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-[(1-methylethyl)oxy]benzamide

HRID 419622Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 419622
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][CH:35]([CH3:37])[CH3:36])=[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.[CH2:38]([O:40][C:41]1[CH:47]=[C:46]([N:48]2[CH2:53][CH2:52][CH:51]([CH2:54][CH2:55][S:56]([CH3:59])(=[O:58])=[O:57])[CH2:50][CH2:49]2)[C:45]([CH3:60])=[CH:44][C:42]=1[NH2:43])[CH3:39].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:43][C:42]3[CH:44]=[C:45]([CH3:60])[C:46]([N:48]4[CH2:53][CH2:52][CH:51]([CH2:54][CH2:55][S:56]([CH3:59])(=[O:58])=[O:57])[CH2:50][CH2:49]4)=[CH:47][C:41]=3[O:40][CH2:38][CH3:39])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH:35]([CH3:37])[CH3:36]

Komponenten

5

Edukt 3

HCID 313Hydrochloric AcidHCID 594527752-(Ethyloxy)-5-methyl-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}anilineHCID 594528525-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-[(1-methylethyl)oxy]benzamide

Produkt 1

HCID 59452612N-(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-[(1-methylethyl)oxy]benzamideAusbeute 24 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 64092,2,2-TrifluoroethanolLösungsmittel

Reaktionsbedingungen

Temperatur
180 °C

Versuchsvorschrift

To 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-[(1-methylethyl)oxy]benzamide (Intermediate Example 7) (0.13 g, 0.25 mmol) and 2-(ethyloxy)-5-methyl-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}aniline (0.087 g, 0.25 mmol) in 2,2,2-trifluoroethanol (1.5 mL) was added HCl (4M in dioxane) (0.13 mL, 0.50 mmol). The reaction was heated to 180° C. for 40 min in a microwave. The reaction was determined to be complete by HPLC. The reaction mixture was quenched with saturated NaHCO3 and sequentially extracted with DCM and EtOAc. The organic layer was dried (MgSO4), filtered, and rotovapped down. Purification by flash chromatography provided the title compound (0.05 g, 0.06 mmol, 24%). 1H NMR (400 MHz, DMSO-d6) δ 9.72 (s, 1H), 9.36 (d, J=5.9 Hz, 1H), 8.37 (s, 1H), 8.28 (d, J=4.9 Hz, 1H), 8.09 (br. s., 1H), 7.74 (dd, J=14.1, 8.9 Hz, 2H), 7.56 (s, 1H), 7.27-7.52 (m, 3H), 7.21 (t, J=7.9 Hz, 2H), 6.96 (t, J=6.6 Hz, 1H), 6.75 (s, 1H), 6.63 (d, J=4.8 Hz, 1H), 4.79-4.97 (m, 1H), 4.07 (q, J=6.7 Hz, 2H), 3.12-3.24 (m, 2H), 3.05 (d, J=11.1 Hz, 2H), 2.98 (s, 3H), 2.61 (t, 2H), 2.14 (s, 3H), 1.62-1.87 (m, 4H), 1.17-1.59 (m, 12H). MS (M+H, ES+) 824.

Aufarbeitung

  1. customThe reaction mixture was quenched with saturated NaHCO3
  2. extractionsequentially extracted with DCM and EtOAc
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. customPurification by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-c91c6c8de7624707ab53320cd0dd1e22
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08093239B2

Notizen zur Reaktion

Wird geladen…