Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[C:3]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8](I)=[CH:7][CH:6]=2.[CH3:18][S:19]([O-:21])=[O:20].[Na+].C(N)CN>CS(C)=O.C(OCC)(=O)C>[OH:1][C:2]1[C:3]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8]([S:19]([CH3:18])(=[O:21])=[O:20])=[CH:7][CH:6]=2
Reactant: CS(=O)[O-]
Reactant: CCOC(=O)c1nc2ccc(I)cc2nc1O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Solvent: NCCN
Product: CCOC(=O)c1nc2ccc(S(C)(=O)=O)cc2nc1O
Temperature: 110 °C

Procedure:
A degassed mixture of ethyl 3-hydroxy-6-iodoquinoxaline-2-carboxylate (351 mg, 1.0 mmol), sodium methanesulfinate (132 mg, 1.3 mmol), copper(I) triflate benzene complex (25 mg, 5 mol %) and ethylenediamine (0.01 mL, 10 mol %) in anhydrous DMSO (1.0 mL) was heated at 110° C. in a sealed reaction vessel for 20 h. The cooled mixture was diluted with ethyl acetate (10 mL) and filtered through a plug of silica gel under reduced pressure, eluting with additional ethyl acetate (50 mL). The filtrate was washed with water (20 mL) and brine (20 mL), dried over sodium sulfate and filtered. The solvents were removed under reduced pressure and the residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate, to provide ethyl 3-hydroxy-6-(methylsulfonyl)quinoxaline-2-carboxylate as a yellow solid: 1H NMR (400 MHz, CDCl3) δ 11.61 (br S, 1H), 8.16 (d, J=8.9 Hz, 1H), 8.01 (s, 1H), 7.91 (d, J=9.9 Hz, 1H), 4.58 (q, J=6.7 Hz, 2H), 3.16 (s, 3H), 1.49 (t, J=6.7 Hz) ppm; ESI MS m/z 297 [M+H]−.
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][C@@H:17]2[CH3:22])[C:5]2[CH:10]([CH3:11])[S:9](=[O:13])(=[O:12])[C:8]([CH3:15])([CH3:14])[C:6]=2[N:7]=1.[CH2:23]([NH:25][C:26]([NH:28][C:29]1[CH:34]=[CH:33][C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH:30]=1)=[O:27])[CH3:24]>>[CH2:23]([NH:25][C:26]([NH:28][C:29]1[CH:34]=[CH:33][C:32]([C:2]2[N:3]=[C:4]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][C@@H:17]3[CH3:22])[C:5]3[CH:10]([CH3:11])[S:9](=[O:13])(=[O:12])[C:8]([CH3:15])([CH3:14])[C:6]=3[N:7]=2)=[CH:31][CH:30]=1)=[O:27])[CH3:24]
Reactant: CCNC(=O)Nc1ccc(B2OC(C)(C)C(C)(C)O2)cc1
Reactant: CC1c2c(N3CCOC[C@@H]3C)nc(Cl)nc2C(C)(C)S1(=O)=O
Product: CCNC(=O)Nc1ccc(-c2nc(N3CCOC[C@@H]3C)c3c(n2)C(C)(C)S(=O)(=O)C3C)cc1

Procedure:
The title compound was synthesised following the procedure in Example 5 (step viii) using 2-chloro-5,7,7-trimethyl-4-((S)-3-methylmorpholino)-5,7-dihydrothieno[3,4-d]pyrimidine 6,6-dioxide and 1-ethyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea. LC-MS (Method D), (ES+) 474, RT=3.00 min.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[CH2:7]([N:9]([CH2:12][CH2:13][N:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([CH:23]3[CH2:28][CH2:27][N:26]([C:29](OC(C)(C)C)=O)[CH2:25][CH2:24]3)[CH:21]=2)[CH:16]=[N:15]1)[CH2:10][CH3:11])[CH3:8]>C1COCC1>[CH2:7]([N:9]([CH2:12][CH2:13][N:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([CH:23]3[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]3)[CH:21]=2)[CH:16]=[N:15]1)[CH2:10][CH3:11])[CH3:8]
Reactant: CCN(CC)CCn1ncc2ccc(C3CCN(C(=O)OC(C)(C)C)CC3)cc21
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CCN(CC)CCn1ncc2ccc(C3CCN(C)CC3)cc21
Temperature: 25 °C
Yield: 75 %

Procedure:
A solution of LAH in THF (1M, 0.25 mL, 0.25 mmol) was added to a solution of 1-(2-(N,N-diethylamino)ethyl)-6-(N-Boc-tetrahydro-4-pyridinyl)-1H-indazole (10.2 mg, 0.025 mmol) in THF (0.5 mL) at room temperature under argon and the resulting solution was refluxed for 2 h. After cooling to room temperature, the reaction was quenched using sodium sulfate decahydrate solid and the resulting solid was removed by filtration, extracting the product into ethyl acetate. The solvent was removed in vacuo and purification using an SPE (solid phase extraction) cartridge containing 1 g of silica gel by eluting with 0-10% 2M methanolic ammonia in dichloromethane yielded 1-(2-(N,N-diethylamino)ethyl)-6-(N-methyltetrahydro-4-pyridinyl)-1H-indazole (5.9 mg, 74%).
Reaction SMILES: [O:1]=[C:2]1[CH:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][N:3]1[CH2:14][C:15]([OH:17])=O.Cl.[F:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[CH2:25][NH:24][CH2:23]2.C(N=C=NCCCN(C)C)C>ClCCl>[F:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[CH2:25][N:24]([C:15](=[O:17])[CH2:14][N:3]1[CH2:4][CH2:5][CH2:6][CH:7]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:2]1=[O:1])[CH2:23]2
Reactant: Fc1ccc2c(c1)CNC2
Reactant: O=C(O)CN1CCCC(c2ccccc2)C1=O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Product: O=C(CN1CCCC(c2ccccc2)C1=O)N1Cc2ccc(F)cc2C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To 2-(2-oxo-3-phenylpiperidin-1-yl)acetic acid (Example 91D, 0.168 g, 0.720 mmol) and 5-fluoroisoindoline hydrochloride (0.138 g, 0.792 mmol) in dichloromethane (0.5 mL) was added N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.191 mL, 1.080 mmol), and the reaction was stirred at ambient temperature overnight. The reaction was loaded directly onto a SF15-12 silica gel column (Analogix®, Burlington, Wis.), and the title compound was eluted using a gradient of 5% to 100% ethyl acetate/hexanes over 20 minutes (flow=30 mL/minute). 1H NMR (300 MHz, CDCl3) δ ppm 7.14-7.36 (m, 6H), 6.92-7.02 (m, 2H), 4.85-4.90 (m, 2H), 4.78-4.83 (m, 2H), 4.43 (dd, J=15.6, 1.7 Hz, 1H), 4.06 (d, J=15.7 Hz, 1H), 3.73 (dd, J=7.7, 6.1 Hz, 1H), 3.65-3.71 (m, 1H), 3.57 (dt, J=11.6, 5.8 Hz, 1H), 2.19-2.29 (m, 1H), 1.97-2.11 (m, 2H), 1.83-2.00 (m, 1H); MS (DCI+) m/z 353 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][C:5]([OH:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[C:12]1(B(O)O)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O>[O:11]=[C:5]1[C:6]([C:7]([OH:9])=[O:8])=[CH:10][C:2]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:3][NH:4]1
Reactant: O=C(O)c1cc(Br)cnc1O
Reactant: OB(O)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C(O)c1cc(-c2ccccc2)c[nH]c1=O
Temperature: 110 °C
Yield: 18.1 %

Procedure:
A mixture of 5-bromo-2-hydroxynicotinic acid (436 mg, 2.00 mmol, Syn. Comm., 19 (3&4), 553–559 (1989)), phenylboronic acid (248 mg, 2.03 mmol), Cs2CO3 (1.20 g) and PdCl2 [(t-Bu)2P(OH)]2 (170 mg, CombiPhos Catalysts, Inc. Princeton, N.J.) in DMF (10 mL) and water (1.0 mL) was purged with Ar gas and heated at 110° C. for 6 h. Additional phenylboronic acid (75 mg) was added and the mixture was heated at 110° C. for 5 h. To the reaction was added TFA (3 mL), and the mixture was concentrated in vacuo to a volume of ˜12 mL. The mixture was purified by preparative HPLC to afford the desired product (78 mg, 18%). 1H NMR (DMF-d7) δ 14.8 (br s, 1H), 13.8 (br s, 1H), 8.73 (s, 1H), 8.46 (s, 1H), 7.74 (d, 1H, J=7.2 Hz), 7.53–7.42 (m, 3H), 5.81 (s, 1H).
Reaction SMILES: [CH2:1](Br)[CH:2]=[CH2:3].[CH2:5]([OH:27])[C@H:6]1[O:11][C@H:10]([O:12][C@:13]2([CH2:22][OH:23])[O:17][C@H:16]([CH2:18][OH:19])[C@@H:15]([OH:20])[C@@H:14]2[OH:21])[C@H:9]([OH:24])[C@@H:8]([OH:25])[C@@H:7]1[OH:26]>O>[CH2:3]=[CH:2][CH2:1][O:27][CH2:5][C@H:6]1[O:11][C@H:10]([O:12][C@:13]2([CH2:22][OH:23])[O:17][C@H:16]([CH2:18][OH:19])[C@@H:15]([OH:20])[C@@H:14]2[OH:21])[C@H:9]([OH:24])[C@@H:8]([OH:25])[C@@H:7]1[OH:26]
Reactant: OC[C@H]1O[C@@](CO)(O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@@H](O)[C@@H]1O
Reactant: C=CCBr
Solvent: O
Product: C=CCOC[C@H]1O[C@H](O[C@]2(CO)O[C@H](CO)[C@@H](O)[C@@H]2O)[C@H](O)[C@@H](O)[C@@H]1O

Procedure:
96 g of ion exchange water and 96 g (2.4 moles) of sodium hydroxide were added to a 1 L four-necked separable flask equipped with a stirrer, a reflux condenser and a dropping funnel to dissolve the sodium hydroxide in the ion exchange water. 68.4 g (0.2 moles) of sucrose was further added, and reacted at 80° C. for 90 minutes while stirring to obtain an alkaline sucrose aqueous solution. 290 g (2.4 moles) of allyl bromide was added dropwise into the alkaline sucrose aqueous solution for 2 hours while controlling rapid heating caused by an etherification reaction. Thereafter, the etherification reaction was completed by aging the reaction solution at 80° C. for 3 hours. After cooling, 400 g of ion exchange water was added to the reaction solution taken from the separable flask, and unwanted water-soluble components were removed from the oils to obtain crude oil-soluble sucrose allyl ether. Subsequently, 250 g of ion exchange water was added, and volatile components formed as the by-products were distilled off together with water using a rotary evaporator. 120 g of n-hexane and 40 g of ion exchange water were further added, and water-soluble impurities were removed again through liquid separation. The n-hexane was distilled off from the separated oily phase using a rotary evaporator to obtain 110 g of purified oil-soluble sucrose allyl ether. The etherification degree of the oil-soluble sucrose allyl ether was 6.5.
Reaction SMILES: N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[C:19]([O:23][C:24]([N:26]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH2:28][CH:27]1[CH2:35][OH:36])=[O:25])([CH3:22])([CH3:21])[CH3:20].C(P(CCCC)CCCC)CCC.O[C:51]1[CH:83]=[CH:82][C:54]([CH2:55][CH:56]2[S:60][C:59](=[O:61])[N:58]([C:62]([C:75]3[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=3)([C:69]3[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=3)[C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=3)[C:57]2=[O:81])=[CH:53][CH:52]=1>O1CCCC1.CN(C)C=O>[C:19]([O:23][C:24]([N:26]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH2:28][CH:27]1[CH2:35][O:36][C:51]1[CH:83]=[CH:82][C:54]([CH2:55][CH:56]2[S:60][C:59](=[O:61])[N:58]([C:62]([C:75]3[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=3)([C:69]3[CH:70]=[CH:71][CH:72]=[CH:73][CH:74]=3)[C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=3)[C:57]2=[O:81])=[CH:53][CH:52]=1)=[O:25])([CH3:22])([CH3:21])[CH3:20]
Reactant: O=C1SC(Cc2ccc(O)cc2)C(=O)N1C(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CC(C)(C)OC(=O)N1c2ccccc2CC1CO
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1c2ccccc2CC1COc1ccc(CC2SC(=O)N(C(c3ccccc3)(c3ccccc3)c3ccccc3)C2=O)cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 20.4 %

Procedure:
A solution of 6.6 g of 1,1'-(azodicarbonyl)dipiperidine in 10 ml of anhydrous tetrahydrofuran and 20 ml of anhydrous dimethylformamide was added dropwise to a mixture of 6.5 g of 1-t-butoxycarbonyl-2-hydroxymethylindoline (prepared as described in Preparation 3), 6.5 ml of tributylphosphine, 12.2 g of 5-(4-hydroxybenzyl)-3-triphenylmethylthiazolidine-2,4-dione [prepared as described in European Patent Publication No. 549 365A1] and 100 ml of anhydrous tetrahydrofuran, and the resulting mixture was stirred at room temperature for about 20 hours. At the end of this time, insoluble materials were filtered off and the filtrate was concentrated by evaporation under reduced pressure. The concentrate thus obtained was purified by column chromatography through silica gel, using a 10:1 by volume mixture of hexane and ethyl acetate as the eluent, to give 3.70 g of the title compound, melting at 85.4-87.2° C.
Reaction SMILES: [C:1]1([CH:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[O:8][CH2:9][CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:23][CH2:24][N:25]1[C:29](=[O:30])[C:28]2=[CH:31][CH:32]=[CH:33][CH:34]=[C:27]2[C:26]1=[O:35].C([O-])([O-])=O.[K+].[K+].[Na+].[I-]>CC(=O)CC>[C:1]1([CH:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[O:8][CH2:9][CH:10]2[CH2:15][CH2:14][N:13]([CH2:23][CH2:24][N:25]3[C:26](=[O:35])[C:27]4[C:28](=[CH:31][CH:32]=[CH:33][CH:34]=4)[C:29]3=[O:30])[CH2:12][CH2:11]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: c1ccc(C(OCC2CCNCC2)c2ccccc2)cc1
Reactant: O=C1c2ccccc2C(=O)N1CCBr
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CCC(C)=O
Product: O=C1c2ccccc2C(=O)N1CCN1CCC(COC(c2ccccc2)c2ccccc2)CC1
Temperature: 25 °C
Yield: 79.8 %

Procedure:
The mixture of 4-(1,1-diphenyl-methoxymethyl)-piperidine (0.760 g, 2.7 mmol, 1.0 eq.), N-(2-bromoethyl)phthalimide (0.686 g, 2.7 mmol, 1.0 eq.), K2CO3 (0.560 g, 4.1 mmol, 1.5 eq.), and NaI (0.567 g, 3.8 mmol, 1.4 eq.) in 2-butanone (10 ml) was refluxed for 2-3 hours. The mixture was then cooled to room temperature. The white solid was filtered off and was washed with small amount of CHCl3. The filtrates were combined and concentrated. The resulted residue was dissolved in CHCl3 (80 ml). The solution was washed with water (3×10 ml), then dried over anhydrous Na2SO4. After removed all solvent, the crude product 2-{2-[4-(1,1-diphenyl-methoxymethyl)-piperidin-1-yl]-ethyl}-isoindole-1,3-dione was yielded (0.980 g, 79.8% yield).
Reaction SMILES: [Br:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][O:7][C:8]2[C:9]([CH2:15][CH2:16][NH2:17])=[N:10][C:11]([CH3:14])=[CH:12][CH:13]=2)=[CH:4][CH:3]=1.[CH:20]([C:22]1[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][CH:23]=1)=O.[BH4-].[Na+].O>C(O)C>[Br:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][O:7][C:8]2[C:9]([CH2:15][CH2:16][NH:17][CH2:20][C:22]3[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][CH:23]=3)=[N:10][C:11]([CH3:14])=[CH:12][CH:13]=2)=[CH:4][CH:3]=1
Reactant: Cc1ccc(OCc2ccc(Br)cc2)c(CCN)n1
Reactant: COC(=O)c1ccc(C=O)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: COC(=O)c1ccc(CNCCc2nc(C)ccc2OCc2ccc(Br)cc2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 35.7 %

Procedure:
A solution of 675 mg (2.10 mmol) of 2-{3-[(4-bromobenzyl)oxy]-6-methyl-2-pyridinyl}ethylamine and 345 mg (2.10 mmol) of methyl 4-formylbenzoate in 5 ml of ethanol is heated at reflux for two hours. The solvent is then removed under reduced pressure and the resulting residue is dissolved in 5 ml of methanol. A total of 159 mg (4.21 mmol) of solid NaBH4 are added a little at a time. After two hours of stirring at room temperature, the mixture is poured into water and extracted with ethyl acetate. The organic extract is washed with saturated sodium chloride solution and dried over Na2SO4. After filtration, the solvent is removed under reduced pressure and the resulting crude product is purified by preparative HPLC. This gives 351 mg (0.75 mmol, 35% yield) of a colorless oil.
Reaction SMILES: [CH2:1](Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:9][C:10]([N:13]1[C:17]([OH:18])=[C:16]([C:19](=[O:39])[C:20]2[CH:25]=[CH:24][C:23]([S:26]([CH3:29])(=[O:28])=[O:27])=[C:22]([C:30]3[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=3)[C:21]=2[CH3:38])[CH:15]=[N:14]1)([CH3:12])[CH3:11].C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>CN(C)C=O>[CH3:12][C:10]([N:13]1[C:17]([O:18][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[C:16]([C:19](=[O:39])[C:20]2[CH:25]=[CH:24][C:23]([S:26]([CH3:29])(=[O:28])=[O:27])=[C:22]([C:30]3[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=3)[C:21]=2[CH3:38])[CH:15]=[N:14]1)([CH3:9])[CH3:11]
Reactant: ClCc1ccccc1
Reactant: COc1ccc(-c2c(S(C)(=O)=O)ccc(C(=O)c3cnn(C(C)(C)C)c3O)c2C)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COc1ccc(-c2c(S(C)(=O)=O)ccc(C(=O)c3cnn(C(C)(C)C)c3OCc3ccccc3)c2C)cc1
Reaction time: 8 h

Procedure:
Benzyl chloride (1.1 mL) was added with stirring under nitrogen to a mixture of 2.0 g (4.5 mmol) of 1-(1,1-dimethylethyl)-5-hydroxy-4-(2-methyl-4-methylsulfonyl-3-(4-methoxyphenyl)benzoyl)pyrazole and 1.3 g of sodium carbonate in about 20 mL of dry N,N-dimethylformamide and the resulting mixture was allowed to stir overnight. Ethyl acetate was then added and the resulting mixture was washed with water several times, dried over magnesium sulfate, filtered, and concentrated by evaporation under reduced pressure. The residual orange oil was chromatographed on silica eluting with an 80:20 mixture and then a 60:40 mixture of hexane and ethyl acetate. The product fractions were combined and concentrated by evaporation under reduced pressure and dried to obtain 1.73 g (72 percent of theory) of the title compound as a yellow glass.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([N:14]([C:19]([C:21]2[N:22]=[N:23][N:24]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[CH3:38])[C:25]=2[CH2:26][CH2:27][CH2:28][CH2:29][O:30][CH3:31])=[O:20])[CH2:15][CH:16]([CH3:18])[CH3:17])[CH2:11][C@@H:10]([C:39](O)=[O:40])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.C(=O)([O-])O.[Na+]>CN(C=O)C>[CH3:31][O:30][CH2:29][CH2:28][CH2:27][CH2:26][C:25]1[N:24]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[CH3:38])[N:23]=[N:22][C:21]=1[C:19]([N:14]([CH2:15][CH:16]([CH3:17])[CH3:18])[C@H:12]1[CH2:11][C@@H:10]([C:39]([N:42]2[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)=[O:40])[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:7])[CH2:13]1)=[O:20]
Reactant: C1COCCN1
Reactant: COCCCCc1c(C(=O)N(CC(C)C)[C@H]2C[C@@H](C(=O)O)CN(C(=O)OC(C)(C)C)C2)nnn1-c1ccccc1C
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C([O-])O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COCCCCc1c(C(=O)N(CC(C)C)[C@H]2C[C@@H](C(=O)N3CCOCC3)CN(C(=O)OC(C)(C)C)C2)nnn1-c1ccccc1C

Procedure:
A solution of (3R,5S)-1-(tert-butoxycarbonyl)-5-[{[5-(4-methoxybutyl)-1-(2-methylphenyl)-1H-1,2,3-triazol-4-yl]carbonyl}(2-methylpropyl)amino]piperidine-3-carboxylic acid (286 mg), morpholine (44 μl), WSC.HCl (144 mg), HOBt (107 mg), diisopropylethylamine (255 μl) and DMF (3 ml) was stirred at room temperature for 15 hr. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate, and the liberated oil was extracted with ethyl acetate (20 ml). The extract was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate was concentrated under reduced pressure to give the object product (255 mg) as an amorphous compound.
Reaction SMILES: [Br:1][C:2]1[C:10]([F:11])=[CH:9][C:8]2[NH:7][N:6]=[CH:5][C:4]=2[C:3]=1[C:12]([O:14][CH3:15])=[O:13].F[B-](F)(F)F.[CH3:21][O+](C)C>C(OCC)(=O)C.C(=O)([O-])O.[Na+]>[Br:1][C:2]1[C:10]([F:11])=[CH:9][C:8]2[C:4](=[CH:5][N:6]([CH3:21])[N:7]=2)[C:3]=1[C:12]([O:14][CH3:15])=[O:13]
Reactant: C[O+](C)C
Reactant: COC(=O)c1c(Br)c(F)cc2[nH]ncc12
Agent: F[B-](F)(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Product: COC(=O)c1c(Br)c(F)cc2nn(C)cc12
Reaction time: 2.5 h
Yield: 77.6 %

Procedure:
To a solution of methyl 5-bromo-6-fluoro-1H-indazole-4-carboxylate (700 mg, 2.56 mmol) in ethyl acetate (26 mL) was added trimethyloxonium tetrafluoroborate (569 mg, 3.85 mmol) at room temperature, and the mixture was stirred for 2.5 hr. The reaction solution was diluted with saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=10/90→50/50) to give the title compound (570 mg, yield 78%).
Reaction SMILES: [C:1]1([C:7]2[CH:11]=[C:10]([CH2:12][CH2:13][CH2:14][OH:15])[NH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:16]Br>C(Cl)Cl.C1COCC1>[Br:16][C:11]1[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[N:8][NH:9][C:10]=1[CH2:12][CH2:13][CH2:14][OH:15]
Reactant: OCCCc1cc(-c2ccccc2)n[nH]1
Reactant: BrBr
Solvent: ClCCl
Solvent: C1CCOC1
Product: OCCCc1[nH]nc(-c2ccccc2)c1Br
Reaction time: 2 h
Yield: 97.9 %

Procedure:
3-(3-Phenyl-1H-pyrazol-5-yl)propan-1-ol (3.0 g, 14.83 mmol) was dissolved in dry DCM (40 mL) and THF (15 mL). The reaction was cooled in an ice bath and Br2 (1.146 mL, 22.25 mmol) pre-dissolved in DCM (10 mL) was added slowly dropwise: via addition funnel. The reaction was stirred for 2 h in an ice bath. The reaction was quenched by the addition of Na2SO3 (20 mL of 10% solution; the reaction went from reddish-brown to clear and some bubbling was observed). The reaction was extracted (100 mL each of H2O and DCM). The aqueous layer was extracted again with DCM (100 mL). The combined organic layer was back extracted again with H2O (200 mL). The organic layer was dried and concentrated to give the title compound (4.08 g) as a yellow solid. LCMS m/z=281.3 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.72-1.83 (m, 2H), 2.61-2.68 (m, 2H), 3.47 (t, J=6.44 Hz, 2H), 7.39 (t, J=7.33 Hz, 1H), 7.47 (t, J=7.45 Hz, 2H), 7.78 (d, J=7.07 Hz, 2H).
Reaction SMILES: C(O[CH:5]1[S:9][C@H:8]([CH2:10][O:11][Si:12]([C:25]([CH3:28])([CH3:27])[CH3:26])([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:7][CH2:6]1)(=O)C.[NH:29]1[CH:37]=[C:35]([CH3:36])[C:33](=[O:34])[NH:32][C:30]1=[O:31].FC(F)(F)C(F)(F)C(F)(F)C(F)(F)S([O-])(=O)=O.[K+].C[Si](N[Si](C)(C)C)(C)C.[Si](Cl)(C)(C)C>>[Si:12]([O:11][CH2:10][C@H:8]1[S:9][C@@H:5]([N:29]2[CH:37]=[C:35]([CH3:36])[C:33](=[O:34])[NH:32][C:30]2=[O:31])[CH2:6][CH2:7]1)([C:25]([CH3:26])([CH3:27])[CH3:28])([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: CC(=O)OC1CC[C@@H](CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)S1
Reactant: Cc1c[nH]c(=O)[nH]c1=O
Agent: C[Si](C)(C)Cl
Agent: C[Si](C)(C)N[Si](C)(C)C
Agent: O=S(=O)([O-])C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Product: Cc1cn([C@H]2CC[C@@H](CO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)S2)c(=O)[nH]c1=O
Yield: 93 %

Procedure:
Using the procedure for Example 11, 4'-thioribose 10 (0.35 g, 0.83 mmol), thymine (0.13 g, 1.05 mmol), potassium nonafluorobutanesulfonate (0.875 g, 2.54 mmol), HMDS (0.175 mL, 0.83 mmol), and TMS-Cl (0.4 mL, 3.2 mmol), following purification by preparative TLC (8:1 dichloromethane/acetonitrile) afforded 371 mg (92.5%) of 14, as a 4:3 α:β anomeric mixture; FAB MS 481 (M+H)+ ; 1H NMR (CDCl3) δ 9.65 (s, 1, NH), 7.7 (m, 4, ArH), 7.4 (m, 6, ArH), 6.3 (m, 1, 1'-Hα,β), 3.88 (m, 1, 4'-Hα), 3.82 (d, 1, 5'-Hβ), 3.66 (d+m, 2, 4'-Hβ, 5'-Hα), 2.4-1.85 (m, 4, 2'-H α,β 's, 3'-Hα,β 's), 1.95 (s, 3, 5β -CH3), 1.77 (s, 3, 5β -CH3), 1.11 (s, 9, β-t-butyl), 1.07 (s, 9, α-t-butyl).
Reaction SMILES: [CH:1]1([CH2:6][N:7]([CH2:38][CH3:39])[C:8]2[N:13]=[C:12]3[N:14]([CH3:18])[N:15]=[C:16]([CH3:17])[C:11]3=[CH:10][C:9]=2[CH2:19][N:20]([CH2:23][C:24]2[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[C:26]([C:34]([F:37])([F:36])[F:35])[CH:25]=2)[C:21]#[N:22])[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH:40]O.[OH-].[K+].O>C(O)C>[F:33][C:30]([F:31])([F:32])[C:28]1[CH:29]=[C:24]([CH:25]=[C:26]([C:34]([F:35])([F:36])[F:37])[CH:27]=1)[CH2:23][N:20]([CH2:19][C:9]1[CH:10]=[C:11]2[C:16]([CH3:17])=[N:15][N:14]([CH3:18])[C:12]2=[N:13][C:8]=1[N:7]([CH2:6][CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5]1)[CH2:38][CH3:39])[C:21]([NH2:22])=[O:40]
Reactant: OO
Reactant: CCN(CC1CCCC1)c1nc2c(cc1CN(C#N)Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)c(C)nn2C
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CCN(CC1CCCC1)c1nc2c(cc1CN(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)C(N)=O)c(C)nn2C
Temperature: 25 °C
Yield: 60 %

Procedure:
To a stirred solution of [6-(cyclopentylmethyl-ethyl-amino)-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-5-ylmethyl-(3,5-bis-trifluoromethyl-benzyl)-cyanamide (0.50 g, 0.880 mmol) in ethanol (15 mL) were added H2O2 (1.5 mL) and a saturated aqueous solution of KOH (0.70 g, 11.97 mmol) at 0° C. This mixture was slowly heated to reflux. After 2 h the reaction mixture was cooled to RT, water (10 mL) was added, and the product was extracted with ethyl acetate (3×40 mL). The combined organic layers were dried over sodium sulfate and evaporated to yield the crude residue. The crude was purified by column chromatography over 100-200 mesh silica gel using 10% ethyl acetate and petroleum ether to yield the title compound as a sticky oil (yield: 60%).