Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N-:1]=[N+]=[N-].[Na+].Cl[CH2:6][CH2:7][CH2:8]/[C:9](/[C:25]1O[C:27]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)=[N:28][N:29]=1)=[CH:10]\[C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]2)=[C:13]([O:23][CH3:24])[CH:12]=1.C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>CS(C)=O>[F:36][C:33]1[CH:34]=[CH:35][C:30]([C:27]2[N:1]3[CH2:6][CH2:7][CH2:8]/[C:9](=[CH:10]\[C:11]4[CH:16]=[CH:15][C:14]([N:17]5[CH:21]=[C:20]([CH3:22])[N:19]=[CH:18]5)=[C:13]([O:23][CH3:24])[CH:12]=4)/[C:25]3=[N:29][N:28]=2)=[CH:31][CH:32]=1
Reactant: [N-]=[N+]=[N-]
Reactant: COc1cc(/C=C(\CCCCl)c2nnc(-c3ccc(F)cc3)o2)ccc1-n1cnc(C)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: COc1cc(/C=C2\CCCn3c2nnc3-c2ccc(F)cc2)ccc1-n1cnc(C)c1
Temperature: 70 °C
Reaction time: 6 h
Yield: 56 %

Procedure:
Sodium azide (0.15 g) was added to a solution of 2-{4-chloro-1-{1-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]-(E)-methylidene}butyl}-5-(4-fluorophenyl)[1,3,4]oxadiazole (366 mg) in DMSO (10 mL) at room temperature, and the reaction solution was stirred at 70° C. for six hours. The reaction solution was left to cool to room temperature. Then, ethyl acetate and a saturated sodium bicarbonate solution were added to the reaction solution, and the organic layer was separated. The resulting organic layer was washed with a saturated sodium chloride solution, dried over magnesium sulfate and then concentrated under reduced pressure. Triphenylphosphine (0.33 g) was added to a mixed solution of the resulting residue in THF (10 mL) and water (0.5 mL) at room temperature, and the reaction solution was stirred at 60° C. for three hours. The reaction solution was left to cool to room temperature and concentrated under reduced pressure. THF and toluene were added to the residue, and the solution was again concentrated under reduced pressure. A solution of the resulting residue in acetic acid (5 mL) was stirred at 150° C. for 1.5 hours. The reaction solution was left to cool to room temperature and concentrated under reduced pressure. A saturated sodium bicarbonate solution was added to the resulting residue, followed by extraction with chloroform. The resulting extract was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane-ethyl acetate system, then ethyl acetate-methanol system), solidified with ethyl acetate and hexane and separated by filtration to obtain 188 mg of the title compound. The property values of the compound are as follows.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:22]([C@@H:23]([CH3:27])[C:24]([OH:26])=O)[C:17]3=[N:18][CH:19]=[CH:20][CH:21]=[C:16]3[N:15]=2)=[CH:10][CH:9]=1.[CH3:28][NH:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(N(CC)CC)C>CN(C)C=O>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[N:22]([C@@H:23]([CH3:27])[C:24]([N:29]([CH3:28])[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[O:26])[C:17]3=[N:18][CH:19]=[CH:20][CH:21]=[C:16]3[N:15]=2)=[CH:12][CH:13]=1
Reactant: CNc1ccccc1
Reactant: C[C@@H](C(=O)O)n1c(-c2ccc(Cl)cc2)nc2cccnc21
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: C[C@@H](C(=O)N(C)c1ccccc1)n1c(-c2ccc(Cl)cc2)nc2cccnc21
Temperature: 50 °C
Yield: 64.7 %

Procedure:
Under a nitrogen atmosphere, oxalyl chloride (2.18 g, 0.0172 mole) was added slowly, dropwise, to a stirred and chilled (10° C.) suspension of (S)-2-(4-chlorophenyl)-α-methyl-3H-imidazo[4,5-b]pyridine-3-acetic acid (5.0 g, 0.0166 mole) in dry dimethylformamide (75 ml). The mixture was stirred at room temperature for 3 hours, heated at 50° C. for one hour and cooled to room temperature. An additional 0.0057 mole of oxalyl chloride was added and the mixture was stirred at room temperature for 30 minutes. N-Methylaniline (1.92 g, 0.0179 mole) was added and the reaction mixture was stirred at room temperature under nitrogen overnight. The mixture was poured into 400 ml of ice water and triethylamine (6 ml) was added. The precipitated solid was collected by filtration, rinsed with water, redissolved in hot isopropyl alcohol, treated with charcoal, filtered hot and allowed to cool. Addition of water caused a solid to form. The solid was collected by filtration, rinsed with water and dried under high vacuum overnight to give 4.2 g (65%) of title compound, mp 174°-177° C.
Reaction SMILES: C([O:3][C:4](=[O:25])[C@:5]1([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][CH:19]=2)[CH2:9][CH2:8][CH2:7][N:6]1[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])C.[Li+].[OH-].C1COCC1.CO>O>[C:13]([O:12][C:10]([N:6]1[CH2:7][CH2:8][CH2:9][C@@:5]1([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][CH:19]=1)[C:4]([OH:25])=[O:3])=[O:11])([CH3:16])([CH3:14])[CH3:15]
Reactant: CCOC(=O)[C@]1(Cc2ccc(Br)cc2)CCCN1C(=O)OC(C)(C)C
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC[C@@]1(Cc1ccc(Br)cc1)C(=O)O
Temperature: 25 °C
Reaction time: 8 h
Yield: 108 %

Procedure:
A mixture of N-(tert-butoxycarbonyl)-2-(4-bromobenzyl)proline ethyl ester (3.00 g), LiOH (10 mmol), THF (25 mL), MeOH (10 mL) and H2O (5 mL) was stirred at room temperature overnight. The mixture was then heated at 74° C. overnight. The mixture was concentrated in vacuo, and water was added. The mixture was washed with Et2O and the aqueous layer was made acidic with the addition of 1N H2SO4. The aqueous layer was extracted with EtOAc. The EtOAc layer was washed with brine, dried over Na2SO4, and evaporated to give N-(tert-butoxycarbonyl)-2-(4-bromobenzyl)proline (3.02 g). MS (m/z) 284 (MH+-t-Boc); mp: 143.9° C.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([C:13]3=[CH:14][C:15]4[O:21][CH2:20][CH2:19][CH2:18][O:17][C:16]=4[CH:22]=[C:12]3[O:11][CH2:10]2)[C:2]1=[O:23].Br[CH2:25][C:26]1[O:27][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:29][CH:30]=1.BrCC1CCCCO1>>[F:32][C:31]([F:34])([F:33])[C:28]1[O:27][C:26]([CH2:25][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]3([C:13]4=[CH:14][C:15]5[O:21][CH2:20][CH2:19][CH2:18][O:17][C:16]=5[CH:22]=[C:12]4[O:11][CH2:10]3)[C:2]2=[O:23])=[CH:30][CH:29]=1
Reactant: FC(F)(F)c1ccc(CBr)o1
Reactant: O=C1Nc2ccccc2C12COc1cc3c(cc12)OCCCO3
Agent: BrCC1CCCCO1
Product: O=C1N(Cc2ccc(C(F)(F)F)o2)c2ccccc2C12COc1cc3c(cc12)OCCCO3

Procedure:
Following the procedure as described in EXAMPLE 4 and making non-critical variations using 3,4-dihydro-2H-spiro[furo[2,3-h][1,5]benzodioxepine-9,3′-indol]-2′(1′H)-one to replace 5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2″(1′H)-one, and 2-(bromomethyl)-5-(trifluoromethyl)furan to replace 2-(bromomethyl)tetrahydro-2H-pyran, 1′-{[5-(trifluoromethyl)furan-2-yl]methyl}-3,4-dihydro-2H-spiro[furo[2,3-h][1,5]benzodioxepine-9,3′-indol]-2′(1′H)-one was obtained (97%) as a colorless solid: mp 162-164° C. (water/methanol); 1H NMR (300 MHz, CDCl3) δ7.30 (ddd, J=7.8, 7.8, 1.2 Hz, 1H), 7.18 (d, J=7.5 Hz, 1H), 7.07 (dd, J=7.5, 7.5 Hz, 1H), 6.98 (d, J=7.8 Hz, 1H), 6.76-6.73 (m, 1H), 6.60 (s, 1H), 6.39 (d, J=3.3 Hz, 1H), 6.32 (s, 1H), 5.07 (d, J=16.4 Hz, 1H), 4.94 (d, J=9.0 Hz, 1H), 4.89 (d, J=16.4 Hz, 1H), 4.68 (d, J=9.0 Hz, 1H), 4.29-4.21 (m, 1H), 4.14-4.02 (m, 2H), 3.99-3.91 (m, 1H), 2.23-2.00 (m, 2H); 13C NMR (75 MHz, CDCl3) δ177.1, 156.8, 153.2, 152.1 (q, J=1.3 Hz), 146.4, 141.8 (q, J=42.9 Hz), 141.4, 132.1, 129.1, 124.2, 124.0, 122.9, 118.9 (q, J=267 Hz), 116.1, 112.8 (q, J=2.7 Hz), 109.4, 109.0, 103.6, 80.4, 70.91, 70.90, 58.0, 37.1, 32.3; MS (ES+) m/z 457.9 (M+1).
Reaction SMILES: [N:1]1[C:9]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[S:3][C:2]=1[C:10]([O-:12])=O.[Na+].Cl.[Cl:15][C:16]1[CH:32]=[CH:31][C:19](/[CH:20]=[CH:21]/[S:22]([N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)(=[O:24])=[O:23])=[CH:18][CH:17]=1>>[ClH:15].[Cl:15][C:16]1[CH:17]=[CH:18][C:19](/[CH:20]=[CH:21]/[S:22]([N:25]2[CH2:30][CH2:29][N:28]([C:10]([C:2]3[S:3][C:4]4[CH:5]=[N:6][CH:7]=[CH:8][C:9]=4[N:1]=3)=[O:12])[CH2:27][CH2:26]2)(=[O:23])=[O:24])=[CH:31][CH:32]=1
Reactant: O=C([O-])c1nc2ccncc2s1
Reactant: O=S(=O)(/C=C/c1ccc(Cl)cc1)N1CCNCC1
Agent: Cl
Agent: [Na+]
Product: O=C(c1nc2ccncc2s1)N1CCN(S(=O)(=O)/C=C/c2ccc(Cl)cc2)CC1

Procedure:
In a similar manner to Example 4 except for the use of sodium thiazolo[5,4-c]pyridine-2-carboxylate and 1-[(E)-4-chlorostyrylsulfonyl)piperazine hydrochloride as the raw materials, the reaction was conducted, whereby the title compound was obtained.
Reaction SMILES: [CH2:1]([C:8]1[NH:9][CH:10]=[C:11]([CH:13]=O)[N:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:15]([O:19][CH2:20][CH3:21])(=[O:18])[NH:16][NH2:17]>C(O)(=O)C.C(O)C>[CH2:20]([O:19][C:15](=[O:18])[NH:16][N:17]=[CH:13][C:11]1[N:12]=[C:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[NH:9][CH:10]=1)[CH3:21]
Reactant: O=Cc1c[nH]c(Cc2ccccc2)n1
Reactant: CCOC(=O)NN
Solvent: CC(=O)O
Solvent: CCO
Product: CCOC(=O)NN=Cc1c[nH]c(Cc2ccccc2)n1

Procedure:
To a 37.2 gm. portion of 2-benzyl-4-imidazolecarboxaldehyde in 200 ml. of ethanol is added 20.8 gm. of ethyl carbazate and a few drops of concentrated acetic acid. The mixture is reacted as described in Example 32 giving the desired product m.p. 184°-185° C.
Reaction SMILES: [F:1][C:2]([N+:11]([O-:13])=[O:12])([N+:8]([O-:10])=[O:9])[CH2:3][CH2:4][C:5](Cl)=[O:6].[F:14][C:15]([F:24])([C:20]([F:23])([F:22])[F:21])[C:16]([NH:18][NH2:19])=[O:17].N1C=CC=CC=1.Cl>C(OCC)C>[F:1][C:2]([N+:11]([O-:13])=[O:12])([N+:8]([O-:10])=[O:9])[CH2:3][CH2:4][C:5]([NH:19][NH:18][C:16](=[O:17])[C:15]([F:14])([F:24])[C:20]([F:22])([F:23])[F:21])=[O:6]
Reactant: O=C(Cl)CCC(F)([N+](=O)[O-])[N+](=O)[O-]
Reactant: NNC(=O)C(F)(F)C(F)(F)F
Agent: Cl
Solvent: CCOCC
Solvent: c1ccncc1
Product: O=C(CCC(F)([N+](=O)[O-])[N+](=O)[O-])NNC(=O)C(F)(F)C(F)(F)F
Reaction time: 0.08 h

Procedure:
To a solution of 0.95 g (0.0045 mole) of 4-fluoro-4,4-dinitrobutyryl chloride in 20 mL of anhydrous diethyl ether stirred at 20° C. was added 0.8 g (0.0045 mole) of N-(perfluoropropionyl)hydrazine followed by the dropwise addition of 0.4 mL of pyridine. After 5 minutes, dilute hydrochloric acid (10 mL) was added, the ether layer was separated, dried (Na2SO4) and the volatiles were removed to give the product N-(4-fluoro-4,4-dinitrobutyryl)-N'-(perfluoropropionyl)hydrazine, 1.05 g, mp 128°-132° C. Crystallization from 1,2-dichloroethane gave 0.93 g (58%), mp 135°-136° C. 1H NMR (acetone d6 +D2O): 2.80 (t, 2H), 3.36, 3.58 (d of t, 2H).
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][O:12][C:13]3[C:22]4[C:17](=[CH:18][C:19]([O:23][CH3:24])=[CH:20][CH:21]=4)[N:16]=[CH:15][CH:14]=3)=[N:9][N:10]=2)[N:7]=1.[CH3:25][C:26]([OH:30])([C:28]#[CH:29])[CH3:27].C(N(CC)CC)C.C(#N)C>[Cu]I>[CH3:24][O:23][C:19]1[CH:18]=[C:17]2[C:22]([C:13]([O:12][CH2:11][C:8]3[N:6]4[N:7]=[C:2]([C:29]#[C:28][C:26]([CH3:27])([OH:30])[CH3:25])[CH:3]=[CH:4][C:5]4=[N:10][N:9]=3)=[CH:14][CH:15]=[N:16]2)=[CH:21][CH:20]=1
Reactant: C#CC(C)(C)O
Reactant: COc1ccc2c(OCc3nnc4ccc(Cl)nn34)ccnc2c1
Agent: [Cu]I
Solvent: CC#N
Solvent: CCN(CC)CC
Product: COc1ccc2c(OCc3nnc4ccc(C#CC(C)(C)O)nn34)ccnc2c1
Temperature: 90 °C
Yield: 51.3 %

Procedure:
A 25×200 mm test tube was charged with 4-((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinoline (0.150 g, 0.439 mmol), 2-methylbut-3-yn-2-ol (0.213 ml, 2.19 mmol), copper (I) iodide (0.0209 g, 0.110 mmol), triethylamine (1.83 ml, 13.2 mmol), and acetonitrile (5.00 ml, 96.2 mmol), flushed with argon, sealed, and placed in a 90° C. oil bath for 30 minutes. PdCl2(dppf)-CH2Cl2Adduct (0.0358 g, 0.0439 mmol) was added in one portion, the tube flushed with argon, sealed, then heated in a 90° C. oil bath for 4 hours. The reaction mixture was filtered thru a pad of silica gel (eluting with EtOAc/DCM/MeOH), then concentrated to yield a dark brown oil. This was purified by MPLC, using a 40 g RediSep column, eluting with 1-7% MeOH/DCM over 40 minutes. The appropriate fractions were collected to give 4-(3-((7-methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-2-methylbut-3-yn-2-ol (0.0877 g, 51.3% yield). MS (ESI pos. ion) m/z: 390 (MH+). Calc'd exact mass for C21H19N5O3: 389.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1O[C:11](=O)[S:10][N:9]=1.[C:14]([O:18][CH2:19][CH3:20])(=[O:17])[C:15]#[CH:16].[C:21]([O:25][CH2:26][CH3:27])(=[O:24])[CH2:22]C>CC1C=CC(C)=CC=1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:16]=[C:15]([C:14]([O:18][CH2:19][CH3:20])=[O:17])[S:10][N:9]=1.[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:22]([C:21]([O:25][CH2:26][CH3:27])=[O:24])=[CH:11][S:10][N:9]=1
Reactant: CCOC(=O)CC
Reactant: O=c1oc(-c2ccccc2F)ns1
Reactant: C#CC(=O)OCC
Solvent: Cc1ccc(C)cc1
Product: CCOC(=O)c1cc(-c2ccccc2F)ns1
Product: CCOC(=O)c1csnc1-c1ccccc1F
Yield: 40 %
Yield: 32 %

Procedure:
A solution of 5-(2-fluorophenyl)[1,3,4]oxathiazolin-2-one (1.97 g, 10 mmol) and ethyl propiolate (1.96 g, 20 mmol) in p-xylene is heated at reflux temperature for 48 h, treated with a further portion of ethyl propionate, heated at reflux temperature for another 48 h, and distilled to remove the solvent. The resultant residue is purified by flash column chromatography (silica gel, toluene) to give ethyl 3-(2-fluorophenyl)isothiazole-5-carboxylate (1.0 g, 40%) as yellow crystals, mp 53°-54° C., plus ethyl 3-(2-fluorophenyl)isothiazole-4-carboxylate (0.8 g, 32%) as a yellow oil.
Reaction SMILES: C([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[CH:15]=[C:16]([N:20]3[CH:24]([C:25]4[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=4[F:32])[CH2:23][C:22]([C:33]([F:39])([F:38])[C:34]([F:37])([F:36])[F:35])=[N:21]3)[CH:17]=[CH:18][CH:19]=2)[CH2:10][CH2:9]1)(OC(C)(C)C)=O.[ClH:40]>C(OCC)(=O)C>[ClH:40].[F:32][C:26]1[CH:27]=[C:28]([F:31])[CH:29]=[CH:30][C:25]=1[CH:24]1[N:20]([C:16]2[CH:17]=[CH:18][CH:19]=[C:14]([C:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH:10]=3)[CH:15]=2)[N:21]=[C:22]([C:33]([F:38])([F:39])[C:34]([F:37])([F:36])[F:35])[CH2:23]1
Reactant: CC(C)(C)OC(=O)N1CC=C(c2cccc(N3N=C(C(F)(F)C(F)(F)F)CC3c3ccc(F)cc3F)c2)CC1
Agent: Cl
Solvent: CCOC(C)=O
Product: Fc1ccc(C2CC(C(F)(F)C(F)(F)F)=NN2c2cccc(C3=CCNCC3)c2)c(F)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
1-[3-(1-BOC-1,2,3,6-tetrahydropyridin-4-yl)-phenyl]-5-(2,4-difluoro-phenyl)-3-pentafluoroethyl-4,5-dihydro-1H-pyrazole (300.0 mg, 0.54 mmol) prepared in Example 205 was added to a saturated solution of hydrochloric acid in ethyl acetate (3.0 mL). The reaction mixture was stirred at room temperature for 2 hours and then concentrated under reduced pressure to give 260.0 mg of the titled compound as a white solid.
Reaction SMILES: [OH:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.CN1CCOCC1.Cl[C:24]([O:26][C:27]1[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=1)=[O:25]>C(Cl)Cl>[C:24](=[O:25])([O:26][C:27]1[CH:28]=[CH:29][C:30]([N+:33]([O-:35])=[O:34])=[CH:31][CH:32]=1)[O:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1
Reactant: CC(C)(C)OC(=O)N1CCC(CO)CC1
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Solvent: ClCCl
Solvent: CN1CCOCC1
Product: CC(C)(C)OC(=O)N1CCC(COC(=O)Oc2ccc([N+](=O)[O-])cc2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 95.8 %

Procedure:
To a solution of tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate (36.1 g, 168 mmol) and NMM (20 mL, 182 mmol) in DCM (500 mL) at 0° C. was added p-nitrophenyl chloroformate (33.9 g, 168 mmol). The reaction mixture was stirred at room temperature overnight and then washed sequentially with 1M aq HCl (500 mL), sat aq NaHCO3 solution (3×500 mL), dried (MgSO4) and concentrated in vacuo to give (1-(tert-butoxy-carbonyl)piperidin-4-yl)methyl 4-nitrophenyl carbonate (61.2 g, 96%) as a yellow solid.
Reaction SMILES: [CH3:1][C:2]1[N:7]=[CH:6][C:5]([O:8][C:9]2[CH:10]=[C:11]([CH:14]=[C:15]([N+:17]([O-])=O)[CH:16]=2)[C:12]#[N:13])=[CH:4][CH:3]=1.O.C([O-])([O-])=O.[Na+].[Na+]>C(O)(=O)C.[Fe]>[NH2:17][C:15]1[CH:14]=[C:11]([CH:10]=[C:9]([O:8][C:5]2[CH:6]=[N:7][C:2]([CH3:1])=[CH:3][CH:4]=2)[CH:16]=1)[C:12]#[N:13]
Reactant: Cc1ccc(Oc2cc(C#N)cc([N+](=O)[O-])c2)cn1
Agent: [Fe]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: Cc1ccc(Oc2cc(N)cc(C#N)c2)cn1
Temperature: 25 °C
Reaction time: 6 h
Yield: 74 %

Procedure:
A mixture of 3-(6-methylpyridin-3-yloxy)-5-nitrobenzonitrile (3 g, 0.012 mol) and iron powder in acetic acid (200 mL) was stirred at RT for 6 h. H2O was added and the mixture was adjusted to pH 7 with saturated Na2CO3 solution. The aqueous layer was extracted with EtOAc, and the combined organics were washed with brine, dried (MgSO4), concentrated in vacuo and purified by silica gel chromatography to afford 3-amino-5-(6-methylpyridin-3-yloxy)benzonitrile (2 g, 76% yield). 1H NMR (400 MHz, DMSO) δ 8.25 (s, 1H), 7.42 (d, J=10 Hz, 1H), 7.30 (d, J=8.4 Hz, 1H), 6.62 (s, 1H), 6.51 (s, 1H), 6.38 (s, 1H), 5.78 (s, 2H), 2.49 (s, 3H); MS (ESI) m/z: 226.2 [M+H]+.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][C:3]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:2]1.Br[CH2:14][CH2:15][N:16]1[C:20](=[O:21])[C:19]2=[CH:22][CH:23]=[CH:24][CH:25]=[C:18]2[C:17]1=[O:26].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[O:26]=[C:17]1[C:18]2[C:19](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20](=[O:21])[N:16]1[CH2:15][CH2:14][N:1]1[CH:5]=[CH:4][C:3]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:2]1
Reactant: CC(C)(C)OC(=O)c1cc[nH]c1
Reactant: O=C1c2ccccc2C(=O)N1CCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)c1ccn(CCN2C(=O)c3ccccc3C2=O)c1
Reaction time: 12 h
Yield: 12.6 %

Procedure:
To a solution of 2.62 g of tert-butyl 1H-pyrrole-3-carboxylate and 7.96 g of N-(2-bromoethyl)phthalimide in DMF (100 ml) was added 10.2 g of cesium carbonate at room temperature, followed by stirring for 12 hours. The reaction solution was diluted with water and extracted with ethyl acetate. The extract was washed with saturated brine and then dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography using hexane/chloroform as an eluent solvent, and washed with diethyl ether to obtain 670 mg of tert-butyl 1-[2-(1,3-dioxo-1,3-dihydro-2H-isoindo1-2-yl)ethyl]-1H-pyrrole-3-carboxylate as a colorless solid.
Reaction SMILES: [H-].[Na+].[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([OH:26])([C:22]([F:25])([F:24])[F:23])[C:18]([F:21])([F:20])[F:19])=[CH:13][C:12]=1[CH2:27][CH2:28][CH3:29])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:30][O:31][CH2:32]Cl.O>O1CCCC1>[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([O:26][CH2:30][O:31][CH3:32])([C:18]([F:19])([F:20])[F:21])[C:22]([F:23])([F:24])[F:25])=[CH:13][C:12]=1[CH2:27][CH2:28][CH3:29])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: COCCl
Reactant: CCCc1cc(C(O)(C(F)(F)F)C(F)(F)F)ccc1OCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CCCc1cc(C(OCOC)(C(F)(F)F)C(F)(F)F)ccc1OCc1ccccc1
Reaction time: 8 h
Yield: 90.6 %

Procedure:
Sodium hydride (purity: 50%) (38.9 mg, 0.81 mmol) was added to a mixed solution of 2-(4-benzyloxy-3-propylphenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol (264.0 mg, 0.67 mmol) in tetrahydrofuran (5 mL) under ice-cooling. Then, chloromethyl methyl ether (65.0 mg, 0.81 mmol) was added, followed by stirring overnight. Water was added to the reaction solution, followed by extraction with ethyl acetate. Then, the organic layer was washed with saturated saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel preparative thin-layer chromatography (hexane:ethyl acetate=10:1) to obtain 264.9 mg of the title compound (yield: 90%) as a pale yellow oil.
Reaction SMILES: [CH3:1][C:2]([CH3:19])([CH3:18])[CH2:3][NH:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([OH:15])[CH:13]=2)[N:8]=[C:7]([C:16]#[N:17])[N:6]=1.Cl.Cl[CH2:22][C:23]1[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[CH3:1][C:2]([CH3:19])([CH3:18])[CH2:3][NH:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH2:22][C:23]3[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=3)[CH:13]=2)[N:8]=[C:7]([C:16]#[N:17])[N:6]=1
Reactant: ClCc1cccnc1
Reactant: CC(C)(C)CNc1nc(C#N)nc2ccc(O)cc12
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)CNc1nc(C#N)nc2ccc(OCc3cccnc3)cc12

Procedure:
4-(2,2-Dimethyl-propylamino)-6-hydroxy-quinazoline-2-carbonitrile (0.25 mmol), 3-chloromethyl-pyridine hydrochloride (0.38 mmol) and cesium carbonate (2.5 mmol) are stirred in DMF (3 ml) at RT for 20 hours. Water is added until a clear solution is formed. Then more water is added until the solution gets turbide. The precipitate formed is filtered off, washed with water and dried (vacuum). A powder with mp. 156-158° C., Rf=0.35 (CH2Cl2/MeOH=15:1) is obtained.
Reaction SMILES: [CH2-:1][C:2]([CH3:4])=[O:3].[CH2-:5][C:6]([CH3:8])=O.O=[CH:10][C@@H:11]([C@@H:13]([C@@H:15]([C@@H:17]([CH2:19][OH:20])[OH:18])[OH:16])[OH:14])[OH:12].[H-].[Na+].[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.CO>C1COCC1.CN(C=O)C.C1COCC1>[CH3:1][C:2]1([CH3:4])[O:12][C@@H:11]([C@H:13]2[O:14][C@@H:19]3[O:20][C:6]([CH3:8])([CH3:5])[O:18][C@@H:17]3[C@@H:15]2[O:16][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:10][O:3]1
Reactant: [CH2-]C(C)=O
Reactant: O=C[C@H](O)[C@H](O)[C@H](O)[C@H](O)CO
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Solvent: CO
Product: CC1(C)O[C@H]2O[C@H]([C@H]3COC(C)(C)O3)[C@@H](OCc3ccccc3)[C@H]2O1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a stirred solution of the allose diacetonide (19.6 g, ca. 75 mmol) in THF-DMF (500 mL, 4:1 v/v) at and under argon was added a 60% sodium hydride dispersion in mineral oil (6.0 g, 150 mmol) portionwise over 30 min. The resulting mixture was allowed to warm to room temperature over 1h, then it was recooled to 0° C. before benzyl bromide (25.7 g, 17.9 mL, 150 mmol) and t-n-butylammonium iodide (1.0 g) were added. The resulting mixture was allowed to warm to room temperature and stir for 16 h. The reaction mixture was cooled to 0° C. and anhydrous methanol (20 mL) was cautiously added over 30 min. The resulting mixture was allowed to warm to room temperature and stir for 1 h before the THF was removed by rotary evaporation. The residue was suspended in H2O (250 mL) and extracted with ethyl acetate (4×200 mL). The combined organic fractions were washed with H2O (500 mL) and brine (200 mL), dried over Na2SO4, filtered, and concentrated to give the crude 3-O-benzyl-1,2:5,6-di-O-isopropylidene-α-D-allofuranose as a clear, yellow oil (46.8 g). This material was used without further purification. ##STR64##
Reaction SMILES: FC(F)(F)S([O:6][CH2:7][C:8]([F:22])([F:21])[C:9]([F:20])([F:19])[C:10]([F:18])([F:17])[CH2:11][O:12][CH2:13][CH2:14][CH2:15][CH3:16])(=O)=O.FC(F)(F)S(O[CH2:31][C:32](F)(F)[C:33](F)(F)[C:34](F)(F)[CH2:35][O:36]CC)(=O)=O>>[CH2:13]([O:12][CH2:11][C:10]([F:17])([F:18])[C:9]([F:19])([F:20])[C:8]([F:21])([F:22])[CH2:7][O:6][C:7]1[CH:8]=[C:9]2[C:33](=[CH:32][CH:31]=1)[CH:34]=[C:35]([OH:36])[CH:11]=[CH:10]2)[CH2:14][CH2:15][CH3:16]
Reactant: CCCCOCC(F)(F)C(F)(F)C(F)(F)COS(=O)(=O)C(F)(F)F
Reactant: CCOCC(F)(F)C(F)(F)C(F)(F)COS(=O)(=O)C(F)(F)F
Product: CCCCOCC(F)(F)C(F)(F)C(F)(F)COc1ccc2cc(O)ccc2c1

Procedure:
In this example, a compound was prepared in essentially the same manner as that described in Example 7, except that 4.0 g (0.010 moles) of 5-butoxy-2,2,3,3,4,4-hexafluoropentyl trifluoromethanesulfonate (prepared essentially as in Example 2) was substituted for the 5-ethoxy-2,2,3,3,4,4-hexafluoropentyl trifluoromethanesulfonate to provide 2.82 g of 6-(5-butoxy-2,2,3,3,4,4-hexafluoropentoxy)-2-hydroxynapthalene product.