Triethylamine → HCID 60205386, compound

HRID 408238Notes

Reaction equation

HRID 408238 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]([F:22])([F:21])[C:15]1([C:18](O)=[O:19])[CH2:17][CH2:16]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:18]([C:15]3([C:14]([F:22])([F:21])[F:13])[CH2:17][CH2:16]3)=[O:19])=[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 27783061-(Trifluoromethyl)cyclopropane-1-carboxylic acidHCID 602052765-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine

Product 1

HCID 60205386HCID 60205386, compoundYield 72.1%

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 1-(trifluoromethyl)cyclopropanecarboxylic acid (161 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 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 was stirred for 1 hour. The solid, which separated, was filtered and washed with water and CH2Cl2 (10 mL). The filtered cake was dried to yield N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-1-(trifluoromethyl)cyclopropanecarboxamide (229.5 mg, 72% yield). 1H NMR (400 MHz, (CD3)2SO) δ 12.15 (br s, 1H), 9.38 (s, 1H), 8.36 (d, 1H), 7.51 (s, 1H), 1.49-1.43 (m, 2H), 1.38-1.33 (m, 2H); LCMS (APCI+) m/z 366, 368 (M+H)+, Retention time=3.32 minutes (Method 3).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. stirringThe residue was stirred in anhydrous THF (10 mL)
  3. additiontreated with 2M LiOH solution (3 mL)
  4. stirringstirred at room temperature for 1 hour
  5. customThe organic solvent was removed in vacuo
  6. additionwater (10 mL) was added
  7. stirringThe reaction was stirred for 1 hour
  8. customThe solid, which separated
  9. filtrationwas filtered
  10. washwashed with water and CH2Cl2 (10 mL)
  11. customThe filtered cake was dried

Sources & evidence

ORD record
ord-d2d3e69508ab4d39967ab01c67e50688
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Reaction notes

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