Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][CH2:11][OH:12])=[CH:4][CH:3]=1.[CH3:13][S:14](Cl)(=[O:16])=[O:15]>N1C=CC=CC=1>[CH3:13][S:14]([O:12][CH2:11][CH2:10][CH2:9][CH2:8][C:5]1[CH:4]=[CH:3][C:2]([NH:1][S:14]([CH3:13])(=[O:16])=[O:15])=[CH:7][CH:6]=1)(=[O:16])=[O:15]
Reactant: Nc1ccc(CCCCO)cc1
Reactant: CS(=O)(=O)Cl
Solvent: c1ccncc1
Product: CS(=O)(=O)Nc1ccc(CCCCOS(C)(=O)=O)cc1
Temperature: -10 °C
Reaction time: 48 h

Procedure:
9.25 g (0.056 mole) 4-aminobenzenebutanol is dissolved in 100 ml pyridine and the solution is cooled to ca. -10° C. 17.33 ml (25.65 g) (0.244 mole) methanesulfonyl chloride is added dropwise with vigorous stirring at a rate such that the reaction temperature does not rise beyond -5° C. After all methanesulfonyl chloride is added, the reaction mixture is left in the freezer for two days. The reaction mixture is poured onto 300 ml ice water and extracted with 3×200 ml methylene chloride. The combined organic layers are washed with 1 liter cold 5% HCl in 3 portions. The organic layer is dried over sodium sulfate, filtered, and stripped. The residue is crystallized from ethyl acetate/ether to obtain the title compound.
Reaction SMILES: [CH3:1][C:2]1([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:11][CH2:10][C:5]2(OCC[O:6]2)[CH2:4][CH2:3]1.CCO.O.Cl>O1CCOCC1>[CH3:1][C:2]1([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:3][CH2:4][C:5](=[O:6])[CH2:10][CH2:11]1
Reactant: CCOC(=O)C1(C)CCC2(CC1)OCCO2
Agent: Cl
Solvent: C1COCCO1
Solvent: CCO
Solvent: O
Product: CCOC(=O)C1(C)CCC(=O)CC1
Temperature: 25 °C
Reaction time: 64 h

Procedure:
In a 50 mL round-bottom flask was mixed with ethyl 8-methyl-1,4-dioxaspiro[4.5]decane-8-carboxylate (Int-6a, 1.99 g, 8.72 mmol), EtOH (10 mL), H2O (5 mL), and 4N HCl in 1,4-dioxane (5 mL). The resulting solution was stirred at room temperature for 64 hours. At this time, the solvent was removed in vacuo and the residue was taken up in DCM. The suspension was washed with saturated NaHCO3(aq) and the organic layer was dried over Na2SO4. The resulting product was taken on without further purification. Yield=1.00 g.
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[C@H:3]1[CH2:8][CH2:7][C@H:6]([C:9]2[CH:14]=[CH:13][C:12]([CH2:15]O)=[CH:11][CH:10]=2)[CH2:5][CH2:4]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)[Br:39].O>C1COCC1.C(OCC)(=O)C>[Br:39][CH2:15][C:12]1[CH:13]=[CH:14][C:9]([C@H:6]2[CH2:7][CH2:8][C@H:3]([C:2]([F:18])([F:17])[F:1])[CH2:4][CH2:5]2)=[CH:10][CH:11]=1
Reactant: BrC(Br)(Br)Br
Reactant: OCc1ccc([C@H]2CC[C@H](C(F)(F)F)CC2)cc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: FC(F)(F)[C@H]1CC[C@H](c2ccc(CBr)cc2)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Under argon, 2 g (7.74 mmol) of {4-[trans-4-(trifluoromethyl)cyclohexyl]phenyl}methanol [for the preparation, see patent application WO 2009/032249-A1, Example 8/Steps C-E] were dissolved in 40 ml of THF, and 2.437 g (9.29 mmol) of triphenylphosphine and 3.081 g (9.29 mmol) of carbon tetrabromide were added in succession. The reaction mixture was stirred at room temperature overnight. Subsequently, first water and then ethyl acetate were added. The organic phase was separated off and then dried over magnesium sulphate, filtered and concentrated to dryness. The residue obtained was purified chromatographically on silica gel (mobile phase: cyclohexane/ethyl acetate 10:1). This gave 2.07 g (6.44 mmol, 83% of theory) of the target compound.
Reaction SMILES: FC(F)(F)C(O)=O.C([O:12][C:13]([C@@:15]12[CH2:22][C:21](=[CH2:23])[CH2:20][C@@H:19]1[C:18](=[O:24])[N:17]([C@@H:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH3:26])[CH2:16]2)=[O:14])(C)(C)C>ClCCl>[CH2:23]=[C:21]1[CH2:22][C@:15]2([C:13]([OH:14])=[O:12])[C@@H:19]([C:18](=[O:24])[N:17]([C@@H:25]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH3:26])[CH2:16]2)[CH2:20]1
Reactant: C=C1C[C@@H]2C(=O)N([C@H](C)c3ccccc3)C[C@]2(C(=O)OC(C)(C)C)C1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: C=C1C[C@@H]2C(=O)N([C@H](C)c3ccccc3)C[C@]2(C(=O)O)C1
Yield: 87 %

Procedure:
Trifluoroacetic acid (26.0 ml) was added to a solution of [(1S,5S)-7-methylene-4-oxo-3-[(1R)-1-phenylethyl]-3-aza-bicyclo[3.3.0]octan-1-yl]carboxylic acid tert-butyl ester (2.47 g, 8.66 mmol) in dichloromethane (26.0 ml) with stirring under ice-cooling, and the mixture was stirred at room temperature for one hour. The reaction solution was concentrated under reduced pressure, and trifluoroacetic acid was azeotropically distilled with toluene (×3). A 1 mol/l sodium hydroxide solution (15.0 ml) was added to the resulting residue under ice-cooling, and the mixture was washed with diethyl ether (60 ml×2). The aqueous layer was made acidic with 6 mol/l hydrochloric acid (4 ml) under ice-cooling, followed by extraction with ethyl acetate (100 ml×2). The organic layers were combined, washed with water (100 mL) and brine (100 ml), and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to give 2.15 g of the title compound as white crystals.
Reaction SMILES: [C:1]1([CH3:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].COP([CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])(OC)=O.O1CC[CH2:26][CH2:25]1>>[CH2:1]([C:6]1[CH2:5][CH:4]2[CH:3]([CH:2]=1)[C:26](=[CH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:25]2)[CH3:7]
Reactant: Cc1ccccc1
Reactant: COP(=O)(CC(=O)OC(C)(C)C)OC
Reactant: C1CCOC1
Agent: [H-]
Agent: [Na+]
Product: CCC1=CC2C(=CC(=O)OC(C)(C)C)CC2C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
4-Ethyl-3-hydroxyhept-6-enoic acid (3.13 g, 18.2 mmol) was dissolved in acetic anhydride (15 mL). To the solution, potassium acetate (4.27 g, 43.6 mmol) was added, and the mixture was stirred at room temperature for 100 minutes. The reaction solution was heated to reflux and stirred for 3.5 hours to form “3-ethylbicyclo[3.2.0]hept-6-en-6-one” in the reaction solution. To the reaction solution, ice water and toluene were then added, and this mixture was stirred overnight at room temperature. The mixture was separated into aqueous and organic layers by the addition of saturated saline (50 mL) and toluene (20 mL). Then, the organic layer was washed with a 1 N aqueous sodium hydroxide solution and saturated saline in this order, then dried over anhydrous magnesium sulfate, and filtered. The filtrate was added to a reaction solution prepared by adding sodium hydride (>65% oil, 761.9 mg, 20 mmol) to a solution of tert-butyl dimethoxyphosphorylacetate (4.48 g, 20 mmol) in tetrahydrofuran (50 mL) under ice cooling, and the mixture was further stirred for 1 hour. The reaction solution was separated into aqueous and organic layers by the addition of a saturated aqueous solution of ammonium chloride and saturated saline. The aqueous layer was subjected to extraction with ethyl acetate. The organic layers were combined, then washed with saturated saline, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the compound of interest as a pale yellow oil substance (1.32 g, 31%, E/Z mixture).
Reaction SMILES: CCCC[N+](CCCC)(CCCC)CCCC.[F-].C[Si]([C:23]#[C:24][C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[N:30]([CH2:34][CH2:35][OH:36])[CH:29]=[CH:28]2)(C)C>C1COCC1>[C:24]([C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[N:30]([CH2:34][CH2:35][OH:36])[CH:29]=[CH:28]2)#[CH:23]
Reactant: C[Si](C)(C)C#Cc1ccc2c(ccn2CCO)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: C#Cc1ccc2c(ccn2CCO)c1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
Under an N2 atmosphere 29 g (91.8 mmol) TBAF are added to a solution of 21.5 g (83.5 mmol) 2-(5-trimethylsilanylethynyl-indol-1-yl)-ethanol in 500 mL THF and the reaction mixture is stirred for 1.5 h at RT. The mixture is evaporated down i.vac., the residue is taken up in 300 mL EtOAc, the organic phase is washed twice with in each case 200 mL water and once with 200 mL saturated NaCl solution and dried over Na2SO4. After the desiccant and solvent have been eliminated the desired product is obtained in the form of a brown oil.
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([OH:14])=O)=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.C(C1NC=CN=1)(C1NC=CN=1)=O.O.[NH2:28][NH2:29]>C1COCC1>[OH:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([NH:28][NH2:29])=[O:14])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1
Reactant: NN
Reactant: O=C(O)c1ccc2c(O)ncnc2c1
Agent: O=C(c1ncc[nH]1)c1ncc[nH]1
Solvent: C1CCOC1
Solvent: O
Product: NNC(=O)c1ccc2c(O)ncnc2c1
Reaction time: 18 h

Procedure:
(4-Hydroxy-quinazolin-7-yl)-carboxylic acid (0.5 g) in dry THF (20 ml) was treated with carbonyl diimidazole (0.85 g) under nitrogen for 6 hours at room temperature. Hydrazine hydrate was added and stirring was continued for 18 hours. The mixture was filtered to give the title compound (0.41 g); m/z (M+1+) 205.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[CH:7][C:6]=1[O:14][C:15](=[O:17])[CH3:16])(=[O:3])[CH3:2].CC(OC(C)=O)=O.[N+:25]([O-])([OH:27])=[O:26]>O1CCOCC1>[C:15]([O:14][C:6]1[CH:7]=[C:8]([CH:12]=[C:13]([N+:25]([O-:27])=[O:26])[C:5]=1[NH:4][C:1](=[O:3])[CH3:2])[C:9]([OH:11])=[O:10])(=[O:17])[CH3:16]
Reactant: O=[N+]([O-])O
Reactant: CC(=O)Nc1ccc(C(=O)O)cc1OC(C)=O
Solvent: CC(=O)OC(C)=O
Solvent: C1COCCO1
Product: CC(=O)Nc1c(OC(C)=O)cc(C(=O)O)cc1[N+](=O)[O-]
Temperature: 0 °C
Yield: 89.9 %

Procedure:
Compound 102 (1.00 g, 4.21 mmol) was suspended with stirring in a mixture of Ac2O (8.33 mL, 8.99 g, 88.2 mmol) and dioxane (6.6 mL). This was cooled to 0° C., and a cold solution of the nitrating mixture made from Ac2O (3.33 mL, 3.59 g, 35.2 mmol) and concentrated HNO3 (3.33 mL) was slowly added to the mixture containing 102. The reaction mixture was then warmed to 30-35° C. until the reaction was complete as evidenced by TLC. The reaction mixture was poured onto ice/water (100 mL), extracted with EtOAc (4×50 mL), dried (NaSO4), and concentrated to dryness on a rotary evaporator to give crude 104 (1.05 g, 89.9%) as an oil. Trituration with CHCl3 gave a solid: mp 196-201° C. (dioxane/hexane).
Reaction SMILES: [OH:1][C:2]1[C:3]([S:8][CH2:9][C:10]([O:12][CH3:13])=[O:11])=[N:4][CH:5]=[CH:6][CH:7]=1.F[C:15]1[CH:20]=[C:19]([N:21]2[C:26](=[O:27])[CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[N:23]([CH3:32])[C:22]2=[O:33])[C:18]([F:34])=[CH:17][C:16]=1[N+:35]([O-:37])=[O:36].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[F:34][C:18]1[C:19]([N:21]2[C:26](=[O:27])[CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[N:23]([CH3:32])[C:22]2=[O:33])=[CH:20][C:15]([O:1][C:2]2[C:3]([S:8][CH2:9][C:10]([O:12][CH3:13])=[O:11])=[N:4][CH:5]=[CH:6][CH:7]=2)=[C:16]([N+:35]([O-:37])=[O:36])[CH:17]=1
Reactant: COC(=O)CSc1ncccc1O
Reactant: Cn1c(C(F)(F)F)cc(=O)n(-c2cc(F)c([N+](=O)[O-])cc2F)c1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)CSc1ncccc1Oc1cc(-n2c(=O)cc(C(F)(F)F)n(C)c2=O)c(F)cc1[N+](=O)[O-]
Temperature: 70 °C
Reaction time: 2 h
Yield: 85.4 %

Procedure:
To a mixture of 0.26 g of 3-hydroxy-2-(methoxycarbonyl)methylthiopyridine, 0.38 g of 2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene, and 2 ml of N,N-dimethylformamide was added 0.17 g of potassium carbonate, and the mixture was stirred at 70° C. for 2 hours. The reaction mixture was cooled to room temperature and then poured into ice water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel column chromatography to give 0.49 g of 3-{4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-2-nitrophenoxy}-2-(methoxycarbonyl)methylthiopyridine.
Reaction SMILES: Br[C:2]1[C:18]([CH3:19])=[CH:17][C:5]([O:6][Si:7]([CH:14]([CH3:16])[CH3:15])([CH:11]([CH3:13])[CH3:12])[CH:8]([CH3:10])[CH3:9])=[CH:4][C:3]=1[CH3:20].C([Li])CCC.[CH3:26][O:27][CH2:28][O:29][C:30]1[CH:37]=[CH:36][C:33]([CH:34]=[O:35])=[CH:32][CH:31]=1>C1COCC1.C(OCC)(=O)C.O>[CH3:20][C:3]1[CH:4]=[C:5]([O:6][Si:7]([CH:14]([CH3:16])[CH3:15])([CH:11]([CH3:13])[CH3:12])[CH:8]([CH3:10])[CH3:9])[CH:17]=[C:18]([CH3:19])[C:2]=1[CH:34]([C:33]1[CH:32]=[CH:31][C:30]([O:29][CH2:28][O:27][CH3:26])=[CH:37][CH:36]=1)[OH:35]
Reactant: Cc1cc(O[Si](C(C)C)(C(C)C)C(C)C)cc(C)c1Br
Reactant: COCOc1ccc(C=O)cc1
Agent: [Li]CCCC
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COCOc1ccc(C(O)c2c(C)cc(O[Si](C(C)C)(C(C)C)C(C)C)cc2C)cc1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
To a solution of (4-bromo-3,5-dimethyl-phenoxy)triisopropylsilane (8.0 g, 23.30 mmol) in THF (50 mL) was added a solution of n-butyllithium (2.5 M in THF, 90 mL) at −78° C. The heterogeneous mixture was stirred at −78° C. for 1 h A solution of 4-methoxymethoxy-benzaldehyde (3.09 g, 18.58 mmol) in THF (5 mL) was added and the mixture was stirred at −78° C. for 1 h then warmed up to r.t. The reaction was then diluted with ethyl acetate and water, the layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried (MgSO4), filtered and concentrated to afford crude (2,6-dimethyl-4-triisopropylsilanyloxyphenyl)-(4-methoxymethoxyphenyl)methanol. Carried on to the next step without further purification.
Reaction SMILES: [CH2:1]([NH2:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[O:20]=[CH:21][C@@H:22]([C@H:24]([C@@H:26]([C@@H:28]([CH2:30][OH:31])[OH:29])[OH:27])[OH:25])O>C(O)C>[CH2:1]([NH:19][CH:30]1[O:31][C@H:22]([CH2:21][OH:20])[C@@H:24]([OH:25])[C@H:26]([OH:27])[C@H:28]1[OH:29])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Reactant: CCCCCCCCCCCCCCCCCCN
Solvent: CCO
Product: CCCCCCCCCCCCCCCCCCNC1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Temperature: 70 °C
Reaction time: 0.25 h

Procedure:
20 g of octadecylamine are dissolved in 120 ml of ethanol and the solution is warmed to 70° C. 11 g of anhydrous D-glucose are added. After a clear solution has formed, stirring is continued at 70° C. for a further 15 minutes. The solution is cooled to 10° C. and left to stand for 15 minutes. The crystal sludge formed is filtered off with suction, washed twice with ethanol and dried in vacuo.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[N:5]=1)#[C:2][CH3:3].[Li+].CC([N-]C(C)C)C.[B:19]([O:24]C)([O:22]C)[O:20]C>>[C:1]([C:4]1[CH:9]=[CH:8][C:7]([O:20][B:19]([OH:24])[OH:22])=[C:6]([F:10])[N:5]=1)#[C:2][CH3:3]
Reactant: CC#Cc1cccc(F)n1
Reactant: COB(OC)OC
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Product: CC#Cc1ccc(OB(O)O)c(F)n1

Procedure:
0.05 mol of 10A, 0.08 mol of LDA and 0.08 mol of trimethyl borate are reacted with one another analogously to Example 1B. Aqueous work-up gives the unpurified product, which is processed further as in 10C.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([N:8]2[C:12]3[CH:13]=[CH:14][C:15]([C:17]([NH:19][CH2:20][C:21]4[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=4)=[O:18])=[CH:16][C:11]=3[N:10]=[CH:9]2)[CH:5]=[CH:6][CH:7]=1.[Cl:27][C:28]1[CH:35]=[CH:34][C:31]([CH:32]=O)=[CH:30][CH:29]=1>CO.CC(O)=O>[Cl:27][C:28]1[CH:35]=[CH:34][C:31]([CH2:32][NH:1][C:2]2[CH:3]=[C:4]([N:8]3[C:12]4[CH:13]=[CH:14][C:15]([C:17]([NH:19][CH2:20][C:21]5[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=5)=[O:18])=[CH:16][C:11]=4[N:10]=[CH:9]3)[CH:5]=[CH:6][CH:7]=2)=[CH:30][CH:29]=1
Reactant: O=Cc1ccc(Cl)cc1
Reactant: Nc1cccc(-n2cnc3cc(C(=O)NCc4cccnc4)ccc32)c1
Solvent: CC(=O)O
Solvent: CO
Product: O=C(NCc1cccnc1)c1ccc2c(c1)ncn2-c1cccc(NCc2ccc(Cl)cc2)c1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A mixture of 1-(3-aminophenyl)-N-(pyridin-3-ylmethyl)-1H-benzimidazole-5-carboxamide (1.0 eq) and 4-chlorobenzaldehyde (1.0 eq) in MeOH:HOAc (10:1 v/v, 0.017M) was stirred for 15 min at rt prior to the addition of (polystyrylmethyl)trimethylammonium cyanoborohydride (3.5-5.0 mmol/g, 2.5 eq). The reaction mixture was shaken at rt overnight in a capped vial and then filtered through a plug of cotton wool. The resin was washed with MeOH and the combined filtrate and MeOH washings were concentrated under reduced pressure and purified by silica gel chromatography eluting with 5% MeOH in DCM to yield 1-{3-[(4-chlorobenzyl)amino]phenyl}-N-pyridin-3-ylmethyl-1H-benzimidazole-5-carboxamide. 1H-NMR (CD3OD, 400 MHz): δ 4.38 (s, 2H), 4.89 (s, 2H), 6.68 (s, 1H), 6.76 (dd, J=2.0 Hz, 7.0 Hz, 2H), 7.20-7.45 (m, 7H), 7.81 (dd, J=8.4 Hz, 1.6 Hz, 1H), 7.89 (d, J=6.0 Hz, 1H), 8.26 (d, J=1.2 Hz, 1H), 8.42 (s, 1H), 8.45 (d, J=4 Hz, 1H), 8.60 (s, 1H). MS (ES+): m/z 469 [MH+]
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([CH3:20])[C:17]([CH2:21][CH:22]([CH3:24])[CH3:23])=[CH:16][N:15]=3)[O:11][N:10]=2)[CH:6]=[C:5]([CH3:25])[C:4]=1[OH:26])[CH3:2].[CH2:27]([C@@H:29]1[O:31][CH2:30]1)Cl>C(O)(C)C.[OH-].[Na+].CC(=O)OCC>[CH2:1]([C:3]1[CH:8]=[C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([CH3:20])[C:17]([CH2:21][CH:22]([CH3:23])[CH3:24])=[CH:16][N:15]=3)[O:11][N:10]=2)[CH:6]=[C:5]([CH3:25])[C:4]=1[O:26][CH2:27][C@@H:29]1[CH2:30][O:31]1)[CH3:2]
Reactant: CCc1cc(-c2noc(-c3cc(C)c(CC(C)C)cn3)n2)cc(C)c1O
Reactant: ClC[C@H]1CO1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CC(C)O
Product: CCc1cc(-c2noc(-c3cc(C)c(CC(C)C)cn3)n2)cc(C)c1OC[C@@H]1CO1
Reaction time: 24 h
Yield: 63.8 %

Procedure:
To a solution of the compound of Example 32 (315 mg, 896 μmol) in isopropanol (10 mL) and 3 N aq. NaOH (2 mL), (R)-epichlorohydrine (249 mg, 2.69 mmol) is added. The mixture is stirred at rt for 18 h before another portion of (R)-epichlorohydrine (249 mg, 2.69 mmol) is added. Stirring is continued at rt for 24 h. The mixture is diluted with EA and washed with water. The org. extract is concentrated and the crude product is purified on prep. TLC plates using heptane:EA 7:3 to give 2-[3-((S)-3-ethyl-5-methyl-4-oxiranylmethoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-5-isobutyl-4-methyl-pyridine (233 mg) as a colourless oil; LC-MS: tR=1.18 min, [M+H]+=408.09.
Reaction SMILES: C([O:5][C:6](=[O:24])[CH2:7][CH2:8][C:9]1[CH:22]=[CH:21][C:20]2[C:11](=[C:12]([NH2:23])[C:13]3[C:18]([N:19]=2)=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH:10]=1)(C)(C)C.[F:25][C:26]([F:31])([F:30])[C:27]([OH:29])=[O:28]>ClCCl.C(OCC)C>[NH2:23][C:12]1[C:13]2[C:18]([N:19]=[C:20]3[C:11]=1[CH:10]=[C:9]([CH2:8][CH2:7][C:6]([OH:24])=[O:5])[CH:22]=[CH:21]3)=[CH:17][CH:16]=[CH:15][CH:14]=2.[C:27]([OH:29])([C:26]([F:31])([F:30])[F:25])=[O:28]
Reactant: CC(C)(C)OC(=O)CCc1ccc2nc3ccccc3c(N)c2c1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: CCOCC
Product: Nc1c2ccccc2nc2ccc(CCC(=O)O)cc12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
3-(9-Amino-acridin-2-yl)-propionic acid tert-butyl ester 7 (55 mg, 0.17 mmol) was dissolved in anhydrous dichloromethane (2 mL) and trifluoroacetic acid (2 mL) was carefully added. The mixture was stirred at room temperature overnight before evaporation of the solvent. Co-evaporation with diethyl ether (3 times) afforded a yellow solid, which was slurried in diethyl ether, filtered and washed with diethyl ether. Pure 3-(9-amino-acridin-2-yl)-propionic acid (Target 1) was isolated as a yellow TFA salt (49 mg, 76%). 1H NMR and LCMS analyses conformed to structure.
Reaction SMILES: CC([C@H:4]([NH:8][C:9]([C@H]1N(C([C@@H](NC(CNC([C@@H](NC([C@@H](NC([C@@H](NC(C(NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC(C)=O)CO)=O)CC2C=CC(O)=CC=2)=O)CO)=O)CCSC)=O)CCC(O)=O)=O)CC2NC=NC=2)=O)CC2C=CC=CC=2)=O)CCCNC(N)=N)=O)CC2C3C(=CC=CC=3)NC=2)=O)=O)CCCCN)=O)CCC1)=O)C(N)=O)C.O=[C:120]1[O:126][C@H:125]([C@H:127]([CH2:129][OH:130])O)[C:123](O)=[C:121]1[OH:122].[O:131]=[C:132]1[O:138][C@H:137]([C@H:139]([CH2:141][OH:142])[OH:140])[C:135]([O-:136])=[C:133]1[OH:134].[Na+:143]>>[CH3:4][NH:8][CH2:9][C@H:129]([OH:130])[C:127]1[CH:125]=[CH:123][C:121]([OH:122])=[C:120]([OH:126])[CH:132]=1.[O:131]=[C:132]1[O:138][C@H:137]([C@H:139]([CH2:141][OH:142])[OH:140])[C:135]([O-:136])=[C:133]1[OH:134].[Na+:143]
Reactant: CSCC[C@H](NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(C)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)NC(Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(N)=O)C(C)C
Reactant: O=C1O[C@H]([C@@H](O)CO)C(O)=C1O
Agent: O=C1O[C@H]([C@@H](O)CO)C([O-])=C1O
Agent: [Na+]
Product: CNC[C@H](O)c1ccc(O)c(O)c1

Procedure:
In a specific non-limiting embodiment of the invention Hu74 Medium is prepared as follows. Glutamine is added to Ham's F12 (GIBCO, Carlsbad, Calif.) at a concentration of 2 mM. Gentamicin is added to the culture medium to obtain a final concentration of 50 μg/ml. Fetal bovine serum (FBS, GIBCO, Carlsbad, Calif.) is added to the medium to obtain a 10% concentration (volume/volume). The medium containing FBS and gentamicin is stored at 4° C. and prepared fresh every two weeks. bFGF (PeproTech, Rocky Hill, N.J.) is dissolved in F12 medium to 2,500 ng/ml and stored in small vials at −70° C. The stored solution is added to the culture medium to obtain a final concentration of 25 ng/ml once a week. HGF (PeproTech, Rocky Hill, N.J.) is dissolved in F12 medium to 10,000 ng/ml and stored in small vials at −70° C. The stored solution is added to the culture medium to obtain a final concentration of 100 ng/ml once a week. An α-MSH solution is obtained by dissolving the α-MSH powder (Sigma, St. Louis, Mo.) to 100 μg/ml and is stored at −70° C. The stored solution of α-MSH is added to the culture medium to obtain a final concentration of 100 ng/ml once a week. (L)-Epinephrine bitartrate (Sigma, St. Louis, Mo.) is dissolved in PBS at 0.15 mg/ml with sodium ascorbate (Sigma, St. Louis, Mo.) (0.5 mg/ml) and stored at −70° C. Ephinedrine and ascorbic acid are added to the culture medium to obtain a final concentration of 1.5 μg/ml of epinephrine and 5 μg/ml sodium ascorbate once a week.
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24]>CN(C)C(=O)C>[C:26]([O:25][C:23](=[O:24])[CH2:22][N:12]1[CH:13]=[C:9]([B:4]2[O:5][C:6]([CH3:7])([CH3:8])[C:2]([CH3:14])([CH3:1])[O:3]2)[CH:10]=[N:11]1)([CH3:29])([CH3:28])[CH3:27]
Reactant: CC(C)(C)OC(=O)CBr
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Product: CC(C)(C)OC(=O)Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Temperature: 25 °C
Reaction time: 4 h
Yield: 77 %

Procedure:
4,4,5,5-Tetramethyl-2-(1H-pyrazol-4-yl)-1,3,2-dioxaborolane (10 g), N,N-dimethylacetamide (100 ml), potassium carbonate (17.8 g) and t-butyl bromoacetate (9.9 ml) were mixed, and the mixture was stirred at room temperature for 4 hr. The reaction mixture was filtered through celite. Water and ethyl ether were added to the filtrate, and the mixture was partitioned in a separatory funnel. The aqueous layer was extracted with ethyl ether, and the organic layers were combined. The organic layer was washed 3 times with water and once with saturated brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, hexane (50 ml) was added to the obtained residue and the mixture was stirred. This slurry was filtered, and the obtained solid was washed with hexane, and dried under reduced pressure to give the title compound (12.23 g, 77%).