Chloride → 3-[(1S,2S)-2-Hydroxycyclohexyl]-6-[(6-methylpyridin-3-yl)methyl]pyrido[3,4-h]quinazolin-4(3H)-one

HRID 1183821Notes

Reaction equation

HRID 1183821 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:10]=[C:11]3[C:16](=[C:17]4[CH:22]=[CH:21][N:20]=[CH:19][C:18]=24)[N:15]=[CH:14][N:13]([C@H:23]2[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]2[OH:29])[C:12]3=[O:30])=[CH:4][CH:3]=1.[Cl-].[CH2:32]1COCC1>C(=O)(O)[O-].[Na+].C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:29][C@H:24]1[CH2:25][CH2:26][CH2:27][CH2:28][C@@H:23]1[N:13]1[C:12](=[O:30])[C:11]2[C:16](=[C:17]3[CH:22]=[CH:21][N:20]=[CH:19][C:18]3=[C:9]([CH2:8][C:5]3[CH:6]=[N:7][C:2]([CH3:32])=[CH:3][CH:4]=3)[CH:10]=2)[N:15]=[CH:14]1

Participants

7

Reactant 3

HCID 312ChlorideHCID 8028TetrahydrofuranHCID 532612286-[(6-Chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]pyrido[3,4-h]quinazolin-4(3H)-one

Product 1

HCID 532612303-[(1S,2S)-2-Hydroxycyclohexyl]-6-[(6-methylpyridin-3-yl)methyl]pyrido[3,4-h]quinazolin-4(3H)-one

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 6-[(6-chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]pyrido[3,4-h]quinazolin-4(3H)-one (Example 1, 0.030 g, 0.071 mmol) in 1 mL of THF under an atmosphere of nitrogen was added methylzine chloride (2 M in THF, 0.107 mL, 0.214 mmol) and tetrakis(triphenylphosphine)palladium(0) (3.0 mg, 0.0026 mmol). The reaction was heated at 90° C. for 3 h, cooled to rt, and diluted with saturated aqueous sodium bicarbonate and ethyl acetate. The layers were partitioned, and the organic solution was washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-10% methanol in dichloromethane, to provide the title compound that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 401.0 for [M+H]+: 1H NMR (400 MHz, CDCl3) δ 9.11 (s, 1H), 8.43 (s, 2H), 8.19 (s, 2H), 7.86 (s, 1H), 7.34-7.32 (m, 1H), 7.04 (s, 1H), 5.30 (s, 2H), 4.53-4.49 (m, 2H), 4.22 (br s, 1H), 2.49 (s, 3H), 2.32-2.29 (m, 1H), 2.04-2.01 (m, 1H), 1.91-1.89 (m, 1H), 1.58-1.46 (m, 3H).

Workup

  1. temperaturecooled to rt
  2. customThe layers were partitioned
  3. washthe organic solution was washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified via silica gel chromatography
  8. washeluting with 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-251bf6beea0a49f89d3c76d04d3b1cb6
Source dataset
uspto-grants-2014_03
Patent number
US08664387B2

Reaction notes

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