2,2-dimethylpentan-1-ol

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

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

Procedure: To a suspension of 2-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (500 mg) and 2,2-dimethylpentanol (3.8 mL) at 50° C. was added sodium hydride (396 mg, 60% dispersion) in portions. To the resultant viscous foam was added a further portion of 2,2-dimethylpentanol (1.5 mL). The reaction was stirred at 50° C. for 72 h. The reaction mixture was cooled then carefully quenched with water (10 mL) and extracted with EtOAc (3×25 mL). The organics were combined, washed with brine (30 mL), dried over MgSO4, filtered and concentrated in vacuo to give a yellow oil. This was azeotroped with toluene (×3) and the resulting viscous yellow oil was purified by C18 reverse phase chromatography (ISCO) using water (0.1% formic acid)-acetonitrile (0.05% formic acid) as eluent (30-80%) to afford the title compound as a brown solid (372 mg). The reaction mixture was cooled then carefully quenched with water (10 mL) extracted with EtOAc (3×25 mL) washed with brine (30 mL) dried over MgSO4 filtered concentrated in vacuo to give a yellow oil This was azeotroped with toluene (×3) the resulting viscous yellow oil was purified by C18 reverse phase chromatography (ISCO)

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

Procedure: To a suspension of 2-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (500 mg) and 2,2-dimethylpentanol (3.8 mL) at 50° C. was added sodium hydride (396 mg, 60% dispersion) in portions. To the resultant viscous foam was added a further portion of 2,2-dimethylpentanol (1.5 mL). The reaction was stirred at 50° C. for 72 h. The reaction mixture was cooled then carefully quenched with water (10 mL) and extracted with EtOAc (3×25 mL). The organics were combined, washed with brine (30 mL), dried over MgSO4, filtered and concentrated in vacuo to give a yellow oil. This was azeotroped with toluene (×3) and the resulting viscous yellow oil was purified by C18 reverse phase chromatography (ISCO) using water (0.1% formic acid)-acetonitrile (0.05% formic acid) as eluent (30-80%) to afford the title compound as a brown solid (372 mg). The reaction mixture was cooled then carefully quenched with water (10 mL) extracted with EtOAc (3×25 mL) washed with brine (30 mL) dried over MgSO4 filtered concentrated in vacuo to give a yellow oil This was azeotroped with toluene (×3) the resulting viscous yellow oil was purified by C18 reverse phase chromatography (ISCO)

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

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

Procedure: The title compound was prepared from 5-{2-[2-(3-chloro-phenyl)-2-hydroxy-ethylamino]-propyl}-benzo[1,3]dioxole-2,2-dicarboxylic acid and 2,2-dimethylpentanol according to the procedure of Example 1 as an off-white solid; 1H NMR(DMSO-d6,400 MHz) 0.8 (m, 18H, 6×CH3), 1.1-1.2 (m, 11H, CH2CH3), 2.6 (m, 1H, CH), 3-3.3 (m, 3H, CH, CH2), 3.4 (brs, 1H, CH), 4.0 (s, 4H, OCH2, OCH2), 5.09 (m, 1H, CH), 6.36 (d, J=4.17 Hz, 1H, OH), 6.86 (dd, J=7.9, 1.32 Hz, 1H, Ar--H), 7.07 (s 1H, Ar--H), 7.09 (d, J=8.35 Hz, Ar--H), 7.35-7.42 (m, 3H, Ar--H), 7.48 (s, 1H, Ar--H), 9.84 (brs, 1H, NH), 9.48 (brs, 1H, NH); IR (KBr, cm-1) 3300 (OH), 2900 (NH), 1760 (CO); MS m/e 617 (M+); Analysis for: C34H48ClNO7 ×HCl: Calc'd: C, 62.38; H, 7.55; N, 2.14; Found: C, 62.47; H, 7.51; N, 2.31.

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

Procedure: To a suspension of 2-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (500 mg) and 2,2-dimethylpentanol (3.8 mL) at 50° C. was added sodium hydride (396 mg, 60% dispersion) in portions. To the resultant viscous foam was added a further portion of 2,2-dimethylpentanol (1.5 mL). The reaction was stirred at 50° C. for 72 h. The reaction mixture was cooled then carefully quenched with water (10 mL) and extracted with EtOAc (3×25 mL). The organics were combined, washed with brine (30 mL), dried over MgSO4, filtered and concentrated in vacuo to give a yellow oil. This was azeotroped with toluene (×3) and the resulting viscous yellow oil was purified by C18 reverse phase chromatography (ISCO) using water (0.1% formic acid)-acetonitrile (0.05% formic acid) as eluent (30-80%) to afford the title compound as a brown solid (372 mg). The reaction mixture was cooled then carefully quenched with water (10 mL) extracted with EtOAc (3×25 mL) washed with brine (30 mL) dried over MgSO4 filtered concentrated in vacuo to give a yellow oil This was azeotroped with toluene (×3) the resulting viscous yellow oil was purified by C18 reverse phase chromatography (ISCO)

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