Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][CH2:15][O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([Cl:30])=[C:24]([N:27]=[C:28]=S)[CH:25]=2)[NH:20][C:19](=[O:31])[C:18]=1[C:32]1[CH:37]=[C:36]([CH3:38])[CH:35]=[C:34]([CH3:39])[CH:33]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:40][C:41]1[C:46]([NH2:47])=[CH:45][N:44]=[CH:43][N:42]=1>[Hg]=O>[NH3:8].[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][CH2:15][O:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([Cl:30])=[C:24]([NH:27][C:28]3[NH:40][C:41]4[C:46]([N:47]=3)=[CH:45][N:44]=[CH:43][N:42]=4)[CH:25]=2)[NH:20][C:19](=[O:31])[C:18]=1[C:32]1[CH:37]=[C:36]([CH3:38])[CH:35]=[C:34]([CH3:39])[CH:33]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: Nc1cncnc1N
Reactant: Cc1cc(C)cc(-c2c(OCCC3CCCCN3C(=O)OC(C)(C)C)c3cc(N=C=S)c(Cl)cc3[nH]c2=O)c1
Agent: O=[Hg]
Product: Cc1cc(C)cc(-c2c(OCCC3CCCCN3C(=O)OC(C)(C)C)c3cc(Nc4nc5cncnc5[nH]4)c(Cl)cc3[nH]c2=O)c1
Product: N
Temperature: 25 °C
Reaction time: 48 h
Yield: 8.4 %

Procedure:
To a solution of 2-{2-[7-chloro-3-(3,5-dimethylphenyl)-6-isothiocyanato-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester (210 mg in 5 mL toluene) was added 250 mg mercury(II) oxide followed by 130 mg 4,5-diaminopyrimidine and the mixture heated to reflux on an oil bath. After 48 hours, the mixture was cooled to room temperature and the reaction quenched by the addition of 2N hydrochloric acid (4 mL). The solvents were removed in vacuo and the residue treated with 2N ammonia in methanol (10 mL) then concentrated once again. The residue was washed with chloroform and the solids removed by filtration. Concentration of the organics and purification by flash chromatography on silica gel (ethyl acetate:hexane, 1:1; then chloroform:2N ammonia in methanol, 9:1) gave the title compound (10 mg).
Reaction SMILES: [CH3:1][N:2]([CH2:4][CH2:5][O:6][C:7]1[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=1[C:9]([OH:11])=O)[CH3:3].Cl.[NH:17]=[C:18]=[NH:19].[OH:20][C:21]1[C:29]2N=NN[C:25]=2[CH:24]=[CH:23][CH:22]=1>CN(C=O)C>[CH3:3][N:2]([CH2:4][CH2:5][O:6][C:7]1[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=1[C:9]1[O:11][N:19]=[C:18]([C:24]2[CH:25]=[CH:29][C:21]([OH:20])=[CH:22][CH:23]=2)[N:17]=1)[CH3:1]
Reactant: Oc1cccc2[nH]nnc12
Reactant: N=C=N
Reactant: CN(C)CCOc1ccccc1C(=O)O
Agent: Cl
Solvent: CN(C)C=O
Product: CN(C)CCOc1ccccc1-c1nc(-c2ccc(O)cc2)no1

Procedure:
2,45 g of 2-[2-(N,N-dimethylamino)ethyl]oxy-benzoic acid are dissolved with 1.91 g of N-ethyl-N-dimethylaminopropyl)carbodiimide hydrochloride and catalytic amounts of hydroxybenzotriazole in 50 ml of DMF. After 15 minutes 1.52 g of 4-hydroxybenzoic acid amidoxime are added and the mixture is heated for 15 minutes at 700 W in the microwave. It is concentrated by evaporation, the residue is taken up in ethyl acetate, washed with water, dried over sodium sulphate and concentrated by evaporation in vacuo. The residue is filtered over silica gel with ethanol and converted into the salt as described above. Yield: 1.1 g (29% of theory). m.p.: 170° C. (decomposition).
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[N:8]=[CH:7][C:6]([CH2:9][NH2:10])=[CH:5][CH:4]=1.[N+:13]([C:16]1[CH:25]=[CH:24][CH:23]=[C:22]2[C:17]=1[CH:18]=[CH:19][O:20][C:21]2=O)([O-:15])=[O:14]>CO>[F:12][C:2]([F:11])([F:1])[C:3]1[N:8]=[CH:7][C:6]([CH2:9][N:10]2[CH:19]=[CH:18][C:17]3[C:22](=[CH:23][CH:24]=[CH:25][C:16]=3[N+:13]([O-:15])=[O:14])[C:21]2=[O:20])=[CH:5][CH:4]=1
Reactant: O=c1occc2c([N+](=O)[O-])cccc12
Reactant: NCc1ccc(C(F)(F)F)nc1
Solvent: CO
Product: O=c1c2cccc([N+](=O)[O-])c2ccn1Cc1ccc(C(F)(F)F)nc1
Temperature: 60 °C
Reaction time: 3 h
Yield: 60.5 %

Procedure:
C-(6-Trifluoromethyl-pyridin-3-yl)-methylamine (1.00 g, 0.00568 mol) and 5-nitro-isochromen-1-one (1.14 g, 0.00568 mol) were suspended in methanol (10 mL) and the suspension was stirred at 60° C. for 3 hours, then the reaction was microwaved at 100 watts at 100° C. for 60 minutes, and then at 120° C. for 30 min. Solid thus formed was filtered out to yield the product as a yellow solid (1.2 g). MS m/z=350.4 (M+H).
Reaction SMILES: [NH2:1][CH2:2][C@H:3]1[C@H:9]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([F:17])[CH:11]=2)[O:8][CH2:7][CH2:6][N:5](C(OC(C)(C)C)=O)[CH2:4]1.[N:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:31](O)=[O:32]>>[ClH:16].[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([C@@H:9]2[O:8][CH2:7][CH2:6][NH:5][CH2:4][C@H:3]2[CH2:2][NH:1][C:31]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][N:25]=2)=[O:32])=[CH:11][C:12]=1[F:17]
Reactant: O=C(O)c1ccccn1
Reactant: CC(C)(C)OC(=O)N1CCO[C@@H](c2ccc(Cl)c(F)c2)[C@H](CN)C1
Product: Cl
Product: O=C(NC[C@@H]1CNCCO[C@H]1c1ccc(Cl)c(F)c1)c1ccccn1

Procedure:
Using tert-butyl (6R,7R)-6-(aminomethyl)-7-(4-chloro-3-fluorophenyl)-1,4-oxazepane-4-carboxylate and pyridine-2-carboxylic acid, and by a method similar to that of Example 39, the title compound was obtained.
Reaction SMILES: [O:1]=[C:2]1[N:8]([CH2:9][C:10]([N:12]([CH:21]([CH3:23])[CH3:22])[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[O:11])[C:7]2[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=2[N:5]([C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)[C:4](=[O:34])[CH:3]1[CH2:35][C:36]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[N:38](C(C2CSC(=O)N2)=O)[N:37]=1.C(=O)([O-])[O-].[K+].[K+]>CO.CCOC(C)=O.O>[NH:38]1[C:39]2[C:44](=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:36]([CH2:35][CH:3]2[C:2](=[O:1])[N:8]([CH2:9][C:10]([N:12]([CH:21]([CH3:23])[CH3:22])[C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)=[O:11])[C:7]3[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=3[N:5]([C:28]3[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=3)[C:4]2=[O:34])=[N:37]1
Reactant: COc1ccc(N(C(=O)CN2C(=O)C(Cc3nn(C(=O)C4CSC(=O)N4)c4ccccc34)C(=O)N(c3cccnc3)c3ccccc32)C(C)C)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CO
Solvent: CCOC(C)=O
Product: COc1ccc(N(C(=O)CN2C(=O)C(Cc3n[nH]c4ccccc34)C(=O)N(c3cccnc3)c3ccccc32)C(C)C)cc1
Reaction time: 0.33 h
Yield: 78.8 %

Procedure:
To a stirred solution of 400 mg (0.556 mmol) of 2-{2,4-Dioxo-3-[1-(2-oxo-thiazolidine-4-carbonyl)-1H-indazol-3-yl methyl]-5-pyridin-3-yl-2,3,4,5-tetrahydro benzo[b][1,4]diazepin-1-yl}-N-isopropyl-N-(4-methoxyphenyl) acetamide, prepared as in Example 71 in 10 mL methanol is added 154 mg (1.11 mmol, 2 equiv.) of potassium carbonate. The suspension is stirred for 20 min and diluted with 25 mL EtOAc and 25 mL H2O. The organic phase is washed with H2O (2×25 mL) and then dried (MgSO4), and the solvents removed in vacuo. The resulting amorphous solid is swirled in 10 mL ether until a free flowing white solid is produced. The solid is filtered to give 258 mg of the title compound: mp. 214°-215° C.; [a]25 =+47.2; 1H NMR (CDCl3, 400 MHz) δ8.49 (d, br, 2H), 7.79 (d, 2H, J=8.0), 7.29-7.07 (m, 8H) 6.95-6.85 (m, 4H) 4.94 (m, 1H), 4.38 (d, br, 1H, J=15.6) 4.25-4.14 (m, 2H) 3.82 (s, 3H) 3.77 (m, 1H) 3.60 (dd, 1H, J=6.0, 16.1) 1.02 (t, 6H, J=7.7); low resolution MS (FAB)m/e 589 (MH+).
Reaction SMILES: C([O:5][C:6](=[C:9]1[C@:26]2([CH3:27])[C@H:12]([C@H:13]3[C:23](=[CH:24][CH2:25]2)[C@:21]2([CH3:22])[C:16](=[CH:17][C:18](=[O:28])[CH2:19][CH2:20]2)[CH2:15][CH2:14]3)[CH2:11][CH2:10]1)[CH:7]=[O:8])(=O)CC.[C:29]([O-:32])(=O)[CH3:30].[K+].[CH3:34]N(C)C=O>>[C:29]([O:8][CH2:7][C:6](=[O:5])[C:9]1[C@:26]2([CH3:27])[C@H:12]([C@H:13]3[C:23](=[CH:24][CH2:25]2)[C@:21]2([CH3:22])[C:16](=[CH:17][C:18](=[O:28])[CH2:19][CH2:20]2)[CH2:15][CH2:14]3)[CH2:11][CH:10]=1)(=[O:32])[CH2:30][CH3:34]
Reactant: CC(=O)[O-]
Reactant: CCC(=O)OC(C=O)=C1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)C3=CC[C@]12C
Reactant: CN(C)C=O
Agent: [K+]
Product: CCC(=O)OCC(=O)C1=CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)C3=CC[C@]12C
Temperature: 25 °C
Reaction time: 48 h
Yield: 78.2 %

Procedure:
Into a reactor were charged 0.2 m mole of the 20-propionyloxy-3-oxo-pregna-4,9(11),17(20)-trien-21-al obtained in Example 10, 0.3 m mole of potassium acetate and 2 ml of dimethylformamide, and stirred under nitrogen at room temperature for 2 days. Then, the resulting mixture was heated to 50% and stirred for 10 hours. After completion of the reaction, the reaction mixture was treated in the same manner as in Referential Example 1 to obtain 21-propionyloxy-pregna-4,9(11),16-triene-3,20-dione of the following structural formula in 78.2% yield: ##STR42##
Reaction SMILES: Cl[Ce](Cl)Cl.[CH2:5]([Mg]Br)[CH3:6].[Si:9]([O:16][C@@H:17]1[C@@:34]2([CH3:35])[C:21](=[CH:22][CH:23]=[C:24]3[C@@H:33]2[CH2:32][CH2:31][C@@:29]2([CH3:30])[C@H:25]3[CH2:26][CH:27]=[C:28]2[CH2:36][O:37][CH2:38][CH2:39][C:40](N(C)C)=[O:41])[CH2:20][C@@H:19]([O:45][Si:46]([C:49]([CH3:52])([CH3:51])[CH3:50])([CH3:48])[CH3:47])[CH2:18]1)([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10].[Cl-].[NH4+].O1CC[CH2:57][CH2:56]1>>[Si:9]([O:16][C@@H:17]1[C@@:34]2([CH3:35])[C:21](=[CH:22][CH:23]=[C:24]3[C@@H:33]2[CH2:32][CH2:31][C@@:29]2([CH3:30])[C@H:25]3[CH2:26][CH:27]=[C:28]2[CH2:36][O:37][CH2:38][CH2:39][C:40]([CH2:5][CH3:6])([OH:41])[CH2:56][CH3:57])[CH2:20][C@@H:19]([O:45][Si:46]([C:49]([CH3:52])([CH3:51])[CH3:50])([CH3:48])[CH3:47])[CH2:18]1)([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10]
Reactant: CC[Mg]Br
Reactant: C1CCOC1
Reactant: CN(C)C(=O)CCOCC1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Agent: Cl[Ce](Cl)Cl
Agent: [Cl-]
Agent: [NH4+]
Product: CCC(O)(CC)CCOCC1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 56 %

Procedure:
Tetrahydrofuran (11 ml) was mixed with anhydrous cerous (III) chloride (2.33 g, 9.46 mmol), stirred under nitrogen stream at room temperature for 30 min., cooled with ice, mixed with ethylmagnesium bromide (0.96 mol/l, 9.0 ml, 8.6 mmol) and stirred for 30 min. The reaction solution was mixed with a solution of 1α,3β-bis(tert-butyldimethylsilyloxy)-17-(N,N-dimethylaminocarbonylethoxymethyl)androsta-5,7,16-triene (553 mg, 0.86 mmol) in tetrahydrofuran (11 ml) at 0° C., followed by stirring for 1 hour at the same temperature. The reaction solution was poured into a saturated aqueous ammonium chloride solution, extracted with ethyl acetate (3 times), washed with saturated brine and water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure to remove solvent, giving a reaction mixture containing a ketone body. The thus obtained mixture was again subjected to the same reaction and worked up; the thus obtained residue was purified by column chromatography (hexane:ethyl acetate=5:1) to give the titled compound (317 mg, 56.0%) as a yellow oil.
Reaction SMILES: [CH:1]1[N:6]=[C:5](Cl)[C:4]2[N:8]=[CH:9][N:10]([C@@H:11]3[O:15][C@H:14]([CH2:16][OH:17])[C@@H:13]([OH:18])[C@H:12]3[OH:19])[C:3]=2[N:2]=1.C(N(CC)CC)C.[CH2:27]([O:34][C@@H:35]1[CH2:39][CH2:38][CH2:37][C@H:36]1[NH2:40])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C(O)C>[C:28]1([CH2:27][O:34][C@@H:35]2[CH2:39][CH2:38][CH2:37][C@H:36]2[NH:40][C:5]2[N:6]=[CH:1][N:2]=[C:3]3[C:4]=2[N:8]=[CH:9][N:10]3[CH:11]2[C@H:12]([OH:19])[C@H:13]([OH:18])[C@@H:14]([CH2:16][OH:17])[O:15]2)[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1
Reactant: N[C@@H]1CCC[C@H]1OCc1ccccc1
Reactant: OC[C@H]1O[C@@H](n2cnc3c(Cl)ncnc32)[C@H](O)[C@@H]1O
Solvent: CCO
Solvent: CCN(CC)CC
Product: OC[C@H]1OC(n2cnc3c(N[C@@H]4CCC[C@H]4OCc4ccccc4)ncnc32)[C@H](O)[C@@H]1O

Procedure:
To a solution of 6-chloropurine riboside (10.0 g, 35 mmol) in ethanol (350 mL) was added triethylamine (10.0 mL, 100 mmol) and (1R,2R)-2-(benzyloxy)-cyclopentylamine (5.2 g, 52 mmol). The mixture was refluxed for 24 hours, during which the reaction went from a suspension to a clear solution. The ethanol was removed under reduced pressure, and the residue was partitioned between ethyl acetate and water (100 mL:200 mL). The organic layer was separated and the aqueous layer washed with ethyl acetate (2×75 mL). The combined organic layers were dried (sodium sulfate), and the solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate (150 mL), and product precipitated by addition of hexane, to afford 2-(6-{[(1R,2R)-2-(phenylmethoxy)cyclopentyl]amino}purin-9-yl)(4S,3R,5R)-5-(hydroxymethyl)oxolane-3,4-diol as a white solid.
Reaction SMILES: [NH2:1][C:2]1[CH:25]=[CH:24][C:5]([C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:12][CH:11]=2)=[O:7])=[CH:4][N:3]=1.C=O.O.[C:29]([O:32][CH2:33]C)(=O)[CH3:30]>C(O)C>[CH2:17]([O:16][C:13]1[CH:14]=[CH:15][C:10]([CH2:9][NH:8][C:6](=[O:7])[C:5]2[CH:24]=[CH:25][C:2]([NH:1][CH2:33][O:32][CH2:29][CH3:30])=[N:3][CH:4]=2)=[CH:11][CH:12]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: CCOC(C)=O
Reactant: Nc1ccc(C(=O)NCc2ccc(OCc3ccccc3)cc2)cn1
Agent: C=O
Solvent: CCO
Solvent: O
Product: CCOCNc1ccc(C(=O)NCc2ccc(OCc3ccccc3)cc2)cn1
Reaction time: 1 h
Yield: 40 %

Procedure:
To a solution of the resulting 6-amino-N-(4-benzyloxy-benzyl)-nicotinamide (200 mg, 0.556 mmol) in ethanol (10 mL) were added 5,5-dimethylimidazophospho-2,4-dione (85 mg, 0.66 mmol) and 37% formaldehyde aqueous solution (1 mL), and the solution was stirred for 1 hour under reflux. Water and ethyl acetate were added to the reaction solution, which was then partitioned, and the organic layer was washed twice. NH silica gel was added to the organic layer, the solvent was evaporated in vacuo for adsorption, purification was carried out by NH silica gel column chromatography (ethyl acetate), and the title compound (95 mg, 0.243 mmol, 40%) was obtained as a white solid.
Reaction SMILES: C(OC(=O)[N:7]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[C:19]([Cl:25])[CH:18]=2)=[CH:12][CH:11]=1)(C)(C)C.OO.C([O-])([O-])=[O:37].[K+].[K+].FC(F)(F)C(O)=O>CS(C)=O.C(Cl)Cl>[CH2:26]([NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]([NH2:24])=[O:37])=[C:19]([Cl:25])[CH:18]=2)=[CH:12][CH:11]=1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: CC(C)(C)OC(=O)N(CCc1ccc(Oc2ccc(C#N)c(Cl)c2)cc1)Cc1ccccc1
Reactant: O=C([O-])[O-]
Agent: OO
Agent: [K+]
Solvent: ClCCl
Solvent: CS(C)=O
Solvent: O=C(O)C(F)(F)F
Product: NC(=O)c1ccc(Oc2ccc(CCNCc3ccccc3)cc2)cc1Cl
Temperature: 25 °C
Reaction time: 4 h
Yield: 149.7 %

Procedure:
Combine the compound of step 1 (95 mg, 0.21 mmol), H2O2 (25 μl) and K2CO3 (15 mg, 0.10 mmol) in DMSO (0.8 mL), and stir the mixture at room temperature overnight. Add water and extract the aqueous layer with EtOAc. Dry the organic layer over Na2SO4 and eliminate the solvent. Purify by flash chromatography (EtOAc/hexane 50/50) to give a yellow oil. Dissolve the oil in CH2Cl2 (3 mL) and add trifluoroacetic acid (240 μL), and stir the mixture at room temperature for 4 hour. Eliminate the solvent. Purify by an SCX column to give the title compound (57 mg, 76%). Electrospray MS M+1 ion=381. 1H-NMR (CDCl3, 400 MHz): 7.82 (d, 1H, J=8.5 Hz), 7.35-7.20 (m, 7H), 6.99-6.95 (m, 3H), 6.90 (dd, 11, J=2.5 and 8.5 Hz), 6.53 (m, 2H), 3.83 (s, 2H), 2.95-2.89 (m, 2H), 2.86-2.81 (m, 2H).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:12]=[CH:11][NH:10][C:9](=[O:13])[N:8]=2)[CH:2]=1.[H-].[Na+].Br[CH2:17][CH2:18][CH2:19][CH2:20][Cl:21].O>CN(C=O)C>[Cl:21][CH2:20][CH2:19][CH2:18][CH2:17][N:10]1[CH:11]=[CH:12][C:7]([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)=[N:8][C:9]1=[O:13]
Reactant: ClCCCCBr
Reactant: O=c1nc(-c2cccnc2)cc[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: O=c1nc(-c2cccnc2)ccn1CCCCCl
Temperature: 100 °C
Reaction time: 8 h
Yield: 52.3 %

Procedure:
To a solution of 4-pyridin-3-yl-1H-pyrimidin-2-one (50 mg, 0.29 mmol) in dry DMF (11 ml), 60% NaH (15 mg, 0.37 mmol) was added portionwise under inert atmosphere. After heating the mixture at 100° C. for 1 hour, 1-bromo-4-chloro-butane (43 μl, 0.37 mmol) was added at room temperature and the mixture was stirred overnight. Water was added and the mixture extracted with diethyl ether to remove the dialkylated product and finally with ethyl acetate. Ethyl acetate was washed with brine, dried (Na2SO4) and evaporated to give 40 mg of the title compound as a solid (54% yield).
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6](Cl)=[N:7]2.[CH3:13][C:14]1[O:18][C:17]([CH2:19][NH2:20])=[CH:16][CH:15]=1.[CH3:21][O:22][CH2:23][CH2:24][O:25][CH2:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][CH:34]=1)[CH2:30][NH2:31]>>[CH3:21][O:22][CH2:23][CH2:24][O:25][CH2:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][CH:34]=1)[CH2:30][NH:31][C:2]1[C:3]2[CH:4]=[CH:5][C:6]([NH:20][CH2:19][C:17]3[O:18][C:14]([CH3:13])=[CH:15][CH:16]=3)=[N:7][C:8]=2[CH:9]=[CH:10][CH:11]=1
Reactant: Cc1ccc(CN)o1
Reactant: Clc1ccc2c(Br)cccc2n1
Reactant: COCCOCc1cccc(CN)c1
Product: COCCOCc1cccc(CNc2cccc3nc(NCc4ccc(C)o4)ccc23)c1

Procedure:
The title compound, MS: m/e=432.3 (M+H+), was prepared in accordance with the general method of example 1 from 5-bromo-2-chloroquinoline, 5-methyl-2-furanmethanamine and 3-(2-methoxy-ethoxymethyl)-benzylamine.
Reaction SMILES: [CH3:1][N:2]1[CH:6]([C:7]2[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]([NH2:15])[CH:8]=2)[CH2:5][NH:4][C:3]1=[O:16].[CH2:17]1[CH:21]2[CH2:22][C:23](=O)[CH:19]([CH2:20]2)[CH2:18]1.C([BH3-])#N.[Na+].[OH-].[Na+]>C(O)(=O)C.CCOCC.C(OCC)(=O)C>[CH3:1][N:2]1[CH:6]([C:7]2[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]([NH:15][CH:18]3[CH2:17][CH:21]4[CH2:20][CH:19]3[CH2:23][CH2:22]4)[CH:8]=2)[CH2:5][NH:4][C:3]1=[O:16]
Reactant: COc1ccc(C2CNC(=O)N2C)cc1N
Reactant: O=C1CC2CCC1C2
Agent: [BH3-]C#N
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CCOCC
Solvent: CC(=O)O
Product: COc1ccc(C2CNC(=O)N2C)cc1NC1CC2CCC1C2
Temperature: 5 °C
Yield: 10.1 %

Procedure:
The aniline of Example 51 (3.07 g, 17.95 mmol) is dissolved in 60 ml of glacial acetic acid and to this is added norcamphor (2.37 g, 21.54 mmol). The reaction is cooled to 5° C. and to it is added sodium cyanoborohydride (1.36 g, 21.54 mmol). The reaction is poured onto ice and is pH adjusted to 7 with 1 normal NaOH solution. The aqueous is extracted with methylene chloride dried over MgSO4, filtered and concentrated in vacuo to afford a brown oil which is flashed on SiO2 with ethyl acetate as the eluent. The appropriate fractions are combined and concentrated in vacuo to yield a white paste which is tritarted with ether to yield 0.57 g (10%) of the product as a white crystalline solid. MP=171°-174° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][NH:8][CH2:7][CH2:6]2.[C:13](Cl)(=[O:21])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].Cl.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl.O.C(N(CC)CC)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][N:8]([C:13](=[O:21])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[CH2:7][CH2:6]2
Reactant: CCCCCCCC(=O)Cl
Reactant: COc1ccc2c(c1)CCNC2
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: CCCCCCCC(=O)N1CCc2cc(OC)ccc2C1

Procedure:
4.0 g of 6-methoxy-1,2,3,4-tetrahydroisoquinoline and 3.5 ml of triethylamine in 50 ml of methylene chloride are initially introduced, and a solution of 4.0 g of octanoyl chloride in 10 ml of methylene chloride is added dropwise with stirring and cooling. The mixture is stirred at room temperature for 1 hour, then shaken with 1N hydrochloric acid, sodium carbonate solution and water, and the organic phase is dried over magnesium sulfate and evaporated in a rotary evaporator. The crude product (6.7 g of colorless oil) is reacted further without purification.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][NH:6]2.[O:11]=[CH:12][C@@H:13]([C@H:15]([C@@H:17]([C@@H:19]([CH2:21][OH:22])[OH:20])[OH:18])[OH:16])O.O>C(O)C>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][N:6]2[C@@H:21]1[O:22][C@H:13]([CH2:12][OH:11])[C@@H:15]([OH:16])[C@H:17]([OH:18])[C@H:19]1[OH:20]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Reactant: Clc1cccc2c1CCN2
Solvent: CCO
Solvent: O
Product: OC[C@H]1O[C@@H](N2CCc3c(Cl)cccc32)[C@H](O)[C@@H](O)[C@@H]1O
Yield: 56.6 %

Procedure:
A mixture of 4-chloroindoline (2.88 g) and D-glucose (3.38 g) in ethyl alcohol (150 ml)-H2O (10 ml) was refluxed under argon atmosphere overnight. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (chloroform:methanol=100:0-88:12) to give 4-chloro-1-(β-D-glucopyranosyl)indoline (3.35 g) as colorless foam. APCI-Mass m/Z 316/318 (M+H). 1H-NMR (DMSO-d6) δ 2.87-3.02 (m, 2H), 3.07-3.12 (m, 1H), 3.20-3.32 (m, 2H), 3.38-3.47 (m, 2H), 3.51-3.60 (m, 2H), 3.68-3.73 (m, 1H), 4.34-4.37 (m, 1H), 4.63 (d, J=8.3 Hz, 1H), 4.93 (d, J=5.1 Hz, 1H), 5.03 (d, J=4.0 Hz, 1H), 5.06 (d, J=4.5 Hz, 1H), 6.53 (d, J=8.0 Hz, 1H), 6.60 (d, J=8.0 Hz, 1H), 6.99 (t, J=7.9 Hz, 1H).
Reaction SMILES: [C:1]1([N:11]([S:18]([F:21])([F:20])[F:19])[C:12]2C=CC=C[CH:13]=2)C2C(=CC=CC=2)C=C[CH:2]=1.C(C1CC[C:29](=[O:32])CC1)(C)(C)C.C(C1CCC(F)(F)CC1)(C)(C)C.C(C1CCC(F)=CC1)(C)(C)C.[CH:56]1([OH:64])CCCCCCC1.COCCN(S(F)(F)F)C>C(Cl)Cl.CCO>[CH3:56][O:64][CH2:2][CH2:1][N:11]([S:18]([F:21])([F:20])[F:19])[CH2:12][CH2:13][O:32][CH3:29]
Reactant: OC1CCCCCCC1
Reactant: CC(C)(C)C1CCC(=O)CC1
Reactant: FS(F)(F)N(c1ccccc1)c1cccc2ccccc12
Agent: CC(C)(C)C1CC=C(F)CC1
Agent: CC(C)(C)C1CCC(F)(F)CC1
Agent: COCCN(C)S(F)(F)F
Solvent: CCO
Solvent: ClCCl
Product: COCCN(CCOC)S(F)(F)F

Procedure:
Table 6 summarizes the results obtained on fluorination of 4-t-butyl cyclohexanone with the aminosulfur trifluorides. All of the compositions examined except N-naphthyl-N-phenylaminosulfur trifluoride converted the ketone to a mixture of 4-t-butyl-difluorocyclohexane and 4-t-butyl-1-fluorocyclohexene, with the former predominating. The fluorination of this ketone was much slower than observed for the fluorination of cyclooctanol. A complete conversion to the fluorinated products required several days at room temperature in CH2Cl2. However, addition of a catalytic amount of HF (generated in-situ from EtOH) accelerated the rate of reaction considerably. The reaction time was reduced from several days to ˜16 h when the diaryl, arylalkyl, and N-methoxyethyl-N-phenylaminosulfur trifluorides were reacted with 4-t-butylcyclohexanone in the presence of HF. The effect of HF on reaction rate was, however, less pronounced with the alkoxyalkyl aminosulfur trifluorides 37 and 41. A reasonable reaction time (40 h) for complete fluorination of the ketone with bis(methoxyethyl-aminosulfur trifluoride (41) was obtained when the reaction was carried out at 40° C.
Reaction SMILES: [CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[NH:17][C:16]([C:21]([OH:23])=O)=[CH:15]3)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].Cl.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[CH3:47][NH:48][CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH2:49]([N:48]([CH3:47])[C:21]([C:16]1[NH:17][C:18]2[C:14]([CH:15]=1)=[CH:13][C:12]([C:10]([N:7]1[CH2:8][CH2:9][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:5][CH2:6]1)=[O:11])=[CH:20][CH:19]=2)=[O:23])[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1
Reactant: CC(C)N1CCN(C(=O)c2ccc3[nH]c(C(=O)O)cc3c2)CC1
Reactant: CNCc1ccccc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)N1CCN(C(=O)c2ccc3[nH]c(C(=O)N(C)Cc4ccccc4)cc3c2)CC1

Procedure:
The title compound was synthesized in analogy to example 1, from 5-(4-isopropyl-piperazine-1-carbonyl)-1H-indole-2-carboxylic acid 1:1 hydrochloride, O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (commercially available), methylbenzylamine (commercially available) and N,N-diisopropylethylamine in N,N-dimethylformamide to give the desired product after purification by preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile/water/formic acid.