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Ammonia → N-(2,6-difluorophenyl)-3-[3-(2-{[4-{4-[4-(2-fluoroethyl)-1-piperazinyl]-1-piperidinyl}-2,5-bis(methyloxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzamide

HRID 419426
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 419426
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]=[C:19]([CH:31]=[CH:32][CH:33]=2)[C:20]([NH:22][C:23]2[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=2[F:30])=[O:21])[CH:5]=[CH:4][N:3]=1.[F:34][CH2:35][CH2:36][N:37]1[CH2:42][CH2:41][N:40]([CH:43]2[CH2:48][CH2:47][N:46]([C:49]3[C:55]([O:56][CH3:57])=[CH:54][C:52]([NH2:53])=[C:51]([O:58][CH3:59])[CH:50]=3)[CH2:45][CH2:44]2)[CH2:39][CH2:38]1.N>CC(O)C.Cl.CO>[F:30][C:24]1[CH:25]=[CH:26][CH:27]=[C:28]([F:29])[C:23]=1[NH:22][C:20](=[O:21])[C:19]1[CH:31]=[CH:32][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:53][C:52]3[CH:54]=[C:55]([O:56][CH3:57])[C:49]([N:46]4[CH2:45][CH2:44][CH:43]([N:40]5[CH2:39][CH2:38][N:37]([CH2:36][CH2:35][F:34])[CH2:42][CH2:41]5)[CH2:48][CH2:47]4)=[CH:50][C:51]=3[O:58][CH3:59])[N:7]=2)[CH:18]=1
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Komponenten

7

Edukt 3

HCID 222AmmoniaHCID 594526854-{4-[4-(2-Fluoroethyl)-1-piperazinyl]-1-piperidinyl}-2,5-bis(methyloxy)anilineHCID 594529693-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide

Produkt 1

HCID 59452735N-(2,6-difluorophenyl)-3-[3-(2-{[4-{4-[4-(2-fluoroethyl)-1-piperazinyl]-1-piperidinyl}-2,5-bis(methyloxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzamide
Ausbeute 32,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 313Hydrochloric AcidKatalysatorHCID 887MethanolLösungsmittelHCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
180 °C

Versuchsvorschrift

In a 5 mL microwave vial with septum cap, 3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (0.200 g, 0.433 mmol), 4-{4-[4-(2-fluoroethyl)-1-piperazinyl]-1-piperidinyl}-2,5-bis(methyloxy)-aniline (0.190 g, 0.520 mmol) were taken up in iPrOH (3 mL) and concentrated HCl (4 drops) was added. The vial was sealed and heated in the microwave at 180° C. for 40 min. Reaction was complete by MS, it was cooled rt, neutralized with 7N ammonia in MeOH, and concentrated in vacuo. The resulting residue was taken up in DCM and purified by column chromatography using basic alumina followed by silica gel flash chromatography. The desired fractions were concentrated and the resulting solid was triturated with DCM and hexane, filtered and vacuum dried to give the title compound (0.110 g, 32%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.24 (s, 1H), 8.52 (s, 1H), 8.33 (s, 1H), 8.24 (d, J=5.1 Hz, 1H), 8.04 (d, J=7.9 Hz, 1H), 7.83 (d, J=7.9 Hz, 1H), 7.73 (d, J=9.0 Hz, 1H), 7.61 (t, J=7.8 Hz, 1H), 7.26-7.53 (m, 3H), 7.13-7.27 (m, 2H), 6.84-7.08 (m, 1H), 6.66 (s, 1H), 6.50 (d, J=5.1 Hz, 1H), 4.56 (t, J=4.9 Hz, 1H), 4.45 (t, J=4.9 Hz, 1H), 3.76 (s, 3H), 3.64 (s, 3H), 3.36-3.53 (m, 2H), 2.37-2.74 (m, 12H), 2.13-2.36 (m, 1H), 1.70-1.94 (m, 2H), 1.39-1.69 (m, 2H). MS (M+H, ES+) 792.

Aufarbeitung

  1. customIn a 5 mL microwave vial with septum cap
  2. customThe vial was sealed
  3. customReaction
  4. temperaturewas cooled rt
  5. concentrationconcentrated in vacuo
  6. custompurified by column chromatography
  7. concentrationThe desired fractions were concentrated
  8. customthe resulting solid was triturated with DCM and hexane
  9. filtrationfiltered
  10. customvacuum dried

Quellen und Nachweise

ORD-Eintrag
ord-f86cb9887b244c3aaa9e724cb32c0916
Quelldatensatz
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08093239B2

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