Hydrochloric Acid → N-benzyl-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopentyl-acetamide

HRID 417154

反応式

HRID 417154 の反応式
C1(C([N:19]2[C:23]3[CH:24]=[C:25]([F:29])[C:26]([F:28])=[CH:27][C:22]=3[N:21]=[C:20]2[C:30]2[C:31](OC)=N[C:33](OC)=[CH:34][CH:35]=2)COC2C=CC(C(O)=O)=CN=2)CCCCC1.C1(C=[O:46])CCCC1.[Cl:47][C:48]1[CH:56]=[CH:55][C:51]([C:52](O)=O)=[CH:50][CH:49]=1.[CH2:57]([N+:64]#[C-:65])[C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1.Cl.C(=O)(O)[O-].[Na+]>CO.O1CCOCC1>[CH2:57]([NH:64][C:65](=[O:46])[CH:20]([N:21]1[C:22]2[CH:27]=[C:26]([F:28])[C:25]([F:29])=[CH:24][C:23]=2[N:19]=[C:52]1[C:51]1[CH:55]=[CH:56][C:48]([Cl:47])=[CH:49][CH:50]=1)[CH:30]1[CH2:35][CH2:34][CH2:33][CH2:31]1)[C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1

参加物

9

反応物 6

HCID 313Hydrochloric AcidHCID 63184-Chlorobenzoic AcidHCID 70106CyclopentanecarbaldehydeHCID 82558Benzyl isocyanideHCID 516892Sodium BicarbonateHCID 461857196-{2-Cyclohexyl-2-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-ethoxy}-nicotinic acid2 回

生成物 1

HCID 66619313N-benzyl-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopentyl-acetamide

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 312751,4-Dioxane溶媒

実験手順

To a solution of 5.0 g (20.47 mmol) (2-amino-4,5-difluoro-phenyl)-carbamic acid tert-butyl ester (Example 73, intermediate g) in 50 ml methanol, 2.21 g (22.57 mmol) cyclopentanecarbaldehyde (commercially available) were added. After stirring for 5 min. at room temperature, 3.2 g (20.5 mmol) p-chlorobenzoic acid and 2.5 ml (20.47 mmol) benzyl isocyanide (commercially available) were added. After stirring for 19 h, 38.38 ml (153.52 mmol) 4 M hydrochloric acid in dioxane were added dropwise over 5 min. After 5 h the solution was poured on 500 ml saturated aqueous sodium bicarbonate solution and the phases were separated. The organic layer was extracted three times with ethyl acetate and the combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered, and evaporated. The residue was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 50:50). Light yellow foam (97%). MS (Turbo Spray): m/z=480.1 [M+H].

後処理

  1. stirringAfter stirring for 19 h
  2. customthe phases were separated
  3. extractionThe organic layer was extracted three times with ethyl acetate
  4. washthe combined organic layers were washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with a gradient of n-heptane:ethyl acetate (100:0 to 50:50)

出典と根拠

ORDレコード
ord-7ba910e01ab445dcaacf5e0c8d94c4be
出典データセット
uspto-grants-2012_01
特許番号
US08088930B2

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