Diisopropylethylamine → (1S,2S)-2-fluoro-N-(7-(5-fluoro-4-methylpyridin-3-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide

HRID 468957Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 468957
[F:1][C:2]1[C:3]([CH3:19])=[C:4]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([NH2:18])[N:14]=[CH:15]3)=[CH:10][N:9]=2)[CH:5]=[N:6][CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:44][C@H:45]1[CH2:47][C@H:46]1[C:48](O)=[O:49].C(N(CC)C(C)C)(C)C>CN(C=O)C.C(OCC)(=O)C>[F:44][C@H:45]1[CH2:47][C@H:46]1[C:48]([NH:18][C:13]1[N:14]=[CH:15][C:16]2[C:11]([CH:12]=1)=[CH:10][N:9]=[C:8]([C:4]1[CH:5]=[N:6][CH:7]=[C:2]([F:1])[C:3]=1[CH3:19])[CH:17]=2)=[O:49]

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 9793716cis-2-Fluorocyclopropanecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 679743607-(5-Fluoro-4-methylpyridin-3-yl)-2,6-naphthyridin-3-amine

Produkt 1

HCID 71115274(1S,2S)-2-fluoro-N-(7-(5-fluoro-4-methylpyridin-3-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamideAusbeute 43 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A mixture of 7-(5-fluoro-4-methyl-3-pyridyl)-2,6-naphthyridin-3-amine (35 mg, 0.14 mmol), HATU (113 mg, 0.29 mmol), (1S,2S)-2-fluorocyclopropanecarboxylic acid (29 mg, 0.28 mmol), and N,N-diisopropylethylamine (0.10 mL, 0.55 mmol) in DMF (1 mL) was heated at 70° C. for 8 hours. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (25 mL). The organic layer was separated, dried over sodium sulfate, filtered and concentrated in vacuo to provide a residue that was purified by reverse phase HPLC purification (5-85% ACN in water w/0.1% NH4OH, 14 min). Desired fractions were combined and evaporated in vacuo to afford the title compound as an off-white solid (20 mg, 43%). 1H NMR (400 MHz, DMSO) δ 11.22 (s, 1H), 9.35 (s, 1H), 8.70 (s, 1H), 8.59 (sz, 1H), 8.58 (s, 1H), 8.24 (s, 1H), 4.98 (m, 1H), 2.37 (d, J=1.9 Hz, 3H), 2.31 (m, 1H), 1.72 (m, 1H), 1.23 (m, 1H). LCMS (Method E): RT=3.978 min, M+H+=341.2.

Aufarbeitung

  1. washwashed with water (25 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide a residue that
  7. customwas purified by reverse phase HPLC purification (5-85% ACN in water w/0.1% NH4OH, 14 min)
  8. customevaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-9eae322a7bbc486f8f39b70ee4ad199c
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08623889B2

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