Diisopropylethylamine → N1-(4-(6-Chloropyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide

HRID 1670190Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1670190
ClC1C=C(OC2C=CC=CC2(N)F)N=CN=1.[Cl:17][C:18]1[N:23]=[CH:22][N:21]=[C:20]([O:24][C:25]2[CH:30]=[CH:29][C:28]([NH:31]C(NC(=O)CC3C=CC(F)=CC=3)=S)=[CH:27][C:26]=2[F:45])[CH:19]=1.[F:46][C:47]1[CH:52]=[CH:51][C:50]([NH:53][C:54](=[O:59])[CH2:55][C:56]([OH:58])=O)=[CH:49][CH:48]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[Cl:17][C:18]1[N:23]=[CH:22][N:21]=[C:20]([O:24][C:25]2[CH:30]=[CH:29][C:28]([NH:31][C:56](=[O:58])[CH2:55][C:54]([NH:53][C:50]3[CH:49]=[CH:48][C:47]([F:46])=[CH:52][CH:51]=3)=[O:59])=[CH:27][C:26]=2[F:45])[CH:19]=1

Komponenten

8

Edukt 5

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 43418433-(4-Fluorophenylamino)-3-oxopropanoic acid2×HCID 115538441-(4-(6-Chloropyrimidin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)thioureaHCID 866014734-Chloro-6-(2-amino-2-fluorophenoxy)pyrimidine

Produkt 1

HCID 59852939N1-(4-(6-Chloropyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamideAusbeute 78 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution of 4-chloro-6-(2-amino-2-fluorophenoxy)pyrimidine (29 mg, 0.12 mmol, Compound B of Example 2), 3-(4-fluorophenylamino)-3-oxopropanoic acid (26 mg, 0.13 mmol, Compound B of Example 1) in DMF (1.5 mL) was treated with DIPEA (24 μl, 0.14 mmol) and TBTU (46 mg, 0.14 mmol). The reaction mixture was stirred at RT overnight, diluted with EtOAc (25 mL), and the organic phase was washed with brine (3×20 mL), dried (MgSO4) and concentrated. The product was purified by flash chromatography using 1-3% MeOH in CH2Cl2 as the eluent to give the title compound as a white solid (35 mg, 78%). 1H NMR (DMSO-d6) δ 10.49 (s, 1H), 10.25 (s, 1H), 8.65 (s, 1H), 7.78 (d, 1H, J=12.1 Hz), 7.63-7.57 (m, 3H), 7.40-7.34 (m, 2H), 7.16 (t, 2H, J=8.8 Hz), 3.48 (s, 2H); MS (ESI+) m/z 419.21 (M+H)+.

Aufarbeitung

  1. washthe organic phase was washed with brine (3×20 mL)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customThe product was purified by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-5233c0ac8e714469b5edf1957878c9b5
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US07989477B2

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