Lithium Hydroxide → (S)-N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxypropanamide

HRID 1034898ノート

反応式

HRID 1034898 の反応式
[Br:1][C:2]1[C:3]([F:12])=[C:4]2[C:10]([NH2:11])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.C([O:16][C@@H:17]([CH3:21])[C:18](O)=[O:19])(=O)C.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.C(N(CC)CC)C.[Li+].[OH-]>C(Cl)Cl.CC#N.O.O>[Br:1][C:2]1[C:3]([F:12])=[C:4]2[C:10]([NH:11][C:18](=[O:19])[C@@H:17]([OH:16])[CH3:21])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

参加物

9

反応物 5

HCID 3939Lithium HydroxideHCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 6326324(2S)-2-(Acetyloxy)propanoic acidHCID 602052765-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine

生成物 1

HCID 60205672(S)-N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxypropanamide収率 9%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 18373917Acetonitrile--water (1/1)溶媒

実験手順

5-Bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine (0.350 g, 1.52 mmol; Example 1, Step H), (S)-2-acetoxypropanoic acid (0.422 g, 3.20 mmol), BOP—Cl (0.813 g, 3.20 mmol), and triethylamine (1.06 mL, 7.61 mmol) were placed in DCM (5 mL) and stirred for 1 hour. 3M aqueous LiOH (3 mL) was then added, and the reaction was stirred for 1 hour and then poured into water and extracted with DCM. The combined organic fractions were dried (MgSO4), filtered, and concentrated to give the crude product, which was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 0-60% CH3CN/water) to give (S)—N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxypropanamide (0.040 g, 9% yield).

後処理

  1. stirringthe reaction was stirred for 1 hour
  2. extractionextracted with DCM
  3. dry with materialThe combined organic fractions were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude product, which
  7. customwas purified by reverse phase chromatography (Biotage SP4

出典と根拠

ORDレコード
ord-f216d623da3a47558a77b17962262895
出典データセット
uspto-grants-2013_10
特許番号
US08545897B2

反応ノート

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