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

HRID 1618679ノート

反応式

HRID 1618679 の反応式
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]2[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][N:14]=2)[C:3]=1[CH3:20].[CH3:21][C:22]1([CH3:37])[C:26]2=[N:27][CH:28]=[C:29]([N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[CH:30]=[C:25]2[NH:24][CH2:23]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC(C)([O-])C.[Na+]>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]>[CH3:21][C:22]1([CH3:37])[C:26]2=[N:27][CH:28]=[C:29]([N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[CH:30]=[C:25]2[N:24]([C:2]2[C:11]3[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=3)[N:5]=[C:4]([C:13]3[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][N:14]=3)[C:3]=2[CH3:20])[CH2:23]1

参加物

7

反応物 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596310864-Chloro-7-fluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolineHCID 672844994-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)-morpholine

生成物 1

HCID 672850644-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(4-methyl-2-pyridinyl)quinoline

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 Y by heating 4-chloro-7-fluoro-3-methyl-2-(4-methylpyridin-2-yl)quinoline (70 mg, 0.244 mmol), 4-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)morpholine (57.0 mg, 0.244 mmol), XPhos (23.3 mg, 0.049 mmol), Pd2dba3 (22.4 mg, 0.024 mmol) and sodium tert butoxide (46.9 mg, 0.488 mmol) in toluene (2.0 mL) at 110° C. in a microwave reactor for 2 h. After this time the reaction was partitioned between EtOAc (70 mL) and water (30 mL). The separated aqueous layer was extracted with EtOAc (30 mL) and the combined organic layers were dried over MgSO4, filtered and evaporated in vacuo. Reverse phase HPLC (10 to 60% acetonitrile in water) gave 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(4-methyl-2-pyridinyl)quinoline. 1H NMR (500 MHz, chloroform-d) δ ppm 8.59 (1H, d, J=4.9 Hz), 7.84 (1H, dd, J=10.0, 2.7 Hz), 7.79 (1H, dd, J=9.3, 6.1 Hz), 7.66-7.70 (1H, m), 7.59 (1H, d, J=2.2 Hz), 7.27-7.32 (1H, m), 7.22 (1H, dd, J=5.0, 1.8 Hz), 5.81 (1H, d, J=2.4 Hz), 3.79-3.83 (2H, m), 3.72-3.78 (4H, m), 2.92-3.05 (4H, m), 2.47-2.52 (3H, m), 2.36 (3H, s), 1.57 (3H, s), 1.52 (3H, s). Mass Spectrum (ESI) m/e=484.2 (M+1).

後処理

  1. customPrepared
  2. customAfter this time the reaction was partitioned between EtOAc (70 mL) and water (30 mL)
  3. extractionThe separated aqueous layer was extracted with EtOAc (30 mL)
  4. dry with materialthe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. customevaporated in vacuo

出典と根拠

ORDレコード
ord-dc81dcb176fa4c81b17752b2174344a3
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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