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

HRID 419570노트

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HRID 419570 반응식
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]([C:38]1[C:39]([N:47]2[CH2:52][CH2:51][N:50]([CH2:53][CH2:54][S:55]([CH3:58])(=[O:57])=[O:56])[CH2:49][CH2:48]2)=[CH:40][C:41]([O:45][CH3:46])=[C:42]([CH:44]=1)[NH2:43])[CH3:37].Cl.O1CCOCC1.N>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:38]([CH2:36][CH3:37])[C:39]([N:47]4[CH2:52][CH2:51][N:50]([CH2:53][CH2:54][S:55]([CH3:58])(=[O:57])=[O:56])[CH2:49][CH2:48]4)=[CH:40][C:41]=3[O:45][CH3:46])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH3:35]

참가 물질

7

반응물 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 594525905-(3-(2-chloropyrimidin-4-yl)imidazo[1,2-a]pyridin-2-yl)-N-(2,6-difluorophenyl)-2-methoxybenzamideHCID 594529565-Ethyl-2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}aniline

생성물 1

HCID 59452582N-(2,6-difluorophenyl)-5-(3-{2-[(5-ethyl-2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl]phenyl)amino}-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide수율 38%

시약·촉매·용매 1

HCID 887Methanol용매

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온도
180 °C

실험 절차

In a microwave vial with septum cap, 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamide (Intermediate Example 2) (0.246 g, 0.5 mmol) and 5-ethyl-2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}aniline (0.171 g, 0.5 mmol) were taken up in 1,1,1-trifluoroethanol (3 mL) and 4M HCl in dioxane (0.25 mL, 1.0 mmol) 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 NH3 in MeOH, and concentrated in vacuo onto silica gel and flash chromatographed. The desired fractions were combined and concentrated and the resulting solid was triturated with diethyl ether, filtered and air dried to give the title compound (0.150 g, 0.19 mmol, 38%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.78 (s, 1H), 9.34 (dd, J=3.1, 2.2 Hz, 1H), 8.49 (s, 1H), 8.24 (d, J=5.1 Hz, 1H), 8.11 (d, J=1.3 Hz, 1H), 7.78 (dd, J=8.9, 1.4 Hz, 1H), 7.70 (d, J=9.0 Hz, 1H), 7.54 (s, 1H), 7.33-7.50 (m, 2H), 7.28 (d, J=8.8 Hz, 1H), 7.18 (t, J=8.1 Hz, 2H), 6.94 (t, J=6.6 Hz, 1H), 6.83 (s, 1H), 6.57 (d, J=4.9 Hz, 1H), 3.98 (s, 3H), 3.80 (s, 3H), 3.28-3.40 (m, 2H), 3.06 (s, 3 H), 2.82-2.92 (m, 4H), 2.77 (t, J=6.5 Hz, 2H), 2.50-2.69 (m, 6H), 1.08 (q, J=7.0 Hz, 3H). MS (M+H, ES+) 797.

후처리

  1. customIn a microwave vial with septum cap
  2. customThe vial was sealed
  3. customReaction
  4. temperaturewas cooled rt
  5. concentrationconcentrated in vacuo onto silica gel and flash
  6. customchromatographed
  7. concentrationconcentrated
  8. customthe resulting solid was triturated with diethyl ether
  9. filtrationfiltered
  10. customair dried

출처 및 근거

ORD 기록
ord-7949a16ac8804c26a69edecaf012aee9
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093239B2

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