Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([C:22]2[CH:27]=[CH:26][C:25](OS(C(F)(F)F)(=O)=O)=[CH:24][CH:23]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CS(C)=[O:38].C(N(CC)CC)C.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:76]([O:78][CH2:79]C)C>CO.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:76][O:78][C:79](=[O:38])[C:25]1[CH:24]=[CH:23][C:22]([C:10]2([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=3)[CH2:11][CH2:12][CH2:13][N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH2:9]2)=[CH:27][CH:26]=1
Reactant: CCOCC
Reactant: COc1cccc(C2(c3ccc(OS(=O)(=O)C(F)(F)F)cc3)CCCN(Cc3ccccc3)C2)c1
Reactant: CS(C)=O
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(CCCP(c2ccccc2)c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CO
Product: COC(=O)c1ccc(C2(c3cccc(OC)c3)CCCN(Cc3ccccc3)C2)cc1
Temperature: 70 °C
Reaction time: 4 h

Procedure:
To a solution of trifluoro-methanesulfonic acid 4-[1-benzyl-3-(3-methoxy-phenyl)-piperidin-3-yl]-phenyl ester (12.9 g, 25.4 mmol) in a Parr pressure bottle in MeOH (39 mL) were added DMSO (18 mL) and triethylamine (21 mL, 151 mmol). To the reaction mixture were added palladium acetate (3.99 g, 17.8 mmol) and 1,3-bis (diphenylphosphino) propane (5.25 g, 12.3 mmol). The mixture was shaken under 40 psi of CO at 70° C. for 4 hours. The 1n reaction mixture was cooled to room temperature and was diluted with diethyl ether (600 mL). The ether layer was washed with water (5×60 mL), dried (MgSO4) and concentrated. The crude residue was purified by flash chromatography with hexanes/EtOAc (3:1) to afford 9.82 g of 4-[1-benzyl-3-(3-methoxy-phenyl)-piperidin-3-yl]-benzoic acid methyl ester. 1HNMR (400 MHz, CDCl3) δ 7.87 (d, 2H), 7.41-7.20 (comp, 7H), 7.12 (t, 1H), 6.77 (s, 1H), 6.73 (d, 1H), 6.66 (d, 1H), 3.86 (s, 3H), 3.71 (s, 3H), 3.51 (s, 2H), 3.05 (br, 1H), 2.68 (br, 1H), 2.55 (br, 1H), 2.41-2.24 (comp, 2H), 2.22-2.18 (m, 1H) 1.61-1.42 (comp, 2H); MS (M+1) 416.3.
Reaction SMILES: [CH3:1][C:2]([CH3:10])([CH3:9])[CH2:3][CH:4]=[CH:5][C:6](=O)[CH3:7].[CH2:11]([O:13][C:14](C=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)=[O:15])[CH3:12].[C:36](O)(=O)C1C=CC=CC=1>C1C=CC=CC=1>[CH2:11]([O:13][C:14](=[O:15])[CH:7]=[C:6]([CH3:36])[CH:5]=[CH:4][CH2:3][C:2]([CH3:10])([CH3:9])[CH3:1])[CH3:12]
Reactant: O=C(O)c1ccccc1
Reactant: CC(=O)C=CCC(C)(C)C
Reactant: CCOC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: c1ccccc1
Product: CCOC(=O)C=C(C)C=CCC(C)(C)C
Temperature: 0 °C

Procedure:
6.0 g. of 6,6-dimethyl-3-hepten-2-one, 15.0 g. of ethoxycarbonylmethylene-triphenyl-phosphorane and 2.5 g. of benzoic acid are dissolved in 90 ml. of absolute benzene and heated under reflux for 65 hours. The cooled reaction mixture is poured onto 75 ml. of ice-water and 15 ml. of 2-N aqueous sodium hydroxide and the benzene layer separated. The aqueous phase is re-extracted twice with diethyl ether and the extracts are washed with 10% by weight aqueous potassium bicarbonate solution, three times with water and once with saturated sodium chloride solution, dried over sodium sulfate and evaporated. The residue is taken up with a small amount of hexane and filtered. The filtrate is chromatographed on silica gel with hexane-diethyl ether (9:1 parts by volume). 3,7,7-Trimethyl-2,4-octadienoic acid ethyl ester is obtained as an isomer mixture which is distilled in a bulb-tube at 65° C./0.05 mmHg; nD20 = 1.4855.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([F:9])[C:5](F)=[N:6][CH:7]=1.[OH-].[NH4+:11]>O>[Cl:1][C:2]1[CH:3]=[C:4]([F:9])[C:5]([NH2:11])=[N:6][CH:7]=1
Reactant: [NH4+]
Reactant: Fc1cc(Cl)cnc1F
Agent: [OH-]
Solvent: O
Product: Nc1ncc(Cl)cc1F
Temperature: 165 °C
Yield: 73 %

Procedure:
To a stainless steel high pressure reactor was added 5-chloro-2,3-difluoropyridine (18.0 g) and ammonium hydroxide (65 mL). The reaction was heated to 165° C. for three hours. The reaction mixture was then cooled to room temperature and diluted with water (100 mL). The resultant solid was filtered, dried, re-dissolved in CH2Cl2, and passed through a silica gel plug to afford 12.8 g (73%) of the title compound as an off-white solid.
Reaction SMILES: C([O:8][C:9]1[CH:10]=[CH:11][C:12]2[C:13]3[N:14]([CH2:30][CH2:31][N:32]=3)[C:15]([NH:21][C:22](=[O:29])[C:23]3[CH:28]=[CH:27][CH:26]=[N:25][CH:24]=3)=[N:16][C:17]=2[C:18]=1[O:19][CH3:20])C1C=CC=CC=1.C(O)(C(F)(F)F)=O>CO>[OH:8][C:9]1[CH:10]=[CH:11][C:12]2[C:13]3[N:14]([CH2:30][CH2:31][N:32]=3)[C:15]([NH:21][C:22](=[O:29])[C:23]3[CH:28]=[CH:27][CH:26]=[N:25][CH:24]=3)=[N:16][C:17]=2[C:18]=1[O:19][CH3:20]
Reactant: COc1c(OCc2ccccc2)ccc2c1N=C(NC(=O)c1cccnc1)N1CCN=C21
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Product: COc1c(O)ccc2c1N=C(NC(=O)c1cccnc1)N1CCN=C21
Temperature: 60 °C
Reaction time: 17 h
Yield: 113.7 %

Procedure:
N-[8-(Benzyloxy)-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]nicotinamide (20 g, 45.1 mmol) was added portionwise over 1 h to a round bottom flask containing TFA (400 mL) precooled with an ice bath. The reaction mixture was heated to 60° C. and allowed to stir at this temperature for 17 h at which time it was cooled to ambient. The reaction mixture was then concentrated under reduced pressure. The resulting residue was taken up in DCM and hexane and concentrated under reduced pressure. The material thus obtained was dissolved in MeOH and DCM (250 mL, 1:1) and concentrated under reduced pressure. The resulting solids were dried overnight under vacuum with low heat to give the title compound (17.3 g, 66%): HPLC MS RT=1.09 min, MH+=481.2; 1H NMR (DMSO-d6+2 drops TFA-d) δ: 13.41 (1H, s), 12.21 (1H, br s), 9.38 (1H, s), 8.78 (1H, d), 8.53 (1H, d), 7.85 (1H, d), 7.59 (1H, m), 7.17 (1H, d), 4.54 (2H, m), 4.21 (2H, m), 3.98 (3H, s).
Reaction SMILES: [CH3:1][C:2]([CH3:7])([CH3:6])[CH2:3][CH:4]=O.[O:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][NH2:14].[S-:15][C:16]#[N:17].[K+].II>C(#N)C.CCOC(C)=O>[C:2]([C:3]1[S:15][C:16](=[NH:17])[N:14]([CH2:13][C@@H:9]2[CH2:10][CH2:11][CH2:12][O:8]2)[CH:4]=1)([CH3:7])([CH3:6])[CH3:1]
Reactant: N#C[S-]
Reactant: CC(C)(C)CC=O
Reactant: NC[C@@H]1CCCO1
Agent: II
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CC(C)(C)c1cn(C[C@@H]2CCCO2)c(=N)s1
Temperature: 22 °C
Reaction time: 12 h

Procedure:
To a solution of 3,3-dimethylbutanal (Aldrich) (1.52 mL, 12.1 mmol) and (S)-(tetrahydrofuran-2-yl)methanamine (Aldrich) (1.00 g, 9.89 mmol) in 12 mL of acetonitrile was added 1.20 g of molecular sieves (4 Å beads, 8-12 mesh). The mixture was stirred for 12 h at 22° C. The mixture was filtered and to the filtrate was added potassium thiocyanate (1.42 g, 14.6 mmol). The temperature was adjusted at 50° C. and the mixture was stirred until all solids were dissolved, then iodine (5.58 g, 22.0 mmol) was added. The reaction was stirred at 50° C. for 12 h. The reaction was cooled to room temperature and diluted with EtOAc. The solution was washed with a solution of sodium bisulfate. The aqueous layers was brought to pH=9 by adding aq. NaOH (25%) and extracted with EtOAc. The organic extracts were combined, dried with sodium sulfate, filtered, and concentrated. The residue was crystallized from EtOAc/Hexane to give the title compound. MS (ESI−) m/z 241 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[CH:9]=2)[NH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:21][CH2:22][N:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1>CN(C=O)C>[Br:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[CH:9]=2)[N:4]([CH2:21][CH2:22][N:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)[N:3]=1
Reactant: ClCCN1CCCC1
Reactant: O=[N+]([O-])c1ccc2[nH]nc(Br)c2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1ccc2c(c1)c(Br)nn2CCN1CCCC1
Temperature: 50 °C
Yield: 133.4 %

Procedure:
A mixture of 3-bromo-5-nitro-1H-indazole (1.8 g, 7.6 mmol) and potassium carbonate (3.1 g 22 mmol) in DMF (20 mL) was stirred for 30 minutes after which 1-(2-chloro-ethyl)-pyrrolidine (0.71 g, 4.2 mmol) was added. The mixture was heated to 50° C. for 6 hours, cooled to room temperature, filtered through a plug of silica gel which was rinsed with triethylamine/ethyl acetate (1/4). The combined filtrate was concentrated under reduced pressure and purified by flash chromatography (silica gel, triethylamine/ethyl acetate 1/30) to provide the title compound (1.9 g, 76%). 1H NMR (300 MHz, DMSO-d6) ppm 1.60 (m, 4H), 2.46 (m, 4H), 2.90 (t, 2H, J=6.44), 4.60 (t, J=6.44, 2H), 8.00 (m, 1H), 8.30 (m, 1H), 8.48 (m, 1H); MS (DCI/NH3) m/z 339 [M+H]+.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[S:19][C:18]4[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=4[CH:16]=3)=[CH:11][CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[F:24][C:25]1[CH:26]=[C:27]([CH:31]=[CH:32][C:33]=1[F:34])[C:28](Cl)=[O:29]>Cl[Ti](Cl)(Cl)Cl>[N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[S:19][C:18]4[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=4[C:16]=3[C:28]([C:27]3[CH:31]=[CH:32][C:33]([F:34])=[C:25]([F:24])[CH:26]=3)=[O:29])=[CH:11][CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: c1ccc2sc(-c3ccc(OCCN4CCCC4)cc3)cc2c1
Reactant: O=C(Cl)c1ccc(F)c(F)c1
Agent: Cl[Ti](Cl)(Cl)Cl
Product: O=C(c1ccc(F)c(F)c1)c1c(-c2ccc(OCCN3CCCC3)cc2)sc2ccccc12
Temperature: 0 °C
Reaction time: 5 h
Yield: 37 %

Procedure:
A slurry of 3.23 g (10 mmol) of 2-[4-[2-(1-pyrrolidinyl)ethoxy)phenyl]benzo[b]thiophene in 50 mL of 1,2′dichloroethane was treated with 1.76 g (10 mmol) of 3,4-difluorobenzoyl chloride at 0° C. The mixture was protected from light and 4.4 mL (40 mmol) TiCl4 was added dropwise. The reaction was stirred at 0° C. for 5 h at which time it was quenched by carefully pouring it into 400 mL of saturated aqueous NaHCO3. To this was added EtOAc (200 mL), and the two layers were separated. The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic layers were dried over Na2SO4 and evaporated in vacuo to give a crude oil which was purified by chromatography (SiO2; 2% MeOH in CHCl3) to afford 1.7 g (3.7 mmol; 37%) of the ketone as a viscous oil.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][C:10]=1[CH2:17][C:18](=O)[CH2:19][CH3:20])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])(CC)C.C1CCCCC1.C([O:37]C(NC1C=CC(OC)=CC=1C)=O)(C)(C)C.CON(C)C(C1CC1)=O>C1COCC1>[CH:18]1([C:17]([C:10]2[CH:11]=[C:12]([O:15][CH3:16])[CH:13]=[CH:14][C:9]=2[NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[O:37])[CH2:20][CH2:19]1
Reactant: COc1ccc(NC(=O)OC(C)(C)C)c(C)c1
Reactant: CCC(=O)Cc1cc(OC)ccc1NC(=O)OC(C)(C)C
Agent: CON(C)C(=O)C1CC1
Agent: [Li]C(C)CC
Solvent: C1CCOC1
Solvent: C1CCCCC1
Product: COc1ccc(NC(=O)OC(C)(C)C)c(C(=O)C2CC2)c1
Temperature: -55 °C
Reaction time: 1 h
Yield: 77 %

Procedure:
1-[2-(tert-Butoxycarbonylamino)-5-methoxyphenyl]-2-butanone. A solution of 1.3M sec-butyl lithium/cyclohexane (100 mL, 0.13 mol) was added slowly to 15.17 g (0.065 mol) of N-tert-butoxycarbonyl-4-methoxy-2-methylaniline in 230 mL of THF while keeping the temperature below −40° C. with a dry ice-ethanol bath. The bath was removed and the temperature allowed to rise to −20° C. and then the bath was replaced. After the temperature had cooled to −55° C., 8.4 g (0.065 mol) of N-methoxy-N-methylcyclopropylcarboxamide in 20 mL of THF was added dropwise. The reaction mixture was stirred 1 hour, the cooling bath removed and stirred an additional 2 hours. It was then poured into 500 mL of water. The organic layer was separated, washed with water, dried over Na2SO4 and concentrated at reduced pressure. The residue was crystallized from hexane to give 15.22 g (77% yield) of [2-(tert-butoxycarbonylamino)-5-methoxyphenyl] cyclopropyl ketone, melting at 96-97° C.,
Reaction SMILES: O1CCCCC1[O:7][NH:8][C:9]([C:11]1[CH:12]=[N:13][C:14]([N:17]2[CH2:22][CH:21]3[CH:19]([CH:20]3[N:23]([S:31]([C:34]3[CH:43]=[CH:42][C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[CH:35]=3)(=[O:33])=[O:32])[CH2:24][CH2:25][N:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)[CH2:18]2)=[N:15][CH:16]=1)=[O:10].C(O)(C(F)(F)F)=O.C(Cl)Cl>CO>[OH:7][NH:8][C:9]([C:11]1[CH:16]=[N:15][C:14]([N:17]2[CH2:22][CH:21]3[CH:19]([CH:20]3[N:23]([S:31]([C:34]3[CH:43]=[CH:42][C:41]4[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=4)[CH:35]=3)(=[O:33])=[O:32])[CH2:24][CH2:25][N:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)[CH2:18]2)=[N:13][CH:12]=1)=[O:10]
Reactant: O=C(NOC1CCCCO1)c1cnc(N2CC3C(C2)C3N(CCN2CCCC2)S(=O)(=O)c2ccc3ccccc3c2)nc1
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(NO)c1cnc(N2CC3C(C2)C3N(CCN2CCCC2)S(=O)(=O)c2ccc3ccccc3c2)nc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 30.2 %

Procedure:
To N-(tetrahydro-2H-pyran-2-yloxy) 2-{6-[(naphthalene-2-sulfonyl)-(2-pyrrolidin-1-ylethyl)amino]-3-azabicyclo[3.1.0]hex-3-yl}pyrimidine-5-carboxamide (0.234 g, 0.38 mmol) was added TFA:DCM:MeOH (6 ml, 1:1:1 mixture). The mixture was stirred for 3 h at r.t. and then concentrated in vacuo. The product was purified by reverse phase HPLC to yield the title compound (60 mg, 30%). LCMS Purity >98%, m/z 523.25 [M+H]+, 1H NMR (300 MHz, d6-DMSO) δ: 1.55-1.68 (4H, m), 1.78 (1H, m), 2.25-2.34 (2H, m), 2.35-2.45 (4H, m), 2.55-2.65 (2H, m), 3.25-3.42 (5H, m), 3.54-3.63 (2H, m), 3.73-3.85 (2H, m), 7.65-7.77 (2H, m), 7.86 (1H, d, J=8.5 Hz), 8.06 (1H, d, J=7.3 Hz), 8.17 (1H, d, J=7.3 Hz), 8.24 (1H, d, J=7.3 Hz), 8.55 (1H, s), 8.61 (2H, s), 9.00 (1H, br s), 11.05 (1H, br s).
Reaction SMILES: [O:1]=[C:2]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([OH:5])=[O:4].[CH2:13]1CCN2C(=NCCC2)CC1.IC.Cl>CN(C=O)C>[O:1]=[C:2]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([O:5][CH3:13])=[O:4]
Reactant: C1CCC2=NCCCN2CC1
Reactant: O=C(O)C(=O)Cc1ccccc1
Agent: Cl
Solvent: CI
Solvent: CN(C)C=O
Product: COC(=O)C(=O)Cc1ccccc1
Temperature: 0 °C

Procedure:
2-Oxo-3-phenylpropanoic acid (20 g), DMF (100 ml) and DBU (18.2 ml) were combined at 0° C. under N2 atmosphere, and the mixture was stirred at 0° C. for an hour. Then iodomethane (15.2 ml) was added to the solution at 0° C. The reaction mixture was stirred at r.t. for 3 hours, and poured into 1N—HCl. The mixture was extracted with AcOEt (twice). The combined organic layer was washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The residue was purified by flash column chromatography over silica gel with CHCl3/AcOEt (30:1) as an eluent, and triturated with IPE/n-Hexane to give methyl 2-oxo-3-phenylpropanoate (11.2 g) as a pale yellow wax.
Reaction SMILES: [NH2:1][C:2]1[CH:31]=[CH:30][C:5]([C:6]([N:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]([N:18]([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)[C:19](=[O:21])[CH3:20])[CH2:10][CH:9]2[CH3:29])=[O:7])=[CH:4][CH:3]=1.C(N(CC)CC)C.Br[CH2:40][CH2:41][O:42][C:43](Cl)=[O:44].C([O-])([O-])=O.[Cs+].[Cs+]>C(Cl)Cl.CN(C=O)C>[Cl:28][C:25]1[CH:24]=[CH:23][C:22]([N:18]([C@H:11]2[C:12]3[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:8]([C:6](=[O:7])[C:5]3[CH:4]=[CH:3][C:2]([N:1]4[CH2:40][CH2:41][O:42][C:43]4=[O:44])=[CH:31][CH:30]=3)[C@@H:9]([CH3:29])[CH2:10]2)[C:19](=[O:21])[CH3:20])=[CH:27][CH:26]=1
Reactant: CC(=O)N(c1ccc(Cl)cc1)C1CC(C)N(C(=O)c2ccc(N)cc2)c2ccccc21
Reactant: O=C(Cl)OCCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(N3CCOC3=O)cc2)c2ccccc21
Temperature: 25 °C
Reaction time: 1 h

Procedure:
N-[1-(4-Amino-benzoyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl]-N-(4-chloro-phenyl)-acetamide (61 mg, 0.142 mmol) was dissolved in methylene chloride (2 mL) and was added triethylamine (0.100 mL, 0.700 mmol). 2-Bromoethylchloroformate (0.023 mL, 0.213 mmol) was added and the reaction was allowed to warm to room temperature. After 1 hour at room temperature, DMF (2 mL) and Cs2CO3 (100 mg, 0.307 mmol) were added and the mixture was stirred over night. The mixture was partitioned between methylene chloride and water; the methylene chloride layer was dried over MgSO4, filtered and concentrated. The crude residue was purified by silica gel chromatography (1/1 hexanes/ethyl acetate to 100% ethyl acetate gradient) to afford the product.
Reaction SMILES: [CH2:1]([O:3][C:4]1[C:9]([C:10]2[NH:11][C:12](=[O:28])[C:13]3[C:14](=[C:16]([CH2:26][CH3:27])[N:17]([CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=4)[N:18]=3)[N:15]=2)=[CH:8][C:7]([S:29]([N:32]2[CH2:37][CH2:36][N:35]([CH2:38][CH3:39])[CH2:34][CH2:33]2)(=[O:31])=[O:30])=[CH:6][N:5]=1)[CH3:2].ClC1C=C(C=CC=1)C(O)=[O:45].ClC1C=C(C=CC=1)C(OO)=O>ClCCl>[CH2:1]([O:3][C:4]1[C:9]([C:10]2[NH:11][C:12](=[O:28])[C:13]3[C:14](=[C:16]([CH2:26][CH3:27])[N:17]([CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=4)[N:18]=3)[N:15]=2)=[CH:8][C:7]([S:29]([N:32]2[CH2:37][CH2:36][N+:35]([CH2:38][CH3:39])([O-:45])[CH2:34][CH2:33]2)(=[O:30])=[O:31])=[CH:6][N:5]=1)[CH3:2]
Reactant: CCOc1ncc(S(=O)(=O)N2CCN(CC)CC2)cc1-c1nc2c(CC)n(Cc3ccccn3)nc2c(=O)[nH]1
Reactant: O=C(O)c1cccc(Cl)c1
Agent: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CCOc1ncc(S(=O)(=O)N2CC[N+]([O-])(CC)CC2)cc1-c1nc2c(CC)n(Cc3ccccn3)nc2c(=O)[nH]1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 180.3 %

Procedure:
A mixture of the title compound of Example 1 (180 mg, 0.32 mmol), 3-chlorobenzoic acid (13 mg, 0.08 mmol) and dichloromethane (10 ml) was stirred at room temperature for 20 minutes, 3-chloroperoxybenzoic acid (112 mg, 0.32 mmol) added and the reaction mixture stirred for a further 18 hours, then partitioned between dichloromethane (20 ml) and aqueous sodium bicarbonate solution (10 ml). The phases were separated, the aqueous phase extracted with dichloromethane (2×20 ml) and the combined organic solutions dried (MgSO4) and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, using dichloromethane:methanol (80:20) as eluant, to furnish the title compound (82 mg, 45%) as a white powder. Found: C, 52.73; H, 5.67; N, 17.69. C26H32N8O5S; 0.50 CH2Cl2 requires C, 52.08; H, 5.44; N, 18.34%. δ (CDCl3): 1.30 (3H, t), 1.40 (3H,t), 1.58 (3H, t), 3.02 (2H, q), 3.20 (2H, m), 3.32 (4H, m), 3.48 (2H, m), 3.72 (2H, m), 4.76 (2H, q), 5.68 (2H, s), 7.08 (1H, d), 7.22 (1H, m), 7.63 (1H, m), 8.58 (1H, d), 8.65 (1H, s), 9.03 (1H, s), 10.70 (1H, s).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH2:9])[C:5]([NH2:8])=[CH:6][CH:7]=1.O=[C:11]([CH3:15])[C:12](O)=[O:13]>O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:6][CH:7]=1)[NH:8][C:12](=[O:13])[C:11]([CH3:15])=[N:9]2.[Cl:1][C:2]1[CH:3]=[C:4]2[C:5]([N:8]=[C:11]([CH3:15])[C:12](=[O:13])[NH:9]2)=[CH:6][CH:7]=1
Reactant: CC(=O)C(=O)O
Reactant: Nc1ccc(Cl)cc1N
Solvent: O
Product: Cc1nc2cc(Cl)ccc2[nH]c1=O
Product: Cc1nc2ccc(Cl)cc2[nH]c1=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 148.1 %

Procedure:
4-chlorobenzene-1,2-diamine (5 g, 35.1 mmol, Eq: 1.00) was stirred in water (50 ml) at room temperature. 2-Oxopropanoic acid (3.09 g, 2.44 ml, 35.1 mmol, Eq: 1.00) in water (20 ml) was added drop wise. The dark mixture was stirred at room temperature for 30 min. The precipitate was filtered off and washed with water and dried under high vacuum to give 6-chloro-3-methyl-1H-quinoxalin-2-one with 7-chloro-3-methyl-1H-quinoxalin-2-one (5.06 g, 37.1%) as brown solid. MS: m/z=195.03 (M+H+)
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1B(O)O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:24]1[CH2:28][O:27][CH2:26][CH2:25]1.O.[C:30]([O:33][CH2:34][CH3:35])(=[O:32])C>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>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:25]1[CH:24]=[CH:28][O:27][C:26]=1[C:30]([O:33][CH2:34][CH3:35])=[O:32])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OB(O)c1ccccc1OCc1ccccc1
Reactant: CCOC(C)=O
Reactant: C1CCOC1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Product: CCOC(=O)c1occc1-c1ccccc1OCc1ccccc1

Procedure:
A mixture of the compound of Reference Example 1 (2.20 g), 2-benzyloxyphenylboronic acid (3.40 g), tetrakis(triphenylphosphine)palladium (1.20 g) and cesium carbonate (4.90 g) in a mixed solvent of THF (30 ml) and water (15 ml) were heated at reflux overnight under an argon atmosphere. After cooling, the reaction solution was diluted with ethyl acetate, and the organic layer was dried over MgSO4. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/20), thereby giving 3.40 g of ethyl 3-(2-benzyloxyphenyl)-2-furancarboxylate.
Reaction SMILES: S(=O)(=O)(O)O.[Cl:6][C:7]1[CH:8]=[C:9]([OH:14])[C:10](=[CH:12][CH:13]=1)[OH:11].[CH2:15]([O:22][C:23]([NH:25][CH:26](O)[C:27]([OH:29])=[O:28])=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C.C(O)(=O)C>[CH2:15]([O:22][C:23]([N:25]([C:13]1[CH:12]=[C:10]([OH:11])[C:9]([OH:14])=[CH:8][C:7]=1[Cl:6])[CH2:26][C:27]([OH:29])=[O:28])=[O:24])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: Oc1ccc(Cl)cc1O
Reactant: O=C(NC(O)C(=O)O)OCc1ccccc1
Agent: O=C([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: O=C(O)CN(C(=O)OCc1ccccc1)c1cc(O)c(O)cc1Cl
Reaction time: 1 h

Procedure:
Acetic acid (27 ml), concentrated sulphuric acid (3 ml) then 4-chlorocatechol (5.06 g. 35 mmole) were added to N-benzyloxycarbonyl 2-hydroxyglycine (6.75 g, 30 mmole) cooled in an ice bath. The mixture was stirred for one hour then poured onto ice and ethyl acetate and adjusted to pH7 with saturated sodium carbonate solution. The aqueous layer was collected, washed with ethyl acetate (100 ml), acidified to pH2 and extracted with ethyl acetate (3×75 ml). The extracts were washed with water (2×75 ml) and brine (50 ml) dried and evaporated to a gum which was crystallised from chloroform-cyclohexane, 5.90 g, 56%, mp 144°-145°, δ[(CD3)2CO] 5.06 (2H, s, OCH2), 5.64(1H, d, J8 Hz, CHNH), 6.6-7.0(1H, m, NH), 6.87 and 6.93(2H, 2×s, Ar), 7.30(5H, s, Ph) 8.0-9.4(3H, broad, 2×OH, CO2H). Found: C. 54.29; H, 4.04; Cl, 9.71; N, 4.07%. C16H14ClNO6 requires C, 54.63; H, 4.01; Cl, 10.08; N, 3.98%.
Reaction SMILES: [OH:1][CH2:2][C:3]1([CH3:7])[CH2:6][O:5][CH2:4]1.[Na].Br[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17]>O1CCOCC1>[CH2:10]([O:1][CH2:2][C:3]1([CH3:7])[CH2:6][O:5][CH2:4]1)[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17]
Reactant: CCCCCCCCBr
Reactant: CC1(CO)COC1
Agent: [Na]
Solvent: C1COCCO1
Product: CCCCCCCCOCC1(C)COC1
Temperature: 25 °C
Reaction time: 72 h
Yield: 53.9 %

Procedure:
Into a 5 liter, three-neck flask, fitted with a stirrer, reflux condenser, and nitrogen inlet tube, were placed 245 g (2.4 mole) of 3-hydroxymethyl-3-methyloxetane and 3000 ml of p-dioxane. To this solution 47 g (2 mole) of solid sodium metal was added, and the pot temperature was raised to reflux. Heat was maintained until all of the sodium had dissolved. 400 g (2 mole) of 1-bromooctane was added, and the reflux was resumed for 3 days. The mixture was cooled to room temperature, and the solid sodium bromide was filtered off using celite. The solvent was removed by evaporation and the product was distilled at 80° C. and 0.3-mm pressure. Redistillation from calcium hydride gave 231 g of polymerizable monomer, representing a 58 percent yield.