Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [ClH:1].[OH:2][NH:3][C:4]([C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[CH2:8][CH2:9][C:10]2=[N:15]O)=[NH:5].N[N:18]1[CH:22]=[C:21]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:20]=[C:19]1[NH2:29]>C(O)(C)C>[ClH:1].[ClH:1].[OH:2][NH:3][C:4]([C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[CH2:8][CH2:9][C:10]2=[N:15][N:18]1[CH:22]=[C:21]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:20]=[C:19]1[NH2:29])=[NH:5]
Reactant: Nc1nc(-c2ccccc2)cn1N
Reactant: N=C(NO)c1cccc2c1CCC2=NO
Agent: Cl
Solvent: CC(C)O
Product: N=C(NO)c1cccc2c1CCC2=Nn1cc(-c2ccccc2)nc1N
Temperature: 80 °C
Reaction time: 5 h

Procedure:
6 ml of 32% hydrochloric acid (Merck, Darmstadt, Germany; p.a.) are added, with stirring, to a mixture of 4.1 g (0.02 mol) of 4-(N-hydroxyamidino)-2,3-dihydro-1H-inden-1-one oxime, 3.5 g (0.02 mol) of 1,2-diamino-4-phenyl-imidazole (see Beyer H. et al., Chem. Ber. 101, 3151 (1968)) and 150 ml of isopropanol, and the mixture is stirred at 80° C. for 5 hours. During that time, the starting materials dissolve and the title compound gradually crystallizes out. At the end of the reaction time, the mixture is cooled. The product that has crystallized out is filtered off with suction, washed with isopropanol and dried. The product crystallizes with one mole of isopropanol, m.p. 238°-240° C., 1H-NMR (DMSO/D2O): δ=8.24 (d, 1H); 7.88 (s, 1H); 7.73 (d, 1H); 7.55-7.68 (m, 3H); 7.34-7.5 (m, 3H); 3.26 (s, 4H).
Reaction SMILES: [NH:1]1[CH:8]=[CH:7][C:5](=[O:6])[NH:4][C:2]1=[O:3].C(O[C@@H:13]1[O:35][C@H:34]([CH2:36][O:37][C:38](=[O:45])[C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C@@H:24]([O:25][C:26](=[O:33])[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C@H:14]1[O:15][C:16](=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)(=O)C.C[Si](N[Si](C)(C)C)(C)C>C(#N)C>[C:16]([O:15][C@@H:14]1[C@H:24]([O:25][C:26](=[O:33])[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C@@H:34]([CH2:36][O:37][C:38](=[O:45])[C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)[O:35][C@H:13]1[N:1]1[CH:8]=[CH:7][C:5](=[O:6])[NH:4][C:2]1=[O:3])(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=c1cc[nH]c(=O)[nH]1
Reactant: CC(=O)O[C@@H]1O[C@H](COC(=O)c2ccccc2)[C@@H](OC(=O)c2ccccc2)[C@H]1OC(=O)c1ccccc1
Agent: C[Si](C)(C)N[Si](C)(C)C
Solvent: CC#N
Product: O=C(OC[C@H]1O[C@@H](n2ccc(=O)[nH]c2=O)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1)c1ccccc1
Reaction time: 20 h
Yield: 40 %

Procedure:
0.56 g. (5 mmol) of uracil, 2.52 g. (5 mmol) of 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose were refluxed in 70 ml. of absolute acetonitrile with 1.41 g. (12 mmol) of NH4ClO4, 0.57 g. (3.5 mmol) of HMDS, and 1.68 g. (15.5 mmol) of TCS for 20 hours. The mixture was worked up as set forth in Example 1, thus producing 40% of crystalline uridine tribenzoate.
Reaction SMILES: [Si]([O:8][CH2:9][CH:10]1[O:14][N:13]=[C:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][C:24]([N:27]4[CH2:31][C@H:30]([CH2:32][N:33]5[CH:37]=[C:36]([CH3:38])[N:35]=[N:34]5)[O:29][C:28]4=[O:39])=[CH:23][C:22]=3[F:40])=[CH:17][CH:16]=2)[CH2:11]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[F:40][C:22]1[CH:23]=[C:24]([N:27]2[CH2:31][C@H:30]([CH2:32][N:33]3[CH:37]=[C:36]([CH3:38])[N:35]=[N:34]3)[O:29][C:28]2=[O:39])[CH:25]=[CH:26][C:21]=1[C:18]1[CH:19]=[CH:20][C:15]([C:12]2[CH2:11][CH:10]([CH2:9][OH:8])[O:14][N:13]=2)=[CH:16][CH:17]=1
Reactant: Cc1cn(C[C@H]2CN(c3ccc(-c4ccc(C5=NOC(CO[Si](C)(C)C(C)(C)C)C5)cc4)c(F)c3)C(=O)O2)nn1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: Cc1cn(C[C@H]2CN(c3ccc(-c4ccc(C5=NOC(CO)C5)cc4)c(F)c3)C(=O)O2)nn1
Reaction time: 0.5 h
Yield: 66.5 %

Procedure:
(5R)-3-{4′-[5-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-4,5-dihydroisoxazol-3-yl]-2-fluoro-1,1′-biphenyl-4-yl}-5-[(4-methyl-1H-1,2,3-triazol-1-yl)methyl]-1,3-oxazolidin-2-one (283 mg, 0.5 mmol) was dissolved in tetrahydrofuran (5 ml) at room temperature. A 1M solution of tetrabutylammonium fluoride in tetrahydrofuran (0.5 ml, 0.5 mmol) was added and the reaction mixture stirred for 30 minutes. The solvent was removed in vacuo then dichloromethane (50 ml) added. This was washed with water (50 ml), separated, dried (magnesium sulfate), filtered then concentrated in vacuo onto silica (2 ml). This was then subjected to chromatography (silica gel 10 g bond elut; 0 to 6% methanol/dichloromethane) to yield 150 mg (66%) of the desired compound.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][N:5]1[C:9](=[O:10])[C:8]2=[CH:11][CH:12]=[CH:13][CH:14]=[C:7]2[C:6]1=[O:15].[OH:16][CH2:17][CH2:18][N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[OH:16][CH2:17][CH2:18][N:19]1[CH2:24][CH2:23][N:22]([CH2:2][CH2:3][CH2:4][N:5]2[C:9](=[O:10])[C:8]3=[CH:11][CH:12]=[CH:13][CH:14]=[C:7]3[C:6]2=[O:15])[CH2:21][CH2:20]1
Reactant: O=C1c2ccccc2C(=O)N1CCCBr
Reactant: OCCN1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: O=C1c2ccccc2C(=O)N1CCCN1CCN(CCO)CC1
Reaction time: 3 h
Yield: 53.2 %

Procedure:
To the solution of N-(3-bromopropyl)phthalimide (40.5 g) in acetone (375 ml) were added 1-(2-hydroxyethyl)piperazine (31.5 g) and potassium carbonate (63.0 g). The resulting mixture was refluxed with stirring for 3 hours. The reaction mixture was filtered and the filtrate was evaporated. The residual oil was subjected to column chromatography on silica gel, eluting with a mixture of chloroform and methanol (9:1). The fractions containing the object compound were collected and then evaporated to give an oil of N-[3-[4-(2-hydroxyethyl)-1-piperazinyl]propyl]phthalimide (25.5 g).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([Br:11])[CH:10]=1)[C:5]([OH:7])=O.CN(C(ON1N=NC2[CH:23]=[CH:24][CH:25]=[N:26]C1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1(N)CC1.CCN(C(C)C)C(C)C>CN(C=O)C>[Br:11][C:9]1[CH:8]=[C:4]([CH:3]=[C:2]([Br:1])[CH:10]=1)[C:5]([NH:26][CH:25]1[CH2:23][CH2:24]1)=[O:7]
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Reactant: O=C(O)c1cc(Br)cc(Br)c1
Agent: F[P-](F)(F)(F)(F)F
Agent: NC1CC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(NC1CC1)c1cc(Br)cc(Br)c1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a stirred solution of 3,5-dibromobenzoic acid (1 eq.) in DMF (0.15 M) was added HATU (1.3 eq.), cyclopropylamine (1.1 eq.) and Hunig's base (3 eq.). The resulting yellow mixture was stirred at RT for 18 h. The reaction was then quenched with saturated aqueous ammonium chloride and extracted with ethyl acetate. The combined organic extracts were washed further with water and brine, dried over Na2SO4, filtered and the filtrate concentrated in vacuo. Trituration of the crude product thus obtained in a mixture of ether and hexanes afforded the title compound as a white solid.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:10]=[C:9]([CH:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)[NH:8][N:7]=1)=[O:5])C.[OH-].[Na+].Cl>O1CCOCC1>[CH:11]1([C:9]2[NH:8][N:7]=[C:6]([C:4]([OH:5])=[O:3])[CH:10]=2)[CH2:12][CH2:13][CH2:14][CH2:15]1
Reactant: CCOC(=O)c1cc(C2CCCC2)[nH]n1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: O=C(O)c1cc(C2CCCC2)[nH]n1
Temperature: 50 °C
Reaction time: 3 h
Yield: 88 %

Procedure:
5-Cyclopentyl-1H-pyrazol-3-carboxylic acid ethyl ester (17.1 g, 82 mmol) and 1M NaOH solution (205 ml, 205 mmol) were dissolved in 1,4-dioxan (300 ml) and the reaction was heated to 50° C. under nitrogen and stirred for 3 hours. The reaction mixture was cooled, adjusted to pH 2 using concentrated hydrochloric acid and the solvent was removed under reduced pressure. The residual solid was azeotrped with toluene (2×30 ml), dissolved in ethyl acetate (500 ml) and washed with water (200 ml). The aqueous phase was removed, extracted with ethyl acetate (2×200 ml) and the combined organic extracts were dried over MgSO4. The solvent was removed under reduced pressure and the residue was azeotrped with dichloromethane (2×50 ml) to give 5-cyclopentyl-1H-pyrazol-3-carboxylic acid (13 g) as a white solid. 1H NMR (400 MHz, DMSO-D6): δ=12.75-12.88 (2H, brs), 6.43 (1H, s), 2.97-3.08 (1H, quin), 1.91-2.02 (2H, m), 1.50-1.76 (6H, 2×m) ppm. LRMS (electrospray): m/z [M−H]+ 179. Anal. Found C, 59.72; H, 6.74; N, 15.37. C9H12N2 requires C, 59.99; H, 6.71; N, 15.55%.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][C:12]([F:15])([F:14])[F:13])=[CH:7][CH:6]=1)=O.[NH2:16][C:17](=[S:23])[C:18]([O:20][CH2:21][CH3:22])=[O:19]>CCO>[F:13][C:12]([F:15])([F:14])[O:11][C:8]1[CH:9]=[CH:10][C:5]([C:3]2[N:16]=[C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[S:23][CH:2]=2)=[CH:6][CH:7]=1
Reactant: O=C(CBr)c1ccc(OC(F)(F)F)cc1
Reactant: CCOC(=O)C(N)=S
Solvent: CCO
Product: CCOC(=O)c1nc(-c2ccc(OC(F)(F)F)cc2)cs1
Yield: 57.7 %

Procedure:
A solution of 2-bromo-1-(4-(trifluoromethoxy)phenyl)ethanone (20.0 g, 71 mmol) and ethyl 2-amino-2-thioxoacetate (9.466 g, 71 mmol) in absolute EtOH (200 mL) was stirred at 80° C. for 16 h. The mixture was concentrated under reduced pressure, diluted with saturated aqueous sodium carbonate (100 mL) and extracted with EtOAc (4×80 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated under reduced pressure, to give the title compound as a white solid (13 g, 57%). MS (ES+) C13H10F3NO3S requires: 317. found: 318 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:25])[C@H:4]([NH:14][C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([NH2:12])=[C:8]([NH2:13])[CH:7]=1.C(N(CC)CC)C.[C:33](N1C=CN=C1)(N1C=CN=C1)=[O:34]>O1CCCC1>[CH3:1][O:2][C:3]([C@H:4]([NH:14][C:15](=[O:16])[O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:5][C:6]1[CH:11]=[CH:10][C:9]2[NH:12][C:33](=[O:34])[NH:13][C:8]=2[CH:7]=1)=[O:25]
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: COC(=O)[C@@H](Cc1ccc(N)c(N)c1)NC(=O)OCc1ccccc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COC(=O)[C@@H](Cc1ccc2[nH]c(=O)[nH]c2c1)NC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 58.8 %

Procedure:
To a dilute solution of (R)-2-benzyloxycarbonylamino-3-(3,4-diamino-phenyl)-propionic acid methyl ester (600 mg, 1.44 mmol) in tetrahydrofuran (125 mL) was added triethylamine (320 mg, 3.17 mmol) followed by 1,1′-carbonyldiimidazole (280 mg, 1.73 mmol). The reaction mixture was stirred at room temperature for 16 h and then filtered to remove solid. The filtrate was evaporated and subjected to flash column chromatography (1:12 methanol/methylene chloride) to give the title compound (313 mg, 59% yield).
Reaction SMILES: Br[CH:2]=[CH:3]Br.[Li]CCCC.[CH3:10][O:11][C@H:12]1[CH2:17][CH2:16][C@H:15]2[C@H:18]3[C@H:28]([CH2:29][CH2:30][C@:13]12[CH3:14])[C@:26]1([CH3:27])[C@H:21]([CH2:22][C:23](=[O:31])[CH2:24][CH2:25]1)[CH2:20][CH2:19]3>C1COCC1.C(Cl)Cl>[C:2]([C@@:23]1([OH:31])[CH2:24][CH2:25][C@@:26]2([CH3:27])[C@H:21]([CH2:20][CH2:19][C@@H:18]3[C@@H:28]2[CH2:29][CH2:30][C@@:13]2([CH3:14])[C@H:15]3[CH2:16][CH2:17][C@@H:12]2[O:11][CH3:10])[CH2:22]1)#[CH:3]
Reactant: CO[C@H]1CC[C@H]2[C@@H]3CC[C@H]4CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C
Reactant: BrC=CBr
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: ClCCl
Product: C#C[C@@]1(O)CC[C@@]2(C)[C@H](CC[C@@H]3[C@@H]2CC[C@]2(C)[C@@H](OC)CC[C@@H]32)C1
Temperature: -70 °C
Reaction time: 0.25 h
Yield: 4.3 %

Procedure:
A solution of 1,2-dibromoethylene (1.7 mL, 21 mmol) in dry THF (25 mL) was treated with n-BuLi (16.8 mL, 2.5 M in THF, 42 mmol) at −65° C. After stirring the mixture at −70° C. for 0.25 hr, a solution of 17β-methoxy-5α-androstan-3-one (2.128 g, 7 mmol) in THF (22 mL) was added and the mixture was stirred at −78° C. for 30 min. The cooling bath was then removed and the mixture was quenched with NH4Cl solution (3 mL). The solvents were removed and the residue was extracted with EtOAc. The organic layer was washed with water, and brine. After drying over anhyd. MgSO4 the solution was filtered and evaporated to yield the crude product. This crude product was then dissolved in a small amount of CH2Cl2 and poured on a column of silica gel. Elution with toluene:acetone mixture (95:5) gave 3β-ethynyl-3α-hydroxy-17β-methoxy-5β-androstane (100 mg) as a colorless solid; mp 138-145° C.; TLC Rf (hexane:acetone 7:3)=0.45; and then 3α-ethynyl-3β-hydroxy-17β-methoxy-5β-androstane (1.6 g) as a colorless solid.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][C@H:10]1[CH2:15][CH2:14][C@H:13]([C:16]2[CH:21]=[CH:20][C:19]([NH:22]C(=O)OCC3C=CC=CC=3)=[CH:18][CH:17]=2)[CH2:12][CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CCO.CCOC(C)=O.[Pd]>[NH2:22][C:19]1[CH:18]=[CH:17][C:16]([C@H:13]2[CH2:12][CH2:11][C@H:10]([CH2:9][NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])[CH2:15][CH2:14]2)=[CH:21][CH:20]=1
Reactant: CC(C)(C)OC(=O)NC[C@H]1CC[C@H](c2ccc(NC(=O)OCc3ccccc3)cc2)CC1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCO
Product: CC(C)(C)OC(=O)NC[C@H]1CC[C@H](c2ccc(N)cc2)CC1

Procedure:
Benzyl [4-(trans-4-{[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)phenyl]carbamate (0.50 g, 1.14 mmol) in EtOH (10 mL) and EtOAc (10 mL) was hydrogenated over 10% Pd/C (100 mg) at ambient pressure and 40° C. After 2 hours the catalyst was removed by filtration and the solution concentrated in vacuo to leave the title compound (320 mg, 86%) as a white solid; 1H NMR δ 0.95-1.02 (2H, m), 1.25-1.39 (12H, m), 1.73-1.75 (4H, m), 2.22-2.25 (1H, m), 2.80 (2H, t), 4.75 (2H, s), 6.46-6.49 (2H, m), 6.78 (1H, t), 6.85 (2H, d)
Reaction SMILES: [I-:1].Cl[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][N+:4]=1[CH3:9].[NH:10]1[CH:14]=[CH:13][CH:12]=[N:11]1.C(N(C(C)C)CC)(C)C>C(#N)C>[I-:1].[CH3:9][N+:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[N:10]1[CH:14]=[CH:13][CH:12]=[N:11]1
Reactant: c1cn[nH]c1
Reactant: C[n+]1ccccc1Cl
Agent: [I-]
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: C[n+]1ccccc1-n1cccn1
Reaction time: 8 h

Procedure:
2-Chloro-1-methylpyridinium iodide (5.0 g), pyrazole (1.3 g) and diisopropylethylamine (2.5 g) were added to acetonitrile (50 ml) and the mixture refluxed for 3.5 hours. The acetonitrile was removed and the residue dissolved in hot ethanol. The solution was left in the refrigerator overnight. The product was collected by filtration Yield, 1.73 g; mp 129°-130° C.
Reaction SMILES: [CH2:1]1[CH2:6][CH2:5]CCC1.[Br:7][CH:8]([CH:11]=[O:12])[CH:9]=[O:10].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(O)C>[Br:7][C:8](=[CH:11][O:12][CH:6]([CH3:5])[CH3:1])[CH:9]=[O:10]
Reactant: O=CC(Br)C=O
Reactant: C1CCCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CC(C)O
Product: CC(C)OC=C(Br)C=O
Temperature: 25 °C
Yield: 103 %

Procedure:
With moderate agitation, a 20 gallon reactor system was charged with cyclohexane (29.12 L), 2-bromo-malonaldehyde (2.33 kg), p-toluenesulfonic acid monohydrate 43.94 g, and 2-propanol (4.65 L). The contents of the reactor were heated to allow for the removal of distillate under atmospheric pressure (jacket temp. 95° C. and process temp. at 66.4° C.). A total of 16 L of distillate was removed from the reaction via the cooling tower. This represents approximately 47% of the total volume of cyclohexane/2-propanol (33.77 L) being removed from the reactor. The reaction solution was cooled to near ambient temperature and transferred to a 10 gallon reactor system at 40° C. An additional 6 L of distillate was removed under vacuum (~64 torr, jacket temp. 62° C., and reaction temp. 25° C.). The mobile dark orange oil was drained from the vessel and transferred to a rotary evaporator receiver flask and further concentrated under house vacuum at ~30° C. using a rotary evaporator. About 0.2 L more of solvent was removed. Total product obtained was 3.072 kg (16 mol, 103% yield). The product was used as obtained in the next step. This material is unstable and must be kept in a freezer (<-5° C., under nitrogen). The shelve-life is about 2 weeks.
Reaction SMILES: [CH2:1]([N:3]([C:11]([CH3:15])([CH3:14])[CH2:12][OH:13])[C:4](=[O:10])[O:5][C:6]([CH3:9])([CH3:8])[CH3:7])C.[CH3:16]C(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C(=O)([O-])O.[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>>[CH3:1][N:3]([C:11]([CH2:15][CH3:16])([CH3:14])[CH:12]=[O:13])[C:4](=[O:10])[O:5][C:6]([CH3:9])([CH3:8])[CH3:7]
Reactant: CCN(C(=O)OC(C)(C)C)C(C)(C)CO
Reactant: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=C([O-])O
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Product: CCC(C)(C=O)N(C)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 4 h
Yield: 69.7 %

Procedure:
To a solution of tert-butyl ethyl(1-hydroxy-2-methylpropan-2-yl)carbamate (2.18 g, 10 mmol, 1.0 equiv) DCM (150 mL) was added Dess-martin periodinane (4.24 g, 10 mmol, 1.0 equiv) portionwise at 0° C. The resulting mixture was stirred for 4 h at room temperature. Saturated solutions of aqueous sodium hydrogencarbonate and sodium thiosulfate were added. The resulting mixture was stirred for 0.5 h. The organic phase was separated, washed with saturated sodium hydrogencarbonate, brine, dried over sodium sulfate and concentrated to give 1.5 g (71%) of tert-butyl methyl(2-ethyl-1-oxopropan-2-yl)carbamate as a colorless oil.
Reaction SMILES: [CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:23])[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.CO[CH:35]1[N:39]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[C:38]([CH3:48])([CH3:47])[CH2:37][CH2:36]1>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:23])[C@H:15]([C@H:35]1[N:39]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[C:38]([CH3:48])([CH3:47])[CH2:37][CH2:36]1)[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Cc1cccc(Cl)c1)N1C(=O)OC[C@H]1Cc1ccccc1
Reactant: COC1CCC(C)(C)N1C(=O)OC(C)(C)C
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1[C@H]([C@@H](C(=O)N2C(=O)OC[C@H]2Cc2ccccc2)c2cccc(Cl)c2)CCC1(C)C
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 62.8 %

Procedure:
A solution of (R)-4-benzyl-3-(2-(3-chlorophenyl)acetyl)oxazolidin-2-one (0.975 g, 2.96 mmol) in dry DCM (125 mL) was cooled to −78° C., and TiCl4 (3.10 mL, 3.10 mmol) was added. DIEA (0.566 mL, 3.25 mmol) was added to this stirring cold solution for 15 minutes. A solution of tert-butyl 5-methoxy-2,2-dimethylpyrrolidine-1-carboxylate (0.881 g, 3.84 mmol) in DCM (20 mL) was added to the cold mixture. The reaction was stirred for 15 minutes at −78° C. and then warmed to −10° C. (ice/acetone) and stirred for 3 hours. The reaction was quenched with NH4Cl, diluted with DCM (50 mL), water (50 mL), and the layers were separated. The aqueous layer was extracted with DCM (25 mL), dried (MgSO4) and concentrated to an oil. TLC (10% ethyl acetate/hexanes) shows desired product at Rf˜0.2. Purification by flash chromatography (5% ethyl acetate/hexanes-10% ethyl acetate/hexanes) gave (S)-tert-butyl 5-((S)-2-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-(3-chlorophenyl)-2-oxoethyl)-2,2-dimethylpyrrolidine-1-carboxylate (0.98 g, 1.86 mmol, 62.9% yield). HPLC, 254 nm, 100% purity, retention time=3.86 minutes.
Reaction SMILES: [Mg].II.Br[CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C[O:15][B:16](OC)[O:17]C>O1CCCC1.CCOCC>[CH2:7]([C:8]1[CH:13]=[CH:12][C:11]([B:16]([OH:17])[OH:15])=[CH:10][CH:9]=1)[CH2:6][CH3:5]
Reactant: COB(OC)OC
Reactant: BrCCCc1ccccc1
Agent: II
Agent: [Mg]
Solvent: C1CCOC1
Solvent: CCOCC
Product: CCCc1ccc(B(O)O)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a suspension of magnesium shavings (217 mg, 8.9 mmol) in 3 mL of dry tetrahydrofuran under argon, a crystal of iodine along with a solution of 4-bromopropylbenzene (1.69 g, 8.5 mmol) dissolved in 6 mL of tetrahydrofuran was added at such a rate that a gentle reflux was maintained. The solution was refluxed for an additional 0.5 h, cooled to room temperature and added in portions over 10 min to a solution of trimethylborate (924 mg, 8.9 mmol) previously dissolved in 4 mL of dry ether at −78° C. After 30 minutes, the solution was warmed to room temperature; and stirring was continued for 90 min. The reaction was then quenched by the addition of 2 mL of a 10% hydrochloric acid solution. The tetrahydrofuran was removed under reduced pressure and the remaining residue was extracted into diethyl ether (3×25 mL). The combined ether extracts was extracted with 1 M NaOH (3×25 mL) and the resulting aqueous layer was acidified to pH 2.0 using 6N HCl, then reextracted back into diethyl ether (3×25 mL). The combined organic layers was washed with water (1×25 mL), brine (1×25 mL) and dried over magnesium sulfate. Evaporation of solvent left a brown solid which was filtered through a small plug of silica gel using 10% MeOH/CHC3. Evaporation left 448 mg (32%) of a brown solid, m.p. 90-93° C.
Reaction SMILES: [Br:1][C:2]1[C:3]([CH3:9])=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.ClC1C=CC=C(C(OO)=[O:18])C=1>C(Cl)(Cl)Cl>[Br:1][C:2]1[C:3]([CH3:9])=[CH:4][C:5]([Cl:8])=[N+:6]([O-:18])[CH:7]=1
Reactant: Cc1cc(Cl)ncc1Br
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClC(Cl)Cl
Product: Cc1cc(Cl)[n+]([O-])cc1Br
Temperature: 25 °C

Procedure:
A solution of 5-bromo-2-chloro-4-methylpyridine (1.0 eq.) and meta-chloroperbenzoic acid (mCPBA) (2.5 eq.) in chloroform (0.1 M) was stirred at 50° C. overnight. After cooling to room temperature, Ca(OH)2 (2.5 eq.) was added to the reaction mixture. The precipitate was filtered and washed with 5% methanol in dichloromethane and ethyl acetate. The filtrate was washed with saturated aqueous Na2S2O3 solution and saturated aqueous NaHCO3 solution. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo into a pale solid that was carried onto the next step without further purification.
Reaction SMILES: [C:1]1([CH:7]=[N:8][N:9]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][CH2:17]Cl)[C:10]2=[O:19])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[I-:20].[Na+]>CC(C)=O>[C:1]1([CH:7]=[N:8][N:9]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][CH2:17][I:20])[C:10]2=[O:19])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C1N(CCCCCl)CCN1N=Cc1ccccc1
Reactant: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Product: O=C1N(CCCCI)CCN1N=Cc1ccccc1
Reaction time: 1 h
Yield: 65 %

Procedure:
A stirred mixture of 1-phenylmethyleneamino-3-(4-chlorobutyl)-2-imidazolidinone (36.4 g, 0.1301 mole), acetone (700 ml) and sodium iodide (42.9 g, 0.2862 mole) is heated to reflux which is maintained for 24 hours. The mixture is filtered hot, removing the solid. After cooling, the filtrate is poured into H2O (2000 ml) and stirred 1 hour. The solid is collected, washed with H2 O, and air-dried to give 31.4 g, (0.0845 mole) of 1-phenylmethyleneamino-3-(4-iodobutyl)-2-imidazolidinone.
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[C:7]([CH3:9])[CH:6]=[CH:5][C:3]=1[NH2:4].C1(S([N:19]2[C:23]3=[N:24][CH:25]=[CH:26][CH:27]=[C:22]3[C:21]([C:28]3[CH:33]=[CH:32][N:31]=[C:30](Cl)[N:29]=3)=[CH:20]2)(=O)=O)C=CC=CC=1>>[CH3:1][C:2]1[CH:8]=[C:7]([CH3:9])[CH:6]=[CH:5][C:3]=1[NH:4][C:30]1[N:29]=[C:28]([C:21]2[C:22]3[C:23](=[N:24][CH:25]=[CH:26][CH:27]=3)[NH:19][CH:20]=2)[CH:33]=[CH:32][N:31]=1
Reactant: Cc1ccc(N)c(C)c1
Reactant: O=S(=O)(c1ccccc1)n1cc(-c2ccnc(Cl)n2)c2cccnc21
Product: Cc1ccc(Nc2nccc(-c3c[nH]c4ncccc34)n2)c(C)c1
Yield: 43.5 %

Procedure:
Using the procedure of example 1, 2,4-dimethylaniline (98 mg) was reacted with compound 1f (100 mg) to provide compound 33 (37 mg, 44%). 1H NMR (400 MHz, CD3OD) δ 8.50 (d, J=8.0 Hz, 1H), 8.21 (d, J=4.8 Hz, 1H), 8.18 (s, 1H), 8.17 (d, J=5.6 Hz, 1H), 7.36 (d, J=8.0 Hz, 1H), 7.14 (s, 1H), 7.12 (d, J=5.6 Hz, 1H), 7.07 (d, J=8.0 Hz, 1H), 7.03 (dd, J=8.0 Hz, 4.8 Hz, 1H), 2.38 (s, 3H), 2.26 (s, 3H). MS (ESI) m/z: 316 (M+H)+.