1-benzyl-3-methylpiperidin-4-amine

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: Ammonium acetate (178.3 g, 2.31 mol) was charged to a solution of 1-benzyl-3-methyl-4-piperidone (47 g, 0.232 mol) in 500 ml methanol. The suspension was stirred for 4 hours at room temperature. Sodium cyanoborohydride (7.3 g, 0.16 mol) was added in lots at 10° C. and it was stirred for 1 hour. it was stirred for 1 hour

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

Procedure: The title compounds were made following the general procedure in Scheme 5 and deprotection in Scheme 4-1, substituting 4-(2-methyl-benzoylamino)-naphthalene-1-sulfonyl chloride for 4-benzoylamino-naphthalene-1-sulfonyl chloride, (±)-4-amino-1-benzyl-3-methyl-piperidine for 4-amino-piperidine-1-carboxylic acid tert-butyl ester and isopropyl chloroformate for 2-isocyanato-propane. C-18: 1H NMR (300 MHz, CDCl3) δ 8.70 (d, 1H), 8.40 (m, 2H), 8.17 (s, 1H), 7.95 (d, 1H), 7.70 (m, 3H), 7.44 (m, 1H), 7.34 (m, 2H), 4.80 (m, 1H), 4.58 (d, 1H), 3.90 (d, 2H), 2.87 (m, 1H), 2.60 (m, 1H), 2.59 (s, 3H), 2.33 (m, 1H), 1.65 (m, 1H), 1.32 (m, 1H), 1.18 (d, 6H), 0.60 (br s, 3H); LC/MS m/z 524 (M+H)+.

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

Procedure: The title compounds were made following general procedure in Scheme 5 and deprotection in scheme 4-1, substituting 4-(2-methyl-benzoylamino)-naphthalene-1-sulfonyl chloride for 4-benzoylamino-naphthalene-1-sulfonyl chloride, 4-amino-1-benzyl-3-methyl-piperidine for 4-amino-piperidine-1-carboxylic acid tert-butyl ester and ethyl isocyanate for 2-isocyanato-propane. 1H NMR (300 MHz, DMSO) δ 8.77 (d, 1H), 8.29 (d, 1H), 8.23 (d, 1H), 7.91 (d, 1H), 7.70 (m, 3H), 7.36 (m, 3H), 3.82 (m, 2H), 3.12 (q, 2H), 2.82 (m, 1H), 2.58 (m, 1H), 2.55 (s, 3H), 2.31 (t, 1H), 1.40 (m, 2H), 1.20 (m, 1H), 1.03 (t, 3H), 0.59 (d, 3H); LC/MS m/z 509 (M+H)+.

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

Procedure: The title compounds were made following general procedure in Scheme 5 and deprotection in scheme 4-1, substituting 4-(2-methyl-benzoylamino)-naphthalene-1-sulfonyl chloride for 4-benzoylamino-naphthalene-1-sulfonyl chloride, 4-amino-1-benzyl-3-methyl-piperidine for 4-amino-piperidine-1-carboxylic acid tert-butyl ester and ethyl isocyanate for 2-isocyanato-propane. 1H NMR (300 MHz, DMSO) δ 8.77 (d, 1H), 8.29 (d, 1H), 8.23 (d, 1H), 7.91 (d, 1H), 7.70 (m, 3H), 7.36 (m, 3H), 3.82 (m, 2H), 3.12 (q, 2H), 2.82 (m, 1H), 2.58 (m, 1H), 2.55 (s, 3H), 2.31 (t, 1H), 1.40 (m, 2H), 1.20 (m, 1H), 1.03 (t, 3H), 0.59 (d, 3H); LC/MS m/z 509 (M+H)+.

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

Procedure: The title compounds were made following the general procedure in Scheme 5 and deprotection in Scheme 4-1, substituting 4-(2-methyl-benzoylamino)-naphthalene-1-sulfonyl chloride for 4-benzoylamino-naphthalene-1-sulfonyl chloride, (±)-4-amino-1-benzyl-3-methyl-piperidine for 4-amino-piperidine-1-carboxylic acid tert-butyl ester and isopropyl chloroformate for 2-isocyanato-propane. 1H NMR (300 MHz, CDCl3) δ 8.72 (d, 1H), 8.43 (d, 1H), 8.35 (d, 1H), 8.12 (d, 1H), 7.95 (d, 2H), 7.72 (m, 3H), 7.46 (m, 1H), 7.35 (d, 2H), 4.85 (m, 1H), 4.66 (d, 1H), 3.55 (m, 1H), 3.37 (m, 1H), 3.17 (m, 2H), 2.59 (s, 3H), 1.74 (m, 1H), 1.58 (m, 1H), 1.40 (m, 2H) 1.18 (dd, 6H), 0.67 (m, 3H); LC/MS m/z 524 (M+H)+.

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

Procedure: The title compounds were made following general procedure in Scheme 5 and deprotection in scheme 4-1, substituting 4-(2-methyl-benzoylamino)-naphthalene-1-sulfonyl chloride for 4-benzoylamino-naphthalene-1-sulfonyl chloride, 4-amino-1-benzyl-3-methyl-piperidine for 4-amino-piperidine-1-carboxylic acid tert-butyl ester and ethyl isocyanate for 2-isocyanato-propane. 1H NMR (300 MHz, CDCl3) δ 8.71 (d, 1H), 8.40 (s, 1H), 8.28 (s, 2H), 7.98 (d, 1H), 7.68 (m, 3H), 7.41 (m, 1H), 7.30 (m, 2H), 5.21 (d, 1H), 4.36 (m, 1H), 3.35 (m, 2H), 3.15 (m, 4H), 2.98 (m, 2H), 2.57 (s, 3H), 1.71 (m, 2H), 1.40 (m, 2H), 1.10 (m, 1H), 1.03 (t, 3H) 0.63 (d, 3H); LC/MS m/z 509 (M+H)+.

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

Procedure: The title compounds were made following general procedure in Scheme 5 and deprotection in scheme 4-1, substituting 4-(2-methyl-benzoylamino)-naphthalene-1-sulfonyl chloride for 4-benzoylamino-naphthalene-1-sulfonyl chloride, 4-amino-1-benzyl-3-methyl-piperidine for 4-amino-piperidine-1-carboxylic acid tert-butyl ester and ethyl isocyanate for 2-isocyanato-propane. 1H NMR (300 MHz, CDCl3) δ 8.71 (d, 1H), 8.40 (s, 1H), 8.28 (s, 2H), 7.98 (d, 1H), 7.68 (m, 3H), 7.41 (m, 1H), 7.30 (m, 2H), 5.21 (d, 1H), 4.36 (m, 1H), 3.35 (m, 2H), 3.15 (m, 4H), 2.98 (m, 2H), 2.57 (s, 3H), 1.71 (m, 2H), 1.40 (m, 2H), 1.10 (m, 1H), 1.03 (t, 3H) 0.63 (d, 3H); LC/MS m/z 509 (M+H)+.

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 25° C. solution of 1-benzyl-3-methyl-piperidin-4-one oxime in anhydrous THF (20 mL) was added LAH (1.0 M solution THF), (15 mL, 15 mmol). After being stirred at 50° C. overnight, the resultant mixture was quenched with 20% KOH solution. The aqueous layer was extracted with CH2Cl2. The organic extracts were combined, washed with brine and dried over MgSO4. The solution was filtered and concentrated in vacuo to give the crude mixture ((±)-cis:(±)-trans=1:1) 1-benzyl-3-methyl-piperidin-4-ylamine (1). LCMS m/z: 205 (M+H)+. This material was used without further purification. the resultant mixture was quenched with 20% KOH solution The aqueous layer was extracted with CH2Cl2 washed with brine dried over MgSO4 The solution was filtered concentrated in vacuo

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

Procedure: The title compounds were made following the general procedure in Scheme 5 and deprotection in Scheme 4-1, substituting 4-(2-methyl-benzoylamino)-naphthalene-1-sulfonyl chloride for 4-benzoylamino-naphthalene-1-sulfonyl chloride, (±)-4-amino-1-benzyl-3-methyl-piperidine for 4-amino-piperidine-1-carboxylic acid tert-butyl ester and isopropyl chloroformate for 2-isocyanato-propane. C-18: 1H NMR (300 MHz, CDCl3) δ 8.70 (d, 1H), 8.40 (m, 2H), 8.17 (s, 1H), 7.95 (d, 1H), 7.70 (m, 3H), 7.44 (m, 1H), 7.34 (m, 2H), 4.80 (m, 1H), 4.58 (d, 1H), 3.90 (d, 2H), 2.87 (m, 1H), 2.60 (m, 1H), 2.59 (s, 3H), 2.33 (m, 1H), 1.65 (m, 1H), 1.32 (m, 1H), 1.18(d, 6H), 0.60 (br s, 3H); LC/MS m/z 524 (M+H)+.

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

Procedure: The title compounds were made following the general procedure in Scheme 5 and deprotection in Scheme 4-1, substituting 4-(2-methyl-benzoylamino)-naphthalene-1-sulfonyl chloride for 4-benzoylamino-naphthalene-1-sulfonyl chloride, (±)-4-amino-1-benzyl-3-methyl-piperidine for 4-amino-piperidine-1-carboxylic acid tert-butyl ester and isopropyl chloroformate for 2-isocyanato-propane. C-18: 1H NMR (300 MHz, CDCl3) δ 8.70 (d, 1H), 8.40 (m, 2H), 8.17 (s, 1H), 7.95 (d, 1H), 7.70 (m, 3H), 7.44 (m, 1H), 7.34 (m, 2H), 4.80 (m, 1H), 4.58 (d, 1H), 3.90 (d, 2H), 2.87 (m, 1H), 2.60 (m, 1H), 2.59 (s, 3H), 2.33 (m, 1H), 1.65 (m, 1H), 1.32 (m, 1H), 1.18(d, 6H), 0.60 (br s, 3H); LC/MS m/z 524 (M+H)+.