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 419622노트

반응식

HRID 419622 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][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]

참가 물질

5

반응물 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

생성물 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]benzamide수율 24%

시약·촉매·용매 1

HCID 64092,2,2-Trifluoroethanol용매

반응 조건

온도
180 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-c91c6c8de7624707ab53320cd0dd1e22
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093239B2

반응 노트

불러오는 중…