tert-butyl 5-diphenoxyphosphoryloxy-2,3-dihydro-1,4-oxazine-4-carboxylate

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

Procedure: This compound was prepared from tert-butyl 5-((diphenoxyphosphoryl)oxy)-2H-1,4-oxazine-4(3H)-carboxylate and 2-phenoxyphenylboronic acid using a procedure similar to that described in Example 2 (Steps 1-3a) above. The product was isolated as a white solid (25% yield); 1H-NMR (d6-DMSO) 1.07 (9H, s), 3.09 (2H, m), 3.97 (2H, m), 6.19 (1H, s), 6.78 (2H, m), 6.97-7.04 (2H, m), 7.15-7.19 (1H, m), 7.26-7.32 (4H, m); MS ES(+) 298.0 (M+-tBu). IR λmax=1692 cm−1.

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

Procedure: This compound was prepared from tert-butyl 5-((diphenoxyphosphoryl)oxy)-2H-1,4-oxazine-4(3H)-carboxylate and tributyl(furan-2-yl) stannane using a procedure similar to that described in Example 2 (Steps 1-3a) above. The product was isolated as a yellow solid (40% yield); 1H-NMR (CDCl3) 1.26 (9H, s), 3.77 (2H, m), 4.16 (2H, m), 6.14 (1H, d), 6.33 (1H, m), 6.35 (1H, s), 7.35 (1H, d); 13C-NMR (d6-DMSO); 27.4, 41.1, 66.6, 104.0, 110.8, 132.2, 141.0; MS ES(+) 252.1 (M++1); HRMS m/z calcd for C13H17NO4+H+ 252.1236 [M+H+]. Found 252.1066. IR λmax=1693 cm−1.

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

Procedure: A mixture of 2-methoxy-6-(tributylstannyl)pyridine (552 mg, 1.39 mmol) and tert-butyl 5-((diphenoxyphosphoryl)oxy)-2H-1,4-oxazine-4(3H)-carboxylate (300 mg, 0.69 mmol) were dissolved in THF (6 ml). Lithium chloride (90 mg, 2.1 mmol) and Pd(PPh3)4 (78 mg, 0.069 mmol) were added and the mixture heated at reflux for 18 hours. The mixture was concentrated and purified on silica gel, eluting with 0-10% ethyl acetate/petrol. This gave the title compound as a brown solid (60 mg, 30%); 1H-NMR (CDCl3) 1.26 (9H, s), 3.77 (2H, t), 3.92 (3H, s), 4.19 (2H, m), 6.55 (1H, d), 6.76 (1H, d), 6.80 (1H, s), 7.49 (1H, t); MS ES(+) 293.2 (M++1); HRMS m/z calcd for C15H20N2O4+H+ 293.1501 [M+H+]. Found 293.1512. IR λmax=1701 cm−1. the mixture heated at reflux for 18 hours The mixture was concentrated purified on silica gel eluting with 0-10% ethyl acetate/petrol

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

Procedure: This compound was prepared from tert-butyl 5-((diphenoxyphosphoryl)oxy)-2H-1,4-oxazine-4(3H)-carboxylate and quinolin-3-ylboronic acid using a procedure similar to that described in Example 2 (Steps 1-3a) above. The product was isolated as a yellow solid (24% yield); 1H-NMR (d6-DMSO) 0.97 (9H, s), 3.78 (2H, t), 4.18 (3H, t), 6.69 (1H, s), 7.55-7.59 (1H, m), 7.66-7.70 (1H, m), 7.92-8.00 (2H, m), 8.08 (1H, d), 8.77 (1H, d); 13C-NMR (CDCl3) 27.7, 41.7, 66.9, 126.8, 127.4, 128.7, 129.2, 133.6, 148.8; MS ES(+) 313.0 (M++1); HRMS m/z calcd for C18H20N2O3+H+ 313.1552 [M+H+]. Found 313.1556. IR λmax=1697, 1636 cm−1.

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

Procedure: This compound was prepared from tert-butyl 5-((diphenoxyphosphoryl)oxy)-2H-1,4-oxazine-4(3H)-carboxylate and benzofuran-2-ylboronic acid using a procedure similar to that described in Example 2 (Steps 1-3a) above. The product was isolated as a yellow solid (58% yield); 1H-NMR (d6-DMSO) 1.08 (9H, s), 3.70 (2H, m), 4.18 (3H, m), 6.68 (1H, s), 6.77 (1H, s), 7.18-7.25 (2H, m), 7.48-7.56 (2H, m); 13C-NMR (CDCl3) 27.7, 41.3, 67.2, 100.7, 110.6, 120.4, 122.8, 123.4, 134.2; MS ES(+) 246.1 (M+-tBu); Anal. Calcd for C17H19NO4: C, 67.76; H, 6.35; N, 4.65. Found: C, 67.34; H, 6.38; N, 4.68. IR λmax=1690 cm−1.

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

Procedure: This compound was prepared from tert-butyl 5-((diphenoxyphosphoryl)oxy)-2H-1,4-oxazine-4(3H)-carboxylate and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole using a procedure similar to that described in Example 2 (Steps 1-3a) above. The product was isolated as a brown solid (45% yield); 1H-NMR (d6-DMSO) 0.80 (9H, s), 3.81 (2H, m), 4.02 (3H, s), 4.18 (2H, m), 6.50 (1H, s), 6.94 (1H, d), 7.31 (1H, t), 7.47 (1H, m), 7.90 (1H, s); 13C-NMR (CDCl3) 27.4, 35.4, 41.3, 66.8, 107.0, 116.5, 126.2, 131.8; MS ES(+) 316.0 (M++1); HRMS m/z calcd for C17H21N3O3+H+ 316.1661 [M+H+]. Found 316.1664. IR λmax=1692, 1638 cm−1.

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

Procedure: This compound was prepared from tert-butyl 5-((diphenoxyphosphoryl)oxy)-2H-1,4-oxazine-4(3H)-carboxylate and 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole using a procedure similar to that described in Example 2 (Steps 1-3a) above. The product was isolated as a brown solid (43% yield); 1H-NMR (d6-DMSO) 1.12 (9H, s), 3.61 (2H, t), 4.02 (2H, t), 5.24 (2H, s), 6.31 (1H, s), 7.27-7.33 (6H, m), 7.64 (1H, s); 13C-NMR (CDCl3) 27.8, 41.9, 56.2, 66.5, 125.5, 128.1, 128.2, 128.8, 130.9, 136.9; MS ES(+) 342.0 (M++1); HRMS m/z calcd for C19H23N3O3+H+ 342.1818 [M+H+]. Found 342.1826. IR λmax=1697 cm−1.

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

Procedure: This compound was prepared from tert-butyl 5-((diphenoxyphosphoryl)oxy)-2H-1,4-oxazine-4(3H)-carboxylate and 6-(tert-butoxycarbonylamino)pyridin-3-ylboronic acid using a procedure similar to that described in Example 2 (Steps 1-3a) above. The product was isolated as a white solid (26% yield); 1H-NMR (d6-DMSO) 1.10 (9H, s), 1.46 (9H, s), 3.69 (2H, t), 4.10 (2H, t), 6.43 (1H, s), 7.51-7.54 (1H, m), 7.73 (1H, m), 8.06 (1H, s), 9.75 (1H, s); 13C-NMR (d6-DMSO) 27.9, 28.3, 41.7, 66.8, 111.3, 132.3, 133.1, 135.0, 143.9; MS ES(+) 378.0 M++1); HRMS m/z calcd for C19H27N3O5+H+ 378.2029 [M+H+]. Found 378.2035. IR λmax=1699 cm−1.

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

Procedure: This compound was prepared from tert-butyl 5-((diphenoxyphosphoryl)oxy)-2H-1,4-oxazine-4(3H)-carboxylate and 5-methoxypyridin-3-ylboronic acid using a procedure similar to that described in Example 2 (Steps 1-3a) above. The product was isolated as a white solid (45% yield); 1H-NMR (d6-DMSO) 1.07 (9H, s), 3.70 (2H, t), 3.81 (3H, s), 4.12 (2H, t), 6.57 (1H, s), 7.14 (1H, m), 8.02 (1H, d), 8.11 (1H, d); MS ES(+) 293.3 (M++1); HRMS m/z calcd for C15H20N20O4+H+ 293.1501 [M+H+]. Found 293.1519. IR λmax=1701 cm−1.

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

Procedure: This compound was prepared from tert-butyl 5-((diphenoxyphosphoryl)oxy)-2H-1,4-oxazine-4(3H)-carboxylate and pyridin-4-ylboronic acid using a procedure similar to that described in Example 2 (Steps 1-3a) above. The product was isolated as a white solid (56% yield); 1H-NMR (d6-DMSO) 1.11 (9H, s), 3.67 (2H, t), 4.13 (1H, t), 6.74 (1H, s), 7.18 (2H, m), 8.43 (2H, m); 13C-NMR (d6-DMSO) 27.7, 41.3, 66.9, 119.3, 134.7, 149.5; MS ES(+) 263.0 (M++1); HRMS m/z calcd for C14H18N2O3+H+ 263.1296 [M+H+]. Found 263.1402. IR λmax=1695 cm−1.

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

Procedure: This compound was prepared from tert-butyl 5-((diphenoxyphosphoryl)oxy)-2H-1,4-oxazine-4(3H)-carboxylate and 4-phenoxyphenylboronic acid using a procedure similar to that described in Example 2 (Steps 1-3a) above. The product was isolated as a white solid (50% yield); 1H-NMR (d6-DMSO) 1.24 (9H, s), 3.68 (2H, t), 4.09 (2H, t), 6.38 (1H, s), 6.96-6.98 (4H, m), 7.11 (1H, m), 7.21 (2H, d), 7.37 (2H, t); MS ES(+) 298.1 (M+-tBu). IR λmax=1697 cm−1.

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

Procedure: This compound was prepared from tert-butyl 5-((diphenoxyphosphoryl)oxy)-2H-1,4-oxazine-4(3H)-carboxylate and 4-benzoylphenylboronic acid using a procedure similar to that described in Example 2 (Steps 1-3a) above. The product was isolated as a white solid (65% yield); 1H-NMR (d6-DMSO) 1.11 (9H, s), 3.71 (2H, t), 4.15 (2H, t), 6.65 (1H, s), 7.37-7.39 (2H, m), 7.57-7.59 (2H, m), 7.68-7.71 (5H, m); MS ES(+) 366.2 (M++1); Anal. Calcd for C22H23NO4: C, 72.31; H, 6.34; N, 3.83. Found: C, 71.95; H, 6.24; N, 9.98. IR λmax=1695, 1645, 1604, 1360 cm−1.