Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4](=[O:26])[C:5]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=3)=[CH:14][CH:13]=2)=[C:6]([CH2:8][CH2:9][CH3:10])[N:7]=1.[CH3:27][N:28]([CH3:40])[C:29]([C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1)=[O:30].C(N(CC)CC)C.N1C=CC=CC=1>C(Cl)Cl.C(OCC)(=O)C.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[C:24]([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[C:15]1[CH:16]=[CH:17][C:12]([CH2:11][C:5]2[C:4](=[O:26])[N:3]([C:34]3[CH:35]=[CH:36][C:31]([C:29]([N:28]([CH3:40])[CH3:27])=[O:30])=[CH:32][CH:33]=3)[C:2]([CH3:1])=[N:7][C:6]=2[CH2:8][CH2:9][CH3:10])=[CH:13][CH:14]=1)#[N:25]
Reactant: CCCc1nc(C)[nH]c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Reactant: CN(C)C(=O)c1ccc(B(O)O)cc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCCc1nc(C)n(-c2ccc(C(=O)N(C)C)cc2)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
To a suspension of 4′-[(2-methyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (1.0 g), {4-[(dimethylamino)carbonyl]phenyl}boronic acid (1.0 g), triethylamine (2.0 mL), pyridine (1.0 mL) and molecular sieves 4 A (3.0 g) in methylene chloride (10 mL) was added copper(II) acetate (1.0 g), and the mixture was stirred at room temperature for 2 days. The reaction mixture was diluted with ethyl acetate, the insoluble material was filtered off through celite, and the filtrate was concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale-yellow viscous substance (0.92 g, 64%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]2[C@H:10]([CH2:11]2)[C@H:9]1[CH2:14][NH2:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:16]1[CH2:21][CH2:20][O:19][C:18]2=[C:22]([C:25](O)=[O:26])[S:23][CH:24]=[C:17]12>>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]2[C@H:10]([CH2:11]2)[C@H:9]1[CH2:14][NH:15][C:25]([C:22]1[S:23][CH:24]=[C:17]2[C:18]=1[O:19][CH2:20][CH2:21][O:16]2)=[O:26])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: O=C(O)c1scc2c1OCCO2
Reactant: CC(C)(C)OC(=O)N1C[C@@H]2C[C@@H]2[C@H]1CN
Product: CC(C)(C)OC(=O)N1C[C@@H]2C[C@@H]2[C@H]1CNC(=O)c1scc2c1OCCO2

Procedure:
prepared by reaction of (1S,2S,5R)-2-Aminomethyl-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester with 2,3-Dihydro-thieno[3,4-b][1,4]dioxine-5-carboxylic acid. LC-MS: tR=0.96 min; [M+H]+=381.1.
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:23])[C@@H:10]([CH2:12][C:13](OCC1C=CC=CC=1)=[O:14])[NH2:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.C[Si](Cl)(C)C>CCOCC>[CH2:1]([O:8][C:9]([C@@H:10]1[NH:11][C:13](=[O:14])[CH2:12]1)=[O:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: N[C@H](CC(=O)OCc1ccccc1)C(=O)OCc1ccccc1
Agent: C[Si](C)(C)Cl
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: O=C1C[C@H](C(=O)OCc2ccccc2)N1
Temperature: 0 °C
Reaction time: 1 h
Yield: 46.5 %

Procedure:
In 485 ml of dry ether was dissolved 45 g (143.8 m mol) of D-aspartic acid dibenzyl ester (42) and after cooling the solution to 0° C. under an argon atmosphere, 20 ml (143.8 m mol) of triethylamine was added dropwise to the solution. Then, 15.6 g (143.9 m mol) of trimethylsilyl chloride was further added dropwise to the mixture at the same temperature as above and the resultant mixture was stirred for one hour. Precipitates thus formed were filtered off under an argon atmosphere and the filtrate was cooled to 0° C. to -5° C. and then 134.8×1.01 m mol of an ether solution of t-butyl magnesium chloride was added dropwise to the mixture with stirring. After further stirring the mixture for 2 hours at 0° C. and then for 3 hours at room temperature, the mixture was cooled to 0° C., 100 ml of 2N HCl (saturated with NH4Cl) was added to the mixture and after stirring the mixture for 30 minutes, 100 ml of a saturated aqueous ammonium chloride solution was added to the mixture. The ether layer thus formed was separated and the aqueous layer was extracted twice each time with 200 ml of ethyl acetate. The ether layer was combined with the ethyl acetate extract, and after washing the mixture with 300 ml of a saturated aqueous ammonium chloride solution and drying with anhydrous magnesium sulfate, ether and ethyl acetate were distilled off under reduced pressure. To the residue was added 10 ml of ethyl acetate to form crystals, which were collected by filtration to provide 13.7 g of (R)-4-benzyloxycarbonyl-2-azetidinone (43). In addition, the mother liquor was concentrated and purified by silica gel column chromatography (eluant:ethyl acetate-n-hexane (2:1)) to provide 5.1 g of the desired product. M.p. 136°-138° C.
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH3:22])=[C:4]([N:8]2[C:12](=[O:13])[CH2:11][N:10]([C:14](=[O:21])[CH2:15][NH:16][CH2:17][CH2:18][O:19][CH3:20])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[C:23]([C:25]1[CH:26]=[C:27]([CH:31]=[CH:32][CH:33]=1)[C:28](Cl)=[O:29])#N>CN1C(=O)CCC1>[Cl:1][C:2]1[C:3]([CH3:22])=[C:4]([N:8]2[C:12](=[O:13])[CH2:11][N:10]([C:14](=[O:21])[CH2:15][N:16]([CH2:17][CH2:18][O:19][CH3:20])[C:28](=[O:29])[C:27]3[CH:31]=[CH:32][CH:33]=[C:25]([CH3:23])[CH:26]=3)[CH2:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: N#Cc1cccc(C(=O)Cl)c1
Reactant: COCCNCC(=O)N1CC(=O)N(c2cccc(Cl)c2C)C1
Solvent: CN1CCCC1=O
Product: COCCN(CC(=O)N1CC(=O)N(c2cccc(Cl)c2C)C1)C(=O)c1cccc(C)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
In a 4 mL vial was taken 100 mg of 3-(3-chloro-2-methyl-phenyl)-1-[2-(2-methoxy-ethylamino)-acetyl]-imidazolidin-4-one (0.31 mmol, 1.00 eq), 61 mg of 3-cyanobenzoyl chloride (0.37 mmol, 1.20 eq), and 500 uL NMP. The mixture was stirred overnight at room temperature and the crude product was purified by reversed phase HPLC (acetonitrile —H2O with 0.1% TFA as the eluent) to yield N-{2-[3-(3-chloro-2-methyl-phenyl)-4-oxo-imidazolidin-1-yl]-2-oxo-ethyl}-3-methyl-N-(2-methoxy-ethyl)-benzamide. MS (ES) M+H expected=444.0, found=444.2.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]#[N:11])[CH:8]=2)[CH:3]=[CH:2]1.[N+:12]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[S:21]Cl)([O-:14])=[O:13]>C(OCC)C>[N+:12]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[S:21][C:3]1[C:4]2[C:9](=[CH:8][C:7]([C:10]#[N:11])=[CH:6][CH:5]=2)[NH:1][CH:2]=1)([O-:14])=[O:13]
Reactant: N#Cc1ccc2cc[nH]c2c1
Reactant: O=[N+]([O-])c1ccccc1SCl
Solvent: CCOCC
Product: N#Cc1ccc2c(Sc3ccccc3[N+](=O)[O-])c[nH]c2c1
Reaction time: 18 h
Yield: 78 %

Procedure:
To a solution of 1H-indole-6-carbonitrile (1.00 g, 7.04 mmol) in diethyl ether (50 mL) was added at rt 2-nitrobenzenesulfenyl chloride (1.34 g, 7.04 mmol) and the reaction mixture was stirred for 18 hrs. The mixture was concentrated and the crude product was purified using column chromatography (ethyl acetate/heptane 1:4→4:1) to give 3-(2-Nitro-phenylsulfanyl)-1H-indole-6-carbonitrile (1.62 g, 5.49 mmol, 78%).
Reaction SMILES: C(OC([N:8]1[CH2:27][CH2:26][N:11]2[C:12](=[O:25])[C:13]3[C:18]([C@@H:10]2[CH2:9]1)=[CH:17][C:16]([O:19][CH3:20])=[CH:15][C:14]=3[C:21]([F:24])([F:23])[F:22])=O)(C)(C)C.[ClH:28]>CCOCC.O>[ClH:28].[CH3:20][O:19][C:16]1[CH:17]=[C:18]2[C:13]([C:12](=[O:25])[N:11]3[CH2:26][CH2:27][NH:8][CH2:9][C@H:10]32)=[C:14]([C:21]([F:24])([F:22])[F:23])[CH:15]=1
Reactant: COc1cc2c(c(C(F)(F)F)c1)C(=O)N1CCN(C(=O)OC(C)(C)C)C[C@@H]21
Agent: Cl
Solvent: O
Solvent: CCOCC
Product: COc1cc2c(c(C(F)(F)F)c1)C(=O)N1CCNC[C@@H]21
Reaction time: 1 h

Procedure:
To a stirring solution of N-(t-butoxycarbonyl)-(R)-1,3,4,10b-tetrahydro-9-methoxy-7-trifluoromethyl-pyrazino[2,1-a]isoindol-6(2H)-one (40 mg, 0.1 mmol) in dry ether (2 mL) was added hydrochloric acid (1 mL). The reaction was stirred for 1 h and then conc. in vacuo to a white solid. The solid was dissolved in water and lyophilized to 10 mg of a white solid. MS (ESI) 287 (M−Cl).
Reaction SMILES: Br[C:2]1[CH:19]=[CH:18][C:5]([CH2:6][C:7]2([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:11][CH2:10][C:9](=[O:12])[NH:8]2)=[CH:4][CH:3]=1.Br[C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][N:22]=1.C[Sn](C)C.C[Sn](C)C.[F-].[Cs+]>O1CCOCC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[F:27][C:24]1[CH:25]=[CH:26][C:21]([C:2]2[CH:19]=[CH:18][C:5]([CH2:6][C:7]3([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:11][CH2:10][C:9](=[O:12])[NH:8]3)=[CH:4][CH:3]=2)=[N:22][CH:23]=1
Reactant: Fc1ccc(Br)nc1
Reactant: CCOC(=O)C1(Cc2ccc(Br)cc2)CCC(=O)N1
Agent: [Pd]
Agent: C[Sn](C)C
Agent: [Cs+]
Solvent: C1COCCO1
Product: CCOC(=O)C1(Cc2ccc(-c3ccc(F)cn3)cc2)CCC(=O)N1

Procedure:
Palladium tetrakis(triphenylphosphine) (213 mg, 0.18 mmol) was added to a degassed, ambient temperature solution of ethyl 2-(4-bromobenzyl)-5-oxopyrrolidine-2-carboxylate (600 mg, 1.84 mmol), 2-bromo-5-fluoropyridine (324 mg, 1.84 mmol) and hexamethylditin (603 mg, 1.84 mmol) in 1,4-dioxane (8 mL). After stirring at reflux overnight, the reaction mixture was cooled and cesium fluoride (50% on celite) was added. After stirring vigorously for 1 h, the reaction mixture was filtered and concentrated in vacuo. Chromatography over silica eluting with 40-100% ethyl acetate/hexane afforded ethyl 2-[4-(5-fluoropyridin-2-yl)benzyl]-5-oxopyrrolidine-2-carboxylate.
Reaction SMILES: [N:1]1([CH:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[CH2:6][CH2:5][CH:4]([N:7]2[C@@H:11]3[CH2:12][CH2:13][CH2:14][CH2:15][C@H:10]3[NH:9][C:8]2=[O:16])[CH2:3][CH2:2]1.[O:23]=[C:24]1[CH2:28][CH2:27][CH2:26][N:25]1[CH2:29][CH2:30][C:31](O)=[O:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C>[O:23]=[C:24]1[CH2:28][CH2:27][CH2:26][N:25]1[CH2:29][CH2:30][C:31]([N:20]1[CH2:21][CH2:22][CH:17]([N:1]2[CH2:2][CH2:3][CH:4]([N:7]3[C@@H:11]4[CH2:12][CH2:13][CH2:14][CH2:15][C@H:10]4[NH:9][C:8]3=[O:16])[CH2:5][CH2:6]2)[CH2:18][CH2:19]1)=[O:32]
Reactant: O=C(O)CCN1CCCC1=O
Reactant: O=C1N[C@@H]2CCCC[C@H]2N1C1CCN(C2CCNCC2)CC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C1CCCN1CCC(=O)N1CCC(N2CCC(N3C(=O)N[C@@H]4CCCC[C@H]43)CC2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 47.6 %

Procedure:
To the solution of (3aR,7aR)-1-(1,4′-bipiperidin-4-yl)octahydro-2H-benzimidazol-2-one (0.25 mmol) in dry DMF (3 mL) was added 3-(2-oxopyrrolidin-1-yl)propanoic acid (47 mg, 0.3 mmol) followed by HATU (114 mg, 0.3 mmol) and diisopropylethylamine (0.10 mL, 0.5 mmol). The mixture was stirred at room temperature for 1 h, and the reaction was quenched with water (5 mL) and the solvent was removed in vacuo. Dichloromethane (15 mL) was added and washed with saturated NaHCO3 (10 mL) and brine (10 mL) and dried over Na2SO4. The crude product was purified with High pH prep-LCMS to provide the title compound (53 mg, 47%) as white powders. 1H NMR (400 MHz, METHANOL-D4): δ ppm 1.26-1.51 (m, 6H), 1.55-1.73 (m, 2H), 1.75-2.08 (m, 9H), 2.19-2.37 (m, 5H), 2.56 (t, J=11.91 Hz, 2H), 2.64 (t, J=7.03 Hz, 2H), 2.87-3.14 (m, 5H), 3.43-3.55 (m, 4H), 3.55-3.69 (m, 1H), 3.99 (d, J=13.28 Hz, 1H), 4.54 (d, J=13.28 Hz, 1H). MS (M+1): 446.3
Reaction SMILES: [CH2:1]([N:7]1[CH2:12][CH:11]2[CH:9]([C:10]2([C:14]2[CH:15]=[C:16]([NH2:20])[CH:17]=[CH:18][CH:19]=2)[CH3:13])[CH2:8]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[F:21][C:22]([F:28])([F:27])[S:23](Cl)(=[O:25])=[O:24]>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[F:21][C:22]([F:28])([F:27])[S:23]([NH:20][C:16]1[CH:17]=[CH:18][CH:19]=[C:14]([C:10]2([CH3:13])[CH:11]3[CH:9]2[CH2:8][N:7]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH2:12]3)[CH:15]=1)(=[O:25])=[O:24]
Reactant: CCCCCCN1CC2C(C1)C2(C)c1cccc(N)c1
Reactant: O=S(=O)(Cl)C(F)(F)F
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Product: CCCCCCN1CC2C(C1)C2(C)c1cccc(NS(=O)(=O)C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A solution of 3-(3-hexyl-6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenylamine (Preparation 12, 0.10 g, 0.37 mmol) in pyridine (10 ml) cooled at 0° C. was treated with trifluoromethanesulphonyl chloride (0.14 g, 0.88 mmol) and 4-dimethylaminopyridine (5 mg). The reaction mixture was stirred at room temperature for 3 h. The reaction mixture was concentrated in vacuo and the residue was poured into saturated aqueous sodium hydrogen carbonate solution (100 ml) and extracted with dichloromethane (3×50 ml). The combined organics were dried (Na2SO4) and then concentrated in vacuo. The crude residue was purified by preparative HPLC (condition 7) to give a brown solid, (17 mg, 12%).
Reaction SMILES: [Cl:1]Cl.[C:3]([O:12][CH3:13])(=[O:11])[C:4]1[C:5](=[CH:7][CH:8]=[CH:9][CH:10]=1)[OH:6]>C(Cl)(Cl)Cl>[Cl:1][C:9]1[CH:10]=[C:4]([C:3]([O:12][CH3:13])=[O:11])[C:5]([OH:6])=[CH:7][CH:8]=1
Reactant: COC(=O)c1ccccc1O
Reactant: ClCl
Solvent: ClC(Cl)Cl
Product: COC(=O)c1cc(Cl)ccc1O

Procedure:
A 85.2 g quantity of chlorine gas was absorbed in a mixture of 152 g (1.0 mole) of methyl salicylate and 500 ml of chloroform at less than 20° C. over a period of 6 hours while the mixture was stirred. The resulting reaction mixture was washed with water and the chloroform was removed. The residue was subjected to fractional distillation at reduced pressure to provide 152 g (81.5%) of a fraction at 117° to 120° C. and 8 mmHg., M.P. 51° C.
Reaction SMILES: [CH3:1][C:2]1[CH2:21][C@@H:20]2[C@:7]([CH3:24])([CH2:8][C:9](=[O:23])[C@H:10]3[C@H:19]2[CH2:18][CH2:17][C@@H:16]2[C@:11]3([CH3:22])[CH2:12][CH:13]=[CH:14][CH2:15]2)[C:3]=1[C:4](=[O:6])[CH3:5].ClC1C=CC=C(C(OO)=[O:33])C=1>C(Cl)Cl>[O:33]1[C@H:14]2[CH2:15][C@H:16]3[C@:11]([CH3:22])([CH2:12][C@@H:13]12)[C@@H:10]1[C@H:19]([C@H:20]2[C@:7]([CH3:24])([CH2:8][C:9]1=[O:23])[C:3]([C:4](=[O:6])[CH3:5])=[C:2]([CH3:1])[CH2:21]2)[CH2:18][CH2:17]3
Reactant: CC(=O)C1=C(C)C[C@H]2[C@@H]3CC[C@H]4CC=CC[C@]4(C)[C@H]3C(=O)C[C@]12C
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CC(=O)C1=C(C)C[C@H]2[C@@H]3CC[C@H]4C[C@@H]5O[C@@H]5C[C@]4(C)[C@H]3C(=O)C[C@]12C
Reaction time: 8 h
Yield: 61.4 %

Procedure:
16-Methyl-5α-pregna-2,16-diene-11,20-dione (800 mg.) in methylene chloride (50 ml.) was treated with m-chloroperbenzoic acid (85%; 535 mg.), and the solution was left to stand at room temperature overnight. More methylene chloride (50 ml.) was added and the solution washed with potassium bicarbonate solution (5%, 100 ml.) and with water (100 ml.), dried over sodium sulphate and evaporated to a crystalline solid (~ 1g.) which was purified by preparative TLC in ethyl acetate/petrol, 1/1 run twice. The main band yielded a white solid (650 mg.) which was recrystallised from acetone/ petrol to give title compound (515 mg.) as white crystals, m.p. 155°-157°, [α]D + 57.8° (c 0.9), λmax. (EtOH) 246.5 nm (ε 9150).
Reaction SMILES: [CH:1]1[CH:6]=[C:5]2[C:7]([C:9]3[C:17](=[O:18])[CH:16]=[CH:15][C:13](=[O:14])[C:10]=3[C:11](=[O:12])[C:4]2=[CH:3][CH:2]=1)=[O:8].[CH2:19]=[CH:20][C:21]([Cl:23])=[CH2:22]>C(O)(=O)C.CCOCC>[Cl:23][C:21]1[CH2:22][CH:16]2[CH:15]([C:13](=[O:14])[C:10]3[C:11](=[O:12])[C:4]4[CH:3]=[CH:2][CH:1]=[CH:6][C:5]=4[C:7](=[O:8])[C:9]=3[C:17]2=[O:18])[CH2:19][CH:20]=1
Reactant: C=CC(=C)Cl
Reactant: O=c1ccc(=O)c2c(=O)c3ccccc3c(=O)c1=2
Solvent: CC(=O)O
Solvent: CCOCC
Product: O=C1C2=C(C(=O)c3ccccc31)C(=O)C1CC(Cl)=CCC1C2=O
Temperature: 25 °C
Reaction time: 60 h
Yield: 72 %

Procedure:
Quinizarinquinone (I) (1.0 g, 4.2 mmol) and chloroprene (1.12 g, 12.6 mmol) were dissolved in acetic acid (6 ml, glacial) and stirred at ambient temperature under nitrogen for 2.5 days. The reaction mixture was then diluted with ether (25 ml), the reaction mixture filtered, the retained precipitate washed with ether and dried under reduced pressure in the presence of phosphorus pentoxide to yield 9-chloro-6a,7,10,10atetrahydro-5,6,11,12-naphthacenetetraone (II) (988 mg, 72%). Recrystalization (chloroform-ether) gave the foregoing compound in analytical purity m.p. 221°-222° C.,
Reaction SMILES: FC(F)(F)C(=N[Si](C)(C)C)O[Si](C)(C)C.[NH:16]1[CH:23]=[N:22][C:20]([NH2:21])=[N:19][C:17]1=[O:18].C(O[CH:28]1[O:40][C@H:39]([CH2:41][O:42]C(=O)C)[C@@H:34]([O:35]C(=O)C)[C@H:29]1[O:30]C(=O)C)(=O)C.C(=O)(O)[O-].[Na+].[OH-].[Na+].C[O-].[Na+]>C(#N)C.O.CO.[Ti](Cl)(Cl)(Cl)Cl.ClCCl>[CH:23]1[N:16]([C@@H:28]2[O:40][C@H:39]([CH2:41][OH:42])[C@@H:34]([OH:35])[C@H:29]2[OH:30])[C:17](=[O:18])[N:19]=[C:20]([NH2:21])[N:22]=1
Reactant: CC(=O)OC[C@H]1OC(OC(C)=O)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: Nc1nc[nH]c(=O)n1
Agent: Cl[Ti](Cl)(Cl)Cl
Agent: C[O-]
Agent: C[Si](C)(C)N=C(O[Si](C)(C)C)C(F)(F)F
Solvent: ClCCl
Solvent: O
Solvent: CC#N
Product: Nc1ncn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c(=O)n1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 36.7 %

Procedure:
34.7 mL of BSTFA are added to a suspension of 6.3 g of azacytosine in 126 mL of acetonitrile. The mixture is brought to 50° C. and it is stirred for 90 minutes. 7 mL titanium tetrachloride and then a solution of 16.7 g of 1,2,3,5-tetra-O-acetyl-D-ribofuranose in 33 mL of acetonitrile are added to the limpid solution, in about ten minutes. Stirring is maintained for 120 minutes, it is cooled to room temperature and it is slowly poured onto a mixture constituted by 500 ml of dichloromethane and 330 mL of water into which 9.5 g of sodium bicarbonate had been previously dissolved. Stirring is carried out for 15 minutes and the pH is adjusted to pH=4.5 using 30% sodium hydroxide in water. It is filtered on earth filter, the mixture is left to settle and phases are separated. The aqueous phase is washed twice using 125 ml of dichloromethane for each washing. The organic phases which are anhydrified by treating them with anhydrous calcium chloride are combined. Concentration is carried out at low pressure until a viscous residue is obtained. The residue is recovered with 250 mL of methanol, it is concentrated once again at low pressure until a viscous residue is obtained. 250 mL of methanol are added, it is heated to 50° C. and 15 mL of a 10% solution of sodium methylate in methanol are added. It is stirred for 1 hour, it is cooled to room temperature, it is stirred to complete precipitation and the solid is filtered by washing it on the filter with methanol. 4.7 g of azacitidine with HPLC purity (UV 254 nm) of 97.2% are obtained after drying at low pressure.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:27])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][C:16]=2[CH2:25]Br)[CH:7]=1)[CH3:2].[CH3:28][C@H:29]1[C@@H:33]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[O:32][C:31](=[O:40])[NH:30]1>>[CH2:1]([O:3][C:4](=[O:27])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][C:16]=2[CH2:25][N:30]2[C@@H:29]([CH3:28])[C@@H:33]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[O:32][C:31]2=[O:40])[CH:7]=1)[CH3:2]
Reactant: CCOC(=O)Cc1ccc(OC)c(Oc2ccc(C(F)(F)F)cc2CBr)c1
Reactant: C[C@@H]1NC(=O)O[C@@H]1c1ccccc1
Product: CCOC(=O)Cc1ccc(OC)c(Oc2ccc(C(F)(F)F)cc2CN2C(=O)O[C@H](c3ccccc3)[C@@H]2C)c1

Procedure:
Prepared according to the procedure described in Example 11, Step 7, using the following starting materials: [3-(2-bromomethyl-4-trifluoromethyl-phenoxy)-4-methoxy-phenyl]-acetic acid ethyl ester and (4S,5R)-(−)-4-methyl-5-phenyl-2-oxazolidinone.
Reaction SMILES: [CH2:1]([N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][N:13]=2)[C:8]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([OH:21])[CH:16]=2)=[C:7]([NH:22][C:23]([NH:25][C:26]2[C:31]([CH:32]([CH3:34])[CH3:33])=[CH:30][CH:29]=[CH:28][C:27]=2[CH:35]([CH3:37])[CH3:36])=[O:24])[C:6]1=[O:38])[CH2:2][CH2:3][CH3:4].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].I[CH2:48][CH2:49][CH3:50]>CN(C=O)C.O>[CH2:1]([N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][N:13]=2)[C:8]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:48][CH2:49][CH3:50])[CH:16]=2)=[C:7]([NH:22][C:23]([NH:25][C:26]2[C:27]([CH:35]([CH3:37])[CH3:36])=[CH:28][CH:29]=[CH:30][C:31]=2[CH:32]([CH3:33])[CH3:34])=[O:24])[C:6]1=[O:38])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCn1c(=O)c(NC(=O)Nc2c(C(C)C)cccc2C(C)C)c(-c2cccc(O)c2)c2cccnc21
Reactant: CCCI
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCCCn1c(=O)c(NC(=O)Nc2c(C(C)C)cccc2C(C)C)c(-c2cccc(OCCC)c2)c2cccnc21
Reaction time: 5 h
Yield: 82.8 %

Procedure:
To a suspension of N-{1-butyl-4-(3-hydroxyphenyl)-1,2-dihydro-2-oxo-1,8-naphthyridin-3-yl }-N'-(2,6-diisopropylphenyl)urea (300 mg, 0.58 mmol), potassium carbonate (96 mg, 0.7 mmol) and potassium iodide (19 mg) in DMF (5 ml) was added 1-iodopropane (99 mg, 0.58 mmol) at room temperature, and the mixture was stirred at 40°-50° C. for five hours. After allowed to stand for cooling, the mixture was poured into water, and the mixture was extracted with ethyl acetate. The extracted was washed with water, washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The resultant was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (20% ethyl acetate in hexane), and crystallized from ether/hexane to give the title compound (253 mg, 0.48 mmol).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9](C)[CH:10]=2)[NH:5][C:4](=O)[N:3]=1.F[C:15](F)(F)C1C=C(C=CC=1)N>C(O)C>[CH3:15][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:6]=1[N:5]=[CH:4][N:3]=[C:2]2[Cl:1]
Reactant: Nc1cccc(C(F)(F)F)c1
Reactant: Cc1ccc2[nH]c(=O)nc(Cl)c2c1
Solvent: CCO
Product: Cc1cccc2c(Cl)ncnc12

Procedure:
0.45 g of 4-chloro 6-methyl quinazolone and 0.405 g, of m-trifluoromethylaniline in 20 ml ethanol were refluxed 1 hour. Treatment with aqueous Na2CO3 and extraction with CH2Cl2 gave 0.2 g of P15 as a white solid, mp-215° C., as the free base. NMR CDCl3 δ 8.78(1H,S), 8.06(2H,m), 7.86(1H,d,J=7.6 Hz), 7.65(2H,m), 7.54(1H,t,J=8.0 Hz), 7.42(1H,m), 2.58(3H,S).
Reaction SMILES: [CH3:1][O:2][CH:3]([O:19][CH3:20])[C@@:4]1([CH3:18])[C@@H:9]2[O:10][C@@H:8]2[C:7]2[CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=[CH:14][C:6]=2[O:5]1.[CH3:21][C:22]1[C:27]([CH3:28])=[CH:26][CH:25]=[CH:24][C:23]=1[NH:29][CH2:30][C:31]1[NH:32][CH:33]=[CH:34][N:35]=1>>[CH3:1][O:2][CH:3]([O:19][CH3:20])[C@@:4]1([CH3:18])[C@H:9]([OH:10])[C@@H:8]([N:29]([C:23]2[CH:24]=[CH:25][CH:26]=[C:27]([CH3:28])[C:22]=2[CH3:21])[CH2:30][C:31]2[NH:35][CH:34]=[CH:33][N:32]=2)[C:7]2[CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=[CH:14][C:6]=2[O:5]1
Reactant: COC(OC)[C@]1(C)Oc2ccc([N+](=O)[O-])cc2[C@H]2O[C@H]21
Reactant: Cc1cccc(NCc2ncc[nH]2)c1C
Product: COC(OC)[C@]1(C)Oc2ccc([N+](=O)[O-])cc2[C@H](N(Cc2ncc[nH]2)c2cccc(C)c2C)[C@H]1O
Yield: 48.7 %

Procedure:
The title compound (416 mg, 49%) was prepared using (2R,3R,4R)-3,4-dihydro-2-dimethoxymethyl-3,4-epoxy-2-methyl-6-nitro-2H-1-benzopyran (500 mg, 1.77 mmol) and 2,3-dimethylphenyl-1H-imidazol-2-ylmethylamine (358 mg, 1.77 mmol), according to the same procedure used for the preparation of example 1 above.
Reaction SMILES: Cl[C:2]1[C:7]2[N:8]=[N:9][S:10][C:6]=2[C:5]([C:11]#[N:12])=[CH:4][CH:3]=1.BrC1C2N=NSC=2C(C#N)=C(Br)C=1.S1C2C(C(O)=O)=CC=CC=2N=N1.COC(C1C2SN=NC=2C=CC=1)=O>>[C:11]([C:5]1[C:6]2[S:10][N:9]=[N:8][C:7]=2[CH:2]=[CH:3][CH:4]=1)#[N:12]
Reactant: N#Cc1ccc(Cl)c2nnsc12
Agent: COC(=O)c1cccc2nnsc12
Agent: N#Cc1c(Br)cc(Br)c2nnsc12
Agent: O=C(O)c1cccc2nnsc12
Product: N#Cc1cccc2nnsc12

Procedure:
4-chloro-7-cyanobenzo-1,2,3-thiadiazole; 4,6-dibromo-7-cyanobenzo-1,2,3-thiadiazole: benzo-1,2,3-thiadiazole-7-carboxylic acid; benzo-1,2,3-thiadiazole-7-carboxylic acid methyl ester.