Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8]C)=[O:7])=[C:4]([O:12][CH3:13])[CH:3]=1.O.O[Li].O.Cl>C1COCC1>[OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([OH:8])=[O:7])=[C:4]([O:12][CH3:13])[CH:3]=1
Reactant: COC(=O)c1ccc(O)cc1OC
Agent: Cl
Agent: [Li]O
Solvent: C1CCOC1
Solvent: O
Product: COc1cc(O)ccc1C(=O)O
Reaction time: 24 h

Procedure:
To a stirred solution of methyl 4-hydroxy-2-methoxybenzoate (11 g, 60 mmol) in THF:H2O (100 mL:10 mL) was added LiOH.H2O (3 g, 71 mmol). The solution was stirred over 24 h and then made slightly acidic (pH 5) with 10% HCl (approx 15 mL). The reaction solution was extracted with CH2Cl2 (3×50 mL). The organic phase was dried (MgSO4) and filtered. The solvent was evaporated under reduced pressure to afford the 4-hydroxy-2-methoxybenzoic acid as a clean white foam.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8]C)=[O:7])=[C:4]([O:12][CH3:13])[CH:3]=1.[OH-].[Na+].Cl>>[OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([OH:8])=[O:7])=[C:4]([O:12][CH3:13])[CH:3]=1
Reactant: COC(=O)c1ccc(O)cc1OC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: COc1cc(O)ccc1C(=O)O
Yield: 101.1 %

Procedure:
Stir a mixture of methyl 4-hydroxy-2-methoxybenzoate (Danishefsky et al., J. Med. Chem. 1979, 101, 7001-7008, 0.37 g, 2 mmol) and 1N NaOH for two hours at room temperature. Acidify with 1N HCl and extract with dichloromethane. Dry (MgSO4) the organic phase, filter and concentrate the filtrate in vacuo. Vacuum dry the residue at room temperature overnight to afford 4-hydroxy-2-methoxybenzoic acid (0.34 g).
Reaction SMILES: [N+:1]([C:4]1[CH:10]=[C:9]([B:11]2[O:15][C:14]([CH3:17])([CH3:16])[C:13]([CH3:19])([CH3:18])[O:12]2)[CH:8]=[CH:7][C:5]=1[NH2:6])([O-])=O>C(OCC)(=O)C.[Pd]>[CH3:16][C:14]1([CH3:17])[C:13]([CH3:18])([CH3:19])[O:12][B:11]([C:9]2[CH:10]=[C:4]([NH2:1])[C:5]([NH2:6])=[CH:7][CH:8]=2)[O:15]1
Reactant: CC1(C)OB(c2ccc(N)c([N+](=O)[O-])c2)OC1(C)C
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CC1(C)OB(c2ccc(N)c(N)c2)OC1(C)C
Temperature: 25 °C
Reaction time: 36 h

Procedure:
In a 250 mL stainless steel pressure bottle a solution of EXAMPLE 1H (5 g, 18.93 mmol) in ethyl acetate (50 mL) was treated with 10% Pd on carbon (1.25 g, 1.175 mmol). The suspension was stirred under a hydrogen atmosphere for 36 hours at 30 psi at ambient temperature. The mixture was filtered through a nylon membrane and concentrated to provide the title compound. MS APCI(+)) m/e 235.19 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[C:7]([C:8]([NH:10][C:11]([CH3:15])([CH3:14])[CH2:12]Cl)=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1>C[Si](C)(C)N[Si](C)(C)C>[Cl:1][C:2]1[C:7]([C:8]2[O:9][CH2:12][C:11]([CH3:15])([CH3:14])[N:10]=2)=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: CC(C)(CCl)NC(=O)c1cccnc1Cl
Agent: C[Si](C)(C)N[Si](C)(C)C
Product: CC1(C)COC(c2cccnc2Cl)=N1
Temperature: 125 °C
Yield: 77.2 %

Procedure:
24.7 g (0.10 mole) of 2-chloro 3-(1,1-dimethyl-2-chloroethyl)aminocarbonylpyridine, prepared as described in Example 2c, are suspended in hexamethyldisilazane and the suspension is heated at reflux for 6 h (about 125° C.). The excess hexamethyldisilazane is evaporated under reduced pressure and the residue is distilled under high vacuum to give 16.27 g of 2-chloro 3-(4,4-dimethyl 2-oxazolinyl)pyridine.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:20]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[C:14]3[C:9]2=[CH:10][CH:11]=[CH:12][CH:13]=3)=[CH:4][CH:3]=1.C([Li])CCC.[B:26](OC)([O:29]C)[O:27]C.Cl>O1CCCC1>[CH:10]1[C:9]2[N:8]([C:5]3[CH:4]=[CH:3][C:2]([B:26]([OH:29])[OH:27])=[CH:7][CH:6]=3)[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]=2[CH:13]=[CH:12][CH:11]=1
Reactant: COB(OC)OC
Reactant: Brc1ccc(-n2c3ccccc3c3ccccc32)cc1
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: OB(O)c1ccc(-n2c3ccccc3c3ccccc32)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 65.9 %

Procedure:
Then, 21.8 g (67.5 mmol) of 9-(4-bromophenyl)carbazole was put into a 500 mL three-necked flask, and the air in the flask was replaced with nitrogen. Then, 200 mL of tetrahydrofuran (THF) was added thereto. The temperature in the flask was set to be −78° C. and then, 48.9 mL (74.3 mmol) of n-butyllithium (1.52 mol/L, hexane solution) was dropped to the mixture and was stirred for 2 hours at the same temperature. Then, 17.4 mL (155 mmol) of trimethyl borate was added thereto. The mixture was stirred for one hour at the same temperature, then, was stirred for 24 hours while raising the temperature to room temperature. After the reaction, 200 mL of hydrochloric acid (1.0 mol/L) was added to the reaction mixture, and then stirred for one hour at room temperature. After that, the organic layer in the reaction mixture was washed with water and the product was extracted with ethyl acetate from the water which was used for the washing. The obtained extraction solution and the organic layer, which was washed with water, were mixed. The mixture was further washed with a saturated aqueous solution of sodium chloride, and then dried with magnesium sulfate. After the drying, the mixture was suction filtrated, and the filtrate was concentrated. The obtained residue was recrystallized with a mixed solvent of chloroform and hexane to give 12.8 g of a white powdered solid of 4-(carbazol-9-yl)phenylboronic acid (yield: 65.9%). A synthesis scheme (f-3) of 4-(carbazol-9-yl)phenylboronic acid is shown below.
Reaction SMILES: [C:1]1([C:7]2[CH:21]=[CH:20][C:10]3[N:11]=[C:12]([CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[S:13][C:9]=3[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1CCN2C(=NCCC2)CC1.[CH3:33][S:34](Cl)(=[O:36])=[O:35]>CN(C=O)C>[CH3:33][S:34]([CH:14]([C:12]1[S:13][C:9]2[CH:8]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH:21]=[CH:20][C:10]=2[N:11]=1)[C:15]([O:17][CH2:18][CH3:19])=[O:16])(=[O:36])=[O:35]
Reactant: CCOC(=O)Cc1nc2ccc(-c3ccccc3)cc2s1
Reactant: CS(=O)(=O)Cl
Solvent: C1CCC2=NCCCN2CC1
Solvent: CN(C)C=O
Product: CCOC(=O)C(c1nc2ccc(-c3ccccc3)cc2s1)S(C)(=O)=O
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 36 %

Procedure:
Ethyl 2-(6-phenylbenzo[d]thiazol-2-yl)acetate (described in WO2011/074560, 550 mg, 1.9 mmol) was dissolved in DMF (10 mL) and cooled to 0° C. DBU (0.61 mL, 4.1 mmol) was added. After 10 minutes, methanesulfonyl chloride (0.2 mL, 3 mmol) was added dropwise. The reaction mixture was removed from the ice bath and stirred at room temperature. After 4 hours, the reaction mixture was cooled back to 0° C., and additional methane sulfonyl chloride (0.11 mL, 1.4 mmol) was added. Following addition, the reaction mixture was removed from ice bath and stirred at room temperature. After 3 days, the reaction mixture was quenched by the addition of water (20 mL), and the resulting solid was collected by filtration. The solids were dissolved in DCM, washed with aqueous 10% LiCl, 1N HCl, brine, dried over MgSO4, concentrated under reduced pressure, and purified by silica gel chromatography (eluting with 0-20% DCM/MeOH) to give Compound B1a (250 mg, 36% yield) as a yellow oil. HPLC: RT=1.03 min (LCMS Method O). MS (ES): m/z=376.0 [M+H]+. 1H NMR (400 MHz, pyridine-d5) δ 8.07 (br. s., 1H), 7.79-7.64 (m, 4H), 7.51 (t, J=7.7 Hz, 2H), 7.40 (s, 1H), 4.39 (d, J=7.0 Hz, 2H), 3.49 (s, 3H), 1.29 (t, J=7.0 Hz, 3H).
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[N:2]1.[N:10]#[C:11][NH2:12].O.[C:14]1([CH3:24])[CH:19]=[CH:18][C:17]([S:20]([OH:23])(=[O:22])=[O:21])=[CH:16][CH:15]=1>O1CCOCC1.CCOCC>[C:14]1([CH3:24])[CH:15]=[CH:16][C:17]([S:20]([OH:23])(=[O:21])=[O:22])=[CH:18][CH:19]=1.[C:11]([N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[N:2]1)(=[NH:10])[NH2:12]
Reactant: c1ccc2[nH]nnc2c1
Reactant: N#CN
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCOCC
Solvent: O
Solvent: C1COCCO1
Product: N=C(N)n1nnc2ccccc21
Temperature: 25 °C

Procedure:
A mixture of benztriazole (11.9 g, 100 mmol), cyanamide (4.2 g, 100 mmol), and p-toluene sulfonic acid hydrate (19.2 g, 100 mmol) in dioxane was refluxed for 24 hours. The reaction mixture was allowed to cool to room temperature and was diluted with ether, stirred vigorously, then filtered. The filter cake was washed with ether and recrystallized from ethanol to give the desired product as a white solid.
Reaction SMILES: CC1C=CC(C2C=CC(C#C)=CC=2)=CC=1.[Br:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[Al+3].[Cl-].[Cl-].[Cl-].[CH3:27][CH:28]([CH3:34])[CH2:29][CH2:30][C:31](O)=[O:32]>>[O:32]=[C:31]([C:20]1[CH:21]=[CH:22][C:17]([Br:16])=[CH:18][CH:19]=1)[CH2:30][CH2:29][CH:28]([CH3:34])[CH3:27]
Reactant: Brc1ccccc1
Reactant: CC(C)CCC(=O)O
Agent: C#Cc1ccc(-c2ccc(C)cc2)cc1
Agent: [Al+3]
Agent: [Cl-]
Product: CC(C)CCC(=O)c1ccc(Br)cc1

Procedure:
Reaction Scheme 5 discloses a specific synthetic route to 4-(4-methylpenyl)-phenylethyne (Compound 26). In accordance with this scheme, bromobenzene (Compound 27) is reacted under Friedel Crafts conditions (AlCl3) with the acid chloride (Compound 28) prepared in situ from 4-methyl valeric acid, to yield 4-(1-oxo-4-methyl-pentyl) bromobenzene (Compuond 29). Compound 29 is reduced under Wolff-Kishner conditions (KOH, NH2NH2) to yield 4-(4-methylpentyl) bromobenzene (Compound 30). The bromobenzene derivative 30 is converted to the ethyne derivative 26 through the intermediate trimethylsilyl ethyne derivative 31 in a manner similar to the conversion described in connection with Reaction Scheme 3. ##STR9##
Reaction SMILES: [NH2:1][C:2]1[C:7](I)=[CH:6][C:5]([Cl:9])=[CH:4][N:3]=1.C(N(CC)CC)C.[C:17]([Si:19]([CH3:22])([CH3:21])[CH3:20])#[CH:18]>O1CCCC1.C(OCC)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1[C:7]([C:18]#[C:17][Si:19]([CH3:22])([CH3:21])[CH3:20])=[CH:6][C:5]([Cl:9])=[CH:4][N:3]=1
Reactant: Nc1ncc(Cl)cc1I
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: C[Si](C)(C)C#Cc1cc(Cl)cnc1N
Temperature: 25 °C
Reaction time: 2 h
Yield: 109.9 %

Procedure:
Under a nitrogen atmosphere, to a solution of 2-amino-5-chloro-3-iodopyridine (4.2 g, 0.017 mol), copper(I) iodide (0.032 g, 0.17 mmol) and triethylamine (7.0 mL, 0.050 mol) in anhydrous tetrahydrofuran (10 mL), dichlorobis(triphenylphosphine)palladium(II) (0.12 g, 0.17 mmol) and ethynyl trimethylsilane (3.0 mL, 0.021 mol) were added and the mixture was stirred at ambient temperature for 2 h. The reaction mixture was diluted with diethyl ether and removed the precipitate by filtration with C elite. The filtrate was concentrated to afford 2-amino-5-chloro-3-[(trimethylsilyl)ethynyl]pyridine as solid (4.2 g).
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].F[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1.O.[Cl-].[Na+]>CS(C)=O.C(OCC)(=O)C>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][O:7][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)=[CH:4][CH:3]=1
Reactant: Fc1ccccn1
Reactant: OCc1ccc(Br)cc1
Agent: CC(C)(C)[O-]
Agent: [Cl-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Solvent: CCOC(C)=O
Product: Brc1ccc(COc2ccccn2)cc1
Reaction time: 0.17 h
Yield: 97.6 %

Procedure:
To a solution of 4-bromobenzyl alcohol (18 g, 94.3 mmol) in dimethylsulfoxide (85 mL) was added potassium tert-butoxide (11.5 g, 99 mmol) little by little under a nitrogen atmosphere at room temperature, which was stirred for 10 minutes. To this solution was added 2-fluoropyridine (12.3 g, 123 mmol) dropwise over 30 minutes under a water bath cooling. After stirring at room temperature for two hours, ethyl acetate and 5% sodium chloride water were added, and extracted. After the organic layer was washed sequentially with water and 5% sodium chloride water, the solvent was evaporated under a reduced pressure to obtain the title compound (24.3 g) as a yellow oily product.
Reaction SMILES: Br[C:2]1[C:3]2[C:4]3[CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12][CH2:11][C:5]=3[NH:6][C:7]=2[CH:8]=[CH:9][CH:10]=1.CC(C)([O-])C.[Na+].[NH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>[Cl-].[Na+].O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:30]1([NH:29][C:2]2[C:3]3[C:4]4[CH2:15][CH2:14][NH:13][CH2:12][CH2:11][C:5]=4[NH:6][C:7]=3[CH:8]=[CH:9][CH:10]=2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: Nc1ccccc1
Reactant: CC(C)(C)OC(=O)N1CCc2[nH]c3cccc(Br)c3c2CC1
Agent: [Pd]
Agent: CC(C)(C)P(c1ccccc1-c1ccccc1)C(C)(C)C
Agent: CC(C)(C)[O-]
Solvent: O
Product: c1ccc(Nc2cccc3[nH]c4c(c23)CCNCC4)cc1
Temperature: 50 °C
Reaction time: 16 h

Procedure:
To a solution of tert-butyl 10-bromo-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (600 mg), sodium t-butoxide (220 mg), tris(dibenzylideneacetone)dipalladium (23 mg), aniline (183 mg) toluene (1.64 ml) was added 2-(di-t-butylphosphino)biphenyl (30 mg) and the reaction mixture was heated at 50° C. The reaction mixture stirred 16 h, was poured into brine, extracted with CH2Cl2, dried over MgSO4, filtered and concentrated. The crude product was stirred in CH2Cl2 (8 ml) and TFA (2 ml) was added. The reaction mixture stirred 1 h, was quenched with 2N NaOH, extracted with CH2Cl2, dried over MgSO4, filtered and concentrated. Purification via flash chromatography (silica gel, CH2Cl2/MeOH, 9/1 with 0.5% NH4OH) provided the title compound: 1H NMR (DMSO-d6) δ 2.68, 2.83-2.90, 6.58-6.67, 6.89, 7.06, 7.54, 10.71.
Reaction SMILES: [CH3:1]C(C)([O-])C.[K+].[Br-].CP(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O=[C:29]1[CH2:32][N:31]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:30]1>C(OCC)C>[CH2:1]=[C:29]1[CH2:32][N:31]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:30]1
Reactant: CC(C)(C)[O-]
Reactant: CC(C)(C)OC(=O)N1CC(=O)C1
Agent: C[PH](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [K+]
Solvent: CCOCC
Product: C=C1CN(C(=O)OC(C)(C)C)C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 100 %

Procedure:
A mixture of potassium tert-butoxide (15.5 g, 137 mmol) and methyltriphenylphosphine bromide (49 g, 137 mmol) in diethyl ether (300 mL) was stirred at room temperature for 1 hour, followed by the addition of 1,1-dimethylethyl 3-oxoazetidine-1-carboxylate (10 g, 58 mmol in 100 mL diethyl ether). The mixture was stirred at 35° C. for 2 hours and then allowed to cool to room temperature. The mixture was filtered through a pad of celite, washing with diethyl ether. The filtrate was partitioned with water and washed twice with water, brine, dried over sodium sulfate, filtered and concentrated in vacuo to give an orange oil which was purified by column chromatography. Eluting with 10% ethyl acetate in hexanes, isolated product was concentrated in vacuo to afford 9.80 g, 58 mmol (100%) of 1,1-dimethylethyl 3-methylideneazetidine-1-carboxylate as a colorless oil. 1H NMR (400 MHz, DMSO): 5.05-4.85 (m, 2H), 4.95-4.63 (m, 4H), 1.45 (s, 9H). GC-MS for C9H15NO2: 169.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:19]([O:21][CH3:22])=[O:20])[CH:5]=[C:6]2[C:11]=1[O:10][C:9]([N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)=[CH:8][C:7]2=[O:18].C([Sn](CCCC)(CCCC)[C:28]([O:30]CC)=[CH2:29])CCC>O1CCOCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:28]([C:2]1[CH:3]=[C:4]([C:19]([O:21][CH3:22])=[O:20])[CH:5]=[C:6]2[C:11]=1[O:10][C:9]([N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)=[CH:8][C:7]2=[O:18])(=[O:30])[CH3:29]
Reactant: COC(=O)c1cc(Br)c2oc(N3CCOCC3)cc(=O)c2c1
Reactant: C=C(OCC)[Sn](CCCC)(CCCC)CCCC
Agent: Cl[Pd]Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Product: COC(=O)c1cc(C(C)=O)c2oc(N3CCOCC3)cc(=O)c2c1
Temperature: 90 °C
Yield: 69.9 %

Procedure:
To a stirred suspension of methyl 8-bromo-2-morpholino-4-oxo-4H-chromene-6-carboxylate (40 g, 108 mmol, as described in Example 1.00) in dioxane (300 mL) was added tributyl(1-ethoxyvinyl)stannane (38.5 mL, 114 mmol) and bis(triphenylphosphine) palladium (II) chloride (3.05 g, 4.35 mmol). The mixture was purged with nitrogen and heated at 90° C. overnight. More tributyl(1-ethoxyvinyl)stannane (20 mL) and bis(triphenylphosphine) palladium (II) chloride (1.5 g) were added and the reaction mixture heated for an additional 3 hrs. The mixture was cooled to room temperature, HC1-2N (81 mL, 163 mmol) was added and the dark suspension heated at 45° C. for 30 min. The dioxane was evaporated under vacuum, the residue was dissolved in DCM and a saturated solution of sodium bicarbonate was added until pH 4. The organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated to afford a crude compound which was triturated in diethylether, filtered and dried to afford methyl 8-acetyl-2-morpholino-4-oxo-4H-chromene-6-carboxylate (25.0 g, 69.5%) as an off-white solid.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[CH:7]=[N:8]O)([O-])=O>O1CCCC1>[NH2:1][C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[CH2:7][NH2:8]
Reactant: O=[N+]([O-])c1cccc(C=NO)c1
Solvent: C1CCOC1
Product: NCc1cccc(N)c1
Yield: 89.2 %

Procedure:
The same procedure as in Example 1 was carried out except using m-nitrobenzaldoxime obtained in Example 2 as the material, tetrahydrofurane as the solvent and a 5% Rh-C catalyst as the catalyst. m-Aminobenzylamine of 99.9% in purity was obtained with an yield of 89.2%.
Reaction SMILES: [CH2:1]([O:8][CH2:9][C@@:10]1([N:35]2[CH:43]=[C:41]([CH3:42])[C:39](=[O:40])[NH:38][C:36]2=[O:37])[O:34][C@H:14]([CH2:15][O:16][Si:17]([C:30]([CH3:33])([CH3:32])[CH3:31])([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@H:12]([OH:13])[CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:44](Cl)([C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)=[O:45]>C(Cl)Cl.CCN(CC)CC>[CH2:1]([O:8][CH2:9][C@@:10]1([N:35]2[CH:43]=[C:41]([CH3:42])[C:39](=[O:40])[NH:38][C:36]2=[O:37])[O:34][C@H:14]([CH2:15][O:16][Si:17]([C:30]([CH3:33])([CH3:32])[CH3:31])([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[C@@H:12]([O:13][C:44](=[O:45])[C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: Cc1cn([C@@]2(COCc3ccccc3)C[C@H](O)[C@@H](CO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)O2)c(=O)[nH]c1=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1cn([C@@]2(COCc3ccccc3)C[C@H](OC(=O)c3ccccc3)[C@@H](CO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)O2)c(=O)[nH]c1=O
Yield: 86.9 %

Procedure:
A stirred solution of 3 (128.0 g, 213.3 mmol) in a 4:1 mixture of CH2Cl2 /Et3N (500 mL) was treated with (48.4 g, 40 mL, 344.6 mmol) of BzCl at 23° C. for 8 h. The resultant precipitate was removed by filtration. The filtrate was concentrated under reduced pressure to leave the crude product as a brownish syrup. Purification of the syrup by silica gel column chromatography (hexanes/AcOEt 10:1 then 1:1) gave 130.7 g (87%) of 4 as a white solid. Rf (Hexanes/AcOEt 1:1) 0.82 1H-NMR (CDCl3): 1.40 (s, 9H, C-Me3), 1.60 (s, 3H, 5-Me), 2.37 (ddd, 1H, J=13.8, 9.3, 7.2 Hz, 2'-Hβ), 2.62 (dd, 1H, J=13.8, 4.3 Hz, 2'-Hβ), 4.09 (m, 2H, 5'-H), 4.26 (m, 1H, 4'-H), 4.74 (s, 2H, O--CH2 -Ph), 5.54 (s, 2H, N--CH2 --O), 5.71 (d, 1H, J=7.2 Hz, 3'-H), 6.57 (dd, 1H, J=9.3, 4.3 Hz, 1'-H), 7.24-7.74 (m, 13H, aromatic-H), 8.05-8.15 (m, 3H, 6-H and aromatic-H). 13C-NMR(CDCl3): 12.82 (-, 5-Me), 19.54 (+, C-Me3), 27.16 (C-Me3), 38.28 (+, 2'-C), 64.41 (+, 5'-C), 70.80 (+, O--C-Ph), 72.29 (+, N--C--O), 75.60 (-, 4'-C), 85.28 (-, 1'-C and 3'-C), 110.95 (+, 5-C), 127.72, 128.23, 128.37, 128.50, 128.63 (-, aromatic-C), 129.43 (+, aromatic-C), 129.84, 130.22 (-, aromatic-C), 132.14, 133.07 (+, aromatic-C), 133.60 (-, 6-C), 133.94, 135.32, 135.65 (-, aromatic-C), 138.15 (+, aromatic-C), 151.19 (+, 2-C), 163.50 (+, 4-C), 166.11 (+, benzoyl C=O).
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][CH:3]=[N:2]1.[CH3:6][N:7]([CH3:12])[S:8](Cl)(=[O:10])=[O:9].C(N(CC)CC)C>C1(C)C=CC=CC=1>[CH3:6][N:7]([CH3:12])[S:8]([N:1]1[CH:5]=[CH:4][CH:3]=[N:2]1)(=[O:10])=[O:9]
Reactant: c1cn[nH]c1
Reactant: CN(C)S(=O)(=O)Cl
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CN(C)S(=O)(=O)n1cccn1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of 1H-pyrazole (5.00 g) in toluene (67.0 mL) were added dimethylsulfamoyl chloride (7.89 mL) and triethylamine (13.3 mL) at room temperature, and the reaction mixture was stirred at room temperature for 18 hr. The resulting solid was removed by filtration, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (6.24 g).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[CH:6]2)#[N:2].[OH-].[Na+].[I:14]I.S([O-])([O-])(=O)=S.[Na+].[Na+]>CN(C=O)C>[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[I:14])#[N:2]
Reactant: II
Reactant: N#Cc1ccc2[nH]ccc2c1
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Product: N#Cc1ccc2[nH]cc(I)c2c1
Temperature: 25 °C
Reaction time: 0.42 h
Yield: 74.9 %

Procedure:
5-Cyanoindole (0.500 g, 3.52 mmol) was dissolved in DMF (25 mL), and sodium hydroxide (0.493 g, 8.79 mmol) and iodine (0.902 g, 3.55 mmol) were added thereto, then the mixture was stirred at room temperature for 25 minutes. A saturated aqueous sodium thiosulfate solution was added to the mixture, and the precipitated solid was filtered off to give 5-cyano-3-iodoindole (0.707 g, 75%).
Reaction SMILES: [CH:1]1[C:15](=[O:16])[N:14]=[C:13]2[N:3]([C@@H:4]3[O:8][C@H:7]([CH2:9][OH:10])[C@@H:6]([OH:11])[C@@H:5]3[O:12]2)[CH:2]=1.C1C=CN=CC=1.[FH:23]>O1CCOCC1>[F:23][C@@H:5]1[C@H:6]([OH:11])[C@@H:7]([CH2:9][OH:10])[O:8][C@H:4]1[N:3]1[CH:2]=[CH:1][C:15](=[O:16])[NH:14][C:13]1=[O:12]
Reactant: F
Reactant: O=c1ccn2c(n1)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]12
Solvent: C1COCCO1
Solvent: c1ccncc1
Product: O=c1ccn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2F)c(=O)[nH]1
Yield: 75 %

Procedure:
2,2'-Cyclouridine is treated with a solution of 70% hydrogen fluoride/pyridine in dioxane at 120° C. for ten hours to provide after solvent removal a 75% yield of 2'-deoxy-2'-fluorouridine. The 5'-DMT and 3'-cyanoethoxydiisopropylphosphoramidite derivitized nucleoside is obtained by standard literature procedures [Gait, Ed., Oligonucleotide Synthesis. A Practical Approach, IRL Press, Washington, D.C. (1984)], or according to the procedure of Example 1A.
Reaction SMILES: CC(OC([N:8]1[CH2:13][CH2:12][N:11]2[C:14](=[O:29])[O:15][C:16]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:10]2[CH2:9]1)=O)(C)C.FC(F)(F)C(O)=O>ClCCl>[C:23]1([C:16]2([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:10]3[CH2:9][NH:8][CH2:13][CH2:12][N:11]3[C:14](=[O:29])[O:15]2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: CC(C)(C)OC(=O)N1CCN2C(=O)OC(c3ccccc3)(c3ccccc3)C2C1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=C1OC(c2ccccc2)(c2ccccc2)C2CNCCN12
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of (1,1-dimethylethyl)tetrahydro-3-oxo-1,1-diphenyl-3H-oxazolo[3,4-a]pyrazine-7(1H)-carboxylate (99 mg, 0.25 mmol) in dichloromethane (2 mL) was added trifluoroacetic acid (0.19 mL, 2.5 mmol), and the mixture was stirred at room temperature for 4 hours. The reaction solution was concentrated under reduced pressure, and the residue was dissolved in ethyl acetate. This solution was washed with sodium hydrogen carbonate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain hexahydro-1,1-diphenyl-3H-oxazolo[3,4-a]pyrazin-3-one as a crude product. The product was dissolved in tetrahydrofuran (2 mL). Diisopropylethylamine (60 μL, 0.35 mmol) and phenyl chlorocarbonate (44 μL, 0.35 mmol) were added thereto, and the mixture was stirred at room temperature for 1 hour. To the reaction solution was added ethyl acetate, and the resulting mixture was washed with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was crystallized from ethyl acetate-hexane to obtain the title compound (70 mg, yield 67%).