Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[C:3]1[CH:13]=[CH:12][CH:11]=[CH:10][C:4]=1[O:5][CH:6]1[CH2:9][NH:8][CH2:7]1.[CH3:16][N:17]=[C:18]=[O:19]>>[CH3:16][NH:17][C:18]([N:8]1[CH2:9][CH:6]([O:5][C:4]2[CH:10]=[CH:11][CH:12]=[CH:13][C:3]=2[C:2]([F:1])([F:14])[F:15])[CH2:7]1)=[O:19]
Reactant: FC(F)(F)c1ccccc1OC1CNC1
Reactant: CN=C=O
Product: CNC(=O)N1CC(Oc2ccccc2C(F)(F)F)C1

Procedure:
The compound was prepared from 3-[2-(trifluoromethyl)phenoxy]azetidine and methylisocyanate as described in Example 5 of U.S. Pat. No. 4,226,861, m.p. 134°-136° C.
Reaction SMILES: [C:1]([NH2:5])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:13][S:14](Cl)(=[O:16])=[O:15]>ClCCl>[C:1]([NH:5][S:14]([CH3:13])(=[O:16])=[O:15])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)N
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)NS(C)(=O)=O
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 59 %

Procedure:
To a 0° C. solution of 10 g (136.7 mmol) of t-butylamine and 15.2 g (150.4 mmol) of triethylamine in 350 mL of dichloromethane was added 15.7 g (136.7 mmol) of methanesulfonyl chloride in 20 mL of dichloromethane over 15 minutes. Continue stirring at 0° C. for 30 minutes then warm to room temperature over one hour. The mixture was washed once with 250 mL of 10% aqueous sodium bisulfate. The organic portion was separated and the aqueous portion was extracted two times with 100 mL each of dichloromethane. The combined organics were dried (Na2SO4), filtered and concentrated in vacuo. The residue was recrystallized from petroleum ether and dried in vacuo to afford 12.2g (59%) N-t-butyl methanesulfonamide.
Reaction SMILES: [C:1]1([NH:7][C:8](=[Se:11])[NH:9][NH2:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:12][Pt-2:13](Cl)(Cl)[Cl:14].[K+].[K+].[OH-].[K+]>>[Cl:12][Pt:13][Cl:14].[C:1]1([NH:7][C:8](=[Se:11])[NH:9][NH2:10])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Cl[Pt-2](Cl)(Cl)Cl
Agent: NNC(=[Se])Nc1ccccc1
Agent: [K+]
Agent: [OH-]
Product: Cl[Pt]Cl
Temperature: 25 °C
Reaction time: 10 h

Procedure:
1.1 g of 4-phenylselenosemicarbazide was added to 30 ml of an aqueous solution containing 1.7 g of potassium tetrachloroplatinate(II) and 560 mg of potassium hydroxide and stirred at room temperature for 10 hours. The resulting precipitate was separated by filtration and dried to obtain 1.2 g of 4-phenylselenosemicarbazide dichloroplatinum.
Reaction SMILES: [C:1]1([CH:8]=[CH:7][C:5]([OH:6])=[CH:4][CH:3]=1)[OH:2].[NH2:9][C:10]1[CH:11]=[C:12]([CH:28]=[CH:29][CH:30]=1)[O:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([NH2:27])[CH:22]=2)[CH:15]=1.I([O-])(=O)=O.[Na+].CO>CCCOCCO.O1CCCC1.O>[NH2:27][C:23]1[CH:22]=[C:21]([CH:26]=[CH:25][CH:24]=1)[O:20][C:16]1[CH:17]=[CH:18][CH:19]=[C:14]([O:13][C:12]2[CH:28]=[CH:29][CH:30]=[C:10]([NH2:9])[CH:11]=2)[CH:15]=1.[C:5]1(=[O:6])[CH:7]=[CH:8][C:1](=[O:2])[CH:3]=[CH:4]1
Reactant: Oc1ccc(O)cc1
Agent: Nc1cccc(Oc2cccc(Oc3cccc(N)c3)c2)c1
Agent: [Na+]
Agent: [O-][I+2]([O-])[O-]
Solvent: C1CCOC1
Solvent: CO
Solvent: CCCOCCO
Product: O=C1C=CC(=O)C=C1
Reaction time: 18 h

Procedure:
About 4.4 g (0.04 mol) hydroquinone and about 11.68 g (0.04 mol) of 1,3-bis(3-aminophenoxy)benzene were dissolved in a mixture of about 65 mL propyl cellosolve (chemical name ethylene glycol monopropyl ether) and about 15 mL of tetrahydrofuran (THF) in a round bottom flask. About 23.75 g (0.12 mol) of sodium iodate was added and the mixture was stirred for about 18 hours at about 60°-65° C. The reaction mixture was filtered through filter paper and then the 1,3-bis(3-aminophenoxy)benzene-p-benzoquinone polymer was precipitated with a about 1:4 mole mixture of methanol and water. The polymer was filtered through filter paper, washed with water and dried in a vacuum desiccator.
Reaction SMILES: [F:1][C:2]([F:11])([F:10])[C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1.Cl>ClCCl.C(OCC)(=O)C>[F:1][C:2]([F:10])([F:11])[C:3]1[CH:4]=[CH:5][C:6]([O:9][CH:13]2[CH2:14][CH2:15][CH2:16][CH2:17][O:12]2)=[CH:7][CH:8]=1
Reactant: C1=COCCC1
Reactant: Oc1ccc(C(F)(F)F)cc1
Agent: Cl
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: FC(F)(F)c1ccc(OC2CCCCO2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 83.7 %

Procedure:
a solution of 4-(trifluoromethyl)phenol (2.44 g, 15 mmol) in dichloromethane (5 ml) was added to a solution of 3,4-dihydro-2H-pyran (4.10 ml, 45 mmol) and a 3.6 M solution of hydrogen chloride in ethyl acetate (0.015 ml, 0.05 mmol) in dichloromethane (10 ml). The reaction mixture was stirred at room temperature for 16 h. It was diluted with ethyl acetate (100 m) and washed with a saturated aqueous solution of sodium hydrogencarbonate (100 ml). The aqueous phase was extracted with ethyl acetate (2×30 ml). The combined organic layers were dried over magnesium sulphate. The solvent was removed in vacuo. The crud product was purified by flash chromatography on silica (90 g), using ethyl acetate/heptane 1:10 as eluent to give 3.09 g of 2-(4-(trifluoromethyl)phenoxy)tetrahydropyran.
Reaction SMILES: [NH2:1][C:2]1[CH:6]=[CH:5][NH:4][N:3]=1.[C:7]1(=O)[O:12][C:10](=[O:11])[C:9]2=[CH:13][CH:14]=[CH:15][CH:16]=[C:8]12.O>CN(C)C=O>[NH:4]1[CH:5]=[CH:6][C:2]([N:1]2[C:10](=[O:11])[C:9]3[C:8](=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:7]2=[O:12])=[N:3]1
Reactant: Nc1cc[nH]n1
Reactant: O=C1OC(=O)c2ccccc21
Solvent: O
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1c1cc[nH]n1
Temperature: 125 °C
Reaction time: 24 h
Yield: 72.9 %

Procedure:
To a stirred mixture of 3-aminopyrazole (5.00 g, 60.2 mmol) dissolved in N,N-dimethylformamide (75 mL) was added phthalic anhydride (8.91 g, 60.2 mmol). After addition was complete, the mixture was stirred at 125° C. for 24 h. Upon cooling to 25° C., water (100 mL) was added, which resulted in precipitation. The white suspension was cooled (−5° C.) and stirred for 30 min. Subsequent filtration, washing with water, and suction drying afforded 2-(1H-pyrazol-3-yl)-isoindole-1,3-dione (9.36 g, 73.0%) as a white solid: LR-ES-MS m/z calculated for C11H7N3O2 [M]+ 213, observed [M+H]+ 214.
Reaction SMILES: [CH2:1]([NH:8][C:9]([CH3:21])([CH2:12][CH2:13][O:14]C1CCCCO1)[CH2:10][OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>Cl>[CH2:1]([NH:8][C:9]([CH3:21])([CH2:12][CH2:13][OH:14])[CH2:10][OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(CO)(CCOC1CCCCO1)NCc1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: CC(CO)(CCO)NCc1ccccc1

Procedure:
The crude 2-benzylamino-2-methyl-4-((tetrahydro-2H-pyran-2-yl)oxy)butanol (12D, 80.1 g, 0.273 mol) was dissolved in 3N HCl (128 mL). After 5 min the mixture was washed with Et2O (200 mL). The aqueous solution was concentrated by rotary evaporation to give a thick oil which was cooled and basified with excess 50% NaOH. The oily amine which formed was extracted with Et2O (3×200 mL). The Et2O extracts were combined and concentrated to give 63.6 g of a thick oil. Distillation gave 49.8 g (94%) of 2-benzylamino-2-methyl-1,4-butanediol as a pale yellow oil (bp 168°-170°/0.35 mm) (C,H,N)
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([Sn](C)(C)C)=[CH:4][CH:3]=1.Br[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[N+:19]([O-:21])=[O:20]>>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[N+:19]([O-:21])=[O:20])=[CH:4][CH:3]=1
Reactant: O=[N+]([O-])c1ccccc1Br
Reactant: Cc1ccc([Sn](C)(C)C)cc1
Product: Cc1ccc(-c2ccccc2[N+](=O)[O-])cc1

Procedure:
Prepared from 4-methylphenyltrimethylstannane (Example 69, Step A) and 2-bromonitrobenzene by the procedure described in Example 69, Step B. 1H NMR (200 MHz,CDCl3): 2.39 (s,3H), 7.23 (m,3H), 7.45 (m,3H), 7.58 (t,7 Hz,1H), 7.80 (d,7 Hz,1H).
Reaction SMILES: C[Sn](C)(C)[C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][CH:4]=1.Br[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[N+:19]([O-:21])=[O:20].[OH-].[K+]>CN(C=O)C.[Cl-].[Na+].O.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>[N+:19]([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][CH:4]=1)([O-:21])=[O:20]
Reactant: Cc1ccc([Sn](C)(C)C)cc1
Reactant: O=[N+]([O-])c1ccccc1Br
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cl-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccc(-c2ccccc2[N+](=O)[O-])cc1
Temperature: 25 °C
Yield: 90 %

Procedure:
A solution of 5.0 g (19.6 mmol) 4-(trimethylstannyl)toluene, 4.08 g (20.2 mmol) 1-bromo-2-nitrobenzene, and 138 mg (0.2 mmol) bis(triphenylphosphine)palladium(II) chloride in 100 mL DMF was heated to 110° C. for 4 hours. The mixture was cooled to room temperature, was poured into a mixture of brine and 1N KOH, then was extracted 3 times with ether. The combined organic material was washed with 1N KOH, was washed with brine, was dried over magnesium sulfate, was stripped of solvent in vacuo, and was chromatographed on silica gel under medium pressure using 5% ethyl acetate in hexanes to give 3.76 g (90% yield) of the title compound as a light lemon-yellow colored oil. Rf 0.31 in 10% EtOAc/hexane, visualized by UV and ammonium molybdate/ceric sulfate stain.
Reaction SMILES: [NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1.[H-].[Na+].[C:12]1([S:18](Cl)(=[O:20])=[O:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.O>O1CCCC1>[C:12]1([S:18]([N:1]2[C:5]3=[N:6][CH:7]=[CH:8][CH:9]=[C:4]3[CH:3]=[CH:2]2)(=[O:20])=[O:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: c1cnc2[nH]ccc2c1
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: O=S(=O)(c1ccccc1)n1ccc2cccnc21
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a stirred solution of pyrrolo[2,3-b]-pyridine (1.0 g, 8.46 mmol) in tetrahydrofuran (15 mL) at room temperature (rt) was added NaH (280 mg of an 80% dispersion in oil, 9.31 mmol) in portions. After 20 min the solution was cooled to 0° C. and benzenesulfonyl chloride (1.13 mL, 8.88 mmol) was added over 10 min. After 30 min the reaction mixture was warmed to rt and stirred for 1 h. Water (30 mL) was added and the mixture was extracted with EtOAc (40 mL). The organic layer was washed with 5% aqueous NaHCO3 then dried (MgSO4). Concentration and crystallization from EtOAc-hexanes gave 1-(benzenesulfonyl)-1H-pyrrolo[2,3-b]pyridine as a solid.
Reaction SMILES: [C:1]1([S:7](Cl)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][N:18]=2)[CH:13]=[CH:12]1.C(N(CC)CC)C>C(Cl)Cl>[C:1]1([S:7]([N:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][N:18]=3)[CH:13]=[CH:12]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: c1cnc2[nH]ccc2c1
Reactant: O=S(=O)(Cl)c1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=S(=O)(c1ccccc1)n1ccc2cccnc21
Temperature: 25 °C
Reaction time: 48 h
Yield: 92.5 %

Procedure:
Benzenesulfonyl chloride (1b) (98.7 g) was added dropwise into a solution of 7-azaindole (1a) (60.0 g) and triethylamine (56.6 g) in DCM (500 mL) at 0° C. The mixture was warmed to rt and stirred for 2 days to produce a white crystalline product. The white crystals were filtered off and the solution was washed with a saturated aqueous NaHCO3 solution and brine, then dried over MgSO4 and concentrated. The residue was recrystallized in ethyl acetate (200 mL) to provide N-phenylsulfonyl-7-azaindole (1c) (121.31 g, 94%) as white crystals. 1H NMR (400 MHz, CDCl3) δ 8.43 (d, J=4.8 Hz, 1H), 8.18 (d, J=8.0 Hz, 2H), 7.85 (d, J=8.0 Hz, 1H), 7.73 (d, J=4.8 Hz, 1H), 7.57 (t, J=7.6 Hz, 1H), 7.48 (t, J=7.6 HZ, 2H), 7.15 (dd, J=8.0 Hz, 4.8 Hz, 1H), 6.58 (d, J=4.8 Hz, 1H).
Reaction SMILES: [CH2-:1][C:2]([CH3:4])=[O:3].[CH2-]C(C)=O.[C:9]([OH:18])(=[O:17])[CH:10]([CH:12]([C:14]([OH:16])=[O:15])O)O.CC(C)([O-])C.[K+].Cl.C(Cl)(=O)C>O1CCCC1.CO>[CH3:1][C:2]1([CH3:4])[O:16][C:14](=[O:15])/[C:12](=[CH:10]/[C:9]([OH:18])=[O:17])/[O:3]1
Reactant: O=C(O)C(O)C(O)C(=O)O
Reactant: [CH2-]C(C)=O
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CO
Solvent: CC(=O)Cl
Solvent: C1CCOC1
Product: CC1(C)OC(=O)/C(=C/C(=O)O)O1
Temperature: -40 °C
Reaction time: 0.25 h
Yield: 77 %

Procedure:
A stirred solution of tartaric acid bis(acetonide) prepared as in Example 1 (1.0 kg) in tetrahydrofuran (5.0 L) was cooled to −40° C. A chilled 0.75 M solution of potassium tert-butoxide in tetrahydrofuran (7.0 L) was added and stirring was continued for 15 min at −40° C. In a separate reactor, a 1.2 M solution of HCl was generated by reaction of acetyl chloride (0.50 L) with methanol (0.31 L) in tetrahydrofuran (5.0 L) 0-5° C. The original reaction is quenched by addition of the chilled HCl solution. The mixture was allowed to warm to room temperature with stirring over the course of 1 h, after which the THF content was reduced to <2% by vacuum distillation. Ethyl acetate (20 L) was added and the mixture was concentrated to 10 L. Deionized water (8.0 L) was added and the pH was adjusted to <2.5 with 1 N HCl. The organic phase was separated and the aqueous phase was further extracted with ethyl acetate (5.0 L). The combined organics were concentrated to a volume of 3 L by vacuum distillation whereupon heptane (6.0 L) was added. The product mixture was vigorously agitated at 15° C. for 1 h after which the crystalline product was collected by filtration and washed with heptane (2×2.0 L). Vacuum drying at 50° C. afforded Z-2,2-dimethyl-5-carboxymethylene-1,3-dioxolan-4-one (577 g, 77%) as fine white needles. NMR and HPLC analysis indicated the product purity was 100%.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])=[CH:4][C:3]=1[Br:13].[CH3:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[N:21]=[C:22]=[O:23]>C1COCC1>[Br:13][C:3]1[CH:4]=[C:5]([CH2:8][C:9]([O:11][CH3:12])=[O:10])[CH:6]=[CH:7][C:2]=1[NH:1][C:22]([NH:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[CH3:14])=[O:23]
Reactant: Cc1ccccc1N=C=O
Reactant: COC(=O)Cc1ccc(N)c(Br)c1
Solvent: C1CCOC1
Product: COC(=O)Cc1ccc(NC(=O)Nc2ccccc2C)c(Br)c1
Reaction time: 21 h
Yield: 71.8 %

Procedure:
To a mixture of methyl 4-amino-3-bromophenylacetate (587 mg, 2.40 mmol) and 2-methylphenyl isocyanate (0.287 ml, 2.40 mmol) in THF (2 ml) was added Et3 N (33 ml, 0.24 mmol) at room temperature. After 21 h stirring, the reaction mixture was concentrated in vacuo. The residue was triturated by the addition of n-hexane to give methyl 3-bromo-4-[N′-(2-methylphenyl)ureido]phenylacetate (650 mg, 72%) as a pale brown powder. 1H-NMR (CDCl3) δ2.34 (s, 3H), 3.53 (s, 2H), 3.68 (s, 3H), 6.18 (br, 1H), 6.96 (br, 1H), 7.18–7.33 (m, 4H), 7.29 (d, J=4.4 Hz, 1H), 7.30 (d, J=7.3 Hz, 1H), 8.19 (d, J=8.3 Hz, 1H); MS (ESI) m/z 377 (M+), 379 (M++2).
Reaction SMILES: [C:1]([O:5][C:6](=[O:27])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18](=[O:26])[CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].CO[CH:30](OC)[N:31]([CH3:33])[CH3:32]>>[C:1]([O:5][C:6](=[O:27])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18](=[O:26])[C:19]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:30][N:31]([CH3:33])[CH3:32])=[CH:16][CH:17]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(OC)N(C)C
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(C(=O)Cc3ccccc3)cc2)CCC1
Product: CN(C)C=C(C(=O)c1ccc(C2(NC(=O)OC(C)(C)C)CCC2)cc1)c1ccccc1
Temperature: 25 °C

Procedure:
A solution of tert-butyl(1-(4-(2-phenylacetyl)phenyl)cyclobutyl)carbamate (25.0 g, 68 mmol) in N,N-dimethylformamide dimethylacetal (150 mL) was heated to 80° C. under a nitrogen atmosphere for 18 hours. The resulting brown solution was allowed to cool to room temperature and concentrated to dryness under reduced pressure to give the desired product as a yellow/brown solid (30.6 g, quantitative yield). 1H-NMR (500 MHz, CDCl3) δ 7.14-7.48 (10H, m), 5.09 (1H, br s), 2.74 (6H, s), 2.45-2.60 (4H, m), 2.04-2.16 (1H, m), 1.80-1.90 (1H, m), 1.10-1.52 (9H, br m).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].S(Cl)([Cl:16])=O>CN(C)C=O>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([Cl:16])=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12]
Reactant: O=C(O)c1ccc(Cl)c([N+](=O)[O-])c1
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: O=C(Cl)c1ccc(Cl)c([N+](=O)[O-])c1

Procedure:
20.1 g (0.1 mol) of 4-chloro-3-nitro-benzoic acid, 11 ml thionyl chloride and 1 drop of dimethylformamide are mixed together and refluxed for two hours. The thionyl chloride is evaporated off.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].CC(C)([O-])C.[K+].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C=O)C>[CH2:18]([O:8][C:5]1[CH:6]=[CH:7][C:2]([NH2:1])=[C:3]([N+:9]([O-:11])=[O:10])[CH:4]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: BrCc1ccccc1
Reactant: Nc1ccc(O)cc1[N+](=O)[O-]
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Nc1ccc(OCc2ccccc2)cc1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 80.8 %

Procedure:
4-Amino-3-nitrophenol (25 g, 162.2 mmol) was dissolved in DMF and cooled to 0° C. 1M potassium tert-butoxide (162.2 mL) was added dropwise over 20 min. After stirring 30 min at 0° C., benzyl bromide (19.8 mL, 162.2 mmol) in DMF was added dropwise. After 30 min at 0° C., the reaction was quenched with NH4Cl solution. 4-benzyloxy-2-nitroaniline (32 g, 131 mmol) was isolated by filtration. MS(CI, NH3) m/e 245 (M+1)+.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[N:11]1[CH2:14][CH:13]([NH:15]C(=O)OC(C)(C)C)[CH2:12]1.[ClH:23]>>[ClH:23].[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[N:11]1[CH2:12][CH:13]([NH2:15])[CH2:14]1
Reactant: CC(C)(C)OC(=O)NC1CN(c2ccc3ccccc3n2)C1
Agent: Cl
Product: NC1CN(c2ccc3ccccc3n2)C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 100 %

Procedure:
To tert-butyl (1-(quinolin-2-yl)azetidin-3-yl)-carbamate (1.14 g, 3.84 mmol) was added hydrogen chloride (4 M solution in methanol, 20 mL). The reaction mixture was stirred at room temperature for 1 hour. It was concentrated to give 1-(quinolin-2-yl)azetidin-3-amine hydrochloride (0.90 g, 3.84 mmol, 100% yield) which was used in the next step without further purification.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[OH:10])[CH:5]=[O:6].[Na+].Cl[C:13]([F:18])([F:17])C([O-])=O.[OH-].[Na+].Cl>CN(C=O)C>[F:17][CH:13]([F:18])[O:10][C:9]1[CH:8]=[CH:7][C:4]([CH:5]=[O:6])=[CH:3][C:2]=1[OH:1]
Reactant: O=Cc1ccc(O)c(O)c1
Reactant: O=C([O-])C(F)(F)Cl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Product: O=Cc1ccc(OC(F)F)c(O)c1
Yield: 24 %

Procedure:
3,4-Dihydroxybenzaldehyde (20 g, 145 mmol), chlorodifluoroacetic acid sodium salt (55.19 g, 362 mmol) and sodium hydroxide (5.50 g, 138 mmol) were stirred in DMF (1200 mL) at 55° C. under nitrogen for 16 hours. The pH was adjusted to 1.0 by the addition of 10% aqueous HCl followed by extraction with ethyl acetate (3×500 mL). The combined extracts were evaporated under vacuum. The residue was purified on silica gel using a 10-20% ethyl acetate/hexane gradient. 4-difluoromethoxy-3-hydroxybenzaldehyde was isolated in 24% yield (6.62 g). 1H NMR (CDCl3, 400 MHz) δ 6.1 (br s, 1H), 6.48-6.85 (t, 1H OCHF2), 7.26 (d, 1H), 7.44 (d, 1H), 7.55 (s, 1H), 9.91 (s, 1H).
Reaction SMILES: [O:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[CH2:15](Br)[CH:16]=[CH2:17].[Cl-].[NH4+]>C1COCC1.[Zn]>[CH2:17]([C:2]1([OH:1])[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]1)[CH:16]=[CH2:15]
Reactant: C=CCBr
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: C1CCOC1
Product: C=CCC1(O)CCN(C(=O)OC(C)(C)C)CC1
Reaction time: 8 h

Procedure:
To a solution of tert-butyl 4-oxopiperidine-1-carboxylate (10 g, 50.2 mmol), allyl bromide (10.8 mL, 124 mmol) in THF (10 mL), and saturated ammonium chloride solution (50 mL) was added Zn dust (6.5 g, 100 mmol) portionwise below 10° C. After addition was complete, the reaction mixture was stirred overnight, when TLC indicated consumption of s.m. The reaction mixture was diluted with water (50 mL) and acidified with several drops of 10% H2SO4 to pH=6. The reaction mixture was extracted with EtOAc (3×200 mL), The organic layers were combined and washed with a saturated solution of NaHCO3, brine and evaporated, to give the crude product which was purified by chromatography to give title compound 11B as colorless oil.
Reaction SMILES: [CH:1]([OH:14])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ON1C(=O)C2=CC=CC=C2C1=O.OO>C(OCC)(=O)C>[C:1]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)(=[O:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OC(c1ccccc1)c1ccccc1
Agent: O=C1c2ccccc2C(=O)N1O
Agent: OO
Solvent: CCOC(C)=O
Product: O=C(c1ccccc1)c1ccccc1
Temperature: 75 °C
Reaction time: 12 h
Yield: 75 %

Procedure:
A mixture of 5 mmol of benzhydrol, 0.5 mmol of N-hydroxyphthalimide, and 5 ml of ethyl acetate was stirred at 75° C. in an air atmosphere (10 atm) for 12 hours. An iodometric analysis of a reaction mixture revealed that hydrogen peroxide was formed in yield of 57% (selectivity: 76%). Separately, as a result of a gas chromatographic analysis of the reaction mixture, the conversion rate from benzhydrol was 75%, and benzophenone was formed in yield of 75%.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:27]=[CH:26][CH:25]=[C:24]4[C:19]=3[CH2:20][CH2:21][N:22](C(OC(C)(C)C)=O)[CH2:23]4)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2].Cl>O1CCOCC1.CO>[CH3:12][CH:10]([O:9][C:8]1[CH:7]=[CH:6][C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:27]=[CH:26][CH:25]=[C:24]4[C:19]=3[CH2:20][CH2:21][NH:22][CH2:23]4)[N:14]=2)=[CH:4][C:3]=1[C:1]#[N:2])[CH3:11]
Reactant: CC(C)Oc1ccc(-c2nc(-c3cccc4c3CCN(C(=O)OC(C)(C)C)C4)no2)cc1C#N
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: CC(C)Oc1ccc(-c2nc(-c3cccc4c3CCNC4)no2)cc1C#N
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A mixture of 1,1-dimethylethyl 5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-3,4-dihydro-2(1H)-isoquinolinecarboxylate (Preparation 4, 512 mg, 1.11 mmol) and 4M HCl in dioxane (20 ml) was stirred at room temperature for 18 h. The mixture was concentrated in vacuo to give a pale yellow solid, which was redissolved in MeOH. This solution was applied to an SCX-3 cartridge (10 g), and the product eluted with 1% NH3 in MeOH. Concentration gave a yellow oil, that became a solid on standing overnight (366 mg, 91%). 1H NMR (400 MHz, d6-DMSO) δ 8.38 (1H, d), 8.32 (1H, dd), 7.94 (1H, d), 7.32-7.17 (2H, m), 7.13 (1H, m), 4.80 (1H, sept), 4.10 (2H, s), 3.20-3.14 (4H, m), 1.48 (6H, d); m/z (ES) 361 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[Br-].[C:10]1([Zn+])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[Cl-].[NH4+]>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:5]=[CH:4][N:3]=1
Reactant: Clc1ccnc(Cl)n1
Reactant: [Zn+]c1ccccc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Br-]
Agent: [Cl-]
Solvent: C1CCOC1
Product: Clc1nccc(-c2ccccc2)n1
Temperature: 50 °C
Reaction time: 8 h

Procedure:
To a solution of 2,4-dichloropyrimidine (149 mg, 1 mmol) in THF (5 mL), tetrakis(triphenylphosphine)palladium (23 mg, 2 mol %) and 0.5M solution of phenylzinc bromide (2.1 mL, 1.05 mmol) in THF were added. The reaction mixture was stirred at 50° C. for overnight. Then it was added saturated ammonium chloride solution and extracted with EtOAc twice. The organic layers were combined, washed with water and dried (MgSO4). Evaporation of solvent gave a yellow residue which was purified by Prep. HPLC to afford a yellowish oil as 2-chloro-4-phenyl-pyrimidine to carry on.