Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[C@@:3]23[C@:23]([CH3:28])([CH2:24][CH2:25][C:26](=[O:27])[C@@H:2]12)[C:22]1[CH2:21][CH2:20][C@@:19]2([CH3:29])[C@@H:7]([CH2:8][CH2:9][C@@H:10]2[C@H:11]([CH3:18])[CH2:12][CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[C:6]=1[CH2:5][CH2:4]3>O1CCCC1>[CH3:17][CH:15]([CH2:14][CH2:13][CH2:12][C@H:11]([C@@H:10]1[C@:19]2([CH3:29])[C@H:7]([C:6]3[CH2:5][CH2:4][C@@:3]4([OH:1])[C@:23]([C:22]=3[CH2:21][CH2:20]2)([CH3:28])[CH2:24][CH2:25][C@H:26]([OH:27])[CH2:2]4)[CH2:8][CH2:9]1)[CH3:18])[CH3:16].[CH3:17][CH:15]([CH2:14][CH2:13][CH2:12][C@H:11]([C@@H:10]1[C@:19]2([CH3:29])[C@H:7]([C:6]3[CH2:5][CH2:4][C@@:3]4([OH:1])[C@:23]([C:22]=3[CH2:21][CH2:20]2)([CH3:28])[CH2:24][CH2:25][C@@H:26]([OH:27])[CH2:2]4)[CH2:8][CH2:9]1)[CH3:18])[CH3:16]
Reactant: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2C3=C(CC[C@]12C)[C@@]1(C)CCC(=O)[C@H]2O[C@]21CC3
Solvent: C1CCOC1
Product: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2C3=C(CC[C@]12C)[C@@]1(C)CC[C@@H](O)C[C@@]1(O)CC3
Product: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2C3=C(CC[C@]12C)[C@@]1(C)CC[C@H](O)C[C@@]1(O)CC3
Reaction time: 15 h

Procedure:
4α,5-Epoxy-5α-cholest-8-en-3-on (75 mg) is dissolved in 3 ml tetrahydrofuran. Lithiumaluminumhydride (30 mg) is added at room temperature. The reaction mixture is stirred for 15 hours. After aqueous work-up and column chromatography 5β-cholest-8-ene-3β,5β-diol (19 mg) and 5β-cholest-8-ene-3α,5β-diol (24 mg) are isolated.
Reaction SMILES: [NH:1](C(OCC1C=CC=CC=1)=O)[C@H:2]([C:13]([NH:15][CH2:16][CH2:17][CH2:18][CH2:19][NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:14])[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1>CO.CN(C=O)C.[Pd]>[NH2:1][C@H:2]([C:13]([NH:15][CH2:16][CH2:17][CH2:18][CH2:19][NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:14])[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1
Reactant: CC(C)(C)OC(=O)NCCCCNC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)OCc1ccccc1
Agent: [Pd]
Solvent: CO
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)NCCCCNC(=O)[C@@H](N)Cc1c[nH]c2ccccc12

Procedure:
Same procedure as above with Z-Trp-NH(CH2)4NHBoc (1.16 g, 2.28 mmol), 10% Pd/C (242 mg) in MeOH/DMF (10 mL, 1/1). After purification by flash chromatography on silica gel (4-25% MeOH/CH2Cl2), Trp-NH(CH2)4NHBoc was isolated as a white foam (701 mg, 82%). 1H NMR (300 MHz, CDCl3) δ 1.39 (m, 4H, 2 CH2), 1.46 (s, 9H, (CH3)3), 3-3.35 (m, 6H, CH2 Trp, 2 CH2N), 3.7 (m, 1H, CHα), 4.71 (m, 1H, NHBoc), 7.05 (d, J=2 Hz, 1 aromatic H), 7.1 (t, J=7.7 Hz, 1 aromatic H), 7.2 (m, 2H, 1 aromatic H, NH amide), 7.38 (d, J=7.9 Hz, 1 aromatic H), 7.65 (d, J=7.9 Hz, 1 aromatic H), 8.94 (broad s, 1H, NH indole). 13C NMR (75 MHz, CDCl3) δ 26.9, 27.6, 30.8 (2 CH2, CH2 Trp), 28.5 ((CH3)3), 38.7, 40.3 (CH2NHCO, CH2NHBoc), 55.6 (CHα), 79.3 (C(CH3)3), 111.3, 111.4, 118.9, 119.5, 122, 123.3, 127.6, 136.4 (8 aromatic C), 156.2 (CO carbamate), 174.8 (CO amide).
Reaction SMILES: [OH:1]O.[Cl:3][C:4]1[CH:5]=[N:6][CH:7]=[C:8]([Cl:27])[C:9]=1[CH2:10][C:11]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)[CH:14]=1)=[O:12]>C(O)(=O)C.C(OCC)(=O)C>[Cl:27][C:8]1[CH:7]=[N+:6]([O-:1])[CH:5]=[C:4]([Cl:3])[C:9]=1[CH2:10][C:11]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)[CH:14]=1)=[O:12]
Reactant: OO
Reactant: COc1ccc(C(=O)Cc2c(Cl)cncc2Cl)cc1OC1CCCC1
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: COc1ccc(C(=O)Cc2c(Cl)c[n+]([O-])cc2Cl)cc1OC1CCCC1
Temperature: 80 °C
Reaction time: 8 h

Procedure:
Aqueous 27.5% hydrogen peroxide (0.32 mL) is added to a solution of 3-cyclopentyloxy-4-methoxyphenyl 3,5-dichloropyrid-4-ylmethyl ketone (990 mg) in glacial acetic acid (13 mL). The reaction is heated at 80° C. for 8 hours then allowed to stand overnight at room temperature. A further aliquot of aqueous 27.5% hydrogen peroxide (0.32 mL) is added and the mixture heated at 80° C. for 2 hours. The reaction mixture is diluted with ethyl acetate (200 mL) and washed with saturated aqueous sodium bicarbonate until the washings remained basic. The mixture is washed with brine (50 mL), dried (MgSO4), concentrated and the residue recrystallized from a mixture of dichloromethane/ethyl acetate/heptane to give 3,5-dichloro-4-(2-(3-cyclopentyloxy4-methoxyphenyl)-2-oxoethyl)pyridine-N-oxide as a yellow solid, m.p. 179°-180° C. [Elemental analysis: C,57.3; H,4.81; N,3.54; Cl,18.0%; calculated for C19 H19Cl2NO4 : C,57.59; H,4.83; N,3.53; Cl,17.89%.]
Reaction SMILES: Cl.CN(C)CCCN=C=NCC.[CH2:13]([N:15]1[C:21](=[O:22])[C:20]([CH3:24])([CH3:23])[C:19](=[O:25])[N:18]([CH3:26])[C:17]2[CH:27]=[C:28]([O:31][CH2:32][CH2:33][CH2:34][NH:35][CH2:36][CH2:37][C:38]3[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=3)[CH:29]=[CH:30][C:16]1=2)[CH3:14].[C:44](O)(=[O:51])[C:45]1[CH:50]=[CH:49][N:48]=[CH:47][CH:46]=1.ON1C2C=CC=CC=2N=N1>C(#N)C>[CH2:13]([N:15]1[C:21](=[O:22])[C:20]([CH3:24])([CH3:23])[C:19](=[O:25])[N:18]([CH3:26])[C:17]2[CH:27]=[C:28]([O:31][CH2:32][CH2:33][CH2:34][N:35]([CH2:36][CH2:37][C:38]3[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=3)[C:44](=[O:51])[C:45]3[CH:50]=[CH:49][N:48]=[CH:47][CH:46]=3)[CH:29]=[CH:30][C:16]1=2)[CH3:14]
Reactant: CCN1C(=O)C(C)(C)C(=O)N(C)c2cc(OCCCNCCc3cccnc3)ccc21
Reactant: O=C(O)c1ccncc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CC#N
Product: CCN1C(=O)C(C)(C)C(=O)N(C)c2cc(OCCCN(CCc3cccnc3)C(=O)c3ccncc3)ccc21
Temperature: 25 °C
Reaction time: 48 h
Yield: 55.8 %

Procedure:
N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (WSC) (0.16 g, 0.85 mmol) was added to an acetonitrile solution (6 ml) of 1-ethyl-3,3,5-trimethyl-7-[3-(2-pyridin-3-ylethylamino)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.3 g, 0.71 mmol), isonicotinic acid (96 mg, 0.78 mmol), and 1-hydroxybenzotriazole (HOBT) (0.138 g, 0.85 mmol), and then stirred at room temperature for 2 days. The solvent was concentrated under reduced pressure. Ethyl acetate and a sodium hydrogen carbonate aqueous solution were added to the reaction mixture, and stirred for 1 hour. Water was added to the reaction mixture, and extraction with ethyl acetate was conducted. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by medium pressure liquid chromatography (silica gel, dichloromethane:methanol=92:8). The purified product was concentrated under reduced pressure and crystallized from ethyl acetate, diethylether and n-hexane. The precipitated crystals were collected by filtration and dried to thereby obtain 0.21 g (yield: 56%) of N-[3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yloxy)propyl]-N-(2-pyridin-3-ylethyl)isonicotinamide as a white powder.
Reaction SMILES: [C:1]([C:3]1[C:8]([F:9])=[CH:7][CH:6]=[CH:5][N:4]=1)#[N:2].[Na].[Cl-:11].[NH4+:12].C(O)(=O)C>CO>[ClH:11].[C:1]([C:3]1[C:8]([F:9])=[CH:7][CH:6]=[CH:5][N:4]=1)(=[NH:12])[NH2:2]
Reactant: [Cl-]
Reactant: [NH4+]
Reactant: N#Cc1ncccc1F
Agent: [Na]
Solvent: CO
Solvent: CC(=O)O
Product: Cl
Product: N=C(N)c1ncccc1F
Temperature: 20 °C
Reaction time: 72 h

Procedure:
10.30 g (84.355 mmol) of the compound from Example II are dissolved in 30 ml of methanol. The solution is admixed with a solution of 0.40 g (17.391 mmol) of sodium in 65 ml of methanol and stirred at 20° C. for 72 hours. 5.44 g (101.682 mmol) of ammonium chloride (ground in a mortar) and 17.39 mmol (1.04 ml) of acetic acid are added and the mixture is stirred at 40° C. for 28 hours and cooled. Insoluble salt is filtered off with suction (1.78 g) and the filtrate is concentrated, concentrated with acetone and subsequently stirred with acetone, filtered off with suction and washed.
Reaction SMILES: [Br:1][C:2]1[C:10]2[NH:9][C:8](=[O:11])[NH:7][C:6]=2[CH:5]=[C:4]([Br:12])[C:3]=1[C:13]([O:15][CH3:16])=[O:14].[H-].[Na+].[CH2:19](Br)[CH2:20][CH:21]([CH3:23])[CH3:22].Cl>CN(C)C=O.O.C(OCC)(=O)C>[Br:1][C:2]1[C:10]2[N:9]([CH2:19][CH2:20][CH:21]([CH3:23])[CH3:22])[C:8](=[O:11])[N:7]([CH2:10][CH2:2][CH:3]([CH3:13])[CH3:4])[C:6]=2[CH:5]=[C:4]([Br:12])[C:3]=1[C:13]([O:15][CH3:16])=[O:14]
Reactant: COC(=O)c1c(Br)cc2[nH]c(=O)[nH]c2c1Br
Reactant: CC(C)CCBr
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)c1c(Br)cc2c(c1Br)n(CCC(C)C)c(=O)n2CCC(C)C
Temperature: 55 °C
Reaction time: 3 h

Procedure:
In 10 ml of N,N-dimethylformamide are suspended 0.95 g of methyl 4,6-dibromo-2-oxo-2,3-dihydro-1H-benzimidazole-5-carboxylate, 0.24 g of 60% sodium hydride and 0.7 ml of isopentyl bromide. The suspension is stirred at 50-60° C. for 3 hours. The reaction mixture is added to a mixture of ethyl acetate and water, pH is adjusted to 2 with 2 mol/L hydrochloric acid, and the organic layer is separated. The organic layer thus obtained is washed with water and saturated aqueous solution of sodium chloride successively and dried over anhydrous magnesium sulfate, and then the solvent is distilled off under reduced pressure. Thus, 0.71 g of methyl 4,6-dibromo-1,3-diisopentyl-2-oxo-2,3-dihydro-1H-benzimidazole-5-carboxylate is obtained as a light brown-colored solid product.
Reaction SMILES: [CH3:1][N:2]1[C:6](=[O:7])[NH:5][NH:4][C:3]1=[O:8].[C:9]([OH:17])(=[O:16])[CH2:10][CH2:11][CH2:12][CH2:13][CH:14]=[CH2:15].[CH:18]1C=CC=CC=1>>[CH3:18][O:16][C:9]([CH2:10][CH2:11][CH2:12][CH:13]=[CH:14][CH2:15][N:4]1[C:3](=[O:8])[N:2]([CH3:1])[C:6](=[O:7])[NH:5]1)=[O:17]
Reactant: Cn1c(=O)[nH][nH]c1=O
Reactant: c1ccccc1
Reactant: C=CCCCCC(=O)O
Product: COC(=O)CCCC=CCn1[nH]c(=O)n(C)c1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Dinitrogen tetroxide was bubbled through a suspension of 4-methyl-1,2,4-triazolidine-3,5-dione (23.0 g, 0.2 mol) in dichloromethane (250 ml) cooled to 0° C., until a clear, homogenous deep red solution was obtained. This solution was then dried (Na2SO4), filtered, and the filtrate evaporated at room temperature in vacuo to give 4-methyl-1,2,4-triazolidine-3,5-dione (m.p. 105° decomp). To the 4-methyl-1,2,4-triazolidine-3,5-dione (23.0 g, 0.2 mol) dissolved in benzene (200 ml) was added dropwise hept-6-enoic acid (23.0 g, 0.18 mol) in benzene (100 ml) and the resultant solution boiled under reflux in an atmosphere of nitrogen, until a pale yellow solution had been obtained (in 1 hr). The resultant solution was evaporated in vacuo and the residue dissolved in a 10% solution of acetyl chloride in methanol (300 ml). This solution was boiled at reflux for 5 hr, stirred at room temperature overnight and then evaporated in vacuo. The residue (44 g) was chromatographed on silica gel (Merck Kieselgel 60, 900 g) using chloroform; methanol as eluant (0-5% methanol), to afford 1-(6'-methoxycarbonyl-n-hex-2-enyl)-4-methyl-1,2,4-triazolidine-3,5,-dione (19.1 g) m.p. 55-7.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:7]=1.B(O)(O)[C:13]1[CH:18]=[CH:17][C:16]([Br:19])=[N:15][CH:14]=1.N1C=CC=CC=1>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.ClCCl>[Br:19][C:16]1[N:15]=[CH:14][C:13]([NH:1][C:2]2[CH:3]=[N:4][C:5]([C:8]([F:11])([F:9])[F:10])=[CH:6][CH:7]=2)=[CH:18][CH:17]=1
Reactant: OB(O)c1ccc(Br)nc1
Reactant: Nc1ccc(C(F)(F)F)nc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: c1ccncc1
Solvent: ClCCl
Product: FC(F)(F)c1ccc(Nc2ccc(Br)nc2)cn1
Reaction time: 8 h

Procedure:
To a solution of 3-amino-6-trifluoromethyl pyridine (0.25 g, 1.2 mmol, 2.0 equiv) and 2-bromopyridyl-5-boronic acid (0.10 g, 0.62 mmol, 1.0 equiv) in 5 Ml dichloromethane was added pyridine (0.10 Ml, 1.2 mmol, 2.0 equiv), copper (II) acetate (0.17 g, 0.93 mmol, 1.5 equiv) and 4 Å molecular sieves. The heterogeneous reaction mixture was allowed to stir vigorously open to air overnight. The reaction was then filtered through Celite, concentrated in vacuo, and purified by silica gel chromatography to afford the title compound: (M+H)+ 319.9.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([CH:35]=[CH:36][CH:37]=1)[CH2:8][N:9]1[C:13](=[O:14])[C:12]2([CH2:19][CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16][CH2:15]2)[N:11]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[CH2:10]1)=[O:4].Cl>O1CCOCC1>[CH3:34][O:33][C:30]1[CH:29]=[CH:28][C:27]([N:11]2[C:12]3([CH2:15][CH2:16][NH:17][CH2:18][CH2:19]3)[C:13](=[O:14])[N:9]([CH2:8][C:7]3[CH:6]=[C:5]([CH:37]=[CH:36][CH:35]=3)[C:3]([O:2][CH3:1])=[O:4])[CH2:10]2)=[CH:32][CH:31]=1
Reactant: COC(=O)c1cccc(CN2CN(c3ccc(OC)cc3)C3(CCN(C(=O)OC(C)(C)C)CC3)C2=O)c1
Agent: Cl
Solvent: C1COCCO1
Product: COC(=O)c1cccc(CN2CN(c3ccc(OC)cc3)C3(CCNCC3)C2=O)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To tert-butyl 3-(3-(methoxycarbonyl)benzyl)-1-(4-methoxyphenyl)-4-oxo-1,3,8-triazaspiro[4.5]decane-8-carboxylate (0.26 g, 0.51 mmol) was added 4M solution of HCl in dioxane (5 mL). After stirring at room temperature for 3 hours, the reaction mixture was concentrated in vacuo to obtain methyl 3-((1-(4-methoxyphenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate as a hydrochloride salt.
Reaction SMILES: ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[CH3:13][NH:14][C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[C:17]([N:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)[CH:16]=1.CCN(C(C)C)C(C)C.[CH3:39][N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1>C(Cl)Cl.C(Cl)(Cl)Cl>[CH3:13][N:14]([C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[C:17]([N:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)[CH:16]=1)[C:5]([N:43]1[CH2:44][CH2:45][N:40]([CH3:39])[CH2:41][CH2:42]1)=[O:11]
Reactant: CN1CCNCC1
Reactant: CNc1ccc([N+](=O)[O-])c(N2CCCCC2)c1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Solvent: CCN(C(C)C)C(C)C
Product: CN1CCN(C(=O)N(C)c2ccc([N+](=O)[O-])c(N3CCCCC3)c2)CC1
Reaction time: 0.17 h
Yield: 86 %

Procedure:
To a solution of triphosgene (40.6 mg, 0.13 mmol) in 2 mL of CH2Cl2 was added methyl-(4-nitro-3-piperidin-1-yl-phenyl)-amine (88 mg, 0.37 mmol) and DIEA (38 μL, 0.22 mmol) in 2 mL of CH2Cl2 over a 15 min. period. A solution of N-methylpiperazine (1.2 eq, 41 μL) and DIEA (38 μL, 0.22 mmol) in 1.5 mL of CH2Cl2 were then added via cannula and stirring was continued for 10 min. The reaction was diluted with CHCl3 (50 mL) and washed with satd aq NaHCO3 (50 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo to give 115 mg (86%) of the title compound a yellow oil. Mass spectrum (ESI, m/z): Calcd. for C18H27N5O3, 362.2 (M+H), found 362.2.
Reaction SMILES: C1C=CC(/C=C/C[O:10][C@@H:11]2[O:16][C@H:15]([CH2:17][OH:18])[C@@H](O)[C@H:13](O)[C@H:12]2O)=CC=1.[C:22]([O-])(=O)C(C)=C.CC(C1C=C2CC[C@H]3[C@@](C(O)=O)(C)CCC[C@]3(C)[C@H]2CC=1)C>S(Cl)(Cl)=O>[C:11]([O:16][CH2:15][CH2:17][OH:18])(=[O:10])[C:12]([CH3:13])=[CH2:22]
Reactant: C=C(C)C(=O)[O-]
Reactant: OC[C@H]1O[C@@H](OC/C=C/c2ccccc2)[C@H](O)[C@@H](O)[C@@H]1O
Agent: CC(C)C1=CC[C@H]2C(=C1)CC[C@@H]1[C@]2(C)CCC[C@@]1(C)C(=O)O
Solvent: O=S(Cl)Cl
Product: C=C(C)C(=O)OCCO

Procedure:
This example is to prepare quaternary ammonium-containing rosin-derived methacrylate polymers, according to the exemplary method shown in FIG. 2. The method involves the synthesis of methacrylate monomers containing Diels-Alder adduct (anhydride) by esterification, and homopolymer by free radical polymerization. Following the amidation and quaternization reactions, the quaternary ammonium group is introduced. A typical procedure for the synthesis is described as follows: levopimaric acid is dissolved in thionyl chloride and refluxed for 12 h. Thionyl chloride is removed by reduced pressure distillation. The methacrylate monomer containing Diels-Alder adduct (anhydride) 3 is obtained by the addition of excess 2-hydroxyethyl methacrylate (2-HEMA) and using triethylamine as catalyst. The homopolymer is prepared by the radical polymerization of monomer 3 in the presence of the toluene and azoisobutyronitrile (AIBN). The homopolymer is dissolved in ethanol and then added with the dimethylethylenediamine. The mixture is stirred at 85° C. for 5 h and precipitated in diethyl ether to obtain the rosin-derived tertiary ammonium homopolymer. The quaternary ammonium unit 4 is then introduced by the reaction between the rosin-derived tertiary ammonium homopolymer and alkyl halide (e.g. bromoethane, bromohexane, bromooctane and bromododecane) in tetrahydrofuran at 40° C. for 48 h.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8]([OH:13])[C:7](O)=[CH:6]2.[Cl:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][C:22]=1[Cl:23])[NH2:19].CN1C(=O)CCC1.Cl>O1CCOCC1.CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8]([OH:13])[CH:7]=[C:6]2[NH:19][C:18]1[CH:20]=[CH:21][C:22]([Cl:23])=[C:16]([Cl:15])[CH:17]=1
Reactant: COc1ccc2nc(O)c(O)cc2c1
Reactant: Nc1ccc(Cl)c(Cl)c1
Agent: Cl
Solvent: CO
Solvent: CN1CCCC1=O
Solvent: C1COCCO1
Product: COc1ccc2nc(O)cc(Nc3ccc(Cl)c(Cl)c3)c2c1
Yield: 23.9 %

Procedure:
6-Methoxyquinolinediol (2.5 g, 13.08 mmol) and 3,4-dichloroaniline (4.2 g, 26.25 mmol) were placed in a 100 mL Teflon vessel for use with an Ethos 1600 Lab Microwave. NMP was then added (9 mL), followed by HCl in dioxane (5 mL, 4 M). The slurry was irradiated to achieve a 200° C. temperature using a 400 W upper setpoint for 30 min. The mixture was cooled, suspended in methanol (20 mL), and filtered to afford 1.049 g of the title compound. 1H NMR (300 MHz, DMSO): 3.84 (s, 3H), 5.84 (s, 1H), 7.23 (td, ?H, J=8.88, 8.48 Hz), 7.35(tt, ?H, J=8.88, 2.42 Hz), 7.56(d, ?H, J=2.42 Hz), 7.66 (˜s, 2H), 8.71(s, 1H), 11.10(s, 1H).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[NH:10][C:9]=2[C:17]([NH2:19])=[O:18])=[CH:4][CH:3]=1.[F:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[N:27]=[C:28]=[O:29]>>[F:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[NH:27][C:28](=[O:29])[NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[NH:10][C:9]=2[C:17]([NH2:19])=[O:18])=[CH:6][CH:7]=1
Reactant: NC(=O)c1[nH]c2ncccc2c1-c1ccc(N)cc1
Reactant: O=C=Nc1ccccc1F
Product: NC(=O)c1[nH]c2ncccc2c1-c1ccc(NC(=O)Nc2ccccc2F)cc1

Procedure:
66.6 mg of solid beige-coloured 3-{4-[3-(2-fluorophenyl)ureido]phenyl}-1H-pyrrolo[2,3-b]pyridine-2-carboxamide are prepared as described in Example 7 starting with 3-(4-aminophenyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide and 2-fluorophenyl isocyanate.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:7]([CH:10]([CH3:12])[CH3:11])=[CH:6][C:3]=1[C:4]#[N:5].F[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[N+:20]([O-:22])=[O:21].[OH-].[Li+]>CS(C)=O.O>[CH:10]([C:7]1[CH:8]=[CH:9][C:2]([NH:1][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[N+:20]([O-:22])=[O:21])=[C:3]([CH:6]=1)[C:4]#[N:5])([CH3:12])[CH3:11]
Reactant: O=[N+]([O-])c1ccccc1F
Reactant: CC(C)c1ccc(N)c(C#N)c1
Agent: [Li+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: O
Product: CC(C)c1ccc(Nc2ccccc2[N+](=O)[O-])c(C#N)c1
Temperature: 25 °C

Procedure:
Combine 2-amino-5-isopropyl-benzonitrile (3.19 g, 20 mmol), 1-fluoro-2-nitro benzene (2.1 mL, 20 mmol) and lithium hydroxide (1.68 g, 40 mmol) in DMSO (40.0 mL) and heat at 55° C. for 19 hours. Cool to ambient temperature and dilute with water (200 mL). The title compound precipitates as 4.56 g of an orange solid: mp 91-96° C.; mass spectrum (ion spray): m/z=280 (M+1).
Reaction SMILES: [CH3:1][C:2]1[S:6][C:5]([CH2:7][CH2:8][C:9]2[CH:18]=[CH:17][C:12]([CH:13]=[CH:14][CH:15]=O)=[CH:11][CH:10]=2)=[N:4][C:3]=1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[O:25]1[CH2:29][C:28](=[O:30])[NH:27][C:26]1=[O:31].N1CCCCC1>C(O)C>[CH3:1][C:2]1[S:6][C:5]([CH2:7][CH2:8][C:9]2[CH:18]=[CH:17][C:12]([CH:13]=[CH:14][CH:15]=[C:29]3[O:25][C:26](=[O:31])[NH:27][C:28]3=[O:30])=[CH:11][CH:10]=2)=[N:4][C:3]=1[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: O=C1COC(=O)N1
Reactant: Cc1sc(CCc2ccc(C=CC=O)cc2)nc1-c1ccccc1
Solvent: CCO
Solvent: C1CCNCC1
Product: Cc1sc(CCc2ccc(C=CC=C3OC(=O)NC3=O)cc2)nc1-c1ccccc1

Procedure:
A mixture of 4-[2-(5-methyl-4-phenyl-2-thiazolyl)ethyl]cinnamaldehyde (2.5 g), 2,4-oxazolidinedione (1.14 g), piperidine (0.211 g) and ethanol (50 ml) was refluxed under heating conditions for 4 hours. After the reaction mixture was concentrated, chloroform was added to the residue; the mixture was washed with 2 N HCl and water. The chloroform layer was washed with water, dried (MgSO4) and then concentrated to yield 5-[4-[2-(5-methyl-4-phenyl-2-thiazolyl)ethyl]cinnamylidene]-2,4-oxazolidinedione[mixture of the (E)- and (Z)- configurations](0.81 g, 26%), which was then recrystallized from ethyl acetate to yield light yellow prisms having a melting point of 161°-162° C.
Reaction SMILES: CN(C(ON1N=[N:16][C:11]2[CH:12]=[CH:13][CH:14]=[N:15][C:10]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][N:26]([CH3:54])[C:27](=[O:53])[NH:28][C:29]1[CH:30]=[C:31]([C:35]2[CH:36]=[C:37]3[C:41](=[CH:42][CH:43]=2)[N:40]([CH:44]2[CH2:49][CH2:48][CH2:47][CH2:46][O:45]2)[N:39]=[C:38]3[C:50](O)=[O:51])[CH:32]=[N:33][CH:34]=1.C(N(C(C)C)CC)(C)C.NC1C=NC=CC=1>CN(C=O)C>[CH3:25][N:26]([CH3:54])[C:27](=[O:53])[NH:28][C:29]1[CH:30]=[C:31]([C:35]2[CH:36]=[C:37]3[C:41](=[CH:42][CH:43]=2)[N:40]([CH:44]2[CH2:49][CH2:48][CH2:47][CH2:46][O:45]2)[N:39]=[C:38]3[C:50]([NH:16][C:11]2[CH:10]=[N:15][CH:14]=[CH:13][CH:12]=2)=[O:51])[CH:32]=[N:33][CH:34]=1
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Reactant: CN(C)C(=O)Nc1cncc(-c2ccc3c(c2)c(C(=O)O)nn3C2CCCCO2)c1
Agent: F[P-](F)(F)(F)(F)F
Agent: Nc1cccnc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CN(C)C(=O)Nc1cncc(-c2ccc3c(c2)c(C(=O)Nc2cccnc2)nn3C2CCCCO2)c1
Temperature: 25 °C

Procedure:
HATU (0.190 g, 0.5 mmol) was added to a solution of 5-(5-(3,3-dimethylureido)pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxylic acid (CXXIV) (0.39 g, 1.21 mmol) and diisopropylethylamine (0.174 mL, 1.0 mmol) in DMF stirred at room temperature under argon. After stirring 5 min, the solution was added with 3-aminopyridine (CXXV) (0.047 g, 0.5 mmol). The solution was stirred overnight at room temperature under argon. The DMF was removed under reduced pressure, and the residue was treated with water, sonicated briefly and filtered. The solids were washed with cold water and dried at room temperature. The product was purified by column chromatography using a 4 g Thomson normal phase silica gel cartridge (100% DCM 5:95 MeOH:DCM) to afford 5-(5-(3,3-dimethylureido)pyridin-3-yl)-N-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxamide (CXXVI) as an off white solid (323 mg, 0.67 mmol, 55% yield). 1H NMR (DMSO-d6) δ ppm 10.56 (s, 1H), 9.06 (d, J=2.0 Hz, 1H), 8.75 (d, J=1.6 Hz, 1H), 8.64 (s, 1H), 8.53 (d, J=1.6 Hz, 1H), 8.46 (s, 1H), 8.34-8.29 (m, 2H), 8.26 (m, 1H), 8.03 (d, J=7.0 Hz, 1H), 7.88 (dd, J=7.0, 1.2 Hz, 1H), 7.43 (dd, J=6.64, 3.84 Hz, 1H), 6.07 (dd, J=8.0, 1.8 Hz, 1H), 3.98 (m, 1H), 3.82 (m, 1H), 2.98 (s, 6H), 2.63-2.60 (m, 1H), 2.11-2.06 (m, 2H), 1.83-1.81 (m, 1H) 1.52 (m, 2H); ESIMS found for C21H23N5O4 m/z 410.0 (M+H).