Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([CH:3]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH2:4][C:5]([OH:7])=O)#[N:2].[OH-].[K+].C(Cl)(=O)C(Cl)=O.[CH:22]([NH:25][CH:26]([CH3:28])[CH3:27])([CH3:24])[CH3:23]>C1C=CC=CC=1.C(OCC)C>[CH:22]([N:25]([CH:26]([CH3:28])[CH3:27])[C:5](=[O:7])[CH2:4][CH:3]([C:1]#[N:2])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([CH3:24])[CH3:23]
Reactant: N#CC(CC(=O)O)c1ccccc1
Reactant: CC(C)NC(C)C
Agent: O=C(Cl)C(=O)Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCOCC
Solvent: c1ccccc1
Product: CC(C)N(C(=O)CC(C#N)c1ccccc1)C(C)C
Temperature: 80 °C
Reaction time: 2 h

Procedure:
3-Cyano-3-phenylpropanoic acid (67.7 g, 0.389 mol) was dissolved in 2-PrOH. To the filtered acid solution was carefully added KOH (18.4 g, 0.33 mol) dissolved in 2-PrOH (200 mL), diethyl ether (100 mL) was added and the precipitate was filtered off. The dried acid salt (51.9 g, 0.24 mol) was suspended in benzene (400 mL) and oxalyl chloride was carefully added. The reaction mixture was stirred at 80° C. for 2 hours. The solvent was evaporated and the residue was co-evaporated twice with benzene. The brown oil was dissolved in benzene (200 mL) and cooled in an ice-bath. A solution of diisopropylamine (82 g, 0.81 mol) in benzene (200 mL) was added to the stirred reaction mixture during 45 min. The mixture was left to slowly warm up to room temperature overnight. The solvent was evaporated and the residue was taken up in diethyl ether and 1 M HCl. The organic phase was washed once with water, once with 1 M NaOH, again with water, dried (Na2SO4) and the solvent evaporated to afford the title compound as a dark brown oil, 41.7 g (41%): 1H NMR (CDCl3) δ1.07 (d, 3H), 1.17 (d, 3H), 1.36 (m, 6H), 2.77 (m, 1H), 2.97 (m, 1H), 3,51 (br, 1H), 3.81 (m, 1H), 4.50 (dd, 1H), 7.39 (m, 5H).
Reaction SMILES: [N:1](=[C:3]([CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[C:4](=O)[CH3:5])O.[CH3:12][C:13](=O)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].[N:21](Cl)=O.N=C=O>[Zn].C(O)(=O)C>[CH3:12][C:13]1[C:14]([CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])=[N:21][C:4]([CH3:5])=[C:3]([CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[N:1]=1
Reactant: CCCCCC(=NO)C(C)=O
Reactant: CCCCCCC(C)=O
Reactant: O=NCl
Agent: N=C=O
Agent: [Zn]
Solvent: CC(=O)O
Product: CCCCCc1nc(C)c(CCCCC)nc1C

Procedure:
g. 2,5-Dimethyl-3,6-diamyl-pyrazine was prepared by first forming 3-oximino-2-octanone by reacting 2-octanone with nitrosyl chloride according to the method of BOUVEAULT (loc.cit.). The autocondensation of two moles of the imino-ketone in the presence of zinc and acetic acid [according to the method described in Chimia 11, 310 (1957)] yielded 2,5-dimethyl-3,6-diamyl-pyrazine which had a b.p. of 78° C./0.03 mm. Hg.
Reaction SMILES: [O:1]=[C:2]1[NH:6][C@H:5]([C:7]([OH:9])=O)[CH2:4][S:3]1.[N+]([O-])(O)=O.[N+:14]([O:17][CH:18]([CH3:21])[CH2:19][NH2:20])([O-:16])=[O:15]>>[N+:14]([O:17][CH:18]([CH3:21])[CH2:19][NH:20][C:7]([C@@H:5]1[CH2:4][S:3][C:2](=[O:1])[NH:6]1)=[O:9])([O-:16])=[O:15]
Reactant: CC(CN)O[N+](=O)[O-]
Reactant: O=C1N[C@H](C(=O)O)CS1
Solvent: O=[N+]([O-])O
Product: CC(CNC(=O)[C@@H]1CSC(=O)N1)O[N+](=O)[O-]

Procedure:
A procedure similar to that described in Example 1 was repeated, but using 2.0 g of (4R)-2-oxothiazolidine4-carboxylic acid and 3.0 g of N-(2-nitrooxypropyl)amine nitrate, to obtain 24 mg of the title compound as pale yellow crystals, melting at 70°-72° C. (after recrystallization from ethanol).
Reaction SMILES: C(N1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10]C=2)[C:6](=O)C1=O)CC.[CH3:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][C:20](=[O:25])[C:19]2=[O:26].BrCCCCCC>>[CH3:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[N:21]([CH2:10][CH2:9][CH2:8][CH:7]([CH3:12])[CH3:6])[C:20](=[O:25])[C:19]2=[O:26]
Reactant: CCCN1C(=O)C(=O)c2ccccc21
Reactant: Cc1ccc2c(c1)C(=O)C(=O)N2
Solvent: CCCCCCBr
Product: Cc1ccc2c(c1)C(=O)C(=O)N2CCCC(C)C

Procedure:
This compound was prepared in a similar method as 1-propylindoline-2,3-dione by reacting commercially available 5-methyl isatin (purchase from Fisher Scientific) with commercially available 1-bromo-5-methylpentane (purchase from Fisher Scientific). 1H NMR δ 7.42 (s, 1H), 7.38 (ddd, 1H), 6.79 (d, 1H), 3.68 (t, 2H), 3.34 (s, 3H), 1.69 (m, 2H), 1.60 (m, 1H), 1.27 (m, 2H), 0.88 (d, 6H).
Reaction SMILES: [C:1]([Si:5]([CH3:25])([CH3:24])[O:6][CH:7]([C:21]([CH3:23])=[CH2:22])[CH2:8][CH2:9]/[C:10](/[CH3:20])=[CH:11]/[CH2:12][CH2:13][C:14]([CH3:19])=[CH:15][CH:16]([OH:18])[CH3:17])([CH3:4])([CH3:3])[CH3:2].CCCCCC.C(OCC)(=O)C>ClCCl.[O-2].[O-2].[Mn+4]>[C:1]([Si:5]([CH3:24])([CH3:25])[O:6][CH:7]([C:21]([CH3:23])=[CH2:22])[CH2:8][CH2:9]/[C:10](/[CH3:20])=[CH:11]/[CH2:12][CH2:13][C:14]([CH3:19])=[CH:15][C:16](=[O:18])[CH3:17])([CH3:4])([CH3:3])[CH3:2]
Reactant: C=C(C)C(CC/C(C)=C/CCC(C)=CC(C)O)O[Si](C)(C)C(C)(C)C
Agent: [Mn+4]
Agent: [O-2]
Solvent: CCCCCC
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: C=C(C)C(CC/C(C)=C/CCC(C)=CC(C)=O)O[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 5 h

Procedure:
5 g of (7E)-11-(tert.-butyldimethylsiloxy)-4,8,12-trimethyl-3,7,12-tridecatrien-2-ol are added dropwise at 0° to a suspension of 25 g of manganese dioxide (active, precipitated) in 50 ml of dichloromethane. After stirring at room temperature for 5 hours the reaction mixture is filtered over sodium sulphate and the filtrate is evaporated. The material obtained is subjected twice more to the same oxidation process with fresh manganese dioxide each time in order to achieve complete reaction. Chromatography of the crude product obtained on silica gel with hexane-ethyl acetate 2%→5% yields (7E)-11-(tert.-butyldimethylsiloxy)-4,8,12-trimethyl-3,7,12-tridecatrien-2-one as a yellowish which has a purity of 95% in accordance with a gas chromatography. NMR (250 MHz, CDCl3): 6.05 (s, H-C(3)); 5.1 (m, H-C(7)); 4.84 and 4.75 (2m, 2H-C(13)); 4.0 (t, J=6.5, H-C(11)); 2.3-1.4 (m, 4CH2, 3CH 3); 0.89 (s, SiC(CH3)3); 0.35 and 0.0 (2s, Si(CH3)2).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([OH:8])=[N:6][CH:7]=1.[Cl:9][C:10]1[CH:15]=[C:14](Cl)[CH:13]=[CH:12][N:11]=1>>[Cl:9][C:10]1[CH:15]=[C:14]([O:8][C:5]2[N:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=2)[CH:13]=[CH:12][N:11]=1
Reactant: Nc1ccc(O)nc1
Reactant: Clc1ccnc(Cl)c1
Product: Nc1ccc(Oc2ccnc(Cl)c2)nc1
Yield: 34.8 %

Procedure:
Using a procedure analogous to Example A1, 5-amino-2-hydroxypyridine (10.15 g, 92 mmol) and 2,4-dichloropyridine (13.64 g, 92 mmol) were combined to provide 6-(2-chloropyridin-4-yloxy)pyridin-3-amine (7.09 g, 35% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.12 (m, 1H), 7.61 (m, 1H), 7.26 (m, 1H), 7.0 (s, 1H), 6.97-6.94 (m, 2H), 5.4 (brs, 214); MS (ESI) m/z: 222.0 (M+H+).
Reaction SMILES: [CH2:1]1[S:6][CH:5]([OH:7])[CH2:4]S[CH:2]1[OH:8].[C:9]([O:17]CC=O)(=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.N1C=CC=CC=1.[CH3:27][O:28][C:29](Cl)=[O:30]>C(Cl)Cl>[C:9]([O:17][CH2:4][C@H:5]1[S:6][CH2:1][C@H:2]([O:8][C:29]([O:28][CH3:27])=[O:30])[O:7]1)(=[O:16])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: O=CCOC(=O)c1ccccc1
Reactant: OC1CSC(O)CS1
Reactant: COC(=O)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: COC(=O)O[C@H]1CS[C@H](COC(=O)c2ccccc2)O1
Temperature: 0 °C
Reaction time: 12 h

Procedure:
A solution of 17.93 g (0.118 mmol) of mercaptoacetaldehyde dimer and 38.70 g (0.236 mmol) of benzoyloxyacetaldehyde in 57.3 mL (3 eq) of pyridine was heated until all the solid dissolved. After cooling, 300 mL of anhydrous methylene chloride were added and the mixture was cooled at 0° C. for ca. 30 minutes. To this solution at 0° C., was slowly added a solution of methylchloroformate (57.3 mL, 0.71 mmol) in 80 mL of methylene chloride. The mixture was stirred for 12 hrs and diluted with ca. 200 mL of methylene chloride and washed several times with brine to remove pyridinium salt and then the organic layer was washed with water. The organic layer was dried over magnesium sulphate at 0° C. and then filtered. Residual pyridine was removed in vacuo and the organic residue was purified by flash chromatography using hexanes:ethyl acetate (2:1) as eluent to yield a mixture of 2:1 trans:cis carbonates (56.3 g, 80%).
Reaction SMILES: O=C1C2C(=CC=CC=2)C(=O)[N:3]1[O:12][C:13](=[CH2:30])[C:14]([O:16][CH:17]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15].O.NN>C(Cl)Cl.C(O)C>[NH2:3][O:12][C:13](=[CH2:30])[C:14]([O:16][CH:17]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15]
Reactant: C=C(ON1C(=O)c2ccccc2C1=O)C(=O)OC(c1ccccc1)c1ccccc1
Agent: NN
Solvent: CCO
Solvent: O
Solvent: ClCCl
Product: C=C(ON)C(=O)OC(c1ccccc1)c1ccccc1
Reaction time: 1 h

Procedure:
To a solution of 2-[(1,3-dioxo-2H-isoindol-2-yl)oxy]-2-propenoic acid, diphenylmethyl ester (6.07 g, 15.2 mmole) in 375 ml of methylene chloride under argon at 0° C. was added hydrazine hydrate (0.76 g, 15.2 mmole) in 4 ml absolute ethanol. After one hour at 0° C., the mixture was evaporated to dryness at +10° C. and triturated with ethyl ether. Filtration and concentration of the filtrates gave 2-aminooxy-2-propenoic acid, diphenylmethyl ester as a residue. This compound was then treated at 20° C. with a solution of 2-amino-4-thiazoleglyoxylic acid (2.61 g, 15.2 mmole) in dimethylformamide (50 ml), followed by 5 ml of water. The reaction was stirred at 20° C. for 20 hours, and was then chilled and diluted with 250 ml of water. Stirring of the resulting gum gave a granular solid which was filtered, washed with water, and then azeotroped with acetonitrile to dryness. The dry solid was slurried with 100 ml of acetonitrile, filtered, and finally washed sequentially with acetonitrile, ethyl ether, and hexane. Drying in air gave 1.97 g of the title compound.
Reaction SMILES: Cl.[NH:2]=[C:3]1[N:9]=[CH:8][CH:7]=[CH:6][N:5](C(OC(C)(C)C)=O)[CH2:4]1.C(N(CC)CC)C.Br[CH2:25][C:26]([C:28]([F:31])([F:30])[F:29])=O>O1CCOCC1>[F:29][C:28]([F:31])([F:30])[C:26]1[N:2]=[C:3]2[CH2:4][NH:5][CH2:6][CH2:7][CH2:8][N:9]2[CH:25]=1
Reactant: CC(C)(C)OC(=O)N1C=CC=NC(=N)C1
Reactant: O=C(CBr)C(F)(F)F
Agent: Cl
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: FC(F)(F)c1cn2c(n1)CNCCC2
Temperature: 120 °C

Procedure:
To a stirred mixture of compound from Step B (0.42 g, 1.68 mmol) and triethylamine (0.64 mL, 4.6 mmol) in dioxane was added 1-bromo-3,3,3-trifluoroacetone. The resultant mixture was heated at 50° C. overnight. After solvent was removed, the residue was dissolved in isopropanol and refluxed overnight. After an aqueous work-up, the residue purified by flash chromatography (silica gel, 4% of 10% methanolic ammonium hydroxide solution in dichloromethane). The intermediate was dissolved in acidic (three drops of concentration hydrochloric acid) methoxyethanol (8 mL) and heated at 120° C. overnight. After solvent was removed, the residue was treated with 4 N hydrogen chloride in dioxane for 3 h. Purification by flash chromatography (silica gel, eluting with 6% of 10% methanolic ammonium hydroxide in dichloromethane) gave the title compound.
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[N:8]([CH3:9])[C:7]([CH2:10][OH:11])=[N:6][CH:5]=1.I[CH3:13]>C1COCC1.CCOC(C)=O>[Br:3][C:4]1[N:8]([CH3:9])[C:7]([CH2:10][O:11][CH3:13])=[N:6][CH:5]=1
Reactant: CI
Reactant: Cn1c(Br)cnc1CO
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COCc1ncc(Br)n1C
Reaction time: 0.25 h
Yield: 27.4 %

Procedure:
NaH (60%, 30 mg) was added to a solution of (5-bromo-1-methyl-1H-imidazol-2-yl)methanol (120 mg, 0.63 mmol) in THF (4 mL). After stirring for 15 minutes, iodomethane (35 uL, 0.57 mmol) was added. The resulting solution was stirred at 60° C. under microwave irradiation for 60 minutes. The reaction mixture was diluted with EtOAc, filtered and concentrated in vacuo. The residue was purified using Biotage silica gel column chromatography eluting with EtOAc to give the title compound as light brown oil (32 mg, 25%).
Reaction SMILES: Cl.[N:2]1([CH2:7][C:8]([OH:10])=O)[CH2:6][CH2:5][CH2:4][CH2:3]1.[NH2:11][C@@H:12]([CH2:30][O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)=[CH:18][CH:17]=1)=[O:14]>>[CH2:32]([O:31][CH2:30][C@H:12]([NH:11][C:8](=[O:10])[CH2:7][N:2]1[CH2:3][CH2:4][CH2:5][CH2:6]1)[C:13]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)=[CH:18][CH:17]=1)=[O:14])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1
Reactant: O=C(O)CN1CCCC1
Reactant: N[C@@H](COCc1ccccc1)C(=O)Nc1ccc(Oc2ccc(F)cc2)cc1
Agent: Cl
Product: O=C(CN1CCCC1)N[C@@H](COCc1ccccc1)C(=O)Nc1ccc(Oc2ccc(F)cc2)cc1
Yield: 74.8 %

Procedure:
Proceeding as in Example 1, but substituting 2-(pyrrolidin-1-yl)acetic acid hydrochloride and (S)-2-amino-3-(benzyloxy)-N-(4-(4-fluorophenoxy)phenyl)propanamide, gave Compound 215, (S)-3-(benzyloxy)-N-(4-(4-fluorophenoxy)phenyl)-2-(2-(pyrrolidin-1-yl)acetamido)propanamide (29.4 mg, 74.8%); Major isomer: 1H-NMR (400 MHz, DMSO-D6): σ 10.21 (s, 1H), 7.92 (d, 1H), 7.60 (d, 2H), 7.27-7.31 (m, 5H), 7.21 (d, 2H), 6.99-4.03 (m, 4H), 4.72 (m, 1H), 4.52 (s, 2H), 3.70-3.75 (m, 2H), 3.12 (d, 2H), 2.55 (d, 4H), 1.72 (m 4H). MS (EI) for C28H30FN3O4. found 492.5 (MH+).
Reaction SMILES: [CH:1]1(Br)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C([O-])([O-])=O.[K+].[K+].[C:14]([O:18][C:19](=[O:44])[CH2:20][N:21]1[C:25]2[CH:26]=[CH:27][C:28]([NH:30][S:31]([C:34]3[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=3)(=[O:33])=[O:32])=[CH:29][C:24]=2[N:23]=[C:22]1[CH2:41][CH2:42][CH3:43])([CH3:17])([CH3:16])[CH3:15]>CC#N.CCOC(C)=O.O>[C:14]([O:18][C:19](=[O:44])[CH2:20][N:21]1[C:25]2[CH:26]=[CH:27][C:28]([N:30]([CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)[S:31]([C:34]3[CH:35]=[CH:36][C:37]([F:40])=[CH:38][CH:39]=3)(=[O:32])=[O:33])=[CH:29][C:24]=2[N:23]=[C:22]1[CH2:41][CH2:42][CH3:43])([CH3:17])([CH3:16])[CH3:15]
Reactant: BrC1CCCCC1
Reactant: CCCc1nc2cc(NS(=O)(=O)c3ccc(F)cc3)ccc2n1CC(=O)OC(C)(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Solvent: CCOC(C)=O
Product: CCCc1nc2cc(N(C3CCCCC3)S(=O)(=O)c3ccc(F)cc3)ccc2n1CC(=O)OC(C)(C)C
Temperature: 80 °C
Reaction time: 8 h

Procedure:
Cyclohexyl bromide (0.27 mmol) and K2CO3 (63 mg, 0.45 mmol) were added to a solution of [5-(4-fluoro-benzenesulfonylamino)-2-propyl-benzoimidazol-1-yl]-acetic acid tert-butyl ester (40 mg, 0.09 mmol) in CH3CN (1 mL), and stirred overnight at 80° C. The reaction mixture was diluted with EtOAc and H2O, and then filtered through an Extrelut column. The column was washed with EtOAc, and the filtrate was concentrated. The crude product was carried onto the next reaction without any further purification or characterization.
Reaction SMILES: [C:1]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:6]=[CH:5][C:4]([C@H:7]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=2)[C@@H:8]([NH2:10])[CH3:9])=[CH:3][CH:2]=1.[C:26](OCC)(=[O:34])[CH2:27][CH2:28][CH2:29][CH2:30][C:31]([O-:33])=[O:32].Cl.C(N=C=NCCCN(C)C)C>CN(C)C1C=CN=CC=1.C(Cl)Cl.C(OCC)C>[C:1]1([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:2]=[CH:3][C:4]([C@H:7]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=2)[C@@H:8]([NH:10][C:26]([CH2:27][CH2:28][CH2:29][CH2:30][C:31]([OH:33])=[O:32])=[O:34])[CH3:9])=[CH:5][CH:6]=1
Reactant: C[C@H](N)[C@@H](Cc1ccc(Cl)c(Cl)c1)c1ccc(-c2ccccc2)cc1
Reactant: CCOC(=O)CCCCC(=O)[O-]
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Solvent: CCOCC
Product: C[C@H](NC(=O)CCCCC(=O)O)[C@@H](Cc1ccc(Cl)c(Cl)c1)c1ccc(-c2ccccc2)cc1
Yield: 49.5 %

Procedure:
24 mg of (1S,2S)-2-(4-biphenylyl)-3-(3,4-dichlorophenyl)-1-methylpropylamine obtained in Example 115, 14 mg of monoethyl adipate and 10 mg of 4-dimethylaminopyridine were dissolved in 2 ml of methylene chloride, and 15 mg of 1-ethyl-3-(3-dimethyaminopropyl)carbodiimide hydrochloride was added thereto with stirring under cooling with ice. The mixture was stirred at room temperature for 3 hours. The reaction solution was diluted with ethyl ether, then sequentially washed with a 10% citric acid aqueous solution, a saturated sodium hydrogencarbonate aqueous solution and a saturated sodium chloride aqueous solution, and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (Wakogel™ C-200, 1 g, hexane/ethyl acetate=2/1), and 28 mg of the obtained amide compound was dissolved in 1 ml of methanol. Then, 0.5 ml of a 2N sodium hydroxide aqueous solution was added thereto, and the mixture was stirred at room temperature overnight. The reaction solution was acidified with 1N hydrochloric acid and then subjected to liquid separation by an addition of ethyl ether and water. The organic layer was collected by separation, then washed with a saturated sodium chloride aqueous solution and dried over anhydrous magnesium sulfate. The drying agent was separated by filtration, and then the solvent was distilled off. The residue was treated with a liquid mixture of isopropyl ether and ethyl ether to obtain 16 mg (yield: 49%) of the above-identified compound as white crystalline powder having a melting point of from 123° to 124° C. and
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][N:3]=1.Cl[C:10]1[C:11](=[O:25])[C:12]2[C:17]([C:18](=[O:21])[C:19]=1Cl)=[C:16]([N+:22]([O-:24])=[O:23])[CH:15]=[CH:14][CH:13]=2>C(O)C>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]2[N:3]([C:10]3[C:11](=[O:25])[C:12]4[CH:13]=[CH:14][CH:15]=[C:16]([N+:22]([O-:24])=[O:23])[C:17]=4[C:18](=[O:21])[C:19]=3[N:1]=2)[CH:4]=1
Reactant: O=C1C(Cl)=C(Cl)C(=O)c2c1cccc2[N+](=O)[O-]
Reactant: Nc1ccc(Cl)cn1
Solvent: CCO
Product: O=C1c2nc3ccc(Cl)cn3c2C(=O)c2cccc([N+](=O)[O-])c21
Yield: 7.2 %

Procedure:
2.50 g (19.0 mmol) of 2-amino-5-chloropyridine are added to a solution of 2.50 g (11.0 mmol) of 2,3-dichloro-1,4-dihydro-1,4-dioxo-5-nitronaphthalene in 500 mL of ethanol. This mixture is heated to reflux for 62 h and 50 min. The solution passes from yellow to claret-colored, then to orange. After cooling, the reaction mixture is filtered. The precipitate is washed with ethanol, then dried in an oven for 20 h. The precipitate obtained is recrystallized in 650 mL of ethanol. This precipitate is purified on a flash column (support: silica; eluent: dichloromethane). 0.260 g of 2-chloro-6,11-dihydro-6,11-dioxo-7-nitronaphtho[2',3':4,5]imidazo[1,2-a]-pyridine or 2-chloro-6,11-dihydro-6,11-dioxo-10-nitronaphtho[2',3':4,5]imidazo[1,2-a] pyridine is obtained in the form of orange crystals, and 0.495 g of 10-chloro-5,6-dihydro-5,6-dioxo-4-nitronaphtho[1',2':4,5] imidazo[1,2-a]pyridine is formed in the form of orange crystals.
Reaction SMILES: [C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([CH3:5])=O.[CH2:9]([NH2:12])[CH2:10][CH3:11].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])([O-])=O.[Na+].[Na+]>C(Cl)(Cl)Cl.C(O)(=O)C.ClCCCl>[CH2:9]([NH:12][CH:2]([CH2:3][CH3:5])[C:1]([O:7][CH3:8])=[O:6])[CH2:10][CH3:11]
Reactant: COC(=O)CC(C)=O
Reactant: CCCN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: CC(=O)O
Solvent: ClCCCl
Product: CCCNC(CC)C(=O)OC
Temperature: 25 °C
Reaction time: 96 h

Procedure:
A mixture of 6 g of methyl acetoacetate, 5 mL of 1-propylamine, 40 mL of 1,2-dichloroethane, 3 mL of glacial acetic acid and 16 g of sodium triacetoxyborohydride was stirred at room temperature for 4 days. The reaction mixture was poured into 200 mL chloroform and 50 mL saturated aqueous Na2CO3 and the layers separated. The aqueous layer was extracted with 200 mL of chloroform and the combined organic layers dried over MgSO4 and concentrated under reduced pressure. After drying under vacuum, 9 g of (±)-methyl 2-(1-propylamino)butyrate was obtained as an oil: TLC (EtOAc); 1H NMR (400 MHz, CDCl3) 6.2 (br s, 1H), 3.65 (s, 3H), 3.2 (complex m, 2H), 2.65 (complex m, 2H), 2.45 (dd, 1H), 1.55 (m, 2H), 1.4 (d, 3H), 0.95 (t, 3H).
Reaction SMILES: [CH3:1][N:2]([N:15]=[O:16])[C:3]([NH:5][C@@H:6]1[O:14][CH2:13][C@@H:11]([OH:12])[C@H:9]([OH:10])[C@H:7]1[OH:8])=[O:4].C(O[C:21](=[O:23])[CH3:22])(=O)C>N1C=CC=CC=1>[CH3:1][N:2]([N:15]=[O:16])[C:3]([NH:5][C@@H:6]1[O:14][CH2:13][C@@H:11]([O:12][C:21](=[O:23])[CH3:22])[C@H:9]([O:10][C:9](=[O:10])[CH3:11])[C@H:7]1[O:8][C:7](=[O:8])[CH3:6])=[O:4]
Reactant: CN(N=O)C(=O)N[C@@H]1OC[C@@H](O)[C@H](O)[C@H]1O
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CO[C@H]1NC(=O)N(C)N=O
Yield: 87 %

Procedure:
1-methyl-1-nitroso-3-(β-D-xylopyranosyl)urea (110 mg) was dissolved in a mixture of pyridine (1 ml) and acetic anhydride (1 ml) and the resulting mixture was allowed to stand at room temperature for effecting the acetylation. The reaction mixture was then concentrated under a reduced pressure to give a crystalline residue which was then crystallized from ethanol, yielding the titled compound (147 mg). Yield 87.0%. mp. 127°-127° C. (with decomposition). [α]D20 -25.4° (c 0.7, chloroform).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4](/[CH:9]=[CH:10]/[CH2:11]O)[CH:5]=[C:6]([F:8])[CH:7]=1.P(Br)(Br)[Br:14].O>CCOCC>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4](/[CH:9]=[CH:10]/[CH2:11][Br:14])[CH:3]=1
Reactant: OC/C=C/c1cc(F)cc(Br)c1
Reactant: BrP(Br)Br
Solvent: O
Solvent: CCOCC
Product: Fc1cc(Br)cc(/C=C/CBr)c1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A solution of 4.2 g (0.0182 mol) of (E)-3-(3-bromo-5-fluorophenyl)-2-propen-1-ol in 65 ml of anhydrous ether is cooled to 0° C. under a nitrogen atmosphere. 3.3 g (0.0121 mol) of phosphorus tribromide are added dropwise and then the mixture is stirred for 1 h at 0° C. and left to return to room temperature overnight. The mixture is poured into water and extraction with ether, washing with water, drying over sodium sulphate, filtration and concentration under vacuum are carried out.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C:3]1=O.[CH3:9][O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][CH:15]=[CH:14]2.P(=O)(O)(O)O>C(O)(=O)C>[CH3:9][O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][CH:15]=[C:14]2[C:5]1[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH:6]=1
Reactant: CN1CCCCC1=O
Reactant: COc1ccc2[nH]ccc2c1
Agent: O=P(O)(O)O
Solvent: CC(=O)O
Product: COc1ccc2[nH]cc(C3=CCN(C)CC3)c2c1

Procedure:
Using the procedure of J. Org. Chem., Vol. 40, No. 17 (1975), p. 2525, 1-methyl-piperidone and 5-methoxy-1H-indole were condensed in refluxing acetic acid in the presence of phosphoric acid to obtain 5-methoxy-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole melting at 235° C.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:15]=[C:14]([OH:16])[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:7]=1)=[O:5])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH2:23](Br)[CH:24]=[CH2:25]>CC(C)=O>[CH2:25]([O:16][C:14]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[N:7]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH:15]=1)[CH:24]=[CH2:23]
Reactant: CCOC(=O)c1cc(O)c2ccccc2n1
Reactant: C=CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: C=CCOc1cc(C(=O)OCC)nc2ccccc12

Procedure:
A well-stirred mixture of 65.1 parts of ethyl-4-hydroxy-quinoline-2-carboxylate, 42 parts of anhydrous potassium carbonate, 38.4 parts of allyl bromide and 800 parts of acetone was boiled under reflux for 24 hours. The cooled reaction mixture was filtered to remove inorganic salts and acetone was removed by evaporation under reduced pressure. A solution of the residual brown oil in ether (360 parts) was washed successively with N-sodium hydroxide solution (3 portions each comprising 50 parts) and water (4 portions each of 100 parts), then dried over magnesium sulphate and evaporated to remove solvent. The resultant viscous oil crystallised on cooling and the crystals were recrystallised from light petroleum (60°-80°C) to yield 57.1 parts of ethyl 4-allyloxyquinoline-2-carboxylate as pale yellow needles, m.pt. 71°-72°C.