Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:3]=1[CH2:4][C:5]1[C:6]([CH2:11][CH3:12])=[N:7][NH:8][C:9]=1[NH2:10].O=[C:19]([C:26]1[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=1)[CH2:20][C:21](OCC)=[O:22]>C(O)(=O)C.O>[Cl:1][C:2]1[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:3]=1[CH2:4][C:5]1[C:6]([CH2:11][CH3:12])=[N:7][N:8]2[C:21]([OH:22])=[CH:20][C:19]([C:26]3[CH:31]=[CH:30][N:29]=[CH:28][CH:27]=3)=[N:10][C:9]=12
Reactant: CCOC(=O)CC(=O)c1ccncc1
Reactant: CCc1n[nH]c(N)c1Cc1cccc(Cl)c1Cl
Solvent: CC(=O)O
Solvent: O
Product: CCc1nn2c(O)cc(-c3ccncc3)nc2c1Cc1cccc(Cl)c1Cl
Temperature: 120 °C
Reaction time: 20 h
Yield: 25.6 %

Procedure:
A mixture of 4-(2,3-dichlorobenzyl)-3-ethyl-1H-pyrazol-5-amine (250 mg, 0.93 mmol), ethyl 3-oxo-3-(pyridin-4-yl)propanoate (198 mg, 1.03 mmol) in acetic acid (10 mL) and water (0.5 mL) was stirred at 120° C. for 20 h, cooled and the pH was carefully adjusted to 8. The mixture was extracted with DCM (100 mL×3). The combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column (PE:EA=10:1) to give the titled compound (95 mg, 26%); LC/MS: MS (ES+) m/e 399 (MH+); 1H NMR (300 MHz, DMSO-d6) δ ppm 1.12 (t, J=7.5 Hz, 3H), 2.56 (q, J=7.5 Hz, 2H), 4.07 (s, 2H), 5.97 (s, 1H), 7.16-7.21 (m, 2H), 7.42 (d, 2.1 Hz, 1H), 7.90 (dd, J=1.5, 4.5 Hz, 1H), 8.56 (dd, J=1.5, 4.5 Hz, 1H).
Reaction SMILES: [C:1]([O:10]CC(CO)O)(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].[N:16]([CH2:23][CH2:24][OH:25])([CH2:20][CH2:21][OH:22])[CH2:17][CH2:18][OH:19].C(OC)(=O)C1C(=CC=CC=1)O.C[O-].[Na+]>>[C:1]([OH:10])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].[N:16]([CH2:23][CH2:24][OH:25])([CH2:20][CH2:21][OH:22])[CH2:17][CH2:18][OH:19]
Reactant: O=C(OCC(O)CO)c1ccccc1O
Agent: C[O-]
Agent: [Na+]
Solvent: OCCN(CCO)CCO
Solvent: COC(=O)c1ccccc1O
Product: O=C(O)c1ccccc1O

Procedure:
Triethanolamine salicylate was prepared by the method described in Example 1 for the preparation of glycerol salicylate except that the reactants were triethanolamine (32.9 g; 0.22 moles), methyl salicylate (67.1 g; 0.44 moles) and sodium methoxide (0.82 g; 0.015 moles). The final methyl salicylate level was 20.0%.
Reaction SMILES: [F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][CH:9]=1)[NH2:6].[CH:12](=O)/[CH:13]=[CH:14]/[CH3:15].C(OCC)(=O)C>Cl.O>[CH3:15][C:14]1[CH:13]=[CH:12][C:7]2[C:5](=[CH:4][C:3]([C:2]([F:10])([F:11])[F:1])=[CH:9][CH:8]=2)[N:6]=1
Reactant: Nc1cccc(C(F)(F)F)c1
Reactant: C/C=C/C=O
Agent: Cl
Solvent: CCOC(C)=O
Solvent: O
Product: Cc1ccc2ccc(C(F)(F)F)cc2n1
Temperature: 25 °C
Yield: 28.9 %

Procedure:
To a solution of 3-(trifluoromethyl)aniline (12.43 mL, 99.92 mmol) in 6 N HCl (50 mL) in water was added (E)-but-2-enal (18.77 mL, 229.8 mmol) dropwise at reflux. The reaction was stirred at reflux for 3 hours. After cooling to ambient temperature, ethyl acetate (200 mL) was added. The aqueous layer was separated, basified with ammonium hydroxide to about pH 9, and extracted with DCM (2×200 mL). The combined organic layers were dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (5:1 hexane/ethyl acetate) to give 2-methyl-7-(trifluoromethyl)quinoline (6.1 g, 28.9%) as a solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:28])[CH:12]([C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)[CH2:13][CH:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)=[N:6][CH:5]=1.[H][H]>C(OCC)(=O)C.CO.[Pd]>[CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:28])[CH:12]([C:19]2[CH:20]=[CH:21][C:22]([NH2:25])=[CH:23][CH:24]=2)[CH2:13][CH:14]2[CH2:15][CH2:16][CH2:17][CH2:18]2)=[N:6][CH:5]=1
Reactant: COC(=O)c1ccc(NC(=O)C(CC2CCCC2)c2ccc([N+](=O)[O-])cc2)nc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CO
Product: COC(=O)c1ccc(NC(=O)C(CC2CCCC2)c2ccc(N)cc2)nc1
Yield: 100.7 %

Procedure:
A solution of 6-[3-cyclopentyl-2-(4-nitro-phenyl)-propionylamino]-nicotinic acid methyl ester (300 mg, 0.75 mmol) in ethyl acetate (30 mL) and methanol (5 mL) was treated with 10% palladium on activated carbon (30 mg). The reaction mixture was shaken under 60 psi of hydrogen gas at 25° C. for 16 h. The catalyst was then removed by filtration through a pad of celite and washed with ethyl acetate. The filtrate was concentrated in vacuo to afford 6-[2-(4-amino-phenyl)-3-cyclopentyl-propionylamino]-nicotinic acid methyl ester (277.4 mg, quant) as a pale yellow glass: mp 65-68° C.; EI-HRMS m/e calcd for C21H25N3O3 (M+) 367.1893, found 367.1899.
Reaction SMILES: [C:1]([OH:5])(=O)[C:2]#[CH:3].[Cl:6][C:7]1[N:16]=[C:15]2[C:10]([CH:11]=[CH:12][C:13]([N:17]3[CH:21]([O:22][C:23]([N:25]4[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]4)=[O:24])[C:20]4[S:31][CH2:32][CH2:33][O:34][C:19]=4[C:18]3=[O:35])=[N:14]2)=[CH:9][CH:8]=1.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl.CO>[Cl:6][C:7]1[N:16]=[C:15]2[C:10]([CH:11]=[CH:12][C:13]([N:17]3[CH:21]([O:22][C:23]([N:25]4[CH2:26][CH2:27][N:28]([C:1](=[O:5])[C:2]#[CH:3])[CH2:29][CH2:30]4)=[O:24])[C:20]4[S:31][CH2:32][CH2:33][O:34][C:19]=4[C:18]3=[O:35])=[N:14]2)=[CH:9][CH:8]=1
Reactant: C#CC(=O)O
Reactant: O=C(OC1C2=C(OCCS2)C(=O)N1c1ccc2ccc(Cl)nc2n1)N1CCNCC1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: ClCCl
Solvent: CO
Product: C#CC(=O)N1CCN(C(=O)OC2C3=C(OCCS3)C(=O)N2c2ccc3ccc(Cl)nc3n2)CC1
Temperature: 25 °C
Yield: 23.9 %

Procedure:
A solution of propiolic acid (0.52 g.) in anhydrous methylene chloride (10 cc.) is added to a suspension of 6-(7-chloro-1,8-naphthyridin-2-yl)-7-oxo-5-(piperazin-1-yl)carbonyloxy-2,3,6,7-tetrahydro-5H-1,4-oxathiino[2,3-c]pyrrole (3 g.) and N,N'-dicyclohexylcarbodiimide (1.52 g.) in anhydrous methylene chloride (70 cc.). The mixture is stirred for one and a half hours at a temperature of about 25° C. and then the insoluble product (dicyclohexylurea) is filtered off and washed with methylene chloride (3×5 cc.). The filtrate is concentrated to dryness under reduced pressure and the residue is treated with boiling ethanol (100 cc.). After cooling, the insoluble product is filtered off and washed with ethanol (20 cc.). This product is then dissolved in methylene chloride (200 cc.) and the solution is washed by decantation successively with 0.1 N methanesulphonic acid (50 cc.) and with water (2×50 cc.). After drying, the organic solution is filtered through silica gel (45 g.) contained in a column of diameter 2.2 cm. Elution is carried out using pure methylene chloride (1,000 cc.). The eluate is discarded. Elution is then carried out using a mixture of methylene chloride and methanol (99.5-0.5 by volume; 350 cc.) and the corresponding eluate is concentrated to dryness under reduced pressure (20 mm. Hg). The residue obtained is dissolved in a mixture of methylene chloride and methanol (90-10 by volume; 300 cc.) and the solution obtained is filtered and then concentrated to dryness under reduced pressure. 6-(7-Chloro-1,8-naphthyridin-2-yl)-7-oxo-5-(4-propioloylpiperazin-1-yl)carbonyloxy-2,3,6,7-tetrahydro-5H-1,4-oxathiino[2,3-c]pyrrole (0.8 g.), which melts at 302° C. with decomposition, is thus obtained.
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:10]=[CH:11][C:12]3[O:16][CH:15]=[CH:14][C:13]=3[CH:17]=2)O1.I[C:20]1[C:28]2[C:23](=[N:24][CH:25]=[N:26][C:27]=2[NH2:29])[N:22]([CH:30]([CH3:32])[CH3:31])[N:21]=1.C([O-])([O-])=O.[Na+].[Na+]>CCO.COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:16]1[C:12]2[CH:11]=[CH:10][C:9]([C:20]3[C:28]4[C:23](=[N:24][CH:25]=[N:26][C:27]=4[NH2:29])[N:22]([CH:30]([CH3:32])[CH3:31])[N:21]=3)=[CH:17][C:13]=2[CH:14]=[CH:15]1
Reactant: CC(C)n1nc(I)c2c(N)ncnc21
Reactant: CC1(C)OB(c2ccc3occc3c2)OC1(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: CCO
Product: CC(C)n1nc(-c2ccc3occc3c2)c2c(N)ncnc21
Temperature: 80 °C
Yield: 64.8 %

Procedure:
A solution of 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran (56 mg, 0.23 mmol) in EtOH (1.65 ml) was added to a solution of 3-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (30 mg, 0.1 mmol) in DME (6 ml). Pd(PPh3)4 (30 mg, 0.03 mmol) and saturated Na2CO3 (0.95 ml) were added and the reaction was heated to 80° C. under an argon atmosphere overnight. After cooling, the reaction was extracted with saturated NaCl and CH2Cl2. Organic phases were combined, concentrated in vacuo and purified by RP-HPLC (MeCN:H2O:0.1% TFA) to yield BA96 (19 mg, 72% yield). ESI-MS (M+H)+ m/z calcd 296.1, found 296.1.
Reaction SMILES: [S:1]1[C:5]2=[CH:6][N+:7]([O-])=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.O.[NH3:23]>C(Cl)(Cl)Cl>[NH2:23][C:6]1[N:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2][S:1][C:5]=12
Reactant: N
Reactant: [O-][n+]1ccc2ccsc2c1
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: O
Solvent: ClC(Cl)Cl
Product: Nc1nccc2ccsc12
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 16.6 g of thieno[2,3-c]pyridine-N-oxide in 500 ml of chloroform was added 25 g of p-toluenesulfonyl chloride portionwise with ice-cooling over a period of 1 hour. After the reaction mixture was stirred for further 30 minutes under the same conditions, 250 ml of 10% ammonia water was added, and stirred at ambient temperature for 16 hours. The reaction mixture was diluted with 400 ml of chloroform, washed with water and saturated saline, and dried over anhydrous magnesium sulfate. The drying agent was removed by filtration, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel to give 2.8 g of the title compound as a brown oily material.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:28]=[CH:29][CH:30]=1)[CH2:6][NH:7][C:8]([C:10]1([CH2:23][CH2:24][CH2:25][CH2:26]Br)[C:22]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[C:16]2[C:11]1=[CH:12][CH:13]=[CH:14][CH:15]=2)=[O:9].[N:31]1([C:37]2[CH:46]=[CH:45][C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[N:38]=2)[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:28]=[CH:29][CH:30]=1)[CH2:6][NH:7][C:8]([C:10]1([CH2:23][CH2:24][CH2:25][CH2:26][N:34]2[CH2:35][CH2:36][N:31]([C:37]3[CH:46]=[CH:45][C:44]4[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=4)[N:38]=3)[CH2:32][CH2:33]2)[C:22]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[C:16]2[C:11]1=[CH:12][CH:13]=[CH:14][CH:15]=2)=[O:9]
Reactant: COc1cccc(CNC(=O)C2(CCCCBr)c3ccccc3-c3ccccc32)c1
Reactant: c1ccc2nc(N3CCNCC3)ccc2c1
Product: COc1cccc(CNC(=O)C2(CCCCN3CCN(c4ccc5ccccc5n4)CC3)c3ccccc3-c3ccccc32)c1

Procedure:
Prepared analogously to Example 2 from 9-(4-bromo-butyl)-9H-fluorene-9-carboxylic acid-3-methoxy-benzylamide and 2-piperazin-1-yl-quinoline.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH3:13])[C:11]([C:14]#[N:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.Cl[C:17]([O:19][CH2:20][CH3:21])=[O:18]>>[CH2:20]([O:19][C:17](=[O:18])[NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH3:13])[C:11]([C:14]#[N:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1)[CH3:21]
Reactant: Cn1c(C#N)ccc1-c1ccc(N)cc1
Reactant: CCOC(=O)Cl
Product: CCOC(=O)Nc1ccc(-c2ccc(C#N)n2C)cc1

Procedure:
The title compound was prepared according to the general procedure for acylation of 5-(4-aminophenyl)-1-methyl-1H-pyrrole-2-carbonitrile using ethyl chloroformate (53 μL, 0.55 mmol) to provide ethyl[4-(5-cyano-1-methyl-1H-pyrrol-2-yl)phenyl]carbamate (0.026 g).
Reaction SMILES: [CH3:1][C:2]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]2C(=O)C3=CC=CC=C3C2=O)[O:6][CH2:5][CH2:4][O:3]1.O.NN>C(O)C>[CH3:1][C:2]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][NH2:13])[O:3][CH2:4][CH2:5][O:6]1
Reactant: CC1(CCCCCCN2C(=O)c3ccccc3C2=O)OCCO1
Agent: NN
Solvent: CCO
Solvent: O
Product: CC1(CCCCCCN)OCCO1
Yield: 48.3 %

Procedure:
A mixture of 125.25 g (0.395 mole) of N-[6-(2-methyl-1,3-dioxolan-2-yl)hexyl]phthalimide, 23 ml of 85% hydrazine hydrate, and 370 ml of 95% ethanol was refluxed for four hours, cooled, filtered and stripped. The residue was mixed with 500 ml of water, basified with 2 N NaOH solution and extracted with methylene chloride. The organic layer was separated, dried over anhydrous potassium carbonate, filtered, and stripped to an orange oil. This material was distilled to give 35.70 g (64%) of clear oil bp 80°-83° (0.100 mm).
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][C:19]([F:22])([F:21])[F:20])=[C:6]2[C:10]=1[N:9]([CH2:11][CH2:12][O:13][CH3:14])[CH:8]=[C:7]2[C:15](O)=[O:16].CCN(CC)CC.Cl.[F:31][C:32]([F:51])([F:50])[C:33]([NH:35][CH2:36][C:37]1[CH:42]=[CH:41][C:40]([F:43])=[C:39]([CH:44]2[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]2)[CH:38]=1)=[O:34].CCN=C=NCCCN(C)C>C(Cl)Cl>[F:51][C:32]([F:50])([F:31])[C:33]([NH:35][CH2:36][C:37]1[CH:42]=[CH:41][C:40]([F:43])=[C:39]([CH:44]2[CH2:49][CH2:48][N:47]([C:15]([C:7]3[C:6]4[C:10](=[C:2]([F:1])[CH:3]=[CH:4][C:5]=4[O:18][C:19]([F:22])([F:20])[F:21])[N:9]([CH2:11][CH2:12][O:13][CH3:14])[CH:8]=3)=[O:16])[CH2:46][CH2:45]2)[CH:38]=1)=[O:34]
Reactant: COCCn1cc(C(=O)O)c2c(OC(F)(F)F)ccc(F)c21
Reactant: O=C(NCc1ccc(F)c(C2CCNCC2)c1)C(F)(F)F
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COCCn1cc(C(=O)N2CCC(c3cc(CNC(=O)C(F)(F)F)ccc3F)CC2)c2c(OC(F)(F)F)ccc(F)c21
Temperature: 25 °C
Reaction time: 8 h
Yield: 99.4 %

Procedure:
A mixture of 8 (19.1 g, 59.6 mmol), Et3N (24.8 mL, 177.9 mmol), 2,2,2-trifluoro-N-(4-fluoro-3-piperidin-4-yl-benzyl)-acetamide hydrochloride (11, 26.4 g, 77.5 mmol) (14), and EDCI (17.1 g, 89.3 mmol) in CH2Cl2 is stirred at rt overnight. Both TLC and LC/MS indicate that the reaction is completed. The mixture is partitioned between H2O and CH2Cl2. The two layers are separated, and the organic layer is washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude material is purified on silica gel with heptane/EtOAc (40/60 to 0/100) as eluant to give 9 (36 g, 99%) as a white foam. 1H NMR (CDCl3) δ 7.37 (s, 1H), 7.20-7.10 (m, 2H), 7.10-6.85 (m, 4H), 4.95 (br s, 1H), 4.60-4.35 (m, 4H), 3.90 (br s, 1 H), 3.73 (t, J=5.0 Hz, 2H), 3.32 (s, 3H), 3.25-2.70 (m, 3H), 2.05-1.50(m, 4H); 19F NMR (CDCl3) δ −57.54 (s, 3F), −75.39 (s, 3F), −119.31 (s, 1F), −134.96 (d, J=11.3 Hz, 1F); MS 608 (M+1, 100%).
Reaction SMILES: Cl[C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C@@H:11]3[O:31][C@H:30]([CH2:32][O:33][CH2:34][C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[C@@H:21]([O:22][CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[C@@H:12]3[O:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:4]=2[N:5]=[CH:6][N:7]=1.[NH2:41][NH2:42]>>[NH:41]([C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C@@H:11]3[O:31][C@H:30]([CH2:32][O:33][CH2:34][C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[C@@H:21]([O:22][CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[C@@H:12]3[O:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:4]=2[N:5]=[CH:6][N:7]=1)[NH2:42]
Reactant: NN
Reactant: Clc1ncnc2c1ccn2[C@@H]1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Product: NNc1ncnc2c1ccn2[C@@H]1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Reaction time: 1 h

Procedure:
A mixture of 10 g of 4-chloro-7-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine and 100 ml of anhydrous hydrazine is heated under reflux and a nitrogen atmosphere for one hour, evaporated in vacuo, and coevaporated with xylenes. The residue is distributed between a mixture of ethyl acetate and water. The aqueous layer is reextracted with ethyl acetate and the dried ethyl acetate solution is evaporated in vacuo to provide 9.0 of crude product. Purification of this material by silica gel chromatography (ethyl acetate) provides pure 4-hydrazino-7-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine as a yellow syrup.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:23])[CH:4]([NH:8][S:9]([C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]#[C:21][CH3:22])=[CH:14][CH:13]=1)(=[O:11])=[O:10])[CH:5]([CH3:7])[CH3:6].[CH2:24](Br)[C:25]#[CH:26]>>[CH2:19]([O:18][C:15]1[CH:14]=[CH:13][C:12]([S:9]([N:8]([CH2:26][C:25]#[CH:24])[CH:4]([CH:5]([CH3:7])[CH3:6])[C:3]([O:2][CH3:1])=[O:23])(=[O:11])=[O:10])=[CH:17][CH:16]=1)[C:20]#[C:21][CH3:22]
Reactant: C#CCBr
Reactant: CC#CCOc1ccc(S(=O)(=O)NC(C(=O)OC)C(C)C)cc1
Product: C#CCN(C(C(=O)OC)C(C)C)S(=O)(=O)c1ccc(OCC#CC)cc1
Yield: 99.9 %

Procedure:
According to the procedure of Example 5, 0.800 g (2.36 mmol) of 2-(4-but-2-ynyloxy-benzenesulfonylamino)-3-methyl-butyric acid methyl ester and 0.53 g (4.72 mmol) of 80% propargyl bromide gave 0.89 g of methyl 2-[{[4-(2-butynyloxy)phenyl]sulfonyl}(2-propynyl)amino]-3-methylbutanoate as a colorless oil. Electrospray Mass Spec 378.2 (M+H)+
Reaction SMILES: Cl.[CH3:2][CH:3]1[C:8]2([CH3:12])[C:9]([CH3:11])=[CH:10][CH:5]([CH:6]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:7]2)[N:4]1[CH2:18]C1C=CC=CC=1.C(N(CC)CC)C.C=O>[Pd].C(O)C>[CH3:18][N:4]1[CH:3]([CH3:2])[C:8]2([CH3:12])[CH:9]([CH3:11])[CH2:10][CH:5]1[CH:6]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:7]2
Reactant: CCOC(=O)C1CC2(C)C(C)=CC1N(Cc1ccccc1)C2C
Agent: [Pd]
Agent: C=O
Agent: Cl
Solvent: CCO
Solvent: CCN(CC)CC
Product: CCOC(=O)C1CC2(C)C(C)CC1N(C)C2C
Temperature: 0 °C
Reaction time: 6 h
Yield: 0.1 %

Procedure:
A mixture of ethyl 3,4,8-trimethyl-2-(phenylmethyl)-2-azabicyclo[2.2.2]-oct-7-ene-6-carboxylate hydrochloride (17.4 g, 49.7 mol), 10% palladium on carbon (1.7 g) and ethanol (200 mL) was hydrogenated on a Parr hydrogenator at 50 psi for 6 hours. The mixture was removed from the Parr hydrogenator, cooled to 0° C. and triethylamine (7.0 mL, 50 mmol), followed by 37% formaldehyde (4.1 mL, 55 mmol) were added. The mixture was then placed back on the Parr hydrogenator at 50 psi for 1 hour. The reaction mixture was removed from the Parr hydrogenator, the catalyst was removed by filtration and the solvent was removed in vacuo. The residue was dissolved in water, basified with concentrated ammonium hydroxide (20 mL) and extracted with ether (3×300 mL). The combined organic layers were washed with brine (50 mL), dried over potassium carbonate and concentrated in vacuo to afford 11.5 g (96%) of ethyl 2,3,4,8-tetramethyl-2-azabicyclo[2.2.2]octane-6-carboxylate as a pale yellow oil.
Reaction SMILES: O=P(Cl)(Cl)Cl.CN([CH:9]=[O:10])C.[CH2:11]1[CH2:19][O:18][C:17]2[C:13](=[CH:14][NH:15][CH:16]=2)[O:12]1.[OH-].[Na+]>C(Cl)Cl>[CH:9]([C:14]1[NH:15][CH:16]=[C:17]2[O:18][CH2:19][CH2:11][O:12][C:13]=12)=[O:10]
Reactant: c1[nH]cc2c1OCCO2
Reactant: CN(C)C=O
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O=P(Cl)(Cl)Cl
Product: O=Cc1[nH]cc2c1OCCO2
Reaction time: 12 h
Yield: 94.2 %

Procedure:
POCl3 (1.67 g, 10.92 mmol) was added to a solution of DMF (0.84 g, 11.44 mmol) in methylene chloride (5.0 mL) at 0° C. and the reaction mixture allowed to come to room temperature. The reaction mixture was then slowly added to a solution of 3,4-ethylenedioxypyrrole (1.3 g, 10.40 mmol) in methylene chloride (5.0 mL) at 0° C. and allowed to come to room temperature. After stirring for 12 h, an excess of 3.0 M NaOH solution was added and stirred for 2 h in a hot water bath. The reaction mixture was extracted with methylene chloride (40 mL×3) and the combined organic layers were dried over MgSO4. Purification of the residue was accomplished by chromatography on silica gel using hexane/ethyl acetate (2:1) as eluent to afford the product as a white solid (1.5 g, 65%): mp 147° C.; 1H NMR (300 MHz, CDCl3) δ9.43 (s, 1H), 9.02 (br, 1H), 6.62 (d, J=3.8 Hz, 1H), 4.24 (m, 4H); Anal. Calcd for C7H7NO3: C, 54.90; H, 4.61; N, 9.15. Found: C, 55.03; H, 4.48; N, 9.14.
Reaction SMILES: [NH2:1][C:2]1[C:7]([CH:8]=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:10][C:11]1[C:12](O)=[C:13]([CH:18]=[CH:19][CH:20]=1)[C:14]([O:16][CH3:17])=[O:15]>CO.ClCCl>[NH2:1][C:2]1[C:7]([CH:8]2[NH:10][C:11]3[CH:20]=[CH:19][CH:18]=[C:13]([C:14]([O:16][CH3:17])=[O:15])[C:12]=3[O:9]2)=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: Nc1ncccc1C=O
Reactant: COC(=O)c1cccc(N)c1O
Solvent: ClCCl
Solvent: CO
Product: COC(=O)c1cccc2c1OC(c1cccnc1N)N2
Temperature: 50 °C
Reaction time: 10 h
Yield: 27.7 %

Procedure:
A 2-aminopyridine-3-carbaldehyde (650 mg) was added to a stirred solution of methyl 3-amino-2-hydroxy-benzoate (890 mg) in methanol (10 ml) and dichloromethane (5 ml). The resulting solution was stirred at 50° C. for 10 hours. The crude product was purified by flash chromatography on silica gel eluting with 1 to 2% methanol in dichloromethane. The solvent was evaporated to dryness to afford methyl 2-(2-amino-3-pyridyl)-2,3-dihydro-1,3-benzoxazole-7-carboxylate (400 mg) as a pale yellow solid. Manganese(IV) oxide (4629 mg) was added to a solution of this yellow solid (400 mg) in dichloromethane (5 ml) and tetrahydrofuran (10 ml), the mixture was stirred at 25° C. for 15 hours. The mixture was filtered and the filtrate was adsorbed on silica gel and purified by flash chromatography on silica gel eluting with 30 to 50% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford methyl 2-(2-amino-3-pyridyl)-1,3-benzoxazole-7-carboxylate (345 mg) as a pale yellow solid. NMR Spectrum: (CDCl3) 4.06 (s, 3H), 6.79 (dd, 1H), 6.89 (bs, 2H), 7.43 (dd, 1H), 7.92 (dd, 1H), 8.00 (dd, 1H), 8.26 (dd, 1H), 8.44 (dd, 1H); Mass spectrum: M+H+ 270;
Reaction SMILES: [F:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][O:7][C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][C:9]=2[CH2:17][CH:18]([CH3:20])[CH3:19])=[CH:4][CH:3]=1.[C:23]([N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)(=[O:27])[CH:24]([CH3:26])[CH3:25]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][O:7][C:8]2[CH:16]=[CH:15][C:11]([C:12]([N:31]3[CH2:32][CH2:33][N:28]([C:23](=[O:27])[CH:24]([CH3:25])[CH3:26])[CH2:29][CH2:30]3)=[O:14])=[CH:10][C:9]=2[CH2:17][CH:18]([CH3:20])[CH3:19])=[CH:21][CH:22]=1
Reactant: CC(C)C(=O)N1CCNCC1
Reactant: CC(C)Cc1cc(C(=O)O)ccc1OCc1ccc(F)cc1
Product: CC(C)Cc1cc(C(=O)N2CCN(C(=O)C(C)C)CC2)ccc1OCc1ccc(F)cc1
Yield: 90 %

Procedure:
As in the case of Example 16, 4-(4-fluorobenzyloxy)-3-isobutylbenzoic acid (1.51 g) was subjected to a condensation reaction with 1-isobutyrylpiperazine (0.78 g). Thus obtained solid was recrystallized (from ether) to yield 1.98 g of the aimed compound.
Reaction SMILES: [CH2:1]([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](Cl)=[N:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N+:19]([C:22]1[CH:27]=[CH:26][C:25]([CH:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[CH:24][CH:23]=1)([O-:21])=[O:20].O>CN1C(=O)CCC1>[CH2:1]([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([N:31]2[CH2:30][CH2:29][CH:28]([C:25]3[CH:26]=[CH:27][C:22]([N+:19]([O-:21])=[O:20])=[CH:23][CH:24]=3)[CH2:33][CH2:32]2)=[N:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Clc1nnc(Cc2ccccc2)c2ccccc12
Reactant: O=[N+]([O-])c1ccc(C2CCNCC2)cc1
Solvent: O
Solvent: CN1CCCC1=O
Product: O=[N+]([O-])c1ccc(C2CCN(c3nnc(Cc4ccccc4)c4ccccc34)CC2)cc1
Temperature: 150 °C
Yield: 81.6 %

Procedure:
To a solution of 1-benzyl-4-chloro-phthalazine (1.08 g, 4.04 mmol) in 8 mL NMP is added 4-(4-nitro-phenyl)piperidine (1 g, 4.85 mmol), TEA (1.68 mL, 12.12 mmol). The reaction mixture was heated to 150° C. for 45 min in a microwave reactor. Water was added to the reaction mixture to form a precipitate and the solid is collected by filtration and dried under vacuum. The resulting solid is purified by HPLC with acetonitril in water (from 20% to 100% with 3% 1-propanol) at 220 nm wavelength detection to provide the title compound (1.4 g, 78%).