(4S)-1,2-oxazolidin-4-ol;hydrochloride

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

Procedure: Prepared as the method of example 1, part g) using the product of step f) and (S)-isoxazolidin-4-ol hydrochloride. δ 1H DMSO 0.84 (3H, td), 1.60 (2H, septet), 3.21 (3H, d), 3.56 (1H, d), 3.73 (3H, m), 3.81 (1H, d), 3.90 (1H, m), 4.61 (2H, dd), 4.79 (1H, s), 5.52 (1H, m), 7.46 (1H, dd), 7.63 (1H, m) 7.79 (1H, m), 8.05 (1H, d), 8.27 (1H, dd), 8.87 (1H, d). MS (APCI) 481.1 (M++H) Prepared as the method of example 1, part g)

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

Procedure: Prepared using the procedure described in example 1 part g) from the product of step b) and (S)-4-hydroxyisoxazolidine hydrochloride [Example 1 part b] to give the title compound after purification by flash silica chromatography eluting with 0-3% methanol in ethyl acetate and recrystallisation from ethyl acetate:isohexane (9:1). MS (APCI) 497.1 [M+H] δ 1HDMSO 0.81-0.84 (6H,m), 2-2.1 (1H, m), 2.44 (3H, s), 3.2 (3H, s), 3.5-3.9 (6H, 3m), 4.1-4.2 (2H, m), 4.7-4.8 (1H,2m), 5.5 (1H, d), 6.82-6.87 (2H, m), 7.28-7.38 (2H, m), 10.95 (1H, bs) Prepared

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

Procedure: Prepared as the method of example 1, part g) using the product of step f) and (S)-isoxazolidin-4-ol hydrochloride. δ 1H DMSO 0.84 (3H, td), 1.60 (2H, septet), 3.21 (3H, d), 3.56 (1H, d), 3.73 (3H, m), 3.81 (1H, d), 3.90 (1H, m), 4.61 (2H, dd), 4.79 (1H, s), 5.52 (1H, m), 7.46 (1H, dd), 7.63 (1H, m) 7.79 (1H, m), 8.05 (1H, d), 8.27 (1H, dd), 8.87 (1H, d). MS (APCI) 481.1 (M++H) Prepared as the method of example 1, part g)

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

Procedure: Prepared using the procedure described in example 1 part g) from the product of step b) and (S)-4-hydroxyisoxazolidine hydrochloride [Example 1 part b] to give the title compound after purification by flash silica chromatography eluting with 0-3% methanol in ethyl acetate and recrystallisation from ethyl acetate:isohexane (9:1). MS (APCI) 497.1 [M+H] δ 1HDMSO 0.81-0.84 (6H,m), 2-2.1 (1H, m), 2.44 (3H, s), 3.2 (3H, s), 3.5-3.9 (6H, 3m), 4.1-4.2 (2H, m), 4.7-4.8 (1H,2m), 5.5 (1H, d), 6.82-6.87 (2H, m), 7.28-7.38 (2H, m), 10.95 (1H, bs) Prepared

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

Procedure: To a slurry of Intermediate 3 (190 mg, 0.5 mmol), (S)-isoxazolidin-4-ol hydrochloride (95 mg, 0.75 mmol) and triethylamine (0.4 mL) in 10 mL of dichloromethane, was added NaBH(OAc)3 (0.32 g, 1.5 mmol) at room temperature. The reaction was stirred for 12 hour at room temperature and then quenched with 1N—NaOH. It was extracted with ethyl acetate and washed twice with brine. The collected organic layer was dried over anhydrous sodium sulfate and then concentrated in vacuo. The resulting residue was purified by silica gel chromatography (DCM/MeOH) to afford desired Compound No. 31 as a pale yellow solid (159 mg, 70%); MS (ESI) m/z 454 [M+H]+. 1H NMR (300 MHz, CDCl3) δ 8.43 (s, 1H), 8.34 (d, J=5.4 Hz, 1H), 7.89 (s, 1H), 7.68 (s, 1H), 7.14-7.16 (m, 3H), 4.73 (brs, 1H), 4.23 (brs, 1H), 3.92-3.96 (m, 2H), 3.84 (brs, 1H), 3.63 (s, 3H), 3.25 (brs, 1H), 2.73 (brs, 1H), 2.40 (s, 3H), 2.36 (s, 3H quenched with 1N—NaOH It was extracted with ethyl acetate washed twice with brine The collected organic layer was dried over anhydrous sodium sulfate concentrated in vacuo The resulting residue was purified by silica gel chromatography (DCM/MeOH)

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

Procedure: To a slurry of intermediate 2 (500 mg, 1.14 mmol), (S)-isoxazolidin-4-ol hydrochloride (220 mg, Tetrahedron Lett., 2006, 47, 7635-7639) and triethylamine (0.79 mL) in 10 mL of dichloromethane and 10 mL of N,N-dimethylacetamide (DMAC), was added NaBH(OAc)3 (730 mg, 3.42 mmol) at room temperature. Volatiles were removed in vacuo. It was extracted with dichloromethane (×3). The collected organic layers were dried over anhydrous sodium sulfate and then concentrated in vacuo. The resulting residue was purified by silica gel chromatography (DCM/MeOH) to give 270 mg (50%) of the desired compound 1 as a pale yellow solid; MS (ESI) m/z 474 [M+H]+, 1H NMR (300 MHz, DMSO-d6) δ 9.85 (s, 1H), 9.30 (s, 1H), 9.02 (s, 1H), 8.48 (d, J=5.4 Hz, 1H), 7.47 (d, J=9.0 Hz, 1H), 7.36 (d, J=8.7 Hz, 1H), 7.13 (d, J=5.4 Hz, 1H), 5.19 (s, 1H), 4.60 (d, 1H), 4.10 (m, 1H), 3.94 (d, 2H), 3.87 (s, 3H), 3.81 (m, 1H), 2.86 (m, 1H), 2.65 (m, 1H), 2.29 (s, 1H), 0.92 (d, J=6.0 Hz, 2H). Volatiles were removed in vacuo It was extracted with dichloromethane (×3) The collected organic layers were dried over anhydrous sodium sulfate concentrated in vacuo The resulting residue was purified by silica gel chromatography (DCM/MeOH)

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

Procedure: Prepared as the method of example 1, part g) using the product of step f) and (S)-isoxazolidin-4-ol hydrochloride. δ 1H DMSO 0.84 (3H, td), 1.60 (2H, septet), 3.21 (3H, d), 3.56 (1H, d), 3.73 (3H, m), 3.81 (1H, d), 3.90 (1H, m), 4.61 (2H, dd), 4.79 (1H, s), 5.52 (1H, m), 7.46 (1H, dd), 7.63 (1H, m) 7.79 (1H, m), 8.05 (1H, d), 8.27 (1H, dd), 8.87 (1H, d). MS (APCI) 481.1 (M++H) Prepared as the method of example 1, part g)

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

Procedure: Prepared using the procedure described in example 1 part g) from the product of step b) and (S)-4-hydroxyisoxazolidine hydrochloride [Example 1 part b] to give the title compound after purification by flash silica chromatography eluting with 0-3% methanol in ethyl acetate and recrystallisation from ethyl acetate:isohexane (9:1). MS (APCI) 497.1 [M+H] δ 1HDMSO 0.81-0.84 (6H,m), 2-2.1 (1H, m), 2.44 (3H, s), 3.2 (3H, s), 3.5-3.9 (6H, 3m), 4.1-4.2 (2H, m), 4.7-4.8 (1H,2m), 5.5 (1H, d), 6.82-6.87 (2H, m), 7.28-7.38 (2H, m), 10.95 (1H, bs) Prepared