Sodium hydride → HCID 86629454, compound

HRID 599297Notes

Reaction equation

HRID 599297 reaction equation
[H-].[Na+].[C:3]([NH:7][C:8]1[C:13]([CH2:14][NH:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[C:18]([N+:23]([O-:25])=[O:24])[CH:17]=2)=[CH:12][N:11]=[C:10]([Cl:26])[CH:9]=1)([CH3:6])([CH3:5])[CH3:4].Cl[C:28](Cl)([O:30]C(=O)OC(Cl)(Cl)Cl)Cl>O1CCOCC1>[C:3]([N:7]1[C:8]2[CH:9]=[C:10]([Cl:26])[N:11]=[CH:12][C:13]=2[CH2:14][N:15]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[C:18]([N+:23]([O-:25])=[O:24])[CH:17]=2)[C:28]1=[O:30])([CH3:6])([CH3:4])[CH3:5]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 94429TriphosgeneHCID 86629453HCID 86629453, compound

Product 1

HCID 86629454HCID 86629454, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

NaH (1.5 g, 36.6 mmol) was added portion wise to a solution of N-tert-butyl-2-chloro-5-((4-fluoro-3-nitrophenylamino)methyl)pyridin-4-amine (4.3 g, 12.2 mmol) in anhydrous dioxane (400 mL) at 0° C. and the resulting mixture was stirred at RT for 10 min. A solution of triphosgene (3.6 g, 12.2 mmol) in dioxane (30 mL) was added to the above mixture at 0° C. After the addition, the mixture was heated at 100° C. for 10 h. The cooled reaction was quenched with water and the pH was adjusted to pH>7 with saturated NaHCO3 solution. The dioxane was removed under reduced pressure and the residue was partitioned between water and EtOAc (3×50 mL). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated in vacuo. Purification by silica gel chromatography provided 1-tert-butyl-7-chloro-3-(4-fluoro-3-nitrophenyl)-3,4-dihydropyrido[4,3-d]pyrimidin-2(1H)-one (3.5 g, 76% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.21 (s, 1 H), 8.07 (m, 1 H), 7.71 (m, 1 H), 7.57 (m, 1 H), 7.32 (s, 1 H), 4.70 (s, 2 H) 1.57 (s, 9 H).

Workup

  1. additionAfter the addition
  2. temperaturethe mixture was heated at 100° C. for 10 h
  3. customThe cooled reaction
  4. customwas quenched with water
  5. customThe dioxane was removed under reduced pressure
  6. customthe residue was partitioned between water and EtOAc (3×50 mL)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-9da82f209001462193135b26b524caeb
Source dataset
uspto-grants-2011_03
Patent number
US07897762B2

Reaction notes

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