Diisopropylethylamine → 2-(3-Fluoro-phenyl)-pyrimidine-5-carboxylic acid (6-fluoro-2,3-dihydro-1,4-benzoxazin-4-yl)-amide

HRID 2382118Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2382118
CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:12]=[C:13]([C:17]2[N:22]=[CH:21][C:20]([C:23]([OH:25])=O)=[CH:19][N:18]=2)[CH:14]=[CH:15][CH:16]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:50][C:51]1[CH:52]=[CH:53][C:54]2[O:59][CH2:58][CH2:57][N:56]([NH2:60])[C:55]=2[CH:61]=1>CN(C=O)C>[F:50][C:51]1[CH:52]=[CH:53][C:54]2[O:59][CH2:58][CH2:57][N:56]([NH:60][C:23]([C:20]3[CH:21]=[N:22][C:17]([C:13]4[CH:14]=[CH:15][CH:16]=[C:11]([F:10])[CH:12]=4)=[N:18][CH:19]=3)=[O:25])[C:55]=2[CH:61]=1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 450733632-(3-Fluorophenyl)pyrimidine-5-carboxylic acidHCID 68554248HCID 68554248, Verbindung

Produkt 1

HCID 592000702-(3-Fluoro-phenyl)-pyrimidine-5-carboxylic acid (6-fluoro-2,3-dihydro-1,4-benzoxazin-4-yl)-amideAusbeute 22 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

DIPEA (174 μL) is added to a mixture of 2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid (218 mg), HATU (380 mg) and 6-fluoro-2,3-dihydro-benzo[1,4]oxazin-4-ylamine (220 mg) in DMF (15 mL) and then heated at 800 C. overnight. The reaction mixture is concentrated in vacuo and the residue is purified by silica gel column chromatography eluting with 30% EtOAc in heptane to afford 2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid (6-fluoro-2,3-dihydro-1,4-benzoxazin-4-yl)-amide (81 mg). MS: 369 (M+H); 1H NMR (300 MHz, DMSO-D6): δ 11.05 (s, 1H), 9.35 (s, 2H), 8.32 (dd, 1H), 8.18 (dd, 1H), 7.65 (m, 1H), 7.5 (m, 1H), 6.8-6.7 (m, 2H), 6.52-6.45 (m, 1H), 4.36-4.33 (m, 2H), 3.65 (m, 2H). IC50=12 nM.

Aufarbeitung

  1. temperatureheated at 800 C
  2. customovernight
  3. concentrationThe reaction mixture is concentrated in vacuo
  4. customthe residue is purified by silica gel column chromatography
  5. washeluting with 30% EtOAc in heptane

Quellen und Nachweise

ORD-Eintrag
ord-a5062436ed2542a395e9e7c9a7faa10b
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08258130B2

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