Methyl Isocyanate → 4-(5,7-difluoro-3-methyl-4-(6'-morpholino-2,3,5,6-tetrahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]-1'(2'H)-yl)quinolin-2-yl)-N-methylpiperazine-1-carboxamide

HRID 1618772ノート

反応式

HRID 1618772 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:20]1[C:28]3[C:23](=[N:24][CH:25]=[C:26]([N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)[CH:27]=3)[C:22]3([CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[CH2:21]1)=[C:5]([CH3:19])[C:6]([N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)=[N:7]2.[CH3:40][N:41]=[C:42]=[O:43]>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:20]1[C:28]3[C:23](=[N:24][CH:25]=[C:26]([N:29]4[CH2:30][CH2:31][O:32][CH2:33][CH2:34]4)[CH:27]=3)[C:22]3([CH2:35][CH2:36][O:37][CH2:38][CH2:39]3)[CH2:21]1)=[C:5]([CH3:19])[C:6]([N:13]1[CH2:18][CH2:17][N:16]([C:42]([NH:41][CH3:40])=[O:43])[CH2:15][CH2:14]1)=[N:7]2

参加物

4

反応物 2

HCID 12228Methyl IsocyanateHCID 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]

生成物 1

HCID 672858154-(5,7-difluoro-3-methyl-4-(6'-morpholino-2,3,5,6-tetrahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]-1'(2'H)-yl)quinolin-2-yl)-N-methylpiperazine-1-carboxamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

1′-(5,7-difluoro-3-methyl-2-(piperazin-1-yl)quinolin-4-yl)-6′-morpholino-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (50 mg, 0.093 mmol) was dissolved in DCM (5.0 mL), and treated with methylisocyanate (5.50 μL, 0.093 mmol) and the reaction was stirred at rt for 2.5 h. After this time the reaction was concentrated to dryness and the residue was purified using an SCX column (compound loaded in MeOH and using 2M ammonia in MeOH as eluent) to give 4-(5,7-difluoro-3-methyl-4-(6′-morpholino-2,3,5,6-tetrahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine]-1′(2′H)-yl)quinolin-2-yl)-N-methylpiperazine-1-carboxamide. 1H NMR (400 MHz, chloroform-d) δ ppm 7.55 (1H, d, J=2.3 Hz), 7.34 (1H, dt, J=9.8, 1.3 Hz), 6.75 (1H, ddd, J=11.8, 9.0, 2.4 Hz), 5.65 (1H, d, J=2.3 Hz), 4.69 (1H, q, J=4.2 Hz), 4.03-4.20 (2H, m), 3.80-3.97 (2H, m), 3.68-3.80 (4H, m), 3.48-3.67 (6H, m), 3.27-3.48 (4H, m), 2.90-3.04 (4H, m), 2.85 (3H, d, J=4.5 Hz), 2.19-2.39 (5H, m), 1.78 (1H, d, J=13.5 Hz), 1.69 (1H, d, J=13.5 Hz). Mass Spectrum (ESI) m/e=594.4 (M+1).

後処理

  1. concentrationAfter this time the reaction was concentrated to dryness
  2. customthe residue was purified

出典と根拠

ORDレコード
ord-1d21d16e457a424ba577102439c92bfc
出典データセット
uspto-grants-2014_07
特許番号
US08765940B2

反応ノート

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