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 1618772노트

반응식

HRID 1618772 반응식
[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

참가 물질

4

반응물 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]

생성물 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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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).

후처리

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

출처 및 근거

ORD 기록
ord-1d21d16e457a424ba577102439c92bfc
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08765940B2

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