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Sodium hydride → (2S)-3-isopropoxy-2-(1-(1-methyl-1H-imidazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyridin-2-yl)propanamide

HRID 1098058
ノート
印刷プレビュー

反応式

HRID 1098058 の反応式
[H-].[Na+].[OH:3][C@@H:4]([CH2:15][O:16][CH:17]([CH3:19])[CH3:18])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][N:9]=1)=[O:6].[CH3:20][N:21]1[CH:25]=[CH:24][N:23]=[C:22]1[N:26]1[C:30]2=[N:31][CH:32]=[N:33][C:34](OC3C=CC=CC=3)=[C:29]2[CH:28]=[N:27]1>C1COCC1>[CH:17]([O:16][CH2:15][C@H:4]([O:3][C:34]1[N:33]=[CH:32][N:31]=[C:30]2[N:26]([C:22]3[N:21]([CH3:20])[CH:25]=[CH:24][N:23]=3)[N:27]=[CH:28][C:29]=12)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][N:9]=1)=[O:6])([CH3:19])[CH3:18]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 57504492HCID 57504492、化合物2 回HCID 575045581-(1-methyl-1H-imidazol-2-yl)-4-phenoxy-1H-pyrazolo[3,4-d]pyrimidine

生成物 1

HCID 57504439(2S)-3-isopropoxy-2-(1-(1-methyl-1H-imidazol-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyridin-2-yl)propanamide

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran
溶媒
2 回

反応条件

温度
0 °C

実験手順

Sodium hydride (60% in oil) (28.8 mg, 0.72 mmol) was added to (S)-2-hydroxy-3-isopropoxy-N-(5-methylpyridin-2-yl)propanamide (Intermediate C7) (143 mg, 0.60 mmol) in anhydrous THF (5 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes and then 1-(1-methyl-1H-imidazol-2-yl)-4-phenoxy-1H-pyrazolo[3,4-d]pyrimidine (Intermediate AV1) (193 mg, 0.66 mmol) in THF (1 mL) was added. The reaction mixture was allowed to warm to room temperature and stirred for 2 hours. The reaction mixture was quenched with 1M citric (2 mL), extracted with EtOAc, the organic layer was washed with water ×2 and brine, dried (MgSO4), filtered and evaporated to afford orange oil. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents to afford the product (90 mg, 34.4%, 100% ee). 1H NMR (400 MHz, CDCl3) δ 1.18 (6H, t), 2.29 (3H, s), 3.65 (3H, s), 3.67-3.76 (1H, m), 4.08 (2H, d), 6.01 (1H, t), 7.01 (1H, d), 7.17 (1H, d), 7.49-7.55 (1H, m), 8.06-8.14 (2H, m), 8.42 (1H, s), 8.65 (1H, s), 8.68 (1H, s); m/z (ES+) (M+H)+=437.51; HPLC tR=1.89 min.

後処理

  1. temperatureto warm to room temperature
  2. stirringstirred for 2 hours
  3. customThe reaction mixture was quenched with 1M citric (2 mL)
  4. extractionextracted with EtOAc
  5. washthe organic layer was washed with water ×2 and brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customto afford orange oil
  10. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length)
  11. customto afford the product (90 mg, 34.4%, 100% ee)

出典と根拠

ORDレコード
ord-37af8147c5b641b795519aeca19fc4fc
出典データセット
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08143263B2

反応ノート

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