Tetrabutylammonium Fluoride → (2S)-2-[1-(2-chlorophenyl)pyrazolo[4,5-e]pyrimidin-4-yl]oxy-N-(5-fluoro-2-pyridyl)-3-(3-hydroxyazetidin-1-yl)propanamide

HRID 1098062ノート

反応式

HRID 1098062 の反応式
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:26][CH:27]1[CH2:30][N:29]([CH2:31][C@H:32]([O:43][C:44]2[N:49]=[CH:48][N:47]=[C:46]3[N:50]([C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=4[Cl:59])[N:51]=[CH:52][C:45]=23)[C:33]([NH:35][C:36]2[CH:41]=[CH:40][C:39]([F:42])=[CH:38][N:37]=2)=[O:34])[CH2:28]1)(C(C)(C)C)(C)C>O1CCCC1>[Cl:59][C:54]1[CH:55]=[CH:56][CH:57]=[CH:58][C:53]=1[N:50]1[C:46]2[N:47]=[CH:48][N:49]=[C:44]([O:43][C@@H:32]([CH2:31][N:29]3[CH2:30][CH:27]([OH:26])[CH2:28]3)[C:33]([NH:35][C:36]3[CH:41]=[CH:40][C:39]([F:42])=[CH:38][N:37]=3)=[O:34])[C:45]=2[CH:52]=[N:51]1

参加物

4

反応物 2

HCID 2724141Tetrabutylammonium FluorideHCID 57504561(2S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-fluoropyridin-2-yl)propanamide

生成物 1

HCID 46175433(2S)-2-[1-(2-chlorophenyl)pyrazolo[4,5-e]pyrimidin-4-yl]oxy-N-(5-fluoro-2-pyridyl)-3-(3-hydroxyazetidin-1-yl)propanamide収率 73.6%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of tetrabutylammonium fluoride (1M in THF) (7.14 mL, 7.14 mmol) was added in one portion to a stirred solution of (2S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-fluoropyridin-2-yl)propanamide (Intermediate AX1) (4.27 g, 7.14 mmol) in tetrahydrofuran (100 mL). The resulting solution was stirred at ambient temperature for 30 minutes. The reaction mixture was quenched with saturated NH4Cl (30 mL), concentrated to approximately 50 mL and then diluted with water (50 mL) and EtOAc (100 mL). The organic layer was separated and the aqueous layer extracted with EtOAc (100 mL). The combined organics were dried (MgSO4), filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in EtOAc to afford the product (2.54 g, 73.6%). 1H NMR (400 MHz, CDCl3) δ 2.35 (1H, s), 3.15-3.21 (3H, m), 3.27-3.31 (1H, m), 3.84-3.91 (2H, m), 4.50-4.57 (1H, m), 5.90-5.93 (1H, m), 7.41-7.54 (4H, m), 7.61-7.63 (1H, m), 8.14 (1H, d), 8.23-8.26 (1H, m), 8.37 (1H, s), 8.59 (1H, s), 9.74 (1H, s); m/z (ES+) (M+H)+=484.17; HPLC tR=1.65 min.

後処理

  1. customThe reaction mixture was quenched with saturated NH4Cl (30 mL)
  2. concentrationconcentrated to approximately 50 mL
  3. additiondiluted with water (50 mL) and EtOAc (100 mL)
  4. customThe organic layer was separated
  5. extractionthe aqueous layer extracted with EtOAc (100 mL)
  6. dry with materialThe combined organics were dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customto afford crude product
  10. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in EtOAc

出典と根拠

ORDレコード
ord-9697db5667354a5590bdace2aedc6a2a
出典データセット
uspto-grants-2012_03
特許番号
US08143263B2

反応ノート

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