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

HRID 408271

反応式

HRID 408271 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.[CH3:13][C:14]1[O:18][N:17]=[C:16]([C:19](O)=[O:20])[CH:15]=1.C(N(CC)CC)C.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.[Li+].[OH-]>C(Cl)Cl>[Br:1][C:2]1[C:3]([F:12])=[C:4]2[C:10]([NH:11][C:19]([C:16]3[CH:15]=[C:14]([CH3:13])[O:18][N:17]=3)=[O:20])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

参加物

7

反応物 5

HCID 3939Lithium HydroxideHCID 8471TriethylamineHCID 769473-Methyl-5-isoxazolecarboxylic acid2 回HCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chloride2 回HCID 602052765-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine

生成物 1

HCID 60205431N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-methylisoxazole-3-carboxamide収率 71.3%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A mixture of 5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine (200 mg, 0.869 mmol, Example 1, Step H), 5-methylisoxazole-3-carboxylic acid (221 mg, 1.74 mmol) and triethylamine (606 μL, 4.35 mmol) in CH2Cl2 (10 mL) at room temperature was treated with BOP-Cl (162 mg, 1.74 mmol). The mixture was stirred at room temperature overnight and additional BOP-Cl (81 mg, 0.87 mmol) and 5-methylisoxazole-3-carboxylic acid (110 mg, 0.87 mmol) were added. The mixture was stirred for an additional 48 hours at room temperature. Next, 2M LiOH (3 mL) was added to the mixture and stirred for 1 hour. The organic solvent was removed in vacuo, and water:CH2Cl2 (11 mL; 10:1) were added to the aqueous residue. The solid formed was filtered, washed with additional water and dried to provide N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-methylisoxazole-3-carboxamide (210 mg, 71% yield) as a solid. 1H NMR (400 MHz, (CD3)2SO) δ 12.12 (s, 1H), 10.22 (s, 1H), 8.33 9d, 1H), 7.58 (s, 1H), 2.45 (s, 3H); LCMS (APCI+) m/z 338.9, 340.9 (M+H)+, Retention time=3.16 minutes (Method 2).

後処理

  1. stirringThe mixture was stirred for an additional 48 hours at room temperature
  2. stirringstirred for 1 hour
  3. customThe organic solvent was removed in vacuo, and water
  4. additionCH2Cl2 (11 mL; 10:1) were added to the aqueous residue
  5. customThe solid formed
  6. filtrationwas filtered
  7. washwashed with additional water
  8. customdried

出典と根拠

ORDレコード
ord-352c6b87e2b74669824476ea2215b6bc
出典データセット
uspto-grants-2014_06
特許番号
US08758830B2

関連ノート

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