Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:14]2[NH:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[S:6][C:5]=2[CH:4]=[CH:3][C:2]=1[C:15]([NH2:17])=O.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:27])=CC=1.N1C=CC=CC=1>O1CCOCC1>[CH:1]1[C:14]2[NH:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[S:6][C:5]=2[CH:4]=[CH:3][C:2]=1[C:15](=[S:27])[NH2:17]
Reactant: NC(=O)c1ccc2c(c1)Nc1ccccc1S2
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: C1COCCO1
Solvent: c1ccncc1
Product: NC(=S)c1ccc2c(c1)Nc1ccccc1S2
Temperature: 110 °C

Procedure:
A reaction mixture comprising 3.4 g (14 mmoles) of 10H-phenothiazine-2-carboxamide (J. Org. Chem. (1961) 26, 1138-1143) and 3.4 g (8.4 mmoles) of Lawesson's reagent in solution in 40 ml of 1,4-dioxane to which 20 ml of pyridine is added is heated at 110° C. for 1 hour 30 minutes. The brown solution is then concentrated under vacuum and the residue is diluted in 200 ml of AcOEt and 100 ml of H2O. After stirring and decanting, the organic phase is washed successively with 100 ml of a 1N aqueous solution of HCl and 100 ml of salt water. After drying over sodium sulphate, filtration and evaporation of the solvent under vacuum, an orange powder is obtained. This powder is washed with Et2O, the filtrate is eliminated, and extraction is carried out with acetone. The acetonic filtrate is then concentrated under vacuum and the evaporation residue is then purified on a silica column (eluent: Heptane/AcOEt: 1/1 to 4/6). Orange powder. Melting point: 208-209° C.
Reaction SMILES: [NH2:1][CH:2]1[N:7]=[C:6]2[N:8]=[C:9]3[C:14]([CH:13]=[CH:12][CH:11]=[CH:10]3)=[C:5]2[C:4](=O)[NH:3]1.P(Cl)(Cl)([Cl:18])=O>O1CCOCC1>[ClH:18].[NH2:1][C:2]1[N:3]=[C:4]([Cl:18])[C:5]2[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[NH:8][C:6]=2[N:7]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: NC1N=C2N=c3ccccc3=C2C(=O)N1
Solvent: C1COCCO1
Product: Cl
Product: Nc1nc(Cl)c2c(n1)[nH]c1ccccc12
Yield: 26.7 %

Procedure:
A suspension of 2-amino-4-oxo-3H-indolo[2,3-d]pyrimidine (490 mg, 2.5 mmol) and phosphoryl chloride (7 ml, 75 mmol) in dioxane (13 ml) is heated under reflux for 4 hr, then concentrated in vacuo. The residue is triturated with ethanol, filtered, and the solids washed with 10:1 Ethanol:Ethyl Acetate to give 170 mg (27%) 2-amino-4-chloroindolo[2,3-d]pyrimidine hydrochloride as a grey solid, mp>250 C.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[C:4]([Cl:9])[N:3]=1.C([OH:12])C.C(OO)(=O)C>C(O)(=O)C>[NH2:1][C:2]1[N+:7]([O-:12])=[C:6]([NH2:8])[CH:5]=[C:4]([Cl:9])[N:3]=1
Reactant: CCO
Reactant: Nc1cc(Cl)nc(N)n1
Agent: CC(=O)OO
Solvent: CC(=O)O
Product: Nc1cc(Cl)nc(N)[n+]1[O-]
Temperature: 35 °C
Reaction time: 0.25 h

Procedure:
144.5 G. of 2,4-diamino-6-chloropyrimidine are suspended in 2000 ml. of ethanol. The suspension is warmed to 35° C. while stirring (about 15 minutes), the greater part of the material passing into solution. This mixture is then cooled down to 6°-8° C. and at this temperature there are added dropwise within 40 minutes 175 ml. of 40% peracetic acid in glacial acetic acid. After completion of the addition, the mixture is stirred at 6°-8° C. for a further 30 minutes. Thereafter, the mixture is left to warm up to room temperature, and stirred at this temperature for 3 hours. 2000 Ml. of petroleum ether are added, the mixture is stirred for 1 hour and then left to stand overnight. The separated precipitate is filtered off, back-washed with 200 ml. of petroleum ether and dried under reduced pressure, there being obtained 2,4-diamino-6-chloro-pyrimidine-3-oxide. Recrystallization yields analytically pure product having a melting point of 193° C.
Reaction SMILES: [NH:1]1[CH2:7][CH2:6][CH2:5][CH:4]([C:8]2[N:16]3[C:11]([C:12]([NH2:17])=[N:13][CH:14]=[N:15]3)=[C:10]([C:18]3[CH:19]=[CH:20][C:21]4[C:25]([CH:26]=3)=[N:24][N:23]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:22]=4)[CH:9]=2)[CH2:3][CH2:2]1.CC(O)=O.C(O[C:41]1(O[Si](C)(C)C)[CH2:43][CH2:42]1)C.C([BH3-])#N.[Na+].[OH-].[Na+]>CO>[CH2:27]([N:23]1[CH:22]=[C:21]2[C:25]([CH:26]=[C:18]([C:10]3[CH:9]=[C:8]([CH:4]4[CH2:5][CH2:6][CH2:7][N:1]([CH:41]5[CH2:43][CH2:42]5)[CH2:2][CH2:3]4)[N:16]4[C:11]=3[C:12]([NH2:17])=[N:13][CH:14]=[N:15]4)[CH:19]=[CH:20]2)=[N:24]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: CCOC1(O[Si](C)(C)C)CC1
Reactant: Nc1ncnn2c(C3CCCNCC3)cc(-c3ccc4cn(Cc5ccccc5)nc4c3)c12
Agent: [BH3-]C#N
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CO
Product: Nc1ncnn2c(C3CCCN(C4CC4)CC3)cc(-c3ccc4cn(Cc5ccccc5)nc4c3)c12
Temperature: 60 °C
Reaction time: 17 h
Yield: 49.2 %

Procedure:
To a solution of 7-azepan-4-yl-5-(2-benzyl-2H-indazol-6-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (100 mg, 0.20 mmol) in MeOH (2 mL) containing 3 Å molecular sieves was added AcOH (112 μL, 2.00 mmol), [(1-ethoxycyclopropyl)oxy]trimethylsilane (236 μL, 1.18 mmol) and sodium cyanoborohydride (55 mg, 0.88 mmol). The reaction was stirred at 60° C. for 17 h. Aqueous NaOH (1N, 15 mL) was added and the mixture was extracted with EtOAc (3×15 mL). The combined organics were washed with brine, dried (Na2SO4) and concentrated. The residue was purified by preparative HPLC using a gradient elution from 15% to 40% acetonitrile in water followed by filtration through an acidic resin, washing with MeOH. The product was eluted with 2M NH3 in MeOH and the filtrate was concentrated to provide 47 mg (50%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 8.23 (s, 1 H), 7.58 (s, 1 H), 7.48 (d, 1 H), 7.28 (s, 1 H), 6.97-7.07 (m, 5 H), 6.84 (dd, 1 H), 6.27 (s, 1 H), 5.34 (s, 2 H), 3.04-3.15 (m, 1 H), 2.56-2.64 (m, 1 H), 2.44-2.53 (m, 2 H), 1.27-1.77 (m, 6 H), 0.07-0.14 (m, 2 H), −0.03-0.05 (m, 2 H); ES-MS m/z 478.33 [M+H]+, HPLC RT (min) 2.10.
Reaction SMILES: [C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C.[Br:41][C:42]1[CH:43]=[C:44]([NH2:54])[CH:45]=[N:46][C:47]=1[O:48][CH2:49][C:50]([F:53])([F:52])[F:51]>CN(C=O)C>[Br:41][C:42]1[CH:43]=[C:44]([NH:54][C:1](=[O:9])[C:2]2[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=2)[CH:45]=[N:46][C:47]=1[O:48][CH2:49][C:50]([F:51])([F:52])[F:53]
Reactant: Nc1cnc(OCC(F)(F)F)c(Br)c1
Reactant: O=C(O)c1cccnc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(Nc1cnc(OCC(F)(F)F)c(Br)c1)c1cccnc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of nicotinic acid (454 mg, 3.69 mmol) in DMF (33 mL) were added successively TBTU (1.18 g, 3.69 mmol), N,N-diisopropylethylamine (3.16 mL, 18.4 mmol) and 5-bromo-6-(2,2,2-trifluoroethoxy)pyridin-3-amine (1 g, 3.69 mmol). The brown mixture was stirred under argon for 3 h at room temperature. After evaporation of DMF, the brown oil was partitioned between ethyl acetate (50 mL) and 1M NaOH (30 mL). The aqueous layers were back-extracted with ethyl acetate (1×50 mL). The organic parts were washed with water (2×25 mL) and brine (25 mL), then dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 10% to 100% ethyl acetate in heptane) to deliver the desired product as a white solid (580 mg; 42%); MS (EI): 376.1; 378.0 (M+H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH2:9][CH2:10][CH2:11][C:12]2[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[CH:14][CH:13]=2)=[CH:4][CH:3]=1.C(O[CH:23](OCC)[C:24]1C=CC(CCCNC2C=CC(F)=CC=2)=C[CH:25]=1)C.BrC(C)C.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C(Cl)(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH:24]([CH3:25])[CH3:23])[CH2:9][CH2:10][CH2:11][C:12]2[CH:13]=[CH:14][C:15]([CH:16]=[O:17])=[CH:18][CH:19]=2)=[CH:4][CH:3]=1
Reactant: O=Cc1ccc(CCCNc2ccc(F)cc2)cc1
Reactant: CCOC(OCC)c1ccc(CCCNc2ccc(F)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: ClC(Cl)Cl
Solvent: CC(C)Br
Product: CC(C)N(CCCc1ccc(C=O)cc1)c1ccc(F)cc1
Yield: 83 %

Procedure:
A mixture of 4-(3-(4-fluorophenylamino)propyl)benzaldehyde (0.09 g, 0.35 mmol) [prepared form the product of Step B by stirring in acidifies CHCl3] and 2-bromopropane (0.2 ml) and K2CO3 (0.1 g; 0.73 mmol) was stirred at reflux in anhydrous DMF (5 ml) for 6 h. The solvent was evaporated under reduced pressure and the residue was diluted to 50 ml with EtOAc and washed with H2O. The organic layer separated and dried over MgSO4 and filtered. The filtrate was evaporated to dryness and the residue was purified by FCC (SiO2, hexane/EtOAc), to give the title compound (0.078 g, 83%) as creamy paste. 1H-NMR (CDCl3) 10 (s, 1H); 7.78 (d, 2H, J=8.13 Hz); 7.32 (d, 2H, J=8.07 Hz); 6.93-6.86 (m, 2H); 6.82-6.66 (m, 2H); 3.07 (t, 2H, J=7.5 Hz); 2.71 (t, 2H, J=7.5 Hz); 2.71 (t, 2H, 7.62 Hz); 2.27-2.21 (m, 1H); 1.86-1.83 (m, 1H); 1.08 (d, 6H, J=6.6 Hz).
Reaction SMILES: [CH:1]1([NH:4][C:5]2[C:6]([NH2:13])=[CH:7][C:8]([O:11][CH3:12])=[CH:9][CH:10]=2)[CH2:3][CH2:2]1.[N:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH:20]=O)[CH:15]=1.OOS([O-])=O.[K+].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[CH:1]1([N:4]2[C:5]3[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:6]=3[N:13]=[C:20]2[C:16]2[CH:15]=[N:14][CH:19]=[CH:18][CH:17]=2)[CH2:3][CH2:2]1
Reactant: O=Cc1cccnc1
Reactant: COc1ccc(NC2CC2)c(N)c1
Agent: O=C([O-])[O-]
Agent: O=S([O-])OO
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccc2c(c1)nc(-c1cccnc1)n2C1CC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of N1-cyclopropyl-4-methoxy-benzene-1,2-diamine (0.2 g, 0.0011 mol) and pyridine-3-carbaldehyde (0.12 g, 0.0011 mol) in DMF (5 ml) and H2O (2 ml) was added OXONE® monopersulphate (0.81 g, 0.00132 map. Reaction mass was stirred at room temperature for 3 h. The reaction mixture was basified with 10% K2CO3 solution to pH˜8-10 and extracted with EtOAc (3×20 ml). The combined organic layers were washed with brine dried over Na2SO4 and concentrated under vacuum to afford the crude compound which was purified by column chromatography to obtain title compound 1-cyclopropyl-5-methoxy-2-(pyridin-3-yl)-1H-benzimidazole (376). 1H NMR (400 MHz, DMSO-d6), δ: 9.16 (s, 1H), 8.70 (s, 1H), 8.37 (d, J=8.8 Hz, 1H), 7.55 (d, J=8.4 Hz, 2H), 7.23 (s, 1H), 6.96 (d, J=8.8 Hz, 1H), 3.80 (s, 3H), 1.10 (d, J=6.4 Hz, 2H), 0.64 (s, 2H). MS (M+1): 266.1, Purity 98.98%.
Reaction SMILES: Cl[CH2:2][CH2:3][O:4][C:5]1[CH:6]=[N:7][C:8]([N:11]2[CH2:16][CH2:15][O:14][C@H:13]([CH2:17][N:18]3[C:22]4=[N:23][C:24]([C:27]5[CH:28]=[N:29][N:30]([CH3:32])[CH:31]=5)=[CH:25][N:26]=[C:21]4[N:20]=[N:19]3)[CH2:12]2)=[N:9][CH:10]=1.[CH3:33][N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1>CN(C=O)C>[CH3:32][N:30]1[CH:31]=[C:27]([C:24]2[N:23]=[C:22]3[N:18]([CH2:17][C@H:13]4[O:14][CH2:15][CH2:16][N:11]([C:8]5[N:7]=[CH:6][C:5]([O:4][CH2:3][CH2:2][N:37]6[CH2:38][CH2:39][N:34]([CH3:33])[CH2:35][CH2:36]6)=[CH:10][N:9]=5)[CH2:12]4)[N:19]=[N:20][C:21]3=[N:26][CH:25]=2)[CH:28]=[N:29]1
Reactant: CN1CCNCC1
Reactant: Cn1cc(-c2cnc3nnn(C[C@@H]4CN(c5ncc(OCCCl)cn5)CCO4)c3n2)cn1
Solvent: CN(C)C=O
Product: CN1CCN(CCOc2cnc(N3CCO[C@H](Cn4nnc5ncc(-c6cnn(C)c6)nc54)C3)nc2)CC1
Temperature: 75 °C
Reaction time: 8 h
Yield: 78.9 %

Procedure:
(S)-4-(5-(2-chloroethoxy)pyrimidin-2-yl)-2-((6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)morpholine 9 mg (0.019 mmol) was dissolved in DMF 1 ml, and 1-methylpiperazine 4 μl (0.39 mmol) and KI 4 mg (0.022 mmol) were added. The mixture was stirred at 75° C. overnight. When the reaction was completed, the reaction mixture was extracted several times with ethyl acetate and brine, and the organic layer was dried over Na2SO4. Prep LC with 7% MeOH/MC gave a product 7.8 mg (76%).
Reaction SMILES: Cl.[NH:2]([C:6]1[CH:14]=[CH:13][C:9]([C:10](Cl)=[O:11])=[CH:8][CH:7]=1)[C:3]([NH2:5])=[NH:4].[O:15]=[S:16]1(=[O:54])[CH2:21][CH2:20][N:19]([C:22](=[O:53])[CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][C:26]=2[C:32]2[CH2:36][C:35]([CH2:45][C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])([CH2:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[O:34][N:33]=2)[CH2:18][CH2:17]1.N1C=CC=CC=1.CN1C(=O)CCC1>C(#N)C>[NH:2]([C:6]1[CH:14]=[CH:13][C:9]([C:10]([O:31][C:28]2[CH:29]=[CH:30][C:25]([CH2:24][CH2:23][C:22]([N:19]3[CH2:18][CH2:17][S:16](=[O:15])(=[O:54])[CH2:21][CH2:20]3)=[O:53])=[C:26]([C:32]3[CH2:36][C:35]([CH2:45][C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])([CH2:37][C:38](=[O:39])[O:40][C:41]([CH3:44])([CH3:42])[CH3:43])[O:34][N:33]=3)[CH:27]=2)=[O:11])=[CH:8][CH:7]=1)[C:3]([NH2:5])=[NH:4]
Reactant: N=C(N)Nc1ccc(C(=O)Cl)cc1
Reactant: CC(C)(C)OC(=O)CC1(CC(=O)OC(C)(C)C)CC(c2cc(O)ccc2CCC(=O)N2CCS(=O)(=O)CC2)=NO1
Agent: Cl
Solvent: c1ccncc1
Solvent: CN1CCCC1=O
Solvent: CC#N
Product: CC(C)(C)OC(=O)CC1(CC(=O)OC(C)(C)C)CC(c2cc(OC(=O)c3ccc(NC(=N)N)cc3)ccc2CCC(=O)N2CCS(=O)(=O)CC2)=NO1
Reaction time: 0.5 h
Yield: 27.4 %

Procedure:
4-Carbamimidamidobenzoyl chloride hydrochloride (56.4 mg) was added to a mixture of di-tert-butyl 2,2′-(3-(2-(3-(1,1-dioxidothiomorpholin-4-yl)-3-oxopropyl)-5-hydroxyphenyl)-4,5-dihydro-1,2-oxazole-5,5-diyl)diacetate (140 mg), pyridine (0.2 mL), and NMP (0.2 mL) at 50 C, and the obtained mixture was stirred at 50 C for 30 minutes. 4-Carbamimidamidobenzoyl chloride hydrochloride (56.4 mg) was further added thereto, and the obtained mixture was stirred at 50 C for 30 minutes. 4-Carbamimidamidobenzoyl chloride hydrochloride (56.4 mg) was further added thereto, and the obtained mixture was stirred at 50 C for 3 hours. Pyridine (0.2 mL) and NMP (0.2 mL) were further added thereto, 4-carbamimidamidobenzoyl chloride hydrochloride (56.4 mg) was added thereto, and then, the obtained mixture was stirred at 50 C for 30 minutes. 4-Carbamimidamidobenzoyl chloride hydrochloride (56.4 mg) was further added thereto, and the obtained mixture was stirred at 50 C for 30 minutes. 4-carbamimidamidobenzoyl chloride hydrochloride (56.4 mg) was further added thereto, and the obtained mixture was stirred overnight at 50 C. To the reaction mixture, acetonitrile was added. The precipitate was filtered off, and then, the filtrate was concentrated under reduced pressure. The residue was fractionated by HPLC (C18, mobile phase: water/acetonitrile (system containing 0.1% TFA)). To the obtained fraction, a saturated aqueous solution of sodium bicarbonate was added, followed by extraction with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain the title compound (49.0 mg).
Reaction SMILES: [C:1]([C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][CH:4]=1)#[N:2].[N+:11]([O-:14])([OH:13])=[O:12].[NH2:15][NH:16][C:17]([NH:19][NH2:20])=[NH:18].[N+]([O-])(O)=O>C(O)C.O>[N+:11]([O-:14])([OH:13])=[O:12].[C:1]([C:3]1[CH:10]=[CH:9][C:6]([CH:7]=[N:15][NH:16][C:17]([NH:19][N:20]=[CH:7][C:6]2[CH:9]=[CH:10][C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)=[NH:18])=[CH:5][CH:4]=1)#[N:2]
Reactant: N#Cc1ccc(C=O)cc1
Reactant: N=C(NN)NN
Solvent: O
Solvent: O=[N+]([O-])O
Solvent: CCO
Product: N#Cc1ccc(C=NNC(=N)NN=Cc2ccc(C#N)cc2)cc1

Procedure:
A boiling solution of 13.1 grams of 4-cyanobenzaldehyde in 250 milliliters of ethanol is stirred vigorously as a solution of 6.1 grams of 1,3-diaminoguanidine nitrate and 0.5 milliliters of concentrated nitric acid in 50 milliliters of water is added in one portion. The reaction mixture is stirred as the temperature recedes to room temperature. The reaction mixture is then allowed to stand for several hours. The precipitate which forms is collected, washed with hot ethanol, air dried and finally dried at 60° C. under reduced pressure. The yield is 15.1 grams of product and the melting point is 205°-210° C. with decomposition.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[NH:16][C:15]2[CH:14]=[N:13][CH:12]=[N:11][C:10]=2[CH:9]=1.[I:17]N1C(=O)CCC1=O>CC(C)=O.CCOC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[NH:16][C:15]2[CH:14]=[N:13][CH:12]=[N:11][C:10]=2[C:9]=1[I:17]
Reactant: O=C1CCC(=O)N1I
Reactant: Fc1ccccc1-c1cc2ncncc2[nH]1
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Product: Fc1ccccc1-c1[nH]c2cncnc2c1I
Temperature: 25 °C
Reaction time: 3 h
Yield: 77 %

Procedure:
To a slurry of 6-(2-fluorophenyl)-5H-pyrrolo[3,2-d]pyrimidine (1.0 g) in acetone (25 mL) was added N-iodosuccinimide (1.4 g). The reaction was stirred at rt for 3 h, until complete conversion was observed by LC-MS. The reaction mixture was diluted with EtOAc (150 mL) and the solid was collected via filtration and washed with EtOAc yielding 1.23 g of desired (77% yield). LC-MS calculated for C12H7FIN3: 339.1, found 339.96 [M+].
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)[N:5]=[CH:4][N:3]=1.[CH3:18][C:19]1[CH:20]=[N:21][C:22]2[CH:23]=[CH:24][CH:25]=[C:26]([OH:29])[C:27]=2[N:28]=1.[H-].[Na+]>CN(C=O)C>[CH3:18][C:19]1[CH:20]=[N:21][C:22]2[C:27](=[C:26]([O:29][C:2]3[CH:7]=[C:6]([C:8]4[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=4)[N:5]=[CH:4][N:3]=3)[CH:25]=[CH:24][CH:23]=2)[N:28]=1
Reactant: Cc1cnc2cccc(O)c2n1
Reactant: FC(F)(F)c1ccc(-c2cc(Cl)ncn2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1cnc2cccc(Oc3cc(-c4ccc(C(F)(F)F)cc4)ncn3)c2n1
Temperature: 60 °C

Procedure:
To a mixture of 4-chloro-6-(4-trifluoromethyl-phenyl)-pyrimidine, (Example 2(a), Method A), (0.20 g, 0.77 mmol) and 3-methyl-quinoxalin-5-ol (0.14 g, 0.85 mmol, prepared according to J. Med. Chem. 1988, 41, 4062–4079.) in DMF (3 mL) was added sodium hydride (0.040 g, 1.0 mmol, 60% dispersion in mineral oil, Aldrich). The reaction was heated at 60° C. for 24 h, allowed to cool to room temperature and partitioned between EtOAc and H2O. The aqueous layer was extracted with EtOAc (4×). The combined organic layers were dried over MgSO4, filtered and the solvent was removed in vacuum. The residue was purified by flash chromatography (0→75% EtOAc/hexanes) to give the title compound as an ivory powder. Mp: 139–141° C., MS (ESI, pos. ion) m/z: 383 (M+1).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:8]2[CH2:9][CH2:10][C:11](=[O:14])[NH:12][N:13]=2)[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:21](Br)[CH:22]=[CH2:23]>CC(C)=O>[CH2:23]([O:1][C:2]1[CH:3]=[C:4]([C:8]2[CH2:9][CH2:10][C:11](=[O:14])[NH:12][N:13]=2)[CH:5]=[CH:6][CH:7]=1)[CH:22]=[CH2:21]
Reactant: O=C1CCC(c2cccc(O)c2)=NN1
Reactant: C=CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: C=CCOc1cccc(C2=NNC(=O)CC2)c1

Procedure:
A stirred mixture of finely powdered 6-(3-hydroxyphenyl)-4,5-dihydro-3(2H)-pyridazinone (13.1 g, 0.07 mole), potassium carbonate (9.5 g, 0.07 mole), allyl bromide (11.75 ml, 0.14 mole), and dry acetone (250 ml) was heated under reflux for 18 hours. Evaporation of the filtered solution under reduced pressure gave 6-(3-allyloxyphenyl)-4,5-dihydro-3(2H)-pyridazinone which was washed with either (13.66 g, 86%, m.p. 111°-113°C). Crystallisation from a small volume of ethanol gave the pure pyridazinone m.p. 112°-114°C.
Reaction SMILES: [Ag:1].[C:2]([OH:14])(=[O:13])[CH2:3][C:4]([CH2:9][C:10]([OH:12])=[O:11])([C:6]([OH:8])=[O:7])[OH:5]>O>[C:2]([O-:14])(=[O:13])[CH2:3][C:4]([CH2:9][C:10]([O-:12])=[O:11])([C:6]([O-:8])=[O:7])[OH:5].[Ag+3:1]
Reactant: [Ag]
Reactant: O=C(O)CC(O)(CC(=O)O)C(=O)O
Solvent: O
Product: O=C([O-])CC(O)(CC(=O)[O-])C(=O)[O-]
Product: [Ag+3]

Procedure:
The process of making a disinfectant comprises electrolytically generating silver ions in a solution of citric acid and water to form an aqueous solution of silver citrate. Preferably, the solution of citric acid and water comprises a solution of approximately 5.0% to 10% citric acid in water by volume. A potential difference of 12 volts to 50 volts provides a flow of silver ions in the range of 0.1 amperes to 0.5 amperes per square inch. A more fuller explanation of the content of the solution within the ion chamber 170 will be described in greater detail hereinafter.
Reaction SMILES: [NH2:1][C:2]1[NH:7][C:6](=[O:8])[NH:5][C:4](=[O:9])[C:3]=1Br.C(=O)([O-])[O-].[K+].[K+].[NH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[SH:24]>C(O)CO>[NH2:1][C:2]1[NH:7][C:6](=[O:8])[NH:5][C:4](=[O:9])[C:3]=1[S:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[NH2:17]
Reactant: Nc1[nH]c(=O)[nH]c(=O)c1Br
Reactant: Nc1ccccc1S
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: OCCO
Product: Nc1ccccc1Sc1c(N)[nH]c(=O)[nH]c1=O
Yield: 32 %

Procedure:
10.3 g of 6-amino-5-bromo-2,4(1H,3H)-pyrimidinedione, 7.0 g of potassium carbonate and 9.0 g of 2-aminothiophenol in 150 ml of ethylene glycol are heated at 170° C. under a nitrogen atmosphere for 4 hours. After filtration, the reaction mixture is poured onto 400 ml of water and decanted from the oily residue. After acidification with acetic acid, 4 g of 6-amino-5-(2-amino-phenylthio)-2,4(1H,3H)-pyrimidinedione are obtained, and are purified by recrystallization from ethanol/water.
Reaction SMILES: [OH:1][C:2]12[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:10][CH:4]([CH2:5]3)[CH:3]1[C:12]#[C:13][C:14]1[N:22]=[C:21]3[C:17]([NH:18][CH:19]=[N:20]3)=[C:16]([NH2:23])[N:15]=1)[CH2:9]2.C(=O)([O-])[O-].[K+].[K+].CC1C=CC(S(O[CH2:41][CH:42]2[CH2:46][CH2:45][CH2:44][CH2:43]2)(=O)=O)=CC=1>CN(C=O)C>[CH:42]1([CH2:41][N:20]2[CH:19]=[N:18][C:17]3[C:21]2=[N:22][C:14]([C:13]#[C:12][CH:3]2[CH:4]4[CH2:5][CH:6]5[CH2:7][CH:8]([CH2:9][C:2]2([OH:1])[CH2:11]5)[CH2:10]4)=[N:15][C:16]=3[NH2:23])[CH2:46][CH2:45][CH2:44][CH2:43]1
Reactant: Nc1nc(C#CC2C3CC4CC(C3)CC2(O)C4)nc2nc[nH]c12
Reactant: Cc1ccc(S(=O)(=O)OCC2CCCC2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Nc1nc(C#CC2C3CC4CC(C3)CC2(O)C4)nc2c1ncn2CC1CCCC1
Temperature: 70 °C
Reaction time: 72 h

Procedure:
2-{2-[Hydroxy-adamantan-2-yl]ethyn-1-yl}adenine (44 mg, 0.1422 mmol) was dissolved in DMF (20 mL) with heating. Anhydrous potassium carbonate (51 mg, 0.3690 mmol) and cyclopentylmethyl 4-methylbenzenesulfonate (54 mg, 0.2123 mmol) were added and the mixture stirred at 70° C. for 72 h. Extra cyclopentylmethyl 4-methylbenzenesulfonate (82 mg, 0.3224 mmol) was added and stirring continued at 100° C. a further 4.5 h. The reaction mixture was adhered to silica and purified by column chromatography, eluting with a gradient of DCM/MeOH (0–6%) to afford the pure 47 as a white solid: yield 38 mg, 68%. 1H NMR (CD3OD) δ 8.15 (s, 1H), 4.14 (d, 2H, J=7.7 Hz), 2.48 (quintet, 1H, J=7.5 Hz), 2.37–2.22, 2.08–2.02, 1.89–1.58, 1.37–1.24 (4×m, 22H). LRMS ESI (M+H+) 392.0.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=1[C:18]([CH3:23])(C)[C:19](O)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)Cl.C1(P([N:41]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.Cl>C(Cl)(Cl)Cl.C(N(CC)CC)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=1[C:18]([NH2:41])([CH3:23])[CH3:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Reactant: CC(C)(C(=O)O)c1cc([N+](=O)[O-])ccc1OCc1ccccc1
Agent: Cl
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CC(C)(N)c1cc([N+](=O)[O-])ccc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 10 h
Yield: 75 %

Procedure:
To a mixture of the compound (1.6 g) obtained in Example 563, methylene chloride (20 ml) and triethylamine (0.92 ml), diphenylphosphorylazide (1.37 ml) was added. The reaction mixture was stirred at room temperature for 10 h and 2 N HCl and chloroform were added. The organic layer was washed with a saturated aqueous sodium chloride solution, dried with anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. To the resulting residue, water (16 ml) and 1,4-dioxane (32 ml) were added. The reaction mixture was heated under reflux for 2 h and 2 N HCl and chloroform were added. After adding 2 N aqueous sodium hydroxide solution and chloroform to the aqueous layer, the organic layer was washed with a saturated aqueous sodium chloride solution, dried with anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The resulting residue was recrystallized from a mixture of ethyl acetate and n-hexane to give 1.09 g of the titled compound (yield, 75%).