Hydrochloric Acid → N-(2,6-difluorophenyl)-5-(3-{2-[(2-(ethyloxy)-5-methyl-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide

HRID 419629Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 419629
Cl[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]3=[N:10][C:9]=2[C:17]2[CH:18]=[CH:19][C:20]([O:34][CH3:35])=[C:21]([CH:33]=2)[C:22]([NH:24][C:25]2[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=2[F:32])=[O:23])[CH:5]=[CH:4][N:3]=1.[CH2:36]([O:38][C:39]1[CH:45]=[C:44]([N:46]2[CH2:51][CH2:50][CH:49]([CH2:52][CH2:53][S:54]([CH3:57])(=[O:56])=[O:55])[CH2:48][CH2:47]2)[C:43]([CH3:58])=[CH:42][C:40]=1[NH2:41])[CH3:37].Cl>FC(F)(F)CO>[F:32][C:26]1[CH:27]=[CH:28][CH:29]=[C:30]([F:31])[C:25]=1[NH:24][C:22](=[O:23])[C:21]1[CH:33]=[C:17]([C:9]2[N:10]=[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]3[C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:41][C:40]3[CH:42]=[C:43]([CH3:58])[C:44]([N:46]4[CH2:51][CH2:50][CH:49]([CH2:52][CH2:53][S:54]([CH3:57])(=[O:56])=[O:55])[CH2:48][CH2:47]4)=[CH:45][C:39]=3[O:38][CH2:36][CH3:37])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH3:35]

Komponenten

5

Edukt 3

HCID 313Hydrochloric AcidHCID 594525905-(3-(2-chloropyrimidin-4-yl)imidazo[1,2-a]pyridin-2-yl)-N-(2,6-difluorophenyl)-2-methoxybenzamideHCID 594527752-(Ethyloxy)-5-methyl-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}aniline

Produkt 1

HCID 25125160N-(2,6-difluorophenyl)-5-(3-{2-[(2-(ethyloxy)-5-methyl-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamideAusbeute 57 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 64092,2,2-TrifluoroethanolLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamide (Intermediate Example 2) (19.7 g, 39.9 mmol) and 2-(ethyloxy)-5-methyl-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}aniline (13.6 g, 39.9 mmol) in 2,2,2-trifluoroethanol (200 mL) was added HCl (4M in dioxane) (19.97 mL, 80 mmol). The reaction mixture was heated at 85° C. for 2 days. The reaction was determined to be complete by LCMS. The reaction was cooled and quenched with solid NaOMe. The suspension was concentrated. Purification by flash chromatography, followed by trituration with EtOH provided the title compound of Step H (18.1 g, 22.7 mmol, 57% yield). Alternatively, this reaction can be effected using microwave irradiation. Additionally, further purification of the title compound can be effected by recrystallization from equal parts DCM and EtOH. 1H NMR (400 MHz, DMSO-d6) δ 9.80 (s, 1H), 9.37 (d, J=6.0 Hz, 1H), 8.38 (s, 1H), 8.27 (d, J=5.1 Hz, 1H), 8.12 (s, 1H), 7.64-7.83 (m, 2H), 7.55 (s, 1H), 7.35-7.52 (m, 2H), 7.29 (d, J=8.6 Hz, 1H), 7.20 (t, J=8.0 Hz, 2H), 6.96 (t, J=6.6 Hz, 1H), 6.75 (s, 1H), 6.59 (d, J=5.0 Hz, 1H), 3.92-4.15 (m, 5H), 3.11-3.27 (m, 2H), 2.91-3.11 (m, 5H), 2.61 (t, 2H), 2.15 (s, 3H), 1.62-1.87 (m, 4H), 1.42-1.57 (m, 1H), 1.21-1.42 (m, 5H). MS (M+H, ES+) 796.

Aufarbeitung

  1. temperatureThe reaction was cooled
  2. customquenched with solid NaOMe
  3. concentrationThe suspension was concentrated
  4. customPurification by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-830a383681ce4e63b60c3f5b10c59bb8
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08093239B2

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