Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:18])=[C:4]([CH:13]=[C:14]([F:17])[C:15]=1[F:16])[C:5]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])=[O:6].[CH:19](OCC)(OCC)[O:20][CH2:21][CH3:22].C(OC(=O)C)(=O)C>>[Cl:1][C:2]1[C:3]([F:18])=[C:4]([CH:13]=[C:14]([F:17])[C:15]=1[F:16])[C:5]([C:7](=[CH:19][O:20][CH2:21][CH3:22])[C:8]([O:10][CH2:11][CH3:12])=[O:9])=[O:6]
Reactant: CCOC(=O)CC(=O)c1cc(F)c(F)c(Cl)c1F
Reactant: CCOC(OCC)OCC
Solvent: CC(=O)OC(C)=O
Product: CCOC=C(C(=O)OCC)C(=O)c1cc(F)c(F)c(Cl)c1F

Procedure:
The reduction of 2,3,4-trichloro-5-fluoronitrobenzene (i) with Fe--HCI in hot water gives 2,3,4-trichloro-5-fluoroaniline (ii), which, by diazotization with NaNO2 --HCI and reaction with sodium tetra-fluoroborate and cuprous cyanide, is converted to 2,3,4-trichloro-5-fluorobenzonitrile (iii). The reaction of (iii) with KF in DMSO at 140° affords 3-chloro-2,4,5-trifluorobenzonitrile (iv), which, by hydrolysis with 30% HBr in refluxing acetic acid, gives 3-chloro-2,4,5-trifluorobenzamide (v). The hydrolysis of (v) with 18N H2SO4 at 135° yields the corrsponding benzoic acid (vi), which is treated with refluxing SOCl2 to afford the acyl chloride (vii). The condensation of (vii) with diethyl malonate (viii) by means of Mg-ethanol in hot toluene gives diethyl 3-chloro-2,4,5-trifluorobenzoylmalonate (ix), which is partially decarboxylated with p-toluenesulfonic acid in refluxing water to give ethyl 3-chloro-2,4,5-trifluorobenzoylacetate (x). The condensation of (x) with triethyl orthoformate (xi) in refluxing acetic anhydride yields ethyl 2-(3-chloro-2,4,5-trifluorobenzoyl)-3-ethoxyacrylate (xii), which is treated with cyclopropylamine (xiii) in ethanol to afford ethyl 2-(3-chloro-2,4,5-trifluorobenzoyl)-3-(cyclopropylamino)acrylate (xiv). The cyclization of (xiv) by means of NaF in DMF at 150° gives ethyl 8-chloro-1-cyclopropyl-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate (xv), which is hydrolyzed with H2SO4 in refluxing water-acetic acid to the corresponding carboxylic acid (xvi).
Reaction SMILES: [K].[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:13][C:12]([C:14](=[O:18])[C:15]([OH:17])=[O:16])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1>>[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[S:13][C:12]([CH:14]([OH:18])[C:15]([OH:17])=[O:16])=[CH:11][CH:10]=2)=[CH:7][CH:8]=1
Reactant: O=C(O)C(=O)c1ccc(-c2ccc(Cl)cc2)s1
Agent: [K]
Product: O=C(O)C(O)c1ccc(-c2ccc(Cl)cc2)s1

Procedure:
When the above procedure was repeated starting with the potassium salt of 5-(4-chlorophenyl)thien-2-ylglyoxylic acid, there was obtained 5-(4-chlorophenyl)thien-2-ylglycolic acid, m.p. 158°-160° C.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][C:5]=1Cl)=[O:3].Cl>[Cu].C1(C)C=CC=CC=1>[CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([Cl:10])=[CH:6][CH:5]=1)=[O:3]
Reactant: CC(=O)c1ccc(Cl)cc1Cl
Agent: [Cu]
Agent: Cl
Solvent: Cc1ccccc1
Product: CC(=O)c1ccc(Cl)cc1
Temperature: 135 °C
Yield: 82.5 %

Procedure:
A 100-mL round-bottom flask was equipped with a magnetic stir bar, reflux condenser, thermometer, nitrogen inlet, and heating mantle attached to a temperature controller. The flask was charged with 2,4-dichloroacetophenone (5.0 g, 26.5 mmol) and copper powder (0.84 g, 13.2 mmol). The flask was purged with nitrogen for 0.5 hour. Meanwhile, a separate flask was charged with acetic acid (30 g) and triethylamine (30 g). The resulting solution was degassed by bubbling nitrogen through the solution for 0.5 hour. A portion of the degassed solution (20 mL) was charged to the reaction flask by syringe and the resulting mixture was heated to 135° C. Additional copper (0.17 g, 2.65 mmol) was added after 2 hours in order to complete the dehalogenation. The reaction was monitored by GC analysis and was judged to be complete when the starting material was no longer detectable (5 hours). The reaction mixture was cooled to room temperature and poured into a 250-mL Erlenmeyer flask; toluene (50 mL) and 2M hydrochloric acid solution (50 mL) were added. The resulting mixture was filtered, and the solids were washed with toluene. The resulting brown organic layer was washed with 2M hydrochloric acid solution (50 mL), water (50 mL), and 5% sodium hydroxide solution (50 mL). Solids precipitated during the base wash. The mixture was filtered through a pad of Florisil® (magnesium silicate), which was rinsed with additional toluene. The filtrates were combined to give a yellow solution. The solvent was removed by evaporation under reduced pressure. The residue was dried under vacuum, yielding 3.38 g of 4-chloroacetophenone as a brown oil.
Reaction SMILES: FC(F)(F)C([NH:5][CH2:6][CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11](/[CH:15]=[CH:16]/[C:17]([OH:24])([CH2:21][CH2:22][CH3:23])[CH2:18][CH2:19][CH3:20])[CH:10]=1)=O.C([O-])([O-])=O.[K+].[K+]>>[NH2:5][CH2:6][CH2:7][CH2:8][C:9]1[CH:10]=[C:11]([CH:12]=[CH:13][CH:14]=1)/[CH:15]=[CH:16]/[C:17]([OH:24])([CH2:18][CH2:19][CH3:20])[CH2:21][CH2:22][CH3:23]
Reactant: CCCC(O)(/C=C/c1cccc(CCCNC(=O)C(F)(F)F)c1)CCC
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CCCC(O)(/C=C/c1cccc(CCCN)c1)CCC

Procedure:
(E)-2,2,2-Trifluoro-N-(3-(3-(3-hydroxy-3-propylhex-1-enyl)phenyl)propyl)acetamide was deprotected according to the method used in Example 79 except that 3 equivalents of K2CO3 were used. Following the reaction, solids were removed by filtration and the filtrate was concentrated under reduced pressure. The residue was dissolved in MeOH, dried over MgSO4 and filtered through Celite. After concentration under reduced pressure, purification by flash chromatography (7:3 EtOAc:hexanes to 7:2:1 EtOAc:hexanes: 7 M NH3 in MeOH gradient) gave Example 83 as a single trans isomer. Yield (0.348 g, quant.): 1H NMR (400 MHz, DMSO-d3) δ 7.18-7.22 (m, 3H), 7.03-7.06 (m, 1H), 6.51 (d, J=16.0 Hz, 1H), 6.20 (d, J=16.4 Hz, 1H), 4.30 (br s, 1H), 2.66 (t, J=7.4 Hz, 2H), 2.64 (t, J=7.8 Hz, 2H), 1.75-1.82 (m, 2H), 1.53-1.59 (m, 4H), 1.33-1.44 (m, 4H), 0.92 (t, J=7.4 Hz, 6H).
Reaction SMILES: C(P(CC[CH2:12][CH3:13])CCCC)CCC.ClCCCl.[Cl:18][SiH:19]([Cl:21])[Cl:20]>>[Cl:18][Si:19]([Cl:21])([Cl:20])[CH2:12][CH2:13][Si:19]([Cl:21])([Cl:20])[Cl:18]
Reactant: CCCCP(CCCC)CCCC
Reactant: Cl[SiH](Cl)Cl
Solvent: ClCCCl
Product: Cl[Si](Cl)(Cl)CC[Si](Cl)(Cl)Cl
Yield: 336.8 %

Procedure:
In the same apparatus and procedure as Example 1 above, 0.30 g (1.5 mmol) of tri-n-butylphosphine, 0.74 g (7.5 mmol) of 1,2-dichloroethane, and 10.2 g (75.0 mmol) of trichlorosilane were reacted at 150° C. for 12 hrs. The resulting mixture was distilled to give 1.5 g of 1,2-bis(trichlorosilyl)ethane (bp; 201° C., yield; 67%) and 0.1 g of 2-(chloroethyl)trichlorosilane (bp; 152-3° C., yield; 5%).
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10]2[C:11]3[CH2:19][CH2:18][NH:17][CH2:16][C:12]=3[N:13]=[CH:14][N:15]=2)=[N:7][CH:8]=1.Cl[C:23]1[C:28]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:27][CH:26]=[CH:25][N:24]=1.C(N(CC)C(C)C)(C)C>C(#N)C>[CH3:32][S:29]([C:28]1[C:23]([N:17]2[CH2:18][CH2:19][C:11]3[C:10]([NH:9][C:6]4[CH:5]=[CH:4][C:3]([C:2]([F:20])([F:1])[F:21])=[CH:8][N:7]=4)=[N:15][CH:14]=[N:13][C:12]=3[CH2:16]2)=[N:24][CH:25]=[CH:26][CH:27]=1)(=[O:31])=[O:30]
Reactant: CS(=O)(=O)c1cccnc1Cl
Reactant: FC(F)(F)c1ccc(Nc2ncnc3c2CCNC3)nc1
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CS(=O)(=O)c1cccnc1N1CCc2c(ncnc2Nc2ccc(C(F)(F)F)cn2)C1
Temperature: 150 °C
Yield: 43.1 %

Procedure:
N-(5-(Trifluoromethyl)pyridine-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-amine (100 mg, 0.34 mmol) was dissolved in a mixture of acetonitrile (2 mL). To the mixture was added 2-chloro-3-methanesulphonylpyridine (122 mg, 0.68 mmol) and N,N-diisopropylethylamine (0.23 mL, 0.68 mmol). The mixture was heated in a sealed tube at 150° C. in microwave (Model, Personal Chemistry) for 16 h. The solvents were removed under vacuum and the residue was dissolved in ethyl acetate and washed with sat. NaHCO3 and brine. The organic layer was dried over Na2SO4, filtered and evaporated to give a brown residue. The residue was purified by flash chromatography over silica gel using a gradient of ethyl acetate:hexane (0-100%) to give the desired compound as an off-white powder (66 mg).
Reaction SMILES: [Br:1][C:2]1[CH:6]=[CH:5][S:4][C:3]=1[S:7](Cl)(=[O:9])=[O:8].[H-].[Na+].[C:13]([O:16][NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])(=[O:15])[CH3:14]>>[C:13]([O:16][N:17]([S:7]([C:3]1[S:4][CH:5]=[CH:6][C:2]=1[Br:1])(=[O:9])=[O:8])[C:18](=[O:19])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])(=[O:15])[CH3:14]
Reactant: O=S(=O)(Cl)c1sccc1Br
Reactant: CC(=O)ONC(=O)OC(C)(C)C
Agent: [H-]
Agent: [Na+]
Product: CC(=O)ON(C(=O)OC(C)(C)C)S(=O)(=O)c1sccc1Br

Procedure:
tert-Butyl (acetyloxy)[(3-bromothiophen-2-yl)sulfonyl]carbamate (43) is prepared from 3-bromothiophene-2-sulfonyl chloride, sodium hydride and [(tert-butoxy)carbonyl]amino acetate according to Scheme 2. (0.8 g, 35%), 1H NMR (250 MHz, CHLOROFORM-d) δ ppm 7.68 (1H, d, 5.3 Hz), 7.15 (1H, d, 5.2 Hz), 2.30 (3H, s), 1.48 (9H, s).
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=1[CH2:4][N:5]=[C:6]=[O:7].[Cl:12][C:13]1[N:18]=[C:17]2[NH:19][N:20]=[C:21]([OH:22])[C:16]2=[C:15]([CH3:23])[CH:14]=1>C1COCC1.CN(C=O)C>[CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=1[CH2:4][NH:5][C:6]([N:20]1[C:21](=[O:22])[C:16]2[C:17](=[N:18][C:13]([Cl:12])=[CH:14][C:15]=2[CH3:23])[NH:19]1)=[O:7]
Reactant: Cc1ccccc1CN=C=O
Reactant: Cc1cc(Cl)nc2[nH]nc(O)c12
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: Cc1ccccc1CNC(=O)n1[nH]c2nc(Cl)cc(C)c2c1=O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
136 μl (0.98 mmol) of 2-methylbenzyl isocyanate were added to 150 mg (0.82 mmol) of 6-chloro-4-methyl-1H-pyrazolo[3,4-b]pyridin-3-ol in 10 ml of THF and 2 ml of DMF at room temperature. The reaction mixture was stirred at room temperature for 2 h and left to stand overnight. Concentration was followed by purification by preparative HPLC (PR18, acetonitrile/water 0.1% TFA). Yield: 139 mg (51%), M+H+: 331.18.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][NH:10][N:9]=2)=[CH:4][CH:3]=1.[H-].[Na+].[CH3:20]I>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]([CH3:20])[N:10]=[CH:11][C:12]=2[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:6][CH:7]=1
Reactant: CI
Reactant: CCOC(=O)c1c[nH]nc1-c1ccc(F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)c1cnn(C)c1-c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 89.4 %

Procedure:
To a solution of ethyl 3-(4-fluorophenyl)-1H-pyrazole-4-carboxylate (15.0 g, 64.0 mmol) in THF was added sodium hydride (55 wt % paraffin oil, 3.35 g, 77.0 mmol) at room temperature and methyl iodide (8.01 mL, 128 mmol) was successively added at room temperature. After stirring at room temperature for 15 min, the reaction mixture was poured into ice water. The mixture was extracted with ethyl acetate, the organic layer was washed with saturated brine and dried, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (solvent; 33% ethyl acetate/hexane) to give a mixture (1:1 (mol/mol), 14.2 g, 90%) of ethyl 5-(4-fluorophenyl)-1-methyl-1H-pyrazole-4-carboxylate and ethyl 3-(4-fluorophenyl)-1-methyl-1H-pyrazole-4-carboxylate as a brown oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:13])[CH:10]([OH:12])[CH3:11].C(N(CC)CC)C.[CH3:21][S:22](Cl)(=[O:24])=[O:23]>C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:13])[CH:10]([O:12][S:22]([CH3:21])(=[O:24])=[O:23])[CH3:11]
Reactant: CC(O)C(=O)c1ccc(F)cc1F
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(OS(C)(=O)=O)C(=O)c1ccc(F)cc1F
Reaction time: 0.25 h

Procedure:
2',4'-Difluoro-2-hydroxypropiophenone (2.8 g) was dissolved in methylene chloride (28 ml), to which were added triethylamine (2.5 ml) and methanesulfonyl chloride (1.3 ml) at 0° C. After stirring for 15 minutes, the mixture was washed with water (30 ml), and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (3 cm×10 cm) and eluted with methylene chloride. The desired fraction was concentrated, to give 2',4'-difluoro-2-methanesulfonyloxypropiophenone (3.0 g) as a colorless oil. This compound (3.0 g) was dissolved in 30 ml of N,N-dimethylformamide, to which were added 1H-1,2,4-triazole (0.94 g) and then 60% sodium hydride suspension in oil (0.5 g) at -10° C. After stirring at 0° C. for 50 minutes, the reaction mixture was added to a mixture of ethyl acetate (100 ml) and water (200 ml) for extraction. The water layer was extracted with ethyl acetate (100 ml) and the ethyl acetate layers were combined, washed with saturated aqueous solution of sodium chloride (30 ml×2), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (3 cm×10 cm) and eluted with ethyl acetate. The desired fraction was concentrated, to give 2',4'-difluoro-2-(1H-1,2,4-triazol-1-yl)propiophenone (1.5 g) as a colorless oil. This compound (1.24 g) was added to a mixture of dimethyl sulfoxide (30 ml), 60% sodium hydride suspension in oil (0.25 g) and trimethylsulfoxonium iodide (1.38 g) at 10° C. and then the temperature was raised to 25° C. Two hours later, the reaction mixture was added to a mixture of diethyl ether (100 ml) and water (150 ml), diethyl ether layer was separated, and the water layer was extracted with diethyl ether (100 ml×2). The organic layers were combined, washed with saturated aqueous solution of sodium chloride (50 ml×2), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (3 cm×10 cm) and eluted with ethyl acetate-hexane (3:1), to give 2-(2,4-difluorophenyl)-2-[1-(1H-1,2,4-triazol-1-yl)ethyl]oxirane as a colorless oil (0.87 g).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH:12]([C:14]([O:16][CH3:17])=[O:15])[CH2:11][CH2:10][NH:9]2)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[C:27](Cl)(=[O:30])[O:28][CH3:29]>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH:12]([C:14]([O:16][CH3:17])=[O:15])[CH2:11][CH2:10][N:9]2[C:27]([O:28][CH3:29])=[O:30])=[CH:4][CH:3]=1
Reactant: COC(=O)C1CCNC(c2ccc(Cl)cc2)C1
Reactant: COC(=O)Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)C1CCN(C(=O)OC)C(c2ccc(Cl)cc2)C1
Temperature: 25 °C
Reaction time: 3 h
Yield: 103.2 %

Procedure:
Methyl 2-(4-chlorophenyl)piperidine-4-carboxylate (3.13 g, 12.34 mmol) was dissolved in DCM (50 mL), then DIPEA (5.39 mL, 30.84 mmol) was added. Methyl carbonochloridate (1.360 mL, 17.27 mmol) was added dropwise to the solution. The mixture was stirred at room temperature for 3 h. The mixture was washed with 0.1 M HCl (2*100 mL) and satd NaHCO3 (100 mL), then dried through a phase-separator and evaporated yielding dimethyl 2-(4-chlorophenyl)piperidine-1,4-dicarboxylate (3.97 g, quant.) as an orange oil. MS m/z 312 (M+H)+
Reaction SMILES: [C:1]1([N:7]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[NH:11][C:10](=[O:18])[CH2:9][C:8]2=[O:19])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCl.[CH2:22]([O-])C.[Na+]>>[C:1]1([N:7]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]([CH3:22])[C:10](=[O:18])[CH2:9][C:8]2=[O:19])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC[O-]
Reactant: O=C1CC(=O)N(c2ccccc2)c2ccccc2N1
Agent: CCl
Agent: [Na+]
Product: CN1C(=O)CC(=O)N(c2ccccc2)c2ccccc21

Procedure:
Starting from 1-phenyl 1,2,4,5-tetrahydro 2,4-dioxo 3H-1,5-benzodiazepine, obtained in the example VIII, by acting methyl chloride in the presence of sodium ethanolate, there is obtained 1-phenyl 5-methyl 1,2,4,5-tetrahydro 2,4-dioxo 3H-1,5-benzodiazepine, melting at 144°-146° C. after recrystallisation in isopropanol.
Reaction SMILES: [NH2:1][C:2]1[N:6]([CH2:7][CH3:8])[N:5]=[CH:4][CH:3]=1.[C:9]1([CH2:15][CH2:16][CH:17]([C:23]([CH3:25])=O)[C:18](OCC)=[O:19])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>O>[CH2:7]([N:6]1[C:2]2[N:1]=[C:23]([CH3:25])[C:17]([CH2:16][CH2:15][C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=3)=[C:18]([OH:19])[C:3]=2[CH:4]=[N:5]1)[CH3:8]
Reactant: CCn1nccc1N
Reactant: CCOC(=O)C(CCc1ccccc1)C(C)=O
Solvent: O
Product: CCn1ncc2c(O)c(CCc3ccccc3)c(C)nc21
Temperature: 25 °C

Procedure:
33 g. of 5-amino-1-ethylpyrazole (0.3 mol.) in 310 g. of polyphosphoric acid are heated to 80° (bath temperature). While stirring, 70.5 g. of 2-(2-phenylethyl)acetoacetic acid, ethyl ester (0.3 mol.) are added to the mixture. The bath temperature is increased to 100°, the temperature of the solution rising to about 130°. As soon as the reaction temperature begins to drop the bath temperature is elevated to 140° and maintained for 45 minutes. After the mixture has cooled to room temperature, 650 ml. of water are added in portions and stirring is continued until the polyphosphoric acid is dissolved. The the aqueous phosphoric acid solution is decanted and the undissolved residue is treated with 400 ml. of 5% aqueous ammonia to neutralize the mixture. The mixture is extracted with chloroform and the chloroform extract is washed with water and dried with Na2SO4. Addition of ether precipitates 37 g. (44%) of 1-ethyl-6-methyl-5-(2-phenylethyl)-1H-pyrazolo[3,4-b]pyridin-4-ol; m.p. 251°-256°. Recrystallization from ethanol raises the m.p. to 258°-260°.
Reaction SMILES: C([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][C:11]([N+:16]([O-:18])=[O:17])=[C:12]([F:15])[CH:13]=2)[N:8]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:7]=1[CH:26]([CH3:28])[CH3:27])=[O:5])C.[OH-].[Na+]>CCO.CCOC(C)=O>[CH2:19]([N:8]1[C:9]2[C:14](=[CH:13][C:12]([F:15])=[C:11]([N+:16]([O-:18])=[O:17])[CH:10]=2)[C:6]([C:4]([OH:5])=[O:3])=[C:7]1[CH:26]([CH3:28])[CH3:27])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: CCOC(=O)c1c(C(C)C)n(Cc2ccccc2)c2cc([N+](=O)[O-])c(F)cc12
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CCO
Product: CC(C)c1c(C(=O)O)c2cc(F)c([N+](=O)[O-])cc2n1Cc1ccccc1
Temperature: 80 °C

Procedure:
General Procedure Z. To a solution of ethyl1-benzyl-5-fluoro-2-isopropyl-6-nitro-1H-indole-3-carboxylate (Compound 169, 546 mg, 1.54 mmol) in EtOH (10 ml) was added 5 M NaOH (3.1 ml, 15.5 mmol). The reaction was heated at 80° C. for 5 h, diluted with EtOAc, washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel (0→50% EtOAc-hexanes) to yield the title compound as a brown solid.
Reaction SMILES: [N+](C1C=CC(C(O[C@@H:11]2[O:31][C@H:30]([CH2:32][O:33][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C@@H:21]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C@H:12]2[O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=O)=CC=1)([O-])=O.[Cl:43][C:44]1[NH:45][C:46]2[C:52]([Cl:53])=[C:51]([Cl:54])[C:50]([Cl:55])=[CH:49][C:47]=2[N:48]=1.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C>C(Cl)Cl.CC#N.CCOC(C)=O>[CH2:14]([O:13][C@@H:12]1[C@H:21]([O:22][CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[C@@H:30]([CH2:32][O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:31][C@H:11]1[N:48]1[C:47]2[CH:49]=[C:50]([Cl:55])[C:51]([Cl:54])=[C:52]([Cl:53])[C:46]=2[N:45]=[C:44]1[Cl:43])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: O=C(O[C@@H]1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@H]1OCc1ccccc1)c1ccc([N+](=O)[O-])cc1
Reactant: Clc1nc2cc(Cl)c(Cl)c(Cl)c2[nH]1
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: ClCCl
Solvent: CC#N
Solvent: CCOC(C)=O
Product: Clc1cc2c(nc(Cl)n2[C@@H]2O[C@H](COCc3ccccc3)[C@@H](OCc3ccccc3)[C@H]2OCc2ccccc2)c(Cl)c1Cl
Temperature: 75 °C
Reaction time: 0.33 h
Yield: 45 %

Procedure:
For the preparation of 1-O-chloro-2,3,5-tri-O-benzyl-D-ribofuranose, HCl gas was allowed to pass through a solution of 1-O-p-nitrobenzoyl-2,3,5-tri-O-benzyl-β-D-ribofuranose (1.479 g, 2.6 mmol) in 10 mL of dry CH2Cl2 at 0° C. for 15 min. The resulting suspension was quickly filtered and the filtrate was evaporated. The residue was coevaporated with dry MeCN and then dissolved in 5 mL of dry MeCN for immediate use in the subsequent glycosylation reaction. To a mixture of 13 (0.512 g, 2 mmol) in 10 mL of dry MeCN, was added 0.5 mL (2 mmol) of BSA. The reaction mixture was stirred at 75° C. for 20 min. This solution was treated with the above MeCN solution of the blocked carbohydrate and 0.464 mL (2.4 mmol) of TMSOTf at 70° C. for 20 min. The reaction mixture was cooled and diluted with EtOAc (50 mL). The EtOAc solution was washed with sat. NaHCO3 solution (50 mL×2), sat. NaCl solution (50 mL), dried (Na2SO4), and evaporated. The residue was chromatographed on a silica column (1.9×38 cm, eluted with hexane, 10%, 15% EtOAc/hexane). Evaporation of fractions 30-37 (15 mL per fraction) gave 0.593 g (45%) of 91a as a colorless syrup. MS: (El) m/e 658.0780 (2%, M+ =658.0774), 1H NMR (DMSO-d6): d 7.93 (s, 1, 7-H), 7.35, 6.92 (2×m, 15, 3×PhCH2), 5.99 (d, 1, 1'-H, J1'-2' =8.0 Hz), 4.72, 4.58, 4.35 (3×m, 9, 2'-H, 3'-H, and 3×PhCH2), 3.76 (dd, 1, 5'-H, J4'-5' =2.0 Hz, J5'-5" =11.0 Hz), 3.65 (dd, 1, 5"-H, J4'-5" =2.5 Hz), 13C NMR (DMSO-d6): d 142.00 (C2), 138.40 (C3a), 137.81. 137.44, 136.74 (3×PhCH2), 131.34 (C7a), 128.08, 128.03. 127.59, 127.40, 127.32, 127.28, 126.97 (3×PhCH2 and C4), 124.64, 122,52 (C5 and C6), 112.65 (C7), 87.46 (C1'), 83.03, 77.08, 74.92 (C2', C3', and C4'), 72.43, 71.44, 71.28 (3×PhCH2), 69.22 (C5'),
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)[C:7]=1[CH2:17][CH2:18][CH2:19][CH3:20])=[O:5])[CH3:2].CI.[C:23](=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:1]([O:3][C:4]([C:6]1[CH:15]=[C:14]([O:16][CH3:23])[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]=1[CH2:17][CH2:18][CH2:19][CH3:20])=[O:5])[CH3:2]
Reactant: O=C([O-])[O-]
Reactant: CCCCc1c(C(=O)OCC)cc(O)c2ccccc12
Agent: [K+]
Solvent: CI
Solvent: CC(C)=O
Product: CCCCc1c(C(=O)OCC)cc(OC)c2ccccc12
Temperature: 25 °C
Reaction time: 24 h
Yield: 90.9 %

Procedure:
1-Butyl-4-hydroxy-2-naphthalenecarboxylic acid ethyl ester (27 g) was reacted with methyl iodide (17 mL) in acetone (200 mL) containing potassium carbonate (13.8 g) with stirring at room temperature for 24 hours. The crude product obtained after the usual work up was distilled on a Kugelrohr apparatus (135°-138° C.; 0.1 mm) to provide 25.8 g of 1-butyl-4-methoxy-2-naphthalenecarboxylic acid ethyl ester as oil. Anal. Calcd for C18H22O3 : C, 75.50; H, 7.74 Found: C, 75.36; H, 7.84
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8][C:9]([O:11]CC)=O)[CH2:3][CH2:2]1.C(O)C.[CH3:17][NH2:18]>>[CH3:17][NH:18][C:9](=[O:11])[CH2:8][CH2:7][CH:4]1[CH2:5][CH2:6][NH:1][CH2:2][CH2:3]1
Reactant: CCOC(=O)CCC1CCNCC1
Reactant: CN
Solvent: CCO
Product: CNC(=O)CCC1CCNCC1

Procedure:
Ethyl 3-(piperid-4-yl)propionate (7 g) (prepared similarly to Preparation 21 A using ethyl alcohol in place of methyl alcohol) was dissolved in ethanolic methylamine (33%, 50 ml) and heated in a stainless steel bomb for 6 hours at 120°. The mixture was then evaporated to dryness in vacuo and the residue partitioned between 2 N NaOH (20 ml) and chloroform (40 ml). The chloroform layer was dried (Na2CO3) and evaporated to give N-methyl-3-(piperid-4-yl)propionamide (6 g) as a crude oil.