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

HRID 408236

Reaction equation

HRID 408236 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[C:15]([C:20](O)=[O:21])=[N:16][CH:17]=[CH:18][CH:19]=1.O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.C(N(CC)CC)C>C(Cl)Cl>[Br:1][C:2]1[C:3]([F:12])=[C:4]2[C:10]([NH:11][C:20](=[O:21])[C:15]3[C:14]([CH3:13])=[CH:19][CH:18]=[CH:17][N:16]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 2687573-Methylpicolinic acidHCID 602052765-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine

Product 1

HCID 60205383N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-methylpicolinamideYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine (200 mg, 0.869 mmol, Example 1, Step H) in CH2Cl2 (10 mL) was treated with 3-methylpicolinic acid (143 mg, 1.04 mmol), bis(2-oxooxazolidin-3-yl)phosphinic chloride (332 mg, 1.30 mmol) and triethylamine (440 mg, 4.35 mmol). The reaction was stirred at room temperature for 1 hour. The mixture was filtered to remove the product, and the filtrate was concentrated in vacuo. The residue was stirred in anhydrous THF (10 mL), treated with 2M LiOH solution (3 mL) and stirred at room temperature for 1 hour. The organic solvent was removed in vacuo, and then water (10 mL) was added. The reaction stirred for 1 hour. The solid, which separated, was filtered and washed with water and CH2Cl2 (10 mL). The combined filtered cakes were dried to yield N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-3-methylpicolinamide (197 mg, 65% yield). 1H NMR (400 MHz, (CD3)2SO) δ 12.13 (br s, 1H), 10.42 (s, 1H), 8.56 (d, 1H), 8.39 (d, 1H), 7.87 (d, 1H), 7.84 (d, 1H), 7.55 (dd, 1H) 2.67 (s, 3H); LCMS (APCI+) m/z 349.1, 351 (M+H)+, Retention time=3.42 minutes (Method 3).

Workup

  1. filtrationThe mixture was filtered
  2. customto remove the product
  3. concentrationthe filtrate was concentrated in vacuo
  4. stirringThe residue was stirred in anhydrous THF (10 mL)
  5. additiontreated with 2M LiOH solution (3 mL)
  6. stirringstirred at room temperature for 1 hour
  7. customThe organic solvent was removed in vacuo
  8. additionwater (10 mL) was added
  9. stirringThe reaction stirred for 1 hour
  10. customThe solid, which separated
  11. filtrationwas filtered
  12. washwashed with water and CH2Cl2 (10 mL)
  13. filtrationThe combined filtered cakes
  14. customwere dried

Sources & evidence

ORD record
ord-3f6a6a8e0c074919982af4d2e167b90f
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Linked notes

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