cyclobutylmethanamine;hydrochloride

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

Procedure: Commercially available 2,2,5,5-tetramethyldihydrofuran-3(2H)-one (Aldrich), triethylamine, cyclobutylmethanamine hydrochloride (prepared from cyclobutanecarbonitrile as described in WO2005075464), potassium thiocyanate (Aldrich) and iodine (EMD chemicals) were processed using the method described in Example 91A to afford the title compound. MS (ESI+) m/z 267 (M+H)+

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

Procedure: Commercially available 2,2,5,5-tetramethyldihydrofuran-3(2H)-one (Aldrich), triethylamine, cyclobutylmethanamine hydrochloride (prepared from cyclobutanecarbonitrile as described in WO2005075464), potassium thiocyanate (Aldrich) and iodine (EMD chemicals) were processed using the method described in Example 91A to afford the title compound. MS (ESI+) m/z 267 (M+H)+

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

Procedure: Commercially available 2,2,5,5-tetramethyldihydrofuran-3(2H)-one (Aldrich), triethyl amine, cyclobutylmethanamine hydrochloride (prepared from cyclobutanecarbonitrile as described in WO 2005075464), potassium thiocyanate (Aldrich) and iodine (EMD chemicals) were processed using the method described in Example 17A to afford the title compound. MS (ESI+) m/z 267 (M+H)+.

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

Procedure: Commercially available dihydrofuran-3(2H)-one (Small Molecules Inc.), triethylamine, cyclobutylmethanamine hydrochloride (prepared from cyclobutanecarbonitrile as described in WO 2005075464), potassium thiocyanate (Aldrich) and iodine (EMD chemicals) were processed using the method described in Example 17A to afford the title compound. LC/MS (ESI+) m/z 211 (M+H)+.

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

Procedure: Commercially available dihydrofuran-3(2H)-one (Small Molecules Inc.), triethylamine, cyclobutylmethanamine hydrochloride (prepared from cyclobutanecarbonitrile as described in WO 2005075464), potassium thiocyanate (Aldrich) and iodine (EMD chemicals) were processed using the method described in Example 17A to afford the title compound. LC/MS (ESI+) m/z 211 (M+H)+.

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

Procedure: Prepared in a similar manner to Example 19 (e) from 7-chloro-1H-pyrrolo[2,3-c]pyridine-4-carboxylic acid using cyclobutylmethylamine hydrochloride (46 mg) instead of tetrahydro-pyran-4-ylmethylamine to give the title compound (39 mg).

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

Procedure: 2-Oxo-cyclopentanecarboxylic acid ethyl ester (0.24 mL, 1.64 mmol) and C-cyclobutyl-methylamine hydrochloride (0.20 g, 1.64 mmol) were dissolved in methanol (8 mL). Sodium acetate (0.27 g, 3.28 mmol) was added followed by 4 Å powdered molecular sieves (0.20 g) and sodium cyanoborohydride (0.21 g, 3.28 mmol). The reaction was stirred at 25° C. for 16 h. The mixture was poured into a mixture of saturated aqueous sodium bicarbonate solution (20 mL) and ethyl acetate (30 mL). After shaking, both layers were passed through a plug of Celite. The organic layer was further washed with saturated aqueous sodium bicarbonate solution (10 mL), saturated aqueous brine solution (10 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to afford the crude product, 2-(cyclobutylmethyl-amino)-cyclopentanecarboxylic acid ethyl ester (0.29 g, 1.30 mmol, 79%) as a clear oil. LC-MS (ESI) calcd for C13H23NO2 225.33, found 226.2 [M+H+]. After shaking The organic layer was further washed with saturated aqueous sodium bicarbonate solution (10 mL), saturated aqueous brine solution (10 mL) dried over magnesium sulfate filtered concentrated in vacuo

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

Procedure: Commercially available 2,2,5,5-tetramethyldihydrofuran-3(2H)-one (Aldrich), triethylamine, cyclobutylmethanamine hydrochloride (prepared from cyclobutanecarbonitrile as described in WO2005075464), potassium thiocyanate (Aldrich) and iodine (EMD chemicals) were processed using the method described in Example 91A to afford the title compound. MS (ESI+) m/z 267 (M+H)+

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

Procedure: Commercially available 2,2,5,5-tetramethyldihydrofuran-3(2H)-one (Aldrich), triethylamine, cyclobutylmethanamine hydrochloride (prepared from cyclobutanecarbonitrile as described in WO2005075464), potassium thiocyanate (Aldrich) and iodine (EMD chemicals) were processed using the method described in Example 91A to afford the title compound. MS (ESI+) m/z 267 (M+H)+

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

Procedure: In the manner of step (a) of Example 1, cyclobutanemethylamine hydrochloride (Buchman and Howton, J. Amer. Chem. Soc. 1948, 70:2517; 7.96 g, 80.5 mmol) was reacted with phosgene to give 1,3-bis(cyclobutylmethyl)urea as white powder (5.20 g, 37%), m.p. 153°-155° C.; 1H-NMR (DMSO-d6) consistent with structure.

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

Procedure: NMM (1.43 mL, 13.0 mmol) was added to a stirred mixture of 4-chlorosulfonyl-3-(N,N-di-t-butoxycarbonylamino)-1-ethyloxycarbonylmethyl-2-pyridinone (as a mixture from Step H, 0.84 g) and cyclobutylmethylamine hydrochloride (348 mg, 2.86 mmol) in methylene chloride (15 mL). After 16 h the reaction was diluted with methylene chloride and washed with 10% citric acid solution. The organic layer was dried (Na2SO4) and evaporated. The residue was purified by flash column chromatography on silica (40% ethyl acetate/hexanes). HCl gas was bubbled through a stirred solution of the resulting compound in ethyl acetate (10 mL) at 0° C. for 15 min. The reaction was warmed to rt and after a further 3 h it was evaporated to give the title compound as a solid; washed with 10% citric acid solution The organic layer was dried (Na2SO4) evaporated The residue was purified by flash column chromatography on silica (40% ethyl acetate/hexanes) HCl gas was bubbled through a stirred solution of the resulting compound in ethyl acetate (10 mL) at 0° C. for 15 min was evaporated

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-chloro-4-trifluoromethyl-pyrimidine-5-carbonyl chloride (613 mg) (Maybridge) and C-cyclobutylmethylamine hydrochloride (304 mg) in dry dichloromethane (10 ml) was cooled to −30° C. and N,N-diisopropylethylamine (958 ul) was added dropwise. The mixture was stirred at room temp for 1 hour. Water (10 ml) was added, the layers separated and the organic layer was washed sequentially with 10 ml portions of water, dilute hydrochloric acid, water, dilute sodium bicarbonate solution and water, dried (MgSO4) and evaporated. Purification by chromatography on silica gel (dichloromethane/ether 25:1) gave the title compound (449 mg). the layers separated the organic layer was washed sequentially with 10 ml portions of water, dilute hydrochloric acid, water, dilute sodium bicarbonate solution and water dried (MgSO4) evaporated Purification by chromatography on silica gel (dichloromethane/ether 25:1)