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2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]-pyridin-1-yl)-5,7-difluoro-3-methyl-2-(1-naphthalenyl)quinoline

HRID 1618657
ノート
印刷プレビュー

反応式

HRID 1618657 の反応式
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:13])=[CH:9][C:10]=2[F:12])[N:5]=[C:4]([C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:17]=[CH:16][CH:15]=2)[C:3]=1[CH3:24].[CH3:25][C:26]1([CH3:41])[C:30]2=[N:31][CH:32]=[C:33]([N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)[CH:34]=[C:29]2[NH:28][CH2:27]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.CC(C)([O-])C.[Na+]>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].C1(C)C=CC=CC=1>[CH3:25][C:26]1([CH3:41])[C:30]2=[N:31][CH:32]=[C:33]([N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)[CH:34]=[C:29]2[N:28]([C:2]2[C:11]3[C:6](=[CH:7][C:8]([F:13])=[CH:9][C:10]=3[F:12])[N:5]=[C:4]([C:14]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[CH:17]=[CH:16][CH:15]=3)[C:3]=2[CH3:24])[CH2:27]1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 672844694-Chloro-5,7-difluoro-3-methyl-2-(naphthalen-1-yl)quinolineHCID 672844994-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)-morpholine

生成物 1

HCID 672848834-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]-pyridin-1-yl)-5,7-difluoro-3-methyl-2-(1-naphthalenyl)quinoline

試薬・触媒・溶媒 2

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

実験手順

4-Chloro-5,7-difluoro-3-methyl-2-(naphthalen-1-yl)quinoline (43.7 mg, 0.129 mmol), 4-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)morpholine (30 mg, 0.129 mmol), Pd2dba3 (11.8 mg, 0.013 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (12.3 mg, 0.026 mmol), sodium tert-butoxide (37.1 mL, 0.386 mmol), and toluene (1.29 mL) were stirred at 105° C. for 2 h. The reaction mixture was then concentrated and the resulting residue partitioned between EtOAc and saturated aqueous sodium bicarbonate solution. The organic layer was washed with brine and water, then dried (MgSO4) and concentrated. Purification of the crude by reverse-phase chromatography (0-70% acetonitrile in water) gave 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]-pyridin-1-yl)-5,7-difluoro-3-methyl-2-(1-naphthalenyl)quinoline. 1H NMR (400 MHz, chloroform-d) δ ppm 8.12 (1H, dd, J=1.3, 0.7 Hz), 8.01 (1H, d, J=8.6 Hz), 7.90-7.98 (2H, m), 7.69-7.76 (2H, m), 7.58 (3H, dt, J=5.5, 2.2 Hz), 7.01 (1H, s), 5.74-5.82 (1H, m), 3.88 (1H, ddd, J=8.6, 1.1, 0.7 Hz), 3.71-3.83 (5H, m), 2.97-3.08 (4H, m), 2.37 (3H, s), 1.58 (3H, s), 1.51 (3H, s). Mass Spectrum (ESI) m/e=537.2 (M+1).

後処理

  1. concentrationThe reaction mixture was then concentrated
  2. customthe resulting residue partitioned between EtOAc and saturated aqueous sodium bicarbonate solution
  3. washThe organic layer was washed with brine and water
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customPurification of the crude by reverse-phase chromatography (0-70% acetonitrile in water)

出典と根拠

ORDレコード
ord-3554d6d00b654bc583ec274a997f3950
出典データセット
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08765940B2

反応ノート

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