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-(methyloxy)benzamide

HRID 419629노트

반응식

HRID 419629 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]([O:38][C:39]1[CH:45]=[C:44]([N:46]2[CH2:51][CH2:50][CH:49]([CH2:52][CH2:53][S:54]([CH3:57])(=[O:56])=[O:55])[CH2:48][CH2:47]2)[C:43]([CH3:58])=[CH:42][C:40]=1[NH2:41])[CH3:37].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:41][C:40]3[CH:42]=[C:43]([CH3:58])[C:44]([N:46]4[CH2:51][CH2:50][CH:49]([CH2:52][CH2:53][S:54]([CH3:57])(=[O:56])=[O:55])[CH2:48][CH2:47]4)=[CH:45][C:39]=3[O:38][CH2:36][CH3:37])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH3:35]

참가 물질

5

반응물 3

HCID 313Hydrochloric AcidHCID 594525905-(3-(2-chloropyrimidin-4-yl)imidazo[1,2-a]pyridin-2-yl)-N-(2,6-difluorophenyl)-2-methoxybenzamideHCID 594527752-(Ethyloxy)-5-methyl-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}aniline

생성물 1

HCID 25125160N-(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-(methyloxy)benzamide수율 57%

시약·촉매·용매 1

HCID 64092,2,2-Trifluoroethanol용매

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온도
85 °C

실험 절차

To 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamide (Intermediate Example 2) (19.7 g, 39.9 mmol) and 2-(ethyloxy)-5-methyl-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}aniline (13.6 g, 39.9 mmol) in 2,2,2-trifluoroethanol (200 mL) was added HCl (4M in dioxane) (19.97 mL, 80 mmol). The reaction mixture was heated at 85° C. for 2 days. The reaction was determined to be complete by LCMS. The reaction was cooled and quenched with solid NaOMe. The suspension was concentrated. Purification by flash chromatography, followed by trituration with EtOH provided the title compound of Step H (18.1 g, 22.7 mmol, 57% yield). Alternatively, this reaction can be effected using microwave irradiation. Additionally, further purification of the title compound can be effected by recrystallization from equal parts DCM and EtOH. 1H NMR (400 MHz, DMSO-d6) δ 9.80 (s, 1H), 9.37 (d, J=6.0 Hz, 1H), 8.38 (s, 1H), 8.27 (d, J=5.1 Hz, 1H), 8.12 (s, 1H), 7.64-7.83 (m, 2H), 7.55 (s, 1H), 7.35-7.52 (m, 2H), 7.29 (d, J=8.6 Hz, 1H), 7.20 (t, J=8.0 Hz, 2H), 6.96 (t, J=6.6 Hz, 1H), 6.75 (s, 1H), 6.59 (d, J=5.0 Hz, 1H), 3.92-4.15 (m, 5H), 3.11-3.27 (m, 2H), 2.91-3.11 (m, 5H), 2.61 (t, 2H), 2.15 (s, 3H), 1.62-1.87 (m, 4H), 1.42-1.57 (m, 1H), 1.21-1.42 (m, 5H). MS (M+H, ES+) 796.

후처리

  1. temperatureThe reaction was cooled
  2. customquenched with solid NaOMe
  3. concentrationThe suspension was concentrated
  4. customPurification by flash chromatography

출처 및 근거

ORD 기록
ord-830a383681ce4e63b60c3f5b10c59bb8
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093239B2

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