Cyclopropanamine, 1-(3-fluorophenyl)-, hydrochloride (1:1)

4~fluoro-2-(4-fluorophenyl)-5-(5-(l-(3-fluorophenyl)cycIopropylcarbatnoyl)-4- methoxy-2-methylpheny l)-N-methylpyrazolo [ 1 , 5-a] py ridin e-3-carboxamide . To a solution containing l-(3-fiuorophenyl)cyclopropanamine hydrochloride (0.022 g, 0.12 mraol), diisopropylethylamine (0.12 mL, 0.71 mmol), 5-(4-fluoro-2-(4- fluororhohenyl)-3-(methylcarbamoyl)pyrazolo[l, 5-a]pyridin-5-yl)-2-methoxy-4- methylbenzoic acid (0.040 g, 0.089 mmol) and DMF (0.60 mL) was added HATU (0.067 g, 0.18 mmol) in one portion. The solution was maintained at room temperature for Ih and concentrated. The resultant residue was purified using preparative HPLC (Waters- Xbridge, 50 x 100 mm, 5 micron, C18 column; 0.1M TFA, 0-100percent B (B = 10percent H2CYCH3OH)/ A (A - 90percent H2O/ CH3OH), 12 rain, gradient, analysis time 15 min.) afforded 4-fluoro-2-(4-fluororhohenyl)-5-(5-(l-(3- fluorophenyl)cyclopropylcarbamoyl)-4-methoxy-2-methylphenyl)~N' methy]rhoyrazolo[l55-a]rhoyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 12.0 min. IH NMR (400 MHz5 CHLOROFORM-^) delta ppm 8.46 (s, 1 H), 8, 34 (d, /=7.03 Hz, 1 H), 8.11 (s, 1 H), 7.80 - 7.89 (m, 2 H), 7.22 - 7.27 (m, 1 H), 7.13 - 7.21 (m, 2 H), 6.96 - 7.06 (m, 3 H), 6.84 - 6.92 (m, 1 H), 6.75 (t, /=6.78 Hz, 1 H), 5.92 (d, J=4.02 Hz, 1 H), 4.08 (s, 3 H), 2.97 (d, J=5.02 Hz, 3 H), 2.34 (s, 3 H), 1.36 - 1.45 (m, 4 H). LCMS retention time: 2.480 min. LC data was recorded on a Shimadzu LC-IOAS liquid chromatograph equipped with a Phenomenex-Luna, 10 micron, C18, 3, 0 x 50 mm column using a SPD-IOAV UV-Vis detector at a detector wave length of 220 iiM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100percent solvent A / 0percent solvent B to 0percent solvent A / 100percent solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 10percent CH3OH / 90percent H2O / 10 mM TFA and solvent B was 10percent H2O / 90percent CH3OH / 10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode, m/z 585 (MH+).To a solution containing l-(3-fluorophenyl)cyclopropanamine hydrochloride (0.022 g, 0.12 mmol), diisopropylethylamine (0.12 mL, 0.71 mmol), 5-(4-fluoro-2-(4- fluorophenyl)-3-(methylcarbamoyl)pyrazolo[l, 5-a]pyridin-5-yl)-2-methoxy-4- methylbenzoic acid (0.040 g, 0.089 mmol) and DMF (0.60 mL) was added HATU (0.067 g, 0.18 mmol) in one portion. The solution was maintained at room temperature for lh and concentrated. The resultant residue was purified using preparative HPLC (Waters- Xbridge, 50 x 100 mm, 5 micron, CI 8 column; 0.1M TFA, 0-100percent B (B = 10percent H20/CH3OH)/ A (A = 90percent H20/ CH3OH), 12 min.gradient, analysis time 15 min.) afforded 4-fluoro-2-(4-fluorophenyl)-5-(5-(l-(3- fluorophenyl)cyclopropylcarbamoyl)-4-methoxy-2-methylphenyl)-N- methylpyrazolo[l, 5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 12.0 min. 1H NMR (400 MHz, CHLOROFORM-if) delta ppm 8.46 (s, 1 H), 8.34 (d, J=7.03 Hz, 1 H), 8.11 (s, 1 H), 7.80 - 7.89 (m, 2 H), 7.22 - 7.27 (m, 1 H), 7.13 - 7.21 (m, 2 H), 6.96 - 7.06 (m, 3 H), 6.84 - 6.92 (m, 1 H), 6.75 (t, J=6.78 Hz, 1 H), 5.92 (d, J=4.02 Hz, 1 H), 4.08 (s, 3 H), 2.97 (d, J=5.02 Hz, 3 H), 2.34 (s, 3 H), 1.36 - 1.45 (m, 4 H). LCMS retention time: 2.480 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 10 micron, C18, 3.0 x 50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100percent solvent A / 0percent solvent B to 0percent solvent A / 100percent solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 10percent CH3OH / 90percent H20 / 10 mM TFA and solvent B was 10percent H20 / 90percent) CH3OH / 10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode, m/z 585 (MH+).To the product of step 2 in 10 mL of diethyl ether at room temperature was added 50 mL of 4 N hydrogen chloride in dioxane. The solution then was stirred at room temperature for 2 hours. The resulting suspension was filtered, and the solids were washed with diethyl ether and then dried to furnish 6.5 g of 1- (3- FLUOROPHENYL)-1-CYCLOPROPYLAMINE (7) as its hydrochloride salt. NMR (300 MHz, DMSO-D6) : 5 9.02 (br s, 3 H), 7.46 (m, 1 H), 7.27 (m, 2 H), 7.19 (t of d, 1 H), 1.42 (m, 2 H), 1.25 (m, 2 H).To a mixture of 3.76 g (20 mmol) of 1- (3- FLUOROPHENYL)-1-CYCLOPROPYLAMINE hydrochloride (7) and 6.2 g (45 mmol) of potassium carbonate in 60 mL of acetonitrile and 10 mL of water at room temperature was added slowly 1. 90 mL (20 mmol) of methyl bromoacetate. The reaction mixture was stirred at room temperature for 70 hours and then filtered. The filtrate was concentrated under vacuum, and the residue was dissolve in ethyl acetate. This solution was washed with saturated aqueous sodium bicarbonate solution, water, and brine, dried over anhydrous sodium sulfate, filtered, and concentrated. Column chromatography on silica gel (elution: 10percent ethyl acetate/methylene chloride) provided 3.3 g of N- [L- (3-FLUOROPHENYL)-1-CYCLOPROPYL] GLYCINE, methyl ESTER (8). NMR (300 MHz, CDC13) : 8 7.27 (m, 1 H), 7.06 (d of d, 1 H), 7.00 (d of t, 1 H), 6.91 (t of d, 1 H), 3. 66 (s, 3 H), 3. 38 (s, 2 H), 1. 07 (m, 2 H), 0. 94 (m, 2 H).

1-(3-Fluorophenyl)cyclopropanamine Hydrochloride is used in the preparation for N-cyclohexylglycines as HIV protease inhibitors.

Molecular Weight:187.64
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:187.0564052
Monoisotopic Mass:187.0564052
Topological Polar Surface Area:26
Heavy Atom Count:12
Complexity:154
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes