1,2-diphenylethanamine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: With 1-phenylethylamine neither a satisfactory yield nor an adequate optical purity could be achieved. Quinine yielded enantiomer in good optical purity but poor yield, no yield was indicated for N-methylephedfine With 1,2-diphenylethylamine the yield is satisfactory and the optical purity very good but the reagent, as is also N-methylephedrine is very expensive. Further, it is known that 2,2-dimethylcyclopropanecarboxylic acid can be separated into the enantiomers by the diastereomeric menthyl esters, which can be obtained from the acid chloride with (+) or (-) menthol (U.S. Pat. No. 4,487,956). This process does provide usable yields and optical purities, but is relatively complicated in working up and requires the relatively expensive menthol. can be separated into the enantiomers by the diastereomeric menthyl esters, which

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Isopropyl N-cyano-3-pyridinecarboximidate (0.60 g, 3.2 mmol) was dissolved in methanol (10 ml), and 1,2-diphenylethylamine (0.69 g, 3.5 mmol) was added. The mixture was stirred at room temperature for 45 minutes. After the reaction was completed, the reaction solution was concentrated under reduced pressure. The residual concentrate thus obtained was subjected to chromatography on a silica gel column (WAKO GEL C-200, 50 g) eluting with chloroform-methanol (100:1). The eluted fractions were concentrated under reduced pressure to give N-cyano-N'-(1,2-diphenylethyl)-3-pyridinecarboximidamide (0.60 g, 1.8 mmol, yield: 58%) as colorless syrup. Next, to this syrup was added a 5% hydrogen chloride solution in methanol (2.5 ml). The solution was crystallized from a methanol-diethyl ether to give N-cyano-N'-(1,2-diphenylethyl)-3-pyridinecarboximidamide hydrochloride as colorless powder. the reaction solution was concentrated under reduced pressure The residual concentrate thus obtained eluting with chloroform-methanol (100:1) The eluted fractions were concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Isopropyl N-cyano-3-pyridinecarboximidate (0.60 g, 3.2 mmol) was dissolved in methanol (10 ml), and 1,2-diphenylethylamine (0.69 g, 3.5 mmol) was added. The mixture was stirred at room temperature for 45 minutes. After the reaction was completed, the reaction solution was concentrated under reduced pressure. The residual concentrate thus obtained was subjected to chromatography on a silica gel column (WAKO GEL C-200, 50 g) eluting with chloroform-methanol (100:1). The eluted fractions were concentrated under reduced pressure to give N-cyano-N'-(1,2-diphenylethyl)-3 pyridinecarboximidamide (0.60 g, 1.8 mmol, yield: 58%) as colorless syrup. Next, to this syrup was added a 5% hydrogen chloride solution in methanol (2.5 ml). The solution was crystallized from methanol-diethyl ether to give N-cyano-N'-(1,2-diphenylethyl)-3-pyridinecarboximidamide hydrochloride as colorless powder. the reaction solution was concentrated under reduced pressure The residual concentrate thus obtained eluting with chloroform-methanol (100:1) The eluted fractions were concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from Compound 47a (Example and 1,2-diphenylethanamine, according to procedure described in the synthesis of Compound 47. MS [m+H] calc'd C30H28BrFN5O2 588; found 588.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from Compound 47a (Example and 1,2-diphenylethanamine, according to procedure described in the synthesis of Compound 47. MS [m+H] calc'd C30H28BrFN5O2 588; found 588.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from Compound 47a (Example 42) and 1,2-diphenylethanamine, according to procedure described in the synthesis of Compound 47. MS [m+H] calc'd C32H31FN5O3 540; found 540.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 1,2-diphenylethylamine (930 mg, 4.20 mmol) in EtOH (30 ml) were added 3-bromo-1-propyne (700 mg, 5.30 mmol) and potassium carbonate (1.38 g, 10. 0 mmol). The mixture was refluxed for 16 h and then more 3-bromo-1-propyne (100 mg) was added The mixture was refluxed another 6 h and then it was cooled, diluted with 1 N NaOH (200 ml) and extracted with CH2Cl2. The extract was dried (MgSO4) and concentrated. The residue was purified by flash chromatography. Elution with 1:1 hexanes-CH2Cl2 gave first N,N-di-propargyl-1,2-diphenylethylamine (218 mg, 19%) [1H NMR (CDCl3) δ 2.34 (t,2), 2.83 (dd, 1), 3.53 (dd, 1), 3.63 (dd, 2), 3.71 (dd, 2), 3.85 (dd, 1), 6.89-6.92 (m, 2), 7.14-7.26 (m, 8); 13C NMR (CDCl3)δ 40.5 (t), 40.9 (t), 68.2 (d), 73.4 (d), 79.4 (d), 126.1, 127.6, 128.1, 128.3, 128.8, 129.7, 129.8 (all d), 138.8, 140.8 (all s)]followed by N-propargyl-1,2-diphenylethylamine. Distillation at 180° C./0.5 mm gave the pure compound (583 mg, 59%) as a colorless oil: 1H NMR (CDCl3) δ 1.69 (bs, 1), 2.20 (t, 1), 2.95 (dd, 1), 3.06 (dd, 1), 3.24 (dd, 1), 3.36 (dd, 1), 4.21 (dd, 1), 7.25-7.50 (m, 10); 13C NMR (CDCl3) δ 36.0 (t), 45.1 (t), 62.6 (d), 71.6 (d), 82.2 (s), 126.7, 127.6, 127.8, 128.7, 129.5 (all d), 138.6, 142.7 (all s). The mixture was refluxed for 16 h was refluxed another 6 h it was cooled extracted with CH2Cl2 The extract was dried (MgSO4) concentrated The residue was purified by flash chromatography Elution with 1:1 hexanes-CH2Cl2

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-(2,2-diethoxyethyl)-diphenylethylamine was prepared according to the procedure of Takayama, H., Chem. Lett. 865 (1978). To a stirred solution of 1,2-diphenylethylamine (3.94 g, 20.0 mmol, Aldrich Co., used as received) in N,N-dimethylformamide (DMF) (10 ml) at 8090° C. was added dropwise over 1 h freshly distilled bromoacetaldehyde diethylacetal (4.50 g, 22.5 mmol, Aldrich Co.). After 13 h, potassium carbonate (2.76 g, 20.0 mmol) was added. After 13 h, the brown mixture was cooled to 25° C, and then the mixture was diluted with 1 N NaOH (200 ml), extracted twice with CH2C12 (total of 100 ml), and dried (MgS04). The solvent was evaporated and the residue was distilled to give N-(2,2-diethoxyethyl)-diphenylethylamine (5.29 g, 84%): bp 150-160° C./0.50 mm: 1H NMR (CDCl3) ≃1.10 (t, 3), 1.12 (t, 3 ), 1.70 (bs, 1), 2.50 (dd, 1), 2.58 (dd, 1) 2.91 (dd, 1), 2.98 (dd, 1), 3.39 (1), 3.59 (dt, 1), 3.86 (dd, 1) 4.53 (dd, 1) 7.16-7.40 (m, 10); 13C NMR (CDCl3) δ15.5 (q), 45.5 (t), 50.0 (t), 62.0 (t), 62.2 (t), 64.9 (d), 102.0 (d), 126.5, 127.3, 128.5, 129.5 (all d), 139.0, 143.8 (all s). N-(2,2-diethoxyethyl)-diphenylethylamine was prepared After 13 h extracted twice with CH2C12 (total of 100 ml) dried (MgS04) The solvent was evaporated the residue was distilled

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A procedure similar to that described in Example 3(b) was repeated, except that S-2-pyridyl 3-cyanoandrosta-3,5-diene-17β-thiocarboxylate [prepared as described in Example 3(a)] and 1,2-diphenylethylamine were employed as starting materials, in relative proportions similar to those used In that Example, to give the title compound in a quantitative yield.