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 2387923노트

반응식

HRID 2387923 반응식
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]

참가 물질

7

반응물 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

생성물 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-methylmethanesulfonamide수율 45%

시약·촉매·용매 2

HCID 962Water용매HCID 1140Toluene용매3회

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-a50f66a0f91241d1b0676f3e14010663
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08269001B2

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