Triethylamine → N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2,2-difluorocyclopropanecarboxamide

HRID 1034825Notes

Reaction equation

HRID 1034825 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.[F:13][C:14]1([F:20])[CH2:16][CH:15]1[C:17](O)=[O:18].C(N(CC)CC)C.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.O[Li].O>C(Cl)Cl.O>[Br:1][C:2]1[C:3]([F:12])=[C:4]2[C:10]([NH:11][C:17]([CH:15]3[CH2:16][C:14]3([F:20])[F:13])=[O:18])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 168937Lithium hydroxide, monohydrateHCID 27828232,2-Difluorocyclopropane-1-carboxylic acidHCID 602052765-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine

Product 1

HCID 60205543N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2,2-difluorocyclopropanecarboxamideYield 54.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 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), 2,2-difluorocyclopropanecarboxylic acid (212 mg, 1.74 mmol), and triethylamine (606 μL, 4.35 mmol) in CH2Cl2 (5 mL) at room temperature was treated with BOP—Cl (162 mg, 1.74 mmol). The mixture was stirred at room temperature for 18 hours. 2M LiOH.H2O (3 mL) was then added to the mixture and stirred for 30 minutes. Water (10 mL) was added, and the formed solid was filtered, washed with additional water (3×5 mL), and dried to provide N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2,2-difluorocyclopropanecarboxamide (158 mg, 54% yield) as a solid. LCMS (APCI+) m/z 334, 336 (M+H)+.

Workup

  1. stirringstirred for 30 minutes
  2. filtrationthe formed solid was filtered
  3. washwashed with additional water (3×5 mL)
  4. customdried

Sources & evidence

ORD record
ord-ac93d35af0f34b7cb2774be627c366c6
Source dataset
uspto-grants-2013_10
Patent number
US08545897B2

Reaction notes

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