Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([NH:8][C:9]1[S:13][C:12]([C:14]([N:16]([CH3:28])[CH2:17][CH2:18][N:19]([CH3:27])[C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:15])=[C:11]([CH3:29])[CH:10]=1)=O)(C)(C)C.FC(F)(F)C(O)=O.C(N(CC)CC)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>C(Cl)Cl>[NH2:8][C:9]1[S:13][C:12]([C:14]([N:16]([CH3:28])[CH2:17][CH2:18][N:19]([CH3:27])[C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:15])=[C:11]([CH3:29])[CH:10]=1
Reactant: Cc1cc(NC(=O)OC(C)(C)C)sc1C(=O)N(C)CCN(C)C(=O)OC(C)(C)C
Agent: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O=C(O)C(F)(F)F
Product: Cc1cc(N)sc1C(=O)N(C)CCN(C)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 99.6 %

Procedure:
The compound (350 mg, 0.819 mmol) obtained in Example 89b was dissolved in methylene chloride (8 mL), trifluoroacetic acid (4 mL) was added under ice cooling, and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated under reduced pressure, and moisture was removed from the resulting residue azeotropically with toluene (×2). The resulting residue was dissolved in methylene chloride (8 mL), triethylamine (0.569 mL, 4.10 mmol) and di-tert-butyl dicarbonate (215 mg, 0.983 mmol) were added, and the mixture was stirred at room temperature for 2 hours. The solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:2, v/v) to give the title compound (267 mg; yield, 100%) as a light yellow solid.
Reaction SMILES: [C:1]([O-:5])(=[O:4])[CH:2]=[CH2:3].[C:6]([O-])(=O)C(C)=C.C(C1C=CC=CC=1)(=O)C1C=CC=CC=1.CC(=C)C.CC1C=CC(C=C)=CC=1.BrCC1C=CC(C=C)=CC=1.[OH-].C([N+](CCCC)(CCCC)CCCC)CCC.C(O)(=O)C=C.OC1C=CC(C(C2C=CC=CC=2)=O)=CC=1>O.CO>[C:1]([OH:5])(=[O:4])[CH:2]=[CH2:3].[C:1]([OH:5])(=[O:4])[C:2]([CH3:6])=[CH2:3]
Reactant: C=C(C)C(=O)[O-]
Reactant: C=CC(=O)[O-]
Agent: C=C(C)C
Agent: C=CC(=O)O
Agent: C=Cc1ccc(C)cc1
Solvent: O
Solvent: CO
Product: C=C(C)C(=O)O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Terpolymer derivatives having either acrylate or methacrylate units and benzophenone moieties substituted on the isobutylene/para-methylstyrene/para-bromomethylstyrene were then prepared. A 5000 ml glass-jacketed reaction vessel fitted with an overhead stirrer, a hose connector and septum was purged with nitrogen. At room temperature under nitrogen, the vessel was charged with toluene (2500 ml) and 450 g of the base isobutylenelparamethylstyrene/para-bromomethylstyrene terpolymer above comprising 2.4 total mole percent para-methylstyrene, including 1.10 mole percent para-bromomethylstyrene, and having a Mooney viscosity of 32 (1+8 min., 125° C.). The base terpolymer was dissolved by stirring at room temperature overnight. A tetrabutylammonium salt of acrylic acid (or methacrylic acid) was prepared in a second flask by charging 101.3 ml tetrabutylammonium hydroxide (1.0M in methanol) and 7.3 ml acrylic acid (7.0 ml methacrylic acid) and 4 g of 4-hydroxybenzophenone and 30 ml of methanol to the flask and stirring at room temperature to give a water-white clear solution. This solution was then added to the flask containing the dissolved base terpolymer, at a circulating bath temperature of 83° C. After 45 minutes, the bath temperature was raised to 95° C. and let to run for 7.5 h. Then the bath temperature was lowered to 70° C., and after a 2.5 h period, the reaction was let to cool. The yellowish viscous solution was quenched and washed with 10 ml HCl in 1000 ml deionized water, and subsequently washed with H2O/IPA (70:30) 5 to 6 times. The polymer was isolated by precipitation into 0.1% BHT in isopropanol (IPA) and dried in vacuo for 48 h at 1 mm Hg and 80° C.
Reaction SMILES: C(N(CC)CC)C.[O:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[O:14][CH2:15][CH2:16][C:17]1[CH:25]=[CH:24][C:20]([CH2:21][CH2:22][OH:23])=[CH:19][CH:18]=1.[CH3:26][S:27](Cl)(=[O:29])=[O:28].O>C(Cl)Cl>[CH3:26][S:27]([O:23][CH2:22][CH2:21][C:20]1[CH:19]=[CH:18][C:17]([CH2:16][CH2:15][O:14][CH:9]2[CH2:10][CH2:11][CH2:12][CH2:13][O:8]2)=[CH:25][CH:24]=1)(=[O:29])=[O:28]
Reactant: CS(=O)(=O)Cl
Reactant: OCCc1ccc(CCOC2CCCCO2)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: CS(=O)(=O)OCCc1ccc(CCOC2CCCCO2)cc1
Yield: 99.9 %

Procedure:
Triethylamine (3.22 g, 31.82 mmol) was added to a solution of 4-(2-(tetrahydropyran-2-yloxy)ethyl)phenethyl alcohol (4.00 g, 15.97 mmol) in methylene chloride (40 ml). The mixture was stirred under ice-cooling, and methanesulfonyl chloride (2.19 g, 19.11 mmol) was added dropwise to the mixture. After the addition, the resulting mixture was stirred under ice-cooling for 10 minutes. Then, water (40 ml) was added. The mixture was extracted with methylene chloride and dried over magnesium sulfate. Evaporation of the solvent gave the desired 4-(2-(tetrahydropyran-2-yloxy)ethyl)phenethyl methanesulfonate (5.24 g, 99%).
Reaction SMILES: [Cl:1][C:2]1[N:3]([C@@H:13]2[O:19][C@H:18]([CH2:20][O:21]C(=O)C)[C@@H:16]([OH:17])[C@H:14]2[OH:15])[C:4]2[C:9]([CH:10]=1)=[CH:8][C:7]([Cl:11])=[C:6]([Cl:12])[CH:5]=2.[C:25](Cl)(=[O:28])[CH2:26][CH3:27]>>[Cl:1][C:2]1[N:3]([C@@H:13]2[O:19][C@H:18]([CH2:20][OH:21])[C@@H:16]([OH:17])[C@H:14]2[OH:15])[C:4]2[C:9]([C:10]=1[C:25](=[O:28])[CH2:26][CH3:27])=[CH:8][C:7]([Cl:11])=[C:6]([Cl:12])[CH:5]=2
Reactant: CCC(=O)Cl
Reactant: CC(=O)OC[C@H]1O[C@@H](n2c(Cl)cc3cc(Cl)c(Cl)cc32)[C@H](O)[C@@H]1O
Product: CCC(=O)c1c(Cl)n([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c2cc(Cl)c(Cl)cc12

Procedure:
The same procedure was used for the synthesis of the 3-propionyl derivative 4.47 (FIG. 6A). 2,5,6-Trichloro-1-(5-O-acetyl-β-D-ribofuranosyl)indole (4.39, FIG. 6A) was acylated under Friedel-Crafts conditions with propionyl chloride and deprotected in two steps to yield the desired 2,5,6-trichloro-3-propionyl-1-(β-D-ribofuranosyl)indole (4.47, FIG. 6A).
Reaction SMILES: C[O:2][C:3](=[O:19])[C@H:4]([CH2:17][OH:18])[NH:5][C:6](=[O:16])[CH2:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[C:10]([F:15])[CH:9]=1.[OH-].[Li+].Cl>C1COCC1.[Cl-].[Na+].O>[F:14][C:12]1[CH:13]=[C:8]([CH2:7][C:6]([NH:5][C@H:4]([C:3]([OH:19])=[O:2])[CH2:17][OH:18])=[O:16])[CH:9]=[C:10]([F:15])[CH:11]=1
Reactant: COC(=O)[C@H](CO)NC(=O)Cc1cc(F)cc(F)c1
Agent: Cl
Agent: [Cl-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: O=C(Cc1cc(F)cc(F)c1)N[C@@H](CO)C(=O)O
Temperature: 25 °C
Yield: 54 %

Procedure:
To a stirred solution of N-[(3,5-difluorophenyl)acetyl]-L-serine methyl ester (4a) in THF (13 mL) was added 1M aqueous lithium hydroxide (13.2 mL) and the mixture stirred at RT for 40H. Brine (50 mL) was added, the aqueous layer made acidic to pH 1 with 1N hydrochloric acid (˜15 mL), and the aqueous layer extracted with 10% Methanol/CHCl3 (2×). The organic phase was collected, dried, filtered and the solvent removed in vacuo to afford the title compound (112 mg, 54%). This material was used without further purification. 1H NMR (300 MHz, d6-DMSO) δ3.57 (d, 2H), 3.7 (m, 1H), 4.27, (m, 1H), 5.03 (bs, 1H), 7.00 (d, 2H), 7.09 (t, 1H), 8.38, (d, 1H). 12.6, (bs, 1H). MS APCI, m/z=274 (M+1). LC/MS: 1.0 min.
Reaction SMILES: Br[C:2]1([CH:13]=[O:14])[C@@H:4]([C:5]([O:7][CH3:8])=[O:6])[C@@H:3]1[C:9]([O:11][CH3:12])=[O:10]>[Zn].C(O)(=O)C>[C:9]([C@@H:3]1[CH:2]([CH:13]=[O:14])[C@H:4]1[C:5]([O:7][CH3:8])=[O:6])([O:11][CH3:12])=[O:10]
Reactant: COC(=O)[C@H]1[C@H](C(=O)OC)C1(Br)C=O
Agent: [Zn]
Solvent: CC(=O)O
Product: COC(=O)[C@@H]1C(C=O)[C@H]1C(=O)OC
Temperature: 25 °C
Reaction time: 4 h
Yield: 88.2 %

Procedure:
A mixture of (1R,2R)-3-bromo-1,2-dicarbomethoxy-3-formyl-cyclopropane (428 mg, 1.6 mmmol), zinc powder (230 mg, 3.5 mmol) and acetic acid (2 ml) was stirred at room temperature over a period of 4 hours. Filtration, evaporation and column chromatography yielded (1R,2R)-1,2-dicarbomethoxy-3-formyl-cyclopropane (265 mg, 88%) as a colorless oil. [α]20D=-48° (c=1 in MeOH); 1H NMR (CDCl3): d 2.53 (ddd, J=5, 6, 8 Hz, 1H), 2.71 (dd, J=6, 8 Hz, 1H), 3.01 (t, J=6 Hz, 1H), 3.76 (s, 6H), 9.42 (d, J=5 Hz, 1H); MS (FAB) m/e 187 [M+H+ ].
Reaction SMILES: O[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]3[CH:14]=[N:13][NH:12][C:10]3=2)[N:5]=[C:4]([CH3:15])[CH:3]=1.P(Cl)(Cl)([Cl:18])=O.CN(C)C=O.[OH-].[Na+]>O>[Cl:18][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]3[CH:14]=[N:13][NH:12][C:10]3=2)[N:5]=[C:4]([CH3:15])[CH:3]=1
Reactant: Cc1cc(O)c2c(ccc3cn[nH]c32)n1
Reactant: O=P(Cl)(Cl)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1cc(Cl)c2c(ccc3cn[nH]c32)n1
Temperature: 80 °C
Yield: 92692.9 %

Procedure:
To a suspension of 9-hydroxy-7-methyl-1H-pyrazolo[3,4-f]quinoline (8.00 g, 0.04 mmol) in phosphorus oxychloride (61.6 g, 0.40 mol) was added slowly N,N-dimethylformamide (40 ml). After the addition was complete, the reaction mixture was warmed to 80° C. for 1 hour and then allowed to cool to room temperature. The reaction was poured onto ice and dissolved in water (2 L total volume) and neutralized to pH 7 with 20% sodium hydroxide (NaOH). The precipitate which formed upon neutralization was collected by filtration, washed with water and dried under vacuum to give 9-chloro-7-methyl-1H-pyrazolo[3,4-f]quinoline as a white solid (8.07 g, 92%).
Reaction SMILES: [CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:9]([O:11][C:12](=[O:17])[CH2:13][N:14]([CH3:16])[CH3:15])[CH3:10].[H-].[Na+].C(O)C>CCOCC>[CH3:15][N:14]([CH3:16])[C:13](=[CH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:12]([O:11][CH2:9][CH3:10])=[O:17]
Reactant: O=Cc1ccccc1
Reactant: CCOC(=O)CN(C)C
Agent: [H-]
Agent: [Na+]
Solvent: CCOCC
Solvent: CCO
Product: CCOC(=O)C(=Cc1ccccc1)N(C)C
Yield: 60 %

Procedure:
Benzaldehyde, N,N-dimethylglycine ethyl ester and sodium hydride were reacted in ether with the addition of a catalytic amount of ethanol according to the method described in Lieb. Ann. Chem. 703 (1967) 37-43 to give ethyl α-dimethylaminocinnamate. This compound was then reacted according to the method described in Tetrahedron Letters, 46, (1978) 4573-4574 with oxalyl chloride and hydrazine in 60% yield to give ethyl 4-phenyl-3-pyrazolecarboxylate, melting point 164°-165° after recrystallization from ethanol/diethyl ether.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C@@H:16]2[C@H:11]([C@H:12]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([NH:24][C:25]([O:27][CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[O:26])=[C:20]([F:35])[CH:19]=3)[CH2:13][S:14][CH2:15]2)[O:10][C:9]1([CH3:37])[CH3:36])=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(O)=[O:40].OO.[O-]S([O-])(=S)=O.[Na+].[Na+]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[C@@H:16]2[C@H:11]([C@H:12]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([NH:24][C:25]([O:27][CH2:28][C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)=[O:26])=[C:20]([F:35])[CH:19]=3)[CH2:13][S@:14](=[O:40])[CH2:15]2)[O:10][C:9]1([CH3:37])[CH3:36])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1[C@H]2CSC[C@@H](Cc3ccc(NC(=O)OCc4ccccc4)c(F)c3)[C@@H]2OC1(C)C
Reactant: CC(=O)O
Agent: O=S([O-])([O-])=S
Agent: OO
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1[C@H]2C[S@@](=O)C[C@@H](Cc3ccc(NC(=O)OCc4ccccc4)c(F)c3)[C@@H]2OC1(C)C
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of (3aR*,7S*,7aS*)-7-(4-benzyloxycarbonylamino-3-fluoro-benzyl)-2,2-dimethyl-tetrahydro-1-oxa-5-thia-3-aza-indene-3-carboxylic acid tert-butyl ester (54.1 g, 102 mmol) in THF (500 mL) was added AcOH (200 mL) and H2O2 (27.8 g, 50% in H2O, 408 mmol) at 0-5° C. and the reaction mixture was stirred for 16 h at 25° C. The reaction mixture was slowly added to a cold 25% aq. Na2S2O3 solution, stirred for 3 h at 0-5° C. and extracted with EtOAc. Combined organic layers were washed with water, saturated K2CO3 solution and brine, dried over MgSO4, filtered and evaporated. The crude product was filtered through a short plug of ammonia deactivated silicagel and the title compound was obtained as a 3:2 mixture of the (3aR*,5R*,7S*,7aS*)- and (3aR*,5S*,7S*,7aS*)-diastereoisomer after crystallization from Et2O-hexane: TLC (EtOAc-MeOH 19:1) Rf=0.51; HPLC RtA=2.34 min and 2.38 min; ESIMS [M+H]+=547. Separation of the racemic 3:2 mixture on Chiralpak IC (heptene-EtOH 85:15) and on Chiralpak AD-I (hexane-EtOH-CHCl3 80:10:10) provided the diastereoisomers (3aR,5R,7S,7aS)-7-(4-benzyloxycarbonylamino-3-fluoro-benzyl)-2,2-dimethyl-5-oxo-hexa-hydro-1-oxa-5lambda*4*-thia-3-aza-indene-3-carboxylic acid tert-butyl ester (peak 1 on Chiralpak IC) in >98% ee: [α]D−21.5° (c 1, CHCl3); 1H NMR (600 MHz, DMSO-d6): δ 9.43 (s, 1H), 7.56 (s, 1H), 7.40 (m, 4H), 7.33 (t, 1H), 7.08 (d, 1H), 6.99 (d, 1H), 5.14 (s, 2H), 3.6-3.8 (m, 2H), 3.40 (t, 1H), 2.92 (m, 2H), 2.6-2.8 (m, 3H), 2.37 (t, 1H), 1.55 (s, 3H), 1.50 (s, 3H), 1.41 (s, 9H) and (3aR,5S,7S,7aS)-7-(4-benzyloxycarbonylamino-3-fluoro-benzyl)-2,2-di-methyl-5-oxo-hexahydro-1-oxa-5lambda*4*-thia-3-aza-indene-3-carboxylic acid tert-butyl ester (peak 2 on Chiralpak IC): 1H NMR (600 MHz, DMSO-d6): δ 9.44 (s, 1H), 7.57 (s, 1H), 7.40 (m, 4H), 7.35 (t, 1H), 7.08 (d, 1H), 6.99 (d, 1H), 5.14 (s, 2H), 3.9-4.2 (m, 1H), 3.65 (t, 1H), 2.5-3.5 (m, 6H), 2.25 (m, 1H), 1.51 (s, 6H), 1.42 (s, 9H) followed by the (3aS,5R,7R,7aR)- and (3aS,5S,7R,7aR)-diastereoisomers (peak 3 and peak 4).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:41]=[CH:40][C:6]([C:7]([N:9]2[C:17]3[C:12](=[CH:13][C:14]([O:18][C:19]([F:22])([F:21])[F:20])=[CH:15][CH:16]=3)[C:11]([CH2:23][C:24]3[CH:25]=[C:26]([CH:36]=[CH:37][CH:38]=3)[O:27][C@@H:28]([CH3:35])[C:29]([O:31]CC=C)=[O:30])=[C:10]2[CH3:39])=[O:8])=[CH:5][CH:4]=1.CC1(C)CC(=O)CC(=O)C1.C(N(CC)C(C)C)(C)C.[Cl-].[NH4+]>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:7]([N:9]2[C:17]3[C:12](=[CH:13][C:14]([O:18][C:19]([F:20])([F:21])[F:22])=[CH:15][CH:16]=3)[C:11]([CH2:23][C:24]3[CH:25]=[C:26]([CH:36]=[CH:37][CH:38]=3)[O:27][C@@H:28]([CH3:35])[C:29]([OH:31])=[O:30])=[C:10]2[CH3:39])=[O:8])=[CH:40][CH:41]=1
Reactant: C=CCOC(=O)[C@H](C)Oc1cccc(Cc2c(C)n(C(=O)c3ccc(OC)cc3)c3ccc(OC(F)(F)F)cc23)c1
Agent: CC1(C)CC(=O)CC(=O)C1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COc1ccc(C(=O)n2c(C)c(Cc3cccc(O[C@@H](C)C(=O)O)c3)c3cc(OC(F)(F)F)ccc32)cc1
Reaction time: 2 h
Yield: 87.1 %

Procedure:
Compound 6 (490 mg, 0.86 mmole) was dissolved in DMF (9 mL). 5,5-Dimethyl-1,3-cyclohexanedione (181 mg, 1.29 mmole), N,N-diisopropylethylamine (0.225 mL, 1.29 mmole) and (tetrakistriphenylphoshine)palladium (50 mg, 0.043 mmole) were then added and the solution stirred for 2 hours. Then aqueous ammonium chloride was added and the solution was extracted repeatedly with dichloromethane. The combined organics were dried over sodium sulfate, filtered and the filtrate was evaporated . The crude isolate was then purified by silica gel chromatography to give the title compound (395 mg, 87%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:12](=O)[C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)=[C:7]([CH:11]=1)[C:8](O)=[O:9].O.[NH2:22][NH2:23]>>[CH3:1][O:2][C:3]1[CH:11]=[C:7]2[C:6]([C:12]([C:13]3[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=3)=[N:22][NH:23][C:8]2=[O:9])=[CH:5][CH:4]=1
Reactant: NN
Reactant: COc1ccc(C(=O)c2ccc(C)cc2)c(C(=O)O)c1
Solvent: O
Product: COc1ccc2c(-c3ccc(C)cc3)n[nH]c(=O)c2c1

Procedure:
This compound is obtained according to the procedure described in 1.2. by reacting unpurified 5-methoxy-2-(4-methylbenzoyl)benzoic acid with hydrazine hydrate.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.[CH2:13]1[O:23][C:22]2[CH:21]=[CH:20][C:17]([CH:18]=O)=[CH:16][C:15]=2[O:14]1.C(O)(C(F)(F)F)=O>>[CH2:13]1[O:23][C:22]2[CH:21]=[CH:20][C:17]([CH:18]3[C:5]4[NH:6][C:7]5[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=5)[C:4]=4[CH2:3][CH2:2][NH:1]3)=[CH:16][C:15]=2[O:14]1
Reactant: O=Cc1ccc2c(c1)OCO2
Reactant: NCCc1c[nH]c2ccccc12
Solvent: O=C(O)C(F)(F)F
Product: c1ccc2c3c([nH]c2c1)C(c1ccc2c(c1)OCO2)NCC3
Yield: 62.7 %

Procedure:
This product was prepared using the same procedure as for Intermediate 1 with tryptamine (20.0 g, 120 mmol), 3,4-methylenedioxybenzaldehyde (20.6 g, 1.1 equiv.) and TFA (18 mL, 2 equiv.) to give the title compound (22 g, 60%) as white crystals after recrystallization from ethanol.
Reaction SMILES: [O:1]=[S:2]1(=[O:20])[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[C:4](NCCCC(OCC)=O)=[N:3]1.Cl.[CH2:22]([O:24][C:25](=[O:28])[CH2:26][NH2:27])[CH3:23].C(N(CC)CC)C>O1CCOCC1>[O:1]=[S:2]1(=[O:20])[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[C:4]([NH:27][CH2:26][C:25]([O:24][CH2:22][CH3:23])=[O:28])=[N:3]1
Reactant: CCOC(=O)CCCNC1=NS(=O)(=O)c2ccccc21
Reactant: CCOC(=O)CN
Agent: Cl
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: CCOC(=O)CNC1=NS(=O)(=O)c2ccccc21

Procedure:
15.0 g. (74.4 mM) of 3-chloro-1,2-benzisothiazole 1,1-dioxide (prepared as in Example 1), 10.4 g. (74.4 mM) of glycine ethyl ester, hydrochloride and 20.4 ml. (148.8 mM) of triethylamine are refluxed in 250 ml of dioxane for 2 hours. The dioxane is evaporated and the residue is taken up in chloroform which is washed with water (2 x) and evaporated. The residue 2-[(1,1-dioxo-1,2-benzisothiazol-3-yl)amino]acetic acid, ethyl ester is recrystallized once from 150 ml of methanol/water (1:1) and once from 200 ml. of water to give 2-[(1,1-dioxo-1,2-benzisothiazol-3-yl)amino]acetic acid, ethyl ester as yellow needles, yield 14.35 g., m.p. 166°-167°.
Reaction SMILES: CS(O[CH2:6][C@H:7]1[CH2:12][CH2:11][C@H:10]([CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[CH2:9][CH2:8]1)(=O)=O.[I-].[Na+].[C-:24]#[N:25].[Na+]>CN(C)C=O>[Si:15]([O:14][CH2:13][C@H:10]1[CH2:11][CH2:12][C@H:7]([CH2:6][C:24]#[N:25])[CH2:8][CH2:9]1)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]
Reactant: [C-]#N
Reactant: CC(C)(C)[Si](C)(C)OC[C@H]1CC[C@H](COS(C)(=O)=O)CC1
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OC[C@H]1CC[C@H](CC#N)CC1
Temperature: 110 °C
Reaction time: 0.75 h

Procedure:
In 100 ml of dry dimethylformamide were suspended 11.0 g of trans-4-methanesulfonyloxymethyl-1-t-butyldimethylsilyloxymethylcyclohexane, 5.87 g of sodium iodide and 1.92 g of sodium cyanide, and the mixture was stirred at 50° C. for 1 hour and 45 minutes and further at 110° C. for 45 minutes. The reaction mixture was poured into 100 ml of ice-water and the mixture was extracted with 300 ml of ether. The extracts were washed with an aqueous citric acid solution, an aqueous sodium chloride solution, an aqueous sodium bicarbonate solution and an aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography employing cyclohexane-ethyl acetate (20:1-5:1) as an eluting solvent to obtain 7.41 g of the desired compound as a colorless oil.
Reaction SMILES: C([O:3][C:4]([CH2:6][CH2:7][CH2:8][O:9][C:10]1[C:11]([Se:24][C:25]2[CH:35]=[CH:34][C:28]([C:29]([O:31]CC)=[O:30])=[CH:27][N:26]=2)=[CH:12][C:13]2[C:14]([CH3:23])([CH3:22])[CH2:15][CH2:16][C:17]([CH3:21])([CH3:20])[C:18]=2[CH:19]=1)=[O:5])C.[OH-].[Na+]>C(O)C>[C:4]([CH2:6][CH2:7][CH2:8][O:9][C:10]1[C:11]([Se:24][C:25]2[CH:35]=[CH:34][C:28]([C:29]([OH:31])=[O:30])=[CH:27][N:26]=2)=[CH:12][C:13]2[C:14]([CH3:23])([CH3:22])[CH2:15][CH2:16][C:17]([CH3:21])([CH3:20])[C:18]=2[CH:19]=1)([OH:5])=[O:3]
Reactant: CCOC(=O)CCCOc1cc2c(cc1[Se]c1ccc(C(=O)OCC)cn1)C(C)(C)CCC2(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CC1(C)CCC(C)(C)c2cc([Se]c3ccc(C(=O)O)cn3)c(OCCCC(=O)O)cc21

Procedure:
In a manner similar to that of Example 2, by reaction of 340 mg (0.62 mmol) of ethyl 6-[3-(3-ethoxycarbonylpropoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl]nicotinate with 250 mg (62.2 mmol) of sodium hydroxide in ethanol (10 ml), 211 mg (69%) of a white powder are obtained. m.p.: 177° C.
Reaction SMILES: Cl.[CH2:2]([O:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([O:18][C:19]2[CH:24]=[CH:23][C:22]([CH2:25][C@H:26]([NH:37]C(OC(C)(C)C)=O)[CH2:27][O:28][C:29]3[CH:30]=[C:31]([CH:34]=[CH:35][CH:36]=3)[C:32]#[N:33])=[CH:21][CH:20]=2)[CH2:14][CH2:13]1)=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(C(C)C)CC)(C)C.[I:54][C:55]1[CH:60]=[CH:59][C:58]([S:61](Cl)(=[O:63])=[O:62])=[CH:57][CH:56]=1>O1CCOCC1.C(OCC)(=O)C>[CH2:2]([O:9][C:10]([N:12]1[CH2:13][CH2:14][CH:15]([O:18][C:19]2[CH:24]=[CH:23][C:22]([CH2:25][C@H:26]([NH:37][S:61]([C:58]3[CH:59]=[CH:60][C:55]([I:54])=[CH:56][CH:57]=3)(=[O:63])=[O:62])[CH2:27][O:28][C:29]3[CH:30]=[C:31]([CH:34]=[CH:35][CH:36]=3)[C:32]#[N:33])=[CH:21][CH:20]=2)[CH2:16][CH2:17]1)=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CC(C)(C)OC(=O)N[C@H](COc1cccc(C#N)c1)Cc1ccc(OC2CCN(C(=O)OCc3ccccc3)CC2)cc1
Reactant: O=S(=O)(Cl)c1ccc(I)cc1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: N#Cc1cccc(OC[C@H](Cc2ccc(OC3CCN(C(=O)OCc4ccccc4)CC3)cc2)NS(=O)(=O)c2ccc(I)cc2)c1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
25 ml of 4 N solution of hydrogen chloride in dioxane and 12.5 ml of dioxane were added to 2.54 g (4.34 mmol) of 3-[(2S)-3-[4-[1-(benzyloxycarbonyl)-4-piperidyloxy]phenyl]-2-(t-butoxycarbonylamino)propoxy]benzonitrile. After stirring at room temperature for 24 hours, the solvent was distilled off under reduced pressure. The residue was dissolved in 40 ml of DMF. 1.77 ml (13.0 mmol) of diisopropylethylamine and 1.97 g (6.51 mmol)) of 4-iodobenzenesulfonyl chloride were added to the solution at 0° C. 30 minutes after, the temperature was elevated to room temperature, and the reaction mixture was stirred for 19 hours. Ater the same isolation process as that of step 1 in Example 1 with ethyl acetate as the extractant, the crude product was obtained, which was purified by the silica gel column chromatography to obtain the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([O:13][CH3:14])=[C:5]([CH3:15])[C:4]=1[CH:16]=O.[Br-].[C:19]([CH2:22][CH2:23][CH2:24][CH2:25][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([OH:21])=[O:20].CC(C)([O-])C.[K+]>CC(O)(C)C.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([O:13][CH3:14])=[C:5]([CH3:15])[C:4]=1[CH:16]=[CH:25][CH2:24][CH2:23][CH2:22][C:19]([OH:21])=[O:20]
Reactant: O=C(O)CCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: COc1c(C)c(C=O)c(OC)c2ccccc12
Agent: CC(C)(C)[O-]
Agent: [Br-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CC(C)(C)O
Product: COc1c(C)c(C=CCCCC(=O)O)c(OC)c2ccccc12
Temperature: 60 °C
Reaction time: 0.5 h
Yield: 65.9 %

Procedure:
To a suspension of 1 g of 1,4-dimethoxy-3-methylnaphthalene-2-carbaldehyde and 3.85 g of (4-carboxybutyl)triphenylphosphonium bromide in 2.5% t-BuOH/toluene at 60° C. was added 1.95 g of potassium t-butoxide. The mixture was stirred at 60° C. for 30 min, extracted with 1N NaOH, and washed with toluene. The aqueous layer was neutralized with iN HCl until pH 4-5, then extracted with ethyl acetate. The organic layer was washed, dried, and concentrated, then the trsidue was purified with column chromatography over silica gel using n-hexane/ethyl acetate (2/1) as an eluent to give 0.9 g of the titled compound as an oil.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]([NH2:15])[CH:11]=[CH:12][C:13]=2[F:14])[CH:5]=[CH:4][N:3]=1.C(N(CC)CC)C.[H][H]>[Pd]>[F:14][C:13]1[CH:12]=[CH:11][C:10]([NH2:15])=[CH:9][C:8]=1[C:6]1[CH:5]=[CH:4][N:3]=[CH:2][N:7]=1
Reactant: [H][H]
Reactant: Nc1ccc(F)c(-c2ccnc(Cl)n2)c1
Agent: [Pd]
Solvent: CCN(CC)CC
Product: Nc1ccc(F)c(-c2ccncn2)c1

Procedure:
To the solution of 3-(2-chloropyrimidin-4-yl)-4-fluorophenylamine from above was added triethylamine (0.48 ml, 3.15 mmol) and palladium on active carbon (100 mg, 10% palladium) and the mixture was reduced under 40 psi hydrogen for 30 minutes. The mixture was filtered and the solvent removed to give 4-fluoro-3-(pyrimidin-4-yl)phenylamine as a yellow solid: MS (ES+) m/z 190 [M+H]+.