Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC(F)(F)C(O)=O.[N+:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[CH:29]=[CH:28][C:20]([C:21]([O:23]C(C)(C)C)=[O:22])=[C:19]([NH:30][C:31]([C:33]2[CH:34]=[N:35][CH:36]=[C:37]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[CH:38]=2)=[O:32])[CH:18]=1)([O-:10])=[O:9]>>[N+:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[CH:29]=[CH:28][C:20]([C:21]([OH:23])=[O:22])=[C:19]([NH:30][C:31]([C:33]2[CH:34]=[N:35][CH:36]=[C:37]([C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)[CH:38]=2)=[O:32])[CH:18]=1)([O-:10])=[O:9]
Reactant: CC(C)(C)OC(=O)c1ccc(-c2ccccc2[N+](=O)[O-])cc1NC(=O)c1cncc(-c2ccccc2)c1
Solvent: O=C(O)C(F)(F)F
Product: O=C(Nc1cc(-c2ccccc2[N+](=O)[O-])ccc1C(=O)O)c1cncc(-c2ccccc2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 77.9 %

Procedure:
Trifluoroacetic acid (3.0 mL) was added to tert-butyl 4-(2-nitrophenyl)-2-(5-phenylpyridine-3-carboxamido)benzoate (68 mg), followed by stirring at room temperature for 1 hour. The solvent was evaporated under reduced pressure, and diisopropyl ether was added to the obtained residue. The solid substance was collected by filtration, and dioxane (3.0 mL) and a 2 mol/L aqueous solution of sodium hydroxide (0.053 mL) were sequentially added to the obtained solid substance, followed by stirring at room temperature for 1 hour and 50 minutes. Water was added to the reaction mixture. After adjusting the pH to 6.3 with 1 mol/L hydrochloric acid, the solid substance was collected by filtration to obtain 47 mg of 4-(2-nitrophenyl)-2-(5-phenylpyridine-3-carboxamido)benzoic acid as a white solid.
Reaction SMILES: Br[C:2]1[N:3]=[C:4]([Br:11])[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[CH:7]=1.[CH3:12][NH2:13]>>[Br:11][C:4]1[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[CH:7]=[C:2]([NH:13][CH3:12])[N:3]=1
Reactant: Brc1cn2ccnc2c(Br)n1
Reactant: CN
Product: CNc1cn2ccnc2c(Br)n1
Reaction time: 12 h
Yield: 96 %

Procedure:
A mixture of 100 mg (0.36 mmol) of 6.8-dibromoimidazo[1,2-a]pyrazine in 5 ml of a 25% aqueous methylamine solution was stirred for 12 h. After the removal of solvent, the residue was purified by chromatography (silica column eluted with ether) to provide 78 mg (yield: 96%) of 8-bromo-6-methylaminoimidazo[1,2-a]pyrazine. ESI-MS (M+H+): 227.
Reaction SMILES: [B:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[C:14]([S:21][CH3:22])[N:13]=[C:12]2[CH2:23][CH2:24][CH2:25][CH3:26])=[CH:6][CH:5]=1)([OH:3])[OH:2].[C:27]1([C:29](=[CH:31][CH:32]=[CH:33][CH:34]=1)O)O>>[CH2:23]([C:12]1[N:11]([CH2:10][C:7]2[CH:8]=[CH:9][C:4]([B:1]3[O:2][C:34]4[CH:33]=[CH:32][CH:31]=[CH:29][C:27]=4[O:3]3)=[CH:5][CH:6]=2)[C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[C:14]([S:21][CH3:22])[N:13]=1)[CH2:24][CH2:25][CH3:26]
Reactant: Oc1ccccc1O
Reactant: CCCCc1nc(SC)c(C(=O)OCC)n1Cc1ccc(B(O)O)cc1
Product: CCCCc1nc(SC)c(C(=O)OCC)n1Cc1ccc(B2Oc3ccccc3O2)cc1

Procedure:
Using the procedure of Preparation 4, 1 g of ethyl 1-[(4-boronophenyl)-methyl]-2-butyl-4-(methylthio)-1H-imidazole-5-carboxylate and 0.293 g of catechol were reacted to obtain the desired product.
Reaction SMILES: Cl[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[S:9])=[CH:6][N:5]=[C:4]([CH3:13])[N:3]=1.[CH3:14][NH2:15].O>ClCCl.C(O)C>[CH3:14][NH:15][C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[S:9])=[CH:6][N:5]=[C:4]([CH3:13])[N:3]=1
Reactant: CN
Reactant: CCOC(=S)c1cnc(C)nc1Cl
Solvent: ClCCl
Solvent: O
Solvent: CCO
Product: CCOC(=S)c1cnc(C)nc1NC
Reaction time: 0.5 h
Yield: 97 %

Procedure:
A solution of 20 g (86 mmol) of ethyl 4-chloro-2-methylthiopyrimidine-5-carboxylate (Aldrich Chemical Co., Milwaukee, Wis., USA) in 250 mL of dichloromethane was cooled to 0° C. and treated slowly with 35 mL (281 mmol) of a 33% solution of methylamine in ethanol. After stirring for 30 minutes, 150 mL of water was added and the phases were separated. The organic phase was dried over magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure to give 19 g (97%) of ethyl 4-methylamino-2-methylthiopyrimidine-5-carboxylate as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[O:19][CH3:20])[C:7]([CH3:21])=[C:6]2[CH2:22][C:23]([OH:25])=[O:24].[CH2:26](OC(=O)CC1C2C(=CC=C(OC)C=2)NC=1C)[CH3:27].[H-].[Na+].COC1C=CC=CC=1CCl>>[CH2:26]([O:24][C:23](=[O:25])[CH2:22][C:6]1[C:5]2[C:9](=[CH:10][CH:11]=[C:3]([O:2][CH3:1])[CH:4]=2)[N:8]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[O:19][CH3:20])[C:7]=1[CH3:21])[CH3:27]
Reactant: CCOC(=O)Cc1c(C)[nH]c2ccc(OC)cc12
Reactant: COc1ccc2c(c1)c(CC(=O)O)c(C)n2Cc1ccccc1OC
Agent: COc1ccccc1CCl
Agent: [H-]
Agent: [Na+]
Product: CCOC(=O)Cc1c(C)n(Cc2ccccc2OC)c2ccc(OC)cc12
Yield: 52 %

Procedure:
5-Methoxy-1-[(2-methoxyphenyl)methyl]-2-methyl-1H-indole-3-acetic acid. Using the procedure described in Example 1, Part F, 2.0 g (8.12 mmol) of 5-methoxy-2-methyl-1H-indole-3-acetic acid ethyl ester was reacted with 325 mg (8.12 mmol) of 60% NaH/mineral oil and 1.272 g (8.12 mmol) of ortho-methoxybenzylchloride and after chromatography on silica (eluting with 25% EtOAc/hexane) there was obtained 1.74 g (52%) of 5-methoxy-1-[(2-methoxyphenyl)methyl]-2-methyl-1H-indole-3-acetic acid ethyl ester as an oil. This oil (1.74 g) in 30 mL of MeOH and 15 mL of 1N NaOH was heated to maintain reflux for 20 hours. The mixture was diluted with water, extracted with EtOAc, then the EtOAc solution was dried (Na2SO4), the solvent removed at reduced pressure and the residue crystallized from MeOH to give 1.1 g (68% yield) of 5-methoxy-1-[(2-methoxyphenyl)methyl]-2-methyl-1H-indole-3-acetic acid, mp 176°-180° C.
Reaction SMILES: S(Cl)([Cl:4])(=O)=O.[CH:6]([O:9][P:10]([CH:16]([CH:18]=[O:19])[CH3:17])(=[O:15])[O:11][CH:12]([CH3:14])[CH3:13])([CH3:8])[CH3:7]>C(Cl)(Cl)(Cl)Cl>[CH:12]([O:11][P:10]([C:16]([CH:18]=[O:19])([Cl:4])[CH3:17])(=[O:15])[O:9][CH:6]([CH3:7])[CH3:8])([CH3:13])[CH3:14]
Reactant: CC(C)OP(=O)(OC(C)C)C(C)C=O
Reactant: O=S(=O)(Cl)Cl
Solvent: ClC(Cl)(Cl)Cl
Product: CC(C)OP(=O)(OC(C)C)C(C)(Cl)C=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 93.5 %

Procedure:
At 10° C., a solution of 14 g (0.104 mole) of sulfuryl chloride in 50 ml of carbon tetrachloride is dripped into a solution of 22.2 g (0.1 mole) of α-formylethanephosphonic acid diisopropyl ester in 150 ml of carbon tetrachloride. The reaction mixture is stirred for 3 hours at room temperature and the solvent is then distilled off under reduced pressure. The residue is taken up in ether, washed with 5% sodium bicarbonate solution and then with saturated sodium chloride solution, and dried over sodium sulfate. The ether is stripped off under reduced pressure. There is obtained 24 g (93.5% of theory) of α-formyl-α-chloroethanephosphonic acid diisopropyl ester.
Reaction SMILES: [C:1](#[N:5])[CH2:2][C:3]#[N:4].[N-:6]([C:9]#[N:10])[C:7]#[N:8].[Na+].CN(C)C(=O)N(C)C>CC(O)CC>[NH2:8][C:7]([NH:6][C:9]#[N:10])=[C:2]([C:1]#[N:5])[C:3]#[N:4]
Reactant: N#CCC#N
Reactant: N#C[N-]C#N
Agent: [Na+]
Solvent: CN(C)C(=O)N(C)C
Solvent: CCC(C)O
Product: N#CNC(N)=C(C#N)C#N
Temperature: 145 °C
Reaction time: 1 h
Yield: 93.9 %

Procedure:
To a 500 ml flask is charged 13.2 gm (0.2 mole) of malononitrile, 18.2 gm (0.2 mole) of sodium dicyanamide and 80 ml of tetramethylurea. The stirred mixture is heated at 145° C. for 2.5 hours; then cooled to about room temperature. The slurry is diluted with 300 ml 2-butanol and stirred in an ice bath for one hour. The solids are filtered, washed with 50 ml of 2-butanol. The product is dried overnight at 70° C. in a vacuum oven to yield 25.0 gm of 1-amino-1-cyanamido-2,2-dicyanoethylene, sodium salt, 80.7% pure or a 65.0% yield.
Reaction SMILES: [C:1]1([CH:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:13]([O:17][CH2:18][CH3:19])(=[O:16])[CH:14]=[CH2:15]>C(OCC)C>[CH2:18]([O:17][C:13](=[O:16])[CH2:14][CH2:15][N:10]1[CH2:9][CH2:8][CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:12][CH2:11]1)[CH3:19]
Reactant: C=CC(=O)OCC
Reactant: c1ccc(C2CCNCC2)cc1
Solvent: CCOCC
Product: CCOC(=O)CCN1CCC(c2ccccc2)CC1
Reaction time: 8 h
Yield: 95 %

Procedure:
25.0 g of 4-phenylpiperidine (0.15 mol) are placed in 50 ml of diethyl ether and, while stirring, 15.1 g of ethyl acrylate are gradually added thereto. With a slight increase in temperature, a clear solution forms. After standing overnight at room temperature, the ether is distilled off. The oil remaining behind is the crude 3-(4-phenylpiperidino)-propionic acid ethyl ester (yield approx. 95%).
Reaction SMILES: C(N(CC)CC)C.[CH3:8][N:9]1[C:21]([CH2:22][CH:23]([CH3:25])[CH3:24])=[C:20]2[C:11]([C:12]([NH2:26])=[N:13][C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=32)=[N:10]1.[C:27](Cl)(=[O:29])[CH3:28]>ClCCl>[CH2:22]([C:21]1[N:9]([CH3:8])[N:10]=[C:11]2[C:20]=1[C:19]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[N:13]=[C:12]2[NH:26][C:27](=[O:29])[CH3:28])[CH:23]([CH3:24])[CH3:25]
Reactant: CC(C)Cc1c2c(nn1C)c(N)nc1ccccc12
Reactant: CC(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)Nc1nc2ccccc2c2c(CC(C)C)n(C)nc12
Temperature: 4 °C
Yield: 56 %

Procedure:
Triethylamine (0.49 mL, 3.53 mmol) was added to a suspension of 2-methyl-1-(2-methylpropyl)-2H-pyrazolo[3,4-c]quinolin-4-amine (prepared as described in Example 3) (0.75 g, 2.95 mmol) in dichloromethane (30 mL) and cooled to 4° C. Acetyl chloride (0.255 g, 3.24 mmol) was added in dichloromethane (5 mL) dropwise over 5 minutes to the reaction mixture and maintained at ambient temperature for 16 hours. The reaction mixture was diluted with dichloromethane (25 mL) and washed sequentially with water (25 mL), 4% sodium bicarbonate (2×25 mL), water (25 mL), and brine (25 mL). The combined organic layers were concentrated under reduced pressure and the residue was purified via column chromatography on silica gel (80 g, eluting with 0-20% CMA/chloroform), concentrated under reduced pressure, and recrystallized from diethyl ether to yield 0.49 g of N-(1-isobutyl-2-methyl-2H-pyrazolo[3,4-c]quinolin-4-yl)acetamide as white crystals, mp 130-131° C.
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH:11]2[CH2:13][CH2:14][O:15][C:16](=[O:17])[CH:10]2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[BH4-]>C1COCC1>[CH2:1]([N:8]1[CH2:9][CH:10]([CH2:16][OH:17])[CH:11]([CH2:13][CH2:14][OH:15])[CH2:12]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1OCCC2CN(Cc3ccccc3)CC12
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCCC1CN(Cc2ccccc2)CC1CO
Temperature: 25 °C
Reaction time: 7 h
Yield: 80.5 %

Procedure:
To a solution of 2-benzylhexahydropyrano[3,4-c]pyrrol-4(2H)-one (2.82 g) in THF (70 mL) was added LiBH4 (0.40 g) at 0° C. under N2. The reaction mixture was stirred for 7 h at room temperature and concentrated in vacuo. The residue was dissolved in MeOH (50 mL) and heated to reflux for 16 h. The mixture was concentrated in vacuo and redissolved in EtOAc (100 mL), then washed with water followed by brine, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo to give the title compound (2.31 g, 80.62%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 236.3 (M+1).
Reaction SMILES: C1C2C(CO[C:16]([NH:18][C@H:19]([C:36]([O:38][CH3:39])=[O:37])[CH2:20][S:21][CH2:22][CH:23]([C:28](=[O:35])[C:29]3[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=3)[CH2:24][C:25]([OH:27])=[O:26])=[O:17])C3C(=CC=CC=3)C=2C=CC=1.[F:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1[N:47]=C=O>>[F:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1[NH:47][C:16]([NH:18][C@H:19]([C:36]([O:38][CH3:39])=[O:37])[CH2:20][S:21][CH2:22][CH:23]([C:28](=[O:35])[C:29]1[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=1)[CH2:24][C:25]([OH:27])=[O:26])=[O:17]
Reactant: O=C=Nc1ccccc1F
Reactant: COC(=O)[C@H](CSCC(CC(=O)O)C(=O)c1cccnc1)NC(=O)OCC1c2ccccc2-c2ccccc21
Product: COC(=O)[C@H](CSCC(CC(=O)O)C(=O)c1cccnc1)NC(=O)Nc1ccccc1F
Yield: 13 %

Procedure:
The title compound was prepared from 3-({(2R)-2-[(fluoren-9-ylmethoxy)carbonylamino]-2-(methoxycarbonyl)ethylthio}methyl)-4-oxo-4-(3-pyridyl)butanoic acid and 2-fluorophenyl isocyanate as described in Example 16 in a 13% yield; ESMS, (M+1)+464.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][CH2:7][N:8]1[C:12](=[O:13])[C:11]([CH3:15])([CH3:14])[NH:10][C:9]1([CH3:17])[CH3:16].C(O[Cl:23])(C)(C)C>CO>[Cl:23][N:10]1[C:11]([CH3:15])([CH3:14])[C:12](=[O:13])[N:8]([CH2:7][CH2:6][O:5][CH2:4][CH2:3][O:2][CH3:1])[C:9]1([CH3:17])[CH3:16]
Reactant: COCCOCCN1C(=O)C(C)(C)NC1(C)C
Reactant: CC(C)(C)OCl
Solvent: CO
Product: COCCOCCN1C(=O)C(C)(C)N(Cl)C1(C)C
Reaction time: 0.5 h
Yield: 82.4 %

Procedure:
A solution of 3-(2-(2-methoxyethoxy)ethyl)-2,2,5,5-tetramethyl-imidazolidin-4-one (715 mg, 2.9 mmol) in methanol (7 ml) was cooled to 0° C. tert-Butylhypochlorite (393 ul, 3.5 mmol) was added. The resulting solution was stirred for 30 minutes, and then concentrated under reduced pressure. The crude material was purified by column chromatography (0 to 12% methanol in dichloromethane) to give the title compound as a clear liquid (666 mg, 2.39 mmol, 82%). 1H NMR (400 MHz, D2O) δ 1.26 (s, 6H), 1.43 (s, 6H), 3.27 (s, 3H), 3.44-3.46 (m, 2H), 3.49-3.51 (m, 2H), 3.57-3.63 (m, 4H). 13C NMR (100 MHz, D2O) δ 22.5, 24.0, 40.1, 57.9, 66.0, 67.6, 69.4, 71.0, 83.7, 175.0. LRMS (ESI/APCI) m/z 279 [M+H]+.
Reaction SMILES: COC1C=CC(C[N:8]([C:22]2[S:23][CH:24]=[CH:25][N:26]=2)[S:9]([C:12]2[CH:13]=[CH:14][C:15]3[NH:20][CH2:19][CH2:18][O:17][C:16]=3[CH:21]=2)(=[O:11])=[O:10])=CC=1.Br[C:30]1[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][C:31]=1[C:32]#[N:33].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC(C)([O-])C.[Na+].[F:88][C:89]([F:94])([F:93])[C:90]([OH:92])=[O:91]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:88][C:89]([F:94])([F:93])[C:90]([OH:92])=[O:91].[C:32]([C:31]1[CH:34]=[C:35]([O:38][CH3:39])[CH:36]=[CH:37][C:30]=1[N:20]1[CH2:19][CH2:18][O:17][C:16]2[CH:21]=[C:12]([S:9]([NH:8][C:22]3[S:23][CH:24]=[CH:25][N:26]=3)(=[O:10])=[O:11])[CH:13]=[CH:14][C:15]1=2)#[N:33]
Reactant: COc1ccc(Br)c(C#N)c1
Reactant: COc1ccc(CN(c2nccs2)S(=O)(=O)c2ccc3c(c2)OCCN3)cc1
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Solvent: Cc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(N2CCOc3cc(S(=O)(=O)Nc4nccs4)ccc32)c(C#N)c1
Temperature: 130 °C
Reaction time: 2 h

Procedure:
A microwave vial was charged with N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (INTERMEDIATE M, 0.125 g, 0.299 mmol), 2-bromo-5-methoxybenzonitrile (ASDI, 0.111 g, 0.524 mmol), Xantphos (0.035 g, 0.060 mmol), Pd2(dba)3 (0.027 g, 0.030 mmol) and sodium tert-butoxide (0.058 g, 0.599 mmol). The mixture was diluted with Toluene (2.00 ml), and purged with nitrogen, and heated at 130° C. in the microwave for 30 minutes. After cooling to RT, trifluoroacetic acid (0.577 ml, 7.48 mmol) was added to the crude reaction mixture, and the reaction was stirred at RT for 2 h ( ), after which the crude reaction was filtered over a plug of Celite (washing with minimal DCM to flush through the product). The reactions were then dried overnight in a hood and purified using reverse phase mass-directed HPLC. The column used was a Waters Xbridge C18 19×100 mm 10 micron column. The mobile phase was run under gradient conditions using Water and CH3CN with 0.1% trifluoroacetic acid. 1H NMR (500 MHz, DMSO-d6) δ ppm 12.57 (br. s., 1 H) 7.55 (d, J=2.86 Hz, 1 H) 7.51 (d, J=8.94 Hz, 1 H) 7.37 (dd, J=8.94, 2.86 Hz, 1 H) 7.21 (d, J=4.47 Hz, 1 H) 7.16 (d, J=1.83 Hz, 1 H) 7.13 (dd, J=8.48, 1.95 Hz, 1 H) 6.78 (d, J=4.47 Hz, 1 H) 6.29 (d, J=8.59 Hz, 1 H) 4.31-4.37 (m, 2 H) 3.84 (s, 3 H) 3.68-3.73 (m, 2 H). m/z (ESI) 428.1 (M+H)+.
Reaction SMILES: Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH3:12])[C:7](=[O:13])[C@@H:6]([CH2:14][CH3:15])[N:5]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:4]=2[N:3]=1.[NH:21]1[CH:25]=[CH:24][N:23]=[C:22]1[C:26]1[CH:27]=[N:28][CH:29]=[N:30][CH:31]=1>>[CH:16]1([N:5]2[C:4]3[N:3]=[C:2]([N:21]4[CH:25]=[CH:24][N:23]=[C:22]4[C:26]4[CH:31]=[N:30][CH:29]=[N:28][CH:27]=4)[N:11]=[CH:10][C:9]=3[N:8]([CH3:12])[C:7](=[O:13])[C@H:6]2[CH2:14][CH3:15])[CH2:20][CH2:19][CH2:18][CH2:17]1
Reactant: c1ncc(-c2ncc[nH]2)cn1
Reactant: CC[C@@H]1C(=O)N(C)c2cnc(Cl)nc2N1C1CCCC1
Product: CC[C@@H]1C(=O)N(C)c2cnc(-n3ccnc3-c3cncnc3)nc2N1C1CCCC1

Procedure:
The title compound was prepared similarly to the methods described in Example 77, with Intermediate B instead of Intermediate C and with 5-(1H-imidazol-2-yl)pyrimidine instead of 2-phenyl-1H-imidazole. LCMS: 405.2 m/z (M+H)+; ret. Time: 5.44 min (Analytical Method C).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][NH:6][C:7]([N:9]1[CH2:15][C:14]2[CH:16]=[CH:17][CH:18]=[CH:19][C:13]=2[CH:12]([CH2:20][C:21]([O:23]C)=[O:22])[CH2:11][CH2:10]1)=[O:8].[CH3:25][CH:26]([N:28]=[C:29]=[O:30])[CH3:27].[OH-].[Na+]>C(OCC)(=O)C>[CH3:25][CH:26]([NH:28][C:29]([NH:1][CH2:2][CH2:3][CH2:4][CH2:5][NH:6][C:7]([N:9]1[CH2:15][C:14]2[CH:16]=[CH:17][CH:18]=[CH:19][C:13]=2[CH:12]([CH2:20][C:21]([OH:23])=[O:22])[CH2:11][CH2:10]1)=[O:8])=[O:30])[CH3:27]
Reactant: CC(C)N=C=O
Reactant: COC(=O)CC1CCN(C(=O)NCCCCN)Cc2ccccc21
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Product: CC(C)NC(=O)NCCCCNC(=O)N1CCC(CC(=O)O)c2ccccc2C1
Temperature: 60 °C

Procedure:
A solution of methyl 2-(2-(N-(4-aminobut-1-yl) carbamoyl)-1H,3H,4H-5H-benzo[e]azapin-5-yl)acetate and 2-propyl isocyanate (1 eq) in ethyl acetate (2 mL) was heated at 60° C. for 48 hrs. The solvent was removed in vacuo and the residue was dissolved in methanol (0.1M) and 1N sodium hydroxide (3 eq). The mixture was heated at 60° C. for 24 hrs. The product was purified by preparative HPLC as a white solid (TFA salt, 55.5 mg, 59%): EI-MS m/z 405 (M+H); 1H-NMR (400 MHz, MeOH-d4): 7.29-7.14 (m, 4H), 4.54 (q, J=15.0 Hz, 2H), 3.79 (m,1H), 3.66 (m, 1H), 3.54 (m, 2H), 3.15-3.06 (m, 4H), 2.84-2.79 (m, 1H), 2.74-2.68 (m, 1H), 2.05-2.00 (m, 1H), 1.62-1.58 (m, 1H), 1.40-1.38 (m, 4H), 1.1 (d, J=6.8 Hz, 6H).
Reaction SMILES: C([O:4][CH2:5][CH2:6][CH2:7][CH2:8][N:9]1[C:16](S(C)=O)=[C:15]([CH2:20][CH3:21])[C:13](=[O:14])[NH:12][C:10]1=[S:11])(=O)C.[C:22]1([SeH:28])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[OH-].[Na+].Cl>CCO>[CH2:20]([C:15]1[C:13](=[O:14])[NH:12][C:10](=[S:11])[N:9]([CH2:8][CH2:7][CH2:6][CH2:5][OH:4])[C:16]=1[Se:28][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH3:21]
Reactant: [SeH]c1ccccc1
Reactant: CCc1c(S(C)=O)n(CCCCOC(C)=O)c(=S)[nH]c1=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CCc1c([Se]c2ccccc2)n(CCCCO)c(=S)[nH]c1=O
Reaction time: 2 h
Yield: 60 %

Procedure:
To a stirred suspension of 1-(4-acetoxybutyl)-5-ethyl-6-(methylsulfinyl)-2-thiouracil (0.33 g, 1.00 mmol) and benzeneselenol (0.11 mL, 1.04 mmol) in EtOH (5 mL) was added 1N methanolic NaOH solution (3.00 mL) at room temperature under a nitrogen atmosphere. After the mixture was stirred for 2 h, 3N HCl in EtOH (1.00 mL) was added and the reaction mixture was evaporated to dryness. The residue was purified by flash column chromatography on silica gel with MeOH-CHCl3 (5:95) as eluent to give 0.23 g of the titled compound.
Reaction SMILES: [CH3:1][N:2]([CH2:4][C:5]1[N:6]=[C:7]2[CH:12]=[CH:11][C:10]([C:13]3[C:22]([CH2:23][CH3:24])=[CH:21][C:16]([C:17]([O:19]C)=[O:18])=[C:15]([O:25]C)[N:14]=3)=[CH:9][N:8]2[CH:27]=1)[CH3:3].Cl>>[CH3:3][N:2]([CH2:4][C:5]1[N:6]=[C:7]2[CH:12]=[CH:11][C:10]([C:13]3[NH:14][C:15](=[O:25])[C:16]([C:17]([OH:19])=[O:18])=[CH:21][C:22]=3[CH2:23][CH3:24])=[CH:9][N:8]2[CH:27]=1)[CH3:1]
Reactant: CCc1cc(C(=O)OC)c(OC)nc1-c1ccc2nc(CN(C)C)cn2c1
Agent: Cl
Product: CCc1cc(C(=O)O)c(=O)[nH]c1-c1ccc2nc(CN(C)C)cn2c1
Yield: 123.3 %

Procedure:
Methyl 6-(2-((dimethylamino)methyl)imidazo[1,2-a]pyridin-6-yl)-5-ethyl-2-methoxynicotinate (100.6 mg, 0.27 mmol) was heated with 6 M HCl (1.50 mL) at 80° C. for 3 h. HCl was removed under reduced pressure affording 6-(2-((dimethylamino)methyl)imidazo[1,2-a]pyridin-6-yl)-5-ethyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid (113.3 mg) as dihydrochloride salt in 99% overall yield.
Reaction SMILES: Cl.[C:2]1([N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[NH2:9])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1Br.CC([O-])(C)C.[Na+].C(NC(C)C)(C)C>CC(O)=O.CC(O)=O.[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[C:2]1([N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[NH:9][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[Cl:16])[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Clc1ccccc1Br
Reactant: NN(c1ccccc1)c1ccccc1
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: Cl
Solvent: CC(=O)O
Solvent: CC(C)NC(C)C
Product: Clc1ccccc1NN(c1ccccc1)c1ccccc1
Temperature: 80 °C
Yield: 74 %

Procedure:
1,1-Diphenylhydrazine hydrochloride (1.2 equiv., 0.6 mmol, 135 mg), 2-chlorobromobenzene (1.0 equiv., 0.5 mmol, 0.06 mL), Pd(OAC)2 (0.05 equiv, 0.025 mmol, 6 mg), BINAP (0.05 equiv., 0.025 mmol, 16 mg), and NaOtBu (1.4 equiv., 0.7 mmol, 67 mg) and diisopropylamine (2 mL) were added to an oven dried test tube which was capped with a septum and purged briefly with argon (˜1 min.) and then heated to 80° C. for 5 hours. The reaction was then cooled to room temperature, diluted with Et2O (2 mL), filtered through Celite and concentrated under vacuum. The crude mixture was purified by flash column chromatography (2% EtOAc/Hex) to give the title product as a white solid (109 mg, 0.37 mmol, 74% yield).
Reaction SMILES: NC1C([OH:8])=CC(O)=C(N)C=1.[OH-].[Na+].N.[O-]O.C1(C(C)C)C=CC=CC=1.[Cl:25][C:26]1[CH:31]=[C:30]([N+:32]([O-:34])=[O:33])[CH:29]=[C:28]([N+:35]([O-:37])=[O:36])[C:27]=1[Cl:38]>C(Cl)Cl>[Cl:25][C:26]1[C:27]([Cl:38])=[C:28]([N+:35]([O-:37])=[O:36])[CH:29]=[C:30]([N+:32]([O-:34])=[O:33])[C:31]=1[OH:8]
Reactant: Nc1cc(N)c(O)cc1O
Reactant: O=[N+]([O-])c1cc(Cl)c(Cl)c([N+](=O)[O-])c1
Agent: N
Agent: [Na+]
Agent: [O-]O
Solvent: CC(C)c1ccccc1
Solvent: ClCCl
Product: O=[N+]([O-])c1cc([N+](=O)[O-])c(Cl)c(Cl)c1O

Procedure:
In a preferred embodiment for making diaminoresorcinol, the base, e.g., sodium hydroxide, is first dissolved in refluxing liquid ammonia in an inert atmosphere. The temperature of refluxing liquid ammonia is dependent upon the pressure and is typically between about -50° C. to about -10° C. Under atmospheric pressure conditions, the refluxing temperature of liquid ammonia is about -33° C. A solution of cumene hydroperoxide and 1,2-dichloro-3,5-dinitrobenzene in methylene chloride is then added to the stirred liquid ammonia reaction mixture at a rate such that the temperature remains at the refluxing temperature. Upon completion of the addition, the ammonia is evaporated and 2,3-dichloro-4,6-dinitrophenol may be isolated by pouring the reaction mixture into excess aqueous hydrochloric acid and extracted with ethyl acetate. Preferably, the 2,3-dichloro-4,6-dinitrophenol product is not isolated or purified, but is directly converted to 4,6-diaminoresorcinol, thus making the production of 4,6-diaminoresorcinol from 1,2-dichloro-3,5-dinitrobenzene a "one pot" process.
Reaction SMILES: [Al+3].[Cl-].[Cl-].[Cl-].[C:5]1([CH:12]=[CH:11][CH:10]=[C:8]([OH:9])[CH:7]=1)[OH:6].Cl[CH:14]([CH3:18])[C:15](Cl)=[O:16]>[N+](C1C=CC=CC=1)([O-])=O>[OH:6][C:5]1[CH:12]=[CH:11][C:10]2[C:15](=[O:16])[CH2:14][CH2:18][O:9][C:8]=2[CH:7]=1
Reactant: CC(Cl)C(=O)Cl
Reactant: Oc1cccc(O)c1
Agent: [Al+3]
Agent: [Cl-]
Solvent: O=[N+]([O-])c1ccccc1
Product: O=C1CCOc2cc(O)ccc21
Yield: 25 %

Procedure:
Under ice cooling, AlCl3 (3 molar equivalent) was added little by little to a solution composed of 11 g of resorcinol, 12.7 g of 2-chloropropionyl chloride and 120 ml of nitrobenzene. After the addition, the mixture was heated at 40° to 50° C. for 4 hours with stirring. The reaction mixture was worked up and purified in a customary manner to give 4.1 g of 2,3-dihydro-7-hydroxy-4-oxobenzopyran. The resulting compound was benzylated, reduced with sodium borohydride in methanol, and then methylated with methyl iodide in tetrahydrofuran in the presence of sodium hydride. In a customary manner, the methylated product was hydrogenated to give 1.7 g (yield 9.4%) of the desired product as a colorless liquid.