Morpholine → 1'-(8-Chloro-2,3-dimethyl-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

HRID 1618709노트

반응식

HRID 1618709 반응식
Br[C:2]1[CH:3]=[C:4]2[N:10]([C:11]3[C:20]4[C:15](=[C:16]([Cl:21])[CH:17]=[CH:18][CH:19]=4)[N:14]=[C:13]([CH3:22])[C:12]=3[CH3:23])[CH2:9][C:8]3([CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[C:5]2=[N:6][CH:7]=1.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:21][C:16]1[CH:17]=[CH:18][CH:19]=[C:20]2[C:15]=1[N:14]=[C:13]([CH3:22])[C:12]([CH3:23])=[C:11]2[N:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)[CH:3]=2)[C:8]2([CH2:24][CH2:25][O:26][CH2:27][CH2:28]2)[CH2:9]1

참가 물질

6

반응물 3

HCID 8083MorpholineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 672845186'-Bromo-1'-(8-chloro-2,3-dimethylquinolin-4-yl)-1',2,2',3,5,6-hexahydrospiro-[pyran-4,3'-pyrrolo[3,2-b]pyridine]

생성물 1

HCID 672857241'-(8-Chloro-2,3-dimethyl-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

실험 절차

Prepared according to procedure N by stirring 6′-bromo-1′-(8-chloro-2,3-dimethylquinolin-4-yl)-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]-pyridine] (25 mg, 0.054 mmol), morpholine (4.75 μL, 0.054 mmol), Pd2dba3 (5 mg, 5.4 μmol) and XPhos (5.2 mg, 10.9 μmol) in toluene (2.0 mL) at reflux for 14 h. Purification by reverse phase HPLC (10 to 60% acetonitrile in water) gave 1′-(8-chloro-2,3-dimethyl-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 7.78 (1H, dd, J=7.4, 1.4 Hz), 7.58-7.62 (2H, m), 7.32-7.36 (1H, m), 5.68 (1H, d, J=2.3 Hz), 4.11-4.20 (2H, m), 3.95-4.00 (1H, m), 3.85-3.91 (1H, m), 3.74 (4H, dd, J=5.3, 4.5 Hz), 3.52-3.62 (2H, m), 2.92-3.05 (4H, m), 2.84 (3H, s), 2.33-2.42 (2H, m), 2.31 (3H, s), 1.73-1.87 (2H, m). Mass Spectrum (ESI) m/e=465.2 (M+1).

후처리

  1. customPrepared
  2. temperatureat reflux for 14 h
  3. customPurification by reverse phase HPLC (10 to 60% acetonitrile in water)

출처 및 근거

ORD 기록
ord-4211f054b6144ddabc3d4424f177c5ef
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08765940B2

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