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 1618752ノート

反応式

HRID 1618752 の反応式
[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

参加物

4

反応物 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

生成物 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]

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
0 °C

実験手順

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).

後処理

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

出典と根拠

ORDレコード
ord-db91f90fe02c4014802c662d395d2de1
出典データセット
uspto-grants-2014_07
特許番号
US08765940B2

反応ノート

読み込み中…