the exothermic nature of the reaction, the speed of the dropwise addition was adjusted so that temperature of the reaction mixture was up to 80° C. After the completion of the dropwise addition, the mixture was distilled at reduced pressure under clean conditions as in the case of Synthetic Example 1 to obtain 1,5-bis(dimethoxymethylsilyl)hexane.
Reaction SMILES: [NH:1]1[CH:8]=[CH:7][C:5](=[O:6])[NH:4][C:2]1=[O:3].C(O[CH:13]1[C@H:17]([O:18][C:19](=[O:21])[CH3:20])[C@H:16]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C@:15]([CH2:33][O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)([CH:30]([F:32])[F:31])[O:14]1)(=O)C.Cl[Sn](Cl)(Cl)Cl>CC#N>[C:19]([O:18][C@@H:17]1[C@H:16]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C@:15]([CH2:33][O:34][CH2:35][C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)([CH:30]([F:31])[F:32])[O:14][C@H:13]1[N:1]1[CH:8]=[CH:7][C:5](=[O:6])[NH:4][C:2]1=[O:3])(=[O:21])[CH3:20]
Reactant: O=c1cc[nH]c(=O)[nH]1
Reactant: CC(=O)OC1O[C@@](COCc2ccccc2)(C(F)F)[C@@H](OCc2ccccc2)[C@H]1OC(C)=O
Agent: Cl[Sn](Cl)(Cl)Cl
Solvent: CC#N
Product: CC(=O)O[C@H]1[C@H](n2ccc(=O)[nH]c2=O)O[C@@](COCc2ccccc2)(C(F)F)[C@H]1OCc1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 40.3 %

Procedure:
The mixture of uracil (482 mg, 4.32 mmol) and BSA (1.75 g, 8.64 mmol) in MeCN (20 ml) was stirred at room temperature for 3 hrs. Compound 5 (1.0 g, 2.16 mmol) and SnCl4 (2.4 g, 9.3 mmol) was added respective, then stirred at 65° C. for 12 hrs. The mixture was quenched with saturated NaHCO3 solution, extracted with EtOAc (200 mL×3), dried over Na2SO4 and purified by silica gel chromatography [ethyl acetate:petroleum ether (1:10)] to afford the product (450 mg, 40%) as a yellow solid. LC-MS (M+H)+=517.1
Reaction SMILES: [C:1]([C:4]1[C:16]([OH:17])=[CH:15][C:7]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]#[N:14])=[C:6]([CH2:18][CH3:19])[CH:5]=1)(=[O:3])[CH3:2]>[Pd].C(O)(=O)C>[NH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][O:8][C:7]1[C:6]([CH2:18][CH3:19])=[CH:5][C:4]([C:1](=[O:3])[CH3:2])=[C:16]([OH:17])[CH:15]=1
Reactant: CCc1cc(C(C)=O)c(O)cc1OCCCCC#N
Agent: [Pd]
Solvent: CC(=O)O
Product: CCc1cc(C(C)=O)c(O)cc1OCCCCCN
Reaction time: 2 h
Yield: 98.5 %

Procedure:
A mixture of 2.0 g of 5-(4-acetyl-2-ethyl-5-hydroxyphenoxy)pentanenitrile, 50 ml of acetic acid, and 2.0 g of 10% palladium on carbon were subjected to hydrogenation for approximately 2 hours. The mixture was then filtered and concentrated in vacuo. The residue was triturated with diethyl ether to provide 2 g of the desired title product, m.p. =75°-76° C. NMR.
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:13]([CH3:14])=[CH:12][N:11]([CH3:15])[N:10]=2)=[CH:5][C:4]=1[CH3:16].Br>C(O)(=O)C>[CH3:15][N:11]1[CH:12]=[C:13]([CH3:14])[C:9]([C:6]2[CH:7]=[CH:8][C:3]([OH:2])=[C:4]([CH3:16])[CH:5]=2)=[N:10]1
Reactant: COc1ccc(-c2nn(C)cc2C)cc1C
Agent: Br
Solvent: CC(=O)O
Product: Cc1cc(-c2nn(C)cc2C)ccc1O
Yield: 93.6 %

Procedure:
A mixture of 3-(4-methoxy-3-methyl-phenyl)-1,4-dimethyl-1H-pyrazole (described in Reference Preparation example 57) 2.4 g, 47% hydrobromic acid 18 ml and acetic acid 18 ml was stirred with heating under reflux for sixteen hours. The solvent was distilled off and to the resulting residues was added ethyl acetate 50 ml, and the resulting mixture was stirred at room temperature for one hour. The precipitates were filtered and were washed with hexane, and were concentrated under reduced pressure to give 4-(1,4-dimethyl-1H-pyrazol-3-yl)-2-methyl-phenol 2.1 g.
Reaction SMILES: [O:1]=[C:2]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=1)[C:3]([O:5]CC)=O.[NH2:19][CH2:20][CH:21]([OH:23])[CH3:22]>C(O)C>[OH:23][CH:21]([CH3:22])[CH2:20][NH:19][C:3](=[O:5])[C:2]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:16])([F:17])[F:18])[CH:10]=1)=[O:1]
Reactant: CC(O)CN
Reactant: CCOC(=O)C(=O)Nc1cccc(C(F)(F)F)c1
Solvent: CCO
Product: CC(O)CNC(=O)C(=O)Nc1cccc(C(F)(F)F)c1
Yield: 98.8 %

Procedure:
Ethyl oxo{[3-(trifluoromethyl)-phenyl]amino}acetate (8.04 g, 30.7 mmol) was dissolved in ethanol (50 ml, 99.5%). To the stirred solution was added 1-amino-2-propanol (racemic, 2.32 g, 31 mmol) in one portion, and the mixture was heated to reflux for 90 minutes. The mixture was allowed to cool and was evaporated to dryness, giving 8.80 g (99%) of N-(2-hydroxypropyl)-N′-[3-(trifluoromethyl)-phenyl]ethanediamide as a white solid.
Reaction SMILES: [C:1]1([OH:9])[CH:6]=[CH:5][C:4]([CH3:7])=[C:3]([CH3:8])[CH:2]=1.[N+:10]([O-])([OH:12])=[O:11].C(OCC)(=O)C>C(O)(=O)C>[CH3:8][C:3]1[C:2]([N+:10]([O-:12])=[O:11])=[C:1]([OH:9])[CH:6]=[CH:5][C:4]=1[CH3:7]
Reactant: Cc1ccc(O)cc1C
Reactant: O=[N+]([O-])O
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: Cc1ccc(O)c([N+](=O)[O-])c1C
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 12.2 g of 3,4-xylenol in 100 ml of acetic acid was added a solution of 7.48 ml of 61% nitric acid in 50 ml of acetic acid while keeping the reaction temperature at 20° C. Then the mixture was reacted with stirring at room temperature for two hours. To the reaction mixture was added 200 ml of ethyl acetate and the mixture was washed successively with water, an aqueous solution of sodium hydrogencarbonate, water and a brine, and then, ethyl acetate was distilled away under reduced pressure. The residue was purified by subjecting to silica-gel column-chromatography [eluent:chloroform] to give 0.69 g of 3,4-dimethyl-2-nitrophenol.
Reaction SMILES: FC(F)(F)C(O)=O.[C:8]1([C:14]2(O)[CH2:19][CH2:18][C:17](=[O:20])[CH2:16][CH2:15]2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(=O)(O)[O-].[Na+]>>[C:8]1([C:14]2[CH2:19][CH2:18][C:17](=[O:20])[CH2:16][CH:15]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: O=C1CCC(O)(c2ccccc2)CC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Product: O=C1CC=C(c2ccccc2)CC1

Procedure:
To 34 ml. of well stirred trifluoroacetic acid, 50 g. of 4-phenyl-4-hydroxycyclohexanone (obtained as in Example 75) is added. After about 5 minutes the mixture is poured into an excess of aqueous sodium bicarbonate solution. The precipitated material is extracted with ether and the extract washed with water and brine and evaporated to dryness to give 4-phenyl-3-cyclohexen-1-one.
Reaction SMILES: COC([NH:5][CH2:6][CH:7]1[O:11][N:10]=[C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:8]1)=O.[OH-].[K+]>Cl>[NH2:5][CH2:6][CH:7]1[O:11][N:10]=[C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:8]1
Reactant: COC(=O)NCC1CC(c2ccccc2)=NO1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Product: NCC1CC(c2ccccc2)=NO1

Procedure:
A 5 g. portion of the product of Example 32 was slurried in 50 percent aqueous hydrochloric acid and refluxed overnight. The mixture was then cooled and neutralized with potassium hydroxide, and extracted with chloroform. The chloroform layer was concentrated to 10 ml., and eluted through a 12-meter column of polystyrene gel beads with chloroform as the eluting solvent. The desired product was the second fraction off the column. The yield was 2 g. of 5-aminomethyl-3-phenyl-2-isoxazoline, an oily liquid, NMR multiplets at 2.57-3.83, 4.43-4.97, 7.08-7.60 and 7.42-7.80 ppm., and a singlet at 1.38 ppm.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:27])[C:7]=1[CH2:8][CH:9]([C:11]1[C:16]2[CH:17]=[C:18]([C:20]([O:22]CC)=[O:21])[O:19][C:15]=2[C:14]([O:25][CH3:26])=[CH:13][CH:12]=1)[OH:10].CC(C)=O.OS(O)(=O)=O.O=[Cr](=O)=O.C(O)(C)C>CC(C)=O>[Cl:27][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C:9]([C:11]1[C:16]2[CH:17]=[C:18]([C:20]([OH:22])=[O:21])[O:19][C:15]=2[C:14]([O:25][CH3:26])=[CH:13][CH:12]=1)=[O:10]
Reactant: CCOC(=O)c1cc2c(C(O)Cc3c(Cl)cncc3Cl)ccc(OC)c2o1
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: CC(C)=O
Solvent: CC(C)O
Product: COc1ccc(C(=O)Cc2c(Cl)cncc2Cl)c2cc(C(=O)O)oc12
Reaction time: 0.33 h
Yield: 90 %

Procedure:
Ethyl 4-[2-(3,5-dichloro-4-pyridyl)-1-hydroxyethyl]-7-methoxybenzofuran-2-carboxylate (10 g) was dissolved in acetone (200 ml), a Jones reagent (a 2.76 mmol/L solution, 9.7 ml) was dropwise added thereto under cooling on ice, and the mixture was stirred for 20 minutes. Isopropanol was added thereto, and the mixture was stirred at room temperature for 30 minutes. The solvent was distilled off under reduced pressure and the residue was extracted with chloroform. The extract was washed with a saturated aqueous sodium chloride solution and dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was suspended in isopropanol and the precipitated crystals were collected by filtration to give the desired compound (8.34 g, 84%) as colorless crystals.