N-methylcyclopropanamine

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:

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

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

Procedure: 6-Chloro-2-methyl-3-nitro-pyridine (0.5 g) was treated with cyclopropyl-methylamine according to General Procedure U to give methyl-(6-methyl-5-nitro-pyridin-2-yl)-amine. LCMS (m/z): 208. This was reduced under hydrogen atmosphere according to General Procedure Z to give N*2*-cyclopropylmethyl-6-methyl-pyridine-2,5-diamine (0.35 g), LCMS (m/z): 178. This was converted to 6-(cyclopropylmethyl-amino)-2-methyl-pyridine-3-sulfonyl chloride according to General Procedure AA. LCMS (m/z): 261.

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

Procedure: This compound was prepared as described in Example 37: 5.0 g (0.013 mol) of product of Example 28, 1.85 g (0.026 mol) of N-methylcyclopropylamine (60% pure) in 30 ml of DMF were reacted at room temperature affording 4.3 g of yellow semi-solid oil. Purification by HPLC using 5% ethyl acetate/cyclohexane as eluting solvent afforded an oil which was kugelrohr distilled at 93 Pa, pot temperature 103° C. to give 1.36 g (24.3%) of product as a yellow solid; mp 56°-58° C. This compound was prepared

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

Procedure: This compound was prepared as described in Example 37: 5.0 g (0.013 mol) of product of Example 28, 1.85 g (0.026 mol) of N-methylcyclopropylamine (60% pure) in 30 ml of DMF were reacted at room temperature affording 4.3 g of yellow semi-solid oil. Purification by HPLC using 5% ethyl acetate/cyclohexane as eluting solvent afforded an oil which was kugelrohr distilled at 93 Pa, pot temperature 103° C. to give 1.36 g (24.3%) of product as a yellow solid; mp 56°-58° C. This compound was prepared

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

Procedure: In analogy to example 1.2a, 1.3, 1.4 and 1.5, reaction of 4-Hydroxy-piperidine with 1,5-dibromopentane, (4-fluoro-phenyl)-acetyl chloride and N-methylcyclopropylamine yielded 1-{4-[5-(Cyclopropyl-methyl-amino)-pentyloxy]-piperidin-1-yl}-2-(4-fluoro-phenyl)-ethanone, MS: 377 (MH+).

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

Procedure: In analogy to example 1.2a, 1.3, 1.4 and 1.5, reaction of 4-Hydroxy-piperidine with 1,5-dibromopentane, (4-fluoro-phenyl)-acetyl chloride and N-methylcyclopropylamine yielded 1-{4-[5-(Cyclopropyl-methyl-amino)-pentyloxy]-piperidin-1-yl}-2-(4-fluoro-phenyl)-ethanone, MS: 377 (MH+).

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

Procedure: In analogy to example 1.2a, 1.5 and 1.3, reaction of 4-Hydroxy-piperidine-1-carboxylic-acid tert-butyl ester and 1,6-dibromohexane, N-methylcyclopropylamine followed by treatment with 4N HCl yielded Cyclopropyl-methyl-[6-(piperidin-4-yloxy)-hexyl]-amine dihydrochloride, MS: 255 (MH+).

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

Procedure: The ethyl 2-(4-chloro-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-2-yl)acetate (7.0 g, 0.0225 mol) and N-methyl cyclopropyl amine (4.8 g, 0.0675 mol) was dissolved in methanol (200 ml). To this reaction mixture, triethyl amine (13.66 g, 0.135 mol) was added slowly at room temperature. The resulting reaction mixture was stirred at room temperature for 18 h. After completion of reaction it was concentrated under reduced pressure. The residue was dissolved in DCM (250 ml) and it was washed with water. Aqueous layer was extracted with DCM (250 ml). Organic extracts were combined and washed with brine. Separated organic layer was dried over anhydrous Na2SO4 and concentrated to get crude compound. It was purified by column chromatography by using 100-200 mesh silica gel and 10% EtOAc:hexane as eluent to give ethyl 2-(4-(cyclopropyl(methyl)amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-2-yl)acetate as a yellow solid. Yield—(6 g, 77.12%); 1H-NMR: (400 MHz, CDCl3); δ=4.20-4.10 (q, 2H), 3.88 (s, 2H), 3.1 (s, 3H), 2.90-2.86 (m, 3H), 2.84-2.83 (m, 2H), 1.93-1.87 (m, 2H), 1.77-1.71 (m, 2H), 1.41 (s, 1H), 1.26-1.23 (t, 3H), 0.72-0.68 (m, 2H), 0.45-0.41 (m, 2H); LC-MS [M+H]=345.9. The resulting reaction mixture After completion of reaction it was concentrated under reduced pressure The residue was dissolved in DCM (250 ml) it was washed with water Aqueous layer was extracted with DCM (250 ml) washed with brine Separated organic layer was dried over anhydrous Na2SO4 concentrated to get crude compound It was purified by column chromatography