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

HRID 408277

Reaktionsgleichung

Reaktionsgleichung von HRID 408277
[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.[CH:13]1([C:17](O)=[O:18])[CH2:16][CH2:15][CH2:14]1.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:13]3[CH2:16][CH2:15][CH2:14]3)=[O:18])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Komponenten

8

Edukt 5

HCID 8471TriethylamineHCID 19494Cyclobutanecarboxylic acidHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 168937Lithium hydroxide, monohydrateHCID 602052765-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine

Produkt 1

HCID 60205443N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)cyclobutanecarboxamideAusbeute 71,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A mixture of 5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-amine (200 mg, 0.869 mmol, Example 1, Step H), cyclobutanecarboxylic acid (218 mg, 2.17 mmol) and triethylamine (606 μL, 4.35 mmol) in CH2Cl2 (10 mL) at room temperature was treated with BOP-Cl (203 mg, 2.17 mmol). The reaction was stirred at room temperature for 42 hours. The reaction mixture was then treated with 2M LiOH.H2O (2 mL) and stirred at room temperature for 18 hours. Water (10 mL) was added to the reaction mixture, and 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)cyclobutanecarboxamide (193 mg, 71% yield) as a solid. 1H NMR (400 MHz, (CD3)2SO) δ 12.04 (br s, 1H), 9.33 (s, 1H), 8.33 (d, 1H), 7.57 (s, 1H), 3.29-3.24 (m, 1H), 2.25-2.18 (m, 2H), 2.15-2.08 (m, 2H), 1.98-1.88 (m, 1H), 1.86-1.78 (m, 1H); LCMS (APCI+) m/z 311.9, 314.0 (M+H)+, Retention time=2.96 minutes (Method 2).

Aufarbeitung

  1. stirringstirred at room temperature for 18 hours
  2. customthe solid formed
  3. filtrationwas filtered
  4. washwashed with additional water
  5. customdried

Quellen und Nachweise

ORD-Eintrag
ord-c1b1a01d0b41409bbe2e4caa912d8b44
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08758830B2

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