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

HRID 419597Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 419597
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][CH2:35][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.[CH2:37]([C:39]1[C:40]([N:49]2[CH2:54][CH2:53][CH:52]([N:55]3[CH2:60][CH2:59][N:58]([S:61]([CH3:64])(=[O:63])=[O:62])[CH2:57][CH2:56]3)[CH2:51][CH2:50]2)=[CH:41][C:42]([O:46][CH2:47][CH3:48])=[C:43]([CH:45]=1)[NH2:44])[CH3:38].Cl>C(O)C(F)(F)F>[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:44][C:43]3[CH:45]=[C:39]([CH2:37][CH3:38])[C:40]([N:49]4[CH2:50][CH2:51][CH:52]([N:55]5[CH2:56][CH2:57][N:58]([S:61]([CH3:64])(=[O:63])=[O:62])[CH2:59][CH2:60]5)[CH2:53][CH2:54]4)=[CH:41][C:42]=3[O:46][CH2:47][CH3:48])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH2:35][CH3:36]

Komponenten

5

Edukt 3

HCID 313Hydrochloric AcidHCID 594526865-Ethyl-2-(ethyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}anilineHCID 594529415-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamide

Produkt 1

HCID 59452902n-(2,6-Difluorophenyl)-5-(3-{2-[(5-ethyl-2-(ethyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(ethyloxy)benzamideAusbeute 64,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 64092,2,2-TrifluoroethanolLösungsmittel

Reaktionsbedingungen

Temperatur
170 °C

Versuchsvorschrift

A mixture of 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamide (Intermediate Example 6) (0.10 g, 0.198 mmol), 5-ethyl-2-(ethyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}aniline (Example 204, Step E) (0.081 g, 0.198 mmol) and HCl (4N,1,4-Dioxane, 0.099 mL, 0.395 mmol) in Trifluoroethanol (8 mL) was heated at 170° C. for 40 min in the microwave. The reaction was quenched with 7N NH3 in MeOH and then concentrated to dryness. The residue was then dissolved in DCM and concentrated onto silica gel. Purification by flash column chromatography followed by recrystallization from DCM and EtOH afforded the title compound N-(2,6-difluorophenyl)-5-(3-{2-[(5-ethyl-2-(ethyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(ethyloxy)benzamide (0.112 g, 61%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.75 (s, 1H), 9.26-9.40 (m, 1H), 8.40 (s, 1H), 8.27 (d, J=5.22 Hz, 1H), 8.07 (d, J=2.02 Hz, 1H), 7.77 (dd, J=8.57, 2.25 Hz, 1H), 7.71 (d, J=8.98 Hz, 1H), 7.59 (s, 1H), 7.33-7.51 (m, 2H), 7.27 (d, J=8.61 Hz, 1H), 7.15-7.24 (m, 2H), 6.88-6.98 (m, 1H), 6.81 (s, 1H), 6.60 (d, J=5.22 Hz, 1H), 4.21-4.34 (m, 2H), 4.07 (q, J=6.93 Hz, 2H), 3.07-3.17 (m, 4H), 2.97-3.06 (m, 2H), 2.87 (s, 3H), 2.59-2.77 (m, 6H), 2.55 (q, J=7.45 Hz, 2H), 2.37-2.46 (m, 1H), 1.79-1.90 (m, 2H), 1.53-1.68 (m, 2H), 1.44 (t, J=6.92 Hz, 3H), 1.26 (t, J=6.97 Hz, 3H), 1.10 (t, J=7.51 Hz, 3H). MS (M-2H, ES−) 878.

Aufarbeitung

  1. customThe reaction was quenched with 7N NH3 in MeOH
  2. concentrationconcentrated to dryness
  3. dissolutionThe residue was then dissolved in DCM
  4. concentrationconcentrated onto silica gel
  5. customPurification by flash column chromatography
  6. customfollowed by recrystallization from DCM and EtOH

Quellen und Nachweise

ORD-Eintrag
ord-98d67868545d4b04a761e35c47ff9dd8
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08093239B2

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