6-Fluoropyridine-2-carboxylic acid → 6-{[4-(6,6-Dimethyl-4-oxo-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridin-2-yl)-3,4-dihydro-2h-1,4-benzoxazin-6-yl]oxy}pyridine-2-carboxylic acid

HRID 885984Notes

Reaction equation

[CH3:1][C:2]1([CH3:23])[NH:7][C:6](=[O:8])[C:5]2[S:9][C:10]([N:12]3[C:17]4[CH:18]=[C:19]([OH:22])[CH:20]=[CH:21][C:16]=4[O:15][CH2:14][CH2:13]3)=[N:11][C:4]=2[CH2:3]1.F[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([OH:33])=[O:32])[N:26]=1.CC(C)([O-])C.[Na+]>C1COCC1>[CH3:1][C:2]1([CH3:23])[NH:7][C:6](=[O:8])[C:5]2[S:9][C:10]([N:12]3[C:17]4[CH:18]=[C:19]([O:22][C:25]5[N:26]=[C:27]([C:31]([OH:33])=[O:32])[CH:28]=[CH:29][CH:30]=5)[CH:20]=[CH:21][C:16]=4[O:15][CH2:14][CH2:13]3)=[N:11][C:4]=2[CH2:3]1

Participants

Conditions

Temperature: 140 °C

Procedure

To a solution of Example 57 (50 mg, 0.151 mmol) in THF (4 mL) was added 2-fluoro-6-pyridinecarboxylic acid (53 mg, 0.378 mmol) and sodium tert-butoxide (73 mg, 0.755 mmol). The mixture was heated to 140° C. under microwave irradiation for 90 minutes, cooled to r.t. and concentrated in vacuo. The residue was purified by preparative HPLC (Method 6) to give the title compound (15 mg, 22%) as an off-white solid. δH (CDCl3) 8.07 (1H, d, J 2.4 Hz), 7.94-7.91 (2H, m), 7.24-7.16 (1H, m), 7.00 (1H, d, J 8.9 Hz), 6.85 (1H, dd, J 8.9 and 2.6 Hz), 5.45 (1H, s), 4.52-4.20 (2H, m), 4.20-4.01 (2H, m), 2.84 (2H, s), 1.38 (6H, s). LCMS (ES+) 453.0 (M+H)+, RT 2.94 minutes (Method 1).

Workup

temperaturecooled to r.t.
concentrationconcentrated in vacuo
customThe residue was purified by preparative HPLC (Method 6)

Sources & evidence

ORD record: ord-cb5fb05a61c64aca9c4cacc7077b1b2a
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08242116B2

Reaction notes

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