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

HRID 1618573
ノート
印刷プレビュー

反応式

HRID 1618573 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]=[CH:17][CH:16]=[CH:15][N:14]=2)[C:3]=1[C:19]#[N: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(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>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>[CH3:21][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]=[CH:17][CH:16]=[CH:15][N:14]=3)[C:3]=2[C:19]#[N:20])[CH2:23]1
参加物反応条件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 672844994-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)-morpholineHCID 672857224-Chloro-7-fluoro-2-(pyridin-2-yl)quinoline-3-carbonitrile

生成物 1

HCID 509386044-(3,3-dimethyl-6-morpholino-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-2-(pyridin-2-yl)quinoline-3-carbonitrile

試薬・触媒・溶媒 2

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

反応条件

温度
105 °C

実験手順

A mixture of 4-chloro-7-fluoro-2-(pyridin-2-yl)quinoline-3-carbonitrile (30 mg, 0.11 mmol) (described herein), 4-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]-pyridin-6-yl)morpholine (30 mg, 0.13 mmol) (described herein), sodium tert-butoxide (30.5 mg, 0.32 mmol), 2-(dicyclohexylphosphino)-2′,4′,6′-tri-i-propyl-1,1′-biphenyl (15.12 mg, 0.032 mmol), Pd2dba3 (14.53 mg, 0.016 mmol), and toluene (1.0 mL) was stirred at 105° C. for 3 h, then cooled to rt and concentrated. The resulting residue was taken up in EtOAc, washed with saturated aqueous sodium bicarbonate solution, 1M NaOH, and brine, and the organic layer dried (MgSO4) and concentrated. Chromatography afforded 4-(3,3-dimethyl-6-morpholino-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-2-(pyridin-2-yl)quinoline-3-carbonitrile as a yellow solid. 1H NMR (400 MHz, chloroform-d) δ ppm 8.83 (1H, ddd, J=4.8, 1.7, 0.9 Hz), 8.19-8.31 (1H, m), 7.82-8.01 (3H, m), 7.72-7.82 (1H, m), 7.42-7.57 (1H, m), 7.28-7.37 (1H, m), 6.05-6.21 (1H, m), 4.60-4.72 (1H, m), 3.83-3.94 (1H, m), 3.70-3.83 (4H, m), 2.90-3.11 (4H, m), 1.55-1.62 (3H, m), 1.48-1.55 (3H, m). Mass Spectrum (ESI) m/e=481 (M+1).

後処理

  1. temperaturecooled to rt
  2. concentrationconcentrated
  3. washwashed with saturated aqueous sodium bicarbonate solution, 1M NaOH, and brine
  4. dry with materialthe organic layer dried (MgSO4)
  5. concentrationconcentrated

出典と根拠

ORDレコード
ord-3458317422744472a27a2aa6a3e185a3
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

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート