Diisopropylethylamine → N-(3-Amino-2,2-difluoro-propyl)-4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzamide

HRID 1985769

Reaktionsgleichung

Reaktionsgleichung von HRID 1985769
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[NH:11][CH2:12][C:13]1[S:17][C:16]([NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)=[N:15][CH:14]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:49][C:50]([F:55])([CH2:53][NH2:54])[CH2:51][NH2:52].CCN(C(C)C)C(C)C>CN(C=O)C.C1COCC1.C(Cl)Cl>[NH2:52][CH2:51][C:50]([F:55])([F:49])[CH2:53][NH:54][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([F:1])=[C:3]([NH:11][CH2:12][C:13]2[S:17][C:16]([NH:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=3)=[N:15][CH:14]=2)[CH:4]=1

Komponenten

8

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 199026522,2-Difluoropropane-1,3-diamineHCID 220190564-Fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzoic acid2×

Produkt 1

HCID 22019140N-(3-Amino-2,2-difluoro-propyl)-4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzamideAusbeute 65 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a mixture of 4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzoic acid (compound 52A, 21 mg, 0.06 mmol) and HATU (38 mg, 0.1 mmol) in DMF (0.2 ml) and THF (0.4 ml), were added 2,2-difluoro-1,3-propanediamine (ref. Tetrahedron, 8617, 1994) (60 mg, 0.54 mmol) and DIPEA (26 mg, 0.2 mmol). The resulting mixture was stirred at RT for 18 h, then diluted with CH2Cl2, washed with brine, dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography [silica gel, 5% (NH3/MeOH(2M) in EtOAc] to afford the title compound (17 mg, 65%) as a white solid. LC/MS; (M+H)+=437.

Aufarbeitung

  1. washwashed with brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customThe residue was purified by flash column chromatography [silica gel, 5% (NH3/MeOH(2M) in EtOAc]

Quellen und Nachweise

ORD-Eintrag
ord-7913a66cfb9b4b26b68b10f5cc238c4e
Quelldatensatz
uspto-grants-2009_06
Patentnummer
US07547711B2

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