Ammonium Chloride → 6-{[6-(1-Hydroxy-1-methylethyl)pyridine-3-yl]methyl}-3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]benzo[h]quinazolin-4(3H)-one

HRID 82450Notes

Reaction equation

HRID 82450 reaction equation
[C:1]([C:4]1[N:9]=[CH:8][C:7]([CH2:10][C:11]2[CH:12]=[C:13]3[C:18](=[C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=24)[N:17]=[CH:16][N:15]([C@H:25]2[CH2:30][CH2:29][O:28][CH2:27][C@@H:26]2[OH:31])[C:14]3=[O:32])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH3:33][Mg]Br.[Cl-].[NH4+]>C1COCC1>[OH:3][C:1]([C:4]1[N:9]=[CH:8][C:7]([CH2:10][C:11]2[CH:12]=[C:13]3[C:18](=[C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=24)[N:17]=[CH:16][N:15]([C@H:25]2[CH2:30][CH2:29][O:28][CH2:27][C@@H:26]2[OH:31])[C:14]3=[O:32])=[CH:6][CH:5]=1)([CH3:33])[CH3:2]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 510007046-[(6-Acetylpyridin-3-yl)methyl]-3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]benzo[h]quinazolin-4(3H)-oneHCID 178418573HCID 178418573, compound

Product 1

HCID 510007816-{[6-(1-Hydroxy-1-methylethyl)pyridine-3-yl]methyl}-3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]benzo[h]quinazolin-4(3H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-[(6-acetylpyridin-3-yl)methyl]-3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]benzo[h]quinazolin-4(3H)-one (Example 10, 0.018 g, 0.042 mmol) in 1 mL of THF at 0° C. was added methylmagnesium bromide (0.035 mL, 3.0 M diethyl ether solution, 0.10 mmol). After 30 min, the mixture was treated with saturated aqueous ammonium chloride and extracted 2× with dichloromethane. The combined organic fractions were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-5% methanol in dichloromethane to provide the title compound that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 446.2067 for [M+H]+ [Calc'd for C26H28N3O4, [M+H]+=446.2074]: 1H NMR (400 MHz, CDCl3) δ 8.95-8.93 (m, 1H), 8.40 (s, 1H), 8.29 (s, 1H), 7.85-7.81 (m, 2H), 7.67-7.60 (m, 2H), 7.39 (d, J=8.2 Hz, 1H), 7.18 (d, J=8.2 Hz, 1H), 4.89-4.80 (m, 2H), 4.33 (s, 2H), 4.25-4.04 (m, 3H), 3.60-3.57 (m, 1H), 3.36-3.28 (m, 1H), 2.30-2.15 (m, 1H), 2.02-1.98 (m, 1H), 1.47 (s, 6H).

Workup

  1. extractionextracted 2× with dichloromethane
  2. dry with materialThe combined organic fractions were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified via silica gel chromatography
  6. washeluting with 0-5% methanol in dichloromethane

Sources & evidence

ORD record
ord-4db8bc4914a240e491d454ef7966720a
Source dataset
uspto-grants-2014_09
Patent number
US08846702B2

Reaction notes

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