Ammonium Chloride → HCID 59639641, compound

HRID 556589Notes

Reaction equation

HRID 556589 reaction equation
[CH2:1]1OCCOCCOCCOCCOCC[O:3][CH2:2]1.FC(F)(F)COP(CC(OC)=O)(=O)OCC(F)(F)F.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[Cl:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=1[NH:55][C:56]1[C:61]([CH:62]=O)=[C:60]([O:64][C:65]2[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=2)[N:59]=[C:58]([S:71][CH3:72])[N:57]=1.[NH4+].[Cl-]>C1(C)C=CC=CC=1.C1COCC1.CCOCC>[Cl:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=1[N:55]1[C:56]2[N:57]=[C:58]([S:71][CH3:72])[N:59]=[C:60]([O:64][C:65]3[CH:66]=[CH:67][CH:68]=[CH:69][CH:70]=3)[C:61]=2[CH:62]=[CH:1][C:2]1=[O:3]

Participants

9

Reactant 5

HCID 25517Ammonium ChlorideHCID 2855718-Crown-6HCID 184894Nsc 634137HCID 3251421Potassium bis(trimethylsilyl)amideHCID 59639611HCID 59639611, compound

Product 1

HCID 59639641HCID 59639641, compoundYield 91%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 18-crown-6 (422 mg, 1.6 mmol, 5 eq) and bis(2,2,2-trifluoroethyl)(methoxycarbonylmethyl)phosphonate (81 μL, 0.38 mmol, 1.2 eq) in anhyd THF (20 mL) was cooled to −78°. To this solution was added potassium bis(trimethylsilyl)amide (0.96 mL, 0.48 mmol, 1.5 eq) as a 0.5 mol solution in toluene. This solution was stirred for additional 30 min at −78° and 4-(2-chloro-phenylamino)-2-methylsulfanyl-6-phenoxy-pyrimidine-5-carbaldehyde (119 mg, 0.32 mmol) in dry THF (1 mL) was added dropwise. The reaction mixture was then stirred for 8 h at −78° and warmed to 23° and stirred 16 h. Saturated aq NH4Cl (5 mL), followed by Et2O (20 mL), was added. The layers were separated. The organic layer was washed with satd aq NaCl, dried (MgSO4) filtered and solvent was removed in vacuo. The yellow residue was then purified by Flash chromatography to give 100 mg (91% yield) of pure 8-(2-chloro-phenyl)-2-methylsulfanyl-4-phenoxy-8H-pyrido[2,3-d]pyrimidin-7-one. 1H-NMR δ 1.89 (s, 3H), 6.55 (d, 1H, J=9.9 Hz), 7.18 (m, 4H), 7.28 (m, 4H), 7.44 (m, 1H), 7.98 (d, 1H, J=9.9 Hz). LC MS (m/e)=396 (MH+). Rt=2.68 min.

Workup

  1. stirringThe reaction mixture was then stirred for 8 h at −78°
  2. temperaturewarmed to 23°
  3. stirringstirred 16 h
  4. additionwas added
  5. customThe layers were separated
  6. washThe organic layer was washed with satd aq NaCl
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customsolvent was removed in vacuo
  10. customThe yellow residue was then purified by Flash chromatography

Sources & evidence

ORD record
ord-d6854eb4a9894df381c6991793071fd1
Source dataset
uspto-grants-2011_11
Patent number
US08058282B2

Reaction notes

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