Methanol → HCID 90409019, compound
Reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[C:16]3[O:15][CH2:14][CH:13]([C:17]4[C:18]([C:23]([OH:25])=[O:24])=[N:19][CH:20]=[CH:21][CH:22]=4)[N:12]4[C:26](=[O:28])[NH:27][C:10]([C:11]=34)=[CH:9][CH:8]=2)=[C:5]([CH3:29])[O:4][N:3]=1.[CH3:30]O>S(=O)(=O)(O)O>[CH3:1][C:2]1[C:6]([C:7]2[C:16]3[O:15][CH2:14][CH:13]([C:17]4[C:18]([C:23]([O:25][CH3:30])=[O:24])=[N:19][CH:20]=[CH:21][CH:22]=4)[N:12]4[C:26](=[O:28])[NH:27][C:10]([C:11]=34)=[CH:9][CH:8]=2)=[C:5]([CH3:29])[O:4][N:3]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 80 °C
Procedure
A solution of 3-[7-(3,5-dimethylisoxazol-4-yl)-2-oxo-1,2,4,5-tetrahydroimidazo[1,5,4-de][1,4]benzoxazin-4-yl]pyridine-2-carboxylic acid (294 mg, 0.7493 mmol) in methanol (60.0 mL) was treated with one drop of concentrated sulfuric acid and heated in a sealed tube overnight at 80° C. The reaction mixture was then concentrated to a crude residue. This residue was diluted with ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate solution and stirred at room temperature for 1 hour. After dissolution, the aqueous layer was separated and extracted with ethyl acetate (2×). The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered, and concentrated to give the crude product. Purification by preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) gave the desired product (300 mg, 99%) as a racemic mixture. 1H NMR (400 MHz, DMSO-d6) δ 8.63 (dd, J=4.6, 1.5 Hz, 1H), 7.56 (dd, J=8.1, 4.6 Hz, 1H), 7.29 (dd, J=8.1, 1.4 Hz, 1H), 6.89 (d, J=8.0 Hz, 1H), 6.80 (d, J=8.0 Hz, 1H), 6.00 (dd, J=2.9, 2.9 Hz, 1H), 4.53 (d, J=2.9 Hz, 2H), 3.91 (s, 3H), 2.26 (s, 3H), 2.09 (s, 3H); LCMS calculated for C21H19N4O5 (M+H)+: m/z=407.1. found: 407.0.