Ammonium Chloride → HCID 69925537, compound

HRID 1183828Notes

Reaction equation

HRID 1183828 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]1[N:8]1[C:17](=[O:18])[C:16]2[C:11](=[C:12]3[CH:31]=[CH:30][N:29]=[CH:28][C:13]3=[C:14]([CH2:19][C:20]3[CH:27]=[CH:26][C:23]([CH:24]=[O:25])=[CH:22][CH:21]=3)[CH:15]=2)[N:10]=[CH:9]1.[CH3:32][Mg]Br.[Cl-].[NH4+]>C1COCC1>[OH:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]1[N:8]1[C:17](=[O:18])[C:16]2[C:11](=[C:12]3[CH:31]=[CH:30][N:29]=[CH:28][C:13]3=[C:14]([CH2:19][C:20]3[CH:21]=[CH:22][C:23]([CH:24]([OH:25])[CH3:32])=[CH:26][CH:27]=3)[CH:15]=2)[N:10]=[CH:9]1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 53261389HCID 53261389, compoundHCID 178418573HCID 178418573, compound2×

Product 1

HCID 69925537HCID 69925537, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-({3-[(1S,2S)-2-hydroxycyclohexyl]-4-oxo-3,4-dihydropyrido[3,4-h]quinazolin-6-yl}methyl)benzaldehyde (Example 10, 0.035 g, 0.085 mmol) in 2 mL of THF at −50° C. was added methylmagnesium bromide (0.028 mL, 3.0 M diethyl ether solution, 0.85 mmol). After 3 h, additional methylmagnesium bromide (0.028 mL, 3.0 M diethyl ether solution, 0.85 mmol) was added. After 1 h, the mixture was treated with saturated aqueous ammonium chloride and extracted 2× with ethyl acetate. 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 430.0 for [M+H]+: 1H NMR (400 MHz, CDCl3) δ 9.25 (s, 1H), 8.53 (s, 1H), 8.42 (d, J=4.5 Hz, 1H), 8.23 (s, 1H), 8.01 (s, 1H), 7.25 (d, J=9.2 Hz, 2H), 7.18 (d, J=8.1 Hz, 2H), 4.88-4.84 (m, 1H), 4.56 (br s, 1H), 4.47 (s, 2H), 4.14-4.12 (m, 1H), 3.65-3.63 (m, 1H), 2.31-2.28 (m, 1H), 2.05-1.84 (m, 4H), 1.62-1.48 (m, 2H), 1.46 (d, J=6.4 Hz, 3H).

Workup

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

Sources & evidence

ORD record
ord-9fa9154514894352b96b31405d6baa52
Source dataset
uspto-grants-2014_03
Patent number
US08664387B2

Reaction notes

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