2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → 3-((3R,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}tetrahydro-2H-pyran-4-yl)-6-{[6-(hydroxymethyl)pyridine-3-yl]methyl}benzo[h]quinazolin-4(3H)-one

HRID 1774912Notes

Reaction equation

HRID 1774912 reaction equation
[Si:1]([O:8][C@@H:9]1[C@@H:14]([N:15]2[C:24](=[O:25])[C:23]3[C:18](=[C:19]4[CH:40]=[CH:39][CH:38]=[CH:37][C:20]4=[C:21]([CH2:26][C:27]4[CH:28]=[CH:29][C:30]([C:33](OC)=[O:34])=[N:31][CH:32]=4)[CH:22]=3)[N:17]=[CH:16]2)[CH2:13][CH2:12][O:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[BH4-].[Na+].[Cl-].[NH4+].ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>C(O)C.C(Cl)(Cl)Cl>[Si:1]([O:8][C@@H:9]1[C@@H:14]([N:15]2[C:24](=[O:25])[C:23]3[C:18](=[C:19]4[CH:40]=[CH:39][CH:38]=[CH:37][C:20]4=[C:21]([CH2:26][C:27]4[CH:32]=[N:31][C:30]([CH2:33][OH:34])=[CH:29][CH:28]=4)[CH:22]=3)[N:17]=[CH:16]2)[CH2:13][CH2:12][O:11][CH2:10]1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 25517Ammonium ChlorideHCID 4311764Sodium borohydride2×HCID 67969714methyl 5-{[3-((3R,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}tetrahydro-2H-pyran-4-yl)-4-oxo-3,4-dihydrobenzo[h]quinazolin-6-yl]methyl}pyridine-2-carboxylate

Product 1

HCID 679698743-((3R,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}tetrahydro-2H-pyran-4-yl)-6-{[6-(hydroxymethyl)pyridine-3-yl]methyl}benzo[h]quinazolin-4(3H)-one

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6212ChloroformSolvent

Procedure

To a solution of methyl 5-{[3-((3R,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}tetrahydro-2H-pyran-4-yl)-4-oxo-3,4-dihydrobenzo[h]quinazolin-6-yl]methyl}pyridine-2-carboxylate (see Example 20, 0.250 g, 0.447 mmol) in 5 mL of ethanol was added sodium borohydride (0.034 g, 0.89 mmol). After 15 h, additional sodium borohydride (0.050 g, 1.32 mmol) was added. After 24 h, 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. To a solution of the residue in 3 mL of chloroform was added 2,3-dichloro-5,6-dicyanobenzoquinone (0.101 g, 0.447 mmol). After 15 min, the mixture was concentrated in vacuo and the residue was purified via silica gel chromatography, eluting with 0-5% methanol in dichloromethane to provide 3-((3R,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}tetrahydro-2H-pyran-4-yl)-6-{[6-(hydroxymethyl)pyridine-3-yl]methyl}benzo[h]quinazolin-4(3H)-one that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 532.0 for [M+H]+.

Workup

  1. waitAfter 24 h
  2. extractionextracted 2× with dichloromethane
  3. dry with materialThe combined organic fractions were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. waitAfter 15 min
  7. concentrationthe mixture was concentrated in vacuo
  8. customthe residue was purified via silica gel chromatography
  9. washeluting with 0-5% methanol in dichloromethane

Sources & evidence

ORD record
ord-34a44a9faf474354a9c9824cb4ba5f10
Source dataset
uspto-grants-2016_02
Patent number
US09260418B2

Reaction notes

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