Trifluoroacetic acid → 1'-(5,7-Difluoro-3-methyl-2-(1-piperazinyl)-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

HRID 1618752노트

반응식

HRID 1618752 반응식
[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[C:4]([N:27]1[C:35]3[C:30](=[N:31][CH:32]=[C:33]([N:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)[CH:34]=3)[C:29]3([CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)[CH2:28]1)=[C:5]([CH3:26])[C:6]([N:13]1[CH2:18][CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15][CH2:14]1)=[N:7]2.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[C:4]([N:27]1[C:35]3[C:30](=[N:31][CH:32]=[C:33]([N:36]4[CH2:37][CH2:38][O:39][CH2:40][CH2:41]4)[CH:34]=3)[C:29]3([CH2:42][CH2:43][O:44][CH2:45][CH2:46]3)[CH2:28]1)=[C:5]([CH3:26])[C:6]([N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)=[N:7]2

참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 67285378US8765940, tert-butyl 4-(5,7-difluoro-3-methyl-4-(6'-(4-morpholinyl)-2,3,5,6-tetrahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridin]-1'(2'H)-yl)-2-quinolinyl)-1-piperazinecarboxylate

생성물 1

HCID 672844611'-(5,7-Difluoro-3-methyl-2-(1-piperazinyl)-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

반응 조건

온도
0 °C

실험 절차

Tert-Butyl 4-(5,7-difluoro-3-methyl-4-(6′-(4-morpholinyl)-2,3,5,6-tetrahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridin]-1′(2′H)-yl)-2-quinolinyl)-1-piperazinecarboxylate (450 mg, 0.70 mmol) was dissolved in DCM (5.0 mL) and cooled to 0° C. TFA (5.0 mL, 65.0 mmol) was then added and the reaction mixture was allowed to warm to rt and stirred for 2.5 h. The reaction was diluted with DCM and concentrated to dryness. The residue was then converted to the free amine by eluting through an SCX column with 0 to 2M ammonia in MeOH to give 1′-(5,7-difluoro-3-methyl-2-(1-piperazinyl)-4-quinolinyl)-6′-(4-morpholinyl)-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine]. 1H NMR (400 MHz, chloroform-d) δ ppm 7.56 (1H, d, J=2.3 Hz), 7.36 (1H, ddd, J=9.9, 2.5, 1.3 Hz), 6.73 (1H, ddd, J=11.8, 9.1, 2.5 Hz), 5.66 (1H, d, J=2.3 Hz), 4.04-4.21 (2H, m), 3.80-3.97 (2H, m), 3.70-3.79 (4H, m), 3.56 (2H, qd, J=11.6, 2.4 Hz), 3.27-3.46 (4H, m), 3.02-3.18 (4H, m), 2.90-3.02 (4H, m), 2.26-2.38 (2H, m), 2.24 (3H, s), 1.97 (1H, br. s.), 1.79 (1H, d, J=13.3 Hz), 1.70 (1H, dd, J=13.6, 1.9 Hz). Mass Spectrum (ESI) m/e=537.3 (M+1).

후처리

  1. temperatureto warm to rt
  2. concentrationconcentrated to dryness
  3. washby eluting through an SCX column with 0 to 2M ammonia in MeOH

출처 및 근거

ORD 기록
ord-db91f90fe02c4014802c662d395d2de1
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08765940B2

반응 노트

불러오는 중…