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 1618709ノート

反応式

HRID 1618709 の反応式
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

参加物

6

反応物 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]

生成物 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]

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

実験手順

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).

後処理

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

出典と根拠

ORDレコード
ord-4211f054b6144ddabc3d4424f177c5ef
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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