Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([Si](C)(C)[O:6][CH2:7][C:8]([N:11]([C:25](=[O:34])[C:26]1[CH:31]=[C:30]([CH3:32])[CH:29]=[C:28]([CH3:33])[CH:27]=1)[NH:12][C:13](=O)[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[C:15]=1[CH2:22][CH3:23])([CH3:10])[CH3:9])(C)(C)C.[F-].[CH2:38]([N+](CCCC)(CCCC)CCCC)CCC.CCOCC>C1COCC1>[CH2:22]([C:15]1[C:16]([O:20][CH3:21])=[CH:17][CH:18]=[CH:19][C:14]=1[C:13]([NH:12][N:11]([C:8]([CH3:9])([CH3:10])[CH2:7][OH:6])[C:25](=[O:34])[C:26]1[CH:31]=[C:30]([CH3:32])[CH:29]=[C:28]([CH3:33])[CH:27]=1)=[CH2:38])[CH3:23]
Reactant: CCc1c(OC)cccc1C(=O)NN(C(=O)c1cc(C)cc(C)c1)C(C)(C)CO[Si](C)(C)C(C)(C)C
Reactant: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOCC
Product: C=C(NN(C(=O)c1cc(C)cc(C)c1)C(C)(C)CO)c1cccc(OC)c1CC
Temperature: 25 °C
Reaction time: 5.5 h
Yield: 67 %

Procedure:
2.78 g (0.00526 mol) of 2-ethyl-3-methoxy-benzoic acid N′-[2-(tert-butyl-dimethyl-silanyloxy)-1,1-dimethyl-ethyl]-N′-(3,5-dimethyl-benzoyl)-hydrazide were dissolved in 24 mL of THF. The mixture was cooled in an ice bath and 6.0 mL (0.006 mol) of a 1 M tetrabutyl ammonium fluoride-solution in THF were added. The reaction was stirred at room temperature for 5-6 hours, and then 100 mL of Et2O were added and the reaction mixture was poured into ice water in a separatory funnel. The aqueous layer was further extracted twice with 25 mL of Et2O and the total ether layer was dried and concentrated. TLC of the product showed a new product (Rf 0.20) below some of the starting material. The product was purified by chromatography, eluting with 40-50% ethyl acetate/hexane to yield 1.42 g of pure 3,5-dimethyl-benzoic acid N′-[1-(2-ethyl-3-methoxy-phenyl)-vinyl]-N-(2-hydroxy-1,1-dimethyl-ethyl)-hydrazide. (67% yield). TLC: Rf=0.20. 1H NMR (CDCl3, 300 MHz) δ (ppm): 7.1-6.8 (m, 5H), 6.0 (d, 1H), 4.3 (d, 1H), 3.78 (s, 3H), 3.5 (d 1H), 2.4 (d, 1H) 2.29 (s, 6H), 2.2 (d, H), 1.56 (s, 3H), 1.45 (s, 3H), 1.00 (t, 3H).
Reaction SMILES: [CH:1]1([C:4]2[C:5]([O:13][CH2:14][CH:15]3[CH2:17][CH2:16]3)=[N:6][CH:7]=[C:8]([CH:12]=2)[C:9]([OH:11])=O)[CH2:3][CH2:2]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.Cl.[F:50][C:51]1[CH:56]=[CH:55][C:54]([N:57]([CH3:59])[NH2:58])=[CH:53][CH:52]=1>CN(C=O)C.O1CCCC1>[F:50][C:51]1[CH:56]=[CH:55][C:54]([N:57]([CH3:59])[NH:58][C:9](=[O:11])[C:8]2[CH:12]=[C:4]([CH:1]3[CH2:2][CH2:3]3)[C:5]([O:13][CH2:14][CH:15]3[CH2:17][CH2:16]3)=[N:6][CH:7]=2)=[CH:53][CH:52]=1
Reactant: CN(N)c1ccc(F)cc1
Reactant: O=C(O)c1cnc(OCC2CC2)c(C2CC2)c1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CN(NC(=O)c1cnc(OCC2CC2)c(C2CC2)c1)c1ccc(F)cc1
Reaction time: 8 h
Yield: 97.5 %

Procedure:
In a 10 mL two-necked flask, the above prepared 5-cyclopropyl-6-cyclopropylmethoxy-nicotinic acid (70 mg, 300 μmol, Eq: 1.00) was combined with tetrahydrofuran (3 mL) and DMF (1 mL) to give a colorless solution. TBTU (145 mg, 450 μmol, Eq: 1.5) and N,N-diisopropylethylamine (194 mg, 262 μl, 1.5 mmol, Eq: 5) were added and the reaction mixture stirred for 10 min at rt, before 1-(4-fluorophenyl)-1-methylhydrazine hydrochloride (63.6 mg, 360 μmol, Eq: 1.2, CAN 1978-54-7) was added and the reaction mixture kept overnight at rt. The reaction mixture was quenched with 1 M HCl (10 mL) and extracted with EtOAc (2×20 mL). The organic layers were washed with 1 M NaOH, then with H2O/NaCl solution, combined, dried over Na2SO4 and concentrated in vacuo. The crude material was eventually purified by flash chromatography (silica gel, 20 g, 15% to 40% EtOAc in heptane) to provide 104 mg of the title product as colorless oil; MS (EI) 354.6 (M−H)−.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:33](=[O:43])[N:34]([CH2:39][CH2:40][CH2:41][CH3:42])[CH2:35][CH2:36][CH2:37][CH3:38])=[N:4][N:5]([C:8]2[CH:16]=[CH:15][C:14]([C:17](=[O:32])[NH:18][S:19]([C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:23]=3)(=[O:21])=[O:20])=[CH:13][C:9]=2[C:10](O)=[O:11])[C:6]=1[CH3:7].[NH2:44][CH2:45][C:46]1[CH:52]=[CH:51][CH:50]=[CH:49][C:47]=1[NH2:48].C(Cl)CCl.ON1C2N=CC=CC=2N=N1>C(Cl)Cl.CN(C=O)C>[NH2:48][C:47]1[CH:49]=[CH:50][CH:51]=[CH:52][C:46]=1[CH2:45][NH:44][C:10](=[O:11])[C:9]1[CH:13]=[C:14]([CH:15]=[CH:16][C:8]=1[N:5]1[C:6]([CH3:7])=[C:2]([Cl:1])[C:3]([C:33](=[O:43])[N:34]([CH2:39][CH2:40][CH2:41][CH3:42])[CH2:35][CH2:36][CH2:37][CH3:38])=[N:4]1)[C:17]([NH:18][S:19]([C:22]1[CH:31]=[CH:30][C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=1)(=[O:21])=[O:20])=[O:32]
Reactant: CCCCN(CCCC)C(=O)c1nn(-c2ccc(C(=O)NS(=O)(=O)c3ccc4ccccc4c3)cc2C(=O)O)c(C)c1Cl
Reactant: NCc1ccccc1N
Agent: On1nnc2cccnc21
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: ClCCCl
Product: CCCCN(CCCC)C(=O)c1nn(-c2ccc(C(=O)NS(=O)(=O)c3ccc4ccccc4c3)cc2C(=O)NCc2ccccc2N)c(C)c1Cl
Temperature: 25 °C
Reaction time: 8 h
Yield: 60 %

Procedure:
To a solution of 2-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-5-(naphthalen-2-ylsulfonylcarbamoyl)benzoic acid (Intermediate 91F, 50 mg, 0.080 mmol) in CH2Cl2 (1.1 mL) and DMF (0.2 mL) was added 2-(aminomethyl)aniline (20 mg, 0.16 mmol) followed by EDC (34 mg, 0.18 mmol) and 1-hydroxy-7-azabenzo-triazole (290 μL, 0.18 mmol, 0.6M solution in DMF). The resulting reaction mixture was stirred at room temperature overnight, then quenched with sat. aq. NH4Cl solution and extracted with EtOAc (3×). The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (gradient from 0% to 10% MeOH/CH2Cl2) provided the title compound (35 mg, 60%) as a pale yellow, oily solid. MS(ESI+) m/z 729.2 (M+H)+.
Reaction SMILES: [CH:1]([C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[NH:9][CH:8]=1)=[CH:2][CH2:3][CH2:4][CH2:5][CH3:6].[H][H]>C(O)C.[Pd]>[CH2:1]([C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[NH:9][CH:8]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: [H][H]
Reactant: CCCCC=Cc1c[nH]c2ccccc12
Agent: [Pd]
Solvent: CCO
Product: CCCCCCc1c[nH]c2ccccc12

Procedure:
3-Hex-1-enyl-1H-indole was dissolved in ethanol and 10% palladium on carbon was added to the solution. The reaction flask was sealed and exposed to hydrogen gas under pressure and was stirred until the hydrogen gas consumption was completely stopped. The reaction mixture was filtered through celite. The solvent was evaporated to afford the product.
Reaction SMILES: Br[C:2]1[C:3](=[O:19])[N:4]([C:8]2[C:13]([CH3:14])=[CH:12][C:11]([N+:15]([O-:17])=[O:16])=[CH:10][C:9]=2[CH3:18])[CH:5]=[CH:6][CH:7]=1.[CH2:20](C([Sn])=C(CCCC)CCCC)[CH2:21]CC>O1CCOCC1.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>[CH3:18][C:9]1[CH:10]=[C:11]([N+:15]([O-:17])=[O:16])[CH:12]=[C:13]([CH3:14])[C:8]=1[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH:20]=[CH2:21])[C:3]1=[O:19]
Reactant: CCCCC([Sn])=C(CCCC)CCCC
Reactant: Cc1cc([N+](=O)[O-])cc(C)c1-n1cccc(Br)c1=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Product: C=Cc1cccn(-c2c(C)cc([N+](=O)[O-])cc2C)c1=O
Temperature: 100 °C
Reaction time: 4 h

Procedure:
132 g (408 mmol) of the compound from Example 59A (alternative synthesis) are dissolved in 1.27 l of anhydrous dioxane, 136 g (428 mmol) of tributylvinyltin and 9.44 g (8.17 mmol) of tetrakis(triphenylphosphine)palladium are added and the mixture is stirred at 100° C. for 4 h. The mixture is allowed to cool and filtered through kieselguhr. The mixture is concentrated to dryness under reduced pressure. The residue is dissolved in dichloromethane and purified by chromatography on silica gel (petroleum ether/ethyl acetate 9:1, then 8:2, then 7:3). The product-containing fractions are combined, the solvents are removed and the residue is triturated with petroleum ether/diethyl ether (10:1). This gives 83 g (75% of theory) of the desired product.
Reaction SMILES: [Cl:1]/[C:2](=[C:6](\[Cl:10])/[C:7]([O-])=[O:8])/[C:3]([O-])=[O:4].[F:11][C:12]1[CH:18]=[CH:17][C:15]([NH3+:16])=[CH:14][CH:13]=1.FC1C=CC([NH3+])=CC=1>O>[F:11][C:12]1[CH:18]=[CH:17][C:15]([N:16]2[C:3](=[O:4])[C:2]([Cl:1])=[C:6]([Cl:10])[C:7]2=[O:8])=[CH:14][CH:13]=1
Reactant: O=C([O-])/C(Cl)=C(/Cl)C(=O)[O-]
Reactant: [NH3+]c1ccc(F)cc1
Solvent: O
Product: O=C1C(Cl)=C(Cl)C(=O)N1c1ccc(F)cc1
Yield: 95 %

Procedure:
5.56g of the thusly resulted 4-fluoroanilinium 2,3-dichloromaleate was suspended in 40 ml of water and allowed to react for 2 hours at reflux temperatures. Upon cooling the reaction mixture, precipitated crystal was separated by filtration to obtain 4.8g of N-(4-fluorophenyl)-2,3-dichloromaleimide melting at 240°-242° C (not corrected) at a yield of 95.0%. An analysis by gas chromatography showed the product had a purity of 99.2%.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)=[CH:3][CH:2]=1.C(N(CC)CC)C.Br[CH2:21][C:22]1[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][CH:23]=1>C(OCC)(=O)C>[N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:8][CH2:9][N:10]([CH2:21][C:22]3[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][CH:23]=3)[CH2:11][CH2:12]2)=[CH:3][CH:2]=1
Reactant: COC(=O)c1ccc(CBr)cc1
Reactant: c1cc(N2CCNCC2)ccn1
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: COC(=O)c1ccc(CN2CCN(c3ccncc3)CC2)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 52.4 %

Procedure:
To a suspension of 4-(4-pyridyl)piperazine (13.1 g) in ethyl acetate (200 ml) was added triethylamine (56 ml) followed dropwise, over 5 hours, by a solution of methyl 4-bromomethylbenzoate (18.41 g). The mixture was stirred at room temperature for 18 hours. The mixture was partitioned between water and ethyl acetate. The organic extracts were dried (MgSO4) and evaporated to give a gum, which was purified by column chromatograhy on silica eluting with increasing concentrations of methanol/dichloromethane to give methyl 4-(4-(4-pyridyl)piperazin-1-ylmethyl)benzoate (13.1 g) as a solid;
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([I:8])[C:3]=1CC#N.[OH:12]S(O)(=O)=O.[O:17]1[CH2:22][CH2:21]OCC1>O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([I:8])[C:3]=1[CH2:21][C:22]([OH:17])=[O:12]
Reactant: N#CCc1c(Cl)cccc1I
Reactant: O=S(=O)(O)O
Reactant: C1COCCO1
Solvent: O
Product: O=C(O)Cc1c(Cl)cccc1I
Temperature: 115 °C
Reaction time: 2 h

Procedure:
A mixture of 2-(2-chloro-6-iodophenyl)acetonitrile (10 g, 36 mmol) in 20 mL dioxane was treated with 25 mL 9M H2SO4. The mixture was stirred at 115° C. for 2 hours. The mixture was transferred into a sealed tube and heated to 150° C. and stirred for 2 hours. The mixture was then cooled to room temperature and diluted with 100 mL water. The mixture was extracted with EtOAc (3×50 mL). The combined organic layers were washed with saturated NaCl (20 mL), dried over sodium sulfate, and concentrated to give crude product 10.3 g as pale yellow solid. MS m/e: (M+H)+ 297.
Reaction SMILES: [C:1]([CH:7]([OH:26])[C@H:8]1[O:12][C@@H:11]([N:13]2[CH:24]=[C:19]([C:20]([F:23])([F:22])[F:21])[C:17](=[O:18])[NH:16][C:14]2=[O:15])[CH2:10][C@@H:9]1[OH:25])(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].Cl.[C:28](Cl)(=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[N:31][CH:30]=1>N1C=CC=CC=1>[N:31]1[CH:32]=[CH:33][CH:34]=[C:29]([C:28]([C@@:9]2([OH:25])[C@@H:8]([CH:7]([C:1](=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3])[OH:26])[O:12][C@@H:11]([N:13]3[CH:24]=[C:19]([C:20]([F:21])([F:22])[F:23])[C:17](=[O:18])[NH:16][C:14]3=[O:15])[CH2:10]2)=[O:35])[CH:30]=1
Reactant: CC(C)(C)C(=O)C(O)[C@H]1O[C@@H](n2cc(C(F)(F)F)c(=O)[nH]c2=O)C[C@@H]1O
Reactant: O=C(Cl)c1cccnc1
Agent: Cl
Solvent: c1ccncc1
Product: CC(C)(C)C(=O)C(O)[C@H]1O[C@@H](n2cc(C(F)(F)F)c(=O)[nH]c2=O)C[C@@]1(O)C(=O)c1cccnc1
Temperature: 25 °C
Reaction time: 72 h
Yield: 87.1 %

Procedure:
To a stirring solution of 450 mg of 5'-pivaloyltrifluorothymidine in 10 mL of pyridine was added 1.0 g of nicotinoyl chloride hydrochloride under ice-cooling. The reaction mixture was stirred at room temperature for 3 days, then was poured into 100 mL of ice water and extracted with 100 mL of ethyl acetate. The extract was washed with water, dried over anhydrous sodium sulfate and then evaporated in vacuo to give an oil. Crystallization from n-hexane afforded 500 mg (87%) of colorless needles melting at 175°-177° C. The product had the structure ##STR134## as further confirmed by NMR spectral analysis.
Reaction SMILES: [NH2:1][C:2]1[N:24]=[C:5]2[NH:6][C:7]([CH3:23])=[C:8]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:9]([C:10]3[CH:15]=[CH:14][C:13]([C:16]#[N:17])=[CH:12][CH:11]=3)[N:4]2[N:3]=1.[C:25]1(=O)[O:30][C:28](=[O:29])[C:27]2=[CH:31][CH:32]=[CH:33][CH:34]=[C:26]12.C(N(CC)CC)C>C1(C)C=CC=CC=1.N1C=CC=CC=1>[C:16]([C:13]1[CH:12]=[CH:11][C:10]([CH:9]2[N:4]3[N:3]=[C:2]([N:1]4[C:28](=[O:29])[C:27]5[C:26](=[CH:34][CH:33]=[CH:32][CH:31]=5)[C:25]4=[O:30])[N:24]=[C:5]3[NH:6][C:7]([CH3:23])=[C:8]2[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:15][CH:14]=1)#[N:17]
Reactant: CCOC(=O)C1=C(C)Nc2nc(N)nn2C1c1ccc(C#N)cc1
Reactant: O=C1OC(=O)c2ccccc21
Solvent: c1ccncc1
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: CCOC(=O)C1=C(C)Nc2nc(N3C(=O)c4ccccc4C3=O)nn2C1c1ccc(C#N)cc1
Reaction time: 12 h

Procedure:
Under argon, ethyl 2-amino-7-(4-cyanophenyl)-5-methyl-4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylate (5.0 g, 15.4 mmol) and phthalic anhydride (3.4 g, 23.1 mmol, 1.5 eq.) were dissolved in a mixture of toluene (400 ml) and pyridine (200 ml), triethylamine (42 μl, 0.3 mmol, 0.2 eq.) was added and the mixture was heated under reflux for 12 h. The reaction mixture was then concentrated under reduced pressure. The residue was taken up in ethyl acetate (600 ml) and extracted twice with saturated sodium bicarbonate solution (150 ml each). The organic phase was washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was suspended in ethanol (100 ml) and stirred for 12 h, and the solid was then filtered off and dried under high vacuum. This gave 6.67 g (95% of theory) of the title compound.
Reaction SMILES: [NH2:1][C:2]1[CH:12]=[CH:11][C:10]([N:13]2[CH2:18][CH2:17][N:16]([C:19](=[O:30])[C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=3)[CH2:15][CH2:14]2)=[CH:9][C:3]=1[CH:4]=[CH:5][C:6]([OH:8])=O.[H][H]>CN(C=O)C.[C].[Pd]>[CH3:29][O:28][C:22]1[CH:21]=[C:20]([CH:25]=[CH:24][C:23]=1[O:26][CH3:27])[C:19]([N:16]1[CH2:15][CH2:14][N:13]([C:10]2[CH:9]=[C:3]3[C:2](=[CH:12][CH:11]=2)[NH:1][C:6](=[O:8])[CH2:5][CH2:4]3)[CH2:18][CH2:17]1)=[O:30]
Reactant: [H][H]
Reactant: COc1ccc(C(=O)N2CCN(c3ccc(N)c(C=CC(=O)O)c3)CC2)cc1OC
Agent: [Pd]
Solvent: CN(C)C=O
Product: COc1ccc(C(=O)N2CCN(c3ccc4c(c3)CCC(=O)N4)CC2)cc1OC
Yield: 60.3 %

Procedure:
2-Amino-5-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]cinnamic acid (5 g) was dissolved in DMF (50 ml), and 5% palladium-carbon (0.5 g) was added to the solution. The mixture was reacted at 80° C. for 4 hours using Parr's apparatus at a hydrogen gas pressure of 3 kg/cm2. After removing hydrogen gas, the content was taken out. After removing the catalyst, the reaction mixture was concentrated to half the original volume and poured into a large volume of water. Crystals which precipitated were collected by filtration and recrystallized from ethanol-chloroform to give 2.9 g of 6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-3,4-dihydrocarbostyril, m.p. 238°-239.5° C., colorless granules.
Reaction SMILES: FC1C=C(CN)C=NC=1.[N:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH2:16][NH2:17].[CH2:18]([N:22]1[CH2:26][CH2:25][N:24]([C:27]2[S:28][C:29]([C:33](O)=[O:34])=[C:30]([CH3:32])[N:31]=2)[C:23]1=[O:36])[CH:19]([CH3:21])[CH3:20]>>[CH2:18]([N:22]1[CH2:26][CH2:25][N:24]([C:27]2[S:28][C:29]([C:33]([NH:17][CH2:16][C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][N:10]=3)=[O:34])=[C:30]([CH3:32])[N:31]=2)[C:23]1=[O:36])[CH:19]([CH3:21])[CH3:20]
Reactant: NCc1ccccn1
Reactant: Cc1nc(N2CCN(CC(C)C)C2=O)sc1C(=O)O
Agent: NCc1cncc(F)c1
Product: Cc1nc(N2CCN(CC(C)C)C2=O)sc1C(=O)NCc1ccccn1
Yield: 46 %

Procedure:
Following the procedure as describe in Example 12, making variations as required to replace (5-fluoropyridin-3-yl)methanamine with pyridin-2-ylmethanamine to react with 2-(3-isobutyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid in place of 2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid, the title compound was obtained as a colorless solid in 46% yield: 1H NMR (300 MHz, CDCl3) δ 8.52-8.50 (m, 1H), 7.65-7.60 (m, 1H), 7.26-7.23 (m, 1H), 7.18-7.14 (m, 1H), 7.11-7.06 (m, 1H), 4.66 (d, J=5.6 Hz, 2H), 4.10-4.05 (m, 2H), 3.58-3.53 (m, 2H), 3.09 (d, J=7.5 Hz, 2H), 2.61 (s, 3H), 1.94-1.85 (m, 1H), 0.91 (d, J=6.4 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 162.5, 157.6, 155.8, 155.6, 152.3, 148.8, 136.5, 122.2, 121.7, 117.7, 51.4, 44.5, 42.7, 41.9, 26.6, 19.8, 17.1; MS (ES+) m/z 373.8 (M+1).
Reaction SMILES: C[C:2]1[CH:7]=[C:6](C)[CH:5]=[C:4]([CH3:9])[C:3]=1S([O-])(=O)=O.[NH2:14][N+:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=1[NH2:22].C(Cl)(=O)C1C=CC=CC=1>N1C=CC=CC=1>[Br:21][C:18]1[CH:19]=[CH:20][N:15]2[N:14]=[C:9]([C:4]3[CH:3]=[CH:2][CH:7]=[CH:6][CH:5]=3)[N:22]=[C:16]2[CH:17]=1
Reactant: Cc1cc(C)c(S(=O)(=O)[O-])c(C)c1
Reactant: Nc1cc(Br)cc[n+]1N
Solvent: O=C(Cl)c1ccccc1
Solvent: c1ccncc1
Product: Brc1ccn2nc(-c3ccccc3)nc2c1
Reaction time: 2 h
Yield: 61.5 %

Procedure:
1,2-Diamino-4-bromopyridinium 2,4,6-trimethylbenzenesulfonate (15.6 g, 40.2 mmole) in pyridine (106 ml) is heated overnight at 100° C. with benzoyl chloride (9.4 ml, 80 mmole) giving a redbrown solution and after 2 hrs a brown suspension. The reaction mixture is concentrated in vacuo and the residue is triturated for 2.5 hr in sat. aqueous ammonium chloride solution (300 ml), while neutralizing to pH 6-7 with sat. aqueous sodium bicarbonate solution. The solid is collected by filtration, washed with water (40 ml) and dried affording 7-bromo-2-phenyl-[1,2,4]triazolo[1,5-a]pyridine (6.78 g, 61.6%) as an off-white solid. mp.: 189-191° C. MS: m/z=276.1, 274.2 (M+H+).
Reaction SMILES: [CH:1]([C:3]1[NH:7][C:6]([C:8]([OH:10])=O)=[CH:5][C:4]=1[CH3:11])=[O:2].[NH2:12][CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>C(#N)C>[N:15]1([CH2:14][CH2:13][NH:12][C:8]([C:6]2[NH:7][C:3]([CH:1]=[O:2])=[C:4]([CH3:11])[CH:5]=2)=[O:10])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1
Reactant: NCCN1CCOCC1
Reactant: Cc1cc(C(=O)O)[nH]c1C=O
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CC#N
Solvent: ClCCCl
Product: Cc1cc(C(=O)NCCN2CCOCC2)[nH]c1C=O
Temperature: 25 °C
Reaction time: 12 h
Yield: 52.2 %

Procedure:
To a suspension of 5-formyl-4-methyl-1H-pyrrole-2-carboxylic acid (2 g, 13 mmol) in acetonitrile was added 4-(2-aminoethyl)morpholine (1.9 mL, 14 mmol), EDC (2.7 g, 14 mmol), HOBt (1.9 g, 14 mmol) and triethylamine (3.6 mL, 26 mmol) sequentially. The reaction mixture was stirred at room temperature for 12 hours and concentrated at reduced pressure. The residue was dissolved in 300 mL of 1N hydrogen chloride solution. The aqueous layer was washed with 150 mL of ethyl acetate twice and basified with sodium bicarbonate. The product was then extracted with 250 mL of dichloromethane twice, dried over MgSO4, and concentrated to afford 1.8 g (53%) of 5-formyl-4-methyl-1H-pyrrole-2-carboxylic acid (2-morpholin4-yl-ethyl)-amide as a yellowish solid. 1H NMR (300 MHz, DMSO-d6) δ 12.19 (br s, 1H, NH), 9.72 (s, 1H, CHO), 8.29 (br t, J=6.6 Hz, 1H, CONH), 6.65 (d, J=1.7 Hz, 1H), 3.5 (m, 4H), 3.3 (m, 2H, CONHCH2), 2.4 (m, 6H), 2.28 (s, 3H, CH3). MS m/z 265 [M+].
Reaction SMILES: [O:1]=C[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O.O[CH2:14][CH:15]([CH2:17][OH:18])O.CC1C=[N:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=1>CS(C)=O>[N:28]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=[CH:14][C:15]=1[C:17]([OH:18])=[O:1]
Reactant: Cc1cnc2ccccc2n1
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Reactant: OCC(O)CO
Solvent: CS(C)=O
Product: O=C(O)c1cnc2ccccc2n1
Reaction time: 48 h

Procedure:
Cells of various microorganisms were grown in the tubes containing 2.5 mL of the dextrose, nutrisoy flour medium as described in EXAMPLE I. Individual tubes were inoculated with spores or vegetative cells (about 1% v/v of spore or vegetative cell stock culture) of various microorganisms stored as frozen glycerol suspensions, and incubated at about 29° C. with agitation (210 rpm) on a rotary shaker. After about 48 hours, 0.05 mL of a 10 mg/mL solution of 2-methylquinoxaline in DMSO was added to each tube. After about 4 days incubation, the contents of each tube were extracted, and the individual extracts were analyzed by HPLC as described in EXAMPLE I. The yields of 2-quinoxalinecarboxylic acid were determined by HPLC and the results are summarized in TABLE 5.
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.[CH2:9]([O:11][C:12]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[CH2:16][CH2:15]1)=[O:13])[CH3:10]>C1(C)C=CC=CC=1.CC1C=CC(S(O)(=O)=O)=CC=1>[CH2:9]([O:11][C:12]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[CH:16]([Br:1])[CH2:15]1)=[O:13])[CH3:10]
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOC(=O)C1CCC(=O)CC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: CCOC(=O)C1CCC(=O)C(Br)C1
Yield: 140.8 %

Procedure:
To a stirred solution of N-bromosuccinimide (1.11 g, 6.274 mmol), PTSA (0.108 g, 0.627 mmol) in toluene (15 mL) was added 4-oxocyclohexanecarboxylic acid ethyl ester (1.068 g, 6.274 mmol) under nitrogen atmosphere and the reaction was refluxed for 2 hrs. Toluene was evaporated under reduced pressure and the residue was partitioned between water (50 mL) and ethyl acetate (50 mL). The layers were separated; the organic layer was washed with sat. sodium bicarbonate solution followed by brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to get title the compound (2.2 g) which was carried without purification for the next step.
Reaction SMILES: Br[C:2]1[N:6]([CH3:7])[C:5]([C:8]([O:10][CH3:11])=[O:9])=[CH:4][CH:3]=1.[C:12]1(B(O)O)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C([O-])([O-])=O.[Na+].[Na+].C(Cl)Cl>COCCOC.O.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>[CH3:7][N:6]1[C:2]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:3][CH:4]=[C:5]1[C:8]([O:10][CH3:11])=[O:9]
Reactant: COC(=O)c1ccc(Br)n1C
Reactant: OB(O)c1ccccc1
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: [Na+]
Solvent: O
Solvent: ClCCl
Solvent: COCCOC
Product: COC(=O)c1ccc(-c2ccccc2)n1C
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 96 %

Procedure:
The product from step 152a is added to a solution of tetrakis(triphenylphosphine)palladium(0) (0.530 g, 0.459 mmol) in 90 mL of ethylene glycol dimethyl ether. The resulting solution is stirred under nitrogen for 5 min and then phenylboronic acid (1.34 g, 11.0 mmol) is added followed by a solution of Na2CO3 (19.5 g, 183 mmol) in 90 mL of H2O. The mixture is heated at reflux for 24 hours. The reaction mixture is allowed to cool to rt, 100 mL of CH2Cl2 is added, and the layers are separated. The aqueous layer is extracted with CH2Cl2 (3×50 mL) and combined organic layers are dried over MgSO4, filtered, and concentrated in vacuo. The crude product is purified by flash column chromatography (5% EtOAc in hexane) to give 1.89 g of methyl 1-methyl-5-phenyl-1H-pyrrole-2-carboxylate as a yellow oil (96% yield). MS for C13H13NO2 (ESI) (M+H)+ m/z 216.1.