2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-amine → 2,2,2-Trifluoro-N-[3-(3-{2-[(2-methyl-1,2,3,4-tetrahydro-7-isoquinolinyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]acetamide

HRID 1159998노트

반응식

HRID 1159998 반응식
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:17]3[CH:18]=[C:19]([NH:23][C:24](=[O:29])[C:25]([F:28])([F:27])[F:26])[CH:20]=[CH:21][CH:22]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[CH:5]=[CH:4][N:3]=1.[CH3:30][N:31]1[CH2:40][CH2:39][C:38]2[C:33](=[CH:34][C:35]([NH2:41])=[CH:36][CH:37]=2)[CH2:32]1>CC(O)C.Cl>[F:26][C:25]([F:28])([F:27])[C:24]([NH:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:17]([C:9]2[C:8]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH:41][C:35]4[CH:34]=[C:33]5[C:38]([CH2:39][CH2:40][N:31]([CH3:30])[CH2:32]5)=[CH:37][CH:36]=4)[N:7]=3)=[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][N:11]3[N:10]=2)[CH:18]=1)=[O:29]

참가 물질

5

반응물 2

HCID 129995062-Methyl-1,2,3,4-tetrahydroisoquinolin-7-amineHCID 59513717N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,2,2-trifluoroacetamide

생성물 1

HCID 595137262,2,2-Trifluoro-N-[3-(3-{2-[(2-methyl-1,2,3,4-tetrahydro-7-isoquinolinyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]acetamide수율 72%

시약·촉매·용매 2

HCID 313Hydrochloric Acid촉매HCID 3776Isopropanol용매

반응 조건

온도
80 °C

실험 절차

To a suspension of N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,2,2-trifluoroacetamide (310 mg, 0.74 mmol, which may be prepared according to Example 11, Step C) and 2-methyl-1,2,3,4-tetrahydro-7-isoquinolinamine (150 mg, 0.92 mmol) in 2-propanol (10 mL) was added 6 drops concentrated HCl. The reaction was stirred for 18 h at 80° C., then partitioned between saturated aqueous NaHCO3 and 20% (v/v) MeOH in EtOAc. The aqueous layer was extracted with 20% (v/v) MeOH in EtOAc, and the combined organic layers were dried over Na2SO4, filtered, and adsorbed onto silica. The crude product was purified by column chromatography to generate the title compound in 72% yield (290 mg, 0.53 mmol). 1H NMR (400 MHz, d6-DMSO) δ 11.39 (s, 1H), 9.45 (s, 1H), 8.85 (d, J=7.0 Hz, 1H), 8.44 (d, J=8.6 Hz, 1H), 8.27 (d, J=5.1 Hz, 1H), 8.02 (s, 1H), 7.83 (d, J=8.6 Hz, 1H), 7.44-7.55 (m, 4H), 7.38 (d, J=8.2 Hz, 1H), 7.14 (t, J=6.9 Hz, 1H), 6.97 (d, J=8.4 Hz, 1H), 6.50 (d, J=5.3 Hz, 1H), 3.39 (s, 2H), 2.75 (t, J=5.7 Hz, 2H), 2.59 (t, J=5.7 Hz, 2H), 2.32 (s, 3H). MS (ESI) m/z=544 [M+H]+.

후처리

  1. custompartitioned between saturated aqueous NaHCO3 and 20% (v/v) MeOH in EtOAc
  2. extractionThe aqueous layer was extracted with 20% (v/v) MeOH in EtOAc
  3. dry with materialthe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. customThe crude product was purified by column chromatography

출처 및 근거

ORD 기록
ord-d4b0aff78d3f45dc98d09947a6660f48
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07812022B2

반응 노트

불러오는 중…