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

HRID 1098066ノート

反応式

HRID 1098066 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]=[N:40][C:39]([CH3:42])=[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[CH2:28][CH:27]([OH:26])[CH2:30]3)[C:33]([NH:35][C:36]3[CH:41]=[N:40][C:39]([CH3:42])=[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 Fluoride2 回HCID 57504564(2S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyrazin-2-yl)propanamide

生成物 1

HCID 46175519(2S)-2-[1-(2-chlorophenyl)pyrazolo[4,5-e]pyrimidin-4-yl]oxy-3-(3-hydroxyazetidin-1-yl)-N-(5-methylpyrazin-2-yl)propanamide収率 31.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

Tetrabutylammonium fluoride (1M in THF) (0.87 mL, 0.87 mmol) was added to (2S)-3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyrazin-2-yl)propanamide (Intermediate BB1) (520 mg, 0.87 mmol) in tetrahydrofuran (25 mL) under nitrogen. The resulting mixture was stirred at ambient temperature for 2 hours. Further tetrabutylammonium fluoride (1M in THF) (1.7 mL, 1.7 mmol) added and the mixture stirred overnight. The reaction mixture was quenched with saturated ammonium chloride solution (20 mL), diluted with ethyl acetate (50 mL) and stirred for 10 minutes. The organic layer was separated, washed with water (50 mL) and brine (50 mL), dried (MgSO4), filtered and evaporated. The crude product was purified by flash silica chromatography, eluting with 0 to 10% methanol in ethyl acetate, to afford the product (130 mg). 1H NMR (400 MHz, DMSO-d6) δ 2.50 (3H, m), 2.98-3.09 (3H, m), 3.15-3.21 (1H, m), 3.67-3.77 (2H, m), 4.19-4.29 (1H, m), 5.31 (1H, d), 5.77-5.84 (1H, m), 7.60-7.76 (3H, m), 7.80-7.82 (1H, m), 8.35-8.37 (1H, m), 8.57 (1H, s), 8.64 (1H, s), 9.11-9.12 (1H, m), 11.17 (1H, s); m/z (ESI+) (M+H)+=481; HPLC tR=1.52 min.

後処理

  1. stirringthe mixture stirred overnight
  2. customThe reaction mixture was quenched with saturated ammonium chloride solution (20 mL)
  3. additiondiluted with ethyl acetate (50 mL)
  4. stirringstirred for 10 minutes
  5. customThe organic layer was separated
  6. washwashed with water (50 mL) and brine (50 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude product was purified by flash silica chromatography
  11. washeluting with 0 to 10% methanol in ethyl acetate

出典と根拠

ORDレコード
ord-30c8f8d039554184b82160b1f5194928
出典データセット
uspto-grants-2012_03
特許番号
US08143263B2

反応ノート

読み込み中…