Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2](=[N:30][OH:31])[CH:3]1[CH2:8][CH2:7][N:6]([C:9]2[CH:18]=[CH:17][C:16]3[C:11](=[CH:12][CH:13]=[C:14]([Cl:29])[C:15]=3[NH:19][C:20](=[O:28])[CH2:21][CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)[N:10]=2)[CH2:5][CH2:4]1.N1C=CC=CC=1.C(C(CCCC)[CH2:41][O:42]C(Cl)=O)C>ClCCl>[Cl:29][C:14]1[C:15]([NH:19][C:20](=[O:28])[CH2:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)=[C:16]2[C:11](=[CH:12][CH:13]=1)[N:10]=[C:9]([N:6]1[CH2:7][CH2:8][CH:3]([C:2]3[NH:1][C:41](=[O:42])[O:31][N:30]=3)[CH2:4][CH2:5]1)[CH:18]=[CH:17]2
Reactant: CCCCC(CC)COC(=O)Cl
Reactant: NC(=NO)C1CCN(c2ccc3c(NC(=O)CC4CCCCC4)c(Cl)ccc3n2)CC1
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=C(CC1CCCCC1)Nc1c(Cl)ccc2nc(N3CCC(c4noc(=O)[nH]4)CC3)ccc12
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To a stirred solution of N-[2-[4[amino(hydroxyimino)methyl]-1-piperidinyl]-6-chloro-5-quinolinyl]-cyclohexaneacetamide (example 102(a)) (0.1 g) and pyridine (0.02 mL) in dichloromethane (5 mL) at 0° C. was added 2-ethylhexylchloroformate (0.064 mL). After 10 minutes the reaction was allowed to warm to room temperature and was then stirred for 2 hours. The solvent was removed under vacuum and the resulting solid was transferred to a 10 mL microwave vial with isohexane (3 mL) and heated within a microwave at 140° C. for 20 minutes. The reaction mixture was filtered and the solid was taken up in boiling methanol (20 mL) and purified by Varian NH2 cartridge (methanol (50 mL) and then acetic acid:methanol 10:90 as eluant) to afford the title product (0.042 g).
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]([OH:10])=[O:9])=[CH:6][N:5]=[CH:4][CH:3]=1.C(O)(=O)C.[Br:15]Br>O>[NH2:1][C:2]1[C:7]([C:8]([OH:10])=[O:9])=[CH:6][N:5]=[CH:4][C:3]=1[Br:15]
Reactant: BrBr
Reactant: Nc1ccncc1C(=O)O
Solvent: O
Solvent: CC(=O)O
Product: Nc1c(Br)cncc1C(=O)O
Temperature: 75 °C
Reaction time: 16 h
Yield: 83.6 %

Procedure:
A sealed tube was charged with 4-aminonicotinic acid 45 (8.00 g, 57.9 mmol), acetic acid (75 mL) and water (75 mL). The reaction was heated at 75° C. and stirred vigorously until homogeneous. After cooling to 50° C., bromine (10.0 mL, 195 mmol) was added and stirring continued for 16 h. Upon cooling to 0° C., the resulting orange precipitate was collected by filtration, rinsed with H2O, and dried under vacuum to give 46 (10.5 g, 84% yield).
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[C:3]([OH:13])([C:9]([F:12])([F:11])[F:10])[CH2:4][S:5]([O-:8])(=[O:7])=[O:6].[C:16]1([S+:22]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(N(CC)CC)C.[C:42]12([C:52](Cl)=[O:53])[CH2:51][CH:46]3[CH2:47][CH:48]([CH2:50][CH:44]([CH2:45]3)[CH2:43]1)[CH2:49]2>CN(C)C1C=CN=CC=1.C(Cl)Cl>[C:42]12([C:52]([O:13][C:3]([C:2]([F:1])([F:14])[F:15])([C:9]([F:12])([F:10])[F:11])[CH2:4][S:5]([O-:8])(=[O:7])=[O:6])=[O:53])[CH2:49][CH:48]3[CH2:47][CH:46]([CH2:45][CH:44]([CH2:50]3)[CH2:43]1)[CH2:51]2.[C:29]1([S+:22]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1
Reactant: O=S(=O)([O-])CC(O)(C(F)(F)F)C(F)(F)F
Reactant: O=C(Cl)C12CC3CC(CC(C3)C1)C2
Agent: CN(C)c1ccncc1
Agent: c1ccc([S+](c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(OC(CS(=O)(=O)[O-])(C(F)(F)F)C(F)(F)F)C12CC3CC(CC(C3)C1)C2
Temperature: 25 °C
Reaction time: 2 h
Yield: 39 %

Procedure:
Into a mixture solution of 5.2 g (10 mmoles) of triphenylsulfonium 3,3,3-trifluoro-2-hydroxy-2-trifluoromethylpropane-1-sulfonate prepared in Synthesis Example 1-9, 1.1 g (11 mmoles) of triethylamine, 0.24 g (2 mmoles) of 4-dimethylaminopyridine, and 21 g of methylene chloride was added 5.5 g (11 mmoles) of a methylene chloride solution of adamantane-1-carbonyl chloride (40% by weight), and they were stirred at room temperature for 2 hours. Thereafter, the reaction was terminated by adding 12 g of 5% hydrochloric acid, and then the organic layer was separated, washed by water, and concentrated under reduced pressure. Into the concentrated solution was added methyl isobutyl ketone, and the resulted mixture was concentrated again under reduced pressure to distil the remaining water out. The obtained residue was washed by diisopropyl ether, and then dried to obtain the intended triphenylsulfonium 2-(adamantane-1-carbonyloxy)-3,3,3-trifluoro-2-trifluoromethylpropane-1-sulfonate (2.7 g of oily substance (yield 39%)). The structure of the intended product is shown below.
Reaction SMILES: O(P(O[C:18]1[C@H:19]([CH3:42])[C@H:20]2[C@@H:37]([C@H:38]([OH:40])[CH3:39])[C:36](=[O:41])[N:21]2[C:22]=1[C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=1)=[O:24])(OC1C=CC=CC=1)=O)C1C=CC=CC=1.[SH:43][C@@H:44]1[CH2:48][N:47]([C:49]([O:51][CH2:52][C:53]2[CH:58]=[CH:57][C:56]([N+:59]([O-:61])=[O:60])=[CH:55][CH:54]=2)=[O:50])[C@H:46]([CH:62]2[CH2:66][NH:65][C:64](=[O:67])[CH:63]2[NH:68][C:69]([O:71][CH2:72][C:73]2[CH:78]=[CH:77][C:76]([N+:79]([O-:81])=[O:80])=[CH:75][CH:74]=2)=[O:70])[CH2:45]1>>[OH:40][C@@H:38]([C@H:37]1[C:36](=[O:41])[N:21]2[C:22]([C:23]([O:25][CH2:26][C:27]3[CH:28]=[CH:29][C:30]([N+:33]([O-:35])=[O:34])=[CH:31][CH:32]=3)=[O:24])=[C:18]([S:43][C@@H:44]3[CH2:48][N:47]([C:49]([O:51][CH2:52][C:53]4[CH:58]=[CH:57][C:56]([N+:59]([O-:61])=[O:60])=[CH:55][CH:54]=4)=[O:50])[C@H:46]([CH:62]4[CH2:66][NH:65][C:64](=[O:67])[CH:63]4[NH:68][C:69]([O:71][CH2:72][C:73]4[CH:74]=[CH:75][C:76]([N+:79]([O-:81])=[O:80])=[CH:77][CH:78]=4)=[O:70])[CH2:45]3)[C@H:19]([CH3:42])[C@H:20]12)[CH3:39]
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(OP(=O)(Oc3ccccc3)Oc3ccccc3)[C@H](C)[C@@H]12
Reactant: O=C(NC1C(=O)NCC1[C@@H]1C[C@H](S)CN1C(=O)OCc1ccc([N+](=O)[O-])cc1)OCc1ccc([N+](=O)[O-])cc1
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@H]3C[C@@H](C4CNC(=O)C4NC(=O)OCc4ccc([N+](=O)[O-])cc4)N(C(=O)OCc4ccc([N+](=O)[O-])cc4)C3)[C@H](C)[C@H]12
Yield: 48.9 %

Procedure:
The same procedure as in Example 1-1 was carried out by using p-nitrobenzyl (1R,5S,6S)-2-diphenoxyphosphoryloxy-6-[(R)-1-hydroxyethyl]-1-methyl-1-carbapen- 2-em-3-carboxylate (155.4 mg, 0.26 mmol) and (2S,4S)-4-mercapto-N-(p-nitrobenzyloxycarbonyl)-2-[3-[(p-nitrobenzyloxycarbonyl)amino]-2-pyrrolidon-4-yl]pyrrolidine (110 mg, 0.197 mmol, compound of Reference Example 20-6) to obtain p-nitrobenzyl (1R,5S,6S)-6-[(R)-1-hydroxyethyl]-1-methyl-2-[(2S,4S)-N-(p-nitrobenzyloxycarbonyl)-2-[3-[(p-nitrobenzyloxycarbonyl)amino]-2-pyrrolidon-4-yl]pyrrolidin-4-ylthio]-1-carbapen-2-em-3-carboxylate (87 mg, yield: 48.9%).
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[CH:3]1.[CH:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9][C:8]=1[C:17](Cl)=[O:18]>C1(C)C=CC=CC=1>[CH:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9][C:8]=1[C:17]([C:3]1[N:2]([CH3:1])[CH:6]=[CH:5][CH:4]=1)=[O:18]
Reactant: Cn1cccc1
Reactant: O=C(Cl)c1ccc2ccccc2c1
Solvent: Cc1ccccc1
Product: Cn1cccc1C(=O)c1ccc2ccccc2c1
Reaction time: 38 h
Yield: 90.3 %

Procedure:
N-Methylpyrrole (19.5 g, 0.24 mole) and 2-napthalenoyl chloride (50.0 g, 0.26 mole) 300 mL of dry toluene were heated under reflux overnight with a nitrogen stream bubbling through the reaction mixture. Another 10 mL of N-methylpyrrole was added to the reaction mixture and the reflux was continued for another 38 hr. 100 mL of 20% aqueous 3-(dimethylamino)propylamine was added and stirred for 30 minutes. Et2O/THF was added and the organics were separated off, washed with 1 N HCl, NaHCO3, water, brine and dried (MgSO4). The solvent was evaporated in vacuo to give 51 g (90%) of (2-naphthalenyl)(1-methyl-1H-pyrrol-2-yl)-methanone. mp 108-110° C. CIMS m/z236 (MH+). 1H NMR (300 MHz, CDCl3) δ 8.35 (Ar, 1H); 8.0-7.9 (Ar, 4H); 7.6-7.5 (Ar, 2H); 6.95 (Ar, 1H); 6.8 (Ar, 1H); 6.2 (Ar, 1H); 4.1 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]2[C:16]3=[C:17]([C@H:19]4[CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22][CH2:21][C@H:20]4[N:15]3[CH2:14][CH2:13][CH2:12]2)[CH:18]=1.[OH-].[Na+]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]2[C:16]3=[C:17]([C@H:19]4[CH2:24][NH:23][CH2:22][CH2:21][C@H:20]4[N:15]3[CH2:14][CH2:13][CH2:12]2)[CH:18]=1
Reactant: CC(C)(C)OC(=O)N1CC[C@@H]2[C@H](C1)c1cc(-c3cccc(Cl)c3Cl)cc3c1N2CCC3
Agent: [Na+]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Clc1cccc(-c2cc3c4c(c2)[C@H]2CNCC[C@H]2N4CCC3)c1Cl
Temperature: 25 °C
Reaction time: 2 h
Yield: 99.7 %

Procedure:
Tert-butyl (±)-cis-2-(2,3-dichlorophenyl)-5,6,8,9,11,11a-hexahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline-10(7aH)-carboxylate (55 mg, 0.12 mmol) was dissolved in 20% TFA in methylene chloride (4 mL) and was stirred at RT for 2 h. The reaction was solution was cooled to 0° C. and basified with 1M NaOH until pH>14. The layers were separated. The aqueous phase was extracted the methylene chloride (2×10 ml). The organic layers were washed with brine and dried. Concentration afforded the title compound (43 mg, 100%) as a pale yellow amorphous solid. 1H NMR (CDCl3, 300 MHz) δ 7.37 (dd, 1H, J=2.6, 7.3 Hz), 7.15-7.23 (m, 2H), 6.97 (s, 1H), 6.92 (s, 1H), 3.43-3.46 (m, 1H), 3.31 (dt, 1H, J=4.4, 10.2), 3.03-3.11 (m, 2H), 2.81-2.94 (m, 2H), 2.60-2.80 (m, 4H), 2.11-2.20 (m, 2H), 1.89-1.98 (m, 1H), 1.74-1.85 (m, 1H) ppm. MS (CI, NH3): 359 (base, M+H).
Reaction SMILES: N[C@H:2]([C:11]([OH:13])=[O:12])CC1C=CC(O)=CC=1.[NH2:14][C@H:15]([C:17]([OH:19])=[O:18])[CH3:16].N[C@H](C(O)=O)CC1C=CC=CC=1.NCC(O)=O.N[C@H](C(O)=O)CC(C)C.N[C@H](C(O)=O)CCCNC(=N)N.CC(CC(O)=O)=O>>[NH2:14][C@H:15]([C:17]([OH:19])=[O:18])[CH2:16][CH2:2][C:11](=[O:12])[OH:13]
Reactant: N[C@@H](Cc1ccc(O)cc1)C(=O)O
Reactant: C[C@H](N)C(=O)O
Agent: CC(=O)CC(=O)O
Agent: CC(C)C[C@H](N)C(=O)O
Agent: N=C(N)NCCC[C@H](N)C(=O)O
Product: N[C@@H](CCC(=O)O)C(=O)O

Procedure:
1.05 His: 1.03 Tyr: 0.99 Ala: 1.02 Phe: 1.00 Gly: 1.07 Leu: 1.00 Arg: 0.94 Pro: 1.02 Recovery 95% (calculated as the diacetate)
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([N:16]2[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]2)=[O:15])[CH2:10][CH2:9]1)=O)(C)(C)C.[ClH:23]>O1CCOCC1.C(OCC)C>[ClH:23].[CH3:22][N:19]1[CH2:18][CH2:17][N:16]([C:14]([CH:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]2)=[O:15])[CH2:21][CH2:20]1
Reactant: CN1CCN(C(=O)C2CCN(C(=O)OC(C)(C)C)CC2)CC1
Agent: Cl
Solvent: CCOCC
Solvent: C1COCCO1
Product: CN1CCN(C(=O)C2CCNCC2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 54 %

Procedure:
A mixture of 4-(4-methyl-piperazine-1-carbonyl)-piperidine-1-carboxylic acid tert-butyl ester (25.8 g, 82.8 mmol), dry dioxane (500 mL) and 6.5 N hydrogen chloride in dioxane (275 mL) was stirred at room temperature overnight, then diluted with diethyl ether and stirred at 0° C. for 1 h. The precipitated crystals were filtered off, washed with diethyl ether and dried to yield 12.44 g (54%) of the title compound. Mp: 305-307° C. (decomposition).
Reaction SMILES: [N:1]([O-:3])=O.[Na+].[NH2:5][C:6]1[N:11]=[C:10]([O:12][CH2:13][CH2:14][OH:15])[CH:9]=[C:8]([NH2:16])[N:7]=1>O.C(O)(=O)C>[NH2:5][C:6]1[N:11]=[C:10]([O:12][CH2:13][CH2:14][OH:15])[C:9]([N:1]=[O:3])=[C:8]([NH2:16])[N:7]=1
Reactant: Nc1cc(OCCO)nc(N)n1
Reactant: O=N[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: Nc1nc(N)c(N=O)c(OCCO)n1
Reaction time: 2 h
Yield: 67.4 %

Procedure:
A solution of 4.55 g (0.066 mol) of sodium nitrite in 20 ml of water was added in drops to a solution of 8.50 g (0.050 mol) of 2-[(2,6-diaminopyrimidin-4-yl)oxy]ethan-1-ol in 100 ml of acetic acid (10% in water) over 1 h at 3-5° C. while stirring was performed. Then stirring was performed further for 2 h at room temperature. The resulting precipitate was sucked off, post-washed with water, and dried, whereby 2-[(2,6-diamino-5-nitrosopyrimidin-4-yl)oxy]ethan-1-ol (6.71 g, 67%) was obtained as a purple solid.
Reaction SMILES: [C:1]([O:5][C:6](=[O:24])[NH:7][CH:8]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH:9]([OH:16])[CH2:10][NH:11][CH2:12][CH:13]([CH3:15])[CH3:14])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH2:32]([O:39][C:40](Cl)=[O:41])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>ClCCl.C([O-])([O-])=O.[Na+].[Na+]>[CH2:32]([O:39][C:40](=[O:41])[N:11]([CH2:10][CH:9]([OH:16])[CH:8]([NH:7][C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:24])[CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[CH2:12][CH:13]([CH3:14])[CH3:15])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: CC(C)CNCC(O)C(Cc1ccccc1)NC(=O)OC(C)(C)C
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)CN(CC(O)C(Cc1ccccc1)NC(=O)OC(C)(C)C)C(=O)OCc1ccccc1
Temperature: -1.5 °C
Reaction time: 24 h
Yield: 100 %

Procedure:
(1-Benzyl-2-hydroxy-3-isobutylamino-propyl)-carbamic acid tert-butyl ester (2) (24.50 g, 72.80 mmol, 1 equiv) and triethylamine (7.37 g, 72.80 mmol, 1 equiv) were dissolved in dichloromethane (500 mL). The solution was cooled to −1.5° C., followed by the dropwise addition of benzylchloroformate (12.40 g, 72.80 mmol, 1 equiv). The solution was stirred at 0° C. for 24 h. Due to the incompleteness of the reaction, benzylchloroformate (2.40 g, 14.07 mmol) and triethylamine (1.44 g, 14.23 mmol) were added to the solution. The solution was stirred at room temperature for 24 h. The solution was diluted with 2% Na2CO3 solution (300 mL) and the mixture was stirred for 10 min. The organic layer was separated, washed with water (2x) and saturated sodium chloride solution (1×). The organic layer was dried on MgSO4, filtered, and evaporated to dryness to obtain the desired product as a yellow colored oil (34.30 g, 72.80 mmol, quantitative). LRMS (ES+): m/z 471 [M+H]+.
Reaction SMILES: CC[O:3][CH2:4][CH3:5].[C:6]1([CH3:16])[CH:11]=[CH:10][C:9](S(O)(=O)=O)=[CH:8][CH:7]=1>CO>[CH2:9]([C:10]([CH2:11][CH2:6][CH3:16])=[CH:9][CH2:8][CH2:7]/[CH:16]=[CH:6]/[CH2:7][CH2:8][CH2:5][CH2:4][OH:3])[CH2:10][CH3:11]
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: CCOCC
Solvent: CO
Product: CCCC(=CCC/C=C/CCCCO)CCC

Procedure:
0.6 g of diethyl 6-propyl-2,5-nonadienylphosphonate was dissolved in 10 ml. of tetrahydofuran, and an equivalent amount of n-butyl lithium was added at -60° C. in an atmosphere of argon. To this solution was further added 0.56g of 4-butyl iodide-1-tetrahydropyranyl ether. The temperature of the reaction system was gradually elevated to room temperature. The reaction mixture was poured into ice water, and extracted with ether. Concentration of the solvent gave a pale yellow viscous oily substance. The oily product was dissolved in 20 ml. of ether, and reduced with 0.2 g of lithium aluminum hydride to afford 0.5g of 10-propyl-trans-5,9-tridecadiene-1-tetrahydropyranyl ether in a yield of 80%. This ether was treated with a catalytic amount of p-toluenesulfonic acid in methanol to split off the protective group. Thus, there was obtained pure 10-propyl-trans-5,9-tridecadienol in a quantitative yield. The properties of this product were as follows:
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[O:11])[NH:8]2)=[CH:4][C:3]=1[F:12].[F:13][C:14]1[CH:21]=[CH:20][C:17]([CH:18]=O)=[CH:16][CH:15]=1.[BH4-].[Na+]>C(O)C>[F:12][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:2]=1[NH:1][CH2:18][C:17]1[CH:20]=[CH:21][C:14]([F:13])=[CH:15][CH:16]=1)[NH:8][C:7](=[O:11])[CH2:6]2
Reactant: O=Cc1ccc(F)cc1
Reactant: Nc1cc2c(cc1F)CC(=O)N2
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: O=C1Cc2cc(F)c(NCc3ccc(F)cc3)cc2N1
Temperature: 25 °C
Yield: 44.8 %

Procedure:
6-Amino-5-fluoro-1,3-dihydro-indol-2-one 3d (2.26 g, 13.6 mmol) was dissolved in 40 ml of ethanol under stirring at room temperature, the resulting solution was cooled down to 0° C. in an ice-water bath, and added with 4-fluoro-benzaldehyde (1.5 ml, 13.6 mmol) to the solution. Upon completion of the addition, the resulting solution was stirred for 1 hour at room temperature, added with sodium borohydride (1.08 g, 28.5 mmol) and heated to reflux for 18 hours. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was naturally cooled down to room temperature, added with ice water and lots of precipitates were formed, filtered and washed with water (50 ml×3). The residue was purified by silica gel column chromatography to obtain the title compound 5-fluoro-6-(4-fluoro-benzylamino)-1,3-dihydro-indol-2-one 3e (1.67 g, yield 45%) as a white solid.
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][C:6]([CH3:9])([CH3:8])[NH:5][C:4]([CH3:11])([CH3:10])[CH2:3]1.[OH-].[Na+].[N:14]#[C:15]Cl>C(Cl)Cl.O>[NH:1]([CH:2]1[CH2:3][C:4]([CH3:11])([CH3:10])[NH:5][C:6]([CH3:9])([CH3:8])[CH2:7]1)[C:15]#[N:14]
Reactant: CC1(C)CC(N)CC(C)(C)N1
Reactant: N#CCl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Product: CC1(C)CC(NC#N)CC(C)(C)N1

Procedure:
156 g (1 mole) of 4-amino-2,2,6,6-tetramethyl piperidine are dissolved in 500 ml of methylene chloride, 40 g (1 mole) of sodium hydroxide in 500 ml of water are introduced and 51 ml of cyanogen chloride are added dropwise at a temperature of 0° to 5° C. The mixture is stirred until it reaches room temperature, after which 4-cyanamido-2,2,6,6-tetramethyl piperidine, which melts at 240° C, is filtered off in a yield of 166 g (corresponding to 91.5% of the theoretical).
Reaction SMILES: CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[OH:25][C:26]1[CH:27]=[C:28]([CH:32]=[CH:33][C:34]=1[N+:35]([O-:37])=[O:36])[C:29]([OH:31])=O.C(N(CC)CC)C.Cl.[CH3:46][O:47][CH:48]1[CH2:51][NH:50][CH2:49]1>ClCCl>[OH:25][C:26]1[CH:27]=[C:28]([C:29]([N:50]2[CH2:51][CH:48]([O:47][CH3:46])[CH2:49]2)=[O:31])[CH:32]=[CH:33][C:34]=1[N+:35]([O-:37])=[O:36]
Reactant: COC1CNC1
Reactant: O=C(O)c1ccc([N+](=O)[O-])c(O)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC1CN(C(=O)c2ccc([N+](=O)[O-])c(O)c2)C1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 65.8 %

Procedure:
HATU (2.1 g, 5.5 mmol) was added to a solution of 3-hydroxy-4-nitrobenzoic acid (915 mg, 5 mmol), triethylamine (1.1 g, 11 mmol)) and 3-methoxyazetidine hydrochloride (740 mg, 5.5 mmol) in dichloromethane (10 mL). The reaction mixture was stirred at room temperature for 30 minutes. The reaction was partitioned between EtOAc (30 mL) and water (30 mL). The organic phase was collected, washed with water, brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a gradient of 100% ethyl acetate to 3% methanol in ethyl acetate to afford the title compound as a pale yellow solid (830 mg, 66%).
Reaction SMILES: [C:1]1([C:7]2[N:8]([CH2:28][C:29]3[N:34]=[C:33]([C:35]([O:37][CH3:38])=[O:36])[CH:32]=[CH:31][CH:30]=3)[C:9]3[C:14]([CH:15]=2)=[CH:13][C:12]([CH2:16][O:17][Si](C(C)C)(C(C)C)C(C)C)=[CH:11][CH:10]=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl-].[NH4+]>O1CCCC1>[OH:17][CH2:16][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:28][C:29]1[N:34]=[C:33]([C:35]([O:37][CH3:38])=[O:36])[CH:32]=[CH:31][CH:30]=1)[C:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[CH:15]2
Reactant: COC(=O)c1cccc(Cn2c(-c3ccccc3)cc3cc(CO[Si](C(C)C)(C(C)C)C(C)C)ccc32)n1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Agent: [F-]
Solvent: C1CCOC1
Product: COC(=O)c1cccc(Cn2c(-c3ccccc3)cc3cc(CO)ccc32)n1
Reaction time: 2 h
Yield: 81.9 %

Procedure:
To a solution of methyl 6-(2-phenyl-5-triisopropylsilanyloxymethylindol-1-ylmethyl)pyridine-2-carboxylate (77.0 mg) in tetrahydrofuran (0.728 mL) was added tetrabutylammonium fluoride (1.0 mol/L tetrahydrofuran solution, 0.190 mL) under cooling with ice. The mixture was stirred under cooling with ice for one hour and then at room temperature for additional 2 hours. A saturated aqueous ammonium chloride solution was added to the reaction mixture and this resulting mixture was extracted with ethyl acetate. The organic layer was washed with saturated saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (44.4 mg).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH2:10][C:11]#[N:12])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[C:13](=O)(OC)OC.C(=O)([O-])[O-].[K+].[K+]>ClCCl>[N+:1]([C:4]1[CH:5]=[C:6]([CH:10]([CH3:13])[C:11]#[N:12])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: COC(=O)OC
Reactant: N#CCc1cccc([N+](=O)[O-])c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: CC(C#N)c1cccc([N+](=O)[O-])c1
Temperature: 170 °C

Procedure:
A mixture of 62 mmol (10 g) of 3-nitrophenylacetonitrile, 1.11 mol (100 g) of dimethyl carbonate and 3.1 mmol (0.43 g) of potassium carbonate is heated for 6 hours at 170° C. in an autoclave. After cooling, 200 ml of dichloromethane are added and the organic phase is washed with 100 ml of water and then with 100 ml of a saturated aqueous solution of sodium chloride. The organic phase is dried over magnesium sulphate and concentrated. The residue obtained is purified by chromatography on silica gel, using as eluant a 90/10 cyclohexane/ethyl acetate mixture, to yield the expected product.
Reaction SMILES: [Br-].[C:2]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([OH:4])=[O:3].[CH:34](=O)[C:35]1[O:39][CH:38]=[CH:37][CH:36]=1>C1COCC1>[O:39]1[CH:38]=[CH:37][CH:36]=[C:35]1[CH:34]=[CH:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][C:2]([OH:4])=[O:3]
Reactant: O=C(O)CCCCCCCCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=Cc1ccco1
Agent: [Br-]
Solvent: C1CCOC1
Product: O=C(O)CCCCCCCCCC=Cc1ccco1
Yield: 45 %

Procedure:
This compound was synthesized from 10-carboxydecyltriphenylphosphonium bromide (10.50 g, 20 mmol) and furfural (1.92 g, 20 mmol) in THF (100 mL) by a Wittig reaction. Crystallization afforded the product (2.38 g, 45%) as pale yellow crystals (mp 38-39° C.); IR: 3450-2500, 1715, 695 cm-1 ; 1H-NMR: 1.35 (m, 14H), 2.35 (t, 4H), 5.60 (m, 1H), 6.30 (m, 3H), 7.35 (s, 1H), 9.40 (bs, 1H). Anal. Calcd. for C16H24O3 : C, 72.69, H, 9.15; Found: C, 72.44, H, 9.06%. Z:E=43:57.
Reaction SMILES: [Cl-].[Ce+3].[Cl-].[Cl-].[I-].[Na+].[Br:7][CH2:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1)=[O:10].[CH2:18]([N:25]1[CH2:30][CH2:29][C:28](=[O:31])[CH2:27][CH2:26]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.Br.C(O)C>O1CCCC1>[BrH:7].[CH2:18]([N:25]1[CH2:30][CH2:29][C:28]([CH2:8][C:9](=[O:10])[C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)([OH:31])[CH2:27][CH2:26]1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: O=C1CCN(Cc2ccccc2)CC1
Reactant: O=C(CBr)c1ccc(Cl)cc1
Agent: Br
Agent: [Ce+3]
Agent: [Cl-]
Solvent: C1CCOC1
Solvent: CCO
Product: O=C(CC1(O)CCN(Cc2ccccc2)CC1)c1ccc(Cl)cc1
Reaction time: 2 h
Yield: 38.3 %

Procedure:
Anhydrous cerium chloride (0.99 g, 4.0 mmol) and sodium iodide (1.8 g, 12.0 mmol) are added to 10 ml of anhydrous tetrahydrofuran as a solvent to form a suspension. Dissolving 0.98 g (4.0 mmol) of 2-bromo-1-(4-chlorophenyl)ethanone and 0.76 g (4.0 mmol) of N-benzyl-4-piperidone in 10 ml of anhydrous tetrahydrofuran, and the solution is added dropwise to the above suspension and reacting at room temperature for 2 hours. Operating according to the post-treatment procedure in General Method three, and a salt is formed by acidifying with hydrobromic acid/ethanol solution, which is recrystallized in ethanol to obtain 0.65 g of a white crystal, with yield of 36.7%.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][CH2:9][CH2:10][C:11]2=[O:14])=[CH:6][CH:5]=1)([O-])=O>C(O)C.[Ni]>[NH2:1][C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][CH2:9][CH2:10][C:11]2=[O:14])=[CH:6][CH:5]=1
Reactant: O=C1CCCc2ccc([N+](=O)[O-])cc21
Agent: [Ni]
Solvent: CCO
Product: Nc1ccc2c(c1)C(=O)CCC2

Procedure:
A solution of 2 g (0.0105 mole) 7-nitro-1-tetralone in 120 ml ethanol was hydrogenated under<5 psi H2 pressure using Raney Ni as catalyst. The solution was filtered with the aid of super cel. and concentrated under reduced pressure to give the 7-amino-1-tetralone.