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 2387923Notes

Reaction equation

HRID 2387923 reaction equation
FC(F)(F)C([O-])=O.[F:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:20]([CH2:21][P+](CCCC)(CCCC)CCCC)=[C:19]([CH:35]([CH3:37])[CH3:36])[N:18]=[C:17]([N:38]([CH3:43])[S:39]([CH3:42])(=[O:41])=[O:40])[N:16]=2)=[CH:11][CH:10]=1.C[Si](C)(C)N[Si](C)(C)C.[Na].[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+]>C1(C)C=CC=CC=1.O>[Si:54]([O:61][C@H:62]1[CH2:67][C:66](=[O:68])[O:65][C@H:64](/[CH:69]=[CH:21]/[C:20]2[C:15]([C:12]3[CH:13]=[CH:14][C:9]([F:8])=[CH:10][CH:11]=3)=[N:16][C:17]([N:38]([CH3:43])[S:39]([CH3:42])(=[O:41])=[O:40])=[N:18][C:19]=2[CH:35]([CH3:36])[CH3:37])[CH2:63]1)([C:57]([CH3:60])([CH3:59])[CH3:58])([CH3:56])[CH3:55]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 16113282(2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxo-tetrahydro-2H-pyran-2-carbaldehydeHCID 45051731Sodium hexamethyidisilazaneHCID 49783151((4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamido)pyrimidin-5-yl)methyl)tributylphosphonium 2,2,2-trifluoro-acetate

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 45%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent3×

Procedure

To a stirred suspension of ((4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethyl-sulfonamido)pyrimidin-5-yl)methyl)tributylphosphonium 2,2,2-trifluoro-acetate (260 mg, 0.4 mmol) at room temperature in dry toluene (4 mL) is added sodium hexamethyldisilazane in toluene (0.67 mL of 0.6 M, 0.4 mmol) portionwise in 10 minutes. The reaction mixture is stirred for 60 min and treated at room temperature with a solution of (2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxo-tetrahydro-2H-pyran-2-carbaldehyde (9) (105 mg, 0.40 mmol) in 13 mL of dry toluene. After 24 hours of stirring at room temperature the solution is treated with saturated ammonium chloride solution or water. 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 104 mg (45%) 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. stirringAfter 24 hours of stirring at room temperature the solution
  2. extractionThe aqueous phase is extracted with t-BuMeO (2×10 mL)
  3. customthe combined organic layers dried
  4. concentrationconcentrated
  5. customThe residue is purified by silica gel chromatography (
  6. washelution with t-BuMeO/hexane mixture)

Sources & evidence

ORD record
ord-a50f66a0f91241d1b0676f3e14010663
Source dataset
uspto-grants-2012_09
Patent number
US08269001B2

Reaction notes

Loading…