Lithium Hydroxide → 5-({3-[(3R,4S)-3-Hydroxytetrahydro-2H-pyran-4-yl]-4-oxo-3,4-dihydrobenzo[h]quinazolin-6-yl}methyl)pyridine-2-carboxylic acid

HRID 82455Notes

Reaction equation

HRID 82455 reaction equation
[OH:1][C@@H:2]1[C@@H:7]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[C:12]4[CH:33]=[CH:32][CH:31]=[CH:30][C:13]4=[C:14]([CH2:19][C:20]4[CH:21]=[CH:22][C:23]([C:26]([O:28]C)=[O:27])=[N:24][CH:25]=4)[CH:15]=3)[N:10]=[CH:9]2)[CH2:6][CH2:5][O:4][CH2:3]1.[OH-].[Li+]>O.C1COCC1>[OH:1][C@@H:2]1[C@@H:7]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[C:12]4[CH:33]=[CH:32][CH:31]=[CH:30][C:13]4=[C:14]([CH2:19][C:20]4[CH:21]=[CH:22][C:23]([C:26]([OH:28])=[O:27])=[N:24][CH:25]=4)[CH:15]=3)[N:10]=[CH:9]2)[CH2:6][CH2:5][O:4][CH2:3]1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 51000623methyl 5-({3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-oxo-3,4-dihydrobenzo[h]quinazolin-6-yl}methyl)pyridine-2-carboxylate

Product 1

HCID 699351085-({3-[(3R,4S)-3-Hydroxytetrahydro-2H-pyran-4-yl]-4-oxo-3,4-dihydrobenzo[h]quinazolin-6-yl}methyl)pyridine-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of methyl 5-({3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]-4-oxo-3,4-dihydrobenzo[h]quinazolin-6-yl}methyl)pyridine-2-carboxylate (0.150 g, 0.337 mmol) in 2 mL of water and 2 mL of THF was added lithium hydroxide (0.016 g, 0.67 mmol). The mixture was heated to 50° C. for 2 h, cooled to rt, and quenched with saturated aqueous potassium phosphate to pH 5. The aqueous solution was extracted 3× with ethyl acetate and the combined organic fractions were dried over sodium sulfate, filtered, and concentrated in vacuo to provide the title compound that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 432.1560 for [M+H]+ [Calc'd for C24H22N3O5, [M+H]+=432.1554]: 1H NMR (400 MHz, CDCl3) δ 896-8.94 (m, 1H), 8.70 (s, 1H), 8.67 (s, 1H), 8.13-8.10 (m, 1H), 7.98 (s, 1H), 8.89 (d, J=8.2 Hz, 1H), 7.78-7.67 (m, 3H), 5.26 (d, J=5.3 Hz, 1H), 4.63 (s, 2H), 4.14-4.03 (m, 1H), 3.94-3.88 (m, 2H), 3.41 (t, J=11.0 Hz, 1H), 3.27 (br s, 1H), 3.12-3.08 (m, 2H), 2.28-2.19 (m, 1H), 1.87-1.83 (m, 1H).

Workup

  1. temperaturecooled to rt
  2. customquenched with saturated aqueous potassium phosphate to pH 5
  3. extractionThe aqueous solution was extracted 3× with ethyl acetate
  4. dry with materialthe combined organic fractions were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5a27ade8136f42428db5c141ee45e005
Source dataset
uspto-grants-2014_09
Patent number
US08846702B2

Reaction notes

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