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

HRID 419654Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 419654
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.[CH3:37][O:38][C:39]1[CH:45]=[C:44]([N:46]2[CH2:51][CH2:50][N:49]([CH2:52][CH2:53][O:54][CH3:55])[CH2:48][CH2:47]2)[CH:43]=[CH:42][C:40]=1[NH2:41].C1(C)C=CC(S(O)(=O)=O)=CC=1.C(O)C(F)(F)F.N>CO.C(Cl)Cl>[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]=[CH:43][C:44]([N:46]4[CH2:51][CH2:50][N:49]([CH2:52][CH2:53][O:54][CH3:55])[CH2:48][CH2:47]4)=[CH:45][C:39]=3[O:38][CH3:37])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH2:35][CH3:36]

Komponenten

8

Edukt 5

HCID 222AmmoniaHCID 6101p-Toluenesulfonic acidHCID 64092,2,2-TrifluoroethanolHCID 594529415-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamideHCID 597120882-(Methyloxy)-4-{4-[2-(methyloxy)ethyl]-1-piperazinyl}aniline

Produkt 1

HCID 59452986N-(2,6-difluorophenyl)-2-(ethyloxy)-5-(3-{2-[(2-(methyloxy)-4-{4-[2-(methyloxy)ethyl]-1-piperazinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzamideAusbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

5-[3-(2-Chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamide (Intermediate Example 6) (100 mg, 0.2 mmol), 2-(methyloxy)-4-{4-[2-(methyloxy)ethyl]-1-piperazinyl}aniline (47 mg, 0.18 mmol), and p-toluenesulfonicacid (90 mg, 0.47 mmol) were weighed into a 20 mL vial. 1 mL of trifluoroethanol was added and the mixture was heated to 100° C. for 72 h. 2 mL of 2 N ammonia in MeOH was added. The solvent was rotovaped down. The residue was taken up in 3 mL of DCM. 1 g of silica gel was added. The solvent was rotovaped down and the pre-absorbed solids were purified by flash chromatography to give the title compound (90 mg, 0.122 mmol, 69%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.75 (s, 1H), 9.36 (s, 1H), 8.46 (s, 1H), 8.19 (d, J=5.13 Hz, 1H), 8.04 (d, J=1.83 Hz, 1H), 7.74 (dd, J=8.80, 2.20 Hz, 1H), 7.69 (d, J=9.17 Hz, 1H), 7.34-7.46 (m, 3H), 7.26 (d, J=8.43 Hz, 1H), 7.19 (t, J=8.07 Hz, 2H), 6.94 (t, J=6.78 Hz, 1H), 6.67 (d, J=2.20 Hz, 1H), 6.52 (d, J=5.13 Hz, 1H), 6.43-6.50 (m, 1H), 4.26 (q, J=6.97 Hz, 2H), 3.79 (s, 3H), 3.42-3.48 (m, 2H), 3.24 (s, 3H), 3.08-3.17 (m, 4H), 2.53-2.58 (m, 4H), 2.49-2.53 (m, 2H), 1.43 (t, J=6.97 Hz, 3H); MS (ESI): 735 [M+H]+.

Aufarbeitung

  1. addition1 g of silica gel was added
  2. customthe pre-absorbed solids were purified by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-5352512bfcb44e94a5720dfd059440b2
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08093239B2

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