Ammonium Chloride → N-(5-((E)-2-((2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxo-tetrahydro-2H-pyran-2-yl)vinyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide

HRID 2387922Notes

Reaction equation

HRID 2387922 reaction equation
[Br-].[F:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:14]([CH2:15][P+](C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)=[C:13]([CH:35]([CH3:37])[CH3:36])[N:12]=[C:11]([N:38]([CH3:43])[S:39]([CH3:42])(=[O:41])=[O:40])[N:10]=2)=[CH:5][CH:4]=1.C[Si](C)(C)N[Si](C)(C)C.[Li].[Si:54]([O:61][C@H:62]1[CH2:67][C:66](=[O:68])[O:65][C@H:64]([CH:69]=O)[CH2:63]1)([C:57]([CH3:60])([CH3:59])[CH3:58])([CH3:56])[CH3:55].[Cl-].[NH4+]>O1CCCC1>[Si:54]([O:61][C@H:62]1[CH2:67][C:66](=[O:68])[O:65][C@H:64](/[CH:69]=[CH:15]/[C:14]2[C:9]([C:6]3[CH:7]=[CH:8][C:3]([F:2])=[CH:4][CH:5]=3)=[N:10][C:11]([N:38]([CH3:43])[S:39]([CH3:42])(=[O:40])=[O:41])=[N:12][C:13]=2[CH:35]([CH3:37])[CH3:36])[CH2:63]1)([C:57]([CH3:60])([CH3:59])[CH3:58])([CH3:56])[CH3:55]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 11239334((4-(4-Fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)pyrimidin-5-yl)methyl)triphenylphosphonium bromideHCID 16113282(2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxo-tetrahydro-2H-pyran-2-carbaldehydeHCID 57426343Lithium bis(trimethylsilyl)amide

Product 1

HCID 16113283N-(5-((E)-2-((2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxo-tetrahydro-2H-pyran-2-yl)vinyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamideYield 65.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-30 °C

Procedure

To a cold (−30° C.), stirred suspension of ((4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)pyrimidin-5-yl)methyl)triphenylphosphonium bromide (376 mg, 0.55 mmol) in dry tetrahydrofuran (10 mL) is added lithium hexamethyldisilazane in THF (0.42 mL of 1.33 M, 0.55 mmol). The reaction mixture is stirred for 30 min, cooled to −78° C., and treated with a solution of (2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxo-tetrahydro-2H-pyran-2-carbaldehyde (9) (130 mg, 0.50 mmol) in 5 mL of tetrahydrofuran. After 60 min, the solution is warmed to ambient temperature, stirred for 10 min, and treated with saturated ammonium chloride solution. The aqueous phase is extracted with t-BuMeO (2×10 mL), and the combined organic layers dried and concentrated. The residue is purified by silica gel chromatography (elution with t-BuMeO/hexane mixture) to give 190 mg (65%) of N-(5-((E)-2-((2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxo-tetrahydro-2H-pyran-2-yl)vinyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide (10) as white amorphous solid.

Workup

  1. stirringThe reaction mixture is stirred for 30 min
  2. temperaturecooled to −78° C.
  3. temperaturethe solution is warmed to ambient temperature
  4. stirringstirred for 10 min
  5. extractionThe aqueous phase is extracted with t-BuMeO (2×10 mL)
  6. customthe combined organic layers dried
  7. concentrationconcentrated
  8. customThe residue is purified by silica gel chromatography (
  9. washelution with t-BuMeO/hexane mixture)

Sources & evidence

ORD record
ord-f22e5c0b990941b5af9bf251b90c8d58
Source dataset
uspto-grants-2012_09
Patent number
US08269001B2

Reaction notes

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