Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:36])[CH2:4][C@@H:5]([NH2:35])[C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:34])[CH2:14][C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22]([NH:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[CH3:31])=[O:23])=[C:17]([O:32][CH3:33])[CH:16]=2)=[CH:8][CH:7]=1.[C:37]1(=[O:44])[O:43][C:41](=[O:42])[CH2:40][CH2:39][CH2:38]1>O1CCCC1>[CH3:1][O:2][C:3](=[O:36])[CH2:4][C@@H:5]([NH:35][C:37](=[O:44])[CH2:38][CH2:39][CH2:40][C:41]([OH:43])=[O:42])[C:6]1[CH:7]=[CH:8][C:9]([NH:12][C:13](=[O:34])[CH2:14][C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22]([NH:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[CH3:31])=[O:23])=[C:17]([O:32][CH3:33])[CH:16]=2)=[CH:10][CH:11]=1
Reactant: COC(=O)C[C@@H](N)c1ccc(NC(=O)Cc2ccc(NC(=O)Nc3ccccc3C)c(OC)c2)cc1
Reactant: O=C1CCCC(=O)O1
Solvent: C1CCOC1
Product: COC(=O)C[C@@H](NC(=O)CCCC(=O)O)c1ccc(NC(=O)Cc2ccc(NC(=O)Nc3ccccc3C)c(OC)c2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 108.2 %

Procedure:
A stirred suspension of (R)-3-amino-3-(4-{3-methoxy-4-[3-(2-methylphenyl)ureido]-phenylacetylamino}phenyl)-propanoic acid methyl ester (0.75 g, Reference Example 30) in anhydrous tetrahydrofuran (25 ml), under an atmosphere of argon, was treated with glutaric anhydride (0.18 g). After stirring at ambient temperature for 4 hours the reaction mixture was evaporated to give the title compound (1.0 g) as a white solid.
Reaction SMILES: [NH:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH3:16])[CH:10]=2)=[CH:5][N:4]=1)[NH2:2].[C:17]([O-])([O-])(OCC)[CH3:18]>>[CH3:16][O:15][C:11]1[CH:10]=[C:9]([C:6]2[CH:7]=[CH:8][C:3]3[N:4]([C:17]([CH3:18])=[N:2][N:1]=3)[CH:5]=2)[CH:14]=[CH:13][CH:12]=1
Reactant: COc1cccc(-c2ccc(NN)nc2)c1
Reactant: CCOC(C)([O-])[O-]
Product: COc1cccc(-c2ccc3nnc(C)n3c2)c1

Procedure:
In the manner described in Example 37, a mixture of 2-hydrazino-5-(3-methoxyphenyl)pyridine and ethyl orthoacetate provides the product of the Example.
Reaction SMILES: [CH2:1]1[CH2:10][NH:9][CH2:8][C:7]2[C:6](=O)[NH:5][C:4]3[CH:12]=[CH:13][CH:14]=[CH:15][C:3]=3[C:2]1=2.O=P(Cl)(Cl)[Cl:18]>>[Cl:18][C:6]1[C:7]2[CH2:8][NH:9][CH2:10][CH2:1][C:2]=2[C:3]2[CH:15]=[CH:14][CH:13]=[CH:12][C:4]=2[N:5]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: O=c1[nH]c2ccccc2c2c1CNCC2
Product: Clc1nc2ccccc2c2c1CNCC2
Temperature: 25 °C
Reaction time: 5 h

Procedure:
A slurry of 2,3,4,6-tetrahydrobenzo[c]-2,7-naphthyridin-5(1H)-one (43.1 g, 215 mmol) in POCl3 (260 mL) was vigorously stirred at reflux under nitrogen in a 2 L three-necked, round-bottomed flask equipped with a heating/cooling bath, mechanical stirrer, condenser, thermocouple, and nitrogen inlet. An aqueous base scrubber set-up was used to capture acidic exhaust gas. After 5 hours, the batch was homogeneous (indicating formation of the intermediate). Heating was continued for an additional 1 hour; then the mixture was allowed to slowly cool to ambient temperature and was stirred for 16 hours. When the starting material had been consumed, a 1 L addition funnel was fitted to the reaction flask, and the batch was cooled (ice-water) and carefully quenched by drop-wise addition of chilled water (˜1 L). The quench addition was completed in ˜6 hours. The resulting dark solution was stirred at ambient temperature for 18 hours. The batch was transferred to a 22 L round-bottomed flask equipped with a mechanical stirrer; the transfer was completed with water (13 L) to forestall salt precipitation that otherwise interferes with extraction. The pH was adjusted to 8.5-9 with aqueous 2 N sodium hydroxide (˜3.9 L). Product was extracted with 17% (v/v) tetrahydrofuran in 2-methyltetrahydrofuran (4×2 L). All organic layers were combined and washed with saturated aqueous sodium chloride (2×150 mL) and dried over anhydrous sodium sulfate (300 g). After removal of the drying agent, solvent was removed under reduced pressure at 35-40° C. The crude solid was swished with 10% (v/v) t-butyl methyl ether in diethyl ether (220 mL) for 1 hour (to remove BHT) and collected on a filter using the filtrate to complete the transfer. The filter cake was rinsed with 10% (v/v) t-butyl methyl ether in diethyl ether (40 mL) and diethyl ether (30 mL), and dried in a vacuum oven to constant weight. In this fashion the title compound was obtained as a light yellow solid of (41.6 g, 87% yield) of 96 A % purity by HPLC assay.
Reaction SMILES: II.[CH:3]([Mg]Br)([CH3:5])[CH3:4].[Li]CCCC.[C:13]([O:17][C:18](=[O:42])[C:19]1[CH:24]=[C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:22](Br)=[C:21]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:20]=1)([CH3:16])([CH3:15])[CH3:14].C([Cu])#N.[Li+].[Cl-].C(Br)C=C>CCOCC.C1COCC1>[C:13]([O:17][C:18](=[O:42])[C:19]1[CH:24]=[C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:22]([CH2:5][CH:3]=[CH2:4])=[C:21]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:20]=1)([CH3:16])([CH3:15])[CH3:14]
Reactant: CC(C)[Mg]Br
Reactant: CC(C)(C)OC(=O)c1cc(OCc2ccccc2)c(Br)c(OCc2ccccc2)c1
Agent: N#C[Cu]
Agent: II
Agent: [Cl-]
Solvent: CCOCC
Solvent: C=CCBr
Solvent: C1CCOC1
Product: C=CCc1c(OCc2ccccc2)cc(C(=O)OC(C)(C)C)cc1OCc1ccccc1
Temperature: -78 °C
Reaction time: 2 h
Yield: 76 %

Procedure:
To a suspension of Mg pieces (5.76 g, 0.24 mol) in Et2O (250 mL) was added catalytic I2, followed by i-PrMgBr (19.7 g, 0.16 mol) in one portion. The mixture was irradiated with heating. After stirring for 2 hr, the resulting solution was added to THF (200 mL). n-BuLi (128 mL, 2.5 M in hexane, 0.32 mol) was added drop wise to the mixture at 0° C. The mixture was cooled to −78° C. and 3,5-bis-benzyloxy-4-bromo-benzoic acid tert-butyl ester (200c) (50 g, 0.107 mol) was added drop wise. After the mixture was stirred for 1 hr, CuCN (2.9 g, 0.032 mol), LiCl (2.7 g, 0.064 mol) and allyl bromide (51.5 g, 0.43 mol) were added sequentially. After stirring for another 30 min at −78° C., TLC (EtOAc/petroleum oil=1/10) showed the reaction was complete. The mixture was quenched with saturated aqueous NH4Cl (150 mL). The aqueous layer was extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated to give the title compound (35 g, 76.4% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.57-7.25 (m, 12H), 5.98 (m, 1H), 5.13 (s, 4H), 5.04-4.88 (m, 2H), 3.57 (m, 2H), 1.59 (s, 9H).
Reaction SMILES: [H-].[Na+].[CH:3]1[C:13]2[CH2:12][O:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=3[NH:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.Cl[C@H:19]1[CH2:24][CH2:23][CH2:22][N:21]([CH2:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[CH:29][CH:28]=2)[CH2:20]1>CS(C)=O>[C:33]([C:30]1[CH:29]=[CH:28][C:27]([CH2:26][CH2:25][N:21]2[CH2:22][CH2:23][CH2:24][C@@H:20]2[CH2:19][N:8]2[C:7]3[CH:6]=[CH:5][CH:4]=[CH:3][C:13]=3[CH2:12][O:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]2=3)=[CH:32][CH:31]=1)#[N:34]
Reactant: c1ccc2c(c1)COc1ccccc1N2
Reactant: N#Cc1ccc(CCN2CCC[C@H](Cl)C2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: N#Cc1ccc(CCN2CCC[C@@H]2CN2c3ccccc3COc3ccccc32)cc1
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 14.4 %

Procedure:
Three-hundred milligrams (7.5 mmols) of 60% sodium hydride were washed with petroleum ether, and then suspended in 30 ml of dimethyl sulfoxide. To the suspension were added 1.4 g (7.1 mmols) of 5,11-dihydrodibenzo[b,e][1,4]oxazepine. The mixture was stirred in a nitrogen atmosphere at room temperature for 40 minutes. To this reaction solution was added dropwise a solution of 1.7 g (6.8 mmols) of (S)-(+)-3-chloro-1-(4-cyanophenethyl)piperidine [[α]D25 =+16.7° (c=0.5, ethanol)] in 10 ml of dimethyl sulfoxide, and the mixed solution was stirred at room temperature for 17 hours and at 40° C. for 6 hours. The reaction solution was poured into ice water, and extracted with ethyl acetate. The organic layer was washed with water and with a saturated aqueous solution of sodium chloride in this order, and dried. Subsequently, the solvent was distilled off under reduced pressure. The resulting residue was subjected to column chromatography, and eluted with a mixed solvent of ethyl acetate and hexane at a ratio of 1:2. This mixed solvent was distilled off under reduced pressure to give 0.4 g of (R)-(+)-5,11-dihydro-5-[1-(4-cyanophenethyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]oxazepine as a pale yellow oil in a yield of 14%.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:22]2[S:26][C:25]([C:27]3([OH:31])[CH2:30][CH2:29][CH2:28]3)=[N:24][CH:23]=2)=[C:4]2[CH:10]=[C:9](I)[N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.[C:32]1(B(O)O)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C(=O)(O)[O-].[OH-].[Na+].Cl>CN(C)C=O.CO.CS(C)=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>[Cl:1][C:2]1[C:3]([C:22]2[S:26][C:25]([C:27]3([OH:31])[CH2:30][CH2:29][CH2:28]3)=[N:24][CH:23]=2)=[C:4]2[CH:10]=[C:9]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[NH:8][C:5]2=[N:6][CH:7]=1
Reactant: Cc1ccc(S(=O)(=O)n2c(I)cc3c(-c4cnc(C5(O)CCC5)s4)c(Cl)cnc32)cc1
Reactant: OB(O)c1ccccc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: Cl
Agent: O=C([O-])O
Solvent: CS(C)=O
Solvent: CN(C)C=O
Solvent: CO
Product: OC1(c2ncc(-c3c(Cl)cnc4[nH]c(-c5ccccc5)cc34)s2)CCC1
Temperature: 70 °C

Procedure:
To a stirred ambient solution of 1-(5-(5-chloro-2-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)thiazol-2-yl)cyclobutanol (Example 8A) (80 mg, 0.137 mmol) and phenylboronic acid (24.97 mg, 0.205 mmol) in N,N-dimethylformamide (2.0 mL) was added saturated aqueous bicarbonate solution (683 μl) followed by bis(triphenylphosphine)palladium dichloride (6.71 mg, 9.56 μmol). The mixture was heated to 70° C. for 4 hours and was then quenched by the addition of water and ethyl acetate. The layers were separated, and the aqueous layer was extracted with additional ethyl acetate. The combined organics were dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was dissolved in a mixture of methanol (2 mL) and 2N aqueous sodium hydroxide solution (341 μl, 0.683 mmol) and heated by microwave irradiation (Biotage, Initiator) to 105° C. for 5 minutes. The reaction was cooled to room temperature, diluted with 1 mL DMSO, and acidified to pH ˜5 with 10% aqueous HCl solution. The sample was purified by reverse phase high performance liquid chromatography (RP HPLC, 19×150 mm Atlantis Prep T3 OBD m column, eluting with a gradient of 5% B in A to 75% B in A over 25 minutes, wherein A is water containing 0.1% v/v trifluoroacetic acid and B is acetonitrile containing 0.1% v/v trifluoroacetic acid). The fractions containing the product were diluted with ethyl acetate and washed with saturated aqueous bicarbonate solution. The ethyl acetate solution was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ 12.58 (bs, 1H), 8.34 (s, 1H), 8.26 (s, 1H), 8.01 (dd, J=7.1, 1.5 Hz, 2H), 7.53-7.43 (m, 2H), 7.43-7.34 (m, 1H), 7.07 (d, J=2.1 Hz, 1H), 6.66 (s, 1H), 2.70-2.57 (m, 2H), 2.46-2.34 (m, 2H), 2.07-1.89 (m, 2H); MS ESI(+) m/z 381.9 [M+H]+.
Reaction SMILES: O.[OH-].[Na+].[CH3:4][CH:5]([CH3:29])[CH2:6][NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]=[CH:10][C:9]=1[NH:18][C:19](=O)[CH2:20][CH2:21][C:22]1([CH3:27])[O:26][CH2:25][CH2:24][O:23]1>C(O)C>[CH3:4][CH:5]([CH3:29])[CH2:6][N:7]1[C:8]2[C:17]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[N:11]=[CH:10][C:9]=2[N:18]=[C:19]1[CH2:20][CH2:21][C:22]1([CH3:27])[O:26][CH2:25][CH2:24][O:23]1
Reactant: CC(C)CNc1c(NC(=O)CCC2(C)OCCO2)cnc2ccccc12
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CC(C)Cn1c(CCC2(C)OCCO2)nc2cnc3ccccc3c21
Temperature: 25 °C
Yield: 95 %

Procedure:
Water (3 mL) followed by solid sodium hydroxide (0.4 g, 10.7 mmol) were added to a stirred solution of N-{4-[(2-methylpropyl)amino]quinolin-3-yl}-3-(2-methyl-1,3-dioxolan-2-yl)propanamide (2.55 g, 7.13 mmol) in ethanol (10 mL). The reaction mixture was heated at reflux for 30 minutes, then was allowed to cool to room temperature and was concentrated under reduced pressure. The resulting aqueous slurry was diluted with water (50 mL) and was extracted with dichloromethane (2×50 mL). The organic layers were combined, washed with brine (50 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to yield 2.3 g of crude 1-(2-methylpropyl)-2-[2-(2-methyl-1,3-dioxolan-2-yl)ethyl]-1H-imidazo[4,5-c]quinoline as a clear oil.
Reaction SMILES: I[C:2]1[O:3][C:4]([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[NH:12][N:11]=[C:10]3[CH3:16])=[CH:5][N:6]=1.[CH2:17]([NH2:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CN1C(=O)CCC1.CO>C(Cl)Cl>[CH2:17]([NH:24][C:2]1[O:3][C:4]([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[NH:12][N:11]=[C:10]3[CH3:16])=[CH:5][N:6]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: Cc1n[nH]c2ccc(-c3cnc(I)o3)cc12
Reactant: NCc1ccccc1
Solvent: CO
Solvent: CN1CCCC1=O
Solvent: ClCCl
Product: Cc1n[nH]c2ccc(-c3cnc(NCc4ccccc4)o3)cc12
Temperature: 165 °C
Yield: 30 %

Procedure:
The title compound was prepared from 5-(2-iodooxazol-5-yl)-3-methyl-1H-indazole, Scheme 5. A glass microwave reaction vessel was charged with 5-(2-iodooxazol-5-yl)-3-methyl-1H-indazole (0.050 g, 154 μmol), benzyl amine (0.120 mL, 1100 μmol) and NMP (1.0 mL). The reaction mixture was stirred and heated in a Smith Synthesizer® microwave reactor (Personal Chemistry, Inc., Upssala, Sweden) at 165° C. for 10 minutes. The obtained product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (12 g), eluting with a gradient of 1% to 10% 2 M NH3.MeOH in DCM, to give the title compound (14 mg, 30% yield) LCMS (API-ES) m/z (%): 305 (100%, M++H); 1H NMR (400 MHz, DMSO-d6) δ ppm 7.69 (s, 1H) 7.48 (dd, J=8.72, 1.40 Hz, 1H) 7.42 (d, J=8.72 Hz, 1H) 7.38 (m, 2H) 7.31 (m, 2H) 7.22 (m, 1H) 7.14 (s 1H) 4.44 (s, 2H).
Reaction SMILES: C(N(CC)C=O)C.C(N1CCCCC1)=O.C(N(C=[N:22][C:23]1[N:31]=[C:30]2[C:26]([NH:27][CH:28]=[N:29]2)=[C:25]([Cl:32])[N:24]=1)CC)C.N1(C=NC2N=C3C(NC=N3)=C(Cl)N=2)CCCCC1>>[NH2:22][C:23]1[N:31]=[C:30]2[C:26]([NH:27][CH:28]=[N:29]2)=[C:25]([Cl:32])[N:24]=1
Reactant: CCN(C=Nc1nc(Cl)c2[nH]cnc2n1)CC
Agent: CCN(C=O)CC
Agent: Clc1nc(N=CN2CCCCC2)nc2nc[nH]c12
Agent: O=CN1CCCCC1
Product: Nc1nc(Cl)c2[nH]cnc2n1

Procedure:
The reaction is carried out in the same manner as in Example 2 except that N,N-diethylformamide or N-formylpiperidine is used in the place of N,N-dimethylformamide to yield, respectively, a crystal of 2-diethylaminomethyleneamino-6-chloropurine or 2-piperidinomethyleneamino-6-chloropurine as an intermediate for further synthesis. A further treatment is carried out in the same manner as in Example 2 on these crystals to yield a white crystal of 2-amino-6-chloropurine.
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[Br:9][C:10]1[CH:11]=[CH:12][C:13]2[N:14]([CH:16]=[C:17]([C:19](OCC)=[O:20])[N:18]=2)[CH:15]=1>>[Br:9][C:10]1[CH:11]=[CH:12][C:13]2[N:14]([CH:16]=[C:17]([C:19]([NH:4][C:3]3[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=3[F:1])=[O:20])[N:18]=2)[CH:15]=1
Reactant: CCOC(=O)c1cn2cc(Br)ccc2n1
Reactant: Nc1ccccc1F
Product: O=C(Nc1ccccc1F)c1cn2cc(Br)ccc2n1

Procedure:
The title compound was prepared by using procedures analogous to those described for the synthesis of Intermediate I, using 2-fluoroaniline and ethyl 6-bromoimidazo[1,2-a]pyridine-2-carboxylate as starting materials.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([CH:11]=[CH:12][CH:13]=1)[C:8](O)=[O:9])=[O:4].[CH3:14][S:15]([NH2:18])(=[O:17])=[O:16].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.[Cl-].[NH4+]>C(Cl)Cl>[CH3:14][S:15]([NH:18][C:8]([C:7]1[CH:6]=[C:5]([CH:13]=[CH:12][CH:11]=1)[C:3]([O:2][CH3:1])=[O:4])=[O:9])(=[O:17])=[O:16]
Reactant: COC(=O)c1cccc(C(=O)O)c1
Reactant: CS(N)(=O)=O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: [Cl-]
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COC(=O)c1cccc(C(=O)NS(C)(=O)=O)c1
Yield: 97.8 %

Procedure:
3-(Methoxycarbonyl)benzoic acid (500 mg, 2.78 mmol), methyl sulfonamide (264 mg, 2.78 mmol), HATU (1.06 g, 2.78 mmol), and diisopropylethylamine (1.45 mL, 8.33 mmol) were mixed in methylene chloride (20 mL) with stirring. The reaction was stirred for 20 hours, added sat'd ammonium chloride, and extracted with methylene chloride. The organic extracts were combined, dried over sodium sulfate and concentrated to give an amber oil which was purified over silica gel (1:1 hexanes/ethyl acetate to 100% ethyl acetate to 4:1 methylene chloride/methanol) to obtain methyl 3-(methylsulfonylcarbamoyl)benzoate (700 mg, 2.72 mmol, 97% yield). MS found: (M+H)+=258.07.
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[C:3]1[CH:4]=[C:5]([CH2:9][S:10][C:11]2[NH:12][C:13]3[CH:18]=[CH:17][N:16]=[CH:15][C:14]=3[N:19]=2)[CH:6]=[CH:7][CH:8]=1.[Se](=O)=[O:23].OO.O>C(O)C>[F:21][C:2]([F:1])([F:20])[C:3]1[CH:4]=[C:5]([CH2:9][S:10]([C:11]2[NH:12][C:13]3[CH:18]=[CH:17][N:16]=[CH:15][C:14]=3[N:19]=2)=[O:23])[CH:6]=[CH:7][CH:8]=1
Reactant: FC(F)(F)c1cccc(CSc2nc3cnccc3[nH]2)c1
Reactant: O=[Se]=O
Agent: OO
Solvent: O
Solvent: CCO
Product: O=S(Cc1cccc(C(F)(F)F)c1)c1nc2cnccc2[nH]1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
2-[[[3-(Trifluoromethyl)phenyl]methyl]thio]-1H-imidazo[4,5-c]pyridine (0.91 g, 0.0029 mol) was dissolved in 10 mL of ethanol. An oxidizing solution was prepared by dissolving 0.32 g (0.0029 mol) of selenium dioxide in 17 mL of ethanol by heating and adding 0.33 g (0.0029 mol) of 30% hydrogen peroxide and 0.25 mL of water. The oxidizing solution was added dropwise to the sulfide solution and the reaction mixture was stirred overnight at room temperature. Water (20 mL) was added to the reaction mixture which was then extracted with chloroform (3×25 mL). The combined organic layers were dried over magnesium sulfate, filtered and evaporated to dryness. The residue amounted to 0.65 g. Purification by HPLC gave a product which on recrystallization from ethanol had a m.p. 194°-197° C.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][N:7]1[C:16](=[O:17])[C:15]2[N:14]([CH2:18][CH2:19][CH3:20])[CH:13]=[N:12][C:11]=2[N:10]([CH3:21])[C:8]1=[O:9].[P:22]([O-:29])([O:26][CH2:27][CH3:28])[O:23][CH2:24][CH3:25]>>[CH3:21][N:10]1[C:11]2[N:12]=[CH:13][N:14]([CH2:18][CH2:19][CH3:20])[C:15]=2[C:16](=[O:17])[N:7]([CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][P:22](=[O:29])([O:26][CH2:27][CH3:28])[O:23][CH2:24][CH3:25])[C:8]1=[O:9]
Reactant: CCCn1cnc2c1c(=O)n(CCCCCBr)c(=O)n2C
Reactant: CCOP([O-])OCC
Product: CCCn1cnc2c1c(=O)n(CCCCCP(=O)(OCC)OCC)c(=O)n2C

Procedure:
The title substance was prepared from 1-(5-bromopentyl)-3-methyl-7-propylxanthine and diethyl phosphite analogously to Example 16.
Reaction SMILES: [N:1]1([CH2:7][C:8]([OH:10])=O)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C.[O:44]1[CH2:49][CH2:48][O:47][CH2:46][CH:45]1[C:50]1[C:58]2[S:57][C:56]([NH2:59])=[N:55][C:54]=2[C:53]([O:60][CH3:61])=[CH:52][CH:51]=1>C1COCC1.C(Cl)(Cl)Cl>[O:44]1[CH2:49][CH2:48][O:47][CH2:46][CH:45]1[C:50]1[C:58]2[S:57][C:56]([NH:59][C:8](=[O:10])[CH2:7][N:1]3[CH2:2][CH2:3][O:4][CH2:5][CH2:6]3)=[N:55][C:54]=2[C:53]([O:60][CH3:61])=[CH:52][CH:51]=1
Reactant: COc1ccc(C2COCCO2)c2sc(N)nc12
Reactant: O=C(O)CN1CCOCC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClC(Cl)Cl
Solvent: C1CCOC1
Product: COc1ccc(C2COCCO2)c2sc(NC(=O)CN3CCOCC3)nc12

Procedure:
From morpholin-4-yl-acetic acid, HATU and N-ethyldiisopropylamine in THF, then treatment with (+)-7-[1,4]dioxan-2-yl-4-methoxy-benzothiazol-2-ylamine. [α]D20=+18.8° (c=1.04, CHCl3), ES-MS m/e (%): 394 (M+H+, 100).
Reaction SMILES: N=[C:2]1[NH:6][C:5](=[O:7])[CH:4]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]3[N:18]=[C:19]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[O:20][C:21]=3[CH3:22])=[CH:11][CH:10]=2)[S:3]1.[OH:29]S(O)(=O)=O.O1CCOCC1>O>[CH3:22][C:21]1[O:20][C:19]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[N:18][C:17]=1[CH2:16][O:15][C:12]1[CH:13]=[CH:14][C:9]([CH2:8][CH:4]2[S:3][C:2](=[O:29])[NH:6][C:5]2=[O:7])=[CH:10][CH:11]=1
Reactant: O=S(=O)(O)O
Reactant: Cc1oc(-c2ccccc2)nc1COc1ccc(CC2SC(=N)NC2=O)cc1
Solvent: O
Solvent: C1COCCO1
Product: Cc1oc(-c2ccccc2)nc1COc1ccc(CC2SC(=O)NC2=O)cc1
Yield: 58.8 %

Procedure:
A mixture of 2-imino-5-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-4-thiazolidinone (11.4 g), 1N.H2SO4 (100 ml) and dioxane (100 ml) was stirred at 80° C. for 5 hours, and poured in water. The aqueous mixture was extracted with chloroform. The chloroform layer was washed with water, dried (MgSO4) and concentrated. The oily residue was chromatographed on a column of silica gel (200 g), and from the fractions eluted with chlorform-methanol (100:1, V/V), there was obtained 5-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-2,4-thiazolidinedione (6.7 g, 58.8%). Recrystallization from ethyl acetate-hexane afforded colorless plates. m.p. 162°-163° C. Elemental analysis for C21H18N2O4S, Calcd.: C, 63.95; H, 4.60; N, 7.10. Found: C, 63.84; H, 4.63; N, 6.90. This product showed the IR and NMR spectra in accordance with those of the compound obtained in Example 6.
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH:9]([OH:11])[CH3:10])=[N:4][C:5]([Cl:8])=[CH:6][CH:7]=1.O[C:13]1[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][CH:14]=1>>[Cl:1][C:2]1[C:3]([CH:9]([O:11][C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][CH:14]=2)[CH3:10])=[N:4][C:5]([Cl:8])=[CH:6][CH:7]=1
Reactant: COC(=O)c1ccc(O)cc1
Reactant: CC(O)c1nc(Cl)ccc1Cl
Product: COC(=O)c1ccc(OC(C)c2nc(Cl)ccc2Cl)cc1

Procedure:
The title compound was prepared from the intermediate from Step A and methyl 4-hydroxybenzoate using the Mitsunobu conditions described in EXAMPLE 4. 1H NMR (500 MHz, CDCl3): δ 7.97 (d, J=8.2 Hz, 2H); 7.67 (d, J=8.4 Hz, 1H); 7.26 (d, J=8.3 Hz, 1H); 6.94 (d, J=8.7 Hz, 2H); 5.85 (q, J=6.5 Hz, 1H); 3.90 (s, 3H); 1.78 (d, J=6.5 Hz, 3H). LCMS1 3.68 min. (M-OPhCO2Me)=174
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:18]=[C:17]3[C:12]([C:13]([OH:25])=[C:14]([C:20](OCC)=[O:21])[C:15](=[O:19])[NH:16]3)=[N:11][CH:10]=2)=[CH:4][CH:3]=1.[CH2:26]([NH2:32])[C:27]1[O:31][CH:30]=[CH:29][CH:28]=1>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:18]=[C:17]3[C:12]([C:13]([OH:25])=[C:14]([C:20]([NH:32][CH2:26][C:27]4[O:31][CH:30]=[CH:29][CH:28]=4)=[O:21])[C:15](=[O:19])[NH:16]3)=[N:11][CH:10]=2)=[CH:4][CH:3]=1
Reactant: NCc1ccco1
Reactant: CCOC(=O)c1c(O)c2ncc(Cc3ccc(F)cc3)cc2[nH]c1=O
Product: O=C(NCc1ccco1)c1c(O)c2ncc(Cc3ccc(F)cc3)cc2[nH]c1=O

Procedure:
This compound was prepared from ethyl 7-[(4-fluorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate and furfurylamine employing methods similar to those described in Example 2 and was obtained as an off-white solid: 1H NMR (d6-DMSO) δ 11.85 (1H, br), 10.70 (1H, br), 8.39 (1H, br s), 7.61 (1H, s), 7.40 (1H, s), 7.31 (2H, m), 7.15 (2H, t, J=8.5 Hz), 6.42 (1H, s), 6.33 (1H, s), 4.54 (2H, s), 4.08 (2H, s); HRMS calcd for C21H16FN3O4+H+: 394.1202. Found: 394.1195.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:10]2[NH:11][CH:12]=[C:13]([C:15]([NH2:17])=[O:16])[N:14]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[CH:18]1(Br)[CH2:22][CH2:21][CH2:20][CH2:19]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[CH:18]1([O:1][C:2]2[CH:3]=[C:4]([C:10]3[NH:11][CH:12]=[C:13]([C:15]([NH2:17])=[O:16])[N:14]=3)[CH:5]=[CH:6][C:7]=2[O:8][CH3:9])[CH2:22][CH2:21][CH2:20][CH2:19]1
Reactant: BrC1CCCC1
Reactant: COc1ccc(-c2nc(C(N)=O)c[nH]2)cc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccc(-c2nc(C(N)=O)c[nH]2)cc1OC1CCCC1
Temperature: 70 °C
Yield: 30.4 %

Procedure:
A mixture of 2-(3-hydroxy-4-methoxyphenyl)-imidazole-4-formamide (110 mg, 0.47 mmol), cyclopentyl bromide (60 μl, 0.56 mmol) and K2CO3 (162 mg, 1.2 mmol) in DMF (10 ml) were heated at 70° C. overnight. A further quantity of cyclopentyl bromide (60 μl, 0.56 mmol) and K2CO3 (162 mg, 1.2 mmol) were added and the reaction mixture was cooled to room temperature, diluted with water (50 ml), extracted with ethyl acetate (2×100 ml). The combined organics were washed with brine (30 ml) dried over Na2SO4 and the volatiles removed in vacuo. Flash chromatography (SiO2 ; CH2Cl2 :EtOH (9:1) (1% NH3)) afforded 2-(3-cyclopentyloxy-4-methoxyphenyl)-imidazole-4-formamide (43 mg,) as a white solid, mp d.>195° C.