Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N+:19]([O-])=O)[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][O:16][CH3:17])[C:10](=[O:18])[CH2:9]1>C(OCC)(=O)C.CN(C=O)C>[NH2:19][C:4]1[CH:5]=[CH:6][C:7]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][O:16][CH3:17])[C:10](=[O:18])[CH2:9]2)=[C:2]([F:1])[CH:3]=1
Reactant: COCCN1CCN(c2ccc([N+](=O)[O-])cc2F)CC1=O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COCCN1CCN(c2ccc(N)cc2F)CC1=O

Procedure:
3-Fluoro-4-(4-{2-methoxyethyl}-3-oxopiperazin-1-yl)nitrobenzene (4 g) was dissolved in a mixture of ethyl acetate (200 ml) and DMF (5 ml), and the solution flushed with argon. Palladium (10% on carbon, 200 mg) was added, and the mixture hydrogenated under ambient pressure. After gas uptake had ceased, the mixture was filtered through celite and solvent was evaporated to give 5-amino-2-(4-{2-methoxyethyl}-3-oxopiperazin-1-yl)fluorobenzene which was used without further purification.
Reaction SMILES: [CH3:1][N:2]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH2:14][CH2:15][CH2:16]Cl)[CH:11]=2)[CH2:6][CH2:5][C:3]1=[O:4].[CH2:18]([CH:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(=O)([O-])O.[Na+].CC(C)=O.[C:40]([OH:45])(=[O:44])[C:41]([OH:43])=[O:42]>CC(C)=O.CN(C)C=O.C(N(CC)CC)C>[C:40]([OH:45])(=[O:44])[C:41]([OH:43])=[O:42].[CH3:1][N:2]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH2:14][CH2:15][CH2:16][N:28]3[CH2:29][CH2:30][CH:25]([CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH2:26][CH2:27]3)[CH:11]=2)[CH2:6][CH2:5][C:3]1=[O:4]
Reactant: c1ccc(CC2CCNCC2)cc1
Reactant: CN1C(=O)CCc2ccc(OCCCCl)cc21
Agent: O=C(O)C(=O)O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: CC(C)=O
Product: CN1C(=O)CCc2ccc(OCCCN3CCC(Cc4ccccc4)CC3)cc21
Yield: 86 %

Procedure:
4.9 Grams of 1-methyl-7-(3-chloropropoxy)-3,4-dihydrocarbostyril, 4.2 g of 4-benzylpiperidine and 3 g of triethylamine were mixed with 60 ml of dimethylformamide. The mixture was heated at 70°-80° C. for 8 hours. After the reaction was completed, the reaction mixture was concentrated under a reduced pressure to dryness. To the residue thus obtained was added 5%-sodium hydrogencarbonate aqueous solution and extracted with chloroform. The chloroform layer was washed with water and dried, then chloroform was removed by distillation. The residue thus obtained was dissolved in 30 ml of acetone, and under stirring condition a 5%-oxalic acid acetone solution was added thereto to make pH 4.5 then was allowed to stand. Precipitates thus formed were obtained by filtration, washed with acetone, then recrystallized from ethanol-ether to obtain 7.9 g (yield: 86%) of 1-methyl-7-[3-(4-benzyl-1-piperidyl)propoxy]-3,4-dihydrocarbostyril monooxalate as in the form of colorless powder. Melting point: 175°-177° C.
Reaction SMILES: [OH-:1].[Li+].[S].[Se].[N+:5]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([O-:7])=[O:6].[O:14]1[CH2:19][CH2:18]OC[CH2:15]1>CO.C(O)(=O)C>[N+:5]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([O-:7])=[O:6].[NH2:5][C:15]([O:14][CH2:19][CH3:18])=[O:1]
Reactant: C1COCCO1
Reactant: [OH-]
Agent: [Li+]
Agent: [S]
Agent: [Se]
Solvent: CO
Solvent: CC(=O)O
Solvent: O=[N+]([O-])c1ccccc1
Product: CCOC(N)=O
Reaction time: 0.75 h

Procedure:
0.29 gram of lithium hydroxide, 0.72 gram of acetic acid, 0.25 gram of sulfur, 0.25 gram of selenium metal, 10 milliliters of nitrobenzene, 15 milliliters of methanol and 15 milliliters of dioxane were charged into a 110 milliliter autoclave maintained under an initial carbon monoxide pressure of 2600 psig and at a temperature of 200° C. for 45 minutes. A nitrobenzene conversion of 98 per cent and a urethane product yield of 88.4 per cent were obtained as determined by gas chromatographic analysis.
Reaction SMILES: [C:1]([O:8][C:9]1[CH:14]=[C:13](Br)[CH:12]=[CH:11][C:10]=1[O:16][C:17]1[CH:22]=[CH:21][C:20]([N:23](C(OC(C)(C)C)=O)[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[CH:19][C:18]=1[F:38])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(O)CC#C.[C:44]([C:46]1[CH:50]=[CH:49][S:48][CH:47]=1)#[CH:45]>>[C:1]([O:8][C:9]1[CH:14]=[C:13]([C:45]#[C:44][C:46]2[CH:50]=[CH:49][S:48][CH:47]=2)[CH:12]=[CH:11][C:10]=1[O:16][C:17]1[CH:22]=[CH:21][C:20]([NH:23][C:24]([O:26][C:27]([CH3:28])([CH3:30])[CH3:29])=[O:25])=[CH:19][C:18]=1[F:38])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]
Reactant: CC(C)(C)OC(=O)Oc1cc(Br)ccc1Oc1ccc(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)cc1F
Reactant: C#Cc1ccsc1
Agent: C#CCCO
Product: CC(C)(C)OC(=O)Nc1ccc(Oc2ccc(C#Cc3ccsc3)cc2OC(=O)OC(C)(C)C)c(F)c1

Procedure:
According to the procedure of example 11 (a) except substituting 5-bromo-2-(2-methoxy-4-propylphenoxy)pyridine by O,N,N-triBoc-2-(4-amino-2-fluorophenoxy)-5-bromophenol (0.62 mmol; 363 mg) and 3-butyn-1-ol by 3-ethynylthiophene (1.55 mmol; 153 μL), the title compound was obtained as a yellow solid (60%, 195 mg) after purification on silica gel (cyclohexane/ethyl acetate gradient).
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([NH:10][CH2:11][CH3:12])[C:3]=1[C:4]#[N:5].N1C=CC=CC=1.[C:19]([O:22][CH2:23][C:24](Cl)=[O:25])(=[O:21])[CH3:20].O>C(Cl)Cl>[C:19]([O:22][CH2:23][C:24]([NH:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([NH:10][CH2:11][CH3:12])[C:3]=1[C:4]#[N:5])=[O:25])(=[O:21])[CH3:20]
Reactant: CCNc1cccc(N)c1C#N
Reactant: CC(=O)OCC(=O)Cl
Solvent: O
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCNc1cccc(NC(=O)COC(C)=O)c1C#N
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 2-amino-6-(ethylamino)benzonitrile (6.7 g) in methylene chloride (100 ml) is added pyridine (4.8 ml), and to the mixture is added dropwise acetoxyacetyl chloride (6.5 ml) which is cooled in an ice bath. The mixture is stirred at room temperature for 1 hour, and thereafter, water is added thereto, and the mixture is extracted with methylene chloride. The organic layer is dried over anhydrous sodium sulfate and the solvent is distilled off under reduced pressure. The resulting crude crystals are recrystallized from ethyl acetate-hexane to give the title compound (7.8 g) having the following physical properties.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2[N:12]([CH3:13])[C:11]3[CH:14]=[CH:15][C:16]([O:18][CH3:19])=[CH:17][C:10]=3[N:9]=2)[CH:5]=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:28]2[CH:29]=[N:30][NH:31][CH:32]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O.C1(C)C=CC=CC=1.C(O)C.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>[CH3:19][O:18][C:16]1[CH:15]=[CH:14][C:11]2[N:12]([CH3:13])[C:8]([C:4]3[CH:5]=[N:6][CH:7]=[C:2]([C:28]4[CH:29]=[N:30][NH:31][CH:32]=4)[CH:3]=3)=[N:9][C:10]=2[CH:17]=1
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Reactant: COc1ccc2c(c1)nc(-c1cncc(Br)c1)n2C
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: Cc1ccccc1
Solvent: O
Solvent: CCO
Product: COc1ccc2c(c1)nc(-c1cncc(-c3cn[nH]c3)c1)n2C
Temperature: 100 °C

Procedure:
To a solution of 2-(5-bromo-pyridin-3-yl)-5-methoxy-1-methyl-1H-benzoimidazole (0.15 g, 0.00047 mol) in ethanol toluene water (6 ml, 3 ml, 1.5 ml, respectively) mixture in a sealed tube was added 4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.18 g, 0.000942 mol) and Na2CO3 (0.14 g, 0.0014 mol) and argon was purged for 15 min. Then Pd (PPh3)4 (0.027 g, 0.000023 mol) was added and heated at 100° C. for 24 h. The solvent was evaporated and the resulting residue was added water. The aqueous layer was extracted with ethyl acetate (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 5-methoxy-1-methyl-2-[5-(1H-pyrazol-4-yl)pyridin-3-yl]-1H-benzimidazole as an off white solid. 1H NMR (400 MHz, DMSO-d6), δ: 13.11 (s, 1H), 9.01 (s, 1H), 8.79 (s, 1H), 8.44 (s, 1H), 8.38 (s, 1H), 8.13 (s, 1H), 7.54 (d, J=8.8 Hz, 1H), 7.22 (s, 1H), 6.95 (d, J=8.8 Hz, 1H), 3.89 (s, 3H), 3.79 (s, 3H). MS (M+1): 306.1, Purity 99.0%.
Reaction SMILES: C1C=CC=CC=1.[CH3:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[C:11]([NH2:16])=[CH:10][C:9]=1[OH:17].[F:18][CH2:19][C:20](OC)=[O:21].C[O-].[Na+]>C(O)(=O)C.O>[CH3:7][C:8]1[CH:13]=[C:12]([O:14][CH3:15])[C:11]([NH:16][C:20](=[O:21])[CH2:19][F:18])=[CH:10][C:9]=1[OH:17]
Reactant: COC(=O)CF
Reactant: COc1cc(C)c(O)cc1N
Agent: C[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Solvent: c1ccccc1
Product: COc1cc(C)c(O)cc1NC(=O)CF
Yield: 13.9 %

Procedure:
Into 15 ml of benzene were added 2.10 g (13.7 mmol) of 2-methyl-4-methoxy-5-aminophenol, 1.28 g (13.9 mmol, 1.0 eq.) of methyl fluoroacetate and 1.64 g (30.4 mmol) of sodium methoxide and the mixture was heated under reflux for 6.5 hours. After allowing to cool, the mixture was poured into 300 ml of water, and neutralized with acetic acid and extracted with 200 ml of ethyl acetate. The organic layer was washed with a saturated aqueous solution of common salt and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain dark-brown crystals. The crystals were purified by silica gel column chromatography (Silica Gel 60, trade name, manufactured by Merck Co., 70-230 mesh, 200 g, eluent: ethyl acetate) and pale brown solid matters were obtained from the 600-900 ml fraction. The solid matters were recrystallized from the solvent mixture of hexane/ethyl acetate (2:1 by volume) to give 230 mg (1.9 mmol) of 2-methyl-4-methoxy-5-fluoroacetylaminophenol. The yield was 8%.
Reaction SMILES: C1(C2C=CC(C(Cl)=O)=CC=2)C=CC=CC=1.[CH3:16][O:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][C:27]=1[O:28][CH3:29])[N:24]=[CH:23][CH:22]=[C:21]2[O:30][C:31]1[CH:37]=[CH:36][C:34]([NH2:35])=[C:33]([F:38])[CH:32]=1.[C:39]1([C:45]2[CH:50]=[CH:49][C:48]([C:51]([N:53]=[C:54]=[S:55])=[O:52])=[CH:47][CH:46]=2)[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>C1(C)C=CC=CC=1.C(O)C>[C:39]1([C:45]2[CH:50]=[CH:49][C:48]([C:51]([N:53]=[C:54]=[S:55])=[O:52])=[CH:47][CH:46]=2)[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1.[C:39]1([C:45]2[CH:50]=[CH:49][C:48]([C:51]([NH:53][C:54]([NH:35][C:34]3[CH:36]=[CH:37][C:31]([O:30][C:21]4[C:20]5[C:25](=[CH:26][C:27]([O:28][CH3:29])=[C:18]([O:17][CH3:16])[CH:19]=5)[N:24]=[CH:23][CH:22]=4)=[CH:32][C:33]=3[F:38])=[S:55])=[O:52])=[CH:47][CH:46]=2)[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1
Reactant: COc1cc2nccc(Oc3ccc(N)c(F)c3)c2cc1OC
Agent: O=C(Cl)c1ccc(-c2ccccc2)cc1
Agent: O=C(N=C=S)c1ccc(-c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: CCO
Product: COc1cc2nccc(Oc3ccc(NC(=S)NC(=O)c4ccc(-c5ccccc5)cc4)c(F)c3)c2cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 47 %

Procedure:
4-Phenyl-1-benzenecarbonyl isothiocyanate was prepared using commercially available 4-phenyl-1benzenecarbonyl chloride (80 mg) as a starting compound according to the description of the literature. 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. A solution of 4-phenyl-1-benzenecarbonyl isothiocyanate in ethanol (1 ml) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (41 mg, yield 47%).
Reaction SMILES: [CH3:1][O:2][C:3]([N:5]1[CH:9]=[C:8]([CH:10]=O)[C:7]([C:12]2[O:13][C:14]([N+:17]([O-:19])=[O:18])=[CH:15][CH:16]=2)=[N:6]1)=[O:4].[NH2:20][N:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1.C(O)(=O)C>CO>[CH3:1][O:2][C:3]([N:5]1[CH:9]=[C:8]([CH:10]=[N:20][N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[C:7]([C:12]2[O:13][C:14]([N+:17]([O-:19])=[O:18])=[CH:15][CH:16]=2)=[N:6]1)=[O:4]
Reactant: COC(=O)n1cc(C=O)c(-c2ccc([N+](=O)[O-])o2)n1
Reactant: NN1CCOCC1
Solvent: CO
Solvent: CC(=O)O
Product: COC(=O)n1cc(C=NN2CCOCC2)c(-c2ccc([N+](=O)[O-])o2)n1
Yield: 70 %

Procedure:
Stir together 6.7 g of 1-methoxycarbonyl-3-(5-nitro-2-furyl)pyrazole-4-carboxaldehyde, 2.85 g of 4-aminomorpholine and 1.6 ml of glacial acetic acid in 125 ml of methanol for 3 hours at room temperature. Cool the resulting admixture on ice to produce a precipitate. Vacuum filter the precipitate and then suspend it once more in ethanol to obtain a 70% yield of 4-[1-methoxycarbonyl-3-(5-nitro-2-furyl)pyrazol-4-ylmethyleneamino]morpholine [m.p. 184° C (with decomposition)].
Reaction SMILES: Cl[CH2:2][C:3](=O)[CH2:4][C:5]([O:7][CH3:8])=[O:6].[Cl:10][CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:23]=[CH:22][C:18]([C:19]([NH2:21])=[O:20])=[CH:17][CH:16]=1>C(#N)CC.ClCCl>[Cl:10][CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:23]=[CH:22][C:18]([C:19]2[O:20][CH:2]=[C:3]([CH2:4][C:5]([O:7][CH3:8])=[O:6])[N:21]=2)=[CH:17][CH:16]=1
Reactant: COC(=O)CC(=O)CCl
Reactant: NC(=O)c1ccc(OCCCCl)cc1
Solvent: CCC#N
Solvent: ClCCl
Product: COC(=O)Cc1coc(-c2ccc(OCCCCl)cc2)n1
Yield: 48.3 %

Procedure:
Methyl 4-chloro-3-oxobutanoate (4.32 ml, 37.44 mmol, 2 eq) is added to a solution of 4-(3-chloropropoxy)benzamide (4 g, 18.72 mmol, 1 eq) in propionitrile (50 ml). The mixture is heated at reflux for 48 h. The mixture is then diluted with dichloromethane and filtered. The solvent is removed under vacuum and the residue is purified on silica gel (eluent: ethyl acetate) to give 2.8 g methyl {2-[4-(3-chloropropoxy)phenyl]-1,3-oxazol-4-yl}acetate ax62 as a brown oil.
Reaction SMILES: [O-:1]CC.[O-:4]CC.[Ca+2:7].[Cl:8][C:9]1[CH:35]=[CH:34][C:12]([O:13][CH2:14][C@@H:15]([F:33])[CH2:16][O:17][C:18]2[CH:19]=[C:20]([CH2:24][C@H:25]([O:29][CH:30]([CH3:32])[CH3:31])[C:26]([OH:28])=[O:27])[CH:21]=[CH:22][CH:23]=2)=[C:11]([C:36]#[N:37])[CH:10]=1>CO>[OH2:1].[OH2:4].[OH2:13].[Cl:8][C:9]1[CH:35]=[CH:34][C:12]([O:13][CH2:14][C@@H:15]([F:33])[CH2:16][O:17][C:18]2[CH:19]=[C:20]([CH2:24][C@H:25]([O:29][CH:30]([CH3:32])[CH3:31])[C:26]([O-:28])=[O:27])[CH:21]=[CH:22][CH:23]=2)=[C:11]([C:36]#[N:37])[CH:10]=1.[Cl:8][C:9]1[CH:35]=[CH:34][C:12]([O:13][CH2:14][C@@H:15]([F:33])[CH2:16][O:17][C:18]2[CH:19]=[C:20]([CH2:24][C@H:25]([O:29][CH:30]([CH3:32])[CH3:31])[C:26]([O-:28])=[O:27])[CH:21]=[CH:22][CH:23]=2)=[C:11]([C:36]#[N:37])[CH:10]=1.[Ca+2:7]
Reactant: CC[O-]
Reactant: CC(C)O[C@@H](Cc1cccc(OC[C@H](F)COc2ccc(Cl)cc2C#N)c1)C(=O)O
Agent: [Ca+2]
Solvent: CO
Product: CC(C)O[C@@H](Cc1cccc(OC[C@H](F)COc2ccc(Cl)cc2C#N)c1)C(=O)[O-]
Product: O
Temperature: 25 °C
Reaction time: 8 h
Yield: 141 %

Procedure:
4.6 g of calcium diethoxide was dissolved in 500 mL of methanol, to which a methanol (300 mL) solution of 30.8 g of (2S)-3-[3-[(2S)-3-(4-chloro-2-cyanophenoxy)-2-fluoropropoxy]phenyl]-2-isopropoxypropionic acid was then added, followed by stirring the reaction mixture overnight at room temperature. Insoluble matter in the reaction mixture was filtered, and the solvent was distilled off under a reduced pressure. To the residue were added 250 mL of methanol and 60 mL of water, followed by heating the reaction mixture to reflux. The reaction mixture was then cooled, followed by filtering the precipitated solid to obtain 32 g of the title compound as a crude product. To this compound was added 1.5 L of ethanol, and the reaction mixture was heated to reflux. Insoluble matter was hot-filtered, and the solution was again heated to reflux. To the reaction mixture was added 20 ml of water to slowly cool the mixture, and the reaction mixture was stirred overnight at room temperature. The precipitated solid was filtered, washed with ethanol:water=9:1, and subjected to forced-air drying at 40° C. for 18 hours. There was obtained 29 g of the title compound in the form of white crystal. The 1H-NMR data thereof coincided with that of the compound of Example 1-(15).
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[C:18](Cl)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:23][CH:24]1[CH2:32][CH:31]2[CH:27]([CH2:28][C:29](=[O:44])[N:30]2[CH2:33][C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][C:35]=2[O:42][CH3:43])[CH2:26][CH2:25]1.C(N(C(C)C)CC)(C)C>CC(O)C>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([N+:20]([O-:22])=[O:21])[C:18]([NH:23][CH:24]4[CH2:32][CH:31]5[CH:27]([CH2:28][C:29](=[O:44])[N:30]5[CH2:33][C:34]5[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][C:35]=5[O:42][CH3:43])[CH2:26][CH2:25]4)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COc1ccc(CN2C(=O)CC3CCC(N)CC32)c(OC)c1
Reactant: O=[N+]([O-])c1cnc2c(ccn2S(=O)(=O)c2ccccc2)c1Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)O
Product: COc1ccc(CN2C(=O)CC3CCC(Nc4c([N+](=O)[O-])cnc5c4ccn5S(=O)(=O)c4ccccc4)CC32)c(OC)c1
Temperature: 120 °C
Yield: 71 %

Procedure:
A mixture of 1-benzenesulfonyl-4-chloro-5-nitro-1H-pyrrolo[2,3-b]pyridine (137.2 mg, 0.4062 mmol), 6-amino-1-(2,4-dimethoxy-benzyl)-octahydro-indol-2-one (107.8 mg, 0.3542 mmol), and diisopropylethylamine (0.10 mL, 0.57 mmol) in propan-2-ol (1.5 ml) was heated in a microwave reactor at 120° C. for 20 minutes. The solvent was evaporated in vacuo and then purified by column chromatography on silica gel (gradient: 0 to 100% ethyl acetate in dichloromethane) affording 152.3 mg (71%) of 6-(1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-ylamino)-1-(2,4-dimethoxy-benzyl)-octahydro-indol-2-one. LCMS (Method E, ESI): RT=1.81 min, m+H=606.0.
Reaction SMILES: [CH3:1][C:2]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH:9]1[C:15](=[O:20])N(OC)C)=[O:7])([CH3:4])[CH3:3].[Cl:21][C:22]1[CH:23]=[C:24]([Cl:31])[C:25]2[O:29][CH:28]=[CH:27][C:26]=2[CH:30]=1>>[C:2]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH:9]1[C:15]([C:28]1[O:29][C:25]2[C:24]([Cl:31])=[CH:23][C:22]([Cl:21])=[CH:30][C:26]=2[CH:27]=1)=[O:20])=[O:7])([CH3:1])([CH3:3])[CH3:4]
Reactant: CON(C)C(=O)C1CN(C)CCN1C(=O)OC(C)(C)C
Reactant: Clc1cc(Cl)c2occc2c1
Product: CN1CCN(C(=O)OC(C)(C)C)C(C(=O)c2cc3cc(Cl)cc(Cl)c3o2)C1

Procedure:
The title compound (0.94 g) was prepared from (RS)-2-(methoxy-methyl-carbamoyl)-4-methyl-piperazine-1-carboxylic acid dimethyl-ethyl ester, D54 (1.00 g) and 5,7-dichloro-benzofuran (0.65 g, FP1.537.206) using the method of Description 2.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]2[C:15]([CH3:26])=[CH:16][C:17]3[NH:22][C:21](=[O:23])[O:20][CH2:19][C:18]=3[C:24]=2[CH3:25])=[CH:4][CH:3]=1.[OH:27]O>>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]2[C:15]([CH3:26])=[CH:16][C:17]3[NH:22][C:21](=[O:23])[O:20][CH2:19][C:18]=3[C:24]=2[CH3:25])=[O:27])=[CH:6][CH:7]=1
Reactant: OO
Reactant: Cc1ccc(SCCCCOc2c(C)cc3c(c2C)COC(=O)N3)cc1
Product: Cc1ccc(S(=O)CCCCOc2c(C)cc3c(c2C)COC(=O)N3)cc1

Procedure:
Prepared analogously to Example 2 from 6-[4-(4-methylphenylmercapto)-butoxy]-5,7-dimethyl-4H-3,1-benzoxazin-2-one and hydrogen peroxide.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][O:12][CH2:13][CH:14]2[CH2:16][O:15]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N-:17]=[N+:18]=[N-:19].[Na+].CO.C(OC)=O>O>[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][O:12][CH2:13][CH:14]([OH:15])[CH2:16][N:17]=[N+:18]=[N-:19])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: c1ccc(CCCCCOCC2CO2)cc1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CO
Solvent: COC=O
Solvent: O
Product: [N-]=[N+]=NCC(O)COCCCCCc1ccccc1
Yield: 94.1 %

Procedure:
A procedure similar to that described in Preparation 12 was repeated, except that 4.0 g of 5-phenylpentyloxymethyloxirane (prepared as described in Preparation 49), 5.9 g of sodium azide, 160 ml of an 8:1 by volume mixture of methanol and water and 40 ml of methyl formate were used, to give 4.5 g of the title compound as a pale yellow oil having an Rf value of 0.25 (on silica gel thin layer chromatography, using a 1:4 by volume mixture of ethyl acetate and hexane as the developing solvent).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([O:7][C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]3[N:18]=[C:19]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[O:20][C:21]=3[C:22]([F:25])([F:24])[F:23])=[O:16])=[CH:10][CH:9]=2)[CH2:2]1.[CH3:32][C:33]1([CH3:41])[CH2:38][C:37](=[O:39])[O:36][C:35](=[O:40])[CH2:34]1.C(N(CC)CC)C>CS(C)=O>[CH3:32][C:33]([CH3:41])([CH2:38][C:37](=[O:39])[N:1]1[CH2:6][CH2:5][CH2:4][CH:3]([O:7][C:8]2[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]3[N:18]=[C:19]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[O:20][C:21]=3[C:22]([F:25])([F:23])[F:24])=[O:16])=[CH:10][CH:9]=2)[CH2:2]1)[CH2:34][C:35]([OH:40])=[O:36]
Reactant: CC1(C)CC(=O)OC(=O)C1
Reactant: O=C(Nc1ccc(OC2CCCNC2)cc1)c1nc(-c2ccccc2)oc1C(F)(F)F
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: CC(C)(CC(=O)O)CC(=O)N1CCCC(Oc2ccc(NC(=O)c3nc(-c4ccccc4)oc3C(F)(F)F)cc2)C1
Yield: 55.4 %

Procedure:
2-Phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [4-(piperidin-3-yloxy)-phenyl]-amide (46.2 mg, 0.107 mmol), 4,4-dimethyl-dihydro-pyran-2,6-dione (18.3 mg, 0.128 mmol) and triethylamine (30 uL, 0.214 mmol) in 1 mL DMSO were treated as above. The crude product was purified by flash chromatography to yield 3,3-dimethyl-5-oxo-5-(3-{4-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenoxy}-piperidin-1-yl)-pentanoic acid as a white solid (34 mg, 55%). ES-MS calcd for C29H30F3N3O6 (m/e) 573.57, obsd 574 (M+H).
Reaction SMILES: [CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[O:32][CH2:33][CH3:34])[CH2:23][CH2:22][C:21]([C:35]([O:37]C)=[O:36])=[CH:20][C:19]=3[CH:39]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].[OH-].[Na+].O.Cl>O1CCCC1.CO>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[O:32][CH2:33][CH3:34])[CH2:23][CH2:22][C:21]([C:35]([OH:37])=[O:36])=[CH:20][C:19]=3[CH:39]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)OC)CCN3Cc2ccccc2OCC)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)O)CCN3Cc2ccccc2OCC)cc1
Temperature: 25 °C
Reaction time: 96 h
Yield: 75.9 %

Procedure:
To a solution of methyl 7-(4-butoxyethoxyphenyl)-1-(2-ethoxybenzyl)-2,3-dihydro-1-benzazepine-4-carboxylate (402 mg) in a mixture of tetrahydrofuran (24 ml) and methanol (24 ml) was added 1N sodium hydroxide solution (8 ml), and the mixture was stirred at room temperature for 4 days. Then, to the mixture was added water at 0° C., and 1N hydrochloric acid was further added to make acidic (pH=4), and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with magnesium sulfate. The solvent was evaporated under reduced pressure, which was recrystallized from hexane ethyl acetate to give 7-(4-butoxyethoxyphenyl)-1-(2-ethoxybenzyl)-2,3-dihydro-1-benzazepine-4-carboxylic acid (297 mg) as yellow crystals.