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

HRID 2203839Notes

Reaction equation

HRID 2203839 reaction equation
[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

Participants

7

Reactant 5

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-62d3bb4bbb634dc6b4e824761b50b2b4
Source dataset
uspto-grants-2016_06
Patent number
US09365568B2

Reaction notes

Loading…