Cyclopropanecarboxylic acid → N-(5-(6-(1-(cyclopropylmethyl)-1H-1,2,3-triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2',4'-difluoro-[1,1'-biphenyl]-3-yl)cyclopropanecarboxamide

HRID 64164

Reaktionsgleichung

Reaktionsgleichung von HRID 64164
[CH:1]1([CH2:4][N:5]2[CH:9]=[C:8]([C:10]3[CH:11]=[C:12]4[N:18]=[CH:17][N:16]([C:19]5[CH:20]=[C:21]([NH2:33])[CH:22]=[C:23]([C:25]6[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=6[F:32])[CH:24]=5)[C:13]4=[N:14][CH:15]=3)[N:7]=[N:6]2)[CH2:3][CH2:2]1.[CH:34]1([C:37](O)=[O:38])[CH2:36][CH2:35]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH:1]1([CH2:4][N:5]2[CH:9]=[C:8]([C:10]3[CH:11]=[C:12]4[N:18]=[CH:17][N:16]([C:19]5[CH:20]=[C:21]([NH:33][C:37]([CH:34]6[CH2:36][CH2:35]6)=[O:38])[CH:22]=[C:23]([C:25]6[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=6[F:32])[CH:24]=5)[C:13]4=[N:14][CH:15]=3)[N:7]=[N:6]2)[CH2:2][CH2:3]1

Komponenten

6

Edukt 4

HCID 15655Cyclopropanecarboxylic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 895014685-(6-(1-(cyclopropylmethyl)-1H-1,2,3-triazol-4-yl)-3H-imidazo-[4,5-b]pyridin-3-yl)-2',4'-difluoro-[1,1'-biphenyl]-3-amine

Produkt 1

HCID 117777721N-(5-(6-(1-(cyclopropylmethyl)-1H-1,2,3-triazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2',4'-difluoro-[1,1'-biphenyl]-3-yl)cyclopropanecarboxamideAusbeute 51 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 5-(6-(1-(cyclopropylmethyl)-1H-1,2,3-triazol-4-yl)-3H-imidazo-[4,5-b]pyridin-3-yl)-2′,4′-difluoro-[1,1′-biphenyl]-3-amine (50 mg, 0.11 mmol) in DMF was added cyclopropanecarboxylic acid (11 mg, 0.13, mmol, 1.2 eq.) followed by HATU (91 mg, 0.24 mmol, 2.0 eq.) and DIPEA (43 mg, 0.33 mmol, 3.0 eq). The mixture was stirred for 16 h and quenched extracted as in Example 1(d). The solvent was distilled off to afford the crude residue which was purified by column chromatography to give the product in 51% yield (25 mg). 1H NMR (300 MHz, DMSO): δ 10.6 (s, 1H) 8.99 (d, 2H), 8.88 (d, 1H), 8.62 (d, 1H), 8.31 (d, 1H), 7.92 (d, 1H), 7.76-7.71 (m, 2H), 7.47-7.40 (m, 1H), 7.29-7.24 (m, 1H), 4.33-4.30 (d, 2H), 3.64-3.62 (m, 2H), 3.12-3.09 (m, 2H), 1.87-1.83 (m, 1H), 0.63-0.61 (t, 2H), 0.49-0.48 (t, 2H); LC-MS (ESI): Calculated mass: 511.5; Observed mass: 511.8 [M+H]+ (rt: 1.63 min).

Aufarbeitung

  1. customquenched
  2. extractionextracted as in Example 1(d)
  3. distillationThe solvent was distilled off

Quellen und Nachweise

ORD-Eintrag
ord-98ad2478c42841e9a426b0ef13b49c4e
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09447091B2

Verknüpfte Notizen

Wird geladen…